Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma

Abstract Background Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study objective was to evaluate the synergic effect of PDT using a new photosensitizer, talaporfin sodium (Laserphyrin), in combination with conventional antica...

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Veröffentlicht in:The Journal of surgical research 2013-05, Vol.181 (2), p.234-241
Hauptverfasser: Nonaka, Yoshikazu, MD, Nanashima, Atsushi, MD, Nonaka, Takashi, MD, Uehara, Masataka, MD, Isomoto, Hajime, MD, Abo, Takafumi, MD, Nagayasu, Takeshi, MD
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container_end_page 241
container_issue 2
container_start_page 234
container_title The Journal of surgical research
container_volume 181
creator Nonaka, Yoshikazu, MD
Nanashima, Atsushi, MD
Nonaka, Takashi, MD
Uehara, Masataka, MD
Isomoto, Hajime, MD
Abo, Takafumi, MD
Nagayasu, Takeshi, MD
description Abstract Background Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study objective was to evaluate the synergic effect of PDT using a new photosensitizer, talaporfin sodium (Laserphyrin), in combination with conventional anticancer drug treatments. Methods The range of the necrotic area, the percentage of apoptosis-positive cells, the vascular endothelial growth factor expression quantification, and the proliferating cell nuclear antigen–labeling index, as treatment effects, were examined in the BDC cell line (NOZ) in vitro and in vivo (4-wk-old male BALB/c mice). Results Tumor viability was determined by an in vitro MTS assay. PDT with a single treatment of 5-fluorouracil, gemcitabine, oxaliplatin, and cis -diamminedichloroplatinum showed a significantly lower viability compared with the control or the PDT-alone group ( P < 0.05). Furthermore, administering PDT combined with two anticancer drugs showed a further decline in the tumor viability. A treatment of PDT combined with oxaliplatin and gemcitabine showed the least viability ( P < 0.05). Thus, this regimen was administered in the in vivo study. The tumor necrotic area, apoptosis positivity, and the vascular endothelial growth factor expression rate were higher in the PDT with anticancer drugs group compared with those of the other groups ( P < 0.05). The proliferating cell nuclear antigen–labeling index results in the PDT with the anticancer drugs group were significantly lower than those of the other groups ( P < 0.05). Conclusions A treatment of PDT combined with gemcitabine and oxaliplatin showed the best synergic effect for necrosis, apoptosis, and cytostatic alterations for the treatment of BDC.
doi_str_mv 10.1016/j.jss.2012.06.047
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The study objective was to evaluate the synergic effect of PDT using a new photosensitizer, talaporfin sodium (Laserphyrin), in combination with conventional anticancer drug treatments. Methods The range of the necrotic area, the percentage of apoptosis-positive cells, the vascular endothelial growth factor expression quantification, and the proliferating cell nuclear antigen–labeling index, as treatment effects, were examined in the BDC cell line (NOZ) in vitro and in vivo (4-wk-old male BALB/c mice). Results Tumor viability was determined by an in vitro MTS assay. PDT with a single treatment of 5-fluorouracil, gemcitabine, oxaliplatin, and cis -diamminedichloroplatinum showed a significantly lower viability compared with the control or the PDT-alone group ( P &lt; 0.05). Furthermore, administering PDT combined with two anticancer drugs showed a further decline in the tumor viability. A treatment of PDT combined with oxaliplatin and gemcitabine showed the least viability ( P &lt; 0.05). Thus, this regimen was administered in the in vivo study. The tumor necrotic area, apoptosis positivity, and the vascular endothelial growth factor expression rate were higher in the PDT with anticancer drugs group compared with those of the other groups ( P &lt; 0.05). The proliferating cell nuclear antigen–labeling index results in the PDT with the anticancer drugs group were significantly lower than those of the other groups ( P &lt; 0.05). Conclusions A treatment of PDT combined with gemcitabine and oxaliplatin showed the best synergic effect for necrosis, apoptosis, and cytostatic alterations for the treatment of BDC.