{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:34:51Z","timestamp":1770816891306,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2011,7,5]],"date-time":"2011-07-05T00:00:00Z","timestamp":1309824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Adult T-cell leukemia\/lymphoma (ATLL) is a highly aggressive disease that occurs in individuals infected with the human T lymphotropic virus type 1 (HTLV-1). Patients with aggressive ATLL have a poor prognosis because the leukemic cells are resistant to conventional chemotherapy. We have investigated the therapeutic efficacy of a biphosphinic cyclopalladated complex {Pd2 [S(\u2212)C2, N-dmpa]2 (\u03bc-dppe)Cl2}, termed C7a, in a patient-derived xenograft model of ATLL, and investigated the mechanism of C7a action in HTLV-1-positive and negative transformed T cell lines in vitro. In vivo survival studies in immunocompromised mice inoculated with human RV-ATL cells and intraperitoneally treated with C7a led to significantly increased survival of the treated mice. We investigated the mechanism of C7a activity in vitro and found that it induced mitochondrial release of cytochrome c, caspase activation, nuclear condensation and DNA degradation. These results suggest that C7a triggers apoptotic cell death in both HTLV-1 infected and uninfected human transformed T-cell lines. Significantly, C7a was not cytotoxic to peripheral blood mononuclear cells (PBMC) from healthy donors and HTLV-1-infected individuals. C7a inhibited more than 60% of the ex vivo spontaneous proliferation of PBMC from HTLV-1-infected individuals. These results support a potential therapeutic role for C7a in both ATLL and HTLV-1-negative T-cell lymphomas.<\/jats:p>","DOI":"10.3390\/v3071041","type":"journal-article","created":{"date-parts":[[2011,7,5]],"date-time":"2011-07-05T11:26:46Z","timestamp":1309865206000},"page":"1041-1058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["C7a, a Biphosphinic Cyclopalladated Compound, Efficiently Controls the Development of a Patient-Derived Xenograft Model of Adult T Cell Leukemia\/Lymphoma"],"prefix":"10.3390","volume":"3","author":[{"given":"Ana B.","family":"Guimaraes-Correa","sequence":"first","affiliation":[{"name":"Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de S\u00e3o Paulo (UNIFESP-EPM), S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey B.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3680-4070","authenticated-orcid":false,"given":"Carlos R.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de S\u00e3o Paulo (UNIFESP-EPM), S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina P.","family":"Gimenes","sequence":"additional","affiliation":[{"name":"Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de S\u00e3o Paulo (UNIFESP-EPM), S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena A.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratorio Avan\u00e7ado de Sa\u00fade P\u00fablica, CPQGM, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador, Bahia 40296-700, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Fernanda Rios","family":"Grassi","sequence":"additional","affiliation":[{"name":"Laboratorio Avan\u00e7ado de Sa\u00fade P\u00fablica, CPQGM, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador, Bahia 40296-700, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerold","family":"Feuer","sequence":"additional","affiliation":[{"name":"Humurine Technologies, Inc., 640 Arrow Highway, La Verne, CA 91750, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz R.","family":"Travassos","sequence":"additional","affiliation":[{"name":"Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de S\u00e3o Paulo (UNIFESP-EPM), S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio C.F.","family":"Caires","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Bioqu\u00edmica, Universidade de Mogi de Cruzes, Mogi das Cruzes, S\u00e3o Paulo 08780-911, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine G.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de S\u00e3o Paulo (UNIFESP-EPM), S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan J.","family":"Marriott","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2011,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nasr, R., El Hajj, H., Kfour, Y., de Th\u00e9, H., Hermine, O., and Bazarbachi, A. 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