Inhibition of a mouse hepatoma by the alkylating agent Trenimon linked to immunoglobulins
Trenimon was conjugated in active alkylating form to rabbit anti-mouse H6 hepatoma globulin (AHG) with retention of antibody activity. H6 hepatoma-inoculated mice were given various combinations of conjugates, free Trenimon, and unconjugated immunoglobulins in daily injections for 5 days. Linkage of...
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Veröffentlicht in: | Cancer Immunology Immunotherapy 1982-01, Vol.13 (3), p.185-189 |
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creator | Ghose, T Guclu, A Raman, R R Blair, A H |
description | Trenimon was conjugated in active alkylating form to rabbit anti-mouse H6 hepatoma globulin (AHG) with retention of antibody activity. H6 hepatoma-inoculated mice were given various combinations of conjugates, free Trenimon, and unconjugated immunoglobulins in daily injections for 5 days. Linkage of Trenimon to immunoglobulins reduced systemic toxicity of the drug, with comparative retention of its antitumor activity. The antitumor action of Trenimon was potentiated by AHG irrespective of whether the drug was directly linked to AHG or free AHG was administered along with Trenimon linked to normal rabbit globulin (NRG). In vitro, Trenimon bound to AHG was less inhibitory to hepatoma cells than free Trenimon, but more inhibitory than Trenimon-NRG conjugates. There was no significant endocytosis of conjugates by the hepatoma cells. This suggests that unlike free Trenimon, the target molecules of Trenimon-immunoglobulin conjugates are not intracellular DNA but are located on the surface of the hepatoma cells. |
doi_str_mv | 10.1007/BF00205386 |
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H6 hepatoma-inoculated mice were given various combinations of conjugates, free Trenimon, and unconjugated immunoglobulins in daily injections for 5 days. Linkage of Trenimon to immunoglobulins reduced systemic toxicity of the drug, with comparative retention of its antitumor activity. The antitumor action of Trenimon was potentiated by AHG irrespective of whether the drug was directly linked to AHG or free AHG was administered along with Trenimon linked to normal rabbit globulin (NRG). In vitro, Trenimon bound to AHG was less inhibitory to hepatoma cells than free Trenimon, but more inhibitory than Trenimon-NRG conjugates. There was no significant endocytosis of conjugates by the hepatoma cells. This suggests that unlike free Trenimon, the target molecules of Trenimon-immunoglobulin conjugates are not intracellular DNA but are located on the surface of the hepatoma cells.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/BF00205386</identifier><identifier>PMID: 6925984</identifier><language>eng</language><publisher>Germany: Springer-Verlag</publisher><subject>Alkylating Agents - administration & dosage ; Animals ; Antibodies, Neoplasm - immunology ; Endocytosis ; Female ; hepatoma ; immunoglobulins ; Immunoglobulins - administration & dosage ; immunotherapy ; Liver Neoplasms, Experimental - drug therapy ; Liver Neoplasms, Experimental - immunology ; Mice ; Mice, Inbred Strains ; Neoplasm Transplantation ; Original ; Rabbits ; triaziquone ; Triaziquone - administration & dosage</subject><ispartof>Cancer Immunology Immunotherapy, 1982-01, Vol.13 (3), p.185-189</ispartof><rights>Springer-Verlag 1982</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c369t-f0178b593cd5adabb53c6f3da13f942aa80fa12ada1d5dadcc89153c42da8ab93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11039288/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11039288/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6925984$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ghose, T</creatorcontrib><creatorcontrib>Guclu, A</creatorcontrib><creatorcontrib>Raman, R R</creatorcontrib><creatorcontrib>Blair, A H</creatorcontrib><title>Inhibition of a mouse hepatoma by the alkylating agent Trenimon linked to immunoglobulins</title><title>Cancer Immunology Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><description>Trenimon was conjugated in active alkylating form to rabbit anti-mouse H6 hepatoma globulin (AHG) with retention of antibody activity. H6 hepatoma-inoculated mice were given various combinations of conjugates, free Trenimon, and unconjugated immunoglobulins in daily injections for 5 days. Linkage of Trenimon to immunoglobulins reduced systemic toxicity of the drug, with comparative retention of its antitumor activity. The antitumor action of Trenimon was potentiated by AHG irrespective of whether the drug was directly linked to AHG or free AHG was administered along with Trenimon linked to normal rabbit globulin (NRG). In vitro, Trenimon bound to AHG was less inhibitory to hepatoma cells than free Trenimon, but more inhibitory than Trenimon-NRG conjugates. There was no significant endocytosis of conjugates by the hepatoma cells. This suggests that unlike free Trenimon, the target molecules of Trenimon-immunoglobulin conjugates are not intracellular DNA but are located on the surface of the hepatoma cells.