Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy
This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 w...
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| Veröffentlicht in: | Oncology reports 2009-07, Vol.22 (1), p.105-113 |
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| creator | CASNEUF, Veerle F DEMETTER, Pieter BOTERBERG, Tom DELRUE, Louke PEETERS, Marc VAN DAMME, Nancy |
| description | This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PlGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P |
| doi_str_mv | 10.3892/or_00000412 |
| format | Article |
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Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PlGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P<0.001, P<0.01 and P<0.05 compared to placebo). MVD was lowest in RT/SUN treated mice [compared to placebo (P<0.05), GEM (P<0.05) and GEM/SUN (P<0.01)]. Highest VEGF levels were seen after RT and RT/SUN treatment [vs. placebo (P<0.001) and vs. other treatments (P<0.01 for all comparisons)]. GEM and SUN in monotherapy lead to an up-regulation of PlGF and EGF, respectively. In conclusion, the combination treatments RT/SUN and GEM/SUN result in a more potent anti-angiogenic and antitumor effect when compared to either treatment alone. Multitargeted angiogenesis inhibitor therapy with sunitinib combined with either radiotherapy or gemcitabine may be a novel approach for human pancreatic cancer.]]></description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or_00000412</identifier><identifier>PMID: 19513511</identifier><language>eng</language><publisher>Athens: Spandidos</publisher><subject><![CDATA[Angiogenesis Inhibitors - administration & dosage ; Animals ; Antimetabolites, Antineoplastic - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Apoptosis - drug effects ; Biological and medical sciences ; Caspase 3 - metabolism ; Cell Line, Tumor ; Chemotherapy, Adjuvant ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Epidermal Growth Factor - metabolism ; fas Receptor - metabolism ; Gastroenterology. Liver. Pancreas. Abdomen ; Indoles - administration & dosage ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Mice ; Microvessels - drug effects ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - enzymology ; Neovascularization, Pathologic - pathology ; Pancreatic Neoplasms - blood supply ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - enzymology ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - radiotherapy ; Placenta Growth Factor ; Pregnancy Proteins - metabolism ; Protein Kinase Inhibitors - administration & dosage ; Pyrroles - administration & dosage ; Radiotherapy, Adjuvant ; Sunitinib ; Time Factors ; Tumors ; Vascular Endothelial Growth Factor A - metabolism]]></subject><ispartof>Oncology reports, 2009-07, Vol.22 (1), p.105-113</ispartof><rights>2009 INIST-CNRS</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-c577ea26f5516e1b7c6b655b636df98b8a61b850375f4403b1aeb308c9bde40f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21649462$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19513511$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CASNEUF, Veerle F</creatorcontrib><creatorcontrib>DEMETTER, Pieter</creatorcontrib><creatorcontrib>BOTERBERG, Tom</creatorcontrib><creatorcontrib>DELRUE, Louke</creatorcontrib><creatorcontrib>PEETERS, Marc</creatorcontrib><creatorcontrib>VAN DAMME, Nancy</creatorcontrib><title>Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description><![CDATA[This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PlGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P<0.001, P<0.01 and P<0.05 compared to placebo). MVD was lowest in RT/SUN treated mice [compared to placebo (P<0.05), GEM (P<0.05) and GEM/SUN (P<0.01)]. Highest VEGF levels were seen after RT and RT/SUN treatment [vs. placebo (P<0.001) and vs. other treatments (P<0.01 for all comparisons)]. GEM and SUN in monotherapy lead to an up-regulation of PlGF and EGF, respectively. In conclusion, the combination treatments RT/SUN and GEM/SUN result in a more potent anti-angiogenic and antitumor effect when compared to either treatment alone. Multitargeted angiogenesis inhibitor therapy with sunitinib combined with either radiotherapy or gemcitabine may be a novel approach for human pancreatic cancer.]]></description><subject>Angiogenesis Inhibitors - administration & dosage</subject><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy, Adjuvant</subject><subject>Deoxycytidine - administration & dosage</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>fas Receptor - metabolism</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Indoles - administration & dosage</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microvessels - drug effects</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - enzymology</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Pancreatic Neoplasms - blood supply</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - enzymology</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - radiotherapy</subject><subject>Placenta Growth Factor</subject><subject>Pregnancy Proteins - metabolism</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Pyrroles - administration & dosage</subject><subject>Radiotherapy, Adjuvant</subject><subject>Sunitinib</subject><subject>Time