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Smac mimetics and innate immune stimuli synergize to promote tumor death.
Beug, Shawn T; Tang, Vera A; LaCasse, Eric C; Cheung, Herman H; Beauregard, Caroline E; Brun, Jan; Nuyens, Jeffrey P; Earl, Nathalie; St-Jean, Martine; Holbrook, Janelle; Dastidar, Himika; Mahoney, Douglas J; Ilkow, Carolina; Le Boeuf, Fabrice; Bell, John C; Korneluk, Robert G.
Afiliación
  • Beug ST; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • Tang VA; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • LaCasse EC; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • Cheung HH; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • Beauregard CE; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • Brun J; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • Nuyens JP; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • Earl N; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • St-Jean M; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • Holbrook J; Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
  • Dastidar H; Alberta Children's Hospital Research Institute, Department of Microbiology, Immunology and Infectious Disease, University of Calgary, Calgary, Alberta, Canada.
  • Mahoney DJ; Alberta Children's Hospital Research Institute, Department of Microbiology, Immunology and Infectious Disease, University of Calgary, Calgary, Alberta, Canada.
  • Ilkow C; Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
  • Le Boeuf F; Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
  • Bell JC; 1] Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. [2] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
  • Korneluk RG; 1] Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada. [2] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Nat Biotechnol ; 32(2): 182-90, 2014 Feb.
Article en En | MEDLINE | ID: mdl-24463573
Smac mimetic compounds (SMC), a class of drugs that sensitize cells to apoptosis by counteracting the activity of inhibitor of apoptosis (IAP) proteins, have proven safe in phase 1 clinical trials in cancer patients. However, because SMCs act by enabling transduction of pro-apoptotic signals, SMC monotherapy may be efficacious only in the subset of patients whose tumors produce large quantities of death-inducing proteins such as inflammatory cytokines. Therefore, we reasoned that SMCs would synergize with agents that stimulate a potent yet safe "cytokine storm." Here we show that oncolytic viruses and adjuvants such as poly(I:C) and CpG induce bystander death of cancer cells treated with SMCs that is mediated by interferon beta (IFN-ß), tumor necrosis factor alpha (TNF-α) and/or TNF-related apoptosis-inducing ligand (TRAIL). This combinatorial treatment resulted in tumor regression and extended survival in two mouse models of cancer. As these and other adjuvants have been proven safe in clinical trials, it may be worthwhile to explore their clinical efficacy in combination with SMCs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Muerte Celular / Proteínas Reguladoras de la Apoptosis / Neoplasias Experimentales / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Muerte Celular / Proteínas Reguladoras de la Apoptosis / Neoplasias Experimentales / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos