bigbio/bionlp_st_2013_cg · Datasets at Hugging Face

id stringlengths 1 3	document_id stringlengths 11 13	passages list	entities list	events list	coreferences list	relations list
0	PMID-15193260	[ { "id": "PMID-15193260__text", "type": "abstract", "text": [ "Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. \nWe identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both proteins. Phosphorylation of BimL by Pak1 prevents it from interacting with and inactivation of Bcl-2, an antiapoptotic protein. Overexpression of DLC1 but not DLC1-Ser88Ala mutant promotes cancerous properties of breast cancer cells. DLC1 protein level is elevated in more than 90% of human breast tumors. The regulation of cell survival functions by Pak1-DLC1 interaction represents a novel mechanism by which a signaling kinase might regulate the cancerous phenotypes.\n" ], "offsets": [ [ 0, 907 ] ] } ]	[ { "id": "PMID-15193260_T1", "type": "Gene_or_gene_product", "text": [ "Dynein light chain 1" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "PMID-15193260_T2", "type": "Gene_or_gene_product", "text": [ "p21-activated kinase 1" ], "offsets": [ [ 24, 46 ] ], "normalized": [] }, { "id": "PMID-15193260_T3", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 79, 88 ] ], "normalized": [] }, { "id": "PMID-15193260_T4", "type": "Gene_or_gene_product", "text": [ "dynein light chain 1" ], "offsets": [ [ 116, 136 ] ], "normalized": [] }, { "id": "PMID-15193260_T5", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 138, 142 ] ], "normalized": [] }, { "id": "PMID-15193260_T6", "type": "Gene_or_gene_product", "text": [ "p21-activated kinase 1" ], "offsets": [ [ 174, 196 ] ], "normalized": [] }, { "id": "PMID-15193260_T7", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 198, 202 ] ], "normalized": [] }, { "id": "PMID-15193260_T8", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 205, 209 ] ], "normalized": [] }, { "id": "PMID-15193260_T9", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 210, 214 ] ], "normalized": [] }, { "id": "PMID-15193260_T10", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 254, 258 ] ], "normalized": [] }, { "id": "PMID-15193260_T11", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 286, 290 ] ], "normalized": [] }, { "id": "PMID-15193260_T12", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 312, 316 ] ], "normalized": [] }, { "id": "PMID-15193260_T13", "type": "Amino_acid", "text": [ "Ser88" ], "offsets": [ [ 320, 325 ] ], "normalized": [] }, { "id": "PMID-15193260_T14", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 327, 331 ] ], "normalized": [] }, { "id": "PMID-15193260_T15", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 363, 367 ] ], "normalized": [] }, { "id": "PMID-15193260_T16", "type": "Gene_or_gene_product", "text": [ "BimL" ], "offsets": [ [ 372, 376 ] ], "normalized": [] }, { "id": "PMID-15193260_T17", "type": "Gene_or_gene_product", "text": [ "BimL" ], "offsets": [ [ 464, 468 ] ], "normalized": [] }, { "id": "PMID-15193260_T18", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 472, 476 ] ], "normalized": [] }, { "id": "PMID-15193260_T19", "type": "Gene_or_gene_product", "text": [ "Bcl-2" ], "offsets": [ [ 531, 536 ] ], "normalized": [] }, { "id": "PMID-15193260_T20", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 582, 586 ] ], "normalized": [] }, { "id": "PMID-15193260_T21", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 595, 599 ] ], "normalized": [] }, { "id": "PMID-15193260_T22", "type": "Amino_acid", "text": [ "Ser88" ], "offsets": [ [ 600, 605 ] ], "normalized": [] }, { "id": "PMID-15193260_T23", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 625, 634 ] ], "normalized": [] }, { "id": "PMID-15193260_T24", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 649, 668 ] ], "normalized": [] }, { "id": "PMID-15193260_T25", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "PMID-15193260_T26", "type": "Organism", "text": [ "human" ], "offsets": [ [ 721, 726 ] ], "normalized": [] }, { "id": "PMID-15193260_T27", "type": "Cancer", "text": [ "breast tumors" ], "offsets": [ [ 727, 740 ] ], "normalized": [] }, { "id": "PMID-15193260_T28", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 760, 764 ] ], "normalized": [] }, { "id": "PMID-15193260_T29", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 787, 791 ] ], "normalized": [] }, { "id": "PMID-15193260_T30", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 792, 796 ] ], "normalized": [] }, { "id": "PMID-15193260_T31", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 885, 894 ] ], "normalized": [] } ]	[ { "id": "PMID-15193260_E1", "type": "Binding", "trigger": { "text": [ "interacting" ], "offsets": [ [ 47, 58 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T2" }, { "role": "Theme", "ref_id": "PMID-15193260_T1" } ] }, { "id": "PMID-15193260_E2", "type": "Positive_regulation", "trigger": { "text": [ "promotes" ], "offsets": [ [ 70, 78 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15193260_T1" }, { "role": "Theme", "ref_id": "PMID-15193260_T3" } ] }, { "id": "PMID-15193260_E3", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 215, 226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T9" }, { "role": "Theme", "ref_id": "PMID-15193260_T8" } ] }, { "id": "PMID-15193260_E4", "type": "Regulation", "trigger": { "text": [ "plays an essential role" ], "offsets": [ [ 227, 250 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15193260_E3" }, { "role": "Theme", "ref_id": "PMID-15193260_E5" } ] }, { "id": "PMID-15193260_E5", "type": "Death", "trigger": { "text": [ "survival" ], "offsets": [ [ 259, 267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T10" } ] }, { "id": "PMID-15193260_E6", "type": "Positive_regulation", "trigger": { "text": [ "depends" ], "offsets": [ [ 275, 282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E5" }, { "role": "Cause", "ref_id": "PMID-15193260_E7" } ] }, { "id": "PMID-15193260_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 293, 308 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T12" }, { "role": "Site", "ref_id": "PMID-15193260_T13" } ] }, { "id": "PMID-15193260_E8", "type": "Positive_regulation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 293, 308 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15193260_T11" }, { "role": "Theme", "ref_id": "PMID-15193260_E7" } ] }, { "id": "PMID-15193260_E9", "type": "Binding", "trigger": { "text": [ "associates" ], "offsets": [ [ 332, 342 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T14" }, { "role": "Theme", "ref_id": "PMID-15193260_T15" }, { "role": "Theme", "ref_id": "PMID-15193260_T16" } ] }, { "id": "PMID-15193260_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 415, 429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T15" } ] }, { "id": "PMID-15193260_E11", "type": "Positive_regulation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 415, 429 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15193260_T14" }, { "role": "Theme", "ref_id": "PMID-15193260_E10" } ] }, { "id": "PMID-15193260_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 415, 429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T16" } ] }, { "id": "PMID-15193260_E13", "type": "Positive_regulation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 415, 429 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15193260_T14" }, { "role": "Theme", "ref_id": "PMID-15193260_E12" } ] }, { "id": "PMID-15193260_E14", "type": "Positive_regulation", "trigger": { "text": [ "Phosphorylation" ], "offsets": [ [ 445, 460 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T17" } ] }, { "id": "PMID-15193260_E15", "type": "Positive_regulation", "trigger": { "text": [ "Phosphorylation" ], "offsets": [ [ 445, 460 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T18" } ] }, { "id": "PMID-15193260_E16", "type": "Negative_regulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 477, 485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E20" }, { "role": "Cause", "ref_id": "PMID-15193260_E14" } ] }, { "id": "PMID-15193260_E17", "type": "Negative_regulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 477, 485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E21" }, { "role": "Cause", "ref_id": "PMID-15193260_E14" } ] }, { "id": "PMID-15193260_E18", "type": "Negative_regulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 477, 485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E21" }, { "role": "Cause", "ref_id": "PMID-15193260_E15" } ] }, { "id": "PMID-15193260_E19", "type": "Negative_regulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 477, 485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E20" }, { "role": "Cause", "ref_id": "PMID-15193260_E15" } ] }, { "id": "PMID-15193260_E20", "type": "Binding", "trigger": { "text": [ "interacting" ], "offsets": [ [ 494, 505 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T19" }, { "role": "Theme", "ref_id": "PMID-15193260_T18" }, { "role": "Theme", "ref_id": "PMID-15193260_T17" } ] }, { "id": "PMID-15193260_E21", "type": "Negative_regulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 515, 527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T19" } ] }, { "id": "PMID-15193260_E22", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 564, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T20" } ] }, { "id": "PMID-15193260_E23", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 564, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T21" } ] }, { "id": "PMID-15193260_E24", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 564, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E23" } ] }, { "id": "PMID-15193260_E25", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 564, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E22" } ] }, { "id": "PMID-15193260_E26", "type": "Positive_regulation", "trigger": { "text": [ "promotes" ], "offsets": [ [ 616, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T23" }, { "role": "Cause", "ref_id": "PMID-15193260_E22" } ] }, { "id": "PMID-15193260_E27", "type": "Positive_regulation", "trigger": { "text": [ "promotes" ], "offsets": [ [ 616, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T23" }, { "role": "Cause", "ref_id": "PMID-15193260_E23" } ] }, { "id": "PMID-15193260_E28", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 692, 700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T25" } ] }, { "id": "PMID-15193260_E29", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 746, 756 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E30" }, { "role": "Cause", "ref_id": "PMID-15193260_E31" } ] }, { "id": "PMID-15193260_E30", "type": "Death", "trigger": { "text": [ "survival" ], "offsets": [ [ 765, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T28" } ] }, { "id": "PMID-15193260_E31", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 797, 808 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T30" }, { "role": "Theme", "ref_id": "PMID-15193260_T29" } ] }, { "id": "PMID-15193260_E32", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 872, 880 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T31" } ] } ]	[ { "id": "PMID-15193260_1", "entity_ids": [ "PMID-15193260_T4", "PMID-15193260_T5" ] }, { "id": "PMID-15193260_2", "entity_ids": [ "PMID-15193260_T6", "PMID-15193260_T7" ] } ]	[]
1	PMID-10913166	[ { "id": "PMID-10913166__text", "type": "abstract", "text": [ "TEL, a putative tumor suppressor, modulates cell growth and cell morphology of ras-transformed cells while repressing the transcription of stromelysin-1. \nTEL is a member of the ETS family of transcription factors that interacts with the mSin3 and SMRT corepressors to regulate transcription. TEL is biallelically disrupted in acute leukemia, and loss of heterozygosity at the TEL locus has been observed in various cancers. Here we show that expression of TEL in Ras-transformed NIH 3T3 cells inhibits cell growth in soft agar and in normal cultures. Unexpectedly, cells expressing both Ras and TEL grew as aggregates. To begin to explain the morphology of Ras-plus TEL-expressing cells, we demonstrated that the endogenous matrix metalloproteinase stromelysin-1 was repressed by TEL. TEL bound sequences in the stromelysin-1 promoter and repressed the promoter in transient-expression assays, suggesting that it is a direct target for TEL-mediated regulation. Mutants of TEL that removed a binding site for the mSin3A corepressor but retained the ETS domain failed to repress stromelysin-1. When BB-94, a matrix metalloproteinase inhibitor, was added to the culture medium of Ras-expressing cells, it caused a cell aggregation phenotype similar to that caused by TEL expression. In addition, TEL inhibited the invasiveness of Ras-transformed cells in vitro and in vivo. Our results suggest that TEL acts as a tumor suppressor, in part, by transcriptional repression of stromelysin-1.\n" ], "offsets": [ [ 0, 1486 ] ] } ]	[ { "id": "PMID-10913166_T1", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-10913166_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 16, 21 ] ], "normalized": [] }, { "id": "PMID-10913166_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 44, 48 ] ], "normalized": [] }, { "id": "PMID-10913166_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 60, 64 ] ], "normalized": [] }, { "id": "PMID-10913166_T5", "type": "Gene_or_gene_product", "text": [ "ras" ], "offsets": [ [ 79, 82 ] ], "normalized": [] }, { "id": "PMID-10913166_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 95, 100 ] ], "normalized": [] }, { "id": "PMID-10913166_T7", "type": "Gene_or_gene_product", "text": [ "stromelysin-1" ], "offsets": [ [ 139, 152 ] ], "normalized": [] }, { "id": "PMID-10913166_T8", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 155, 158 ] ], "normalized": [] }, { "id": "PMID-10913166_T9", "type": "Gene_or_gene_product", "text": [ "ETS" ], "offsets": [ [ 178, 181 ] ], "normalized": [] }, { "id": "PMID-10913166_T10", "type": "Gene_or_gene_product", "text": [ "mSin3" ], "offsets": [ [ 238, 243 ] ], "normalized": [] }, { "id": "PMID-10913166_T11", "type": "Gene_or_gene_product", "text": [ "SMRT" ], "offsets": [ [ 248, 252 ] ], "normalized": [] }, { "id": "PMID-10913166_T12", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 293, 296 ] ], "normalized": [] }, { "id": "PMID-10913166_T13", "type": "Cancer", "text": [ "acute leukemia" ], "offsets": [ [ 327, 341 ] ], "normalized": [] }, { "id": "PMID-10913166_T14", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "PMID-10913166_T15", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 416, 423 ] ], "normalized": [] }, { "id": "PMID-10913166_T16", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 457, 460 ] ], "normalized": [] }, { "id": "PMID-10913166_T17", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 464, 467 ] ], "normalized": [] }, { "id": "PMID-10913166_T18", "type": "Cell", "text": [ "NIH 3T3 cells" ], "offsets": [ [ 480, 493 ] ], "normalized": [] }, { "id": "PMID-10913166_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 503, 507 ] ], "normalized": [] }, { "id": "PMID-10913166_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 566, 571 ] ], "normalized": [] }, { "id": "PMID-10913166_T21", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 588, 591 ] ], "normalized": [] }, { "id": "PMID-10913166_T22", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 596, 599 ] ], "normalized": [] }, { "id": "PMID-10913166_T23", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 658, 661 ] ], "normalized": [] }, { "id": "PMID-10913166_T24", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 667, 670 ] ], "normalized": [] }, { "id": "PMID-10913166_T25", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-10913166_T26", "type": "Gene_or_gene_product", "text": [ "matrix metalloproteinase stromelysin-1" ], "offsets": [ [ 725, 763 ] ], "normalized": [] }, { "id": "PMID-10913166_T27", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 781, 784 ] ], "normalized": [] }, { "id": "PMID-10913166_T28", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 786, 789 ] ], "normalized": [] }, { "id": "PMID-10913166_T29", "type": "Gene_or_gene_product", "text": [ "stromelysin-1" ], "offsets": [ [ 813, 826 ] ], "normalized": [] }, { "id": "PMID-10913166_T30", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 937, 940 ] ], "normalized": [] }, { "id": "PMID-10913166_T31", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 973, 976 ] ], "normalized": [] }, { "id": "PMID-10913166_T32", "type": "Gene_or_gene_product", "text": [ "mSin3A" ], "offsets": [ [ 1013, 1019 ] ], "normalized": [] }, { "id": "PMID-10913166_T33", "type": "Gene_or_gene_product", "text": [ "stromelysin-1" ], "offsets": [ [ 1078, 1091 ] ], "normalized": [] }, { "id": "PMID-10913166_T34", "type": "Simple_chemical", "text": [ "BB-94" ], "offsets": [ [ 1098, 1103 ] ], "normalized": [] }, { "id": "PMID-10913166_T35", "type": "Gene_or_gene_product", "text": [ "matrix metalloproteinase" ], "offsets": [ [ 1107, 1131 ] ], "normalized": [] }, { "id": "PMID-10913166_T36", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 1178, 1181 ] ], "normalized": [] }, { "id": "PMID-10913166_T37", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [] }, { "id": "PMID-10913166_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1212, 1216 ] ], "normalized": [] }, { "id": "PMID-10913166_T39", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 1265, 1268 ] ], "normalized": [] }, { "id": "PMID-10913166_T40", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 1294, 1297 ] ], "normalized": [] }, { "id": "PMID-10913166_T41", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 1328, 1331 ] ], "normalized": [] }, { "id": "PMID-10913166_T42", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1344, 1349 ] ], "normalized": [] }, { "id": "PMID-10913166_T43", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 1397, 1400 ] ], "normalized": [] }, { "id": "PMID-10913166_T44", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1411, 1416 ] ], "normalized": [] }, { "id": "PMID-10913166_T45", "type": "Gene_or_gene_product", "text": [ "stromelysin-1" ], "offsets": [ [ 1471, 1484 ] ], "normalized": [] }, { "id": "PMID-10913166_T63", "type": "DNA_domain_or_region", "text": [ "promoter" ], "offsets": [ [ 827, 835 ] ], "normalized": [] } ]	[ { "id": "PMID-10913166_E1", "type": "Regulation", "trigger": { "text": [ "modulates" ], "offsets": [ [ 34, 43 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_T1" }, { "role": "Theme", "ref_id": "PMID-10913166_E2" } ] }, { "id": "PMID-10913166_E2", "type": "Cell_proliferation", "trigger": { "text": [ "growth" ], "offsets": [ [ 49, 55 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T3" } ] }, { "id": "PMID-10913166_E3", "type": "Planned_process", "trigger": { "text": [ "transformed" ], "offsets": [ [ 83, 94 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10913166_T5" }, { "role": "Theme", "ref_id": "PMID-10913166_T6" } ] }, { "id": "PMID-10913166_E4", "type": "Negative_regulation", "trigger": { "text": [ "repressing" ], "offsets": [ [ 107, 117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_E5" }, { "role": "Cause", "ref_id": "PMID-10913166_T1" } ] }, { "id": "PMID-10913166_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 122, 135 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T7" } ] }, { "id": "PMID-10913166_E6", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 219, 228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T10" }, { "role": "Theme", "ref_id": "PMID-10913166_T11" }, { "role": "Theme", "ref_id": "PMID-10913166_T8" } ] }, { "id": "PMID-10913166_E7", "type": "Mutation", "trigger": { "text": [ "disrupted" ], "offsets": [ [ 314, 323 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T12" }, { "role": "AtLoc", "ref_id": "PMID-10913166_T13" } ] }, { "id": "PMID-10913166_E8", "type": "Mutation", "trigger": { "text": [ "loss of heterozygosity" ], "offsets": [ [ 347, 369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T14" }, { "role": "AtLoc", "ref_id": "PMID-10913166_T15" } ] }, { "id": "PMID-10913166_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 443, 453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T16" } ] }, { "id": "PMID-10913166_E10", "type": "Planned_process", "trigger": { "text": [ "transformed" ], "offsets": [ [ 468, 479 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10913166_T17" }, { "role": "Theme", "ref_id": "PMID-10913166_T18" } ] }, { "id": "PMID-10913166_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 494, 502 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_E9" }, { "role": "Theme", "ref_id": "PMID-10913166_E12" } ] }, { "id": "PMID-10913166_E12", "type": "Cell_proliferation", "trigger": { "text": [ "growth" ], "offsets": [ [ 508, 514 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T19" } ] }, { "id": "PMID-10913166_E13", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 572, 582 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T21" }, { "role": "Theme", "ref_id": "PMID-10913166_T22" } ] }, { "id": "PMID-10913166_E14", "type": "Growth", "trigger": { "text": [ "grew" ], "offsets": [ [ 600, 604 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T20" } ] }, { "id": "PMID-10913166_E15", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 671, 681 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T24" }, { "role": "Theme", "ref_id": "PMID-10913166_T23" } ] }, { "id": "PMID-10913166_E16", "type": "Negative_regulation", "trigger": { "text": [ "repressed" ], "offsets": [ [ 768, 777 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T26" }, { "role": "Cause", "ref_id": "PMID-10913166_T27" } ] }, { "id": "PMID-10913166_E17", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 790, 795 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T29" }, { "role": "Theme", "ref_id": "PMID-10913166_T28" }, { "role": "Site", "ref_id": "PMID-10913166_T63" } ] }, { "id": "PMID-10913166_E18", "type": "Negative_regulation", "trigger": { "text": [ "repressed" ], "offsets": [ [ 840, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_E19" }, { "role": "Cause", "ref_id": "PMID-10913166_T28" } ] }, { "id": "PMID-10913166_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 876, 886 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T29" } ] }, { "id": "PMID-10913166_E20", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 992, 999 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T31" } ] }, { "id": "PMID-10913166_E21", "type": "Negative_regulation", "trigger": { "text": [ "repress" ], "offsets": [ [ 1070, 1077 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T33" } ] }, { "id": "PMID-10913166_E22", "type": "Planned_process", "trigger": { "text": [ "added" ], "offsets": [ [ 1147, 1152 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10913166_T34" }, { "role": "Theme", "ref_id": "PMID-10913166_T37" } ] }, { "id": "PMID-10913166_E23", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1182, 1192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T36" } ] }, { "id": "PMID-10913166_E24", "type": "Positive_regulation", "trigger": { "text": [ "caused" ], "offsets": [ [ 1203, 1209 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_T34" }, { "role": "Theme", "ref_id": "PMID-10913166_E25" } ] }, { "id": "PMID-10913166_E25", "type": "Binding", "trigger": { "text": [ "aggregation" ], "offsets": [ [ 1217, 1228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T38" } ] }, { "id": "PMID-10913166_E26", "type": "Positive_regulation", "trigger": { "text": [ "caused" ], "offsets": [ [ 1255, 1261 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_E27" }, { "role": "Theme", "ref_id": "PMID-10913166_E25" } ] }, { "id": "PMID-10913166_E27", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1269, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T39" } ] }, { "id": "PMID-10913166_E28", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1298, 1307 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_T40" }, { "role": "Theme", "ref_id": "PMID-10913166_T42" } ] }, { "id": "PMID-10913166_E29", "type": "Planned_process", "trigger": { "text": [ "transformed" ], "offsets": [ [ 1332, 1343 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10913166_T41" }, { "role": "Theme", "ref_id": "PMID-10913166_T42" } ] }, { "id": "PMID-10913166_E30", "type": "Negative_regulation", "trigger": { "text": [ "suppressor" ], "offsets": [ [ 1417, 1427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T44" }, { "role": "Cause", "ref_id": "PMID-10913166_E32" } ] }, { "id": "PMID-10913166_E31", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 1441, 1456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T45" } ] }, { "id": "PMID-10913166_E32", "type": "Negative_regulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 1457, 1467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_E31" }, { "role": "Cause", "ref_id": "PMID-10913166_T43" } ] } ]	[]	[]
2	PMID-12484699	[ { "id": "PMID-12484699__text", "type": "abstract", "text": [ "Regulation of transforming growth factor-beta signaling and vascular diseases.\nPURPOSE: Members of the transforming growth factor (TGF)-beta superfamily play critical roles in regulation of various cellular functions. Dysregulation of the signaling mechanisms of the TGF-beta superfamily proteins is associated with clinical diseases such as cancer, fibrotic diseases, and vascular disorders. Therefore, understanding these signaling mechanisms may provide us with novel ways to develop strategies for treating clinical diseases induced by these cytokines. METHODS: This review discusses our current understanding of the mechanisms of TGF-beta signaling, focusing on the roles of TGF-beta in regulation of vascular wall cells and on the regulation of TGF-beta superfamily signals by inhibitory Smads.\n" ], "offsets": [ [ 0, 801 ] ] } ]	[ { "id": "PMID-12484699_T1", "type": "Gene_or_gene_product", "text": [ "transforming growth factor-beta" ], "offsets": [ [ 14, 45 ] ], "normalized": [] }, { "id": "PMID-12484699_T2", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 60, 68 ] ], "normalized": [] }, { "id": "PMID-12484699_T3", "type": "Gene_or_gene_product", "text": [ "transforming growth factor (TGF)-beta" ], "offsets": [ [ 103, 140 ] ], "normalized": [] }, { "id": "PMID-12484699_T4", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 198, 206 ] ], "normalized": [] }, { "id": "PMID-12484699_T5", "type": "Gene_or_gene_product", "text": [ "TGF-beta" ], "offsets": [ [ 267, 275 ] ], "normalized": [] }, { "id": "PMID-12484699_T6", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 342, 348 ] ], "normalized": [] }, { "id": "PMID-12484699_T7", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 373, 381 ] ], "normalized": [] }, { "id": "PMID-12484699_T8", "type": "Gene_or_gene_product", "text": [ "TGF-beta" ], "offsets": [ [ 635, 643 ] ], "normalized": [] }, { "id": "PMID-12484699_T9", "type": "Gene_or_gene_product", "text": [ "TGF-beta" ], "offsets": [ [ 680, 688 ] ], "normalized": [] }, { "id": "PMID-12484699_T10", "type": "Cell", "text": [ "vascular wall cells" ], "offsets": [ [ 706, 725 ] ], "normalized": [] }, { "id": "PMID-12484699_T11", "type": "Gene_or_gene_product", "text": [ "TGF-beta" ], "offsets": [ [ 751, 759 ] ], "normalized": [] }, { "id": "PMID-12484699_T12", "type": "Gene_or_gene_product", "text": [ "Smads" ], "offsets": [ [ 794, 799 ] ], "normalized": [] } ]	[ { "id": "PMID-12484699_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_E2" } ] }, { "id": "PMID-12484699_E2", "type": "Pathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 46, 55 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-12484699_T1" } ] }, { "id": "PMID-12484699_E3", "type": "Regulation", "trigger": { "text": [ "Dysregulation" ], "offsets": [ [ 218, 231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T5" } ] }, { "id": "PMID-12484699_E4", "type": "Pathway", "trigger": { "text": [ "signaling mechanisms" ], "offsets": [ [ 239, 259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T5" } ] }, { "id": "PMID-12484699_E5", "type": "Regulation", "trigger": { "text": [ "associated" ], "offsets": [ [ 300, 310 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T6" }, { "role": "Cause", "ref_id": "PMID-12484699_E3" } ] }, { "id": "PMID-12484699_E6", "type": "Pathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 644, 653 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-12484699_T8" } ] }, { "id": "PMID-12484699_E7", "type": "Regulation", "trigger": { "text": [ "roles" ], "offsets": [ [ 671, 676 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12484699_T9" }, { "role": "Theme", "ref_id": "PMID-12484699_E8" } ] }, { "id": "PMID-12484699_E8", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 692, 702 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T10" } ] }, { "id": "PMID-12484699_E9", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 737, 747 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T11" }, { "role": "Cause", "ref_id": "PMID-12484699_E10" } ] }, { "id": "PMID-12484699_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibitory" ], "offsets": [ [ 783, 793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T12" } ] } ]	[]	[]
3	PMID-16268479	[ { "id": "PMID-16268479__text", "type": "abstract", "text": [ "Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt.\nDomain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the P13-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response toVEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3alpha HKa and D5 inhibit phosphorylation of Akt and GSK-3alpha after stimulation withVEGF and S1P. Inhibitors of Akt and P13-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters P13-kinase-Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.\n" ], "offsets": [ [ 0, 1758 ] ] } ]	[ { "id": "PMID-16268479_T1", "type": "Gene_or_gene_product", "text": [ "high molecular weight kininogen" ], "offsets": [ [ 20, 51 ] ], "normalized": [] }, { "id": "PMID-16268479_T2", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 61, 77 ] ], "normalized": [] }, { "id": "PMID-16268479_T3", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 96, 99 ] ], "normalized": [] }, { "id": "PMID-16268479_T4", "type": "Gene_or_gene_product", "text": [ "high molecular weight kininogen" ], "offsets": [ [ 126, 157 ] ], "normalized": [] }, { "id": "PMID-16268479_T5", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 159, 162 ] ], "normalized": [] }, { "id": "PMID-16268479_T6", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 198, 214 ] ], "normalized": [] }, { "id": "PMID-16268479_T7", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 243, 247 ] ], "normalized": [] }, { "id": "PMID-16268479_T8", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 279, 282 ] ], "normalized": [] }, { "id": "PMID-16268479_T9", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 304, 320 ] ], "normalized": [] }, { "id": "PMID-16268479_T10", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 397, 400 ] ], "normalized": [] }, { "id": "PMID-16268479_T11", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 448, 464 ] ], "normalized": [] }, { "id": "PMID-16268479_T12", "type": "Gene_or_gene_product", "text": [ "sphingosine 1-phosphate" ], "offsets": [ [ 476, 499 ] ], "normalized": [] }, { "id": "PMID-16268479_T13", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 501, 504 ] ], "normalized": [] }, { "id": "PMID-16268479_T14", "type": "Gene_or_gene_product", "text": [ "vascular endothelial growth factor" ], "offsets": [ [ 510, 544 ] ], "normalized": [] }, { "id": "PMID-16268479_T15", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 546, 550 ] ], "normalized": [] }, { "id": "PMID-16268479_T16", "type": "Gene_or_gene_product", "text": [ "P13-kinase" ], "offsets": [ [ 574, 584 ] ], "normalized": [] }, { "id": "PMID-16268479_T17", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 585, 588 ] ], "normalized": [] }, { "id": "PMID-16268479_T18", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 608, 611 ] ], "normalized": [] }, { "id": "PMID-16268479_T19", "type": "Organism", "text": [ "bovine" ], "offsets": [ [ 627, 633 ] ], "normalized": [] }, { "id": "PMID-16268479_T20", "type": "Cell", "text": [ "pulmonary artery endothelial cell" ], "offsets": [ [ 634, 667 ] ], "normalized": [] }, { "id": "PMID-16268479_T21", "type": "Cell", "text": [ "BPAE" ], "offsets": [ [ 669, 673 ] ], "normalized": [] }, { "id": "PMID-16268479_T22", "type": "Cell", "text": [ "human umbilical vein endothelial cell" ], "offsets": [ [ 678, 715 ] ], "normalized": [] }, { "id": "PMID-16268479_T23", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-16268479_T24", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 780, 783 ] ], "normalized": [] }, { "id": "PMID-16268479_T25", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 816, 819 ] ], "normalized": [] }, { "id": "PMID-16268479_T26", "type": "Gene_or_gene_product", "text": [ "urokinase-type plasminogen activator receptor" ], "offsets": [ [ 849, 894 ] ], "normalized": [] }, { "id": "PMID-16268479_T27", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 901, 904 ] ], "normalized": [] }, { "id": "PMID-16268479_T28", "type": "Cell", "text": [ "BPAE cell" ], "offsets": [ [ 934, 943 ] ], "normalized": [] }, { "id": "PMID-16268479_T29", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 1033, 1036 ] ], "normalized": [] }, { "id": "PMID-16268479_T30", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 1040, 1044 ] ], "normalized": [] }, { "id": "PMID-16268479_T31", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 1046, 1049 ] ], "normalized": [] }, { "id": "PMID-16268479_T32", "type": "Gene_or_gene_product", "text": [ "paxillin" ], "offsets": [ [ 1084, 1092 ] ], "normalized": [] }, { "id": "PMID-16268479_T33", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 1100, 1115 ] ], "normalized": [] }, { "id": "PMID-16268479_T34", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 1122, 1125 ] ], "normalized": [] }, { "id": "PMID-16268479_T35", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "PMID-16268479_T36", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], 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"text": [ "stimulation" ], "offsets": [ [ 1561, 1572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_T28" }, { "role": "Cause", "ref_id": "PMID-16268479_T51" } ] }, { "id": "PMID-16268479_E56", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1561, 1572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_T28" }, { "role": "Cause", "ref_id": "PMID-16268479_T52" } ] }, { "id": "PMID-16268479_E57", "type": "Regulation", "trigger": { "text": [ "alters" ], "offsets": [ [ 1644, 1650 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-16268479_T53" }, { "role": "Theme", "ref_id": "PMID-16268479_E58" }, { "role": "CSite", "ref_id": "PMID-16268479_T106" } ] }, { "id": "PMID-16268479_E58", "type": "Pathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 1666, 1675 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-16268479_T54" }, { "role": "Participant", "ref_id": "PMID-16268479_T55" } ] }, { "id": "PMID-16268479_E59", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1679, 1686 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_E60" }, { "role": "Cause", "ref_id": "PMID-16268479_E57" } ] }, { "id": "PMID-16268479_E60", "type": "Localization", "trigger": { "text": [ "migration" ], "offsets": [ [ 1704, 1713 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_T56" } ] }, { "id": "PMID-16268479_E61", "type": "Regulation", "trigger": { "text": [ "alterations" ], "offsets": [ [ 1722, 1733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_T57" } ] } ]	[ { "id": "PMID-16268479_1", "entity_ids": [ "PMID-16268479_T4", "PMID-16268479_T5" ] }, { "id": "PMID-16268479_2", "entity_ids": [ "PMID-16268479_T12", "PMID-16268479_T13" ] }, { "id": "PMID-16268479_3", "entity_ids": [ "PMID-16268479_T14", "PMID-16268479_T15" ] }, { "id": "PMID-16268479_4", "entity_ids": [ "PMID-16268479_T20", "PMID-16268479_T21" ] }, { "id": "PMID-16268479_5", "entity_ids": [ "PMID-16268479_T64", "PMID-16268479_T63" ] } ]	[]
