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Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma
To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma. Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperito...
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| Published in: | Journal of experimental & clinical cancer research 2016-11, Vol.35 (1), p.171-171, Article 171 |
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| creator | Kim, Dong Yoon Choi, Jeong A Koh, Jae-Young Yoon, Young Hee |
| description | To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma.
Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperitoneally injected with aflibercept (25 mg/kg body weight) or saline twice a week for 3 weeks. Tumor size was measured weekly and compared between the two groups. At 4 weeks, animals were sacrificed and an immunohistochemical examination was conducted to compare the microvascular density and degree of apoptosis between groups. In addition, the degree of choroidal invasion was also analyzed in the orthotopic xenotransplantation model. A co-culture system of Y-79 or WERI-Rb-1 cells and human umbilical vein endothelial cells (HUVECs) was used for in vitro experiments, and the anti-angiogenic effect of aflibercept was evaluated by analyzing cell numbers.
In the Y-79 xenotransplantation model, aflibercept treatment significantly inhibited tumor growth at 4 weeks versus baseline compared with saline-injected mice (188.53 ± 118.53 mm
vs. 747.87 ± 118.83 mm
, respectively, P |
| doi_str_mv | 10.1186/s13046-016-0451-7 |
| format | article |
| fullrecord | <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_adb5e1528b3943c7b93ec52ae911e60a</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A470585700</galeid><doaj_id>oai_doaj_org_article_adb5e1528b3943c7b93ec52ae911e60a</doaj_id><sourcerecordid>A470585700</sourcerecordid><originalsourceid>FETCH-LOGICAL-c661t-8e5efcfcb17bf58c2fdae022ca6589f049b867a7f606372a3f60a01065ca4b483</originalsourceid><addsrcrecordid>eNptkl2L1DAUhoso7of-AG-kIIg3XZOmSdobYVnWdWHBC_U6nKYnMxnaZEwyA_PvTWfWYUYkCTlJnvOGc3iL4h0lN5S24nOkjDSiIjSvhtNKviguqeSi6johXp7EF8VVjCtCBO1o97q4qGVLGynpZfHj3hirQe9KcEMZwWDald6UYEbbY9C4TqV189zaFPye2h-2vpz8gGOc6YDJOt-PEJOf4E3xysAY8e3zfl38-nr_8-5b9fT94fHu9qnSQtBUtcjRaKN7KnvDW12bAZDUtQbB286QputbIUEaQQSTNbAcAKFEcA1N37Tsung86A4eVmod7ARhpzxYtb_wYaEgJKtHVDD0HCmv2551DdOy7xhqXgN2lGKWzVpfDlrrTT_hoNGlAOOZ6PmLs0u18FvFSScbJrPAp2eB4H9vMCY12ahxHMGh30RFWyYkq4VgGf3wD7rym-Byq_ZUzdhc8ZFaQC7AOuPzv3oWVbeNJLzlkpBM3fyHymPAyWrv0Nh8f5bw8SRhiTCmZfTjJlnv4jlID6AOPsaA5tgMStRsP3Wwn8r2U7P91NyE96ddPGb89Rv7A45e03c</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1836233606</pqid></control><display><type>article</type><title>Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma</title><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>Kim, Dong Yoon ; Choi, Jeong A ; Koh, Jae-Young ; Yoon, Young Hee</creator><creatorcontrib>Kim, Dong Yoon ; Choi, Jeong A ; Koh, Jae-Young ; Yoon, Young Hee</creatorcontrib><description>To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma.
Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperitoneally injected with aflibercept (25 mg/kg body weight) or saline twice a week for 3 weeks. Tumor size was measured weekly and compared between the two groups. At 4 weeks, animals were sacrificed and an immunohistochemical examination was conducted to compare the microvascular density and degree of apoptosis between groups. In addition, the degree of choroidal invasion was also analyzed in the orthotopic xenotransplantation model. A co-culture system of Y-79 or WERI-Rb-1 cells and human umbilical vein endothelial cells (HUVECs) was used for in vitro experiments, and the anti-angiogenic effect of aflibercept was evaluated by analyzing cell numbers.
