Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells
Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and So...
Gespeichert in:
| Veröffentlicht in: | PloS one 2024-09, Vol.19 (9), p.e0309533 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 9 |
| container_start_page | e0309533 |
| container_title | PloS one |
| container_volume | 19 |
| creator | Osada, Naoki Kikuchi, Jiro Okada, Yosuke Matsuoka, Sae Morishita, Kazuhiro Nakasone, Hideki Furukawa, Yusuke |
| description | Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and South West Japan. The prognosis of ATL remains dismal due to rapid acquired resistance to treatment with cytotoxic chemotherapeutic agents. In particular, the development of novel therapies for relapsed or refractory (R/R) ATL is an unmet need. Previous clinical trials revealed that bendamustine (BDM) was effective as the first-line treatment for indolent lymphoma and R/R cases of diffuse large B-cell lymphoma. Its major advantage is that it has few side effects such as hair loss and peripheral neuropathy, and does not impair the quality of life. However, its efficacy has not been verified for ATL in pre-clinical or clinical studies. In this study, we have shown the cytotoxicity of BDM alone and in combination with novel agents including the histone deacetylase (HDAC) inhibitor tucidinostat, the enhancer of zeste homolog 1/2 (EZH1/2) dual inhibitor valemetostat, and the Bcl2 family inhibitor ABT-737. The combined in vitro effects of BDM and tucidinostat were reproduced in a murine model without any obvious hematological toxicity. Our present results suggest that the combination of tucidinostat and BDM could additively prolong the survival of patients with R/R progressive ATL. The efficacy and safety of this combination are thus worthy of investigation in clinical settings. |
| doi_str_mv | 10.1371/journal.pone.0309533 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_3111459110</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A810663221</galeid><sourcerecordid>A810663221</sourcerecordid><originalsourceid>FETCH-LOGICAL-c506t-29c9755417aa85355d498c5de53cc752103360f2d913c8cca0695647b9482713</originalsourceid><addsrcrecordid>eNqNkl9r2zAUxc3YWLts32BsgsHYoMkky5Ktp1HC_hQKhS3sVdzIcqJOljJLbptvP5m4JR59GHqwZP_Oub5XJ8teE7wgtCSfrn3fObCLnXd6gSkWjNIn2SkRNJ_zHNOnR_uT7EUI1xgzWnH-PDuhghYVLflpZpf76KO_M8rEPfINWmtXQ9uHaJw-Q2CTOwJXI-OQ8u3aOIjGO3Rr4hY5f6Mtgo12MZyh6G-hqxHUvY1oNVfaWmR1_1u3BtBwCi-zZw3YoF-Nz1m2-vpltfw-v7z6drE8v5wrhnmc50KJkrGClAAVo4zVhagUqzWjSpUsJ5hSjpu8FoSqSinAXDBelGtRVHlJ6Cx7e7DdWR_kOKcgKSGkYIIk-Sz7PBL9utW1Sg10YOWuMy10e-nByOkXZ7Zy429kcigIL8vk8GF06PyfXocoWxOGJsFp3x-KccppXiT03T_o4780UhuwWhrX-FRYDabyvCKYJ6t8aG3xCJVWnaas0l01Jr2fCD5OBImJ-i5uoA9BXvz88f_s1a8p-_6I3WqwcRu87YdwhClYHEDV-RA63TxMmWA5BPl-GnIIshyDnGRvjm_oQXSfXPoXbtTsyQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3111459110</pqid></control><display><type>article</type><title>Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Osada, Naoki ; Kikuchi, Jiro ; Okada, Yosuke ; Matsuoka, Sae ; Morishita, Kazuhiro ; Nakasone, Hideki ; Furukawa, Yusuke</creator><contributor>Pilotti, Elisabetta</contributor><creatorcontrib>Osada, Naoki ; Kikuchi, Jiro ; Okada, Yosuke ; Matsuoka, Sae ; Morishita, Kazuhiro ; Nakasone, Hideki ; Furukawa, Yusuke ; Pilotti, Elisabetta</creatorcontrib><description>Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and South West Japan. The prognosis of ATL remains dismal due to rapid acquired resistance to treatment with cytotoxic chemotherapeutic agents. In particular, the development of novel therapies for relapsed or refractory (R/R) ATL is an unmet need. Previous clinical trials revealed that bendamustine (BDM) was effective as the first-line treatment for indolent lymphoma and R/R cases of diffuse large B-cell lymphoma. Its major advantage is that it has few side effects such as hair loss and peripheral neuropathy, and does not impair the quality of life. However, its efficacy has not been verified for ATL in pre-clinical or clinical studies. In this study, we have shown the cytotoxicity of BDM alone and in combination with novel agents including the histone deacetylase (HDAC) inhibitor tucidinostat, the enhancer of zeste homolog 1/2 (EZH1/2) dual inhibitor valemetostat, and the Bcl2 family inhibitor ABT-737. The combined in vitro effects of BDM and tucidinostat were reproduced in a murine model without any obvious hematological toxicity. Our present results suggest that the combination of tucidinostat and BDM could additively prolong the survival of patients with R/R progressive ATL. The efficacy and safety of this combination are thus worthy of investigation in clinical settings.