4	PMID-11121230	[ { "id": "PMID-11121230__text", "type": "abstract", "text": [ "RNA damage and inhibition of neoplastic endothelial cell growth: effects of human and amphibian ribonucleases.\nAngiogenesis defines the many steps involved in the growth and migration of endothelial cell-derived blood vessels. This process is necessary for the growth and metastasis of tumors, and considerable effort is being expended to find inhibitors of tumor angiogenesis. This usually involves screening of potential anti-angiogenic compounds on endothelial cells. To this end, two candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, were screened for their effects on endothelial cell proliferation using three distinct types of endothelial cells in culture: HPV-16 E6/E7-immortalized human umbilical vein endothelial cells (HUVECs), a Kras-transformed HPV-16 E6/E7 HUVEC (Rhim et al., Carcinogenesis 4, 673-681, 1998), and primary HUVECs. Onconase similarly inhibited proliferation in all three cell lines (IC(50) = 0.3-1.0 microM) while (-4)rhEDN was more effective on immortalized HUVEC cell lines (IC(50) = 0.02-0.06 microM) than on primary HUVECs (IC(50) > 0.1 microM). Differential sensitivity to these agents implies that more than one endothelial cell type must be used in proliferation assays to screen for novel anti-angiogenic compounds.\n" ], "offsets": [ [ 0, 1275 ] ] } ]	[ { "id": "PMID-11121230_T1", "type": "Cell", "text": [ "neoplastic endothelial cell" ], "offsets": [ [ 29, 56 ] ], "normalized": [] }, { "id": "PMID-11121230_T2", "type": "Organism", "text": [ "human" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "PMID-11121230_T3", "type": "Gene_or_gene_product", "text": [ "ribonucleases" ], "offsets": [ [ 96, 109 ] ], "normalized": [] }, { "id": "PMID-11121230_T4", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 187, 203 ] ], "normalized": [] }, { "id": "PMID-11121230_T5", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 212, 225 ] ], "normalized": [] }, { "id": "PMID-11121230_T6", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 286, 292 ] ], "normalized": [] }, { "id": "PMID-11121230_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 358, 363 ] ], "normalized": [] }, { "id": "PMID-11121230_T8", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 452, 469 ] ], "normalized": [] }, { "id": "PMID-11121230_T9", "type": "Simple_chemical", "text": [ "onconase" ], "offsets": [ [ 535, 543 ] ], "normalized": [] }, { "id": "PMID-11121230_T10", "type": "Simple_chemical", "text": [ "(-4)rhEDN" ], "offsets": [ [ 548, 557 ] ], "normalized": [] }, { "id": "PMID-11121230_T11", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 594, 610 ] ], "normalized": [] }, { "id": "PMID-11121230_T12", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 655, 672 ] ], "normalized": [] }, { "id": "PMID-11121230_T13", "type": "Organism", "text": [ "HPV-16 E6" ], "offsets": [ [ 685, 694 ] ], "normalized": [] }, { "id": "PMID-11121230_T14", "type": "Organism", "text": [ "E7" ], "offsets": [ [ 695, 697 ] ], "normalized": [] }, { "id": "PMID-11121230_T15", "type": "Cell", "text": [ "human umbilical vein endothelial cells" ], "offsets": [ [ 711, 749 ] ], "normalized": [] }, { "id": "PMID-11121230_T16", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 751, 757 ] ], "normalized": [] }, { "id": "PMID-11121230_T17", "type": "Gene_or_gene_product", "text": [ "Kras" ], "offsets": [ [ 762, 766 ] ], "normalized": [] }, { "id": "PMID-11121230_T18", "type": "Organism", "text": [ "HPV-16 E6" ], "offsets": [ [ 779, 788 ] ], "normalized": [] }, { "id": "PMID-11121230_T19", "type": "Organism", "text": [ "E7" ], "offsets": [ [ 789, 791 ] ], "normalized": [] }, { "id": "PMID-11121230_T20", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 792, 797 ] ], "normalized": [] }, { "id": "PMID-11121230_T21", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 858, 864 ] ], "normalized": [] }, { "id": "PMID-11121230_T22", "type": "Simple_chemical", "text": [ "Onconase" ], "offsets": [ [ 866, 874 ] ], "normalized": [] }, { "id": "PMID-11121230_T23", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 922, 932 ] ], "normalized": [] }, { "id": "PMID-11121230_T24", "type": "Simple_chemical", "text": [ "(-4)rhEDN" ], "offsets": [ [ 965, 974 ] ], "normalized": [] }, { "id": "PMID-11121230_T25", "type": "Cell", "text": [ "HUVEC cell lines" ], "offsets": [ [ 1010, 1026 ] ], "normalized": [] }, { "id": "PMID-11121230_T26", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 1071, 1077 ] ], "normalized": [] }, { "id": "PMID-11121230_T27", "type": "Cell", "text": [ "endothelial cell type" ], "offsets": [ [ 1169, 1190 ] ], "normalized": [] } ]	[ { "id": "PMID-11121230_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 15, 25 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_E2" } ] }, { "id": "PMID-11121230_E2", "type": "Cell_proliferation", "trigger": { "text": [ "growth" ], "offsets": [ [ 57, 63 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T1" } ] }, { "id": "PMID-11121230_E3", "type": "Blood_vessel_development", "trigger": { "text": [ "Angiogenesis" ], "offsets": [ [ 111, 123 ] ] }, "arguments": [] }, { "id": "PMID-11121230_E4", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 163, 169 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T5" } ] }, { "id": "PMID-11121230_E5", "type": "Localization", "trigger": { "text": [ "migration" ], "offsets": [ [ 174, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T5" } ] }, { "id": "PMID-11121230_E6", "type": "Development", "trigger": { "text": [ "derived" ], "offsets": [ [ 204, 211 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T5" } ] }, { "id": "PMID-11121230_E7", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 243, 252 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_E3" }, { "role": "Theme", "ref_id": "PMID-11121230_E9" } ] }, { "id": "PMID-11121230_E8", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 243, 252 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_E3" }, { "role": "Theme", "ref_id": "PMID-11121230_E10" } ] }, { "id": "PMID-11121230_E9", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 261, 267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T6" } ] }, { "id": "PMID-11121230_E10", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 272, 282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T6" } ] }, { "id": "PMID-11121230_E11", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 364, 376 ] ] }, "arguments": [ { "role": "AtLoc", "ref_id": "PMID-11121230_T7" } ] }, { "id": "PMID-11121230_E12", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 428, 438 ] ] }, "arguments": [] }, { "id": "PMID-11121230_E13", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 503, 513 ] ] }, "arguments": [] }, { "id": "PMID-11121230_E14", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 583, 590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_E16" }, { "role": "Cause", "ref_id": "PMID-11121230_T10" } ] }, { "id": "PMID-11121230_E15", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 583, 590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_E16" }, { "role": "Cause", "ref_id": "PMID-11121230_T9" } ] }, { "id": "PMID-11121230_E16", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 611, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T11" } ] }, { "id": "PMID-11121230_E17", "type": "Planned_process", "trigger": { "text": [ "immortalized" ], "offsets": [ [ 698, 710 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T15" }, { "role": "Instrument", "ref_id": "PMID-11121230_T14" } ] }, { "id": "PMID-11121230_E18", "type": "Planned_process", "trigger": { "text": [ "immortalized" ], "offsets": [ [ 698, 710 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T15" }, { "role": "Instrument", "ref_id": "PMID-11121230_T13" } ] }, { "id": "PMID-11121230_E19", "type": "Planned_process", "trigger": { "text": [ "transformed" ], "offsets": [ [ 767, 778 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-11121230_T17" }, { "role": "Theme", "ref_id": "PMID-11121230_T20" } ] }, { "id": "PMID-11121230_E20", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 885, 894 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_T22" }, { "role": "Theme", "ref_id": "PMID-11121230_E21" } ] }, { "id": "PMID-11121230_E21", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 895, 908 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T23" } ] }, { "id": "PMID-11121230_E22", "type": "Positive_regulation", "trigger": { "text": [ "effective" ], "offsets": [ [ 984, 993 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_T24" }, { "role": "Theme", "ref_id": "PMID-11121230_T25" } ] }, { "id": "PMID-11121230_E23", "type": "Positive_regulation", "trigger": { "text": [ "effective" ], "offsets": [ [ 984, 993 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_T24" }, { "role": "Theme", "ref_id": "PMID-11121230_T26" } ] }, { "id": "PMID-11121230_E24", "type": "Planned_process", "trigger": { "text": [ "immortalized" ], "offsets": [ [ 997, 1009 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T25" } ] }, { "id": "PMID-11121230_E25", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 1207, 1220 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T27" } ] }, { "id": "PMID-11121230_E26", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 1253, 1263 ] ] }, "arguments": [] } ]	[ { "id": "PMID-11121230_1", "entity_ids": [ "PMID-11121230_T15", "PMID-11121230_T16" ] } ]	[]
5	PMID-12610665	[ { "id": "PMID-12610665__text", "type": "abstract", "text": [ "Arteriogenesis: the development and growth of collateral arteries.\nIn patients with atherosclerotic vascular diseases, collateral vessels bypassing major arterial obstructions have frequently been observed. This may explain why some patients remain without symptoms or signs of ischemia. The term \"arteriogenesis\" was introduced to differentiate the formation of collateral arteries from angiogenesis, which mainly occurs in the ischemic, collateral flow-dependent tissue. Many observations in various animal models and humans support that the remodeling of preexisting collateral vessels is the mechanism of collateral artery formation. This remodeling process seems to be mainly flow-mediated. It involves endothelial cell activation, basal membrane degradation, leukocyte invasion, proliferation of vascular cells, neointima formation (in most species studied), and changes of the extracellular matrix. The contribution of ischemia to arteriogenesis is still unclear, but arteriogenesis clearly can occur in the absence of any significant ischemia. It is questionable, whether collateral arteries also form de novo in ischemic vascular diseases. A better understanding of the mechanisms of arteriogenesis will be important for the design of more effective strategies for the treatment of patients with ischemic vascular diseases.\n" ], "offsets": [ [ 0, 1333 ] ] } ]	[ { "id": "PMID-12610665_T1", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 46, 65 ] ], "normalized": [] }, { "id": "PMID-12610665_T2", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 70, 78 ] ], "normalized": [] }, { "id": "PMID-12610665_T3", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 100, 108 ] ], "normalized": [] }, { "id": "PMID-12610665_T4", "type": "Multi-tissue_structure", "text": [ "collateral vessels" ], "offsets": [ [ 119, 137 ] ], "normalized": [] }, { "id": "PMID-12610665_T5", "type": "Pathological_formation", "text": [ "arterial obstructions" ], "offsets": [ [ 154, 175 ] ], "normalized": [] }, { "id": "PMID-12610665_T6", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 233, 241 ] ], "normalized": [] }, { "id": "PMID-12610665_T7", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 363, 382 ] ], "normalized": [] }, { "id": "PMID-12610665_T8", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 465, 471 ] ], "normalized": [] }, { "id": "PMID-12610665_T9", "type": "Organism", "text": [ "humans" ], "offsets": [ [ 520, 526 ] ], "normalized": [] }, { "id": "PMID-12610665_T10", "type": "Multi-tissue_structure", "text": [ "collateral vessels" ], "offsets": [ [ 570, 588 ] ], "normalized": [] }, { "id": "PMID-12610665_T11", "type": "Multi-tissue_structure", "text": [ "collateral artery" ], "offsets": [ [ 609, 626 ] ], "normalized": [] }, { "id": "PMID-12610665_T12", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 708, 724 ] ], "normalized": [] }, { "id": "PMID-12610665_T13", "type": "Cellular_component", "text": [ "basal membrane" ], "offsets": [ [ 737, 751 ] ], "normalized": [] }, { "id": "PMID-12610665_T14", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 765, 774 ] ], "normalized": [] }, { "id": "PMID-12610665_T15", "type": "Cell", "text": [ "vascular cells" ], "offsets": [ [ 802, 816 ] ], "normalized": [] }, { "id": "PMID-12610665_T16", "type": "Tissue", "text": [ "neointima" ], "offsets": [ [ 818, 827 ] ], "normalized": [] }, { "id": "PMID-12610665_T17", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 884, 904 ] ], "normalized": [] }, { "id": "PMID-12610665_T18", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 1080, 1099 ] ], "normalized": [] }, { "id": "PMID-12610665_T19", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1130, 1138 ] ], "normalized": [] }, { "id": "PMID-12610665_T20", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 1291, 1299 ] ], "normalized": [] }, { "id": "PMID-12610665_T21", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1314, 1322 ] ], "normalized": [] } ]	[ { "id": "PMID-12610665_E1", "type": "Blood_vessel_development", "trigger": { "text": [ "Arteriogenesis" ], "offsets": [ [ 0, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T1" } ] }, { "id": "PMID-12610665_E2", "type": "Development", "trigger": { "text": [ "development" ], "offsets": [ [ 20, 31 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T1" } ] }, { "id": "PMID-12610665_E3", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 36, 42 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T1" } ] }, { "id": "PMID-12610665_E4", "type": "Blood_vessel_development", "trigger": { "text": [ "arteriogenesis" ], "offsets": [ [ 298, 312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T7" } ] }, { "id": "PMID-12610665_E5", "type": "Development", "trigger": { "text": [ "formation" ], "offsets": [ [ 350, 359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T7" } ] }, { "id": "PMID-12610665_E6", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 388, 400 ] ] }, "arguments": [] }, { "id": "PMID-12610665_E7", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 455, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T8" } ] }, { "id": "PMID-12610665_E8", "type": "Remodeling", "trigger": { "text": [ "remodeling" ], "offsets": [ [ 544, 554 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T10" } ] }, { "id": "PMID-12610665_E9", "type": "Development", "trigger": { "text": [ "formation" ], "offsets": [ [ 627, 636 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T11" } ] }, { "id": "PMID-12610665_E10", "type": "Remodeling", "trigger": { "text": [ "remodeling" ], "offsets": [ [ 643, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T10" } ] }, { "id": "PMID-12610665_E11", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E17" } ] }, { "id": "PMID-12610665_E12", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E18" } ] }, { "id": "PMID-12610665_E13", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E19" } ] }, { "id": "PMID-12610665_E14", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E20" } ] }, { "id": "PMID-12610665_E15", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E21" } ] }, { "id": "PMID-12610665_E16", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E22" } ] }, { "id": "PMID-12610665_E17", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 725, 735 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T12" } ] }, { "id": "PMID-12610665_E18", "type": "Breakdown", "trigger": { "text": [ "degradation" ], "offsets": [ [ 752, 763 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T13" } ] }, { "id": "PMID-12610665_E19", "type": "Localization", "trigger": { "text": [ "invasion" ], "offsets": [ [ 775, 783 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T14" } ] }, { "id": "PMID-12610665_E20", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 785, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T15" } ] }, { "id": "PMID-12610665_E21", "type": "Development", "trigger": { "text": [ "formation" ], "offsets": [ [ 828, 837 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T16" } ] }, { "id": "PMID-12610665_E22", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 869, 876 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T17" } ] }, { "id": "PMID-12610665_E23", "type": "Blood_vessel_development", "trigger": { "text": [ "arteriogenesis" ], "offsets": [ [ 938, 952 ] ] }, "arguments": [] }, { "id": "PMID-12610665_E24", "type": "Blood_vessel_development", "trigger": { "text": [ "arteriogenesis" ], "offsets": [ [ 975, 989 ] ] }, "arguments": [] }, { "id": "PMID-12610665_E25", "type": "Development", "trigger": { "text": [ "form" ], "offsets": [ [ 1105, 1109 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T18" } ] }, { "id": "PMID-12610665_E26", "type": "Blood_vessel_development", "trigger": { "text": [ "arteriogenesis" ], "offsets": [ [ 1193, 1207 ] ] }, "arguments": [] } ]	[]	[]
6	PMID-20978953	[ { "id": "PMID-20978953__text", "type": "abstract", "text": [ "Role of stromal myofibroblasts in invasive breast cancer: stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome. \nBACKGROUND: Recently, the desmoplastic reaction has been implicated as having an important function in epithelial solid tumor biology. There have been no reports showing the relativity of invasive breast cancer and the desmoplastic reaction by a quantitative analysis of the myofibroblasts that were an important player in the desmoplastic reaction. The purpose of this study was to immunohistochemically investigate the correlation between the desmoplastic reaction and the clinicopathology of invasive breast cancer. METHODS: The study included 60 patients with a known prognosis of invasive breast cancer. We quantified the expression of alpha-SMA as a marker of myofibroblasts in the invasive breast cancer. After staining samples for alpha-SMA, their expression was extracted and quantified as a relative percentage by computer-assisted image analysis. RESULTS: There was relatively wide variation in the expression of alpha-SMA with the percentage of the area from 0.68 to 28.15% (mean 8.48 +/- 5.40%). The metastasis group showed significantly higher alpha-SMA expression compared with the no metastasis group (p < 0.001). When the patients were divided into two groups according to their alpha-SMA expression using a cutoff point at the mean value of 8.48%, the high alpha-SMA group had a significantly poorer overall survival rate (p < 0.001). Multivariate analysis demonstrated that alpha-SMA and lymph node metastasis were identified as independent predictive factors of metastasis. CONCLUSION: Myofibroblasts represent an important prognostic factor for invasive growth that is translated into a poor clinical prognosis for patients with invasive breast cancer.\n" ], "offsets": [ [ 0, 1821 ] ] } ]	[ { "id": "PMID-20978953_T1", "type": "Cell", "text": [ "stromal myofibroblasts" ], "offsets": [ [ 8, 30 ] ], "normalized": [] }, { "id": "PMID-20978953_T2", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 43, 56 ] ], "normalized": [] }, { "id": "PMID-20978953_T3", "type": "Cell", "text": [ "stromal" ], "offsets": [ [ 58, 65 ] ], "normalized": [] }, { "id": "PMID-20978953_T4", "type": "Gene_or_gene_product", "text": [ "alpha-smooth muscle actin" ], "offsets": [ [ 80, 105 ] ], "normalized": [] }, { "id": "PMID-20978953_T5", "type": "Cancer", "text": [ "epithelial solid tumor" ], "offsets": [ [ 250, 272 ] ], "normalized": [] }, { "id": "PMID-20978953_T6", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 344, 357 ] ], "normalized": [] }, { "id": "PMID-20978953_T7", "type": "Cell", "text": [ "myofibroblasts" ], "offsets": [ [ 422, 436 ] ], "normalized": [] }, { "id": "PMID-20978953_T8", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 651, 664 ] ], "normalized": [] }, { "id": "PMID-20978953_T9", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 697, 705 ] ], "normalized": [] }, { "id": "PMID-20978953_T10", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 732, 754 ] ], "normalized": [] }, { "id": "PMID-20978953_T11", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 788, 797 ] ], "normalized": [] }, { "id": "PMID-20978953_T12", "type": "Cell", "text": [ "myofibroblasts" ], "offsets": [ [ 813, 827 ] ], "normalized": [] }, { "id": "PMID-20978953_T13", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 844, 857 ] ], "normalized": [] }, { "id": "PMID-20978953_T14", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 886, 895 ] ], "normalized": [] }, { "id": "PMID-20978953_T15", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1071, 1080 ] ], "normalized": [] }, { "id": "PMID-20978953_T16", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1205, 1214 ] ], "normalized": [] }, { "id": "PMID-20978953_T17", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 1286, 1294 ] ], "normalized": [] }, { "id": "PMID-20978953_T18", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1343, 1352 ] ], "normalized": [] }, { "id": "PMID-20978953_T19", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1422, 1431 ] ], "normalized": [] }, { "id": "PMID-20978953_T20", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1540, 1549 ] ], "normalized": [] }, { "id": "PMID-20978953_T21", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 1554, 1564 ] ], "normalized": [] }, { "id": "PMID-20978953_T22", "type": "Cell", "text": [ "Myofibroblasts" ], "offsets": [ [ 1653, 1667 ] ], "normalized": [] }, { "id": "PMID-20978953_T23", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 1783, 1791 ] ], "normalized": [] }, { "id": "PMID-20978953_T24", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 1797, 1819 ] ], "normalized": [] } ]	[ { "id": "PMID-20978953_E1", "type": "Regulation", "trigger": { "text": [ "Role" ], "offsets": [ [ 0, 4 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-20978953_T1" }, { "role": "Theme", "ref_id": "PMID-20978953_E2" } ] }, { "id": "PMID-20978953_E2", "type": "Localization", "trigger": { "text": [ "invasive" ], "offsets": [ [ 34, 42 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T2" } ] }, { "id": "PMID-20978953_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 66, 76 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T4" } ] }, { "id": "PMID-20978953_E4", "type": "Regulation", "trigger": { "text": [ "having an important function" ], "offsets": [ [ 218, 246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T5" } ] }, { "id": "PMID-20978953_E5", "type": "Localization", "trigger": { "text": [ "invasive" ], "offsets": [ [ 335, 343 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T6" } ] }, { "id": "PMID-20978953_E6", "type": "Localization", "trigger": { "text": [ "invasive" ], "offsets": [ [ 642, 650 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T8" } ] }, { "id": "PMID-20978953_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 774, 784 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T11" } ] }, { "id": "PMID-20978953_E8", "type": "Localization", "trigger": { "text": [ "invasive" ], "offsets": [ [ 835, 843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T13" } ] }, { "id": "PMID-20978953_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 903, 913 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T14" } ] }, { "id": "PMID-20978953_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1057, 1067 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T15" } ] }, { "id": "PMID-20978953_E11", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 1160, 1170 ] ] }, "arguments": [] }, { "id": "PMID-20978953_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1215, 1225 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T16" } ] }, { "id": "PMID-20978953_E13", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 1247, 1257 ] ] }, "arguments": [] }, { "id": "PMID-20978953_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1353, 1363 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T18" } ] }, { "id": "PMID-20978953_E15", "type": "Death", "trigger": { "text": [ "survival" ], "offsets": [ [ 1473, 1481 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T17" } ] }, { "id": "PMID-20978953_E16", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 1565, 1575 ] ] }, "arguments": [ { "role": "ToLoc", "ref_id": "PMID-20978953_T21" } ] }, { "id": "PMID-20978953_E17", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 1629, 1639 ] ] }, "arguments": [] }, { "id": "PMID-20978953_E18", "type": "Localization", "trigger": { "text": [ "invasive" ], "offsets": [ [ 1713, 1721 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T22" } ] }, { "id": "PMID-20978953_E19", "type": "Cell_proliferation", "trigger": { "text": [ "growth" ], "offsets": [ [ 1722, 1728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-20978953_T22" } ] } ]	[]	[]
7	PMID-7474113	[ { "id": "PMID-7474113__text", "type": "abstract", "text": [ "The inhibition of cultured myoblast differentiation by the simian virus 40 large T antigen occurs after myogenin expression and Rb up-regulation and is not exerted by transformation-competent cytoplasmic mutants. \nWe have investigated the mechanism by which the simian virus 40 large T antigen (SVLT) interferes with the differentiation of C2 myoblasts. SVLT mutants, defective either in the Rb binding site, near the N-terminal end, in a region that affects binding to p53, or in the nuclear transport signal, were also employed to determine whether the interference was especially dependent on these functional domains. It was found that wild-type (wt) SVLT strongly inhibited the terminal differentiation of mouse C2 myoblasts, but this arrest occurred only after the synthesis of myogenin, an initial step in biochemical differentiation. Neither the synthesis nor some basic activities of MyoD appeared to be affected by wt SVLT. In these transformants, mitogen depletion elicited an increase in the Rb level comparable to that in normal C2 cells; wt SVLT, however, promoted the phosphorylation of a large part of the induced Rb. Mutations affecting nuclear transport were far more critical for the ability to interfere with myogenic differentiation than were those affecting the transforming potential; cytoplasmic SVLT expression was fully compatible with the terminal differentiation of C2 cells, despite enabling them to grow in semisolid medium, thus showing that the myogenesis-inhibiting property can be dissociated from transforming competence. The remaining SVLT mutants presented different degrees of ability to inhibit differentiation (as shown by the expression of tissue-specific markers in transformants). The inhibiting mutants, including the Rb binding site mutant, were able to promote a higher state of Rb phosphorylation than that observed in either normal cells or cytoplasmic-SVLT transformants.\n" ], "offsets": [ [ 0, 1921 ] ] } ]	[ { "id": "PMID-7474113_T1", "type": "Cell", "text": [ "myoblast" ], "offsets": [ [ 27, 35 ] ], "normalized": [] }, { "id": "PMID-7474113_T2", "type": "Organism", "text": [ "simian virus 40" ], "offsets": [ [ 59, 74 ] ], "normalized": [] }, { "id": "PMID-7474113_T3", "type": "Gene_or_gene_product", "text": [ "large T antigen" ], "offsets": [ [ 75, 90 ] ], "normalized": [] }, { "id": "PMID-7474113_T4", "type": "Gene_or_gene_product", "text": [ "myogenin" ], "offsets": [ [ 104, 112 ] ], "normalized": [] }, { "id": "PMID-7474113_T5", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 128, 130 ] ], "normalized": [] }, { "id": "PMID-7474113_T6", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 192, 203 ] ], "normalized": [] }, { "id": "PMID-7474113_T7", "type": "Organism", "text": [ "simian virus 40" ], "offsets": [ [ 262, 277 ] ], "normalized": [] }, { "id": "PMID-7474113_T8", "type": "Gene_or_gene_product", "text": [ "large T antigen" ], "offsets": [ [ 278, 293 ] ], "normalized": [] }, { "id": "PMID-7474113_T9", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 295, 299 ] ], "normalized": [] }, { "id": "PMID-7474113_T10", "type": "Cell", "text": [ "C2 myoblasts" ], "offsets": [ [ 340, 352 ] ], "normalized": [] }, { "id": "PMID-7474113_T11", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 354, 358 ] ], "normalized": [] }, { "id": "PMID-7474113_T12", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 392, 394 ] ], "normalized": [] }, { "id": "PMID-7474113_T13", "type": "Gene_or_gene_product", "text": [ "p53" ], "offsets": [ [ 470, 473 ] ], "normalized": [] }, { "id": "PMID-7474113_T14", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 655, 659 ] ], "normalized": [] }, { "id": "PMID-7474113_T15", "type": "Organism", "text": [ "mouse" ], "offsets": [ [ 711, 716 ] ], "normalized": [] }, { "id": "PMID-7474113_T16", "type": "Cell", "text": [ "C2 myoblasts" ], "offsets": [ [ 717, 729 ] ], "normalized": [] }, { "id": "PMID-7474113_T17", "type": "Gene_or_gene_product", "text": [ "myogenin" ], "offsets": [ [ 784, 792 ] ], "normalized": [] }, { "id": "PMID-7474113_T18", "type": "Gene_or_gene_product", "text": [ "MyoD" ], "offsets": [ [ 893, 897 ] ], "normalized": [] }, { "id": "PMID-7474113_T19", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 928, 932 ] ], "normalized": [] }, { "id": "PMID-7474113_T20", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 943, 956 ] ], "normalized": [] }, { "id": "PMID-7474113_T21", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 1004, 1006 ] ], "normalized": [] }, { "id": "PMID-7474113_T22", "type": "Cell", "text": [ "C2 cells" ], "offsets": [ [ 1042, 1050 ] ], "normalized": [] }, { "id": "PMID-7474113_T23", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 1055, 1059 ] ], "normalized": [] }, { "id": "PMID-7474113_T24", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 1130, 1132 ] ], "normalized": [] }, { "id": "PMID-7474113_T25", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1154, 1161 ] ], "normalized": [] }, { "id": "PMID-7474113_T26", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1308, 1319 ] ], "normalized": [] }, { "id": "PMID-7474113_T27", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 1320, 1324 ] ], "normalized": [] }, { "id": "PMID-7474113_T28", "type": "Cell", "text": [ "C2 cells" ], "offsets": [ [ 1394, 1402 ] ], "normalized": [] }, { "id": "PMID-7474113_T29", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 1571, 1575 ] ], "normalized": [] }, { "id": "PMID-7474113_T30", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1681, 1687 ] ], "normalized": [] }, { "id": "PMID-7474113_T31", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 1708, 1721 ] ], "normalized": [] }, { "id": "PMID-7474113_T32", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 1762, 1764 ] ], "normalized": [] }, { "id": "PMID-7474113_T33", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 1825, 1827 ] ], "normalized": [] }, { "id": "PMID-7474113_T34", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1880, 1885 ] ], "normalized": [] }, { "id": "PMID-7474113_T35", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1889, 1900 ] ], "normalized": [] }, { "id": "PMID-7474113_T36", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 1901, 1905 ] ], "normalized": [] }, { "id": "PMID-7474113_T37", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 1906, 1919 ] ], "normalized": [] } ]	[ { "id": "PMID-7474113_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 4, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E2" }, { "role": "Cause", "ref_id": "PMID-7474113_T3" } ] }, { "id": "PMID-7474113_E2", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 36, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T1" } ] }, { "id": "PMID-7474113_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 113, 123 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T4" } ] }, { "id": "PMID-7474113_E4", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 131, 144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T5" } ] }, { "id": "PMID-7474113_E5", "type": "Negative_regulation", "trigger": { "text": [ "interferes" ], "offsets": [ [ 301, 311 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-7474113_T8" }, { "role": "Theme", "ref_id": "PMID-7474113_E6" } ] }, { "id": "PMID-7474113_E6", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 321, 336 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T10" } ] }, { "id": "PMID-7474113_E7", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 395, 402 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T12" } ] }, { "id": "PMID-7474113_E8", "type": "Regulation", "trigger": { "text": [ "affects" ], "offsets": [ [ 451, 458 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E9" } ] }, { "id": "PMID-7474113_E9", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 459, 466 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T13" } ] }, { "id": "PMID-7474113_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-7474113_T14" }, { "role": "Theme", "ref_id": "PMID-7474113_E11" } ] }, { "id": "PMID-7474113_E11", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 692, 707 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T16" } ] }, { "id": "PMID-7474113_E12", "type": "Negative_regulation", "trigger": { "text": [ "arrest" ], "offsets": [ [ 740, 746 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E11" } ] }, { "id": "PMID-7474113_E13", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 771, 780 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T17" } ] }, { "id": "PMID-7474113_E14", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 854, 863 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T18" } ] }, { "id": "PMID-7474113_E15", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 913, 921 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E14" }, { "role": "Cause", "ref_id": "PMID-7474113_T19" } ] }, { "id": "PMID-7474113_E16", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 913, 921 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T18" }, { "role": "Cause", "ref_id": "PMID-7474113_T19" } ] }, { "id": "PMID-7474113_E17", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 988, 996 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T21" } ] }, { "id": "PMID-7474113_E18", "type": "Positive_regulation", "trigger": { "text": [ "promoted" ], "offsets": [ [ 1070, 1078 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-7474113_T23" }, { "role": "Theme", "ref_id": "PMID-7474113_E19" } ] }, { "id": "PMID-7474113_E19", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1083, 1098 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T24" } ] }, { "id": "PMID-7474113_E20", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1122, 1129 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T24" } ] }, { "id": "PMID-7474113_E21", "type": "Mutation", "trigger": { "text": [ "Mutations" ], "offsets": [ [ 1134, 1143 ] ] }, "arguments": [] }, { "id": "PMID-7474113_E22", "type": "Regulation", "trigger": { "text": [ "affecting" ], "offsets": [ [ 1144, 1153 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-7474113_E21" }, { "role": "Theme", "ref_id": "PMID-7474113_E23" } ] }, { "id": "PMID-7474113_E23", "type": "Localization", "trigger": { "text": [ "transport" ], "offsets": [ [ 1162, 1171 ] ] }, "arguments": [ { "role": "ToLoc", "ref_id": "PMID-7474113_T25" }, { "role": "Theme", "ref_id": "PMID-7474113_T27" } ] }, { "id": "PMID-7474113_E24", "type": "Positive_regulation", "trigger": { "text": [ "critical" ], "offsets": [ [ 1186, 1194 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-7474113_E21" }, { "role": "Theme", "ref_id": "PMID-7474113_E25" } ] }, { "id": "PMID-7474113_E25", "type": "Negative_regulation", "trigger": { "text": [ "interfere" ], "offsets": [ [ 1214, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E26" } ] }, { "id": "PMID-7474113_E26", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1238, 1253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" } ] }, { "id": "PMID-7474113_E27", "type": "Regulation", "trigger": { "text": [ "affecting" ], "offsets": [ [ 1270, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E28" }, { "role": "Cause", "ref_id": "PMID-7474113_E21" } ] }, { "id": "PMID-7474113_E28", "type": "Cell_transformation", "trigger": { "text": [ "transforming" ], "offsets": [ [ 1284, 1296 ] ] }, "arguments": [] }, { "id": "PMID-7474113_E29", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1325, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T27" } ] }, { "id": "PMID-7474113_E30", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1375, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" } ] }, { "id": "PMID-7474113_E31", "type": "Cell_proliferation", "trigger": { "text": [ "grow" ], "offsets": [ [ 1429, 1433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" } ] }, { "id": "PMID-7474113_E32", "type": "Negative_regulation", "trigger": { "text": [ "inhibiting" ], "offsets": [ [ 1488, 1498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" }, { "role": "Cause", "ref_id": "PMID-7474113_T27" } ] }, { "id": "PMID-7474113_E33", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1626, 1633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E34" } ] }, { "id": "PMID-7474113_E34", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1634, 1649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" } ] }, { "id": "PMID-7474113_E35", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1765, 1772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T32" } ] }, { "id": "PMID-7474113_E36", "type": "Positive_regulation", "trigger": { "text": [ "promote" ], "offsets": [ [ 1799, 1806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E37" } ] }, { "id": "PMID-7474113_E37", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1828, 1843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T33" } ] } ]	[ { "id": "PMID-7474113_1", "entity_ids": [ "PMID-7474113_T8", "PMID-7474113_T9" ] } ]	[]
