Arsenic trioxide inhibits growth of human T‐cell leukaemia virus type I infected T‐cell lines more effectively than retinoic acids
Adult T‐cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T‐cell leukaemia virus type I (HTLV‐I) infected T‐cell lines and fresh ATL cells by ar...
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Veröffentlicht in: | British journal of haematology 1998-12, Vol.103 (3), p.721-728 |
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creator | Ishitsuka, Kenji Hanada, Shuichi Suzuki, Shinsuke Utsunomiya, Atae Chyuman, Yoshiko Takeuchi, Syogo Takeshita, Taketsugu Shimotakahara, Sigemi Uozumi, Kimiharu Makino, Torahiko Arima, Terukatsu |
description | Adult T‐cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T‐cell leukaemia virus type I (HTLV‐I) infected T‐cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV‐I‐infected T‐cell lines was significantly reduced within 72 h by 1.0 μmol/l As2O3. Growth of two out of four HTLV‐I‐infected T‐cell lines was also inhibited by 1.0 μmol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by As2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 μmol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA. |
doi_str_mv | 10.1046/j.1365-2141.1998.01068.x |
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Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T‐cell leukaemia virus type I (HTLV‐I) infected T‐cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV‐I‐infected T‐cell lines was significantly reduced within 72 h by 1.0 μmol/l As2O3. Growth of two out of four HTLV‐I‐infected T‐cell lines was also inhibited by 1.0 μmol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by As2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 μmol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1046/j.1365-2141.1998.01068.x</identifier><identifier>PMID: 9858223</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, U.K. and Cambridge, USA: Blackwell Science Ltd</publisher><subject>adult T‐cell leukaemia ; AIDS/HIV ; Antineoplastic agents ; Antineoplastic Agents - therapeutic use ; apoptosis ; Apoptosis - drug effects ; Arsenic Trioxide ; Arsenicals - therapeutic use ; Biological and medical sciences ; Cell Division ; General aspects ; growth inhibition ; Hematology ; HTLV-I Infections - drug therapy ; HTLV-I Infections - pathology ; HTLV-I Infections - virology ; Human T-lymphotropic virus 1 - growth & development ; Humans ; Medical sciences ; Oxides - therapeutic use ; Pharmacology. 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Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T‐cell leukaemia virus type I (HTLV‐I) infected T‐cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV‐I‐infected T‐cell lines was significantly reduced within 72 h by 1.0 μmol/l As2O3. Growth of two out of four HTLV‐I‐infected T‐cell lines was also inhibited by 1.0 μmol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by As2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 μmol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. 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Drug treatments</subject><subject>retinoic acid</subject><subject>T-Lymphocytes - pathology</subject><subject>T-Lymphocytes - virology</subject><subject>Tretinoin - therapeutic use</subject><subject>Tumor Cells, Cultured</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkb1uFDEUhS0ECkvgEZAshOhmuLbnxy4okghIUCSaUFsezzXrZX4WeybZ7aioeUaeBA-7CoiKypbOd8699iGEMsgZFNXrTc5EVWacFSxnSskcGFQy3z0gq3vhIVkBQJ0lg3xMnsS4AWACSnZCTpQsJediRb6fhYiDt3QKftz5Fqkf1r7xU6Sfw3g3reno6HruzUBvfn77YbHraIfzF4O9N_TWhznSab9FepWMDu2E7V-gHzDSfgxI0S2iv8VuT6d1Sgs4-WFMg431bXxKHjnTRXx2PE_Jp3dvby4us-uP768uzq4zW9QgM86dKOvGcigaNLWshBVlZSy2NTqhLDeuRiFLB0KBYEaVFqEpq5rXheCsEqfk1SF3G8avM8ZJ9z4uu5oBxznqSoEUaUQCX_wDbsY5DGk3zdLnKaWAJ0geIBvGGAM6vQ2-N2GvGeilJ73RSx16qUMvPenfPeldsj4_5s9Nj-298VhM0l8edROt6Vwwg_XxT34pK-DLe94csDvf4f6_x-vzD5fLTfwC_uywjQ</recordid><startdate>199812</startdate><enddate>199812</enddate><creator>Ishitsuka, Kenji</creator><creator>Hanada, Shuichi</creator><creator>Suzuki, Shinsuke</creator><creator>Utsunomiya, Atae</creator><creator>Chyuman, Yoshiko</creator><creator>Takeuchi, Syogo</creator><creator>Takeshita, Taketsugu</creator><creator>Shimotakahara, Sigemi</creator><creator>Uozumi, Kimiharu</creator><creator>Makino, Torahiko</creator><creator>Arima, Terukatsu</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Blackwell