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Anti-tumor therapy with macroencapsulated endostatin producer cells
Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a...
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Published in: | BMC biotechnology 2010-03, Vol.10 (1), p.19-19, Article 19 |
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description | Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors.
Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.
This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors. |
doi_str_mv | 10.1186/1472-6750-10-19 |
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Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.
This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.</description><identifier>ISSN: 1472-6750</identifier><identifier>EISSN: 1472-6750</identifier><identifier>DOI: 10.1186/1472-6750-10-19</identifier><identifier>PMID: 20196841</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Angiogenesis ; Angiogenesis Inhibitors - therapeutic use ; Animals ; Antineoplastic Agents - therapeutic use ; Carcinoma, Ehrlich Tumor - therapy ; Care and treatment ; Cell Transplantation ; Design ; Diagnosis ; Dosage and administration ; Endostatin ; Endostatins - secretion ; Endostatins - therapeutic use ; Fibroblasts ; Fibroblasts - metabolism ; Genetic aspects ; Immune system ; Immunotherapy ; Implants, Experimental ; Male ; Melanoma ; Melanoma, Experimental - therapy ; Methods ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Neovascularization, Pathologic - prevention & control ; Proteins ; Research article ; Rodents ; Tumors ; Wound healing</subject><ispartof>BMC biotechnology, 2010-03, Vol.10 (1), p.19-19, Article 19</ispartof><rights>COPYRIGHT 2010 BioMed Central Ltd.</rights><rights>2010 Rodrigues et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright ©2010 Rodrigues et al; licensee BioMed Central Ltd. 2010 Rodrigues et al; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b747t-ca47e5ee42fc8350153e2ceca8972532e6a068e78d79a008292121338090bf223</citedby><cites>FETCH-LOGICAL-b747t-ca47e5ee42fc8350153e2ceca8972532e6a068e78d79a008292121338090bf223</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/PMC2845092/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1037676706?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20196841$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodrigues, Danielle B</creatorcontrib><creatorcontrib>Chammas, Roger</creatorcontrib><creatorcontrib>Malavasi, Natália V</creatorcontrib><creatorcontrib>da Costa, Patrícia L N</creatorcontrib><creatorcontrib>Chura-Chambi, Rosa M</creatorcontrib><creatorcontrib>Balduino, Keli N</creatorcontrib><creatorcontrib>Morganti, Ligia</creatorcontrib><title>Anti-tumor therapy with macroencapsulated endostatin producer cells</title><title>BMC biotechnology</title><addtitle>BMC Biotechnol</addtitle><description>Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors.
Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.
This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.</description><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - therapeutic use</subject><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Carcinoma, Ehrlich Tumor - therapy</subject><subject>Care and treatment</subject><subject>Cell Transplantation</subject><subject>Design</subject><subject>Diagnosis</subject><subject>Dosage and administration</subject><subject>Endostatin</subject><subject>Endostatins - secretion</subject><subject>Endostatins - therapeutic use</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Genetic aspects</subject><subject>Immune system</subject><subject>Immunotherapy</subject><subject>Implants, Experimental</subject><subject>Male</subject><subject>Melanoma</subject><subject>Melanoma, Experimental - therapy</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Neovascularization, Pathologic - prevention & control</subject><subject>Proteins</subject><subject>Research article</subject><subject>Rodents</subject><subject>Tumors</subject><subject>Wound healing</subject><issn>1472-6750</issn><issn>1472-6750</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk8tv1DAQxiMEoqVw5oYicQAOaf1I_LggLSseKyoV8bpajjPZdZXEi-0A_e9xumVpUEGVLdka__xpPN84yx5jdIyxYCe45KRgvEIFTlPeyQ73kbvX9gfZgxDOEcJcIHY_OyAISyZKfJgtF0O0RRx75_O4Aa-3F_kPGzd5r413MBi9DWOnIzQ5DI0LUUc75FvvmtGAzw10XXiY3Wt1F-DR1XqUfXnz-vPyXXF69na1XJwWNS95LIwuOVQAJWmNoBXCFQViwGghOakoAaYRE8BFw6VGSBBJMMGUCiRR3RJCj7LVTrdx-lxtve21v1BOW3UZcH6ttI_WdKAkayhmQgpW1qVsaM2xAVlJKjBrCRdJ6-VOazvWPTQGhuh1NxOdnwx2o9buuyKirJCcknm1E6it-4fA_MS4Xk2GqMkQhdOUSeTZVRbefRshRNXbMNVUD-DGoPjl6ytEE_n8vyRGkpZVKilK6NO_0HM3-iE5kyjKWRqI_aHWOtXLDq1LWZpJVC0ISQ1CsKwSdXwDlUYDvTVugNam-OzCi9mFxET4Gdd6DEG9_7C6Nbv69PH27NnXOXuyY1MHh-Ch3bsyVT19mxt8eHK9G_b8739CfwF_2Qxb</recordid><startdate>20100302</startdate><enddate>20100302</enddate><creator>Rodrigues, Danielle