TY - JOUR
T1 - In vitro chemosensitivity of gastric adenocarcinomas to histone deacetylase inhibitors, compared to established drugs
AU - Yoon, Sang Nam
AU - Roh, Seon Ae
AU - Cho, Dong Hyung
AU - Kim, Moon Bo
AU - Hyun, Young Lan
AU - Ro, Seonggu
AU - Kim, Byung Sik
AU - Kim, Seon Young
AU - Kim, Yong Sung
AU - Kim, Jin Cheon
PY - 2010/5
Y1 - 2010/5
N2 - BACKGROUND/AIMS: This study was performed to determine the efficacy of histone deacetylase inhibitors in gastric cancer, together with other established regimens. METHODOLOGY: The chemosensitivities of 93 gastric cancer patients to established drugs, and three histone deacetylase inhibitors (SAHA, PXD101, and a novel candidate, CG-2) were evaluated using the histoculture drug response assay. RESULTS: Tumor growth inhibition rates were the highest with cisplatin, followed by PXD101, taxol, docetaxel, and TS-1, in descending order. The response rates were 41.9-68.8%, and 37.6-47.3%, respectively, at an inhibition rate cutoff value of 30%. Synergistic activity was evident with most combinations of established drugs and histone deacetylase inhibitors. Diffuse- or mixed-type carcinomas on Lauren classification were closely associated with increased chemosensitivity to TS-1 (p = 0.044). Node-positive and "other than tubular type" tumors on WHO classification were chemosensitive to cisplatin (p = 0.011 and 0.014, respectively). CG-2 chemosensitivity was markedly associated with low preoperative CA72-4 level (≤4 U/ml) (p = 0.046). CONCLUSIONS: This in vitro chemosensitivity assay validates the comparable chemo-response of gastric cancers to histone deacetylase inhibitors and established drugs, indicating considerable therapeutic efficacy of these agents. Additionally, a number of clinicopathological parameters are significantly associated with specific regimens.
AB - BACKGROUND/AIMS: This study was performed to determine the efficacy of histone deacetylase inhibitors in gastric cancer, together with other established regimens. METHODOLOGY: The chemosensitivities of 93 gastric cancer patients to established drugs, and three histone deacetylase inhibitors (SAHA, PXD101, and a novel candidate, CG-2) were evaluated using the histoculture drug response assay. RESULTS: Tumor growth inhibition rates were the highest with cisplatin, followed by PXD101, taxol, docetaxel, and TS-1, in descending order. The response rates were 41.9-68.8%, and 37.6-47.3%, respectively, at an inhibition rate cutoff value of 30%. Synergistic activity was evident with most combinations of established drugs and histone deacetylase inhibitors. Diffuse- or mixed-type carcinomas on Lauren classification were closely associated with increased chemosensitivity to TS-1 (p = 0.044). Node-positive and "other than tubular type" tumors on WHO classification were chemosensitive to cisplatin (p = 0.011 and 0.014, respectively). CG-2 chemosensitivity was markedly associated with low preoperative CA72-4 level (≤4 U/ml) (p = 0.046). CONCLUSIONS: This in vitro chemosensitivity assay validates the comparable chemo-response of gastric cancers to histone deacetylase inhibitors and established drugs, indicating considerable therapeutic efficacy of these agents. Additionally, a number of clinicopathological parameters are significantly associated with specific regimens.
KW - Chemosensitivity
KW - Gastric adenocarcinomas
KW - Histoculture drug response assay (HDRA)
KW - Histone deacetylase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=77955502396&partnerID=8YFLogxK
M3 - Article
C2 - 20698245
AN - SCOPUS:77955502396
SN - 0172-6390
VL - 57
SP - 657
EP - 662
JO - Hepato-Gastroenterology
JF - Hepato-Gastroenterology
IS - 99-100
ER -