Publishing Ltd</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>199812</creationdate><title>Arsenic trioxide inhibits growth of human T‐cell leukaemia virus type I infected T‐cell lines more effectively than retinoic acids</title><author>Ishitsuka, Kenji ; Hanada, Shuichi ; Suzuki, Shinsuke ; Utsunomiya, Atae ; Chyuman, Yoshiko ; Takeuchi, Syogo ; Takeshita, Taketsugu ; Shimotakahara, Sigemi ; Uozumi, Kimiharu ; Makino, Torahiko ; Arima, Terukatsu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4708-22f357bc204bea7863c356aced7ef39c2af7e385f039031a95ce0b56727432163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>adult T‐cell leukaemia</topic><topic>AIDS/HIV</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Arsenic Trioxide</topic><topic>Arsenicals - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cell Division</topic><topic>General aspects</topic><topic>growth inhibition</topic><topic>Hematology</topic><topic>HTLV-I Infections - drug therapy</topic><topic>HTLV-I Infections - pathology</topic><topic>HTLV-I Infections - virology</topic><topic>Human T-lymphotropic virus 1 - growth & development</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Oxides - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>retinoic acid</topic><topic>T-Lymphocytes - pathology</topic><topic>T-Lymphocytes - virology</topic><topic>Tretinoin - therapeutic use</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ishitsuka, Kenji</creatorcontrib><creatorcontrib>Hanada, Shuichi</creatorcontrib><creatorcontrib>Suzuki, Shinsuke</creatorcontrib><creatorcontrib>Utsunomiya, Atae</creatorcontrib><creatorcontrib>Chyuman, Yoshiko</creatorcontrib><creatorcontrib>Takeuchi, Syogo</creatorcontrib><creatorcontrib>Takeshita, Taketsugu</creatorcontrib><creatorcontrib>Shimotakahara, Sigemi</creatorcontrib><creatorcontrib>Uozumi, Kimiharu</creatorcontrib><creatorcontrib>Makino, Torahiko</creatorcontrib><creatorcontrib>Arima, Terukatsu</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ishitsuka, Kenji</au><au>Hanada, Shuichi</au><au>Suzuki, Shinsuke</au><au>Utsunomiya, Atae</au><au>Chyuman, Yoshiko</au><au>Takeuchi, Syogo</au><au>Takeshita, Taketsugu</au><au>Shimotakahara, Sigemi</au><au>Uozumi, Kimiharu</au><au>Makino, Torahiko</au><au>Arima, Terukatsu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Arsenic trioxide inhibits growth of human T‐cell leukaemia virus type I infected T‐cell lines more effectively than retinoic acids</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>1998-12</date><risdate>1998</risdate><volume>103</volume><issue>3</issue><spage>721</spage><epage>728</epage><pages>721-728</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Adult T‐cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T‐cell leukaemia virus type I (HTLV‐I) infected T‐cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV‐I‐infected T‐cell lines was significantly reduced within 72 h by 1.0 μmol/l As2O3. Growth of two out of four HTLV‐I‐infected T‐cell lines was also inhibited by 1.0 μmol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by As2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 μmol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.</abstract><cop>Oxford, U.K. and Cambridge, USA</cop><pub>Blackwell Science Ltd</pub><pmid>9858223</pmid><doi>10.1046/j.1365-2141.1998.01068.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | adult T‐cell leukaemia AIDS/HIV Antineoplastic agents Antineoplastic Agents - therapeutic use apoptosis Apoptosis - drug effects Arsenic Trioxide Arsenicals - therapeutic use Biological and medical sciences Cell Division General aspects growth inhibition Hematology HTLV-I Infections - drug therapy HTLV-I Infections - pathology HTLV-I Infections - virology Human T-lymphotropic virus 1 - growth & development Humans Medical sciences Oxides - therapeutic use Pharmacology. Drug treatments retinoic acid T-Lymphocytes - pathology T-Lymphocytes - virology Tretinoin - therapeutic use Tumor Cells, Cultured |
title | Arsenic trioxide inhibits growth of human T‐cell leukaemia virus type I infected T‐cell lines more effectively than retinoic acids |
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