High Antimetastatic Efficacy of MEN4901/T-0128, a Novel Camptothecin Carboxymethyldextran Conjugate
The antimetastatic activity of a novel camptothecan conjugate, MEN4901/T-0128, in which 7-ethyl-10-aminopropyloxy-camptothecin (T-2513) is bound to a biodegradable carboxymethyldextran via a Gly-Gly-Gly linker, was observed in this study. High antimetastatic activity of MEN4901/T-0128 was demonstrat...
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| Veröffentlicht in: | The Journal of surgical research 2011-12, Vol.171 (2), p.684-690 |
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| creator | Ma, Huaiyu, M.D Li, Xiaoming, M.D., Ph.D Yang, Zhijian, M.D Okuno, Satoshi, Ph.D Kawaguchi, Takayuki, Ph.D Yagi, Shigeo, Ph.D Bouvet, Michael, M.D Hoffman, Robert M., Ph.D |
| description | The antimetastatic activity of a novel camptothecan conjugate, MEN4901/T-0128, in which 7-ethyl-10-aminopropyloxy-camptothecin (T-2513) is bound to a biodegradable carboxymethyldextran via a Gly-Gly-Gly linker, was observed in this study. High antimetastatic activity of MEN4901/T-0128 was demonstrated in a clinically-relevant orthotopic mouse model of human colon cancer. MEN4901/T-0128 and irinotecan were compared for anti-metastatic activity as well as efficacy against the primary tumor. An imageable, metastatic model was made by surgical orthotopic implantation (SOI) of the green fluorescent protein (GFP)-expressing HT-29 tumor in nude mice. MEN4901/T-0128 and irinotecan were administered intravenously at various doses and schedules. MEN4901/T-0128, with treatment beginning on d 49 after SOI, was highly effective on lymph node metastasis as well as against the primary tumor. Both GFP imaging and histology demonstrated a markedly lower metastatic incidence of lymph nodes in all MEN4901/T-0128 treated mice compared with irinotecan-treated and untreated mice. At the most efficacious dose of MEN4901/T-0128, only 1 of 12 animals had lymph node metastasis compared with 19 of 20 in the control group. The present study demonstrates the principle that when a camptothecan is conjugated to an appropriate polymer, the drug can become extremely effective with important clinical potential for antimetastatic therapy, a most urgent need. |
| doi_str_mv | 10.1016/j.jss.2010.05.066 |
| format | Article |
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High antimetastatic activity of MEN4901/T-0128 was demonstrated in a clinically-relevant orthotopic mouse model of human colon cancer. MEN4901/T-0128 and irinotecan were compared for anti-metastatic activity as well as efficacy against the primary tumor. An imageable, metastatic model was made by surgical orthotopic implantation (SOI) of the green fluorescent protein (GFP)-expressing HT-29 tumor in nude mice. MEN4901/T-0128 and irinotecan were administered intravenously at various doses and schedules. MEN4901/T-0128, with treatment beginning on d 49 after SOI, was highly effective on lymph node metastasis as well as against the primary tumor. Both GFP imaging and histology demonstrated a markedly lower metastatic incidence of lymph nodes in all MEN4901/T-0128 treated mice compared with irinotecan-treated and untreated mice. At the most efficacious dose of MEN4901/T-0128, only 1 of 12 animals had lymph node metastasis compared with 19 of 20 in the control group. The present study demonstrates the principle that when a camptothecan is conjugated to an appropriate polymer, the drug can become extremely effective with important clinical potential for antimetastatic therapy, a most urgent need.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2010.05.066</identifier><identifier>PMID: 20851421</identifier><identifier>CODEN: JSGRA2</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - secondary ; Animals ; Antineoplastic Agents, Phytogenic - pharmacology ; Biological and medical sciences ; Body Weight - drug effects ; camptothecin ; Camptothecin - analogs & derivatives ; Camptothecin - pharmacology ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - pathology ; Dextrans - pharmacokinetics ; Dextrans - pharmacology ; Dose-Response Relationship, Drug ; efficacy ; General aspects ; Green Fluorescent Proteins - genetics ; HT29 Cells ; Humans ; Irinotecan ; Medical sciences ; metastasis ; Mice ; Mice, Nude ; nude mice ; orthotopic model ; polymer conjugate ; Prodrugs - pharmacology ; Surgery ; Topotecan - analogs & derivatives ; Topotecan - pharmacology ; Xenograft Model Antitumor Assays</subject><ispartof>The Journal of surgical research, 2011-12, Vol.171 (2), p.684-690</ispartof><rights>Elsevier Inc.</rights><rights>2011 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><rights>2010 Elsevier Inc. All rights reserved. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-ac76847a07c0d66920d754a0b8ad8a0e0057b520a8b2fa22af7b5cca449a22a13</citedby><cites>FETCH-LOGICAL-c535t-ac76847a07c0d66920d754a0b8ad8a0e0057b520a8b2fa22af7b5cca449a22a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jss.2010.05.066$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25229855$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20851421$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Huaiyu, M.D</creatorcontrib><creatorcontrib>Li, Xiaoming, M.D., Ph.D</creatorcontrib><creatorcontrib>Yang, Zhijian, M.D</creatorcontrib><creatorcontrib>Okuno, Satoshi, Ph.D</creatorcontrib><creatorcontrib>Kawaguchi, Takayuki, Ph.D</creatorcontrib><creatorcontrib>Yagi, Shigeo, Ph.D</creatorcontrib><creatorcontrib>Bouvet, Michael, M.D</creatorcontrib><creatorcontrib>Hoffman, Robert M., Ph.D</creatorcontrib><title>High Antimetastatic Efficacy of MEN4901/T-0128, a Novel Camptothecin Carboxymethyldextran Conjugate</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>The antimetastatic activity of a novel camptothecan conjugate, MEN4901/T-0128, in which 7-ethyl-10-aminopropyloxy-camptothecin (T-2513) is bound to a biodegradable carboxymethyldextran via a Gly-Gly-Gly linker, was observed in this study. High antimetastatic activity of MEN4901/T-0128 was demonstrated in a clinically-relevant orthotopic mouse model of human colon cancer. MEN4901/T-0128 and irinotecan were compared for anti-metastatic activity as well as efficacy against the primary tumor. An imageable, metastatic model was made by surgical orthotopic implantation (SOI) of the green fluorescent protein (GFP)-expressing HT-29 tumor in nude mice. MEN4901/T-0128 and irinotecan were administered intravenously at various doses and schedules. MEN4901/T-0128, with treatment beginning on d 49 after SOI, was highly effective on lymph node metastasis as well as against the primary tumor. Both GFP imaging and histology demonstrated a markedly lower metastatic incidence of lymph nodes in all MEN4901/T-0128 treated mice compared with irinotecan-treated and untreated mice. At the most efficacious dose of MEN4901/T-0128, only 1 of 12 animals had lymph node metastasis compared with 19 of 20 in the control group. The present study demonstrates the principle that when a camptothecan is conjugated to an appropriate polymer, the drug can become extremely effective with important clinical potential for antimetastatic therapy, a most urgent need.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - secondary</subject><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Body Weight - drug effects</subject><subject>camptothecin</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - pharmacology</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - pathology</subject><subject>Dextrans - pharmacokinetics</subject><subject>Dextrans - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>efficacy</subject><subject>General aspects</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Irinotecan</subject><subject>Medical sciences</subject><subject>metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>nude mice</subject><subject>orthotopic model</subject><subject>polymer conjugate</subject><subject>Prodrugs - pharmacology</subject><subject>Surgery</subject><subject>Topotecan - analogs & derivatives</subject><subject>Topotecan - pharmacology</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kk9v1DAQxS0EokvhA3BBuXBrtmMnThwhVapWC0Uq5UA5WxPH2XXIxqvYu2q-PRNtKX8OnKznvPc8-mUYe8thyYEXl92yC2EpgDTIJRTFM7bgUMlUFWX2nC0AhEhzBfkZexVCB6SrMnvJzgQoyXPBF8zcuM02uR6i29mIIWJ0Jlm3rTNopsS3yZf1XV4Bv7xPgQt1kWBy54-2T1a420cft9a4gcRY-4eJKrZT39iHOCJd-qE7bDDa1-xFi32wbx7Pc_b94_p-dZPefv30eXV9mxqZyZiiKQuVlwilgaYoKgFNKXOEWmGjECyALGspAFUtWhQCW5LGYJ5Xs-LZObs69e4P9c42xg40R6_3o9vhOGmPTv_9ZXBbvfFHnQGoLCupgJ8KzOhDGG37lOWgZ-K600Rcz8Q1SE3EKfPuz0efEr8Qk-H9owGDwb4lNMaF3z4pRKWkJN-Hk88SoqOzow7G2cHYxo3WRN14998xrv5Jm94N9Bf7H3ayofOHcSD2musgNOhv82rMm8FpKeQ85k9J5LNq</recordid><startdate>20111201</startdate><enddate>20111201</enddate><creator>Ma, Huaiyu, M.D</creator><creator>Li, Xiaoming, M.D., Ph.D</creator><creator>Yang, Zhijian, M.D</creator><creator>Okuno, Satoshi, Ph.D</creator><creator>Kawaguchi, Takayuki, Ph.D</creator><creator>Yagi, Shigeo, Ph.D</creator><creator>Bouvet, Michael, M.D</creator><creator>Hoffman, Robert M., Ph.D</creator><general>Elsevier Inc</general><general>Elsevier</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>5PM</scope></search><sort><creationdate>20111201</creationdate><title>High Antimetastatic Efficacy of MEN4901/T-0128, a Novel Camptothecin Carboxymethyldextran Conjugate</title><author>Ma, Huaiyu, M.D ; Li, Xiaoming, M.D., Ph.D ; Yang, Zhijian, M.D ; Okuno, Satoshi, Ph.D ; Kawaguchi, Takayuki, Ph.D ; Yagi, Shigeo, Ph.D ; Bouvet, Michael, M.D ; Hoffman, Robert M., Ph.