상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

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

Authors 

J C KimE S ShinC W KimS A RohD H ChoY S NaT W KimM B KimY L HyunS RoSeon-Young KimYong Sung Kim

Publisher 

International Institute of Anticancer Research (IIAR)

Issue Date 

2009

Citation 

Anticancer Research, vol. 29, no. 8, pp. 3027-3034

Keywords 

Histone deacetylase inhibitorcombinationchemosensitivityin vitro assaycolorectal adenocarcinomas

Abstract 

Background: 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.

ISSN 

0250-7005

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)