8	PMID-17462601	[ { "id": "PMID-17462601__text", "type": "abstract", "text": [ "An antibody directed against PDGF receptor beta enhances the antitumor and the anti-angiogenic activities of an anti-VEGF receptor 2 antibody.\nPlatelet-derived growth factor (PDGF) and its receptors (PDGFR) play important roles in tumorigenesis through stimulating tumor growth and promoting angiogenesis via enhancing pericyte recruitment and vessel maturation. Here we produced a neutralizing antibody, 1B3, directed against mouse PDGFRbeta. 1B3 binds to PDGFRbeta with high affinity (9x10(-11)M) and blocks PDGF-BB from binding to the receptor with an IC(50) of approximately 1.2 nM. The antibody also blocks ligand-stimulated activation of PDGFRbeta and downstream signaling molecules, including Akt and MAPK p42/44, in tumor cells. In animal studies, 1B3 significantly enhanced the antitumor and the anti-angiogenic activities of DC101, an antibody directed against mouse vascular endothelial growth factor receptor 2, in a pancreatic (BxPC-3) and a non-small cell lung (NCI-H460) tumor xenograft models. Treatment with the combination of 1B3 and DC101 in BxPC-3 xenograft-bearing mice resulted in tumor regression in 58% of mice compared to that in 18% of mice treated with DC101 alone. Taken together, these results lend great support to use PDGFRbeta antagonists in combinations with other antitumor and/or anti-angiogenic agents in the treatment of a variety of cancers.\n" ], "offsets": [ [ 0, 1380 ] ] } ]	[ { "id": "PMID-17462601_T1", "type": "Gene_or_gene_product", "text": [ "antibody directed against PDGF receptor beta" ], "offsets": [ [ 3, 47 ] ], "normalized": [] }, { "id": "PMID-17462601_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 65, 70 ] ], "normalized": [] }, { "id": "PMID-17462601_T3", "type": "Gene_or_gene_product", "text": [ "anti-VEGF receptor 2 antibody" ], "offsets": [ [ 112, 141 ] ], "normalized": [] }, { "id": "PMID-17462601_T4", "type": "Gene_or_gene_product", "text": [ "Platelet-derived growth factor" ], "offsets": [ [ 143, 173 ] ], "normalized": [] }, { "id": "PMID-17462601_T5", "type": "Gene_or_gene_product", "text": [ "PDGF" ], "offsets": [ [ 175, 179 ] ], "normalized": [] }, { "id": "PMID-17462601_T6", "type": "Gene_or_gene_product", "text": [ "PDGFR" ], "offsets": [ [ 200, 205 ] ], "normalized": [] }, { "id": "PMID-17462601_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 265, 270 ] ], "normalized": [] }, { "id": "PMID-17462601_T8", "type": "Cell", "text": [ "pericyte" ], "offsets": [ [ 319, 327 ] ], "normalized": [] }, { "id": "PMID-17462601_T9", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 344, 350 ] ], "normalized": [] }, { "id": "PMID-17462601_T10", "type": "Simple_chemical", "text": [ "1B3" ], "offsets": [ [ 405, 408 ] ], "normalized": [] }, { "id": "PMID-17462601_T11", "type": "Organism", "text": [ "mouse" ], "offsets": [ [ 427, 432 ] ], "normalized": [] }, { "id": "PMID-17462601_T12", "type": "Gene_or_gene_product", "text": [ "PDGFRbeta" ], "offsets": [ [ 433, 442 ] ], "normalized": [] }, { "id": "PMID-17462601_T13", "type": "Simple_chemical", "text": [ "1B3" ], "offsets": [ [ 444, 447 ] ], "normalized": [] }, { "id": "PMID-17462601_T14", "type": "Gene_or_gene_product", "text": [ "PDGFRbeta" ], "offsets": [ [ 457, 466 ] ], "normalized": [] }, { "id": "PMID-17462601_T15", "type": "Gene_or_gene_product", "text": [ "PDGF-BB" ], "offsets": [ [ 510, 517 ] ], "normalized": [] }, { "id": "PMID-17462601_T16", "type": "Gene_or_gene_product", "text": [ "PDGFRbeta" ], "offsets": [ [ 644, 653 ] ], "normalized": [] }, { "id": "PMID-17462601_T17", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 700, 703 ] ], "normalized": [] }, { "id": "PMID-17462601_T18", "type": "Gene_or_gene_product", "text": [ "MAPK p42/44" ], "offsets": [ [ 708, 719 ] ], "normalized": [] }, { "id": "PMID-17462601_T19", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 724, 735 ] ], "normalized": [] }, { "id": "PMID-17462601_T20", "type": "Simple_chemical", "text": [ "1B3" ], "offsets": [ [ 756, 759 ] ], "normalized": [] }, { "id": "PMID-17462601_T21", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 791, 796 ] ], "normalized": [] }, { "id": "PMID-17462601_T22", "type": "Simple_chemical", "text": [ "DC101" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "PMID-17462601_T23", "type": "Organism", "text": [ "mouse" ], "offsets": [ [ 871, 876 ] ], "normalized": [] }, { "id": "PMID-17462601_T24", "type": "Gene_or_gene_product", "text": [ "vascular endothelial growth factor receptor 2" ], "offsets": [ [ 877, 922 ] ], "normalized": [] }, { "id": "PMID-17462601_T25", "type": "Cancer", "text": [ "pancreatic" ], "offsets": [ [ 929, 939 ] ], "normalized": [] }, { "id": "PMID-17462601_T26", "type": "Cancer", "text": [ "BxPC-3" ], "offsets": [ [ 941, 947 ] ], "normalized": [] }, { "id": "PMID-17462601_T27", "type": "Cancer", "text": [ "non-small cell lung (NCI-H460) tumor xenograft" ], "offsets": [ [ 955, 1001 ] ], "normalized": [] }, { "id": "PMID-17462601_T28", "type": "Simple_chemical", "text": [ "1B3" ], "offsets": [ [ 1044, 1047 ] ], "normalized": [] }, { "id": "PMID-17462601_T29", "type": "Simple_chemical", "text": [ "DC101" ], "offsets": [ [ 1052, 1057 ] ], "normalized": [] }, { "id": "PMID-17462601_T30", "type": "Cancer", "text": [ "BxPC-3 xenograft" ], "offsets": [ [ 1061, 1077 ] ], "normalized": [] }, { "id": "PMID-17462601_T31", "type": "Organism", "text": [ "mice" ], "offsets": [ [ 1086, 1090 ] ], "normalized": [] }, { "id": "PMID-17462601_T32", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1103, 1108 ] ], "normalized": [] }, { "id": "PMID-17462601_T33", "type": "Organism", "text": [ "mice" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "PMID-17462601_T34", "type": "Organism", "text": [ "mice" ], "offsets": [ [ 1162, 1166 ] ], "normalized": [] }, { "id": "PMID-17462601_T35", "type": "Simple_chemical", "text": [ "DC101" ], "offsets": [ [ 1180, 1185 ] ], "normalized": [] }, { "id": "PMID-17462601_T36", "type": "Gene_or_gene_product", "text": [ "PDGFRbeta antagonists" ], "offsets": [ [ 1249, 1270 ] ], "normalized": [] }, { "id": "PMID-17462601_T37", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1302, 1307 ] ], "normalized": [] }, { "id": "PMID-17462601_T38", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 1371, 1378 ] ], "normalized": [] } ]	[ { "id": "PMID-17462601_E1", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 48, 56 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T1" }, { "role": "Theme", "ref_id": "PMID-17462601_T3" } ] }, { "id": "PMID-17462601_E2", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 48, 56 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T1" }, { "role": "Theme", "ref_id": "PMID-17462601_E5" } ] }, { "id": "PMID-17462601_E3", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 48, 56 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T1" }, { "role": "Theme", "ref_id": "PMID-17462601_E6" } ] }, { "id": "PMID-17462601_E4", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 84, 94 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E5", "type": "Negative_regulation", "trigger": { "text": [ "activities" ], "offsets": [ [ 95, 105 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T3" }, { "role": "Theme", "ref_id": "PMID-17462601_E4" } ] }, { "id": "PMID-17462601_E6", "type": "Negative_regulation", "trigger": { "text": [ "activities" ], "offsets": [ [ 95, 105 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T3" }, { "role": "Theme", "ref_id": "PMID-17462601_T2" } ] }, { "id": "PMID-17462601_E7", "type": "Regulation", "trigger": { "text": [ "roles" ], "offsets": [ [ 222, 227 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E9" }, { "role": "Cause", "ref_id": "PMID-17462601_T4" } ] }, { "id": "PMID-17462601_E8", "type": "Regulation", "trigger": { "text": [ "roles" ], "offsets": [ [ 222, 227 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E9" }, { "role": "Cause", "ref_id": "PMID-17462601_T6" } ] }, { "id": "PMID-17462601_E9", "type": "Carcinogenesis", "trigger": { "text": [ "tumorigenesis" ], "offsets": [ [ 231, 244 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E10", "type": "Positive_regulation", "trigger": { "text": [ "stimulating" ], "offsets": [ [ 253, 264 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T6" }, { "role": "Theme", "ref_id": "PMID-17462601_E12" } ] }, { "id": "PMID-17462601_E11", "type": "Positive_regulation", "trigger": { "text": [ "stimulating" ], "offsets": [ [ 253, 264 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T4" }, { "role": "Theme", "ref_id": "PMID-17462601_E12" } ] }, { "id": "PMID-17462601_E12", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 271, 277 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T7" } ] }, { "id": "PMID-17462601_E13", "type": "Positive_regulation", "trigger": { "text": [ "promoting" ], "offsets": [ [ 282, 291 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T6" }, { "role": "Theme", "ref_id": "PMID-17462601_E15" } ] }, { "id": "PMID-17462601_E14", "type": "Positive_regulation", "trigger": { "text": [ "promoting" ], "offsets": [ [ 282, 291 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T4" }, { "role": "Theme", "ref_id": "PMID-17462601_E15" } ] }, { "id": "PMID-17462601_E15", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 292, 304 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E16", "type": "Positive_regulation", "trigger": { "text": [ "enhancing" ], "offsets": [ [ 309, 318 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E18" }, { "role": "Cause", "ref_id": "PMID-17462601_T6" } ] }, { "id": "PMID-17462601_E17", "type": "Positive_regulation", "trigger": { "text": [ "enhancing" ], "offsets": [ [ 309, 318 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E19" }, { "role": "Cause", "ref_id": "PMID-17462601_T4" } ] }, { "id": "PMID-17462601_E18", "type": "Localization", "trigger": { "text": [ "recruitment" ], "offsets": [ [ 328, 339 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T8" } ] }, { "id": "PMID-17462601_E19", "type": "Development", "trigger": { "text": [ "maturation" ], "offsets": [ [ 351, 361 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T9" } ] }, { "id": "PMID-17462601_E20", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 448, 453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T13" }, { "role": "Theme", "ref_id": "PMID-17462601_T14" } ] }, { "id": "PMID-17462601_E21", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 503, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E22" }, { "role": "Cause", "ref_id": "PMID-17462601_T13" } ] }, { "id": "PMID-17462601_E22", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 523, 530 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T15" } ] }, { "id": "PMID-17462601_E23", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 605, 611 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T13" }, { "role": "Theme", "ref_id": "PMID-17462601_E26" } ] }, { "id": "PMID-17462601_E24", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 605, 611 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T13" }, { "role": "Theme", "ref_id": "PMID-17462601_E27" } ] }, { "id": "PMID-17462601_E25", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 605, 611 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T13" }, { "role": "Theme", "ref_id": "PMID-17462601_E28" } ] }, { "id": "PMID-17462601_E26", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 630, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T16" } ] }, { "id": "PMID-17462601_E27", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 630, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T17" } ] }, { "id": "PMID-17462601_E28", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 630, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T18" } ] }, { "id": "PMID-17462601_E29", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 774, 782 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T20" }, { "role": "Theme", "ref_id": "PMID-17462601_E32" } ] }, { "id": "PMID-17462601_E30", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 774, 782 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T20" }, { "role": "Theme", "ref_id": "PMID-17462601_E33" } ] }, { "id": "PMID-17462601_E31", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 810, 820 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E32", "type": "Negative_regulation", "trigger": { "text": [ "activities" ], "offsets": [ [ 821, 831 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T22" }, { "role": "Theme", "ref_id": "PMID-17462601_E31" } ] }, { "id": "PMID-17462601_E33", "type": "Negative_regulation", "trigger": { "text": [ "activities" ], "offsets": [ [ 821, 831 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T22" }, { "role": "Theme", "ref_id": "PMID-17462601_T21" } ] }, { "id": "PMID-17462601_E34", "type": "Planned_process", "trigger": { "text": [ "Treatment" ], "offsets": [ [ 1010, 1019 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-17462601_T28" }, { "role": "Instrument", "ref_id": "PMID-17462601_T29" }, { "role": "Theme", "ref_id": "PMID-17462601_T31" } ] }, { "id": "PMID-17462601_E35", "type": "Positive_regulation", "trigger": { "text": [ "resulted" ], "offsets": [ [ 1091, 1099 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_E34" }, { "role": "Theme", "ref_id": "PMID-17462601_E36" } ] }, { "id": "PMID-17462601_E36", "type": "Negative_regulation", "trigger": { "text": [ "regression" ], "offsets": [ [ 1109, 1119 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T32" } ] }, { "id": "PMID-17462601_E37", "type": "Planned_process", "trigger": { "text": [ "treated" ], "offsets": [ [ 1167, 1174 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-17462601_T35" }, { "role": "Theme", "ref_id": "PMID-17462601_T34" } ] }, { "id": "PMID-17462601_E38", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 1320, 1330 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E39", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 1345, 1354 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T38" }, { "role": "Instrument", "ref_id": "PMID-17462601_T36" } ] } ]	[ { "id": "PMID-17462601_1", "entity_ids": [ "PMID-17462601_T4", "PMID-17462601_T5" ] } ]	[]
9	PMID-19369582	[ { "id": "PMID-19369582__text", "type": "abstract", "text": [ "Characterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets.\nAngiogenesis is a fundamental process to normal and abnormal tissue growth and repair, which consists of recruiting endothelial cells toward an angiogenic stimulus. The cells subsequently proliferate and differentiate to form endothelial tubes and capillary-like structures. Little is known about the metabolic adaptation of endothelial cells through such a transformation. We studied the metabolic changes of endothelial cell activation by growth factors using human umbilical vein endothelial cells (HUVECs), [1,2-(13)C(2)]-glucose and mass isotopomer distribution analysis. The metabolism of [1,2-(13)C(2)]-glucose by HUVEC allows us to trace many of the main glucose metabolic pathways, including glycogen synthesis, the pentose cycle and the glycolytic pathways. So we established that these pathways were crucial to endothelial cell proliferation under vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) stimulation. A specific VEGF receptor-2 inhibitor demonstrated the importance of glycogen metabolism and pentose cycle pathway. Furthermore, we showed that glycogen was depleted in a low glucose medium, but conserved under hypoxic conditions. Finally, we demonstrated that direct inhibition of key enzymes to glycogen metabolism and pentose phosphate pathways reduced HUVEC viability and migration. In this regard, inhibitors of these pathways have been shown to be effective antitumoral agents. To sum up, our data suggest that the inhibition of metabolic pathways offers a novel and powerful therapeutic approach, which simultaneously inhibits tumor cell proliferation and tumor-induced angiogenesis.\n" ], "offsets": [ [ 0, 1782 ] ] } ]	[ { "id": "PMID-19369582_T1", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 204, 210 ] ], "normalized": [] }, { "id": "PMID-19369582_T2", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 259, 276 ] ], "normalized": [] }, { "id": "PMID-19369582_T3", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 312, 317 ] ], "normalized": [] }, { "id": "PMID-19369582_T4", "type": "Tissue", "text": [ "endothelial tubes" ], "offsets": [ [ 369, 386 ] ], "normalized": [] }, { "id": "PMID-19369582_T5", "type": "Tissue", "text": [ "capillary-like structures" ], "offsets": [ [ 391, 416 ] ], "normalized": [] }, { "id": "PMID-19369582_T6", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 468, 485 ] ], "normalized": [] }, { "id": "PMID-19369582_T7", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 553, 569 ] ], "normalized": [] }, { "id": "PMID-19369582_T8", "type": "Cell", "text": [ "human umbilical vein endothelial cells" ], "offsets": [ [ 605, 643 ] ], "normalized": [] }, { "id": "PMID-19369582_T9", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 645, 651 ] ], "normalized": [] }, { "id": "PMID-19369582_T10", "type": "Simple_chemical", "text": [ "[1,2-(13)C(2)]-glucose" ], "offsets": [ [ 654, 676 ] ], "normalized": [] }, { "id": "PMID-19369582_T11", "type": "Simple_chemical", "text": [ "[1,2-(13)C(2)]-glucose" ], "offsets": [ [ 738, 760 ] ], "normalized": [] }, { "id": "PMID-19369582_T12", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 764, 769 ] ], "normalized": [] }, { "id": "PMID-19369582_T13", "type": "Simple_chemical", "text": [ "glucose" ], "offsets": [ [ 806, 813 ] ], "normalized": [] }, { "id": "PMID-19369582_T14", "type": "Simple_chemical", "text": [ "glycogen" ], "offsets": [ [ 844, 852 ] ], "normalized": [] }, { "id": "PMID-19369582_T15", "type": "Simple_chemical", "text": [ "pentose" ], "offsets": [ [ 868, 875 ] ], "normalized": [] }, { "id": "PMID-19369582_T16", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 965, 981 ] ], "normalized": [] }, { "id": "PMID-19369582_T17", "type": "Gene_or_gene_product", "text": [ "vascular endothelial growth factor" ], "offsets": [ [ 1002, 1036 ] ], "normalized": [] }, { "id": "PMID-19369582_T18", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 1038, 1042 ] ], "normalized": [] }, { "id": "PMID-19369582_T19", "type": "Gene_or_gene_product", "text": [ "fibroblast growth factor" ], "offsets": [ [ 1048, 1072 ] ], "normalized": [] }, { "id": "PMID-19369582_T20", "type": "Gene_or_gene_product", "text": [ "FGF" ], "offsets": [ [ 1074, 1077 ] ], "normalized": [] }, { "id": "PMID-19369582_T21", "type": "Gene_or_gene_product", "text": [ "VEGF receptor-2" ], "offsets": [ [ 1103, 1118 ] ], "normalized": [] }, { "id": "PMID-19369582_T22", "type": "Simple_chemical", "text": [ "glycogen" ], "offsets": [ [ 1160, 1168 ] ], "normalized": [] }, { "id": "PMID-19369582_T23", "type": "Simple_chemical", "text": [ "pentose" ], "offsets": [ [ 1184, 1191 ] ], "normalized": [] }, { "id": "PMID-19369582_T24", "type": "Simple_chemical", "text": [ "glycogen" ], "offsets": [ [ 1235, 1243 ] ], "normalized": [] }, { "id": "PMID-19369582_T25", "type": "Simple_chemical", "text": [ "glucose" ], "offsets": [ [ 1266, 1273 ] ], "normalized": [] }, { "id": "PMID-19369582_T26", "type": "Simple_chemical", "text": [ "glycogen" ], "offsets": [ [ 1388, 1396 ] ], "normalized": [] }, { "id": "PMID-19369582_T27", "type": "Simple_chemical", "text": [ "pentose" ], "offsets": [ [ 1412, 1419 ] ], "normalized": [] }, { "id": "PMID-19369582_T28", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 1447, 1452 ] ], "normalized": [] }, { "id": "PMID-19369582_T29", "type": "Cancer", "text": [ "tumoral" ], "offsets": [ [ 1559, 1566 ] ], "normalized": [] }, { "id": "PMID-19369582_T30", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1725, 1735 ] ], "normalized": [] }, { "id": "PMID-19369582_T31", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1754, 1759 ] ], "normalized": [] } ]	[ { "id": "PMID-19369582_E1", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 67, 77 ] ] }, "arguments": [] }, { "id": "PMID-19369582_E2", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 78, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_E1" } ] }, { "id": "PMID-19369582_E3", "type": "Blood_vessel_development", "trigger": { "text": [ "Angiogenesis" ], "offsets": [ [ 143, 155 ] ] }, "arguments": [] }, { "id": "PMID-19369582_E4", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 211, 217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T1" } ] }, { "id": "PMID-19369582_E5", "type": "Remodeling", "trigger": { "text": [ "repair" ], "offsets": [ [ 222, 228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T1" } ] }, { "id": "PMID-19369582_E6", "type": "Localization", "trigger": { "text": [ "recruiting" ], "offsets": [ [ 248, 258 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T2" } ] }, { "id": "PMID-19369582_E7", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 287, 297 ] ] }, "arguments": [] }, { "id": "PMID-19369582_E8", "type": "Cell_proliferation", "trigger": { "text": [ "proliferate" ], "offsets": [ [ 331, 342 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T3" } ] }, { "id": "PMID-19369582_E9", "type": "Cell_differentiation", "trigger": { "text": [ "differentiate" ], "offsets": [ [ 347, 360 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T3" } ] }, { "id": "PMID-19369582_E10", "type": "Development", "trigger": { "text": [ "form" ], "offsets": [ [ 364, 368 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T4" } ] }, { "id": "PMID-19369582_E11", "type": "Development", "trigger": { "text": [ "form" ], "offsets": [ [ 364, 368 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T5" } ] }, { "id": "PMID-19369582_E12", "type": "Cell_transformation", "trigger": { "text": [ "transformation" ], "offsets": [ [ 501, 515 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T6" } ] }, { "id": "PMID-19369582_E13", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 542, 549 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_E14" } ] }, { "id": "PMID-19369582_E14", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 570, 580 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T7" } ] }, { "id": "PMID-19369582_E15", "type": "Metabolism", "trigger": { "text": [ "metabolism" ], "offsets": [ [ 724, 734 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T11" } ] }, { "id": "PMID-19369582_E16", "type": "Pathway", "trigger": { "text": [ "metabolic pathways" ], "offsets": [ [ 814, 832 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-19369582_T13" } ] }, { "id": "PMID-19369582_E17", "type": "Synthesis", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 853, 862 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T14" } ] }, { "id": "PMID-19369582_E18", "type": "Pathway", "trigger": { "text": [ "cycle" ], "offsets": [ [ 876, 881 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-19369582_T15" } ] }, { "id": "PMID-19369582_E19", "type": "Glycolysis", "trigger": { "text": [ "glycolytic pathways" ], "offsets": [ [ 890, 909 ] ] }, "arguments": [] }, { "id": "PMID-19369582_E20", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 982, 995 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T16" } ] }, { "id": "PMID-19369582_E21", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1079, 1090 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T19" } ] }, { "id": "PMID-19369582_E22", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1079, 1090 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T17" } ] }, { "id": "PMID-19369582_E23", "type": "Metabolism", "trigger": { "text": [ "metabolism" ], "offsets": [ [ 1169, 1179 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T22" } ] }, { "id": "PMID-19369582_E24", "type": "Pathway", "trigger": { "text": [ "cycle pathway" ], "offsets": [ [ 1192, 1205 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-19369582_T23" } ] }, { "id": "PMID-19369582_E25", "type": "Catabolism", "trigger": { "text": [ "depleted" ], "offsets": [ [ 1248, 1256 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T24" } ] }, { "id": "PMID-19369582_E26", "type": "Metabolism", "trigger": { "text": [ "metabolism" ], "offsets": [ [ 1397, 1407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T26" } ] }, { "id": "PMID-19369582_E27", "type": "Pathway", "trigger": { "text": [ "phosphate pathways" ], "offsets": [ [ 1420, 1438 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-19369582_T27" } ] }, { "id": "PMID-19369582_E28", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1439, 1446 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_E29" } ] }, { "id": "PMID-19369582_E29", "type": "Localization", "trigger": { "text": [ "migration" ], "offsets": [ [ 1467, 1476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T28" } ] }, { "id": "PMID-19369582_E30", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1716, 1724 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_E32" } ] }, { "id": "PMID-19369582_E31", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1716, 1724 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_E34" } ] }, { "id": "PMID-19369582_E32", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 1736, 1749 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T30" } ] }, { "id": "PMID-19369582_E33", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1760, 1767 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-19369582_T31" }, { "role": "Theme", "ref_id": "PMID-19369582_E34" } ] }, { "id": "PMID-19369582_E34", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 1768, 1780 ] ] }, "arguments": [] } ]	[ { "id": "PMID-19369582_1", "entity_ids": [ "PMID-19369582_T8", "PMID-19369582_T9" ] }, { "id": "PMID-19369582_2", "entity_ids": [ "PMID-19369582_T17", "PMID-19369582_T18" ] }, { "id": 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10	PMID-10589785	[ { "id": "PMID-10589785__text", "type": "abstract", "text": [ "The antiangiogenic agent linomide inhibits the growth rate of von Hippel-Lindau paraganglioma xenografts to mice.\nThe aim of this study was to ascertain the potential usefulness of the antiangiogenic compound linomide for treatment of von Hippel-Lindau (VHL)-related tumors. Paraganglioma tissue fragments obtained at surgery from a VHL type 2a patient were transplanted s.c. to male BALB/c nu/nu (nude) mice: (a) 2-3-mm fragments for \"prevention\" experiments; and (b) 2-3-mm fragments allowed to grow to 1 cm for \"intervention\" studies. Both groups received either 0.5 mg/ml linomide in drinking water or acidified water and were followed until tumor diameter reached 3 cm or for 4 weeks. In both the prevention and intervention experiments, a significant diminution of tumor size and weight was observed in the drug-treated animals. In vivo nuclear magnetic resonance analysis of tumor blood flow in linomide-treated animals showed localization of blood vessels almost exclusively to the periphery of the poorly vascularized tumors with a significant reduction of both vascular functionality and vasodilation. Histological examination of tumors from linomide-treated animals revealed marked avascularity. Treated animals also displayed a 2.4-fold reduction of tumor vascular endothelial growth factor mRNA levels. Taken together, our data indicate that in VHL disease, therapy directed at inhibition of constitutively expressed VEGF induction of angiogenesis by VHL tumors may constitute an effective medical treatment.\n" ], "offsets": [ [ 0, 1522 ] ] } ]	[ { "id": "PMID-10589785_T1", "type": "Simple_chemical", "text": [ "linomide" ], "offsets": [ [ 25, 33 ] ], "normalized": [] }, { "id": "PMID-10589785_T2", "type": "Cancer", "text": [ "von Hippel-Lindau paraganglioma xenografts" ], "offsets": [ [ 62, 104 ] ], "normalized": [] }, { "id": "PMID-10589785_T3", "type": "Organism", "text": [ "mice" ], "offsets": [ [ 108, 112 ] ], "normalized": [] }, { "id": "PMID-10589785_T4", "type": "Simple_chemical", "text": [ "linomide" ], "offsets": [ [ 209, 217 ] ], "normalized": [] }, { "id": "PMID-10589785_T5", "type": "Cancer", "text": [ "von Hippel-Lindau (VHL)-related tumors" ], "offsets": [ [ 235, 273 ] ], "normalized": [] }, { "id": "PMID-10589785_T6", "type": "Tissue", "text": [ "Paraganglioma tissue fragments" ], "offsets": [ [ 275, 305 ] ], "normalized": [] }, { "id": "PMID-10589785_T7", "type": "Organism", "text": [ "patient" ], "offsets": [ [ 345, 352 ] ], "normalized": [] }, { "id": "PMID-10589785_T8", "type": "Organism", "text": [ "BALB/c nu/nu (nude) mice" ], "offsets": [ [ 384, 408 ] ], "normalized": [] }, { "id": "PMID-10589785_T9", "type": "Simple_chemical", "text": [ "linomide" ], "offsets": [ [ 576, 584 ] ], "normalized": [] }, { "id": "PMID-10589785_T10", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 646, 651 ] ], "normalized": [] }, { "id": "PMID-10589785_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 771, 776 ] ], "normalized": [] }, { "id": "PMID-10589785_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 882, 887 ] ], "normalized": [] }, { "id": "PMID-10589785_T13", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 888, 893 ] ], "normalized": [] }, { "id": "PMID-10589785_T14", "type": "Simple_chemical", "text": [ "linomide" ], "offsets": [ [ 902, 910 ] ], "normalized": [] }, { "id": "PMID-10589785_T15", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 950, 963 ] ], "normalized": [] }, { "id": "PMID-10589785_T16", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1027, 1033 ] ], "normalized": [] }, { "id": "PMID-10589785_T17", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1071, 1079 ] ], "normalized": [] }, { "id": "PMID-10589785_T18", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1140, 1146 ] ], "normalized": [] }, { "id": "PMID-10589785_T19", "type": "Simple_chemical", "text": [ "linomide" ], "offsets": [ [ 1152, 1160 ] ], "normalized": [] }, { "id": "PMID-10589785_T20", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1262, 1267 ] ], "normalized": [] }, { "id": "PMID-10589785_T21", "type": "Gene_or_gene_product", "text": [ "vascular endothelial growth factor" ], "offsets": [ [ 1268, 1302 ] ], "normalized": [] }, { "id": "PMID-10589785_T22", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 1430, 1434 ] ], "normalized": [] }, { "id": "PMID-10589785_T23", "type": "Cancer", "text": [ "VHL tumors" ], "offsets": [ [ 1464, 1474 ] ], "normalized": [] } ]	[ { "id": "PMID-10589785_E1", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 8, 18 ] ] }, "arguments": [] }, { "id": "PMID-10589785_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 34, 42 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_E3" }, { "role": "Cause", "ref_id": "PMID-10589785_T1" } ] }, { "id": "PMID-10589785_E3", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 47, 53 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_T2" } ] }, { "id": "PMID-10589785_E4", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 189, 199 ] ] }, "arguments": [] }, { "id": "PMID-10589785_E5", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 222, 231 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10589785_T4" }, { "role": "Theme", "ref_id": "PMID-10589785_T5" } ] }, { "id": "PMID-10589785_E6", "type": "Planned_process", "trigger": { "text": [ "obtained" ], "offsets": [ [ 306, 314 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_T6" } ] }, { "id": "PMID-10589785_E7", "type": "Planned_process", "trigger": { "text": [ "transplanted" ], "offsets": [ [ 358, 370 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10589785_T6" }, { "role": "Theme", "ref_id": "PMID-10589785_T8" } ] }, { "id": "PMID-10589785_E8", "type": "Planned_process", "trigger": { "text": [ "received" ], "offsets": [ [ 550, 558 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10589785_T9" } ] }, { "id": "PMID-10589785_E9", "type": "Negative_regulation", "trigger": { "text": [ "diminution" ], "offsets": [ [ 757, 767 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_T11" } ] }, { "id": "PMID-10589785_E10", "type": "Planned_process", "trigger": { "text": [ "treated" ], "offsets": [ [ 911, 918 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10589785_T14" } ] }, { "id": "PMID-10589785_E11", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 934, 946 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_T15" } ] }, { "id": "PMID-10589785_E12", "type": "Blood_vessel_development", "trigger": { "text": [ "vascularized" ], "offsets": [ [ 1014, 1026 ] ] }, "arguments": [ { "role": "AtLoc", "ref_id": "PMID-10589785_T16" } ] }, { "id": "PMID-10589785_E13", "type": "Planned_process", "trigger": { "text": [ "treated" ], "offsets": [ [ 1161, 1168 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10589785_T19" } ] }, { "id": "PMID-10589785_E14", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1249, 1258 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_T21" } ] }, { "id": "PMID-10589785_E15", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1391, 1401 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_E17" }, { "role": "Cause", "ref_id": "PMID-10589785_T23" } ] }, { "id": "PMID-10589785_E16", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1420, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_T22" } ] }, { "id": "PMID-10589785_E17", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1435, 1444 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10589785_E18" }, { "role": "Cause", "ref_id": "PMID-10589785_T22" } ] }, { "id": "PMID-10589785_E18", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 1448, 1460 ] ] }, "arguments": [] } ]	[]	[]