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-ac76847a07c0d66920d754a0b8ad8a0e0057b520a8b2fa22af7b5cca449a22a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - secondary</topic><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Body Weight - drug effects</topic><topic>camptothecin</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - pharmacology</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - pathology</topic><topic>Dextrans - pharmacokinetics</topic><topic>Dextrans - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>efficacy</topic><topic>General aspects</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Irinotecan</topic><topic>Medical sciences</topic><topic>metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>nude mice</topic><topic>orthotopic model</topic><topic>polymer conjugate</topic><topic>Prodrugs - pharmacology</topic><topic>Surgery</topic><topic>Topotecan - analogs & derivatives</topic><topic>Topotecan - pharmacology</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Huaiyu, M.D</creatorcontrib><creatorcontrib>Li, Xiaoming, M.D., Ph.D</creatorcontrib><creatorcontrib>Yang, Zhijian, M.D</creatorcontrib><creatorcontrib>Okuno, Satoshi, Ph.D</creatorcontrib><creatorcontrib>Kawaguchi, Takayuki, Ph.D</creatorcontrib><creatorcontrib>Yagi, Shigeo, Ph.D</creatorcontrib><creatorcontrib>Bouvet, Michael, M.D</creatorcontrib><creatorcontrib>Hoffman, Robert M., Ph.D</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>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Huaiyu, M.D</au><au>Li, Xiaoming, M.D., Ph.D</au><au>Yang, Zhijian, M.D</au><au>Okuno, Satoshi, Ph.D</au><au>Kawaguchi, Takayuki, Ph.D</au><au>Yagi, Shigeo, Ph.D</au><au>Bouvet, Michael, M.D</au><au>Hoffman, Robert M., Ph.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High Antimetastatic Efficacy of MEN4901/T-0128, a Novel Camptothecin Carboxymethyldextran Conjugate</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>171</volume><issue>2</issue><spage>684</spage><epage>690</epage><pages>684-690</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><coden>JSGRA2</coden><abstract>The antimetastatic activity of a novel camptothecan conjugate, MEN4901/T-0128, in which 7-ethyl-10-aminopropyloxy-camptothecin (T-2513) is bound to a biodegradable carboxymethyldextran via a Gly-Gly-Gly linker, was observed in this study. High antimetastatic activity of MEN4901/T-0128 was demonstrated in a clinically-relevant orthotopic mouse model of human colon cancer. MEN4901/T-0128 and irinotecan were compared for anti-metastatic activity as well as efficacy against the primary tumor. An imageable, metastatic model was made by surgical orthotopic implantation (SOI) of the green fluorescent protein (GFP)-expressing HT-29 tumor in nude mice. MEN4901/T-0128 and irinotecan were administered intravenously at various doses and schedules. MEN4901/T-0128, with treatment beginning on d 49 after SOI, was highly effective on lymph node metastasis as well as against the primary tumor. Both GFP imaging and histology demonstrated a markedly lower metastatic incidence of lymph nodes in all MEN4901/T-0128 treated mice compared with irinotecan-treated and untreated mice. At the most efficacious dose of MEN4901/T-0128, only 1 of 12 animals had lymph node metastasis compared with 19 of 20 in the control group. The present study demonstrates the principle that when a camptothecan is conjugated to an appropriate polymer, the drug can become extremely effective with important clinical potential for antimetastatic therapy, a most urgent need.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20851421</pmid><doi>10.1016/j.jss.2010.05.066</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of surgical research, 2011-12, Vol.171 (2), p.684-690 |
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| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - secondary Animals Antineoplastic Agents, Phytogenic - pharmacology Biological and medical sciences Body Weight - drug effects camptothecin Camptothecin - analogs & derivatives Camptothecin - pharmacology Colonic Neoplasms - drug therapy Colonic Neoplasms - pathology Dextrans - pharmacokinetics Dextrans - pharmacology Dose-Response Relationship, Drug efficacy General aspects Green Fluorescent Proteins - genetics HT29 Cells Humans Irinotecan Medical sciences metastasis Mice Mice, Nude nude mice orthotopic model polymer conjugate Prodrugs - pharmacology Surgery Topotecan - analogs & derivatives Topotecan - pharmacology Xenograft Model Antitumor Assays |
| title | High Antimetastatic Efficacy of MEN4901/T-0128, a Novel Camptothecin Carboxymethyldextran Conjugate |
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