Synergistic Effects of Oncolytic Reovirus and Cisplatin Chemotherapy in Murine Malignant Melanoma
Purpose: To test combination treatment schedules of reovirus and cisplatin chemotherapy in human and murine melanoma cell lines and murine models of melanoma and to investigate the possible mechanisms of synergistic antitumor effects. Experimental Design: The effects of reovirus ± chemotherapy on in...
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| Veröffentlicht in: | Clinical cancer research 2009-10, Vol.15 (19), p.6158-6166 |
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| creator | PANDHA, Hardev S HEINEMANN, Lucy SIMPSON, Guy R MELCHER, Alan PRESTWICH, Robin ERRINGTON, Fiona COFFEY, Matt HARRINGTON, Kevin J MORGAN, Richard |
| description | Purpose: To test combination treatment schedules of reovirus and cisplatin chemotherapy in human and murine melanoma cell lines and
murine models of melanoma and to investigate the possible mechanisms of synergistic antitumor effects.
Experimental Design: The effects of reovirus ± chemotherapy on in vitro cytotoxicity and viral replication were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium assay and plaque assay. Interactions between agents were assessed by combination index analysis. Mode of cell
death was assessed by Annexin V/propidium iodide fluorescence-activated cell sorting–based assays; gene expression profiling
of single versus combination treatments was completed using the Agilent microarray system. Single agent and combination therapy
effects were tested in vivo in two immunocompetent models of murine melanoma.
Results: Variable degrees of synergistic cytotoxicity between live reovirus and several chemotherapy agents were observed in B16.F10
mouse melanoma cells, most significantly with cisplatin (combination index of 0.42 ± 0.03 at ED 50 ). Combination of cisplatin and reovirus exposure led to increased late apoptotic/necrotic cell populations. Cisplatin almost
completely abrogated the inflammatory cytokine gene up-regulation induced by reovirus. Combination therapy led to significantly
delayed tumor growth and improved survival in vivo ( P < 0.0001 and P = 0.0003, respectively). Cisplatin had no effect on the humoral response to reovirus in mice. However, cisplatin treatment
suppressed the cytokine and chemokine response to reovirus in vitro and in vivo .
Conclusion: The combination of reovirus and several chemotherapeutic agents synergistically enhanced cytotoxicity in human and murine
melanoma cell lines in vitro and murine tumors in vivo . The data support the current reovirus/chemotherapy combination phase I clinical studies currently ongoing in the clinic.
(Clin Cancer Res 2009;15(19):6158–66) |
| doi_str_mv | 10.1158/1078-0432.CCR-09-0796 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_734067177</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>734067177</sourcerecordid><originalsourceid>FETCH-LOGICAL-c485t-8048fc44dec2d6377cf9b5fe953ab7c020d0b993d7cfeb94f8cc23d4cd54543b3</originalsourceid><addsrcrecordid>eNpFkEtv3CAURlHUKo9pf0IrNlXUhVMwYMyyspKmUkaR0naNML6MqWw8BTvR_PtizTRd8Tr33o-D0AdKbigV9RdKZF0QzsqbpnkqiCqIVNUZuqRCyIKVlXiT9_-YC3SV0m9CKKeEn6MLqqRkTMpLZH4cAsSdT7O3-NY5sHPCk8OPwU7DYb18gunZxyVhEzrc-LQfzOwDbnoYp7mHaPYHnM_bJfoAeGsGvwsmzHgLgwnTaN6ht84MCd6f1g36dXf7s7kvHh6_fW--PhSW12IuasJrZznvwJZdlbNZp1rhQAlmWmlJSTrSKsW6_ACt4q62tmQdt53ggrOWbdD1se8-Tn8WSLMefbIw5BQwLUlLxkklaf74BokjaeOUUgSn99GPJh40JXqVq1dxehWns1xNlF7l5rqPpwlLO0L3v-pkMwOfToBJ1gwummB9euXKknDOCM3c5yPX-13_4iNom0mIERKYaHtNRW6qqxyF_QUacJIX</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>734067177</pqid></control><display><type>article</type><title>Synergistic Effects of Oncolytic Reovirus and Cisplatin Chemotherapy in Murine Malignant Melanoma</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>PANDHA, Hardev S ; HEINEMANN, Lucy ; SIMPSON, Guy R ; MELCHER, Alan ; PRESTWICH, Robin ; ERRINGTON, Fiona ; COFFEY, Matt ; HARRINGTON, Kevin J ; MORGAN, Richard</creator><creatorcontrib>PANDHA, Hardev S ; HEINEMANN, Lucy ; SIMPSON, Guy R ; MELCHER, Alan ; PRESTWICH, Robin ; ERRINGTON, Fiona ; COFFEY, Matt ; HARRINGTON, Kevin J ; MORGAN, Richard</creatorcontrib><description>Purpose: To test combination treatment schedules of reovirus and cisplatin chemotherapy in human and murine melanoma cell lines and
murine models of melanoma and to investigate the possible mechanisms of synergistic antitumor effects.