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0309533</identifier><identifier>PMID: 39348376</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animals ; Antibodies ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Antineoplastic drugs ; Apoptosis - drug effects ; Bcl-2 protein ; Bendamustine ; Bendamustine Hydrochloride - pharmacology ; Bendamustine Hydrochloride - therapeutic use ; Biology and Life Sciences ; Care and treatment ; Cell growth ; Cell Line, Tumor ; Chemotherapy ; Clinical trials ; Complications and side effects ; Cytotoxicity ; Diagnosis ; Disease resistance ; DNA damage ; Effectiveness ; Histone deacetylase ; Histone Deacetylase Inhibitors - pharmacology ; Histone Deacetylase Inhibitors - therapeutic use ; Humans ; Inhibitors ; Laboratory animals ; Leukemia ; Leukemia-Lymphoma, Adult T-Cell - drug therapy ; Leukemia-Lymphoma, Adult T-Cell - pathology ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Lymphoma ; Medical prognosis ; Medicine and Health Sciences ; Mice ; Multiple myeloma ; Patient outcomes ; Patients ; People and Places ; Peripheral neuropathy ; Physical Sciences ; Quality of life ; Research and Analysis Methods ; Side effects ; T cell lymphoma ; Toxicity ; Tumors ; Xenograft Model Antitumor Assays</subject><ispartof>PloS one, 2024-09, Vol.19 (9), p.e0309533</ispartof><rights>Copyright: © 2024 Osada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Osada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Osada et al 2024 Osada et al</rights><rights>2024 Osada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c506t-29c9755417aa85355d498c5de53cc752103360f2d913c8cca0695647b9482713</cites><orcidid>0009-0004-8791-3263</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441677/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441677/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39348376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Pilotti, Elisabetta</contributor><creatorcontrib>Osada, Naoki</creatorcontrib><creatorcontrib>Kikuchi, Jiro</creatorcontrib><creatorcontrib>Okada, Yosuke</creatorcontrib><creatorcontrib>Matsuoka, Sae</creatorcontrib><creatorcontrib>Morishita, Kazuhiro</creatorcontrib><creatorcontrib>Nakasone, Hideki</creatorcontrib><creatorcontrib>Furukawa, Yusuke</creatorcontrib><title>Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and South West Japan. The prognosis of ATL remains dismal due to rapid acquired resistance to treatment with cytotoxic chemotherapeutic agents. In particular, the development of novel therapies for relapsed or refractory (R/R) ATL is an unmet need. Previous clinical trials revealed that bendamustine (BDM) was effective as the first-line treatment for indolent lymphoma and R/R cases of diffuse large B-cell lymphoma. Its major advantage is that it has few side effects such as hair loss and peripheral neuropathy, and does not impair the quality of life. However, its efficacy has not been verified for ATL in pre-clinical or clinical studies. In this study, we have shown the cytotoxicity of BDM alone and in combination with novel agents including the histone deacetylase (HDAC) inhibitor tucidinostat, the enhancer of zeste homolog 1/2 (EZH1/2) dual inhibitor valemetostat, and the Bcl2 family inhibitor ABT-737. The combined in vitro effects of BDM and tucidinostat were reproduced in a murine model without any obvious hematological toxicity. Our present results suggest that the combination of tucidinostat and BDM could additively prolong the survival of patients with R/R progressive ATL. The efficacy and safety of this combination are thus worthy of investigation in clinical settings.