In the Y-79 xenotransplantation model, aflibercept treatment significantly inhibited tumor growth at 4 weeks versus baseline compared with saline-injected mice (188.53 ± 118.53 mm
vs. 747.87 ± 118.83 mm
, respectively, P < 0.001). Tumors isolated from aflibercept-treated mice contained fewer blood vessels (8.59 % ± 7.60 % vs. 14.91 % ± 4.53 %, respectively, P < 0.05) and an increased number of apoptotic cells (15.10 ± 9.13 vs. 4.44 ± 2.24, respectively, P < 0.05). In the orthotopic model, the degree of subretinal invasion of tumor cells was significantly reduced after aflibercept treatment (0.07 ± 0.06 vs. 0.15 ± 0.10, P < 0.05). And addition of aflibercept to co-cultures of HUVECs and Y-79, WERI-Rb-1 cells significantly reduced HUVEC proliferation.
Aflibercept reduced retinoblastoma angiogenesis in association with a significant reduction in tumor growth and invasion. These findings suggest that aflibercept could be used in an adjuvant role together with systemic chemotherapy to reduce tumor size and angiogenesis in retinoblastoma.</description><identifier>ISSN: 1756-9966</identifier><identifier>ISSN: 0392-9078</identifier><identifier>EISSN: 1756-9966</identifier><identifier>DOI: 10.1186/s13046-016-0451-7</identifier><identifier>PMID: 27814771</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Aflibercept ; Analysis ; Angiogenesis Inhibitors - administration & dosage ; Angiogenesis Inhibitors - pharmacology ; Animals ; Apoptosis ; Cancer ; Care and treatment ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Chemotherapy ; Choroidal invasion ; Coculture Techniques ; Health aspects ; Human Umbilical Vein Endothelial Cells ; Humans ; Injections, Intraperitoneal ; Mice ; Neoplasm Invasiveness ; Receptors, Vascular Endothelial Growth Factor - administration & dosage ; Recombinant Fusion Proteins - administration & dosage ; Recombinant Fusion Proteins - pharmacology ; Retinal Neoplasms - blood supply ; Retinal Neoplasms - drug therapy ; Retinoblastoma ; Retinoblastoma - blood supply ; Retinoblastoma - drug therapy ; Treatment ; Xenograft Model Antitumor Assays</subject><ispartof>Journal of experimental & clinical cancer research, 2016-11, Vol.35 (1), p.171-171, Article 171</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c661t-8e5efcfcb17bf58c2fdae022ca6589f049b867a7f606372a3f60a01065ca4b483</citedby><cites>FETCH-LOGICAL-c661t-8e5efcfcb17bf58c2fdae022ca6589f049b867a7f606372a3f60a01065ca4b483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097437/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1836233606?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27814771$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Dong Yoon</creatorcontrib><creatorcontrib>Choi, Jeong A</creatorcontrib><creatorcontrib>Koh, Jae-Young</creatorcontrib><creatorcontrib>Yoon, Young Hee</creatorcontrib><title>Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma</title><title>Journal of experimental & clinical cancer research</title><addtitle>J Exp Clin Cancer Res</addtitle><description>To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma.
Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperitoneally injected with aflibercept (25 mg/kg body weight) or saline twice a week for 3 weeks. Tumor size was measured weekly and compared between the two groups. At 4 weeks, animals were sacrificed and an immunohistochemical examination was conducted to compare the microvascular density and degree of apoptosis between groups. In addition, the degree of choroidal invasion was also analyzed in the orthotopic xenotransplantation model. A co-culture system of Y-79 or WERI-Rb-1 cells and human umbilical vein endothelial cells (HUVECs) was used for in vitro experiments, and the anti-angiogenic effect of aflibercept was evaluated by analyzing cell numbers.
