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rdf:type |
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lifeskim:mentions |
umls-concept:C0013216,
umls-concept:C0026809,
umls-concept:C0038952,
umls-concept:C0332161,
umls-concept:C0346647,
umls-concept:C0442805,
umls-concept:C0871261,
umls-concept:C0920591,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
7
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pubmed:dateCreated |
2010-4-2
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pubmed:abstractText |
Failure of chemotherapy in the treatment of pancreatic cancer is often due to resistance to therapy-induced apoptosis. A major mechanism for such resistance is the expression and activity of inhibitors of apoptosis proteins (IAP). Smac (second mitochondria-derived activator of caspase) is a mitochondrial protein that inhibits IAPs. We show that JP1201, a Smac mimetic, is a potent enhancer of chemotherapy in robust mouse models of pancreatic cancer. Combination of JP1201 with gemcitabine reduced primary and metastatic tumor burden in orthotopic xenograft and syngenic tumor models, induced regression of established tumors, and prolonged survival in xenograft and transgenic models of pancreatic cancer. The effect of JP1201 was phenocopied by XIAP small interfering RNA in vitro and correlated with elevated levels of tumor necrosis factor alpha protein in vivo. The continued development of JP1201 and other strategies designed to enhance therapy-induced apoptosis in pancreatic cancer is warranted.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-10647931,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-12042762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-12559172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-12605713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-14681207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-15314185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-16628085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-17094439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-17237035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-17339366,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-17846863,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-17996648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-18022362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-18022363,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-18089776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-18485876,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-18519694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-18652674,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-18829553,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-19010913,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-19258513,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-19509265,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20332237-19524512
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DIABLO protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytidine,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/gemcitabine
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1538-7445
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pubmed:author |
pubmed-author:BardeesyNabeelN,
pubmed-author:BrekkenRolf ARA,
pubmed-author:CarbonJuliet GJG,
pubmed-author:DineenSean PSP,
pubmed-author:GreerRachelR,
pubmed-author:GuptaPujaP,
pubmed-author:MinnaJohn DJD,
pubmed-author:RolandChristina LCL,
pubmed-author:SunHaizhouH,
pubmed-author:ToombsJason EJE,
pubmed-author:WilliamsNoelleN
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2852-61
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:20332237-Animals,
pubmed-meshheading:20332237-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:20332237-Biomimetic Materials,
pubmed-meshheading:20332237-Carcinoma, Pancreatic Ductal,
pubmed-meshheading:20332237-Cell Line, Tumor,
pubmed-meshheading:20332237-Deoxycytidine,
pubmed-meshheading:20332237-Drug Synergism,
pubmed-meshheading:20332237-Female,
pubmed-meshheading:20332237-Humans,
pubmed-meshheading:20332237-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:20332237-Mice,
pubmed-meshheading:20332237-Mice, Inbred C57BL,
pubmed-meshheading:20332237-Mice, Nude,
pubmed-meshheading:20332237-Mice, SCID,
pubmed-meshheading:20332237-Mice, Transgenic,
pubmed-meshheading:20332237-Mitochondrial Proteins,
pubmed-meshheading:20332237-Pancreatic Neoplasms,
pubmed-meshheading:20332237-RNA, Small Interfering,
pubmed-meshheading:20332237-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:20332237-Tumor Necrosis Factor-alpha,
pubmed-meshheading:20332237-X-Linked Inhibitor of Apoptosis Protein
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pubmed:year |
2010
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pubmed:articleTitle |
Smac mimetic increases chemotherapy response and improves survival in mice with pancreatic cancer.
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pubmed:affiliation |
Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical School, Dallas, TX, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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