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Antineoplastic drugs</subject><subject>Apoptosis - drug effects</subject><subject>Bcl-2 protein</subject><subject>Bendamustine</subject><subject>Bendamustine Hydrochloride - pharmacology</subject><subject>Bendamustine Hydrochloride - therapeutic use</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Complications and side effects</subject><subject>Cytotoxicity</subject><subject>Diagnosis</subject><subject>Disease resistance</subject><subject>DNA damage</subject><subject>Effectiveness</subject><subject>Histone deacetylase</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histone Deacetylase Inhibitors - therapeutic use</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Laboratory animals</subject><subject>Leukemia</subject><subject>Leukemia-Lymphoma, Adult T-Cell - drug therapy</subject><subject>Leukemia-Lymphoma, Adult T-Cell - pathology</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Multiple myeloma</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>People and Places</subject><subject>Peripheral neuropathy</subject><subject>Physical Sciences</subject><subject>Quality of life</subject><subject>Research and Analysis Methods</subject><subject>Side effects</subject><subject>T cell lymphoma</subject><subject>Toxicity</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkl9r2zAUxc3YWLts32BsgsHYoMkky5Ktp1HC_hQKhS3sVdzIcqJOljJLbptvP5m4JR59GHqwZP_Oub5XJ8teE7wgtCSfrn3fObCLnXd6gSkWjNIn2SkRNJ_zHNOnR_uT7EUI1xgzWnH-PDuhghYVLflpZpf76KO_M8rEPfINWmtXQ9uHaJw-Q2CTOwJXI-OQ8u3aOIjGO3Rr4hY5f6Mtgo12MZyh6G-hqxHUvY1oNVfaWmR1_1u3BtBwCi-zZw3YoF-Nz1m2-vpltfw-v7z6drE8v5wrhnmc50KJkrGClAAVo4zVhagUqzWjSpUsJ5hSjpu8FoSqSinAXDBelGtRVHlJ6Cx7e7DdWR_kOKcgKSGkYIIk-Sz7PBL9utW1Sg10YOWuMy10e-nByOkXZ7Zy429kcigIL8vk8GF06PyfXocoWxOGJsFp3x-KccppXiT03T_o4780UhuwWhrX-FRYDabyvCKYJ6t8aG3xCJVWnaas0l01Jr2fCD5OBImJ-i5uoA9BXvz88f_s1a8p-_6I3WqwcRu87YdwhClYHEDV-RA63TxMmWA5BPl-GnIIshyDnGRvjm_oQXSfXPoXbtTsyQ</recordid><startdate>20240930</startdate><enddate>20240930</enddate><creator>Osada, Naoki</creator><creator>Kikuchi, Jiro</creator><creator>Okada, Yosuke</creator><creator>Matsuoka, Sae</creator><creator>Morishita, Kazuhiro</creator><creator>Nakasone, Hideki</creator><creator>Furukawa, Yusuke</creator><general>Public Library of Science</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0009-0004-8791-3263</orcidid></search><sort><creationdate>20240930</creationdate><title>Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells</title><author>Osada, Naoki ; Kikuchi, Jiro ; Okada, Yosuke ; Matsuoka, Sae ; Morishita, Kazuhiro ; Nakasone, Hideki ; Furukawa, Yusuke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c506t-29c9755417aa85355d498c5de53cc752103360f2d913c8cca0695647b9482713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Antineoplastic drugs</topic><topic>Apoptosis - drug effects</topic><topic>Bcl-2 protein</topic><topic>Bendamustine</topic><topic>Bendamustine Hydrochloride - pharmacology</topic><topic>Bendamustine Hydrochloride - therapeutic use</topic><topic>Biology and Life Sciences</topic><topic>Care and treatment</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Complications and side effects</topic><topic>Cytotoxicity</topic><topic>Diagnosis</topic><topic>Disease resistance</topic><topic>DNA damage</topic><topic>Effectiveness</topic><topic>Histone deacetylase</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Histone Deacetylase Inhibitors - therapeutic use</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>Laboratory animals</topic><topic>Leukemia</topic><topic>Leukemia-Lymphoma, Adult T-Cell - drug therapy</topic><topic>Leukemia-Lymphoma, Adult T-Cell - pathology</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Multiple myeloma</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>People and Places</topic><topic>Peripheral neuropathy</topic><topic>Physical Sciences</topic><topic>Quality of life</topic><topic>Research and Analysis Methods</topic><topic>Side effects</topic><topic>T cell