C7a, a Biphosphinic Cyclopalladated Compound, Efficiently Controls the Development of a Patient-Derived Xenograft Model of Adult T Cell Leukemia/Lymphoma

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dc.contributor.authorGuimarães-Corrêa, Ana Beatriz [UNIFESP]
dc.contributor.authorCrawford, Lindsey B.
dc.contributor.authorFigueiredo, Carlos Rogerio [UNIFESP]
dc.contributor.authorGimenes, Karina P. [UNIFESP]
dc.contributor.authorPinto, Lorena A.
dc.contributor.authorRios Grassi, Maria Fernanda
dc.contributor.authorFeuer, Gerold
dc.contributor.authorTravassos, Luiz Rodolpho [UNIFESP]
dc.contributor.authorCaires, Antonio C. F.
dc.contributor.authorRodrigues, Elaine Guadelupe [UNIFESP]
dc.contributor.authorMarriott, Susan J.
dc.contributor.institutionBaylor Coll Med
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionSUNY Upstate Med Univ
dc.contributor.institutionFundacao Oswaldo Cruz FIOCRUZ
dc.contributor.institutionUniv Mogi das Cruzes
dc.contributor.institutionHumurine Technol Inc
dc.date.accessioned2016-01-24T14:16:55Z
dc.date.available2016-01-24T14:16:55Z
dc.date.issued2011-07-01
dc.description.abstractAdult 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 {Pd-2 [S(-)C2, N-dmpa](2) (mu-dppe)Cl-2}, 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.en
dc.description.affiliationBaylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
dc.description.affiliationUniversidade Federal de São Paulo UNIFESP EPM, Dept Microbiol Imunol & Parasitol, Unidade Oncol Expt, BR-04023062 São Paulo, Brazil
dc.description.affiliationSUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY 13210 USA
dc.description.affiliationFundacao Oswaldo Cruz FIOCRUZ, CPQGM, Lab Avancado Saude Publ, BR-40296700 Salvador, BA, Brazil
dc.description.affiliationUniv Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, BR-08780911 São Paulo, Brazil
dc.description.affiliationHumurine Technol Inc, La Verne, CA 91750 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo UNIFESP EPM, Dept Microbiol Imunol & Parasitol, Unidade Oncol Expt, BR-04023062 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipNew York State Department of Health
dc.description.sponsorshipIDNational Institutes of Health: AI078307
dc.description.sponsorshipIDNational Institutes of Health: CA77371
dc.description.sponsorshipIDNew York State Department of Health: C023059
dc.description.sponsorshipIDNew York State Department of Health: N08G-127
dc.format.extent1041-1058
dc.identifierhttp://dx.doi.org/10.3390/v3071041
dc.identifier.citationViruses-basel. Basel: Mdpi Ag, v. 3, n. 7, p. 1041-1058, 2011.
dc.identifier.doi10.3390/v3071041
dc.identifier.fileWOS000293070000005.pdf
dc.identifier.issn1999-4915
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33835
dc.identifier.wosWOS:000293070000005
dc.language.isoeng
dc.publisherMdpi Ag
dc.relation.ispartofViruses-basel
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectcyclopalladated compounden
dc.subjectHTLV-1en
dc.subjectATLLen
dc.subjectchemotherapyen
dc.subjectxenograft modelen
dc.subjectapoptosisen
dc.titleC7a, a Biphosphinic Cyclopalladated Compound, Efficiently Controls the Development of a Patient-Derived Xenograft Model of Adult T Cell Leukemia/Lymphomaen
dc.typeinfo:eu-repo/semantics/article
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