Factors</subject><subject>Tumors</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkUFv1DAQhS1ERUvLiTvyBYmKBuw4dpLeVhUUpEpcQOIWjZ3JriFrR7ZTmr_YX1VHuwJ8sJ-sb55m5hHymrMPomnLjz50bD0VL5-RM163vCgrwZ9nzUpeCCF_npKXMf5irKyZal-QU95KLiTnZ-Rx45IFt7V-i84aeo8hzpGaJfnkH_JH2mGACeeUNUxT8GB2GKl1FOjezxHz3eNI_UAncCYgrKTJEsM13TiKDxMGu0eXYKQxzf1C_9i0W8vnMdkEYYuJpiX4aB3S39ZBNrVuZ7VNPtB3cXY2WWf15RXd4t7kEr2S4HoaoLf-0OJyQU4GGCO-Or7n5MfnT99vvhR3326_3mzuCiNklQoj6xqhVIOUXCHXtVFaSamVUP3QNroBxXUjmajlUFVMaA6oBWtMq3us2CDOyfuDr8ktx4BDN-X5ICwdZ92aSPdfIpl-c6CnWe-x_8ceI8jA2yMA0cA4hLw6G_9yJVdVW6lSPAFPT5oe</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>CASNEUF, Veerle F</creator><creator>DEMETTER, Pieter</creator><creator>BOTERBERG, Tom</creator><creator>DELRUE, Louke</creator><creator>PEETERS, Marc</creator><creator>VAN DAMME, Nancy</creator><general>Spandidos</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></search><sort><creationdate>20090701</creationdate><title>Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy</title><author>CASNEUF, Veerle F ; DEMETTER, Pieter ; BOTERBERG, Tom ; DELRUE, Louke ; PEETERS, Marc ; VAN DAMME, Nancy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-c577ea26f5516e1b7c6b655b636df98b8a61b850375f4403b1aeb308c9bde40f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Angiogenesis Inhibitors - administration & dosage</topic><topic>Animals</topic><topic>Antimetabolites, Antineoplastic - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy, Adjuvant</topic><topic>Deoxycytidine - administration & dosage</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Epidermal Growth Factor - metabolism</topic><topic>fas Receptor - metabolism</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Indoles - administration & dosage</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microvessels - drug effects</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Neovascularization, Pathologic - enzymology</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Pancreatic Neoplasms - blood supply</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - enzymology</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pancreatic Neoplasms - radiotherapy</topic><topic>Placenta Growth Factor</topic><topic>Pregnancy Proteins - metabolism</topic><topic>Protein Kinase Inhibitors - administration & dosage</topic><topic>Pyrroles - administration & dosage</topic><topic>Radiotherapy, Adjuvant</topic><topic>Sunitinib</topic><topic>Time Factors</topic><topic>Tumors</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>CASNEUF, Veerle F</creatorcontrib><creatorcontrib>DEMETTER, Pieter</creatorcontrib><creatorcontrib>BOTERBERG, Tom</creatorcontrib><creatorcontrib>DELRUE, Louke</creatorcontrib><creatorcontrib>PEETERS, Marc</creatorcontrib><creatorcontrib>VAN DAMME, Nancy</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><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CASNEUF, Veerle F</au><au>DEMETTER, Pieter</au><au>BOTERBERG, Tom</au><au>DELRUE, Louke</au><au>PEETERS, Marc</au><au>VAN DAMME, Nancy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>22</volume><issue>1</issue><spage>105</spage><epage>113</epage><pages>105-113</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract><![CDATA[This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PlGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P<0.001, P<0.01 and P<0.05 compared to placebo). MVD was lowest in RT/SUN treated mice [compared to placebo (P<0.05), GEM (P<0.05) and GEM/SUN (P<0.01)]. Highest VEGF levels were seen after RT and RT/SUN treatment [vs. placebo (P<0.001) and vs. other treatments (P<0.01 for all comparisons)]. GEM and SUN in monotherapy lead to an up-regulation of PlGF and EGF, respectively. In conclusion, the combination treatments RT/SUN and GEM/SUN result in a more potent anti-angiogenic and antitumor effect when compared to either treatment alone. Multitargeted angiogenesis inhibitor therapy with sunitinib combined with either radiotherapy or gemcitabine may be a novel approach for human pancreatic cancer.]]></abstract><cop>Athens</cop><pub>Spandidos</pub><pmid>19513511</pmid><doi>10.3892/or_00000412</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncology reports, 2009-07, Vol.22 (1), p.105-113 |
| issn | 1021-335X 1791-2431 |
| language | eng |
| recordid | cdi_crossref_primary_10_3892_or_00000412 |
| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Angiogenesis Inhibitors - administration & dosage Animals Antimetabolites, Antineoplastic - administration & dosage Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis - drug effects Biological and medical sciences Caspase 3 - metabolism Cell Line, Tumor Chemotherapy, Adjuvant Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives Epidermal Growth Factor - metabolism fas Receptor - metabolism Gastroenterology. Liver. Pancreas. Abdomen Indoles - administration & dosage Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Mice Microvessels - drug effects Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - enzymology Neovascularization, Pathologic - pathology Pancreatic Neoplasms - blood supply Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - enzymology Pancreatic Neoplasms - pathology Pancreatic Neoplasms - radiotherapy Placenta Growth Factor Pregnancy Proteins - metabolism Protein Kinase Inhibitors - administration & dosage Pyrroles - administration & dosage Radiotherapy, Adjuvant Sunitinib Time Factors Tumors Vascular Endothelial Growth Factor A - metabolism |
| title | Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy |
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