Experimental Design: The effects of reovirus ± chemotherapy on in vitro cytotoxicity and viral replication were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium assay and plaque assay. Interactions between agents were assessed by combination index analysis. Mode of cell
death was assessed by Annexin V/propidium iodide fluorescence-activated cell sorting–based assays; gene expression profiling
of single versus combination treatments was completed using the Agilent microarray system. Single agent and combination therapy
effects were tested in vivo in two immunocompetent models of murine melanoma.
Results: Variable degrees of synergistic cytotoxicity between live reovirus and several chemotherapy agents were observed in B16.F10
mouse melanoma cells, most significantly with cisplatin (combination index of 0.42 ± 0.03 at ED 50 ). Combination of cisplatin and reovirus exposure led to increased late apoptotic/necrotic cell populations. Cisplatin almost
completely abrogated the inflammatory cytokine gene up-regulation induced by reovirus. Combination therapy led to significantly
delayed tumor growth and improved survival in vivo ( P < 0.0001 and P = 0.0003, respectively). Cisplatin had no effect on the humoral response to reovirus in mice. However, cisplatin treatment
suppressed the cytokine and chemokine response to reovirus in vitro and in vivo .
Conclusion: The combination of reovirus and several chemotherapeutic agents synergistically enhanced cytotoxicity in human and murine
melanoma cell lines in vitro and murine tumors in vivo . The data support the current reovirus/chemotherapy combination phase I clinical studies currently ongoing in the clinic.
(Clin Cancer Res 2009;15(19):6158–66)</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-09-0796</identifier><identifier>PMID: 19773377</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis - physiology ; Biological and medical sciences ; chemotherapy ; cisplatin ; Cisplatin - administration & dosage ; Combined Modality Therapy ; Dermatology ; Humans ; Medical sciences ; melanoma ; Melanoma, Experimental - pathology ; Melanoma, Experimental - therapy ; Mice ; Mice, Inbred C57BL ; NIH 3T3 Cells ; oncolytic ; Oncolytic Virotherapy ; Oncolytic Viruses - physiology ; Pharmacology. Drug treatments ; Reoviridae - physiology ; reovirus ; Treatment Outcome ; Tumor Cells, Cultured ; Tumors of the skin and soft tissue. Premalignant lesions ; Virus Replication - drug effects</subject><ispartof>Clinical cancer research, 2009-10, Vol.15 (19), p.6158-6166</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-8048fc44dec2d6377cf9b5fe953ab7c020d0b993d7cfeb94f8cc23d4cd54543b3</citedby><cites>FETCH-LOGICAL-c485t-8048fc44dec2d6377cf9b5fe953ab7c020d0b993d7cfeb94f8cc23d4cd54543b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22044301$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19773377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PANDHA, Hardev S</creatorcontrib><creatorcontrib>HEINEMANN, Lucy</creatorcontrib><creatorcontrib>SIMPSON, Guy R</creatorcontrib><creatorcontrib>MELCHER, Alan</creatorcontrib><creatorcontrib>PRESTWICH, Robin</creatorcontrib><creatorcontrib>ERRINGTON, Fiona</creatorcontrib><creatorcontrib>COFFEY, Matt</creatorcontrib><creatorcontrib>HARRINGTON, Kevin J</creatorcontrib><creatorcontrib>MORGAN, Richard</creatorcontrib><title>Synergistic Effects of Oncolytic Reovirus and Cisplatin Chemotherapy in Murine Malignant Melanoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: To test combination treatment schedules of reovirus and cisplatin chemotherapy in human and murine melanoma cell lines and
murine models of melanoma and to investigate the possible mechanisms of synergistic antitumor effects.