</description><subject>Alkylating Agents - administration & dosage</subject><subject>Animals</subject><subject>Antibodies, Neoplasm - immunology</subject><subject>Endocytosis</subject><subject>Female</subject><subject>hepatoma</subject><subject>immunoglobulins</subject><subject>Immunoglobulins - administration & dosage</subject><subject>immunotherapy</subject><subject>Liver Neoplasms, Experimental - drug therapy</subject><subject>Liver Neoplasms, Experimental - immunology</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Neoplasm Transplantation</subject><subject>Original</subject><subject>Rabbits</subject><subject>triaziquone</subject><subject>Triaziquone - administration & dosage</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1982</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkTFPwzAQhS0EKqWwsCN5YkAK2HGS2hOCikKlSixlYLIusZOYJnaJE6T-e4xaFZjudPfdu6c7hC4puaWETO8e54TEJGU8O0JjmrA4Ijylx2hMWEKiKSHJKTrz_iMkMRFihEaZiFPBkzF6X9ja5KY3zmJXYsCtG7zGtd5A71rA-Rb3tcbQrLcN9MZWGCpte7zqtDVtGGqMXWuFe4dN2w7WVY3Lh1D05-ikhMbri32coLf502r2Ei1fnxezh2VUsEz0UUnolOepYIVKQUGep6zISqaAslIkMQAnJdA4tKhKFaii4IIGJokVcMgFm6D7ne5myFutiuCug0ZuOtNCt5UOjPzfsaaWlfuSlBImYs6DwvVeoXOfg_a9bI0vdNOA1eEakrKMBYPTAN7swKJz3ne6PGyhRP58Qv5-IsBXf30d0P3p2TcvjoZz</recordid><startdate>19820101</startdate><enddate>19820101</enddate><creator>Ghose, T</creator><creator>Guclu, A</creator><creator>Raman, R R</creator><creator>Blair, A H</creator><general>Springer-Verlag</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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>M7Z</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>19820101</creationdate><title>Inhibition of a mouse hepatoma by the alkylating agent Trenimon linked to immunoglobulins</title><author>Ghose, T ; Guclu, A ; Raman, R R ; Blair, A H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-f0178b593cd5adabb53c6f3da13f942aa80fa12ada1d5dadcc89153c42da8ab93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1982</creationdate><topic>Alkylating Agents - administration & dosage</topic><topic>Animals</topic><topic>Antibodies, Neoplasm - immunology</topic><topic>Endocytosis</topic><topic>Female</topic><topic>hepatoma</topic><topic>immunoglobulins</topic><topic>Immunoglobulins - administration & dosage</topic><topic>immunotherapy</topic><topic>Liver Neoplasms, Experimental - drug therapy</topic><topic>Liver Neoplasms, Experimental - immunology</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Neoplasm Transplantation</topic><topic>Original</topic><topic>Rabbits</topic><topic>triaziquone</topic><topic>Triaziquone - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ghose, T</creatorcontrib><creatorcontrib>Guclu, A</creatorcontrib><creatorcontrib>Raman, R R</creatorcontrib><creatorcontrib>Blair, A H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghose, T</au><au>Guclu, A</au><au>Raman, R R</au><au>Blair, A H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of a mouse hepatoma by the alkylating agent Trenimon linked to immunoglobulins</atitle><jtitle>Cancer Immunology Immunotherapy</jtitle><addtitle>Cancer Immunol Immunother</addtitle><date>1982-01-01</date><risdate>1982</risdate><volume>13</volume><issue>3</issue><spage>185</spage><epage>189</epage><pages>185-189</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Trenimon was conjugated in active alkylating form to rabbit anti-mouse H6 hepatoma globulin (AHG) with retention of antibody activity. H6 hepatoma-inoculated mice were given various combinations of conjugates, free Trenimon, and unconjugated immunoglobulins in daily injections for 5 days. Linkage of Trenimon to immunoglobulins reduced systemic toxicity of the drug, with comparative retention of its antitumor activity. The antitumor action of Trenimon was potentiated by AHG irrespective of whether the drug was directly linked to AHG or free AHG was administered along with Trenimon linked to normal rabbit globulin (NRG). In vitro, Trenimon bound to AHG was less inhibitory to hepatoma cells than free Trenimon, but more inhibitory than Trenimon-NRG conjugates. There was no significant endocytosis of conjugates by the hepatoma cells. This suggests that unlike free Trenimon, the target molecules of Trenimon-immunoglobulin conjugates are not intracellular DNA but are located on the surface of the hepatoma cells.</abstract><cop>Germany</cop><pub>Springer-Verlag</pub><pmid>6925984</pmid><doi>10.1007/BF00205386</doi><tpages>5</tpages></addata></record> |
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source | MEDLINE; Springer Nature - Complete Springer Journals; PubMed Central |
subjects | Alkylating Agents - administration & dosage Animals Antibodies, Neoplasm - immunology Endocytosis Female hepatoma immunoglobulins Immunoglobulins - administration & dosage immunotherapy Liver Neoplasms, Experimental - drug therapy Liver Neoplasms, Experimental - immunology Mice Mice, Inbred Strains Neoplasm Transplantation Original Rabbits triaziquone Triaziquone - administration & dosage |
title | Inhibition of a mouse hepatoma by the alkylating agent Trenimon linked to immunoglobulins |
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