11	PMID-12140030	[ { "id": "PMID-12140030__text", "type": "abstract", "text": [ "Optimizing treatment of choroidal neovascularization feeder vessels associated with age-related macular degeneration.\nPURPOSE: To optimize the method of treating choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). DESIGN: Experimental study and interventional case series. METHODS: The parameters associated with locating and then photocoagulating CNV feeder vessels were identified and optimized using published data and data derived from modeling the choroidal vasculature. Based on these optimized parameters, a prototype diagnostic/treatment system was designed that captures high-speed indocyanine green (ICG) angiogram images and facilitates analysis of the images by enhancing visualization of dye movement through CNV feeder vessels (FVs). The system also permits precise aiming and delivery of 810- nm wavelength photocoagulation laser energy to target FVs on a real-time ICG angiogram image of the choroidal vasculature. Target FVs are tracked by a joy-stick controlled laser aiming beam until an intravenously-injected high-concentration ICG dye bolus is observed to enter the target vessel, at which time the laser is fired. Proof of principle of the combined diagnosis/treatment system design for performing dye-enhanced photocoagulation (DEP) in the clinical setting and determination of the minimum DEP laser energy needed to close CNV FVs was made in 11 AMD patients requiring treatment of CNV, but for whom other treatment was not appropriate. RESULTS: Using ICG-DEP, CNV feeder vessels were closed with single pulse laser energy, delivering as little as 0.6 to 1.8 J of energy to the fundus, producing no visible change in the fundus. Successful FV closure was usually indicated immediately by presence of incarcerated ICG dye in the vessel adjacent to the burn site. The prototype system proved relatively easy to operate. After acquiring and interpreting diagnostic angiograms and repositioning a patient in front of the device, feeder vessel DEP and treatment evaluation required 15 to 20 minutes. CONCLUSIONS: Indocyanine green dye-enhanced photocoagulation of CNV feeder vessels, facilitated by use of a device that permits real-time visualization of the choroidal circulation while aiming the treatment laser beam, appears to minimize the amount of energy applied to the fundus and the volume of fundus tissue affected by treatment, compared with other treatment modalities. The combination diagnosis/treatment device should be useful in optimizing FV treatment and in refining and evaluating the efficacy of DEP in future clinical trials.\n" ], "offsets": [ [ 0, 2603 ] ] } ]	[ { "id": "PMID-12140030_T1", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 24, 33 ] ], "normalized": [] }, { "id": "PMID-12140030_T2", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 53, 67 ] ], "normalized": [] }, { "id": "PMID-12140030_T3", "type": "Tissue", "text": [ "macular" ], "offsets": [ [ 96, 103 ] ], "normalized": [] }, { "id": "PMID-12140030_T4", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 162, 171 ] ], "normalized": [] }, { "id": "PMID-12140030_T5", "type": "Tissue", "text": [ "macular" ], "offsets": [ [ 225, 232 ] ], "normalized": [] }, { "id": "PMID-12140030_T6", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 391, 405 ] ], "normalized": [] }, { "id": "PMID-12140030_T7", "type": "Multi-tissue_structure", "text": [ "choroidal vasculature" ], "offsets": [ [ 492, 513 ] ], "normalized": [] }, { "id": "PMID-12140030_T8", "type": "Simple_chemical", "text": [ "indocyanine green" ], "offsets": [ [ 630, 647 ] ], "normalized": [] }, { "id": "PMID-12140030_T9", "type": "Simple_chemical", "text": [ "ICG" ], "offsets": [ [ 649, 652 ] ], "normalized": [] }, { "id": "PMID-12140030_T10", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 765, 779 ] ], "normalized": [] }, { "id": "PMID-12140030_T11", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 781, 784 ] ], "normalized": [] }, { "id": "PMID-12140030_T12", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 901, 904 ] ], "normalized": [] }, { "id": "PMID-12140030_T13", "type": "Simple_chemical", "text": [ "ICG" ], "offsets": [ [ 920, 923 ] ], "normalized": [] }, { "id": "PMID-12140030_T14", "type": "Multi-tissue_structure", "text": [ "choroidal vasculature" ], "offsets": [ [ 947, 968 ] ], "normalized": [] }, { "id": "PMID-12140030_T15", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 977, 980 ] ], "normalized": [] }, { "id": "PMID-12140030_T16", "type": "Immaterial_anatomical_entity", "text": [ "intravenously" ], "offsets": [ [ 1046, 1059 ] ], "normalized": [] }, { "id": "PMID-12140030_T17", "type": "Simple_chemical", "text": [ "ICG dye" ], "offsets": [ [ 1088, 1095 ] ], "normalized": [] }, { "id": "PMID-12140030_T18", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1134, 1140 ] ], "normalized": [] }, { "id": "PMID-12140030_T19", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 1390, 1393 ] ], "normalized": [] }, { "id": "PMID-12140030_T20", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 1413, 1421 ] ], "normalized": [] }, { "id": "PMID-12140030_T21", "type": "Simple_chemical", "text": [ "ICG" ], "offsets": [ [ 1515, 1518 ] ], "normalized": [] }, { "id": "PMID-12140030_T22", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 1528, 1542 ] ], "normalized": [] }, { "id": "PMID-12140030_T23", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 1641, 1647 ] ], "normalized": [] }, { "id": "PMID-12140030_T24", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 1684, 1690 ] ], "normalized": [] }, { "id": "PMID-12140030_T25", "type": "Multi-tissue_structure", "text": [ "FV" ], "offsets": [ [ 1703, 1705 ] ], "normalized": [] }, { "id": "PMID-12140030_T26", "type": "Simple_chemical", "text": [ "ICG dye" ], "offsets": [ [ 1776, 1783 ] ], "normalized": [] }, { "id": "PMID-12140030_T27", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1791, 1797 ] ], "normalized": [] }, { "id": "PMID-12140030_T28", "type": "Organism", "text": [ "patient" ], "offsets": [ [ 1956, 1963 ] ], "normalized": [] }, { "id": "PMID-12140030_T29", "type": "Multi-tissue_structure", "text": [ "feeder vessel" ], "offsets": [ [ 1988, 2001 ] ], "normalized": [] }, { "id": "PMID-12140030_T30", "type": "Simple_chemical", "text": [ "Indocyanine green dye" ], "offsets": [ [ 2071, 2092 ] ], "normalized": [] }, { "id": "PMID-12140030_T31", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 2126, 2140 ] ], "normalized": [] }, { "id": "PMID-12140030_T32", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 2217, 2226 ] ], "normalized": [] }, { "id": "PMID-12140030_T33", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 2334, 2340 ] ], "normalized": [] }, { "id": "PMID-12140030_T34", "type": "Tissue", "text": [ "fundus tissue" ], "offsets": [ [ 2359, 2372 ] ], "normalized": [] }, { "id": "PMID-12140030_T35", "type": "Multi-tissue_structure", "text": [ "FV" ], "offsets": [ [ 2512, 2514 ] ], "normalized": [] } ]	[ { "id": "PMID-12140030_E1", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 11, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E2" } ] }, { "id": "PMID-12140030_E2", "type": "Blood_vessel_development", "trigger": { "text": [ "neovascularization" ], "offsets": [ [ 34, 52 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T2" }, { "role": "AtLoc", "ref_id": "PMID-12140030_T1" } ] }, { "id": "PMID-12140030_E3", "type": "Regulation", "trigger": { "text": [ "associated" ], "offsets": [ [ 68, 78 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E4" }, { "role": "Cause", "ref_id": "PMID-12140030_E2" } ] }, { "id": "PMID-12140030_E4", "type": "Breakdown", "trigger": { "text": [ "degeneration" ], "offsets": [ [ 104, 116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T3" } ] }, { "id": "PMID-12140030_E5", "type": "Planned_process", "trigger": { "text": [ "treating" ], "offsets": [ [ 153, 161 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E6" } ] }, { "id": "PMID-12140030_E6", "type": "Blood_vessel_development", "trigger": { "text": [ "neovascularization" ], "offsets": [ [ 172, 190 ] ] }, "arguments": [ { "role": "AtLoc", "ref_id": "PMID-12140030_T4" } ] }, { "id": "PMID-12140030_E7", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 192, 195 ] ] }, "arguments": [] }, { "id": "PMID-12140030_E8", "type": "Regulation", "trigger": { "text": [ "associated" ], "offsets": [ [ 197, 207 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E9" }, { "role": "Cause", "ref_id": "PMID-12140030_E6" } ] }, { "id": "PMID-12140030_E9", "type": "Breakdown", "trigger": { "text": [ "degeneration" ], "offsets": [ [ 233, 245 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T5" } ] }, { "id": "PMID-12140030_E10", "type": "Planned_process", "trigger": { "text": [ "photocoagulating" ], "offsets": [ [ 370, 386 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T6" } ] }, { "id": "PMID-12140030_E11", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 387, 390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T6" } ] }, { "id": "PMID-12140030_E12", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 761, 764 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T10" } ] }, { "id": "PMID-12140030_E13", "type": "Planned_process", "trigger": { "text": [ "injected" ], "offsets": [ [ 1060, 1068 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-12140030_T17" } ] }, { "id": "PMID-12140030_E14", "type": "Localization", "trigger": { "text": [ "observed" ], "offsets": [ [ 1105, 1113 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T17" }, { "role": "ToLoc", "ref_id": "PMID-12140030_T18" } ] }, { "id": "PMID-12140030_E15", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 1386, 1389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T19" } ] }, { "id": "PMID-12140030_E16", "type": "Positive_regulation", "trigger": { "text": [ "requiring" ], "offsets": [ [ 1422, 1431 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12140030_E17" }, { "role": "Theme", "ref_id": "PMID-12140030_T20" } ] }, { "id": "PMID-12140030_E17", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 1432, 1441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E18" } ] }, { "id": "PMID-12140030_E18", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 1445, 1448 ] ] }, "arguments": [] }, { "id": "PMID-12140030_E19", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 1524, 1527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T22" } ] }, { "id": "PMID-12140030_E20", "type": "Planned_process", "trigger": { "text": [ "closed" ], "offsets": [ [ 1548, 1554 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T22" }, { "role": "Instrument", "ref_id": "PMID-12140030_T21" } ] }, { "id": "PMID-12140030_E21", "type": "Planned_process", "trigger": { "text": [ "closure" ], "offsets": [ [ 1706, 1713 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T25" } ] }, { "id": "PMID-12140030_E22", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 2093, 2101 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12140030_T30" }, { "role": "Theme", "ref_id": "PMID-12140030_E23" } ] }, { "id": "PMID-12140030_E23", "type": "Planned_process", "trigger": { "text": [ "photocoagulation" ], "offsets": [ [ 2102, 2118 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T31" } ] }, { "id": "PMID-12140030_E24", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 2122, 2125 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T31" } ] }, { "id": "PMID-12140030_E25", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 2515, 2524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T35" } ] } ]	[ { "id": "PMID-12140030_1", "entity_ids": [ "PMID-12140030_T8", "PMID-12140030_T9" ] }, { "id": "PMID-12140030_2", "entity_ids": [ "PMID-12140030_T10", "PMID-12140030_T11" ] } ]	[]
12	PMID-11238633	[ { "id": "PMID-11238633__text", "type": "abstract", "text": [ "IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endothelial cell cross-talk.\nIn vivo IL-12-dependent tumor inhibition rests on the ability of IL-12 to activate a CD8-mediated cytotoxicity, inhibit angiogenesis, and cause vascular injury. Although in vivo studies have shown that such inhibition stems from complex interactions of immune cells and the production of IFN-gamma and other downstream angiostatic chemokines, the mechanisms involved are still poorly defined. Here we show that IL-12 activates an anti-angiogenic program in Con A-activated mouse spleen cells (activated spc) or human PBMC (activated PBMC). The soluble factors they release in its presence arrest the cycle of endothelial cells (EC), inhibit in vitro angiogenesis, negatively modulate the production of matrix metalloproteinase-9, and the ability of EC to adhere to vitronectin and up-regulate ICAM-1 and VCAM-1 expression. These effects do not require direct cell-cell contact, yet result from continuous interaction between activated lymphoid cells and EC. We used neutralizing Abs to show that the IFN-inducible protein-10 and monokine-induced by IFN-gamma chemokines are pivotal in inducing these effects. Experiments with nu/nu mice, nonobese diabetic-SCID mice, or activated spc enriched in specific cell subpopulations demonstrated that CD4(+), CD8(+), and NK cells are all needed to mediate the full anti-angiogenetic effect of IL-12.\n" ], "offsets": [ [ 0, 1457 ] ] } ]	[ { "id": "PMID-11238633_T1", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-11238633_T2", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 20, 36 ] ], "normalized": [] }, { "id": "PMID-11238633_T3", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 75, 85 ] ], "normalized": [] }, { "id": "PMID-11238633_T4", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 86, 102 ] ], "normalized": [] }, { "id": "PMID-11238633_T5", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 123, 128 ] ], "normalized": [] }, { "id": "PMID-11238633_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 139, 144 ] ], "normalized": [] }, { "id": "PMID-11238633_T7", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 180, 185 ] ], "normalized": [] }, { "id": "PMID-11238633_T8", "type": "Gene_or_gene_product", "text": [ "CD8" ], "offsets": [ [ 200, 203 ] ], "normalized": [] }, { "id": "PMID-11238633_T9", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 259, 267 ] ], "normalized": [] }, { "id": "PMID-11238633_T10", "type": "Cell", "text": [ "immune cells" ], "offsets": [ [ 368, 380 ] ], "normalized": [] }, { "id": "PMID-11238633_T11", "type": "Gene_or_gene_product", "text": [ "IFN-gamma" ], "offsets": [ [ 403, 412 ] ], "normalized": [] }, { "id": "PMID-11238633_T12", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 526, 531 ] ], "normalized": [] }, { "id": "PMID-11238633_T13", "type": "Simple_chemical", "text": [ "Con A" ], "offsets": [ [ 572, 577 ] ], "normalized": [] }, { "id": "PMID-11238633_T14", "type": "Organism", "text": [ "mouse" ], "offsets": [ [ 588, 593 ] ], "normalized": [] }, { "id": "PMID-11238633_T15", "type": "Cell", "text": [ "spleen cells" ], "offsets": [ [ 594, 606 ] ], "normalized": [] }, { "id": "PMID-11238633_T16", "type": "Cell", "text": [ "spc" ], "offsets": [ [ 618, 621 ] ], "normalized": [] }, { "id": "PMID-11238633_T17", "type": "Organism", "text": [ "human" ], "offsets": [ [ 626, 631 ] ], "normalized": [] }, { "id": "PMID-11238633_T18", "type": "Cell", "text": [ "PBMC" ], "offsets": [ [ 632, 636 ] ], "normalized": [] }, { "id": "PMID-11238633_T19", "type": "Cell", "text": [ "PBMC" ], "offsets": [ [ 648, 652 ] ], "normalized": [] }, { "id": "PMID-11238633_T20", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 724, 741 ] ], "normalized": [] }, { "id": "PMID-11238633_T21", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 743, 745 ] ], "normalized": [] }, { "id": "PMID-11238633_T22", "type": "Gene_or_gene_product", "text": [ "matrix metalloproteinase-9" ], "offsets": [ [ 817, 843 ] ], "normalized": [] }, { "id": "PMID-11238633_T23", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 864, 866 ] ], "normalized": [] }, { "id": "PMID-11238633_T24", "type": "Gene_or_gene_product", "text": [ "vitronectin" ], "offsets": [ [ 880, 891 ] ], "normalized": [] }, { "id": "PMID-11238633_T25", "type": "Gene_or_gene_product", "text": [ "ICAM-1" ], "offsets": [ [ 908, 914 ] ], "normalized": [] }, { "id": "PMID-11238633_T26", "type": "Gene_or_gene_product", "text": [ "VCAM-1" ], "offsets": [ [ 919, 925 ] ], "normalized": [] }, { "id": "PMID-11238633_T27", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 974, 978 ] ], "normalized": [] }, { "id": "PMID-11238633_T28", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 979, 983 ] ], "normalized": [] }, { "id": "PMID-11238633_T29", "type": "Cell", "text": [ "lymphoid cells" ], "offsets": [ [ 1050, 1064 ] ], "normalized": [] }, { "id": "PMID-11238633_T30", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1069, 1071 ] ], "normalized": [] }, { "id": "PMID-11238633_T31", "type": "Gene_or_gene_product", "text": [ "IFN-inducible protein-10" ], "offsets": [ [ 1115, 1139 ] ], "normalized": [] }, { "id": "PMID-11238633_T32", "type": "Organism", "text": [ "nu/nu mice" ], "offsets": [ [ 1241, 1251 ] ], "normalized": [] }, { "id": "PMID-11238633_T33", "type": "Organism", "text": [ "nonobese diabetic-SCID mice" ], "offsets": [ [ 1253, 1280 ] ], "normalized": [] }, { "id": "PMID-11238633_T34", "type": "Cell", "text": [ "spc" ], "offsets": [ [ 1295, 1298 ] ], "normalized": [] }, { "id": "PMID-11238633_T35", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1320, 1324 ] ], "normalized": [] }, { "id": "PMID-11238633_T36", "type": "Gene_or_gene_product", "text": [ "CD4" ], "offsets": [ [ 1358, 1361 ] ], "normalized": [] }, { "id": "PMID-11238633_T37", "type": "Cell", "text": [ "CD4(+)" ], "offsets": [ [ 1358, 1364 ] ], "normalized": [] }, { "id": "PMID-11238633_T38", "type": "Gene_or_gene_product", "text": [ "CD8" ], "offsets": [ [ 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13	PMID-16310808	[ { "id": "PMID-16310808__text", "type": "abstract", "text": [ "Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells.\nAngiogenesis, new blood vessel formation, is a multistep process, precisely regulated by pro-angiogenic cytokines, which stimulate endothelial cells to migrate, proliferate and differentiate to form new capillary microvessels. Excessive vascular development and blood vessel remodeling appears in psoriasis, rheumatoid arthritis, diabetic retinopathy and solid tumors formation. Thalidomide [alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor of angiogenesis, but the mechanism of its inhibitory action remains unclear. The aim of the study was to investigate the potential influence of thalidomide on the several steps of angiogenesis, using in vitro models. We have evaluated the effect of thalidomide on VEGF secretion, cell migration, adhesion as well as in capillary formation of human endothelial cell line EA.hy 926. Thalidomide at the concentrations of 0.01 microM and 10 microM inhibited VEGF secretion into supernatants, decreased the number of formed capillary tubes and increased cell adhesion to collagen. Administration of thalidomide at the concentration of 0.01 microM increased cell migration, while at 10 microM, it decreased cell migration. Thalidomide in concentrations from 0.1 microM to 10 microM did not change cell proliferation of 72-h cell cultures. We conclude that anti-angiogenic action of thalidomide is due to direct inhibitory action on VEGF secretion and capillary microvessel formation as well as immunomodulatory influence on EA.hy 926 cells migration and adhesion.\n" ], "offsets": [ [ 0, 1659 ] ] } ]	[ { "id": "PMID-16310808_T1", "type": "Simple_chemical", "text": [ "thalidomide" ], "offsets": [ [ 10, 21 ] ], "normalized": [] }, { "id": "PMID-16310808_T2", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 32, 36 ] ], "normalized": [] }, { "id": "PMID-16310808_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 48, 52 ] ], "normalized": [] }, { "id": "PMID-16310808_T4", "type": "Tissue", "text": [ "capillary tube" ], "offsets": [ [ 77, 91 ] ], "normalized": [] }, { "id": "PMID-16310808_T5", "type": "Organism", "text": [ "human" ], "offsets": [ [ 105, 110 ] ], "normalized": [] }, { "id": "PMID-16310808_T6", "type": "Cell", "text": [ "endothelial EA.hy 926 cells" ], "offsets": [ [ 111, 138 ] ], "normalized": [] }, { "id": "PMID-16310808_T7", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 158, 170 ] ], "normalized": [] }, { "id": "PMID-16310808_T8", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 271, 288 ] ], "normalized": [] }, { "id": "PMID-16310808_T9", "type": "Tissue", "text": [ "capillary microvessels" ], "offsets": [ [ 343, 365 ] ], "normalized": [] }, { "id": "PMID-16310808_T10", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 377, 385 ] ], "normalized": [] }, { "id": "PMID-16310808_T11", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 402, 414 ] ], "normalized": [] }, { "id": "PMID-16310808_T12", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 495, 507 ] ], "normalized": [] }, { "id": "PMID-16310808_T13", "type": "Simple_chemical", "text": [ "Thalidomide" ], "offsets": [ [ 519, 530 ] ], "normalized": [] }, { "id": "PMID-16310808_T14", "type": "Simple_chemical", "text": [ "alpha-(N-phthalimido)-glutarimide" ], "offsets": [ [ 532, 565 ] ], "normalized": [] }, { "id": "PMID-16310808_T15", "type": "Simple_chemical", "text": [ "thalidomide" ], "offsets": [ [ 745, 756 ] ], "normalized": [] }, { "id": "PMID-16310808_T16", "type": "Simple_chemical", "text": [ "thalidomide" ], "offsets": [ [ 850, 861 ] ], "normalized": [] }, { "id": "PMID-16310808_T17", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 865, 869 ] ], "normalized": [] }, { "id": "PMID-16310808_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 881, 885 ] ], "normalized": [] }, { "id": "PMID-16310808_T19", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 920, 929 ] ], "normalized": [] }, { "id": "PMID-16310808_T20", "type": "Organism", "text": [ "human" ], "offsets": [ [ 943, 948 ] ], "normalized": [] }, { "id": "PMID-16310808_T21", "type": "Cell", "text": [ "endothelial cell line EA.hy 926" ], "offsets": [ [ 949, 980 ] ], "normalized": 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14	PMID-16855378	[ { "id": "PMID-16855378__text", "type": "abstract", "text": [ "Differential mechanisms of radiosensitization by 2-deoxy-D-glucose in the monolayers and multicellular spheroids of a human glioma cell line.\nIn vitro studies using monolayer cultures of human tumor cell lines have shown that 2-DG selectively inhibits energy-dependent DNA repair and cellular recovery processes in cancer cells. However, monolayer cultures differ greatly from the complex environmental conditions generated in solid tumors that develop inhomogeneous hypoxic and necrotic regions. In contrast, multicellular spheroids mimic heterogeneous cellular behavior and the consequent functional characteristics of in vivo solid tumors, and serve as important in vitro model to investigate tumor biology and responses to potential therapeutic agents. The present study compares the radiomodification by 2-DG in monolayer cultures and spheroids of a human glioma cell line (BMG-1) to gain insight into the effects in solid tumors. In spheroids, the glucose consumption (2.1 p mole/cell/h) and lactate production (3.67 p mole/cell/h) was nearly 2-3 fold higher than in monolayer cells (0.83 and 1.43 p mole/cell/h respectively). Presence of 2-DG (5 mM) for 2-4 h inhibited the glucose usage and lactate production by 70% in spheroids, while a 35% reduction was observed in monolayer cells. Under these conditions, 2-DG drastically enhanced the radiation-induced cell death of spheroids (by 2-3 folds); while a 40% increase was observed in monolayer cells. Radiosensitization by 2-DG in monolayer cells was primarily due to an increase in mitotic death (23%) linked to cytogenetic damage (micronuclei), whereas a profound induction of apoptosis (40%) accounted for the sensitization in spheroids. Although the Bcl-2 and Bax levels were significantly higher in spheroids, Bcl-2/Bax ratio was similar in monolayers and spheroids. Comet assay revealed a late onset of DNA breaks in the presence of 2- DG following irradiation only in spheroids, which corroborated well with the late onset of oxidative stress. 2-DG did not induce a significant cell cycle delay in monolayers, while a transient G(2) delay was apparent in spheroids.\n" ], "offsets": [ [ 0, 2132 ] ] } ]	[ { "id": "PMID-16855378_T1", "type": "Simple_chemical", "text": [ "2-deoxy-D-glucose" ], "offsets": [ [ 49, 66 ] ], "normalized": [] }, { "id": "PMID-16855378_T2", "type": "Cell", "text": [ "monolayers" ], "offsets": [ [ 74, 84 ] ], "normalized": [] }, { "id": "PMID-16855378_T3", "type": "Cell", "text": [ "multicellular spheroids" ], "offsets": [ [ 89, 112 ] ], "normalized": [] }, { "id": "PMID-16855378_T4", "type": "Organism", "text": [ "human" ], "offsets": [ [ 118, 123 ] ], "normalized": [] }, { "id": "PMID-16855378_T5", "type": "Cell", "text": [ "glioma cell line" ], "offsets": [ [ 124, 140 ] ], "normalized": [] }, { "id": "PMID-16855378_T6", "type": "Cell", "text": [ "monolayer cultures" ], "offsets": [ [ 165, 183 ] ], "normalized": [] }, { "id": "PMID-16855378_T7", "type": "Organism", "text": [ "human" ], "offsets": [ [ 187, 192 ] ], "normalized": [] }, { "id": "PMID-16855378_T8", "type": "Cell", "text": [ "tumor cell lines" ], "offsets": [ [ 193, 209 ] ], "normalized": [] }, { "id": "PMID-16855378_T9", "type": "Simple_chemical", "text": [ "2-DG" ], "offsets": [ [ 226, 230 ] ], "normalized": [] }, { "id": "PMID-16855378_T10", "type": "Cellular_component", "text": [ "DNA" ], "offsets": [ [ 269, 272 ] ], "normalized": [] }, { "id": "PMID-16855378_T11", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 284, 292 ] ], "normalized": [] }, { "id": "PMID-16855378_T12", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 315, 327 ] ], "normalized": [] }, { "id": "PMID-16855378_T13", "type": "Cell", "text": [ "monolayer cultures" ], "offsets": [ [ 338, 356 ] ], "normalized": [] }, { "id": "PMID-16855378_T14", "type": 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15	PMID-15725689	[ { "id": "PMID-15725689__text", "type": "abstract", "text": [ "Role of thrombogenic factors in the development of atherosclerosis.\nHemostatic factors play a crucial role in generating thrombotic plugs at sites of vascular damage (atherothrombosis). However, whether hemostatic factors contribute directly or indirectly to the pathogenesis of atherosclerosis remains uncertain. Autopsy studies have revealed that intimal thickening represents the first stage of atherosclerosis and that lipid-rich plaque arises from such lesions. Several factors contribute to the start of intimal thickening. Platelets release several growth factors and bioactive agents that play a central role in development of not only thrombus but also of intimal thickening. We have been investigating which coagulation factors simultaneously, or subsequently with platelet aggregation, participate in thrombus formation. Tissue factor (TF) is an essential initiator of blood coagulation that is expressed in various stages of atherosclerotic lesions in humans and other animals. Factors including thrombin and fibrin, which are downstream of the coagulation cascade activated by TF, also contribute to atherosclerosis. TF is involved in cell migration, embryogenesis and angiogenesis. Thus TF, in addition to factors downstream of the coagulation cascade and the protease-activated receptor 2 activation system, would be a multifactorial regulator of atherogenesis.\n" ], "offsets": [ [ 0, 1377 ] ] } ]	[ { "id": "PMID-15725689_T1", "type": "Gene_or_gene_product", "text": [ "thrombogenic factors" ], "offsets": [ [ 8, 28 ] ], "normalized": [] }, { "id": "PMID-15725689_T2", "type": "Gene_or_gene_product", "text": [ "Hemostatic factors" ], "offsets": [ [ 68, 86 ] ], "normalized": [] }, { "id": "PMID-15725689_T3", "type": "Pathological_formation", "text": [ "thrombotic plugs" ], "offsets": [ [ 121, 137 ] ], "normalized": [] }, { "id": "PMID-15725689_T4", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 150, 158 ] ], "normalized": [] }, { "id": "PMID-15725689_T5", "type": "Gene_or_gene_product", "text": [ "hemostatic factors" ], "offsets": [ [ 203, 221 ] ], "normalized": [] }, { "id": "PMID-15725689_T6", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 349, 356 ] ], "normalized": [] }, { "id": "PMID-15725689_T7", "type": "Pathological_formation", "text": [ "lipid-rich plaque" ], "offsets": [ [ 423, 440 ] ], "normalized": [] }, { "id": "PMID-15725689_T8", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 458, 465 ] ], "normalized": [] }, { "id": "PMID-15725689_T9", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 510, 517 ] ], "normalized": [] }, { "id": "PMID-15725689_T10", "type": "Cell", "text": [ "Platelets" ], "offsets": [ [ 530, 539 ] ], "normalized": [] }, { "id": "PMID-15725689_T11", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 644, 652 ] ], "normalized": [] }, { "id": "PMID-15725689_T12", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 665, 672 ] ], "normalized": [] }, { "id": "PMID-15725689_T13", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 775, 783 ] ], "normalized": [] }, { "id": "PMID-15725689_T14", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 812, 820 ] ], "normalized": [] }, { "id": "PMID-15725689_T15", "type": "Gene_or_gene_product", "text": [ "Tissue factor" ], "offsets": [ [ 832, 845 ] ], "normalized": [] }, { "id": "PMID-15725689_T16", "type": "Gene_or_gene_product", "text": [ "TF" ], "offsets": [ [ 847, 849 ] ], "normalized": [] }, { "id": "PMID-15725689_T17", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 880, 885 ] ], "normalized": [] }, { "id": "PMID-15725689_T18", "type": "Pathological_formation", "text": [ "atherosclerotic lesions" ], "offsets": [ [ 937, 960 ] ], "normalized": [] }, { "id": "PMID-15725689_T19", "type": "Organism", "text": [ "humans" ], "offsets": [ [ 964, 970 ] ], "normalized": [] }, { "id": "PMID-15725689_T20", "type": "Gene_or_gene_product", "text": [ "thrombin" ], "offsets": [ [ 1008, 1016 ] ], "normalized": [] }, { "id": "PMID-15725689_T21", "type": "Gene_or_gene_product", "text": [ "fibrin" ], "offsets": [ [ 1021, 1027 ] ], "normalized": [] }, { "id": "PMID-15725689_T22", "type": "Gene_or_gene_product", "text": [ "TF" ], "offsets": [ [ 1090, 1092 ] ], "normalized": [] }, { "id": "PMID-15725689_T23", "type": "Gene_or_gene_product", "text": [ "TF" ], "offsets": [ [ 1130, 1132 ] ], "normalized": [] }, { "id": "PMID-15725689_T24", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1148, 1152 ] ], "normalized": [] }, { "id": "PMID-15725689_T25", "type": "Gene_or_gene_product", "text": [ "TF" ], "offsets": [ [ 1201, 1203 ] ], "normalized": [] }, { "id": "PMID-15725689_T26", "type": "Gene_or_gene_product", "text": [ "protease-activated receptor 2" ], "offsets": [ [ 1274, 1303 ] ], "normalized": [] } ]	[ { "id": "PMID-15725689_E1", "type": "Positive_regulation", "trigger": { "text": [ "play a crucial role" ], "offsets": [ [ 87, 106 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15725689_T2" }, { "role": "Theme", "ref_id": "PMID-15725689_E2" } ] }, { "id": "PMID-15725689_E2", "type": "Development", 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"type": "Pathway", "trigger": { "text": [ "coagulation cascade" ], "offsets": [ [ 1057, 1076 ] ] }, "arguments": [] }, { "id": "PMID-15725689_E18", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1077, 1086 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15725689_T22" }, { "role": "Theme", "ref_id": "PMID-15725689_E17" } ] }, { "id": "PMID-15725689_E19", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 1136, 1144 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15725689_T23" }, { "role": "Theme", "ref_id": "PMID-15725689_E22" } ] }, { "id": "PMID-15725689_E20", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 1136, 1144 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-15725689_T23" }, { "role": "Theme", "ref_id": "PMID-15725689_E21" } ] }, { "id": "PMID-15725689_E21", "type": "Localization", "trigger": { "text": [ "migration" ], "offsets": [ [ 1153, 1162 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15725689_T24" } ] }, { "id": "PMID-15725689_E22", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 1182, 1194 ] ] }, "arguments": [] }, { "id": "PMID-15725689_E23", "type": "Pathway", "trigger": { "text": [ "coagulation cascade" ], "offsets": [ [ 1246, 1265 ] ] }, "arguments": [] }, { "id": "PMID-15725689_E24", "type": "Pathway", "trigger": { "text": [ "activation system" ], "offsets": [ [ 1304, 1321 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-15725689_T26" } ] } ]	[ { "id": "PMID-15725689_1", "entity_ids": [ "PMID-15725689_T15", "PMID-15725689_T16" ] } ]	[]
16	PMID-9206208	[ { "id": "PMID-9206208__text", "type": "abstract", "text": [ "[Expression of metastasis suppressor gene nm23 in human hepatocellular carcinoma]. \nFor the purpose of investigating the relationship between the metastatic potential of the tumor as well as the expression of nm23-H1 mRNA, and for determing the location of the positive sites in the cells, tumor metastasis suppressor gene nm23-H1 in human hepatocellular carcinoma (and the nonneoplastic area surrounding the tumor) was detected by in situ hybridization using digoxiginin-labeled nm23-H1 antisense complementary RNA probe. The primary results indicated (i) positive results of in situ hybridization are presence of granules or masses in the cytoplasm; (ii) the less expression of nm23-H1 mRNA, the higher metastatic rate of the human hepatocellular carcinoma (P < 0.05); (iii) expression of nm23-H1 mRNA dose not correlate with some other factors such as tumor size and the background of other liver diseases.\n" ], "offsets": [ [ 0, 910 ] ] } ]	[ { "id": "PMID-9206208_T1", "type": "Gene_or_gene_product", "text": [ "nm23" ], "offsets": [ [ 42, 46 ] ], "normalized": [] }, { "id": "PMID-9206208_T2", "type": "Organism", "text": [ "human" ], "offsets": [ [ 50, 55 ] ], "normalized": [] }, { "id": "PMID-9206208_T3", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 56, 80 ] ], "normalized": [] }, { "id": "PMID-9206208_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 174, 179 ] ], "normalized": [] }, { "id": "PMID-9206208_T5", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 209, 216 ] ], "normalized": [] }, { "id": "PMID-9206208_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 283, 288 ] ], "normalized": [] }, { "id": "PMID-9206208_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 290, 295 ] ], "normalized": [] }, { "id": "PMID-9206208_T8", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 323, 330 ] ], "normalized": [] }, { "id": "PMID-9206208_T9", "type": "Organism", "text": [ "human" ], "offsets": [ [ 334, 339 ] ], "normalized": [] }, { "id": "PMID-9206208_T10", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 340, 364 ] ], "normalized": [] }, { "id": "PMID-9206208_T11", "type": "Multi-tissue_structure", "text": [ "nonneoplastic area" ], "offsets": [ [ 374, 392 ] ], "normalized": [] }, { "id": "PMID-9206208_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 409, 414 ] ], "normalized": [] }, { "id": "PMID-9206208_T13", "type": "Simple_chemical", "text": [ "digoxiginin" ], "offsets": [ [ 460, 471 ] ], "normalized": [] }, { "id": "PMID-9206208_T14", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 480, 487 ] ], "normalized": [] }, { "id": "PMID-9206208_T15", "type": "Cellular_component", "text": [ "granules" ], "offsets": [ [ 615, 623 ] ], "normalized": [] }, { "id": "PMID-9206208_T16", "type": "Organism_substance", "text": [ "cytoplasm" ], "offsets": [ [ 641, 650 ] ], "normalized": [] }, { "id": "PMID-9206208_T17", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 680, 687 ] ], "normalized": [] }, { "id": "PMID-9206208_T18", "type": "Organism", "text": [ "human" ], "offsets": [ [ 728, 733 ] ], "normalized": [] }, { "id": "PMID-9206208_T19", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 734, 758 ] ], "normalized": [] }, { "id": "PMID-9206208_T20", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 791, 798 ] ], "normalized": [] }, { "id": "PMID-9206208_T21", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 855, 860 ] ], "normalized": [] }, { "id": "PMID-9206208_T22", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 894, 899 ] ], "normalized": [] } ]	[ { "id": "PMID-9206208_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 1, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T1" } ] }, { "id": "PMID-9206208_E2", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 15, 25 ] ] }, "arguments": [] }, { "id": "PMID-9206208_E3", "type": "Metastasis", "trigger": { "text": [ "metastatic" ], "offsets": [ [ 146, 156 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T4" } ] }, { "id": "PMID-9206208_E4", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 195, 205 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T5" } ] }, { "id": "PMID-9206208_E5", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 296, 306 ] ] }, "arguments": [] }, { "id": "PMID-9206208_E6", "type": "Planned_process", "trigger": { "text": [ "labeled" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-9206208_T13" } ] }, { "id": "PMID-9206208_E7", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 666, 676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T17" } ] }, { "id": "PMID-9206208_E8", "type": "Metastasis", "trigger": { "text": [ "metastatic" ], "offsets": [ [ 705, 715 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T19" } ] }, { "id": "PMID-9206208_E9", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 777, 787 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T20" } ] } ]	[]	[]

