In Vitro Evaluation of Histone Deacetylase Inhibitors as Combination Agents for Colorectal Cancer
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 Method...
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| Veröffentlicht in: | Anticancer research 2009-08, Vol.29 (8), p.3027-3034 |
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| creator | KIM, Jin C SHIN, Eui S KIM, Seon Y KIM, Yong S KIM, Chan W ROH, Seon A CHO, Dong H NA, Young S KIM, Tae W KIM, Moon B HYUN, Young L RO, Seonggu |
| description | 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 â¥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%) (pâ¤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 (pâ¤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. |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_pasca</sourceid><recordid>TN_cdi_pubmed_primary_19661311</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>19661311</sourcerecordid><originalsourceid>FETCH-LOGICAL-h269t-9ac67b19ac90679bfc5478a5c9587987e228847dd188c343e1d95eb3be7045393</originalsourceid><addsrcrecordid>eNpFkE9LAzEUxIMotla_guTicSF_NpvkWGq1hYIX9bq8zWa7keymJKnSb--CVU8Dw2-Gee8CzanUtJCCk0s0J0yQQhIiZugmpQ9Cqkorfo1mVFcV5ZTOEWxH_O5yDHj9Cf4I2YURhw5vXMphtPjRgrH55CFZvB1717gcYsKQ8CoMjRt_Asu9HXPCXYiT7UO0JoPHKxiNjbfoqgOf7N1ZF-jtaf262hS7l-ftarkrelbpXGgwlWzoJJpUUjedEaVUIIwWSmolLWNKlbJtqVKGl9zSVgvb8MZKUgqu-QLd__Qejs1g2_oQ3QDxVP_eOgEPZwCSAd_FaZ5LfxybPieFYv9c7_b9l4u2TgN4P9XyGiLTtao5YZJ_A8aAasA</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>In Vitro Evaluation of Histone Deacetylase Inhibitors as Combination Agents for Colorectal Cancer</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>KIM, Jin C ; SHIN, Eui S ; KIM, Seon Y ; KIM, Yong S ; KIM, Chan W ; ROH, Seon A ; CHO, Dong H ; NA, Young S ; KIM, Tae W ; KIM, Moon B ; HYUN, Young L ; RO, Seonggu</creator><creatorcontrib>KIM, Jin C ; SHIN, Eui S ; KIM, Seon Y ; KIM, Yong S ; KIM, Chan W ; ROH, Seon A ; CHO, Dong H ; NA, Young S ; KIM, Tae W ; KIM, Moon B ; HYUN, Young L ; RO, Seonggu</creatorcontrib><description>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 â¥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%) (pâ¤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 (pâ¤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.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 19661311</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - enzymology ; Adenocarcinoma - secondary ; Adenocarcinoma, Mucinous - drug therapy ; Adenocarcinoma, Mucinous - enzymology ; Adenocarcinoma, Mucinous - secondary ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Cell Proliferation - drug effects ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - enzymology ; Colorectal Neoplasms - pathology ; Dose-Response Relationship, Drug ; Drug Synergism ; Drug Therapy, Combination ; Enzyme Inhibitors - therapeutic use ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Histone Deacetylase Inhibitors ; Humans ; In Vitro Techniques ; Male ; Medical sciences ; Middle Aged ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Treatment Outcome ; Tumors</subject><ispartof>Anticancer research, 2009-08, Vol.29 (8), p.3027-3034</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21797582$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19661311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KIM, Jin C</creatorcontrib><creatorcontrib>SHIN, Eui S</creatorcontrib><creatorcontrib>KIM, Seon Y</creatorcontrib><creatorcontrib>KIM, Yong S</creatorcontrib><creatorcontrib>KIM, Chan W</creatorcontrib><creatorcontrib>ROH, Seon A</creatorcontrib><creatorcontrib>CHO, Dong H</creatorcontrib><creatorcontrib>NA, Young S</creatorcontrib><creatorcontrib>KIM, Tae W</creatorcontrib><creatorcontrib>KIM, Moon B</creatorcontrib><creatorcontrib>HYUN, Young L</creatorcontrib><creatorcontrib>RO, Seonggu</creatorcontrib><title>In Vitro Evaluation of Histone Deacetylase Inhibitors as Combination Agents for Colorectal Cancer</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>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 â¥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%) (pâ¤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 (pâ¤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.