In the Y-79 xenotransplantation model, aflibercept treatment significantly inhibited tumor growth at 4 weeks versus baseline compared with saline-injected mice (188.53 ± 118.53 mm
vs. 747.87 ± 118.83 mm
, respectively, P < 0.001). Tumors isolated from aflibercept-treated mice contained fewer blood vessels (8.59 % ± 7.60 % vs. 14.91 % ± 4.53 %, respectively, P < 0.05) and an increased number of apoptotic cells (15.10 ± 9.13 vs. 4.44 ± 2.24, respectively, P < 0.05). In the orthotopic model, the degree of subretinal invasion of tumor cells was significantly reduced after aflibercept treatment (0.07 ± 0.06 vs. 0.15 ± 0.10, P < 0.05). And addition of aflibercept to co-cultures of HUVECs and Y-79, WERI-Rb-1 cells significantly reduced HUVEC proliferation.
Aflibercept reduced retinoblastoma angiogenesis in association with a significant reduction in tumor growth and invasion. These findings suggest that aflibercept could be used in an adjuvant role together with systemic chemotherapy to reduce tumor size and angiogenesis in retinoblastoma.</description><subject>Aflibercept</subject><subject>Analysis</subject><subject>Angiogenesis Inhibitors - administration & dosage</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Chemotherapy</subject><subject>Choroidal invasion</subject><subject>Coculture Techniques</subject><subject>Health aspects</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Injections, Intraperitoneal</subject><subject>Mice</subject><subject>Neoplasm Invasiveness</subject><subject>Receptors, Vascular Endothelial Growth Factor - administration & dosage</subject><subject>Recombinant Fusion Proteins - administration & dosage</subject><subject>Recombinant Fusion Proteins - pharmacology</subject><subject>Retinal Neoplasms - blood supply</subject><subject>Retinal Neoplasms - drug therapy</subject><subject>Retinoblastoma</subject><subject>Retinoblastoma - blood supply</subject><subject>Retinoblastoma - drug therapy</subject><subject>Treatment</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1756-9966</issn><issn>0392-9078</issn><issn>1756-9966</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkl2L1DAUhoso7of-AG-kIIg3XZOmSdobYVnWdWHBC_U6nKYnMxnaZEwyA_PvTWfWYUYkCTlJnvOGc3iL4h0lN5S24nOkjDSiIjSvhtNKviguqeSi6johXp7EF8VVjCtCBO1o97q4qGVLGynpZfHj3hirQe9KcEMZwWDald6UYEbbY9C4TqV189zaFPye2h-2vpz8gGOc6YDJOt-PEJOf4E3xysAY8e3zfl38-nr_8-5b9fT94fHu9qnSQtBUtcjRaKN7KnvDW12bAZDUtQbB286QputbIUEaQQSTNbAcAKFEcA1N37Tsung86A4eVmod7ARhpzxYtb_wYaEgJKtHVDD0HCmv2551DdOy7xhqXgN2lGKWzVpfDlrrTT_hoNGlAOOZ6PmLs0u18FvFSScbJrPAp2eB4H9vMCY12ahxHMGh30RFWyYkq4VgGf3wD7rym-Byq_ZUzdhc8ZFaQC7AOuPzv3oWVbeNJLzlkpBM3fyHymPAyWrv0Nh8f5bw8SRhiTCmZfTjJlnv4jlID6AOPsaA5tgMStRsP3Wwn8r2U7P91NyE96ddPGb89Rv7A45e03c</recordid><startdate>20161104</startdate><enddate>20161104</enddate><creator>Kim, Dong Yoon</creator><creator>Choi, Jeong A</creator><creator>Koh, Jae-Young</creator><creator>Yoon, Young Hee</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20161104</creationdate><title>Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma</title><author>Kim, Dong Yoon ; Choi, Jeong A ; Koh, Jae-Young ; Yoon, Young Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c661t-8e5efcfcb17bf58c2fdae022ca6589f049b867a7f606372a3f60a01065ca4b483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aflibercept</topic><topic>Analysis</topic><topic>Angiogenesis Inhibitors - administration & dosage</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Chemotherapy</topic><topic>Choroidal invasion</topic><topic>Coculture Techniques</topic><topic>Health aspects</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Injections, Intraperitoneal</topic><topic>Mice</topic><topic>Neoplasm Invasiveness</topic><topic>Receptors, Vascular Endothelial Growth Factor - administration & dosage</topic><topic>Recombinant Fusion Proteins - administration & dosage</topic><topic>Recombinant Fusion Proteins - pharmacology</topic><topic>Retinal Neoplasms - blood supply</topic><topic>Retinal Neoplasms - drug therapy</topic><topic>Retinoblastoma</topic><topic>Retinoblastoma - blood supply</topic><topic>Retinoblastoma - drug therapy</topic><topic>Treatment</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Dong Yoon</creatorcontrib><creatorcontrib>Choi, Jeong A</creatorcontrib><creatorcontrib>Koh, Jae-Young</creatorcontrib><creatorcontrib>Yoon, Young Hee</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Journal of experimental & clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Dong Yoon</au><au>Choi, Jeong A</au><au>Koh, Jae-Young</au><au>Yoon, Young Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma</atitle><jtitle>Journal of experimental & clinical cancer research</jtitle><addtitle>J Exp Clin Cancer Res</addtitle><date>2016-11-04</date><risdate>2016</risdate><volume>35</volume><issue>1</issue><spage>171</spage><epage>171</epage><pages>171-171</pages><artnum>171</artnum><issn>1756-9966</issn><issn>0392-9078</issn><eissn>1756-9966</eissn><abstract>To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma.
Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperitoneally injected with aflibercept (25 mg/kg body weight) or saline twice a week for 3 weeks. Tumor size was measured weekly and compared between the two groups. At 4 weeks, animals were sacrificed and an immunohistochemical examination was conducted to compare the microvascular density and degree of apoptosis between groups. In addition, the degree of choroidal invasion was also analyzed in the orthotopic xenotransplantation model. A co-culture system of Y-79 or WERI-Rb-1 cells and human umbilical vein endothelial cells (HUVECs) was used for in vitro experiments, and the anti-angiogenic effect of aflibercept was evaluated by analyzing cell numbers.
In the Y-79 xenotransplantation model, aflibercept treatment significantly inhibited tumor growth at 4 weeks versus baseline compared with saline-injected mice (188.53 ± 118.53 mm
vs. 747.87 ± 118.83 mm
, respectively, P < 0.001). Tumors isolated from aflibercept-treated mice contained fewer blood vessels (8.59 % ± 7.60 % vs. 14.91 % ± 4.53 %, respectively, P < 0.05) and an increased number of apoptotic cells (15.10 ± 9.13 vs. 4.44 ± 2.24, respectively, P < 0.05). In the orthotopic model, the degree of subretinal invasion of tumor cells was significantly reduced after aflibercept treatment (0.07 ± 0.06 vs. 0.15 ± 0.10, P < 0.05). And addition of aflibercept to co-cultures of HUVECs and Y-79, WERI-Rb-1 cells significantly reduced HUVEC proliferation.
Aflibercept reduced retinoblastoma angiogenesis in association with a significant reduction in tumor growth and invasion. These findings suggest that aflibercept could be used in an adjuvant role together with systemic chemotherapy to reduce tumor size and angiogenesis in retinoblastoma.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27814771</pmid><doi>10.1186/s13046-016-0451-7</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aflibercept Analysis Angiogenesis Inhibitors - administration & dosage Angiogenesis Inhibitors - pharmacology Animals Apoptosis Cancer Care and treatment Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Chemotherapy Choroidal invasion Coculture Techniques Health aspects Human Umbilical Vein Endothelial Cells Humans Injections, Intraperitoneal Mice Neoplasm Invasiveness Receptors, Vascular Endothelial Growth Factor - administration & dosage Recombinant Fusion Proteins - administration & dosage Recombinant Fusion Proteins - pharmacology Retinal Neoplasms - blood supply Retinal Neoplasms - drug therapy Retinoblastoma Retinoblastoma - blood supply Retinoblastoma - drug therapy Treatment Xenograft Model Antitumor Assays |
| title | Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma |
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