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2012.06.047</identifier><identifier>PMID: 22835954</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject><![CDATA[Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis ; Apoptosis - drug effects ; Bile duct carcinoma ; Bile Duct Neoplasms - drug therapy ; Bile Duct Neoplasms - metabolism ; Biomarkers, Tumor - metabolism ; Cell Line, Tumor ; Cell Survival - drug effects ; Cisplatin - administration & dosage ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Drug Synergism ; Fluorouracil - administration & dosage ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Mice ; Mice, Inbred BALB C ; Organoplatinum Compounds - administration & dosage ; Photochemotherapy ; Photodynamic therapy ; Photosensitizing Agents - pharmacology ; Photosensitizing Agents - therapeutic use ; Porphyrins - pharmacology ; Porphyrins - therapeutic use ; Proliferating Cell Nuclear Antigen - metabolism ; Surgery ; Synergic effect ; Talaporfin sodium ; Treatment Outcome ; Vascular Endothelial Growth Factor A - metabolism]]></subject><ispartof>The Journal of surgical research, 2013-05, Vol.181 (2), p.234-241</ispartof><rights>Elsevier Inc.</rights><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-e2a6725f5ac653d848adfb79a6f6ed9c41e9c544b9225c77d16e9d70f27d173e3</citedby><cites>FETCH-LOGICAL-c495t-e2a6725f5ac653d848adfb79a6f6ed9c41e9c544b9225c77d16e9d70f27d173e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022480412006099$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22835954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nonaka, Yoshikazu, MD</creatorcontrib><creatorcontrib>Nanashima, Atsushi, MD</creatorcontrib><creatorcontrib>Nonaka, Takashi, MD</creatorcontrib><creatorcontrib>Uehara, Masataka, MD</creatorcontrib><creatorcontrib>Isomoto, Hajime, MD</creatorcontrib><creatorcontrib>Abo, Takafumi, MD</creatorcontrib><creatorcontrib>Nagayasu, Takeshi, MD</creatorcontrib><title>Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Abstract Background Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study objective was to evaluate the synergic effect of PDT using a new photosensitizer, talaporfin sodium (Laserphyrin), in combination with conventional anticancer drug treatments. Methods The range of the necrotic area, the percentage of apoptosis-positive cells, the vascular endothelial growth factor expression quantification, and the proliferating cell nuclear antigen–labeling index, as treatment effects, were examined in the BDC cell line (NOZ) in vitro and in vivo (4-wk-old male BALB/c mice). Results Tumor viability was determined by an in vitro MTS assay. PDT with a single treatment of 5-fluorouracil, gemcitabine, oxaliplatin, and cis -diamminedichloroplatinum showed a significantly lower viability compared with the control or the PDT-alone group ( P &lt; 0.05). Furthermore, administering PDT combined with two anticancer drugs showed a further decline in the tumor viability. A treatment of PDT combined with oxaliplatin and gemcitabine showed the least viability ( P &lt; 0.05). Thus, this regimen was administered in the in vivo study. The tumor necrotic area, apoptosis positivity, and the vascular endothelial growth factor expression rate were higher in the PDT with anticancer drugs group compared with those of the other groups ( P &lt; 0.05). The proliferating cell nuclear antigen–labeling index results in the PDT with the anticancer drugs group were significantly lower than those of the other groups ( P &lt; 0.05). Conclusions A treatment of PDT combined with gemcitabine and oxaliplatin showed the best synergic effect for necrosis, apoptosis, and cytostatic alterations for the treatment of BDC.</description><subject>Animals</subject><subject>Antineoplastic Agents - administration &amp; dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bile duct carcinoma</subject><subject>Bile Duct Neoplasms - drug therapy</subject><subject>Bile Duct Neoplasms - metabolism</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cisplatin - administration &amp; dosage</subject><subject>Deoxycytidine - administration &amp; dosage</subject><subject>Deoxycytidine - analogs &amp; derivatives</subject><subject>Drug Synergism</subject><subject>Fluorouracil - administration &amp; 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Nanashima, Atsushi, MD ; Nonaka, Takashi, MD ; Uehara, Masataka, MD ; Isomoto, Hajime, MD ; Abo, Takafumi, MD ; Nagayasu, Takeshi, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-e2a6725f5ac653d848adfb79a6f6ed9c41e9c544b9225c77d16e9d70f27d173e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - administration &amp; dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bile duct carcinoma</topic><topic>Bile Duct