In vitro evaluation of histone deacetylase inhibitors as combination agents for colorectal cancer

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dc.contributor.authorJ C Kim-
dc.contributor.authorE S Shin-
dc.contributor.authorC W Kim-
dc.contributor.authorS A Roh-
dc.contributor.authorD H Cho-
dc.contributor.authorY S Na-
dc.contributor.authorT W Kim-
dc.contributor.authorM B Kim-
dc.contributor.authorY L Hyun-
dc.contributor.authorS Ro-
dc.contributor.authorSeon-Young Kim-
dc.contributor.authorYong Sung Kim-
dc.date.accessioned2017-04-19T09:14:15Z-
dc.date.available2017-04-19T09:14:15Z-
dc.date.issued2009-
dc.identifier.issn0250-7005-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/9067-
dc.description.abstractBackground: Our primary aim was to evaluate the additive efficacy of histone deacetylase inhibitors (HDACIs) in established treatment regimens for colorectal cancer in concurrence with identifying the clinicopathological markers significantly associated with tumor responsiveness. Patients and Methods: The chemosensitivities of 125 colorectal carcinomas to established regimens [FLOX (5-FU +leucovorin + oxaliplatin) and FLIRI (5-FU + leucovorin +irinotecan)], two biologically targeted drugs (avastin and erbitux), and two hydroxamic acid derivatives (vorinostat, SAHA?, and a novel candidate, CG2) were comparatively evaluated using an in vitro tumor response assay. Results: The response rates of tumors (inhibition rate ≥30% ) were significantly greater for FLOX and combinations (55.2-68%) compared to FLIRI and combinations (44-63.2% ) (p=0.001 to 0.048), except in the case of the CG2 combination. The additive effects of HDACIs on the respective established regimens were considerably greater for non-responsive tumors (64.3-80% ) than responsive tumors (32.7-45% ) (p≤0.0001 to 0.008). A number of biological parameters, including less advanced tumors and p53 overexpression, were significantly associated with additive chemosensitivity to HDACIs in combination with FLOX and FLIRI in multivariate analyses (p≤0.001 to 0.023). Expanding tumor growth, diffuse cytoplasmic carcinoembryonic antigen (CEA) expression and synchronous adenoma were associated with combination regimens with targeted drugs (p=0.013 to 0.032). Conclusion: Our findings show additive chemoresponsiveness of colorectal tumors to HDAC inhibitors in combination with established regimens. The significant parameters associated with combination regimens of targeted drugs and HDACIs may be applied as effective chemosensitive markers in future clinical trials.-
dc.publisherInt Inst Anticancer Research-
dc.titleIn vitro evaluation of histone deacetylase inhibitors as combination agents for colorectal cancer-
dc.title.alternativeIn vitro evaluation of histone deacetylase inhibitors as combination agents for colorectal cancer-
dc.typeArticle-
dc.citation.titleAnticancer Research-
dc.citation.number8-
dc.citation.endPage3034-
dc.citation.startPage3027-
dc.citation.volume29-
dc.contributor.affiliatedAuthorSeon-Young Kim-
dc.contributor.affiliatedAuthorYong Sung Kim-
dc.contributor.alternativeName김진천-
dc.contributor.alternativeName신의-
dc.contributor.alternativeName김찬-
dc.contributor.alternativeName노선애-
dc.contributor.alternativeName조동형-
dc.contributor.alternativeName나영순-
dc.contributor.alternativeName김태원-
dc.contributor.alternativeName김문보-
dc.contributor.alternativeName현영-
dc.contributor.alternativeName노승구-
dc.contributor.alternativeName김선영-
dc.contributor.alternativeName김용성-
dc.identifier.bibliographicCitationAnticancer Research, vol. 29, no. 8, pp. 3027-3034-
dc.subject.keywordHistone deacetylase inhibitor-
dc.subject.keywordcombination-
dc.subject.keywordchemosensitivity-
dc.subject.keywordin vitro assay-
dc.subject.keywordcolorectal adenocarcinomas-
dc.subject.localHistone deacetylase inhibitor-
dc.subject.localhistone deacetylase inhibitor-
dc.subject.localcombination-
dc.subject.localChemosensitivity-
dc.subject.localchemosensitivity-
dc.subject.localIn vitro assay-
dc.subject.localin vitro assay-
dc.subject.localColorectal adenocarcinomas-
dc.subject.localColorectal adenocarcinoma-
dc.subject.localcolorectal adenocarcinomas-
dc.description.journalClassY-
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