Experimental Design: The effects of reovirus ± chemotherapy on in vitro cytotoxicity and viral replication were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium assay and plaque assay. Interactions between agents were assessed by combination index analysis. Mode of cell
death was assessed by Annexin V/propidium iodide fluorescence-activated cell sorting–based assays; gene expression profiling
of single versus combination treatments was completed using the Agilent microarray system. Single agent and combination therapy
effects were tested in vivo in two immunocompetent models of murine melanoma.
Results: Variable degrees of synergistic cytotoxicity between live reovirus and several chemotherapy agents were observed in B16.F10
mouse melanoma cells, most significantly with cisplatin (combination index of 0.42 ± 0.03 at ED 50 ). Combination of cisplatin and reovirus exposure led to increased late apoptotic/necrotic cell populations. Cisplatin almost
completely abrogated the inflammatory cytokine gene up-regulation induced by reovirus. Combination therapy led to significantly
delayed tumor growth and improved survival in vivo ( P < 0.0001 and P = 0.0003, respectively). Cisplatin had no effect on the humoral response to reovirus in mice. However, cisplatin treatment
suppressed the cytokine and chemokine response to reovirus in vitro and in vivo .
Conclusion: The combination of reovirus and several chemotherapeutic agents synergistically enhanced cytotoxicity in human and murine
melanoma cell lines in vitro and murine tumors in vivo . The data support the current reovirus/chemotherapy combination phase I clinical studies currently ongoing in the clinic.
(Clin Cancer Res 2009;15(19):6158–66)</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Apoptosis - physiology</subject><subject>Biological and medical sciences</subject><subject>chemotherapy</subject><subject>cisplatin</subject><subject>Cisplatin - administration & dosage</subject><subject>Combined Modality Therapy</subject><subject>Dermatology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>melanoma</subject><subject>Melanoma, Experimental - pathology</subject><subject>Melanoma, Experimental - therapy</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>NIH 3T3 Cells</subject><subject>oncolytic</subject><subject>Oncolytic Virotherapy</subject><subject>Oncolytic Viruses - physiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Reoviridae - physiology</subject><subject>reovirus</subject><subject>Treatment Outcome</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors of the skin and soft tissue. Premalignant lesions</subject><subject>Virus Replication - drug effects</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtv3CAURlHUKo9pf0IrNlXUhVMwYMyyspKmUkaR0naNML6MqWw8BTvR_PtizTRd8Tr33o-D0AdKbigV9RdKZF0QzsqbpnkqiCqIVNUZuqRCyIKVlXiT9_-YC3SV0m9CKKeEn6MLqqRkTMpLZH4cAsSdT7O3-NY5sHPCk8OPwU7DYb18gunZxyVhEzrc-LQfzOwDbnoYp7mHaPYHnM_bJfoAeGsGvwsmzHgLgwnTaN6ht84MCd6f1g36dXf7s7kvHh6_fW--PhSW12IuasJrZznvwJZdlbNZp1rhQAlmWmlJSTrSKsW6_ACt4q62tmQdt53ggrOWbdD1se8-Tn8WSLMefbIw5BQwLUlLxkklaf74BokjaeOUUgSn99GPJh40JXqVq1dxehWns1xNlF7l5rqPpwlLO0L3v-pkMwOfToBJ1gwummB9euXKknDOCM3c5yPX-13_4iNom0mIERKYaHtNRW6qqxyF_QUacJIX</recordid><startdate>20091001</startdate><enddate>20091001</enddate><creator>PANDHA, Hardev S</creator><creator>HEINEMANN, Lucy</creator><creator>SIMPSON, Guy R</creator><creator>MELCHER, Alan</creator><creator>PRESTWICH, Robin</creator><creator>ERRINGTON, Fiona</creator><creator>COFFEY, Matt</creator><creator>HARRINGTON, Kevin J</creator><creator>MORGAN, Richard</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20091001</creationdate><title>Synergistic Effects of Oncolytic Reovirus and Cisplatin Chemotherapy in Murine Malignant Melanoma</title><author>PANDHA, Hardev S ; HEINEMANN, Lucy ; SIMPSON, Guy R ; MELCHER, Alan ; PRESTWICH, Robin ; ERRINGTON, Fiona ; COFFEY, Matt ; HARRINGTON, Kevin J ; MORGAN, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-8048fc44dec2d6377cf9b5fe953ab7c020d0b993d7cfeb94f8cc23d4cd54543b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Apoptosis - physiology</topic><topic>Biological and medical sciences</topic><topic>chemotherapy</topic><topic>cisplatin</topic><topic>Cisplatin - administration & dosage</topic><topic>Combined Modality Therapy</topic><topic>Dermatology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>melanoma</topic><topic>Melanoma, Experimental - pathology</topic><topic>Melanoma, Experimental - therapy</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>NIH 3T3 Cells</topic><topic>oncolytic</topic><topic>Oncolytic Virotherapy</topic><topic>Oncolytic Viruses - physiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Reoviridae - physiology</topic><topic>reovirus</topic><topic>Treatment Outcome</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors of the skin and soft tissue. Premalignant lesions</topic><topic>Virus Replication - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PANDHA, Hardev S</creatorcontrib><creatorcontrib>HEINEMANN, Lucy</creatorcontrib><creatorcontrib>SIMPSON, Guy R</creatorcontrib><creatorcontrib>MELCHER, Alan</creatorcontrib><creatorcontrib>PRESTWICH, Robin</creatorcontrib><creatorcontrib>ERRINGTON, Fiona</creatorcontrib><creatorcontrib>COFFEY, Matt</creatorcontrib><creatorcontrib>HARRINGTON, Kevin J</creatorcontrib><creatorcontrib>MORGAN, Richard</creatorcontrib><collection>Pascal-Francis</collection><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>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PANDHA, Hardev S</au><au>HEINEMANN, Lucy</au><au>SIMPSON, Guy R</au><au>MELCHER, Alan</au><au>PRESTWICH, Robin</au><au>ERRINGTON, Fiona</au><au>COFFEY, Matt</au><au>HARRINGTON, Kevin J</au><au>MORGAN, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic Effects of Oncolytic Reovirus and Cisplatin Chemotherapy in Murine Malignant Melanoma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2009-10-01</date><risdate>2009</risdate><volume>15</volume><issue>19</issue><spage>6158</spage><epage>6166</epage><pages>6158-6166</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>Purpose: To test combination treatment schedules of reovirus and cisplatin chemotherapy in human and murine melanoma cell lines and
murine models of melanoma and to investigate the possible mechanisms of synergistic antitumor effects.
Experimental Design: The effects of reovirus ± chemotherapy on in vitro cytotoxicity and viral replication were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium assay and plaque assay. Interactions between agents were assessed by combination index analysis. Mode of cell
death was assessed by Annexin V/propidium iodide fluorescence-activated cell sorting–based assays; gene expression profiling
of single versus combination treatments was completed using the Agilent microarray system. Single agent and combination therapy
effects were tested in vivo in two immunocompetent models of murine melanoma.
Results: Variable degrees of synergistic cytotoxicity between live reovirus and several chemotherapy agents were observed in B16.F10
mouse melanoma cells, most significantly with cisplatin (combination index of 0.42 ± 0.03 at ED 50 ). Combination of cisplatin and reovirus exposure led to increased late apoptotic/necrotic cell populations. Cisplatin almost
completely abrogated the inflammatory cytokine gene up-regulation induced by reovirus. Combination therapy led to significantly
delayed tumor growth and improved survival in vivo ( P < 0.0001 and P = 0.0003, respectively). Cisplatin had no effect on the humoral response to reovirus in mice. However, cisplatin treatment
suppressed the cytokine and chemokine response to reovirus in vitro and in vivo .
Conclusion: The combination of reovirus and several chemotherapeutic agents synergistically enhanced cytotoxicity in human and murine
melanoma cell lines in vitro and murine tumors in vivo . The data support the current reovirus/chemotherapy combination phase I clinical studies currently ongoing in the clinic.
(Clin Cancer Res 2009;15(19):6158–66)</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>19773377</pmid><doi>10.1158/1078-0432.CCR-09-0796</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis - physiology Biological and medical sciences chemotherapy cisplatin Cisplatin - administration & dosage Combined Modality Therapy Dermatology Humans Medical sciences melanoma Melanoma, Experimental - pathology Melanoma, Experimental - therapy Mice Mice, Inbred C57BL NIH 3T3 Cells oncolytic Oncolytic Virotherapy Oncolytic Viruses - physiology Pharmacology. Drug treatments Reoviridae - physiology reovirus Treatment Outcome Tumor Cells, Cultured Tumors of the skin and soft tissue. Premalignant lesions Virus Replication - drug effects |
| title | Synergistic Effects of Oncolytic Reovirus and Cisplatin Chemotherapy in Murine Malignant Melanoma |
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