lymphoma</topic><topic>Toxicity</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Osada, Naoki</creatorcontrib><creatorcontrib>Kikuchi, Jiro</creatorcontrib><creatorcontrib>Okada, Yosuke</creatorcontrib><creatorcontrib>Matsuoka, Sae</creatorcontrib><creatorcontrib>Morishita, Kazuhiro</creatorcontrib><creatorcontrib>Nakasone, Hideki</creatorcontrib><creatorcontrib>Furukawa, Yusuke</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>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Osada, Naoki</au><au>Kikuchi, Jiro</au><au>Okada, Yosuke</au><au>Matsuoka, Sae</au><au>Morishita, Kazuhiro</au><au>Nakasone, Hideki</au><au>Furukawa, Yusuke</au><au>Pilotti, Elisabetta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-09-30</date><risdate>2024</risdate><volume>19</volume><issue>9</issue><spage>e0309533</spage><pages>e0309533-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and South West Japan. The prognosis of ATL remains dismal due to rapid acquired resistance to treatment with cytotoxic chemotherapeutic agents. In particular, the development of novel therapies for relapsed or refractory (R/R) ATL is an unmet need. Previous clinical trials revealed that bendamustine (BDM) was effective as the first-line treatment for indolent lymphoma and R/R cases of diffuse large B-cell lymphoma. Its major advantage is that it has few side effects such as hair loss and peripheral neuropathy, and does not impair the quality of life. However, its efficacy has not been verified for ATL in pre-clinical or clinical studies. In this study, we have shown the cytotoxicity of BDM alone and in combination with novel agents including the histone deacetylase (HDAC) inhibitor tucidinostat, the enhancer of zeste homolog 1/2 (EZH1/2) dual inhibitor valemetostat, and the Bcl2 family inhibitor ABT-737. The combined in vitro effects of BDM and tucidinostat were reproduced in a murine model without any obvious hematological toxicity. Our present results suggest that the combination of tucidinostat and BDM could additively prolong the survival of patients with R/R progressive ATL. The efficacy and safety of this combination are thus worthy of investigation in clinical settings.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39348376</pmid><doi>10.1371/journal.pone.0309533</doi><tpages>e0309533</tpages><orcidid>https://orcid.org/0009-0004-8791-3263</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2024-09, Vol.19 (9), p.e0309533 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_3111459110 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animal models Animals Antibodies Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Antineoplastic drugs Apoptosis - drug effects Bcl-2 protein Bendamustine Bendamustine Hydrochloride - pharmacology Bendamustine Hydrochloride - therapeutic use Biology and Life Sciences Care and treatment Cell growth Cell Line, Tumor Chemotherapy Clinical trials Complications and side effects Cytotoxicity Diagnosis Disease resistance DNA damage Effectiveness Histone deacetylase Histone Deacetylase Inhibitors - pharmacology Histone Deacetylase Inhibitors - therapeutic use Humans Inhibitors Laboratory animals Leukemia Leukemia-Lymphoma, Adult T-Cell - drug therapy Leukemia-Lymphoma, Adult T-Cell - pathology Lymphocytes Lymphocytes B Lymphocytes T Lymphoma Medical prognosis Medicine and Health Sciences Mice Multiple myeloma Patient outcomes Patients People and Places Peripheral neuropathy Physical Sciences Quality of life Research and Analysis Methods Side effects T cell lymphoma Toxicity Tumors Xenograft Model Antitumor Assays |
| title | Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T13%3A04%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cytotoxicity%20of%20bendamustine,%20alone%20and%20in%20combination%20with%20novel%20agents,%20toward%20adult%20T-cell%20leukemia%20cells&rft.jtitle=PloS%20one&rft.au=Osada,%20Naoki&rft.date=2024-09-30&rft.volume=19&rft.issue=9&rft.spage=e0309533&rft.pages=e0309533-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0309533&rft_dat=%3Cgale_plos_%3EA810663221%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3111459110&rft_id=info:pmid/39348376&rft_galeid=A810663221&rfr_iscdi=true |