0

PMID-15193260

[ { "id": "PMID-15193260__text", "type": "abstract", "text": [ "Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. \nWe identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both proteins. Phosphorylation of BimL by Pak1 prevents it from interacting with and inactivation of Bcl-2, an antiapoptotic protein. Overexpression of DLC1 but not DLC1-Ser88Ala mutant promotes cancerous properties of breast cancer cells. DLC1 protein level is elevated in more than 90% of human breast tumors. The regulation of cell survival functions by Pak1-DLC1 interaction represents a novel mechanism by which a signaling kinase might regulate the cancerous phenotypes.\n" ], "offsets": [ [ 0, 907 ] ] } ]

[ { "id": "PMID-15193260_T1", "type": "Gene_or_gene_product", "text": [ "Dynein light chain 1" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "PMID-15193260_T2", "type": "Gene_or_gene_product", "text": [ "p21-activated kinase 1" ], "offsets": [ [ 24, 46 ] ], "normalized": [] }, { "id": "PMID-15193260_T3", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 79, 88 ] ], "normalized": [] }, { "id": "PMID-15193260_T4", "type": "Gene_or_gene_product", "text": [ "dynein light chain 1" ], "offsets": [ [ 116, 136 ] ], "normalized": [] }, { "id": "PMID-15193260_T5", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 138, 142 ] ], "normalized": [] }, { "id": "PMID-15193260_T6", "type": "Gene_or_gene_product", "text": [ "p21-activated kinase 1" ], "offsets": [ [ 174, 196 ] ], "normalized": [] }, { "id": "PMID-15193260_T7", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 198, 202 ] ], "normalized": [] }, { "id": "PMID-15193260_T8", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 205, 209 ] ], "normalized": [] }, { "id": "PMID-15193260_T9", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 210, 214 ] ], "normalized": [] }, { "id": "PMID-15193260_T10", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 254, 258 ] ], "normalized": [] }, { "id": "PMID-15193260_T11", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 286, 290 ] ], "normalized": [] }, { "id": "PMID-15193260_T12", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 312, 316 ] ], "normalized": [] }, { "id": "PMID-15193260_T13", "type": "Amino_acid", "text": [ "Ser88" ], "offsets": [ [ 320, 325 ] ], "normalized": [] }, { "id": "PMID-15193260_T14", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 327, 331 ] ], "normalized": [] }, { "id": "PMID-15193260_T15", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 363, 367 ] ], "normalized": [] }, { "id": "PMID-15193260_T16", "type": "Gene_or_gene_product", "text": [ "BimL" ], "offsets": [ [ 372, 376 ] ], "normalized": [] }, { "id": "PMID-15193260_T17", "type": "Gene_or_gene_product", "text": [ "BimL" ], "offsets": [ [ 464, 468 ] ], "normalized": [] }, { "id": "PMID-15193260_T18", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 472, 476 ] ], "normalized": [] }, { "id": "PMID-15193260_T19", "type": "Gene_or_gene_product", "text": [ "Bcl-2" ], "offsets": [ [ 531, 536 ] ], "normalized": [] }, { "id": "PMID-15193260_T20", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 582, 586 ] ], "normalized": [] }, { "id": "PMID-15193260_T21", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 595, 599 ] ], "normalized": [] }, { "id": "PMID-15193260_T22", "type": "Amino_acid", "text": [ "Ser88" ], "offsets": [ [ 600, 605 ] ], "normalized": [] }, { "id": "PMID-15193260_T23", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 625, 634 ] ], "normalized": [] }, { "id": "PMID-15193260_T24", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 649, 668 ] ], "normalized": [] }, { "id": "PMID-15193260_T25", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "PMID-15193260_T26", "type": "Organism", "text": [ "human" ], "offsets": [ [ 721, 726 ] ], "normalized": [] }, { "id": "PMID-15193260_T27", "type": "Cancer", "text": [ "breast tumors" ], "offsets": [ [ 727, 740 ] ], "normalized": [] }, { "id": "PMID-15193260_T28", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 760, 764 ] ], "normalized": [] }, { "id": "PMID-15193260_T29", "type": "Gene_or_gene_product", "text": [ "Pak1" ], "offsets": [ [ 787, 791 ] ], "normalized": [] }, { "id": "PMID-15193260_T30", "type": "Gene_or_gene_product", "text": [ "DLC1" ], "offsets": [ [ 792, 796 ] ], "normalized": [] }, { "id": "PMID-15193260_T31", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 885, 894 ] ], "normalized": [] } ]

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"role": "Cause", "ref_id": "PMID-15193260_E14" } ] }, { "id": "PMID-15193260_E18", "type": "Negative_regulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 477, 485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E21" }, { "role": "Cause", "ref_id": "PMID-15193260_E15" } ] }, { "id": "PMID-15193260_E19", "type": "Negative_regulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 477, 485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E20" }, { "role": "Cause", "ref_id": "PMID-15193260_E15" } ] }, { "id": "PMID-15193260_E20", "type": "Binding", "trigger": { "text": [ "interacting" ], "offsets": [ [ 494, 505 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T19" }, { "role": "Theme", "ref_id": "PMID-15193260_T18" }, { "role": "Theme", "ref_id": "PMID-15193260_T17" } ] }, { "id": "PMID-15193260_E21", "type": "Negative_regulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 515, 527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T19" } ] }, { "id": "PMID-15193260_E22", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 564, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T20" } ] }, { "id": "PMID-15193260_E23", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 564, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T21" } ] }, { "id": "PMID-15193260_E24", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 564, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E23" } ] }, { "id": "PMID-15193260_E25", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 564, 578 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E22" } ] }, { "id": "PMID-15193260_E26", "type": "Positive_regulation", "trigger": { "text": [ "promotes" ], "offsets": [ [ 616, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T23" }, { "role": "Cause", "ref_id": "PMID-15193260_E22" } ] }, { "id": "PMID-15193260_E27", "type": "Positive_regulation", "trigger": { "text": [ "promotes" ], "offsets": [ [ 616, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T23" }, { "role": "Cause", "ref_id": "PMID-15193260_E23" } ] }, { "id": "PMID-15193260_E28", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 692, 700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T25" } ] }, { "id": "PMID-15193260_E29", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 746, 756 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_E30" }, { "role": "Cause", "ref_id": "PMID-15193260_E31" } ] }, { "id": "PMID-15193260_E30", "type": "Death", "trigger": { "text": [ "survival" ], "offsets": [ [ 765, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T28" } ] }, { "id": "PMID-15193260_E31", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 797, 808 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T30" }, { "role": "Theme", "ref_id": "PMID-15193260_T29" } ] }, { "id": "PMID-15193260_E32", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 872, 880 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15193260_T31" } ] } ]

[ { "id": "PMID-15193260_1", "entity_ids": [ "PMID-15193260_T4", "PMID-15193260_T5" ] }, { "id": "PMID-15193260_2", "entity_ids": [ "PMID-15193260_T6", "PMID-15193260_T7" ] } ]

[]

1

PMID-10913166

[ { "id": "PMID-10913166__text", "type": "abstract", "text": [ "TEL, a putative tumor suppressor, modulates cell growth and cell morphology of ras-transformed cells while repressing the transcription of stromelysin-1. \nTEL is a member of the ETS family of transcription factors that interacts with the mSin3 and SMRT corepressors to regulate transcription. TEL is biallelically disrupted in acute leukemia, and loss of heterozygosity at the TEL locus has been observed in various cancers. Here we show that expression of TEL in Ras-transformed NIH 3T3 cells inhibits cell growth in soft agar and in normal cultures. Unexpectedly, cells expressing both Ras and TEL grew as aggregates. To begin to explain the morphology of Ras-plus TEL-expressing cells, we demonstrated that the endogenous matrix metalloproteinase stromelysin-1 was repressed by TEL. TEL bound sequences in the stromelysin-1 promoter and repressed the promoter in transient-expression assays, suggesting that it is a direct target for TEL-mediated regulation. Mutants of TEL that removed a binding site for the mSin3A corepressor but retained the ETS domain failed to repress stromelysin-1. When BB-94, a matrix metalloproteinase inhibitor, was added to the culture medium of Ras-expressing cells, it caused a cell aggregation phenotype similar to that caused by TEL expression. In addition, TEL inhibited the invasiveness of Ras-transformed cells in vitro and in vivo. Our results suggest that TEL acts as a tumor suppressor, in part, by transcriptional repression of stromelysin-1.\n" ], "offsets": [ [ 0, 1486 ] ] } ]

[ { "id": "PMID-10913166_T1", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-10913166_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 16, 21 ] ], "normalized": [] }, { "id": "PMID-10913166_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 44, 48 ] ], "normalized": [] }, { "id": "PMID-10913166_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 60, 64 ] ], "normalized": [] }, { "id": "PMID-10913166_T5", "type": "Gene_or_gene_product", "text": [ "ras" ], "offsets": [ [ 79, 82 ] ], "normalized": [] }, { "id": "PMID-10913166_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 95, 100 ] ], "normalized": [] }, { "id": "PMID-10913166_T7", "type": "Gene_or_gene_product", "text": [ "stromelysin-1" ], "offsets": [ [ 139, 152 ] ], "normalized": [] }, { "id": "PMID-10913166_T8", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 155, 158 ] ], "normalized": [] }, { "id": "PMID-10913166_T9", "type": "Gene_or_gene_product", "text": [ "ETS" ], "offsets": [ [ 178, 181 ] ], "normalized": [] }, { "id": "PMID-10913166_T10", "type": "Gene_or_gene_product", "text": [ "mSin3" ], "offsets": [ [ 238, 243 ] ], "normalized": [] }, { "id": "PMID-10913166_T11", "type": "Gene_or_gene_product", "text": [ "SMRT" ], "offsets": [ [ 248, 252 ] ], "normalized": [] }, { "id": "PMID-10913166_T12", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 293, 296 ] ], "normalized": [] }, { "id": "PMID-10913166_T13", "type": "Cancer", "text": [ "acute leukemia" ], "offsets": [ [ 327, 341 ] ], "normalized": [] }, { "id": "PMID-10913166_T14", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "PMID-10913166_T15", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 416, 423 ] ], "normalized": [] }, { "id": "PMID-10913166_T16", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 457, 460 ] ], "normalized": [] }, { "id": "PMID-10913166_T17", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 464, 467 ] ], "normalized": [] }, { "id": "PMID-10913166_T18", "type": "Cell", "text": [ "NIH 3T3 cells" ], "offsets": [ [ 480, 493 ] ], "normalized": [] }, { "id": "PMID-10913166_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 503, 507 ] ], "normalized": [] }, { "id": "PMID-10913166_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 566, 571 ] ], "normalized": [] }, { "id": "PMID-10913166_T21", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 588, 591 ] ], "normalized": [] }, { "id": "PMID-10913166_T22", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 596, 599 ] ], "normalized": [] }, { "id": "PMID-10913166_T23", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 658, 661 ] ], "normalized": [] }, { "id": "PMID-10913166_T24", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 667, 670 ] ], "normalized": [] }, { "id": "PMID-10913166_T25", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-10913166_T26", "type": "Gene_or_gene_product", "text": [ "matrix metalloproteinase stromelysin-1" ], "offsets": [ [ 725, 763 ] ], "normalized": [] }, { "id": "PMID-10913166_T27", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 781, 784 ] ], "normalized": [] }, { "id": "PMID-10913166_T28", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 786, 789 ] ], "normalized": [] }, { "id": "PMID-10913166_T29", "type": "Gene_or_gene_product", "text": [ "stromelysin-1" ], "offsets": [ [ 813, 826 ] ], "normalized": [] }, { "id": "PMID-10913166_T30", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 937, 940 ] ], "normalized": [] }, { "id": "PMID-10913166_T31", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 973, 976 ] ], "normalized": [] }, { "id": "PMID-10913166_T32", "type": "Gene_or_gene_product", "text": [ "mSin3A" ], "offsets": [ [ 1013, 1019 ] ], "normalized": [] }, { "id": "PMID-10913166_T33", "type": "Gene_or_gene_product", "text": [ "stromelysin-1" ], "offsets": [ [ 1078, 1091 ] ], "normalized": [] }, { "id": "PMID-10913166_T34", "type": "Simple_chemical", "text": [ "BB-94" ], "offsets": [ [ 1098, 1103 ] ], "normalized": [] }, { "id": "PMID-10913166_T35", "type": "Gene_or_gene_product", "text": [ "matrix metalloproteinase" ], "offsets": [ [ 1107, 1131 ] ], "normalized": [] }, { "id": "PMID-10913166_T36", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 1178, 1181 ] ], "normalized": [] }, { "id": "PMID-10913166_T37", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [] }, { "id": "PMID-10913166_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1212, 1216 ] ], "normalized": [] }, { "id": "PMID-10913166_T39", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 1265, 1268 ] ], "normalized": [] }, { "id": "PMID-10913166_T40", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 1294, 1297 ] ], "normalized": [] }, { "id": "PMID-10913166_T41", "type": "Gene_or_gene_product", "text": [ "Ras" ], "offsets": [ [ 1328, 1331 ] ], "normalized": [] }, { "id": "PMID-10913166_T42", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1344, 1349 ] ], "normalized": [] }, { "id": "PMID-10913166_T43", "type": "Gene_or_gene_product", "text": [ "TEL" ], "offsets": [ [ 1397, 1400 ] ], "normalized": [] }, { "id": "PMID-10913166_T44", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1411, 1416 ] ], "normalized": [] }, { "id": "PMID-10913166_T45", "type": "Gene_or_gene_product", "text": [ "stromelysin-1" ], "offsets": [ [ 1471, 1484 ] ], "normalized": [] }, { "id": "PMID-10913166_T63", "type": "DNA_domain_or_region", "text": [ "promoter" ], "offsets": [ [ 827, 835 ] ], "normalized": [] } ]

[ { "id": "PMID-10913166_E1", "type": "Regulation", "trigger": { "text": [ "modulates" ], "offsets": [ [ 34, 43 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_T1" }, { "role": "Theme", "ref_id": "PMID-10913166_E2" } ] }, { "id": "PMID-10913166_E2", "type": "Cell_proliferation", "trigger": { "text": [ "growth" ], "offsets": [ [ 49, 55 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T3" } ] }, { "id": "PMID-10913166_E3", "type": "Planned_process", "trigger": { "text": [ "transformed" ], "offsets": [ [ 83, 94 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10913166_T5" }, { "role": "Theme", "ref_id": "PMID-10913166_T6" } ] }, { "id": "PMID-10913166_E4", "type": "Negative_regulation", "trigger": { "text": [ "repressing" ], "offsets": [ [ 107, 117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_E5" }, { "role": "Cause", "ref_id": "PMID-10913166_T1" } ] }, { "id": "PMID-10913166_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 122, 135 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T7" } ] }, { "id": "PMID-10913166_E6", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 219, 228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T10" }, { "role": "Theme", "ref_id": "PMID-10913166_T11" }, { "role": "Theme", "ref_id": "PMID-10913166_T8" } ] }, { "id": "PMID-10913166_E7", "type": "Mutation", "trigger": { "text": [ "disrupted" ], "offsets": [ [ 314, 323 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T12" }, { "role": "AtLoc", "ref_id": "PMID-10913166_T13" } ] }, { "id": "PMID-10913166_E8", "type": "Mutation", "trigger": { "text": [ "loss of heterozygosity" ], "offsets": [ [ 347, 369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T14" }, { "role": "AtLoc", "ref_id": "PMID-10913166_T15" } ] }, { "id": "PMID-10913166_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 443, 453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T16" } ] }, { "id": "PMID-10913166_E10", "type": "Planned_process", "trigger": { "text": [ "transformed" ], "offsets": [ [ 468, 479 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10913166_T17" }, { "role": "Theme", "ref_id": "PMID-10913166_T18" } ] }, { "id": "PMID-10913166_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 494, 502 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_E9" }, { "role": "Theme", "ref_id": "PMID-10913166_E12" } ] }, { "id": "PMID-10913166_E12", "type": "Cell_proliferation", "trigger": { "text": [ "growth" ], "offsets": [ [ 508, 514 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T19" } ] }, { "id": "PMID-10913166_E13", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 572, 582 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T21" }, { "role": "Theme", "ref_id": "PMID-10913166_T22" } ] }, { "id": "PMID-10913166_E14", "type": "Growth", "trigger": { "text": [ "grew" ], "offsets": [ [ 600, 604 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T20" } ] }, { "id": "PMID-10913166_E15", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 671, 681 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T24" }, { "role": "Theme", "ref_id": "PMID-10913166_T23" } ] }, { "id": "PMID-10913166_E16", "type": "Negative_regulation", "trigger": { "text": [ "repressed" ], "offsets": [ [ 768, 777 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T26" }, { "role": "Cause", "ref_id": "PMID-10913166_T27" } ] }, { "id": "PMID-10913166_E17", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 790, 795 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T29" }, { "role": "Theme", "ref_id": "PMID-10913166_T28" }, { "role": "Site", "ref_id": "PMID-10913166_T63" } ] }, { "id": "PMID-10913166_E18", "type": "Negative_regulation", "trigger": { "text": [ "repressed" ], "offsets": [ [ 840, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_E19" }, { "role": "Cause", "ref_id": "PMID-10913166_T28" } ] }, { "id": "PMID-10913166_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 876, 886 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T29" } ] }, { "id": "PMID-10913166_E20", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 992, 999 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T31" } ] }, { "id": "PMID-10913166_E21", "type": "Negative_regulation", "trigger": { "text": [ "repress" ], "offsets": [ [ 1070, 1077 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T33" } ] }, { "id": "PMID-10913166_E22", "type": "Planned_process", "trigger": { "text": [ "added" ], "offsets": [ [ 1147, 1152 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10913166_T34" }, { "role": "Theme", "ref_id": "PMID-10913166_T37" } ] }, { "id": "PMID-10913166_E23", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1182, 1192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T36" } ] }, { "id": "PMID-10913166_E24", "type": "Positive_regulation", "trigger": { "text": [ "caused" ], "offsets": [ [ 1203, 1209 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_T34" }, { "role": "Theme", "ref_id": "PMID-10913166_E25" } ] }, { "id": "PMID-10913166_E25", "type": "Binding", "trigger": { "text": [ "aggregation" ], "offsets": [ [ 1217, 1228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T38" } ] }, { "id": "PMID-10913166_E26", "type": "Positive_regulation", "trigger": { "text": [ "caused" ], "offsets": [ [ 1255, 1261 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_E27" }, { "role": "Theme", "ref_id": "PMID-10913166_E25" } ] }, { "id": "PMID-10913166_E27", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1269, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T39" } ] }, { "id": "PMID-10913166_E28", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1298, 1307 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-10913166_T40" }, { "role": "Theme", "ref_id": "PMID-10913166_T42" } ] }, { "id": "PMID-10913166_E29", "type": "Planned_process", "trigger": { "text": [ "transformed" ], "offsets": [ [ 1332, 1343 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-10913166_T41" }, { "role": "Theme", "ref_id": "PMID-10913166_T42" } ] }, { "id": "PMID-10913166_E30", "type": "Negative_regulation", "trigger": { "text": [ "suppressor" ], "offsets": [ [ 1417, 1427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T44" }, { "role": "Cause", "ref_id": "PMID-10913166_E32" } ] }, { "id": "PMID-10913166_E31", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 1441, 1456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_T45" } ] }, { "id": "PMID-10913166_E32", "type": "Negative_regulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 1457, 1467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-10913166_E31" }, { "role": "Cause", "ref_id": "PMID-10913166_T43" } ] } ]

[]

2

PMID-12484699

[ { "id": "PMID-12484699__text", "type": "abstract", "text": [ "Regulation of transforming growth factor-beta signaling and vascular diseases.\nPURPOSE: Members of the transforming growth factor (TGF)-beta superfamily play critical roles in regulation of various cellular functions. Dysregulation of the signaling mechanisms of the TGF-beta superfamily proteins is associated with clinical diseases such as cancer, fibrotic diseases, and vascular disorders. Therefore, understanding these signaling mechanisms may provide us with novel ways to develop strategies for treating clinical diseases induced by these cytokines. METHODS: This review discusses our current understanding of the mechanisms of TGF-beta signaling, focusing on the roles of TGF-beta in regulation of vascular wall cells and on the regulation of TGF-beta superfamily signals by inhibitory Smads.\n" ], "offsets": [ [ 0, 801 ] ] } ]

[ { "id": "PMID-12484699_T1", "type": "Gene_or_gene_product", "text": [ "transforming growth factor-beta" ], "offsets": [ [ 14, 45 ] ], "normalized": [] }, { "id": "PMID-12484699_T2", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 60, 68 ] ], "normalized": [] }, { "id": "PMID-12484699_T3", "type": "Gene_or_gene_product", "text": [ "transforming growth factor (TGF)-beta" ], "offsets": [ [ 103, 140 ] ], "normalized": [] }, { "id": "PMID-12484699_T4", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 198, 206 ] ], "normalized": [] }, { "id": "PMID-12484699_T5", "type": "Gene_or_gene_product", "text": [ "TGF-beta" ], "offsets": [ [ 267, 275 ] ], "normalized": [] }, { "id": "PMID-12484699_T6", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 342, 348 ] ], "normalized": [] }, { "id": "PMID-12484699_T7", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 373, 381 ] ], "normalized": [] }, { "id": "PMID-12484699_T8", "type": "Gene_or_gene_product", "text": [ "TGF-beta" ], "offsets": [ [ 635, 643 ] ], "normalized": [] }, { "id": "PMID-12484699_T9", "type": "Gene_or_gene_product", "text": [ "TGF-beta" ], "offsets": [ [ 680, 688 ] ], "normalized": [] }, { "id": "PMID-12484699_T10", "type": "Cell", "text": [ "vascular wall cells" ], "offsets": [ [ 706, 725 ] ], "normalized": [] }, { "id": "PMID-12484699_T11", "type": "Gene_or_gene_product", "text": [ "TGF-beta" ], "offsets": [ [ 751, 759 ] ], "normalized": [] }, { "id": "PMID-12484699_T12", "type": "Gene_or_gene_product", "text": [ "Smads" ], "offsets": [ [ 794, 799 ] ], "normalized": [] } ]