B</creator><creator>Chammas, Roger</creator><creator>Malavasi, Natália V</creator><creator>da Costa, Patrícia L N</creator><creator>Chura-Chambi, Rosa M</creator><creator>Balduino, Keli N</creator><creator>Morganti, Ligia</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>IOV</scope><scope>ISR</scope><scope>KPI</scope><scope>3V.</scope><scope>7QO</scope><scope>7TB</scope><scope>7U5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L7M</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</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>20100302</creationdate><title>Anti-tumor therapy with macroencapsulated endostatin producer cells</title><author>Rodrigues, Danielle B ; Chammas, Roger ; Malavasi, Natália V ; da Costa, Patrícia L N ; Chura-Chambi, Rosa M ; Balduino, Keli N ; Morganti, Ligia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b747t-ca47e5ee42fc8350153e2ceca8972532e6a068e78d79a008292121338090bf223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Angiogenesis</topic><topic>Angiogenesis Inhibitors - therapeutic use</topic><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Carcinoma, Ehrlich Tumor - therapy</topic><topic>Care and treatment</topic><topic>Cell Transplantation</topic><topic>Design</topic><topic>Diagnosis</topic><topic>Dosage and administration</topic><topic>Endostatin</topic><topic>Endostatins - secretion</topic><topic>Endostatins - therapeutic use</topic><topic>Fibroblasts</topic><topic>Fibroblasts - metabolism</topic><topic>Genetic aspects</topic><topic>Immune system</topic><topic>Immunotherapy</topic><topic>Implants, Experimental</topic><topic>Male</topic><topic>Melanoma</topic><topic>Melanoma, Experimental - therapy</topic><topic>Methods</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Neovascularization, Pathologic - prevention & control</topic><topic>Proteins</topic><topic>Research article</topic><topic>Rodents</topic><topic>Tumors</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodrigues, Danielle B</creatorcontrib><creatorcontrib>Chammas, Roger</creatorcontrib><creatorcontrib>Malavasi, Natália V</creatorcontrib><creatorcontrib>da Costa, Patrícia L N</creatorcontrib><creatorcontrib>Chura-Chambi, Rosa M</creatorcontrib><creatorcontrib>Balduino, Keli N</creatorcontrib><creatorcontrib>Morganti, Ligia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>Gale In Context: Global Issues</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</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>BMC biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodrigues, Danielle B</au><au>Chammas, Roger</au><au>Malavasi, Natália V</au><au>da Costa, Patrícia L N</au><au>Chura-Chambi, Rosa M</au><au>Balduino, Keli N</au><au>Morganti, Ligia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-tumor therapy with macroencapsulated endostatin producer cells</atitle><jtitle>BMC biotechnology</jtitle><addtitle>BMC Biotechnol</addtitle><date>2010-03-02</date><risdate>2010</risdate><volume>10</volume><issue>1</issue><spage>19</spage><epage>19</epage><pages>19-19</pages><artnum>19</artnum><issn>1472-6750</issn><eissn>1472-6750</eissn><abstract>Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors.
Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.
This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>20196841</pmid><doi>10.1186/1472-6750-10-19</doi><oa>free_for_read</oa></addata></record> |
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subjects | Angiogenesis Angiogenesis Inhibitors - therapeutic use Animals Antineoplastic Agents - therapeutic use Carcinoma, Ehrlich Tumor - therapy Care and treatment Cell Transplantation Design Diagnosis Dosage and administration Endostatin Endostatins - secretion Endostatins - therapeutic use Fibroblasts Fibroblasts - metabolism Genetic aspects Immune system Immunotherapy Implants, Experimental Male Melanoma Melanoma, Experimental - therapy Methods Mice Mice, Inbred C3H Mice, Inbred C57BL Neovascularization, Pathologic - prevention & control Proteins Research article Rodents Tumors Wound healing |
title | Anti-tumor therapy with macroencapsulated endostatin producer cells |
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