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - enzymology</subject><subject>Adenocarcinoma - secondary</subject><subject>Adenocarcinoma, Mucinous - drug therapy</subject><subject>Adenocarcinoma, Mucinous - enzymology</subject><subject>Adenocarcinoma, Mucinous - secondary</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation - drug effects</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - enzymology</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Synergism</subject><subject>Drug Therapy, Combination</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Histone Deacetylase Inhibitors</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE9LAzEUxIMotla_guTicSF_NpvkWGq1hYIX9bq8zWa7keymJKnSb--CVU8Dw2-Gee8CzanUtJCCk0s0J0yQQhIiZugmpQ9Cqkorfo1mVFcV5ZTOEWxH_O5yDHj9Cf4I2YURhw5vXMphtPjRgrH55CFZvB1717gcYsKQ8CoMjRt_Asu9HXPCXYiT7UO0JoPHKxiNjbfoqgOf7N1ZF-jtaf262hS7l-ftarkrelbpXGgwlWzoJJpUUjedEaVUIIwWSmolLWNKlbJtqVKGl9zSVgvb8MZKUgqu-QLd__Qejs1g2_oQ3QDxVP_eOgEPZwCSAd_FaZ5LfxybPieFYv9c7_b9l4u2TgN4P9XyGiLTtao5YZJ_A8aAasA</recordid><startdate>20090801</startdate><enddate>20090801</enddate><creator>KIM, Jin C</creator><creator>SHIN, Eui S</creator><creator>KIM, Seon Y</creator><creator>KIM, Yong S</creator><creator>KIM, Chan W</creator><creator>ROH, Seon A</creator><creator>CHO, Dong H</creator><creator>NA, Young S</creator><creator>KIM, Tae W</creator><creator>KIM, Moon B</creator><creator>HYUN, Young L</creator><creator>RO, Seonggu</creator><general>International Institute of Anticancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20090801</creationdate><title>In Vitro Evaluation of Histone Deacetylase Inhibitors as Combination Agents for Colorectal Cancer</title><author>KIM, Jin C ; SHIN, Eui S ; KIM, Seon Y ; KIM, Yong S ; KIM, Chan W ; ROH, Seon A ; CHO, Dong H ; NA, Young S ; KIM, Tae W ; KIM, Moon B ; HYUN, Young L ; RO, Seonggu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h269t-9ac67b19ac90679bfc5478a5c9587987e228847dd188c343e1d95eb3be7045393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - enzymology</topic><topic>Adenocarcinoma - secondary</topic><topic>Adenocarcinoma, Mucinous - drug therapy</topic><topic>Adenocarcinoma, Mucinous - enzymology</topic><topic>Adenocarcinoma, Mucinous - secondary</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation - drug effects</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - enzymology</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Synergism</topic><topic>Drug Therapy, Combination</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Histone Deacetylase Inhibitors</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KIM, Jin C</creatorcontrib><creatorcontrib>SHIN, Eui S</creatorcontrib><creatorcontrib>KIM, Seon Y</creatorcontrib><creatorcontrib>KIM, Yong S</creatorcontrib><creatorcontrib>KIM, Chan W</creatorcontrib><creatorcontrib>ROH, Seon A</creatorcontrib><creatorcontrib>CHO, Dong H</creatorcontrib><creatorcontrib>NA, Young S</creatorcontrib><creatorcontrib>KIM, Tae W</creatorcontrib><creatorcontrib>KIM, Moon B</creatorcontrib><creatorcontrib>HYUN, Young L</creatorcontrib><creatorcontrib>RO, Seonggu</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KIM, Jin C</au><au>SHIN, Eui S</au><au>KIM, Seon Y</au><au>KIM, Yong S</au><au>KIM, Chan W</au><au>ROH, Seon A</au><au>CHO, Dong H</au><au>NA, Young S</au><au>KIM, Tae W</au><au>KIM, Moon B</au><au>HYUN, Young L</au><au>RO, Seonggu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vitro Evaluation of Histone Deacetylase Inhibitors as Combination Agents for Colorectal Cancer</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2009-08-01</date><risdate>2009</risdate><volume>29</volume><issue>8</issue><spage>3027</spage><epage>3034</epage><pages>3027-3034</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><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 â¥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%) (pâ¤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 (pâ¤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.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>19661311</pmid><tpages>8</tpages></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - enzymology Adenocarcinoma - secondary Adenocarcinoma, Mucinous - drug therapy Adenocarcinoma, Mucinous - enzymology Adenocarcinoma, Mucinous - secondary Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Cell Proliferation - drug effects Colorectal Neoplasms - drug therapy Colorectal Neoplasms - enzymology Colorectal Neoplasms - pathology Dose-Response Relationship, Drug Drug Synergism Drug Therapy, Combination Enzyme Inhibitors - therapeutic use Female Gastroenterology. Liver. Pancreas. Abdomen Histone Deacetylase Inhibitors Humans In Vitro Techniques Male Medical sciences Middle Aged Neoplasm Staging Prognosis Prospective Studies Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Treatment Outcome Tumors |
| title | In Vitro Evaluation of Histone Deacetylase Inhibitors as Combination Agents for Colorectal Cancer |
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