[ { "id": "PMID-12484699_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_E2" } ] }, { "id": "PMID-12484699_E2", "type": "Pathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 46, 55 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-12484699_T1" } ] }, { "id": "PMID-12484699_E3", "type": "Regulation", "trigger": { "text": [ "Dysregulation" ], "offsets": [ [ 218, 231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T5" } ] }, { "id": "PMID-12484699_E4", "type": "Pathway", "trigger": { "text": [ "signaling mechanisms" ], "offsets": [ [ 239, 259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T5" } ] }, { "id": "PMID-12484699_E5", "type": "Regulation", "trigger": { "text": [ "associated" ], "offsets": [ [ 300, 310 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T6" }, { "role": "Cause", "ref_id": "PMID-12484699_E3" } ] }, { "id": "PMID-12484699_E6", "type": "Pathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 644, 653 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-12484699_T8" } ] }, { "id": "PMID-12484699_E7", "type": "Regulation", "trigger": { "text": [ "roles" ], "offsets": [ [ 671, 676 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12484699_T9" }, { "role": "Theme", "ref_id": "PMID-12484699_E8" } ] }, { "id": "PMID-12484699_E8", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 692, 702 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T10" } ] }, { "id": "PMID-12484699_E9", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 737, 747 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T11" }, { "role": "Cause", "ref_id": "PMID-12484699_E10" } ] }, { "id": "PMID-12484699_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibitory" ], "offsets": [ [ 783, 793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12484699_T12" } ] } ]

[]

3

PMID-16268479

[ { "id": "PMID-16268479__text", "type": "abstract", "text": [ "Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt.\nDomain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the P13-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response toVEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3alpha HKa and D5 inhibit phosphorylation of Akt and GSK-3alpha after stimulation withVEGF and S1P. Inhibitors of Akt and P13-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters P13-kinase-Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.\n" ], "offsets": [ [ 0, 1758 ] ] } ]

[ { "id": "PMID-16268479_T1", "type": "Gene_or_gene_product", "text": [ "high molecular weight kininogen" ], "offsets": [ [ 20, 51 ] ], "normalized": [] }, { "id": "PMID-16268479_T2", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 61, 77 ] ], "normalized": [] }, { "id": "PMID-16268479_T3", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 96, 99 ] ], "normalized": [] }, { "id": "PMID-16268479_T4", "type": "Gene_or_gene_product", "text": [ "high molecular weight kininogen" ], "offsets": [ [ 126, 157 ] ], "normalized": [] }, { "id": "PMID-16268479_T5", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 159, 162 ] ], "normalized": [] }, { "id": "PMID-16268479_T6", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 198, 214 ] ], "normalized": [] }, { "id": "PMID-16268479_T7", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 243, 247 ] ], "normalized": [] }, { "id": "PMID-16268479_T8", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 279, 282 ] ], "normalized": [] }, { "id": "PMID-16268479_T9", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 304, 320 ] ], "normalized": [] }, { "id": "PMID-16268479_T10", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 397, 400 ] ], "normalized": [] }, { "id": "PMID-16268479_T11", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 448, 464 ] ], "normalized": [] }, { "id": "PMID-16268479_T12", "type": "Gene_or_gene_product", "text": [ "sphingosine 1-phosphate" ], "offsets": [ [ 476, 499 ] ], "normalized": [] }, { "id": "PMID-16268479_T13", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 501, 504 ] ], "normalized": [] }, { "id": "PMID-16268479_T14", "type": "Gene_or_gene_product", "text": [ "vascular endothelial growth factor" ], "offsets": [ [ 510, 544 ] ], "normalized": [] }, { "id": "PMID-16268479_T15", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 546, 550 ] ], "normalized": [] }, { "id": "PMID-16268479_T16", "type": "Gene_or_gene_product", "text": [ "P13-kinase" ], "offsets": [ [ 574, 584 ] ], "normalized": [] }, { "id": "PMID-16268479_T17", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 585, 588 ] ], "normalized": [] }, { "id": "PMID-16268479_T18", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 608, 611 ] ], "normalized": [] }, { "id": "PMID-16268479_T19", "type": "Organism", "text": [ "bovine" ], "offsets": [ [ 627, 633 ] ], "normalized": [] }, { "id": "PMID-16268479_T20", "type": "Cell", "text": [ "pulmonary artery endothelial cell" ], "offsets": [ [ 634, 667 ] ], "normalized": [] }, { "id": "PMID-16268479_T21", "type": "Cell", "text": [ "BPAE" ], "offsets": [ [ 669, 673 ] ], "normalized": [] }, { "id": "PMID-16268479_T22", "type": "Cell", "text": [ "human umbilical vein endothelial cell" ], "offsets": [ [ 678, 715 ] ], "normalized": [] }, { "id": "PMID-16268479_T23", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-16268479_T24", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 780, 783 ] ], "normalized": [] }, { "id": "PMID-16268479_T25", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 816, 819 ] ], "normalized": [] }, { "id": "PMID-16268479_T26", "type": "Gene_or_gene_product", "text": [ "urokinase-type plasminogen activator receptor" ], "offsets": [ [ 849, 894 ] ], "normalized": [] }, { "id": "PMID-16268479_T27", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 901, 904 ] ], "normalized": [] }, { "id": "PMID-16268479_T28", "type": "Cell", "text": [ "BPAE cell" ], "offsets": [ [ 934, 943 ] ], "normalized": [] }, { "id": "PMID-16268479_T29", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 1033, 1036 ] ], "normalized": [] }, { "id": "PMID-16268479_T30", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 1040, 1044 ] ], "normalized": [] }, { "id": "PMID-16268479_T31", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 1046, 1049 ] ], "normalized": [] }, { "id": "PMID-16268479_T32", "type": "Gene_or_gene_product", "text": [ "paxillin" ], "offsets": [ [ 1084, 1092 ] ], "normalized": [] }, { "id": "PMID-16268479_T33", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 1100, 1115 ] ], "normalized": [] }, { "id": "PMID-16268479_T34", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 1122, 1125 ] ], "normalized": [] }, { "id": "PMID-16268479_T35", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "PMID-16268479_T36", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1173, 1186 ] ], "normalized": [] }, { "id": "PMID-16268479_T37", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 1233, 1236 ] ], "normalized": [] }, { "id": "PMID-16268479_T38", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 1263, 1266 ] ], "normalized": [] }, { "id": "PMID-16268479_T39", "type": "Gene_or_gene_product", "text": [ "GSK-3alpha" ], "offsets": [ [ 1296, 1306 ] ], "normalized": [] }, { "id": "PMID-16268479_T40", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 1307, 1310 ] ], "normalized": [] }, { "id": "PMID-16268479_T41", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 1345, 1348 ] ], "normalized": [] }, { "id": "PMID-16268479_T42", "type": "Gene_or_gene_product", "text": [ "GSK-3alpha" ], "offsets": [ [ 1353, 1363 ] ], "normalized": [] }, { "id": "PMID-16268479_T43", "type": "Gene_or_gene_product", "text": [ "withVEGF" ], "offsets": [ [ 1382, 1390 ] ], "normalized": [] }, { "id": "PMID-16268479_T44", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 1395, 1398 ] ], "normalized": [] }, { "id": "PMID-16268479_T45", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 1414, 1417 ] ], "normalized": [] }, { "id": "PMID-16268479_T46", "type": "Gene_or_gene_product", "text": [ "P13-kinase" ], "offsets": [ [ 1422, 1432 ] ], "normalized": [] }, { "id": "PMID-16268479_T47", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 1460, 1463 ] ], "normalized": [] }, { "id": "PMID-16268479_T48", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1471, 1487 ] ], "normalized": [] }, { "id": "PMID-16268479_T49", "type": "Gene_or_gene_product", "text": [ "paxillin" ], "offsets": [ [ 1510, 1518 ] ], "normalized": [] }, { "id": "PMID-16268479_T50", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 1539, 1554 ] ], "normalized": [] }, { "id": "PMID-16268479_T51", "type": "Gene_or_gene_product", "text": [ "VEGF" ], "offsets": [ [ 1578, 1582 ] ], "normalized": [] }, { "id": "PMID-16268479_T52", "type": "Gene_or_gene_product", "text": [ "S1P" ], "offsets": [ [ 1587, 1590 ] ], "normalized": [] }, { "id": "PMID-16268479_T53", "type": "Gene_or_gene_product", "text": [ "HKa" ], "offsets": [ [ 1618, 1621 ] ], "normalized": [] }, { "id": "PMID-16268479_T54", "type": "Gene_or_gene_product", "text": [ "P13-kinase" ], "offsets": [ [ 1651, 1661 ] ], "normalized": [] }, { "id": "PMID-16268479_T55", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 1662, 1665 ] ], "normalized": [] }, { "id": "PMID-16268479_T56", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1687, 1703 ] ], "normalized": [] }, { "id": "PMID-16268479_T57", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 1741, 1756 ] ], "normalized": [] }, { "id": "PMID-16268479_T58", "type": "Protein_domain_or_region", "text": [ "Domain 5" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "PMID-16268479_T63", "type": "Protein_domain_or_region", "text": [ "Domain 5" ], "offsets": [ [ 101, 109 ] ], "normalized": [] }, { "id": "PMID-16268479_T64", "type": "Protein_domain_or_region", "text": [ "D5" ], "offsets": [ [ 111, 113 ] ], "normalized": [] }, { "id": "PMID-16268479_T71", "type": "Protein_domain_or_region", "text": [ "D5" ], "offsets": [ [ 287, 289 ] ], "normalized": [] }, { "id": "PMID-16268479_T74", "type": "Protein_domain_or_region", "text": [ "D5" ], "offsets": [ [ 405, 407 ] ], "normalized": [] }, { "id": "PMID-16268479_T79", "type": "Protein_domain_or_region", "text": [ "D5" ], "offsets": [ [ 616, 618 ] ], "normalized": [] }, { "id": "PMID-16268479_T86", "type": "Protein_domain_or_region", "text": [ "D5" ], "offsets": [ [ 909, 911 ] ], "normalized": [] }, { "id": "PMID-16268479_T90", "type": "Protein_domain_or_region", "text": [ "D5" ], "offsets": [ [ 1054, 1056 ] ], "normalized": [] }, { "id": "PMID-16268479_T97", "type": "Protein_domain_or_region", "text": [ "D5" ], "offsets": [ [ 1315, 1317 ] ], "normalized": [] }, { "id": "PMID-16268479_T106", "type": "Protein_domain_or_region", "text": [ "D5" ], "offsets": [ [ 1634, 1636 ] ], "normalized": [] } ]

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"cleaved" ], "offsets": [ [ 118, 125 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_T4" } ] }, { "id": "PMID-16268479_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 164, 172 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_E8" }, { "role": "Cause", "ref_id": "PMID-16268479_T4" }, { "role": "CSite", "ref_id": "PMID-16268479_T63" } ] }, { "id": "PMID-16268479_E7", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 173, 185 ] ] }, "arguments": [] }, { "id": "PMID-16268479_E8", "type": "Localization", "trigger": { "text": [ "migration" ], "offsets": [ [ 215, 224 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_T6" } ] }, { "id": "PMID-16268479_E9", "type": "Pathway", "trigger": { "text": [ "signaling pathways" ], "offsets": [ [ 248, 266 ] ] }, "arguments": [] }, { "id": "PMID-16268479_E10", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 267, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_E11" }, { "role": "Cause", "ref_id": "PMID-16268479_E9" } ] }, { "id": "PMID-16268479_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 290, 300 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_E12" }, { "role": "Cause", "ref_id": "PMID-16268479_T8" }, { "role": "CSite", "ref_id": "PMID-16268479_T71" } ] }, { "id": "PMID-16268479_E12", "type": "Localization", "trigger": { "text": [ "migration" ], "offsets": [ [ 321, 330 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_T9" } ] }, { "id": "PMID-16268479_E13", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 408, 418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16268479_T14" }, { "role": "Cause", "ref_id": "PMID-16268479_E16" } ] }, { "id": "PMID-16268479_E14", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], 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[ { "id": "PMID-16268479_1", "entity_ids": [ "PMID-16268479_T4", "PMID-16268479_T5" ] }, { "id": "PMID-16268479_2", "entity_ids": [ "PMID-16268479_T12", "PMID-16268479_T13" ] }, { "id": "PMID-16268479_3", "entity_ids": [ "PMID-16268479_T14", "PMID-16268479_T15" ] }, { "id": "PMID-16268479_4", "entity_ids": [ "PMID-16268479_T20", "PMID-16268479_T21" ] }, { "id": "PMID-16268479_5", "entity_ids": [ "PMID-16268479_T64", "PMID-16268479_T63" ] } ]

[]

4

PMID-11121230

[ { "id": "PMID-11121230__text", "type": "abstract", "text": [ "RNA damage and inhibition of neoplastic endothelial cell growth: effects of human and amphibian ribonucleases.\nAngiogenesis defines the many steps involved in the growth and migration of endothelial cell-derived blood vessels. This process is necessary for the growth and metastasis of tumors, and considerable effort is being expended to find inhibitors of tumor angiogenesis. This usually involves screening of potential anti-angiogenic compounds on endothelial cells. To this end, two candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, were screened for their effects on endothelial cell proliferation using three distinct types of endothelial cells in culture: HPV-16 E6/E7-immortalized human umbilical vein endothelial cells (HUVECs), a Kras-transformed HPV-16 E6/E7 HUVEC (Rhim et al., Carcinogenesis 4, 673-681, 1998), and primary HUVECs. Onconase similarly inhibited proliferation in all three cell lines (IC(50) = 0.3-1.0 microM) while (-4)rhEDN was more effective on immortalized HUVEC cell lines (IC(50) = 0.02-0.06 microM) than on primary HUVECs (IC(50) > 0.1 microM). Differential sensitivity to these agents implies that more than one endothelial cell type must be used in proliferation assays to screen for novel anti-angiogenic compounds.\n" ], "offsets": [ [ 0, 1275 ] ] } ]

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"derived" ], "offsets": [ [ 204, 211 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T5" } ] }, { "id": "PMID-11121230_E7", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 243, 252 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_E3" }, { "role": "Theme", "ref_id": "PMID-11121230_E9" } ] }, { "id": "PMID-11121230_E8", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 243, 252 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_E3" }, { "role": "Theme", "ref_id": "PMID-11121230_E10" } ] }, { "id": "PMID-11121230_E9", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 261, 267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T6" } ] }, { "id": "PMID-11121230_E10", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 272, 282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T6" } ] }, { "id": "PMID-11121230_E11", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 364, 376 ] ] }, "arguments": [ { "role": "AtLoc", "ref_id": "PMID-11121230_T7" } ] }, { "id": "PMID-11121230_E12", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 428, 438 ] ] }, "arguments": [] }, { "id": "PMID-11121230_E13", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 503, 513 ] ] }, "arguments": [] }, { "id": "PMID-11121230_E14", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 583, 590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_E16" }, { "role": "Cause", "ref_id": "PMID-11121230_T10" } ] }, { "id": "PMID-11121230_E15", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 583, 590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_E16" }, { "role": "Cause", "ref_id": "PMID-11121230_T9" } ] }, { "id": "PMID-11121230_E16", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 611, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T11" } ] }, { "id": "PMID-11121230_E17", "type": "Planned_process", "trigger": { "text": [ "immortalized" ], "offsets": [ [ 698, 710 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T15" }, { "role": "Instrument", "ref_id": "PMID-11121230_T14" } ] }, { "id": "PMID-11121230_E18", "type": "Planned_process", "trigger": { "text": [ "immortalized" ], "offsets": [ [ 698, 710 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T15" }, { "role": "Instrument", "ref_id": "PMID-11121230_T13" } ] }, { "id": "PMID-11121230_E19", "type": "Planned_process", "trigger": { "text": [ "transformed" ], "offsets": [ [ 767, 778 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-11121230_T17" }, { "role": "Theme", "ref_id": "PMID-11121230_T20" } ] }, { "id": "PMID-11121230_E20", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 885, 894 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_T22" }, { "role": "Theme", "ref_id": "PMID-11121230_E21" } ] }, { "id": "PMID-11121230_E21", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 895, 908 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T23" } ] }, { "id": "PMID-11121230_E22", "type": "Positive_regulation", "trigger": { "text": [ "effective" ], "offsets": [ [ 984, 993 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_T24" }, { "role": "Theme", "ref_id": "PMID-11121230_T25" } ] }, { "id": "PMID-11121230_E23", "type": "Positive_regulation", "trigger": { "text": [ "effective" ], "offsets": [ [ 984, 993 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11121230_T24" }, { "role": "Theme", "ref_id": "PMID-11121230_T26" } ] }, { "id": "PMID-11121230_E24", "type": "Planned_process", "trigger": { "text": [ "immortalized" ], "offsets": [ [ 997, 1009 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T25" } ] }, { "id": "PMID-11121230_E25", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 1207, 1220 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11121230_T27" } ] }, { "id": "PMID-11121230_E26", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 1253, 1263 ] ] }, "arguments": [] } ]

[ { "id": "PMID-11121230_1", "entity_ids": [ "PMID-11121230_T15", "PMID-11121230_T16" ] } ]

[]

5

PMID-12610665

[ { "id": "PMID-12610665__text", "type": "abstract", "text": [ "Arteriogenesis: the development and growth of collateral arteries.\nIn patients with atherosclerotic vascular diseases, collateral vessels bypassing major arterial obstructions have frequently been observed. This may explain why some patients remain without symptoms or signs of ischemia. The term \"arteriogenesis\" was introduced to differentiate the formation of collateral arteries from angiogenesis, which mainly occurs in the ischemic, collateral flow-dependent tissue. Many observations in various animal models and humans support that the remodeling of preexisting collateral vessels is the mechanism of collateral artery formation. This remodeling process seems to be mainly flow-mediated. It involves endothelial cell activation, basal membrane degradation, leukocyte invasion, proliferation of vascular cells, neointima formation (in most species studied), and changes of the extracellular matrix. The contribution of ischemia to arteriogenesis is still unclear, but arteriogenesis clearly can occur in the absence of any significant ischemia. It is questionable, whether collateral arteries also form de novo in ischemic vascular diseases. A better understanding of the mechanisms of arteriogenesis will be important for the design of more effective strategies for the treatment of patients with ischemic vascular diseases.\n" ], "offsets": [ [ 0, 1333 ] ] } ]

[ { "id": "PMID-12610665_T1", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 46, 65 ] ], "normalized": [] }, { "id": "PMID-12610665_T2", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 70, 78 ] ], "normalized": [] }, { "id": "PMID-12610665_T3", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 100, 108 ] ], "normalized": [] }, { "id": "PMID-12610665_T4", "type": "Multi-tissue_structure", "text": [ "collateral vessels" ], "offsets": [ [ 119, 137 ] ], "normalized": [] }, { "id": "PMID-12610665_T5", "type": "Pathological_formation", "text": [ "arterial obstructions" ], "offsets": [ [ 154, 175 ] ], "normalized": [] }, { "id": "PMID-12610665_T6", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 233, 241 ] ], "normalized": [] }, { "id": "PMID-12610665_T7", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 363, 382 ] ], "normalized": [] }, { "id": "PMID-12610665_T8", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 465, 471 ] ], "normalized": [] }, { "id": "PMID-12610665_T9", "type": "Organism", "text": [ "humans" ], "offsets": [ [ 520, 526 ] ], "normalized": [] }, { "id": "PMID-12610665_T10", "type": "Multi-tissue_structure", "text": [ "collateral vessels" ], "offsets": [ [ 570, 588 ] ], "normalized": [] }, { "id": "PMID-12610665_T11", "type": "Multi-tissue_structure", "text": [ "collateral artery" ], "offsets": [ [ 609, 626 ] ], "normalized": [] }, { "id": "PMID-12610665_T12", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 708, 724 ] ], "normalized": [] }, { "id": "PMID-12610665_T13", "type": "Cellular_component", "text": [ "basal membrane" ], "offsets": [ [ 737, 751 ] ], "normalized": [] }, { "id": "PMID-12610665_T14", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 765, 774 ] ], "normalized": [] }, { "id": "PMID-12610665_T15", "type": "Cell", "text": [ "vascular cells" ], "offsets": [ [ 802, 816 ] ], "normalized": [] }, { "id": "PMID-12610665_T16", "type": "Tissue", "text": [ "neointima" ], "offsets": [ [ 818, 827 ] ], "normalized": [] }, { "id": "PMID-12610665_T17", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 884, 904 ] ], "normalized": [] }, { "id": "PMID-12610665_T18", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 1080, 1099 ] ], "normalized": [] }, { "id": "PMID-12610665_T19", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1130, 1138 ] ], "normalized": [] }, { "id": "PMID-12610665_T20", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 1291, 1299 ] ], "normalized": [] }, { "id": "PMID-12610665_T21", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1314, 1322 ] ], "normalized": [] } ]

[ { "id": "PMID-12610665_E1", "type": "Blood_vessel_development", "trigger": { "text": [ "Arteriogenesis" ], "offsets": [ [ 0, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T1" } ] }, { "id": "PMID-12610665_E2", "type": "Development", "trigger": { "text": [ "development" ], "offsets": [ [ 20, 31 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T1" } ] }, { "id": "PMID-12610665_E3", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 36, 42 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T1" } ] }, { "id": "PMID-12610665_E4", "type": "Blood_vessel_development", "trigger": { "text": [ "arteriogenesis" ], "offsets": [ [ 298, 312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T7" } ] }, { "id": "PMID-12610665_E5", "type": "Development", "trigger": { "text": [ "formation" ], "offsets": [ [ 350, 359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T7" } ] }, { "id": "PMID-12610665_E6", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 388, 400 ] ] }, "arguments": [] }, { "id": "PMID-12610665_E7", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 455, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T8" } ] }, { "id": "PMID-12610665_E8", "type": "Remodeling", "trigger": { "text": [ "remodeling" ], "offsets": [ [ 544, 554 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T10" } ] }, { "id": "PMID-12610665_E9", "type": "Development", "trigger": { "text": [ "formation" ], "offsets": [ [ 627, 636 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T11" } ] }, { "id": "PMID-12610665_E10", "type": "Remodeling", "trigger": { "text": [ "remodeling" ], "offsets": [ [ 643, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T10" } ] }, { "id": "PMID-12610665_E11", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E17" } ] }, { "id": "PMID-12610665_E12", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E18" } ] }, { "id": "PMID-12610665_E13", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E19" } ] }, { "id": "PMID-12610665_E14", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E20" } ] }, { "id": "PMID-12610665_E15", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E21" } ] }, { "id": "PMID-12610665_E16", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 699, 707 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12610665_E10" }, { "role": "Theme", "ref_id": "PMID-12610665_E22" } ] }, { "id": "PMID-12610665_E17", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 725, 735 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T12" } ] }, { "id": "PMID-12610665_E18", "type": "Breakdown", "trigger": { "text": [ "degradation" ], "offsets": [ [ 752, 763 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T13" } ] }, { "id": "PMID-12610665_E19", "type": "Localization", "trigger": { "text": [ "invasion" ], "offsets": [ [ 775, 783 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T14" } ] }, { "id": "PMID-12610665_E20", "type": "Cell_proliferation", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 785, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T15" } ] }, { "id": "PMID-12610665_E21", "type": "Development", "trigger": { "text": [ "formation" ], "offsets": [ [ 828, 837 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T16" } ] }, { "id": "PMID-12610665_E22", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 869, 876 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T17" } ] }, { "id": "PMID-12610665_E23", "type": "Blood_vessel_development", "trigger": { "text": [ "arteriogenesis" ], "offsets": [ [ 938, 952 ] ] }, "arguments": [] }, { "id": "PMID-12610665_E24", "type": "Blood_vessel_development", "trigger": { "text": [ "arteriogenesis" ], "offsets": [ [ 975, 989 ] ] }, "arguments": [] }, { "id": "PMID-12610665_E25", "type": "Development", "trigger": { "text": [ "form" ], "offsets": [ [ 1105, 1109 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12610665_T18" } ] }, { "id": "PMID-12610665_E26", "type": "Blood_vessel_development", "trigger": { "text": [ "arteriogenesis" ], "offsets": [ [ 1193, 1207 ] ] }, "arguments": [] } ]

[]

6

PMID-20978953

[ { "id": "PMID-20978953__text", "type": "abstract", "text": [ "Role of stromal myofibroblasts in invasive breast cancer: stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome. \nBACKGROUND: Recently, the desmoplastic reaction has been implicated as having an important function in epithelial solid tumor biology. There have been no reports showing the relativity of invasive breast cancer and the desmoplastic reaction by a quantitative analysis of the myofibroblasts that were an important player in the desmoplastic reaction. The purpose of this study was to immunohistochemically investigate the correlation between the desmoplastic reaction and the clinicopathology of invasive breast cancer. METHODS: The study included 60 patients with a known prognosis of invasive breast cancer. We quantified the expression of alpha-SMA as a marker of myofibroblasts in the invasive breast cancer. After staining samples for alpha-SMA, their expression was extracted and quantified as a relative percentage by computer-assisted image analysis. RESULTS: There was relatively wide variation in the expression of alpha-SMA with the percentage of the area from 0.68 to 28.15% (mean 8.48 +/- 5.40%). The metastasis group showed significantly higher alpha-SMA expression compared with the no metastasis group (p < 0.001). When the patients were divided into two groups according to their alpha-SMA expression using a cutoff point at the mean value of 8.48%, the high alpha-SMA group had a significantly poorer overall survival rate (p < 0.001). Multivariate analysis demonstrated that alpha-SMA and lymph node metastasis were identified as independent predictive factors of metastasis. CONCLUSION: Myofibroblasts represent an important prognostic factor for invasive growth that is translated into a poor clinical prognosis for patients with invasive breast cancer.\n" ], "offsets": [ [ 0, 1821 ] ] } ]

[ { "id": "PMID-20978953_T1", "type": "Cell", "text": [ "stromal myofibroblasts" ], "offsets": [ [ 8, 30 ] ], "normalized": [] }, { "id": "PMID-20978953_T2", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 43, 56 ] ], "normalized": [] }, { "id": "PMID-20978953_T3", "type": "Cell", "text": [ "stromal" ], "offsets": [ [ 58, 65 ] ], "normalized": [] }, { "id": "PMID-20978953_T4", "type": "Gene_or_gene_product", "text": [ "alpha-smooth muscle actin" ], "offsets": [ [ 80, 105 ] ], "normalized": [] }, { "id": "PMID-20978953_T5", "type": "Cancer", "text": [ "epithelial solid tumor" ], "offsets": [ [ 250, 272 ] ], "normalized": [] }, { "id": "PMID-20978953_T6", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 344, 357 ] ], "normalized": [] }, { "id": "PMID-20978953_T7", "type": "Cell", "text": [ "myofibroblasts" ], "offsets": [ [ 422, 436 ] ], "normalized": [] }, { "id": "PMID-20978953_T8", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 651, 664 ] ], "normalized": [] }, { "id": "PMID-20978953_T9", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 697, 705 ] ], "normalized": [] }, { "id": "PMID-20978953_T10", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 732, 754 ] ], "normalized": [] }, { "id": "PMID-20978953_T11", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 788, 797 ] ], "normalized": [] }, { "id": "PMID-20978953_T12", "type": "Cell", "text": [ "myofibroblasts" ], "offsets": [ [ 813, 827 ] ], "normalized": [] }, { "id": "PMID-20978953_T13", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 844, 857 ] ], "normalized": [] }, { "id": "PMID-20978953_T14", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 886, 895 ] ], "normalized": [] }, { "id": "PMID-20978953_T15", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1071, 1080 ] ], "normalized": [] }, { "id": "PMID-20978953_T16", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1205, 1214 ] ], "normalized": [] }, { "id": "PMID-20978953_T17", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 1286, 1294 ] ], "normalized": [] }, { "id": "PMID-20978953_T18", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1343, 1352 ] ], "normalized": [] }, { "id": "PMID-20978953_T19", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1422, 1431 ] ], "normalized": [] }, { "id": "PMID-20978953_T20", "type": "Gene_or_gene_product", "text": [ "alpha-SMA" ], "offsets": [ [ 1540, 1549 ] ], "normalized": [] }, { "id": "PMID-20978953_T21", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 1554, 1564 ] ], "normalized": [] }, { "id": "PMID-20978953_T22", "type": "Cell", "text": [ "Myofibroblasts" ], "offsets": [ [ 1653, 1667 ] ], "normalized": [] }, { "id": "PMID-20978953_T23", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 1783, 1791 ] ], "normalized": [] }, { "id": "PMID-20978953_T24", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 1797, 1819 ] ], "normalized": [] } ]

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[]

7

PMID-7474113

[ { "id": "PMID-7474113__text", "type": "abstract", "text": [ "The inhibition of cultured myoblast differentiation by the simian virus 40 large T antigen occurs after myogenin expression and Rb up-regulation and is not exerted by transformation-competent cytoplasmic mutants. \nWe have investigated the mechanism by which the simian virus 40 large T antigen (SVLT) interferes with the differentiation of C2 myoblasts. SVLT mutants, defective either in the Rb binding site, near the N-terminal end, in a region that affects binding to p53, or in the nuclear transport signal, were also employed to determine whether the interference was especially dependent on these functional domains. It was found that wild-type (wt) SVLT strongly inhibited the terminal differentiation of mouse C2 myoblasts, but this arrest occurred only after the synthesis of myogenin, an initial step in biochemical differentiation. Neither the synthesis nor some basic activities of MyoD appeared to be affected by wt SVLT. In these transformants, mitogen depletion elicited an increase in the Rb level comparable to that in normal C2 cells; wt SVLT, however, promoted the phosphorylation of a large part of the induced Rb. Mutations affecting nuclear transport were far more critical for the ability to interfere with myogenic differentiation than were those affecting the transforming potential; cytoplasmic SVLT expression was fully compatible with the terminal differentiation of C2 cells, despite enabling them to grow in semisolid medium, thus showing that the myogenesis-inhibiting property can be dissociated from transforming competence. The remaining SVLT mutants presented different degrees of ability to inhibit differentiation (as shown by the expression of tissue-specific markers in transformants). The inhibiting mutants, including the Rb binding site mutant, were able to promote a higher state of Rb phosphorylation than that observed in either normal cells or cytoplasmic-SVLT transformants.\n" ], "offsets": [ [ 0, 1921 ] ] } ]