Neoplasms - drug therapy</topic><topic>Bile Duct Neoplasms - metabolism</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cisplatin - administration &amp; dosage</topic><topic>Deoxycytidine - administration &amp; dosage</topic><topic>Deoxycytidine - analogs &amp; derivatives</topic><topic>Drug Synergism</topic><topic>Fluorouracil - administration &amp; dosage</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Organoplatinum Compounds - administration &amp; dosage</topic><topic>Photochemotherapy</topic><topic>Photodynamic therapy</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Photosensitizing Agents - therapeutic use</topic><topic>Porphyrins - pharmacology</topic><topic>Porphyrins - therapeutic use</topic><topic>Proliferating Cell Nuclear Antigen - metabolism</topic><topic>Surgery</topic><topic>Synergic effect</topic><topic>Talaporfin sodium</topic><topic>Treatment Outcome</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nonaka, Yoshikazu, MD</creatorcontrib><creatorcontrib>Nanashima, Atsushi, MD</creatorcontrib><creatorcontrib>Nonaka, Takashi, MD</creatorcontrib><creatorcontrib>Uehara, Masataka, MD</creatorcontrib><creatorcontrib>Isomoto, Hajime, MD</creatorcontrib><creatorcontrib>Abo, Takafumi, MD</creatorcontrib><creatorcontrib>Nagayasu, Takeshi, MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nonaka, Yoshikazu, MD</au><au>Nanashima, Atsushi, MD</au><au>Nonaka, Takashi, MD</au><au>Uehara, Masataka, MD</au><au>Isomoto, Hajime, MD</au><au>Abo, Takafumi, MD</au><au>Nagayasu, Takeshi, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2013-05-15</date><risdate>2013</risdate><volume>181</volume><issue>2</issue><spage>234</spage><epage>241</epage><pages>234-241</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>Abstract Background Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study objective was to evaluate the synergic effect of PDT using a new photosensitizer, talaporfin sodium (Laserphyrin), in combination with conventional anticancer drug treatments. Methods The range of the necrotic area, the percentage of apoptosis-positive cells, the vascular endothelial growth factor expression quantification, and the proliferating cell nuclear antigen–labeling index, as treatment effects, were examined in the BDC cell line (NOZ) in vitro and in vivo (4-wk-old male BALB/c mice). Results Tumor viability was determined by an in vitro MTS assay. PDT with a single treatment of 5-fluorouracil, gemcitabine, oxaliplatin, and cis -diamminedichloroplatinum showed a significantly lower viability compared with the control or the PDT-alone group ( P &lt; 0.05). Furthermore, administering PDT combined with two anticancer drugs showed a further decline in the tumor viability. A treatment of PDT combined with oxaliplatin and gemcitabine showed the least viability ( P &lt; 0.05). Thus, this regimen was administered in the in vivo study. The tumor necrotic area, apoptosis positivity, and the vascular endothelial growth factor expression rate were higher in the PDT with anticancer drugs group compared with those of the other groups ( P &lt; 0.05). The proliferating cell nuclear antigen–labeling index results in the PDT with the anticancer drugs group were significantly lower than those of the other groups ( P &lt; 0.05). Conclusions A treatment of PDT combined with gemcitabine and oxaliplatin showed the best synergic effect for necrosis, apoptosis, and cytostatic alterations for the treatment of BDC.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22835954</pmid><doi>10.1016/j.jss.2012.06.047</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Apoptosis
Apoptosis - drug effects
Bile duct carcinoma
Bile Duct Neoplasms - drug therapy
Bile Duct Neoplasms - metabolism
Biomarkers, Tumor - metabolism
Cell Line, Tumor
Cell Survival - drug effects
Cisplatin - administration & dosage
Deoxycytidine - administration & dosage
Deoxycytidine - analogs & derivatives
Drug Synergism
Fluorouracil - administration & dosage
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Male
Mice
Mice, Inbred BALB C
Organoplatinum Compounds - administration & dosage
Photochemotherapy
Photodynamic therapy
Photosensitizing Agents - pharmacology
Photosensitizing Agents - therapeutic use
Porphyrins - pharmacology
Porphyrins - therapeutic use
Proliferating Cell Nuclear Antigen - metabolism
Surgery
Synergic effect
Talaporfin sodium
Treatment Outcome
Vascular Endothelial Growth Factor A - metabolism
title Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma
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