[ { "id": "PMID-7474113_T1", "type": "Cell", "text": [ "myoblast" ], "offsets": [ [ 27, 35 ] ], "normalized": [] }, { "id": "PMID-7474113_T2", "type": "Organism", "text": [ "simian virus 40" ], "offsets": [ [ 59, 74 ] ], "normalized": [] }, { "id": "PMID-7474113_T3", "type": "Gene_or_gene_product", "text": [ "large T antigen" ], "offsets": [ [ 75, 90 ] ], "normalized": [] }, { "id": "PMID-7474113_T4", "type": "Gene_or_gene_product", "text": [ "myogenin" ], "offsets": [ [ 104, 112 ] ], "normalized": [] }, { "id": "PMID-7474113_T5", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 128, 130 ] ], "normalized": [] }, { "id": "PMID-7474113_T6", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 192, 203 ] ], "normalized": [] }, { "id": "PMID-7474113_T7", "type": "Organism", "text": [ "simian virus 40" ], "offsets": [ [ 262, 277 ] ], "normalized": [] }, { "id": "PMID-7474113_T8", "type": "Gene_or_gene_product", "text": [ "large T antigen" ], "offsets": [ [ 278, 293 ] ], "normalized": [] }, { "id": "PMID-7474113_T9", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 295, 299 ] ], "normalized": [] }, { "id": "PMID-7474113_T10", "type": "Cell", "text": [ "C2 myoblasts" ], "offsets": [ [ 340, 352 ] ], "normalized": [] }, { "id": "PMID-7474113_T11", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 354, 358 ] ], "normalized": [] }, { "id": "PMID-7474113_T12", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 392, 394 ] ], "normalized": [] }, { "id": "PMID-7474113_T13", "type": "Gene_or_gene_product", "text": [ "p53" ], "offsets": [ [ 470, 473 ] ], "normalized": [] }, { "id": "PMID-7474113_T14", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 655, 659 ] ], "normalized": [] }, { "id": "PMID-7474113_T15", "type": "Organism", "text": [ "mouse" ], "offsets": [ [ 711, 716 ] ], "normalized": [] }, { "id": "PMID-7474113_T16", "type": "Cell", "text": [ "C2 myoblasts" ], "offsets": [ [ 717, 729 ] ], "normalized": [] }, { "id": "PMID-7474113_T17", "type": "Gene_or_gene_product", "text": [ "myogenin" ], "offsets": [ [ 784, 792 ] ], "normalized": [] }, { "id": "PMID-7474113_T18", "type": "Gene_or_gene_product", "text": [ "MyoD" ], "offsets": [ [ 893, 897 ] ], "normalized": [] }, { "id": "PMID-7474113_T19", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 928, 932 ] ], "normalized": [] }, { "id": "PMID-7474113_T20", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 943, 956 ] ], "normalized": [] }, { "id": "PMID-7474113_T21", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 1004, 1006 ] ], "normalized": [] }, { "id": "PMID-7474113_T22", "type": "Cell", "text": [ "C2 cells" ], "offsets": [ [ 1042, 1050 ] ], "normalized": [] }, { "id": "PMID-7474113_T23", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 1055, 1059 ] ], "normalized": [] }, { "id": "PMID-7474113_T24", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 1130, 1132 ] ], "normalized": [] }, { "id": "PMID-7474113_T25", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1154, 1161 ] ], "normalized": [] }, { "id": "PMID-7474113_T26", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1308, 1319 ] ], "normalized": [] }, { "id": "PMID-7474113_T27", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 1320, 1324 ] ], "normalized": [] }, { "id": "PMID-7474113_T28", "type": "Cell", "text": [ "C2 cells" ], "offsets": [ [ 1394, 1402 ] ], "normalized": [] }, { "id": "PMID-7474113_T29", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 1571, 1575 ] ], "normalized": [] }, { "id": "PMID-7474113_T30", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1681, 1687 ] ], "normalized": [] }, { "id": "PMID-7474113_T31", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 1708, 1721 ] ], "normalized": [] }, { "id": "PMID-7474113_T32", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 1762, 1764 ] ], "normalized": [] }, { "id": "PMID-7474113_T33", "type": "Gene_or_gene_product", "text": [ "Rb" ], "offsets": [ [ 1825, 1827 ] ], "normalized": [] }, { "id": "PMID-7474113_T34", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1880, 1885 ] ], "normalized": [] }, { "id": "PMID-7474113_T35", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1889, 1900 ] ], "normalized": [] }, { "id": "PMID-7474113_T36", "type": "Gene_or_gene_product", "text": [ "SVLT" ], "offsets": [ [ 1901, 1905 ] ], "normalized": [] }, { "id": "PMID-7474113_T37", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 1906, 1919 ] ], "normalized": [] } ]

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"PMID-7474113_T24" } ] }, { "id": "PMID-7474113_E20", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1122, 1129 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T24" } ] }, { "id": "PMID-7474113_E21", "type": "Mutation", "trigger": { "text": [ "Mutations" ], "offsets": [ [ 1134, 1143 ] ] }, "arguments": [] }, { "id": "PMID-7474113_E22", "type": "Regulation", "trigger": { "text": [ "affecting" ], "offsets": [ [ 1144, 1153 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-7474113_E21" }, { "role": "Theme", "ref_id": "PMID-7474113_E23" } ] }, { "id": "PMID-7474113_E23", "type": "Localization", "trigger": { "text": [ "transport" ], "offsets": [ [ 1162, 1171 ] ] }, "arguments": [ { "role": "ToLoc", "ref_id": "PMID-7474113_T25" }, { "role": "Theme", "ref_id": "PMID-7474113_T27" } ] }, { "id": "PMID-7474113_E24", "type": "Positive_regulation", "trigger": { "text": [ "critical" ], "offsets": [ [ 1186, 1194 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-7474113_E21" }, { "role": "Theme", "ref_id": "PMID-7474113_E25" } ] }, { "id": "PMID-7474113_E25", "type": "Negative_regulation", "trigger": { "text": [ "interfere" ], "offsets": [ [ 1214, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E26" } ] }, { "id": "PMID-7474113_E26", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1238, 1253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" } ] }, { "id": "PMID-7474113_E27", "type": "Regulation", "trigger": { "text": [ "affecting" ], "offsets": [ [ 1270, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E28" }, { "role": "Cause", "ref_id": "PMID-7474113_E21" } ] }, { "id": "PMID-7474113_E28", "type": "Cell_transformation", "trigger": { "text": [ "transforming" ], "offsets": [ [ 1284, 1296 ] ] }, "arguments": [] }, { "id": "PMID-7474113_E29", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1325, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T27" } ] }, { "id": "PMID-7474113_E30", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1375, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" } ] }, { "id": "PMID-7474113_E31", "type": "Cell_proliferation", "trigger": { "text": [ "grow" ], "offsets": [ [ 1429, 1433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" } ] }, { "id": "PMID-7474113_E32", "type": "Negative_regulation", "trigger": { "text": [ "inhibiting" ], "offsets": [ [ 1488, 1498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" }, { "role": "Cause", "ref_id": "PMID-7474113_T27" } ] }, { "id": "PMID-7474113_E33", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1626, 1633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E34" } ] }, { "id": "PMID-7474113_E34", "type": "Cell_differentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1634, 1649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T28" } ] }, { "id": "PMID-7474113_E35", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1765, 1772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T32" } ] }, { "id": "PMID-7474113_E36", "type": "Positive_regulation", "trigger": { "text": [ "promote" ], "offsets": [ [ 1799, 1806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_E37" } ] }, { "id": "PMID-7474113_E37", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1828, 1843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7474113_T33" } ] } ]

[ { "id": "PMID-7474113_1", "entity_ids": [ "PMID-7474113_T8", "PMID-7474113_T9" ] } ]

[]

8

PMID-17462601

[ { "id": "PMID-17462601__text", "type": "abstract", "text": [ "An antibody directed against PDGF receptor beta enhances the antitumor and the anti-angiogenic activities of an anti-VEGF receptor 2 antibody.\nPlatelet-derived growth factor (PDGF) and its receptors (PDGFR) play important roles in tumorigenesis through stimulating tumor growth and promoting angiogenesis via enhancing pericyte recruitment and vessel maturation. Here we produced a neutralizing antibody, 1B3, directed against mouse PDGFRbeta. 1B3 binds to PDGFRbeta with high affinity (9x10(-11)M) and blocks PDGF-BB from binding to the receptor with an IC(50) of approximately 1.2 nM. The antibody also blocks ligand-stimulated activation of PDGFRbeta and downstream signaling molecules, including Akt and MAPK p42/44, in tumor cells. In animal studies, 1B3 significantly enhanced the antitumor and the anti-angiogenic activities of DC101, an antibody directed against mouse vascular endothelial growth factor receptor 2, in a pancreatic (BxPC-3) and a non-small cell lung (NCI-H460) tumor xenograft models. Treatment with the combination of 1B3 and DC101 in BxPC-3 xenograft-bearing mice resulted in tumor regression in 58% of mice compared to that in 18% of mice treated with DC101 alone. Taken together, these results lend great support to use PDGFRbeta antagonists in combinations with other antitumor and/or anti-angiogenic agents in the treatment of a variety of cancers.\n" ], "offsets": [ [ 0, 1380 ] ] } ]

[ { "id": "PMID-17462601_T1", "type": "Gene_or_gene_product", "text": [ "antibody directed against PDGF receptor beta" ], "offsets": [ [ 3, 47 ] ], "normalized": [] }, { "id": "PMID-17462601_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 65, 70 ] ], "normalized": [] }, { "id": "PMID-17462601_T3", "type": "Gene_or_gene_product", "text": [ "anti-VEGF receptor 2 antibody" ], "offsets": [ [ 112, 141 ] ], "normalized": [] }, { "id": "PMID-17462601_T4", "type": "Gene_or_gene_product", "text": [ "Platelet-derived growth factor" ], "offsets": [ [ 143, 173 ] ], "normalized": [] }, { "id": "PMID-17462601_T5", "type": "Gene_or_gene_product", "text": [ "PDGF" ], "offsets": [ [ 175, 179 ] ], "normalized": [] }, { "id": "PMID-17462601_T6", "type": "Gene_or_gene_product", "text": [ "PDGFR" ], "offsets": [ [ 200, 205 ] ], "normalized": [] }, { "id": "PMID-17462601_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 265, 270 ] ], "normalized": [] }, { "id": "PMID-17462601_T8", "type": "Cell", "text": [ "pericyte" ], "offsets": [ [ 319, 327 ] ], "normalized": [] }, { "id": "PMID-17462601_T9", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 344, 350 ] ], "normalized": [] }, { "id": "PMID-17462601_T10", "type": "Simple_chemical", "text": [ "1B3" ], "offsets": [ [ 405, 408 ] ], "normalized": [] }, { "id": "PMID-17462601_T11", "type": "Organism", "text": [ "mouse" ], "offsets": [ [ 427, 432 ] ], "normalized": [] }, { "id": "PMID-17462601_T12", "type": "Gene_or_gene_product", "text": [ "PDGFRbeta" ], "offsets": [ [ 433, 442 ] ], "normalized": [] }, { "id": "PMID-17462601_T13", "type": "Simple_chemical", "text": [ "1B3" ], "offsets": [ [ 444, 447 ] ], "normalized": [] }, { "id": "PMID-17462601_T14", "type": "Gene_or_gene_product", "text": [ "PDGFRbeta" ], "offsets": [ [ 457, 466 ] ], "normalized": [] }, { "id": "PMID-17462601_T15", "type": "Gene_or_gene_product", "text": [ "PDGF-BB" ], "offsets": [ [ 510, 517 ] ], "normalized": [] }, { "id": "PMID-17462601_T16", "type": "Gene_or_gene_product", "text": [ "PDGFRbeta" ], "offsets": [ [ 644, 653 ] ], "normalized": [] }, { "id": "PMID-17462601_T17", "type": "Gene_or_gene_product", "text": [ "Akt" ], "offsets": [ [ 700, 703 ] ], "normalized": [] }, { "id": "PMID-17462601_T18", "type": "Gene_or_gene_product", "text": [ "MAPK p42/44" ], "offsets": [ [ 708, 719 ] ], "normalized": [] }, { "id": "PMID-17462601_T19", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 724, 735 ] ], "normalized": [] }, { "id": "PMID-17462601_T20", "type": "Simple_chemical", "text": [ "1B3" ], "offsets": [ [ 756, 759 ] ], "normalized": [] }, { "id": "PMID-17462601_T21", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 791, 796 ] ], "normalized": [] }, { "id": "PMID-17462601_T22", "type": "Simple_chemical", "text": [ "DC101" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "PMID-17462601_T23", "type": "Organism", "text": [ "mouse" ], "offsets": [ [ 871, 876 ] ], "normalized": [] }, { "id": "PMID-17462601_T24", "type": "Gene_or_gene_product", "text": [ "vascular endothelial growth factor receptor 2" ], "offsets": [ [ 877, 922 ] ], "normalized": [] }, { "id": "PMID-17462601_T25", "type": "Cancer", "text": [ "pancreatic" ], "offsets": [ [ 929, 939 ] ], "normalized": [] }, { "id": "PMID-17462601_T26", "type": "Cancer", "text": [ "BxPC-3" ], "offsets": [ [ 941, 947 ] ], "normalized": [] }, { "id": "PMID-17462601_T27", "type": "Cancer", "text": [ "non-small cell lung (NCI-H460) tumor xenograft" ], "offsets": [ [ 955, 1001 ] ], "normalized": [] }, { "id": "PMID-17462601_T28", "type": "Simple_chemical", "text": [ "1B3" ], "offsets": [ [ 1044, 1047 ] ], "normalized": [] }, { "id": "PMID-17462601_T29", "type": "Simple_chemical", "text": [ "DC101" ], "offsets": [ [ 1052, 1057 ] ], "normalized": [] }, { "id": "PMID-17462601_T30", "type": "Cancer", "text": [ "BxPC-3 xenograft" ], "offsets": [ [ 1061, 1077 ] ], "normalized": [] }, { "id": "PMID-17462601_T31", "type": "Organism", "text": [ "mice" ], "offsets": [ [ 1086, 1090 ] ], "normalized": [] }, { "id": "PMID-17462601_T32", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1103, 1108 ] ], "normalized": [] }, { "id": "PMID-17462601_T33", "type": "Organism", "text": [ "mice" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "PMID-17462601_T34", "type": "Organism", "text": [ "mice" ], "offsets": [ [ 1162, 1166 ] ], "normalized": [] }, { "id": "PMID-17462601_T35", "type": "Simple_chemical", "text": [ "DC101" ], "offsets": [ [ 1180, 1185 ] ], "normalized": [] }, { "id": "PMID-17462601_T36", "type": "Gene_or_gene_product", "text": [ "PDGFRbeta antagonists" ], "offsets": [ [ 1249, 1270 ] ], "normalized": [] }, { "id": "PMID-17462601_T37", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1302, 1307 ] ], "normalized": [] }, { "id": "PMID-17462601_T38", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 1371, 1378 ] ], "normalized": [] } ]

[ { "id": "PMID-17462601_E1", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 48, 56 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T1" }, { "role": "Theme", "ref_id": "PMID-17462601_T3" } ] }, { "id": "PMID-17462601_E2", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 48, 56 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T1" }, { "role": "Theme", "ref_id": "PMID-17462601_E5" } ] }, { "id": "PMID-17462601_E3", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 48, 56 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T1" }, { "role": "Theme", "ref_id": "PMID-17462601_E6" } ] }, { "id": "PMID-17462601_E4", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 84, 94 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E5", "type": "Negative_regulation", "trigger": { "text": [ "activities" ], "offsets": [ [ 95, 105 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T3" }, { "role": "Theme", "ref_id": "PMID-17462601_E4" } ] }, { "id": "PMID-17462601_E6", "type": "Negative_regulation", "trigger": { "text": [ "activities" ], "offsets": [ [ 95, 105 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T3" }, { "role": "Theme", "ref_id": "PMID-17462601_T2" } ] }, { "id": "PMID-17462601_E7", "type": "Regulation", "trigger": { "text": [ "roles" ], "offsets": [ [ 222, 227 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E9" }, { "role": "Cause", "ref_id": "PMID-17462601_T4" } ] }, { "id": "PMID-17462601_E8", "type": "Regulation", "trigger": { "text": [ "roles" ], "offsets": [ [ 222, 227 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E9" }, { "role": "Cause", "ref_id": "PMID-17462601_T6" } ] }, { "id": "PMID-17462601_E9", "type": "Carcinogenesis", "trigger": { "text": [ "tumorigenesis" ], "offsets": [ [ 231, 244 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E10", "type": "Positive_regulation", "trigger": { "text": [ "stimulating" ], "offsets": [ [ 253, 264 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T6" }, { "role": "Theme", "ref_id": "PMID-17462601_E12" } ] }, { "id": "PMID-17462601_E11", "type": "Positive_regulation", "trigger": { "text": [ "stimulating" ], "offsets": [ [ 253, 264 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T4" }, { "role": "Theme", "ref_id": "PMID-17462601_E12" } ] }, { "id": "PMID-17462601_E12", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 271, 277 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T7" } ] }, { "id": "PMID-17462601_E13", "type": "Positive_regulation", "trigger": { "text": [ "promoting" ], "offsets": [ [ 282, 291 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T6" }, { "role": "Theme", "ref_id": "PMID-17462601_E15" } ] }, { "id": "PMID-17462601_E14", "type": "Positive_regulation", "trigger": { "text": [ "promoting" ], "offsets": [ [ 282, 291 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T4" }, { "role": "Theme", "ref_id": "PMID-17462601_E15" } ] }, { "id": "PMID-17462601_E15", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 292, 304 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E16", "type": "Positive_regulation", "trigger": { "text": [ "enhancing" ], "offsets": [ [ 309, 318 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E18" }, { "role": "Cause", "ref_id": "PMID-17462601_T6" } ] }, { "id": "PMID-17462601_E17", "type": "Positive_regulation", "trigger": { "text": [ "enhancing" ], "offsets": [ [ 309, 318 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E19" }, { "role": "Cause", "ref_id": "PMID-17462601_T4" } ] }, { "id": "PMID-17462601_E18", "type": "Localization", "trigger": { "text": [ "recruitment" ], "offsets": [ [ 328, 339 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T8" } ] }, { "id": "PMID-17462601_E19", "type": "Development", "trigger": { "text": [ "maturation" ], "offsets": [ [ 351, 361 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T9" } ] }, { "id": "PMID-17462601_E20", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 448, 453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T13" }, { "role": "Theme", "ref_id": "PMID-17462601_T14" } ] }, { "id": "PMID-17462601_E21", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 503, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_E22" }, { "role": "Cause", "ref_id": "PMID-17462601_T13" } ] }, { "id": "PMID-17462601_E22", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 523, 530 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T15" } ] }, { "id": "PMID-17462601_E23", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 605, 611 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T13" }, { "role": "Theme", "ref_id": "PMID-17462601_E26" } ] }, { "id": "PMID-17462601_E24", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 605, 611 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T13" }, { "role": "Theme", "ref_id": "PMID-17462601_E27" } ] }, { "id": "PMID-17462601_E25", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 605, 611 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T13" }, { "role": "Theme", "ref_id": "PMID-17462601_E28" } ] }, { "id": "PMID-17462601_E26", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 630, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T16" } ] }, { "id": "PMID-17462601_E27", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 630, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T17" } ] }, { "id": "PMID-17462601_E28", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 630, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T18" } ] }, { "id": "PMID-17462601_E29", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 774, 782 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T20" }, { "role": "Theme", "ref_id": "PMID-17462601_E32" } ] }, { "id": "PMID-17462601_E30", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 774, 782 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T20" }, { "role": "Theme", "ref_id": "PMID-17462601_E33" } ] }, { "id": "PMID-17462601_E31", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 810, 820 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E32", "type": "Negative_regulation", "trigger": { "text": [ "activities" ], "offsets": [ [ 821, 831 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T22" }, { "role": "Theme", "ref_id": "PMID-17462601_E31" } ] }, { "id": "PMID-17462601_E33", "type": "Negative_regulation", "trigger": { "text": [ "activities" ], "offsets": [ [ 821, 831 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_T22" }, { "role": "Theme", "ref_id": "PMID-17462601_T21" } ] }, { "id": "PMID-17462601_E34", "type": "Planned_process", "trigger": { "text": [ "Treatment" ], "offsets": [ [ 1010, 1019 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-17462601_T28" }, { "role": "Instrument", "ref_id": "PMID-17462601_T29" }, { "role": "Theme", "ref_id": "PMID-17462601_T31" } ] }, { "id": "PMID-17462601_E35", "type": "Positive_regulation", "trigger": { "text": [ "resulted" ], "offsets": [ [ 1091, 1099 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-17462601_E34" }, { "role": "Theme", "ref_id": "PMID-17462601_E36" } ] }, { "id": "PMID-17462601_E36", "type": "Negative_regulation", "trigger": { "text": [ "regression" ], "offsets": [ [ 1109, 1119 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T32" } ] }, { "id": "PMID-17462601_E37", "type": "Planned_process", "trigger": { "text": [ "treated" ], "offsets": [ [ 1167, 1174 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-17462601_T35" }, { "role": "Theme", "ref_id": "PMID-17462601_T34" } ] }, { "id": "PMID-17462601_E38", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenic" ], "offsets": [ [ 1320, 1330 ] ] }, "arguments": [] }, { "id": "PMID-17462601_E39", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 1345, 1354 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-17462601_T38" }, { "role": "Instrument", "ref_id": "PMID-17462601_T36" } ] } ]

[ { "id": "PMID-17462601_1", "entity_ids": [ "PMID-17462601_T4", "PMID-17462601_T5" ] } ]

[]

9

PMID-19369582

[ { "id": "PMID-19369582__text", "type": "abstract", "text": [ "Characterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets.\nAngiogenesis is a fundamental process to normal and abnormal tissue growth and repair, which consists of recruiting endothelial cells toward an angiogenic stimulus. The cells subsequently proliferate and differentiate to form endothelial tubes and capillary-like structures. Little is known about the metabolic adaptation of endothelial cells through such a transformation. We studied the metabolic changes of endothelial cell activation by growth factors using human umbilical vein endothelial cells (HUVECs), [1,2-(13)C(2)]-glucose and mass isotopomer distribution analysis. The metabolism of [1,2-(13)C(2)]-glucose by HUVEC allows us to trace many of the main glucose metabolic pathways, including glycogen synthesis, the pentose cycle and the glycolytic pathways. So we established that these pathways were crucial to endothelial cell proliferation under vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) stimulation. A specific VEGF receptor-2 inhibitor demonstrated the importance of glycogen metabolism and pentose cycle pathway. Furthermore, we showed that glycogen was depleted in a low glucose medium, but conserved under hypoxic conditions. Finally, we demonstrated that direct inhibition of key enzymes to glycogen metabolism and pentose phosphate pathways reduced HUVEC viability and migration. In this regard, inhibitors of these pathways have been shown to be effective antitumoral agents. To sum up, our data suggest that the inhibition of metabolic pathways offers a novel and powerful therapeutic approach, which simultaneously inhibits tumor cell proliferation and tumor-induced angiogenesis.\n" ], "offsets": [ [ 0, 1782 ] ] } ]

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pathways" ], "offsets": [ [ 1420, 1438 ] ] }, "arguments": [ { "role": "Participant", "ref_id": "PMID-19369582_T27" } ] }, { "id": "PMID-19369582_E28", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1439, 1446 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_E29" } ] }, { "id": "PMID-19369582_E29", "type": "Localization", "trigger": { "text": [ "migration" ], "offsets": [ [ 1467, 1476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_T28" } ] }, { "id": "PMID-19369582_E30", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1716, 1724 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_E32" } ] }, { "id": "PMID-19369582_E31", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1716, 1724 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-19369582_E34" } ] }, { "id": "PMID-19369582_E32", "type": "Cell_proliferation", "trigger": { "text": 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[]

10

PMID-10589785

[ { "id": "PMID-10589785__text", "type": "abstract", "text": [ "The antiangiogenic agent linomide inhibits the growth rate of von Hippel-Lindau paraganglioma xenografts to mice.\nThe aim of this study was to ascertain the potential usefulness of the antiangiogenic compound linomide for treatment of von Hippel-Lindau (VHL)-related tumors. Paraganglioma tissue fragments obtained at surgery from a VHL type 2a patient were transplanted s.c. to male BALB/c nu/nu (nude) mice: (a) 2-3-mm fragments for \"prevention\" experiments; and (b) 2-3-mm fragments allowed to grow to 1 cm for \"intervention\" studies. Both groups received either 0.5 mg/ml linomide in drinking water or acidified water and were followed until tumor diameter reached 3 cm or for 4 weeks. In both the prevention and intervention experiments, a significant diminution of tumor size and weight was observed in the drug-treated animals. In vivo nuclear magnetic resonance analysis of tumor blood flow in linomide-treated animals showed localization of blood vessels almost exclusively to the periphery of the poorly vascularized tumors with a significant reduction of both vascular functionality and vasodilation. Histological examination of tumors from linomide-treated animals revealed marked avascularity. Treated animals also displayed a 2.4-fold reduction of tumor vascular endothelial growth factor mRNA levels. Taken together, our data indicate that in VHL disease, therapy directed at inhibition of constitutively expressed VEGF induction of angiogenesis by VHL tumors may constitute an effective medical treatment.\n" ], "offsets": [ [ 0, 1522 ] ] } ]

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[]

11

PMID-12140030

[ { "id": "PMID-12140030__text", "type": "abstract", "text": [ "Optimizing treatment of choroidal neovascularization feeder vessels associated with age-related macular degeneration.\nPURPOSE: To optimize the method of treating choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). DESIGN: Experimental study and interventional case series. METHODS: The parameters associated with locating and then photocoagulating CNV feeder vessels were identified and optimized using published data and data derived from modeling the choroidal vasculature. Based on these optimized parameters, a prototype diagnostic/treatment system was designed that captures high-speed indocyanine green (ICG) angiogram images and facilitates analysis of the images by enhancing visualization of dye movement through CNV feeder vessels (FVs). The system also permits precise aiming and delivery of 810- nm wavelength photocoagulation laser energy to target FVs on a real-time ICG angiogram image of the choroidal vasculature. Target FVs are tracked by a joy-stick controlled laser aiming beam until an intravenously-injected high-concentration ICG dye bolus is observed to enter the target vessel, at which time the laser is fired. Proof of principle of the combined diagnosis/treatment system design for performing dye-enhanced photocoagulation (DEP) in the clinical setting and determination of the minimum DEP laser energy needed to close CNV FVs was made in 11 AMD patients requiring treatment of CNV, but for whom other treatment was not appropriate. RESULTS: Using ICG-DEP, CNV feeder vessels were closed with single pulse laser energy, delivering as little as 0.6 to 1.8 J of energy to the fundus, producing no visible change in the fundus. Successful FV closure was usually indicated immediately by presence of incarcerated ICG dye in the vessel adjacent to the burn site. The prototype system proved relatively easy to operate. After acquiring and interpreting diagnostic angiograms and repositioning a patient in front of the device, feeder vessel DEP and treatment evaluation required 15 to 20 minutes. CONCLUSIONS: Indocyanine green dye-enhanced photocoagulation of CNV feeder vessels, facilitated by use of a device that permits real-time visualization of the choroidal circulation while aiming the treatment laser beam, appears to minimize the amount of energy applied to the fundus and the volume of fundus tissue affected by treatment, compared with other treatment modalities. The combination diagnosis/treatment device should be useful in optimizing FV treatment and in refining and evaluating the efficacy of DEP in future clinical trials.\n" ], "offsets": [ [ 0, 2603 ] ] } ]

[ { "id": "PMID-12140030_T1", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 24, 33 ] ], "normalized": [] }, { "id": "PMID-12140030_T2", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 53, 67 ] ], "normalized": [] }, { "id": "PMID-12140030_T3", "type": "Tissue", "text": [ "macular" ], "offsets": [ [ 96, 103 ] ], "normalized": [] }, { "id": "PMID-12140030_T4", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 162, 171 ] ], "normalized": [] }, { "id": "PMID-12140030_T5", "type": "Tissue", "text": [ "macular" ], "offsets": [ [ 225, 232 ] ], "normalized": [] }, { "id": "PMID-12140030_T6", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 391, 405 ] ], "normalized": [] }, { "id": "PMID-12140030_T7", "type": "Multi-tissue_structure", "text": [ "choroidal vasculature" ], "offsets": [ [ 492, 513 ] ], "normalized": [] }, { "id": "PMID-12140030_T8", "type": "Simple_chemical", "text": [ "indocyanine green" ], "offsets": [ [ 630, 647 ] ], "normalized": [] }, { "id": "PMID-12140030_T9", "type": "Simple_chemical", "text": [ "ICG" ], "offsets": [ [ 649, 652 ] ], "normalized": [] }, { "id": "PMID-12140030_T10", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 765, 779 ] ], "normalized": [] }, { "id": "PMID-12140030_T11", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 781, 784 ] ], "normalized": [] }, { "id": "PMID-12140030_T12", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 901, 904 ] ], "normalized": [] }, { "id": "PMID-12140030_T13", "type": "Simple_chemical", "text": [ "ICG" ], "offsets": [ [ 920, 923 ] ], "normalized": [] }, { "id": "PMID-12140030_T14", "type": "Multi-tissue_structure", "text": [ "choroidal vasculature" ], "offsets": [ [ 947, 968 ] ], "normalized": [] }, { "id": "PMID-12140030_T15", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 977, 980 ] ], "normalized": [] }, { "id": "PMID-12140030_T16", "type": "Immaterial_anatomical_entity", "text": [ "intravenously" ], "offsets": [ [ 1046, 1059 ] ], "normalized": [] }, { "id": "PMID-12140030_T17", "type": "Simple_chemical", "text": [ "ICG dye" ], "offsets": [ [ 1088, 1095 ] ], "normalized": [] }, { "id": "PMID-12140030_T18", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1134, 1140 ] ], "normalized": [] }, { "id": "PMID-12140030_T19", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 1390, 1393 ] ], "normalized": [] }, { "id": "PMID-12140030_T20", "type": "Organism", "text": [ "patients" ], "offsets": [ [ 1413, 1421 ] ], "normalized": [] }, { "id": "PMID-12140030_T21", "type": "Simple_chemical", "text": [ "ICG" ], "offsets": [ [ 1515, 1518 ] ], "normalized": [] }, { "id": "PMID-12140030_T22", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 1528, 1542 ] ], "normalized": [] }, { "id": "PMID-12140030_T23", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 1641, 1647 ] ], "normalized": [] }, { "id": "PMID-12140030_T24", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 1684, 1690 ] ], "normalized": [] }, { "id": "PMID-12140030_T25", "type": "Multi-tissue_structure", "text": [ "FV" ], "offsets": [ [ 1703, 1705 ] ], "normalized": [] }, { "id": "PMID-12140030_T26", "type": "Simple_chemical", "text": [ "ICG dye" ], "offsets": [ [ 1776, 1783 ] ], "normalized": [] }, { "id": "PMID-12140030_T27", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1791, 1797 ] ], "normalized": [] }, { "id": "PMID-12140030_T28", "type": "Organism", "text": [ "patient" ], "offsets": [ [ 1956, 1963 ] ], "normalized": [] }, { "id": "PMID-12140030_T29", "type": "Multi-tissue_structure", "text": [ "feeder vessel" ], "offsets": [ [ 1988, 2001 ] ], "normalized": [] }, { "id": "PMID-12140030_T30", "type": "Simple_chemical", "text": [ "Indocyanine green dye" ], "offsets": [ [ 2071, 2092 ] ], "normalized": [] }, { "id": "PMID-12140030_T31", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 2126, 2140 ] ], "normalized": [] }, { "id": "PMID-12140030_T32", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 2217, 2226 ] ], "normalized": [] }, { "id": "PMID-12140030_T33", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 2334, 2340 ] ], "normalized": [] }, { "id": "PMID-12140030_T34", "type": "Tissue", "text": [ "fundus tissue" ], "offsets": [ [ 2359, 2372 ] ], "normalized": [] }, { "id": "PMID-12140030_T35", "type": "Multi-tissue_structure", "text": [ "FV" ], "offsets": [ [ 2512, 2514 ] ], "normalized": [] } ]

[ { "id": "PMID-12140030_E1", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 11, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E2" } ] }, { "id": "PMID-12140030_E2", "type": "Blood_vessel_development", "trigger": { "text": [ "neovascularization" ], "offsets": [ [ 34, 52 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T2" }, { "role": "AtLoc", "ref_id": "PMID-12140030_T1" } ] }, { "id": "PMID-12140030_E3", "type": "Regulation", "trigger": { "text": [ "associated" ], "offsets": [ [ 68, 78 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E4" }, { "role": "Cause", "ref_id": "PMID-12140030_E2" } ] }, { "id": "PMID-12140030_E4", "type": "Breakdown", "trigger": { "text": [ "degeneration" ], "offsets": [ [ 104, 116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T3" } ] }, { "id": "PMID-12140030_E5", "type": "Planned_process", "trigger": { "text": [ "treating" ], "offsets": [ [ 153, 161 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E6" } ] }, { "id": "PMID-12140030_E6", "type": "Blood_vessel_development", "trigger": { "text": [ "neovascularization" ], "offsets": [ [ 172, 190 ] ] }, "arguments": [ { "role": "AtLoc", "ref_id": "PMID-12140030_T4" } ] }, { "id": "PMID-12140030_E7", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 192, 195 ] ] }, "arguments": [] }, { "id": "PMID-12140030_E8", "type": "Regulation", "trigger": { "text": [ "associated" ], "offsets": [ [ 197, 207 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E9" }, { "role": "Cause", "ref_id": "PMID-12140030_E6" } ] }, { "id": "PMID-12140030_E9", "type": "Breakdown", "trigger": { "text": [ "degeneration" ], "offsets": [ [ 233, 245 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T5" } ] }, { "id": "PMID-12140030_E10", "type": "Planned_process", "trigger": { "text": [ "photocoagulating" ], "offsets": [ [ 370, 386 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T6" } ] }, { "id": "PMID-12140030_E11", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 387, 390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T6" } ] }, { "id": "PMID-12140030_E12", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 761, 764 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T10" } ] }, { "id": "PMID-12140030_E13", "type": "Planned_process", "trigger": { "text": [ "injected" ], "offsets": [ [ 1060, 1068 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-12140030_T17" } ] }, { "id": "PMID-12140030_E14", "type": "Localization", "trigger": { "text": [ "observed" ], "offsets": [ [ 1105, 1113 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T17" }, { "role": "ToLoc", "ref_id": "PMID-12140030_T18" } ] }, { "id": "PMID-12140030_E15", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 1386, 1389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T19" } ] }, { "id": "PMID-12140030_E16", "type": "Positive_regulation", "trigger": { "text": [ "requiring" ], "offsets": [ [ 1422, 1431 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12140030_E17" }, { "role": "Theme", "ref_id": "PMID-12140030_T20" } ] }, { "id": "PMID-12140030_E17", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 1432, 1441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_E18" } ] }, { "id": "PMID-12140030_E18", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 1445, 1448 ] ] }, "arguments": [] }, { "id": "PMID-12140030_E19", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 1524, 1527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T22" } ] }, { "id": "PMID-12140030_E20", "type": "Planned_process", "trigger": { "text": [ "closed" ], "offsets": [ [ 1548, 1554 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T22" }, { "role": "Instrument", "ref_id": "PMID-12140030_T21" } ] }, { "id": "PMID-12140030_E21", "type": "Planned_process", "trigger": { "text": [ "closure" ], "offsets": [ [ 1706, 1713 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T25" } ] }, { "id": "PMID-12140030_E22", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 2093, 2101 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-12140030_T30" }, { "role": "Theme", "ref_id": "PMID-12140030_E23" } ] }, { "id": "PMID-12140030_E23", "type": "Planned_process", "trigger": { "text": [ "photocoagulation" ], "offsets": [ [ 2102, 2118 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T31" } ] }, { "id": "PMID-12140030_E24", "type": "Blood_vessel_development", "trigger": { "text": [ "CNV" ], "offsets": [ [ 2122, 2125 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T31" } ] }, { "id": "PMID-12140030_E25", "type": "Planned_process", "trigger": { "text": [ "treatment" ], "offsets": [ [ 2515, 2524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12140030_T35" } ] } ]

[ { "id": "PMID-12140030_1", "entity_ids": [ "PMID-12140030_T8", "PMID-12140030_T9" ] }, { "id": "PMID-12140030_2", "entity_ids": [ "PMID-12140030_T10", "PMID-12140030_T11" ] } ]

[]

12

PMID-11238633

[ { "id": "PMID-11238633__text", "type": "abstract", "text": [ "IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endothelial cell cross-talk.\nIn vivo IL-12-dependent tumor inhibition rests on the ability of IL-12 to activate a CD8-mediated cytotoxicity, inhibit angiogenesis, and cause vascular injury. Although in vivo studies have shown that such inhibition stems from complex interactions of immune cells and the production of IFN-gamma and other downstream angiostatic chemokines, the mechanisms involved are still poorly defined. Here we show that IL-12 activates an anti-angiogenic program in Con A-activated mouse spleen cells (activated spc) or human PBMC (activated PBMC). The soluble factors they release in its presence arrest the cycle of endothelial cells (EC), inhibit in vitro angiogenesis, negatively modulate the production of matrix metalloproteinase-9, and the ability of EC to adhere to vitronectin and up-regulate ICAM-1 and VCAM-1 expression. These effects do not require direct cell-cell contact, yet result from continuous interaction between activated lymphoid cells and EC. We used neutralizing Abs to show that the IFN-inducible protein-10 and monokine-induced by IFN-gamma chemokines are pivotal in inducing these effects. Experiments with nu/nu mice, nonobese diabetic-SCID mice, or activated spc enriched in specific cell subpopulations demonstrated that CD4(+), CD8(+), and NK cells are all needed to mediate the full anti-angiogenetic effect of IL-12.\n" ], "offsets": [ [ 0, 1457 ] ] } ]

[ { "id": "PMID-11238633_T1", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-11238633_T2", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 20, 36 ] ], "normalized": [] }, { "id": "PMID-11238633_T3", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 75, 85 ] ], "normalized": [] }, { "id": "PMID-11238633_T4", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 86, 102 ] ], "normalized": [] }, { "id": "PMID-11238633_T5", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 123, 128 ] ], "normalized": [] }, { "id": "PMID-11238633_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 139, 144 ] ], "normalized": [] }, { "id": "PMID-11238633_T7", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 180, 185 ] ], "normalized": [] }, { "id": "PMID-11238633_T8", "type": "Gene_or_gene_product", "text": [ "CD8" ], "offsets": [ [ 200, 203 ] ], "normalized": [] }, { "id": "PMID-11238633_T9", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 259, 267 ] ], "normalized": [] }, { "id": "PMID-11238633_T10", "type": "Cell", "text": [ "immune cells" ], "offsets": [ [ 368, 380 ] ], "normalized": [] }, { "id": "PMID-11238633_T11", "type": "Gene_or_gene_product", "text": [ "IFN-gamma" ], "offsets": [ [ 403, 412 ] ], "normalized": [] }, { "id": "PMID-11238633_T12", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 526, 531 ] ], "normalized": [] }, { "id": "PMID-11238633_T13", "type": "Simple_chemical", "text": [ "Con A" ], "offsets": [ [ 572, 577 ] ], "normalized": [] }, { "id": "PMID-11238633_T14", "type": "Organism", "text": [ "mouse" ], "offsets": [ [ 588, 593 ] ], "normalized": [] }, { "id": "PMID-11238633_T15", "type": "Cell", "text": [ "spleen cells" ], "offsets": [ [ 594, 606 ] ], "normalized": [] }, { "id": "PMID-11238633_T16", "type": "Cell", "text": [ "spc" ], "offsets": [ [ 618, 621 ] ], "normalized": [] }, { "id": "PMID-11238633_T17", "type": "Organism", "text": [ "human" ], "offsets": [ [ 626, 631 ] ], "normalized": [] }, { "id": "PMID-11238633_T18", "type": "Cell", "text": [ "PBMC" ], "offsets": [ [ 632, 636 ] ], "normalized": [] }, { "id": "PMID-11238633_T19", "type": "Cell", "text": [ "PBMC" ], "offsets": [ [ 648, 652 ] ], "normalized": [] }, { "id": "PMID-11238633_T20", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 724, 741 ] ], "normalized": [] }, { "id": "PMID-11238633_T21", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 743, 745 ] ], "normalized": [] }, { "id": "PMID-11238633_T22", "type": "Gene_or_gene_product", "text": [ "matrix metalloproteinase-9" ], "offsets": [ [ 817, 843 ] ], "normalized": [] }, { "id": "PMID-11238633_T23", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 864, 866 ] ], "normalized": [] }, { "id": "PMID-11238633_T24", "type": "Gene_or_gene_product", "text": [ "vitronectin" ], "offsets": [ [ 880, 891 ] ], "normalized": [] }, { "id": "PMID-11238633_T25", "type": "Gene_or_gene_product", "text": [ "ICAM-1" ], "offsets": [ [ 908, 914 ] ], "normalized": [] }, { "id": "PMID-11238633_T26", "type": "Gene_or_gene_product", "text": [ "VCAM-1" ], "offsets": [ [ 919, 925 ] ], "normalized": [] }, { "id": "PMID-11238633_T27", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 974, 978 ] ], "normalized": [] }, { "id": "PMID-11238633_T28", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 979, 983 ] ], "normalized": [] }, { "id": "PMID-11238633_T29", "type": "Cell", "text": [ "lymphoid cells" ], "offsets": [ [ 1050, 1064 ] ], "normalized": [] }, { "id": "PMID-11238633_T30", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1069, 1071 ] ], "normalized": [] }, { "id": "PMID-11238633_T31", "type": "Gene_or_gene_product", "text": [ "IFN-inducible protein-10" ], "offsets": [ [ 1115, 1139 ] ], "normalized": [] }, { "id": "PMID-11238633_T32", "type": "Organism", "text": [ "nu/nu mice" ], "offsets": [ [ 1241, 1251 ] ], "normalized": [] }, { "id": "PMID-11238633_T33", "type": "Organism", "text": [ "nonobese diabetic-SCID mice" ], "offsets": [ [ 1253, 1280 ] ], "normalized": [] }, { "id": "PMID-11238633_T34", "type": "Cell", "text": [ "spc" ], "offsets": [ [ 1295, 1298 ] ], "normalized": [] }, { "id": "PMID-11238633_T35", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1320, 1324 ] ], "normalized": [] }, { "id": "PMID-11238633_T36", "type": "Gene_or_gene_product", "text": [ "CD4" ], "offsets": [ [ 1358, 1361 ] ], "normalized": [] }, { "id": "PMID-11238633_T37", "type": "Cell", "text": [ "CD4(+)" ], "offsets": [ [ 1358, 1364 ] ], "normalized": [] }, { "id": "PMID-11238633_T38", "type": "Gene_or_gene_product", "text": [ "CD8" ], "offsets": [ [ 1366, 1369 ] ], "normalized": [] }, { "id": "PMID-11238633_T39", "type": "Cell", "text": [ "CD8(+)" ], "offsets": [ [ 1366, 1372 ] ], "normalized": [] }, { "id": "PMID-11238633_T40", "type": "Cell", "text": [ "NK cells" ], "offsets": [ [ 1378, 1386 ] ], "normalized": [] }, { "id": "PMID-11238633_T41", "type": "Gene_or_gene_product", "text": [ "IL-12" ], "offsets": [ [ 1450, 1455 ] ], "normalized": [] } ]

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"offsets": [ [ 145, 155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11238633_T6" } ] }, { "id": "PMID-11238633_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 227, 234 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-11238633_T7" }, { "role": "Theme", "ref_id": "PMID-11238633_E7" } ] }, { "id": "PMID-11238633_E7", "type": "Blood_vessel_development", "trigger": { "text": [ "angiogenesis" ], "offsets": [ [ 235, 247 ] ] }, "arguments": [] }, { "id": "PMID-11238633_E8", "type": "Positive_regulation", "trigger": { "text": [ "cause" ], "offsets": [ [ 253, 258 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11238633_E9" }, { "role": "Cause", "ref_id": "PMID-11238633_T7" } ] }, { "id": "PMID-11238633_E9", "type": "Breakdown", "trigger": { "text": [ "injury" ], "offsets": [ [ 268, 274 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-11238633_T9" } ] }, { "id": "PMID-11238633_E10", "type": "Gene_expression", "trigger": 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[ { "id": "PMID-11238633_1", "entity_ids": [ "PMID-11238633_T16", "PMID-11238633_T15" ] }, { "id": "PMID-11238633_2", "entity_ids": [ "PMID-11238633_T19", "PMID-11238633_T18" ] }, { "id": "PMID-11238633_3", "entity_ids": [ "PMID-11238633_T20", "PMID-11238633_T21" ] } ]

[]

13

PMID-16310808

[ { "id": "PMID-16310808__text", "type": "abstract", "text": [ "Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells.\nAngiogenesis, new blood vessel formation, is a multistep process, precisely regulated by pro-angiogenic cytokines, which stimulate endothelial cells to migrate, proliferate and differentiate to form new capillary microvessels. Excessive vascular development and blood vessel remodeling appears in psoriasis, rheumatoid arthritis, diabetic retinopathy and solid tumors formation. Thalidomide [alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor of angiogenesis, but the mechanism of its inhibitory action remains unclear. The aim of the study was to investigate the potential influence of thalidomide on the several steps of angiogenesis, using in vitro models. We have evaluated the effect of thalidomide on VEGF secretion, cell migration, adhesion as well as in capillary formation of human endothelial cell line EA.hy 926. Thalidomide at the concentrations of 0.01 microM and 10 microM inhibited VEGF secretion into supernatants, decreased the number of formed capillary tubes and increased cell adhesion to collagen. Administration of thalidomide at the concentration of 0.01 microM increased cell migration, while at 10 microM, it decreased cell migration. Thalidomide in concentrations from 0.1 microM to 10 microM did not change cell proliferation of 72-h cell cultures. We conclude that anti-angiogenic action of thalidomide is due to direct inhibitory action on VEGF secretion and capillary microvessel formation as well as immunomodulatory influence on EA.hy 926 cells migration and adhesion.\n" ], "offsets": [ [ 0, 1659 ] ] } ]

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[]

14

PMID-16855378

[ { "id": "PMID-16855378__text", "type": "abstract", "text": [ "Differential mechanisms of radiosensitization by 2-deoxy-D-glucose in the monolayers and multicellular spheroids of a human glioma cell line.\nIn vitro studies using monolayer cultures of human tumor cell lines have shown that 2-DG selectively inhibits energy-dependent DNA repair and cellular recovery processes in cancer cells. However, monolayer cultures differ greatly from the complex environmental conditions generated in solid tumors that develop inhomogeneous hypoxic and necrotic regions. In contrast, multicellular spheroids mimic heterogeneous cellular behavior and the consequent functional characteristics of in vivo solid tumors, and serve as important in vitro model to investigate tumor biology and responses to potential therapeutic agents. The present study compares the radiomodification by 2-DG in monolayer cultures and spheroids of a human glioma cell line (BMG-1) to gain insight into the effects in solid tumors. In spheroids, the glucose consumption (2.1 p mole/cell/h) and lactate production (3.67 p mole/cell/h) was nearly 2-3 fold higher than in monolayer cells (0.83 and 1.43 p mole/cell/h respectively). Presence of 2-DG (5 mM) for 2-4 h inhibited the glucose usage and lactate production by 70% in spheroids, while a 35% reduction was observed in monolayer cells. Under these conditions, 2-DG drastically enhanced the radiation-induced cell death of spheroids (by 2-3 folds); while a 40% increase was observed in monolayer cells. Radiosensitization by 2-DG in monolayer cells was primarily due to an increase in mitotic death (23%) linked to cytogenetic damage (micronuclei), whereas a profound induction of apoptosis (40%) accounted for the sensitization in spheroids. Although the Bcl-2 and Bax levels were significantly higher in spheroids, Bcl-2/Bax ratio was similar in monolayers and spheroids. Comet assay revealed a late onset of DNA breaks in the presence of 2- DG following irradiation only in spheroids, which corroborated well with the late onset of oxidative stress. 2-DG did not induce a significant cell cycle delay in monolayers, while a transient G(2) delay was apparent in spheroids.\n" ], "offsets": [ [ 0, 2132 ] ] } ]

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"id": "PMID-16855378_T9", "type": "Simple_chemical", "text": [ "2-DG" ], "offsets": [ [ 226, 230 ] ], "normalized": [] }, { "id": "PMID-16855378_T10", "type": "Cellular_component", "text": [ "DNA" ], "offsets": [ [ 269, 272 ] ], "normalized": [] }, { "id": "PMID-16855378_T11", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 284, 292 ] ], "normalized": [] }, { "id": "PMID-16855378_T12", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 315, 327 ] ], "normalized": [] }, { "id": "PMID-16855378_T13", "type": "Cell", "text": [ "monolayer cultures" ], "offsets": [ [ 338, 356 ] ], "normalized": [] }, { "id": "PMID-16855378_T14", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 427, 439 ] ], "normalized": [] }, { "id": "PMID-16855378_T15", "type": "Pathological_formation", "text": [ "inhomogeneous hypoxic" ], "offsets": [ [ 453, 474 ] ], "normalized": [] }, { "id": "PMID-16855378_T16", "type": "Pathological_formation", "text": [ "necrotic regions" ], "offsets": [ [ 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"normalized": [] }, { "id": "PMID-16855378_T25", "type": "Cell", "text": [ "glioma cell line" ], "offsets": [ [ 861, 877 ] ], "normalized": [] }, { "id": "PMID-16855378_T26", "type": "Cell", "text": [ "BMG-1" ], "offsets": [ [ 879, 884 ] ], "normalized": [] }, { "id": "PMID-16855378_T27", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 922, 934 ] ], "normalized": [] }, { "id": "PMID-16855378_T28", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 939, 948 ] ], "normalized": [] }, { "id": "PMID-16855378_T29", "type": "Simple_chemical", "text": [ "glucose" ], "offsets": [ [ 954, 961 ] ], "normalized": [] }, { "id": "PMID-16855378_T30", "type": "Simple_chemical", "text": [ "lactate" ], "offsets": [ [ 998, 1005 ] ], "normalized": [] }, { "id": "PMID-16855378_T31", "type": "Cell", "text": [ "monolayer cells" ], "offsets": [ [ 1073, 1088 ] ], "normalized": [] }, { "id": "PMID-16855378_T32", "type": "Simple_chemical", "text": [ "2-DG" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] }, { "id": "PMID-16855378_T33", "type": "Simple_chemical", "text": [ "glucose" ], "offsets": [ [ 1181, 1188 ] ], "normalized": [] }, { "id": "PMID-16855378_T34", "type": "Simple_chemical", "text": [ "lactate" ], "offsets": [ [ 1199, 1206 ] ], "normalized": [] }, { "id": "PMID-16855378_T35", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 1228, 1237 ] ], "normalized": [] }, { "id": "PMID-16855378_T36", "type": "Cell", "text": [ "monolayer cells" ], "offsets": [ [ 1277, 1292 ] ], "normalized": [] }, { "id": "PMID-16855378_T37", "type": "Simple_chemical", "text": [ "2-DG" ], "offsets": [ [ 1318, 1322 ] ], "normalized": [] }, { "id": "PMID-16855378_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1366, 1370 ] ], "normalized": [] }, { "id": "PMID-16855378_T39", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 1380, 1389 ] ], "normalized": [] }, { "id": "PMID-16855378_T40", "type": "Cell", "text": [ "monolayer cells" ], "offsets": [ [ 1443, 1458 ] ], 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"offsets": [ [ 1189, 1194 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T33" } ] }, { "id": "PMID-16855378_E11", "type": "Synthesis", "trigger": { "text": [ "production" ], "offsets": [ [ 1207, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T34" } ] }, { "id": "PMID-16855378_E12", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1251, 1260 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_E10" } ] }, { "id": "PMID-16855378_E13", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1251, 1260 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_E11" } ] }, { "id": "PMID-16855378_E14", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1335, 1343 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_E17" }, { "role": "Cause", "ref_id": "PMID-16855378_T37" } ] }, { "id": "PMID-16855378_E15", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1358, 1365 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_E17" } ] }, { "id": "PMID-16855378_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1358, 1365 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_E18" } ] }, { "id": "PMID-16855378_E17", "type": "Death", "trigger": { "text": [ "death" ], "offsets": [ [ 1371, 1376 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T39" } ] }, { "id": "PMID-16855378_E18", "type": "Death", "trigger": { "text": [ "death" ], "offsets": [ [ 1371, 1376 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T40" } ] }, { "id": "PMID-16855378_E19", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1418, 1426 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-16855378_T37" }, { "role": "Theme", "ref_id": "PMID-16855378_E18" } ] }, { "id": "PMID-16855378_E20", "type": "Planned_process", "trigger": { "text": [ "Radiosensitization" ], "offsets": [ [ 1460, 1478 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-16855378_T41" }, { "role": "Theme", "ref_id": "PMID-16855378_T42" } ] }, { "id": "PMID-16855378_E21", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1530, 1538 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_E22" } ] }, { "id": "PMID-16855378_E22", "type": "Death", "trigger": { "text": [ "mitotic death" ], "offsets": [ [ 1542, 1555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T42" } ] }, { "id": "PMID-16855378_E23", "type": "Breakdown", "trigger": { "text": [ "damage" ], "offsets": [ [ 1584, 1590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T43" } ] }, { "id": "PMID-16855378_E24", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1625, 1634 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_E25" } ] }, { "id": "PMID-16855378_E25", "type": "Cell_death", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 1638, 1647 ] ] }, "arguments": [] }, { "id": "PMID-16855378_E26", "type": "Localization", "trigger": { "text": [ "presence" ], "offsets": [ [ 1886, 1894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T53" } ] }, { "id": "PMID-16855378_E27", "type": "Planned_process", "trigger": { "text": [ "irradiation" ], "offsets": [ [ 1914, 1925 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T54" } ] }, { "id": "PMID-16855378_E28", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 2023, 2029 ] ] }, "arguments": [ { "role": "Cause", "ref_id": "PMID-16855378_T55" }, { "role": "Theme", "ref_id": "PMID-16855378_E29" } ] }, { "id": "PMID-16855378_E29", "type": "Negative_regulation", "trigger": { "text": [ "delay" ], "offsets": [ [ 2055, 2060 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T57" } ] }, { "id": "PMID-16855378_E30", "type": "Negative_regulation", "trigger": { "text": [ "delay" ], "offsets": [ [ 2099, 2104 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16855378_T58" }, { "role": "Cause", "ref_id": "PMID-16855378_T55" } ] } ]

[ { "id": "PMID-16855378_1", "entity_ids": [ "PMID-16855378_T25", "PMID-16855378_T26" ] } ]

[]

15

PMID-15725689

[ { "id": "PMID-15725689__text", "type": "abstract", "text": [ "Role of thrombogenic factors in the development of atherosclerosis.\nHemostatic factors play a crucial role in generating thrombotic plugs at sites of vascular damage (atherothrombosis). However, whether hemostatic factors contribute directly or indirectly to the pathogenesis of atherosclerosis remains uncertain. Autopsy studies have revealed that intimal thickening represents the first stage of atherosclerosis and that lipid-rich plaque arises from such lesions. Several factors contribute to the start of intimal thickening. Platelets release several growth factors and bioactive agents that play a central role in development of not only thrombus but also of intimal thickening. We have been investigating which coagulation factors simultaneously, or subsequently with platelet aggregation, participate in thrombus formation. Tissue factor (TF) is an essential initiator of blood coagulation that is expressed in various stages of atherosclerotic lesions in humans and other animals. Factors including thrombin and fibrin, which are downstream of the coagulation cascade activated by TF, also contribute to atherosclerosis. TF is involved in cell migration, embryogenesis and angiogenesis. Thus TF, in addition to factors downstream of the coagulation cascade and the protease-activated receptor 2 activation system, would be a multifactorial regulator of atherogenesis.\n" ], "offsets": [ [ 0, 1377 ] ] } ]

[ { "id": "PMID-15725689_T1", "type": "Gene_or_gene_product", "text": [ "thrombogenic factors" ], "offsets": [ [ 8, 28 ] ], "normalized": [] }, { "id": "PMID-15725689_T2", "type": "Gene_or_gene_product", "text": [ "Hemostatic factors" ], "offsets": [ [ 68, 86 ] ], "normalized": [] }, { "id": "PMID-15725689_T3", "type": "Pathological_formation", "text": [ "thrombotic plugs" ], "offsets": [ [ 121, 137 ] ], "normalized": [] }, { "id": "PMID-15725689_T4", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 150, 158 ] ], "normalized": [] }, { "id": "PMID-15725689_T5", "type": "Gene_or_gene_product", "text": [ "hemostatic factors" ], "offsets": [ [ 203, 221 ] ], "normalized": [] }, { "id": "PMID-15725689_T6", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 349, 356 ] ], "normalized": [] }, { "id": "PMID-15725689_T7", "type": "Pathological_formation", "text": [ "lipid-rich plaque" ], "offsets": [ [ 423, 440 ] ], "normalized": [] }, { "id": "PMID-15725689_T8", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 458, 465 ] ], "normalized": [] }, { "id": "PMID-15725689_T9", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 510, 517 ] ], "normalized": [] }, { "id": "PMID-15725689_T10", "type": "Cell", "text": [ "Platelets" ], "offsets": [ [ 530, 539 ] ], "normalized": [] }, { "id": "PMID-15725689_T11", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 644, 652 ] ], "normalized": [] }, { "id": "PMID-15725689_T12", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 665, 672 ] ], "normalized": [] }, { "id": "PMID-15725689_T13", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 775, 783 ] ], "normalized": [] }, { "id": "PMID-15725689_T14", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 812, 820 ] ], "normalized": [] }, { "id": "PMID-15725689_T15", "type": "Gene_or_gene_product", "text": [ "Tissue factor" ], "offsets": [ [ 832, 845 ] ], "normalized": [] }, { "id": "PMID-15725689_T16", "type": "Gene_or_gene_product", "text": [ "TF" ], "offsets": [ [ 847, 849 ] ], "normalized": [] }, { "id": "PMID-15725689_T17", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 880, 885 ] ], "normalized": [] }, { "id": "PMID-15725689_T18", "type": "Pathological_formation", "text": [ "atherosclerotic lesions" ], "offsets": [ [ 937, 960 ] ], "normalized": [] }, { "id": "PMID-15725689_T19", "type": "Organism", "text": [ "humans" ], "offsets": [ [ 964, 970 ] ], "normalized": [] }, { "id": "PMID-15725689_T20", "type": "Gene_or_gene_product", "text": [ "thrombin" ], "offsets": [ [ 1008, 1016 ] ], "normalized": [] }, { "id": "PMID-15725689_T21", "type": "Gene_or_gene_product", "text": [ "fibrin" ], "offsets": [ [ 1021, 1027 ] ], "normalized": [] }, { "id": "PMID-15725689_T22", "type": "Gene_or_gene_product", "text": [ "TF" ], "offsets": [ [ 1090, 1092 ] ], "normalized": [] }, { "id": "PMID-15725689_T23", "type": "Gene_or_gene_product", "text": [ "TF" ], "offsets": [ [ 1130, 1132 ] ], "normalized": [] }, { "id": "PMID-15725689_T24", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1148, 1152 ] ], "normalized": [] }, { "id": "PMID-15725689_T25", "type": "Gene_or_gene_product", "text": [ "TF" ], "offsets": [ [ 1201, 1203 ] ], "normalized": [] }, { "id": "PMID-15725689_T26", "type": "Gene_or_gene_product", "text": [ "protease-activated receptor 2" ], "offsets": [ [ 1274, 1303 ] ], "normalized": [] } ]

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[ { "id": "PMID-15725689_1", "entity_ids": [ "PMID-15725689_T15", "PMID-15725689_T16" ] } ]

[]

16

PMID-9206208

[ { "id": "PMID-9206208__text", "type": "abstract", "text": [ "[Expression of metastasis suppressor gene nm23 in human hepatocellular carcinoma]. \nFor the purpose of investigating the relationship between the metastatic potential of the tumor as well as the expression of nm23-H1 mRNA, and for determing the location of the positive sites in the cells, tumor metastasis suppressor gene nm23-H1 in human hepatocellular carcinoma (and the nonneoplastic area surrounding the tumor) was detected by in situ hybridization using digoxiginin-labeled nm23-H1 antisense complementary RNA probe. The primary results indicated (i) positive results of in situ hybridization are presence of granules or masses in the cytoplasm; (ii) the less expression of nm23-H1 mRNA, the higher metastatic rate of the human hepatocellular carcinoma (P < 0.05); (iii) expression of nm23-H1 mRNA dose not correlate with some other factors such as tumor size and the background of other liver diseases.\n" ], "offsets": [ [ 0, 910 ] ] } ]

[ { "id": "PMID-9206208_T1", "type": "Gene_or_gene_product", "text": [ "nm23" ], "offsets": [ [ 42, 46 ] ], "normalized": [] }, { "id": "PMID-9206208_T2", "type": "Organism", "text": [ "human" ], "offsets": [ [ 50, 55 ] ], "normalized": [] }, { "id": "PMID-9206208_T3", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 56, 80 ] ], "normalized": [] }, { "id": "PMID-9206208_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 174, 179 ] ], "normalized": [] }, { "id": "PMID-9206208_T5", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 209, 216 ] ], "normalized": [] }, { "id": "PMID-9206208_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 283, 288 ] ], "normalized": [] }, { "id": "PMID-9206208_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 290, 295 ] ], "normalized": [] }, { "id": "PMID-9206208_T8", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 323, 330 ] ], "normalized": [] }, { "id": "PMID-9206208_T9", "type": "Organism", "text": [ "human" ], "offsets": [ [ 334, 339 ] ], "normalized": [] }, { "id": "PMID-9206208_T10", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 340, 364 ] ], "normalized": [] }, { "id": "PMID-9206208_T11", "type": "Multi-tissue_structure", "text": [ "nonneoplastic area" ], "offsets": [ [ 374, 392 ] ], "normalized": [] }, { "id": "PMID-9206208_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 409, 414 ] ], "normalized": [] }, { "id": "PMID-9206208_T13", "type": "Simple_chemical", "text": [ "digoxiginin" ], "offsets": [ [ 460, 471 ] ], "normalized": [] }, { "id": "PMID-9206208_T14", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 480, 487 ] ], "normalized": [] }, { "id": "PMID-9206208_T15", "type": "Cellular_component", "text": [ "granules" ], "offsets": [ [ 615, 623 ] ], "normalized": [] }, { "id": "PMID-9206208_T16", "type": "Organism_substance", "text": [ "cytoplasm" ], "offsets": [ [ 641, 650 ] ], "normalized": [] }, { "id": "PMID-9206208_T17", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 680, 687 ] ], "normalized": [] }, { "id": "PMID-9206208_T18", "type": "Organism", "text": [ "human" ], "offsets": [ [ 728, 733 ] ], "normalized": [] }, { "id": "PMID-9206208_T19", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 734, 758 ] ], "normalized": [] }, { "id": "PMID-9206208_T20", "type": "Gene_or_gene_product", "text": [ "nm23-H1" ], "offsets": [ [ 791, 798 ] ], "normalized": [] }, { "id": "PMID-9206208_T21", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 855, 860 ] ], "normalized": [] }, { "id": "PMID-9206208_T22", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 894, 899 ] ], "normalized": [] } ]

[ { "id": "PMID-9206208_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 1, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T1" } ] }, { "id": "PMID-9206208_E2", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 15, 25 ] ] }, "arguments": [] }, { "id": "PMID-9206208_E3", "type": "Metastasis", "trigger": { "text": [ "metastatic" ], "offsets": [ [ 146, 156 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T4" } ] }, { "id": "PMID-9206208_E4", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 195, 205 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T5" } ] }, { "id": "PMID-9206208_E5", "type": "Metastasis", "trigger": { "text": [ "metastasis" ], "offsets": [ [ 296, 306 ] ] }, "arguments": [] }, { "id": "PMID-9206208_E6", "type": "Planned_process", "trigger": { "text": [ "labeled" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Instrument", "ref_id": "PMID-9206208_T13" } ] }, { "id": "PMID-9206208_E7", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 666, 676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T17" } ] }, { "id": "PMID-9206208_E8", "type": "Metastasis", "trigger": { "text": [ "metastatic" ], "offsets": [ [ 705, 715 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T19" } ] }, { "id": "PMID-9206208_E9", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 777, 787 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9206208_T20" } ] } ]

[]

Datasets:

bigbio
/

bionlp_st_2013_cg

Dataset Card for BioNLP 2013 CG

Citation Information