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Evaluation of the molecular mechanisms of p53/ARF and IFN-beta pathways involved in the the response of melanoma cells to treatment with the p19Arf and IFN-beta transgenes.

Grant number: 11/10656-5
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2011
Effective date (End): November 30, 2015
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Bryan Eric Strauss
Grantee:Aline Hunger Ribeiro
Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Malignant melanoma is type of cancer with high death rates due, in part, to its propensity to form metastases. Approximately 90% of melanoma cases maintain wild-type p53 and perhaps this could be used as a tool to drive expression from the vector interest. Viral Vector Group (VVG - Incor - FMUSP) has developed adenoviral vectors in which transgene expression is controlled by the transcription factor and tumor suppressor, p53. The VVG has also improved these vectors by modifying the fiber knob protein, allowing efficient transduction of a wide range of target cells without dependence on the wild-type adenovirus receptor, CAR. Using these vectors, the VVG has shown that combined treatment with p19Arf and IFN-beta together, but not alone, had induced B16 (murine melanoma) cell death. In this regard, we propose new studies to identify critical genes activated by the combined treatment and that act as mediators in the cellular response to the gene transfer strategy. In this project, we will transfer the combination of the p19Arf and IFN-beta to B16 cells and compare gene expression profile of these cells and cells that have received only one of these factors. We will also perform functional assays in order to verify the role of the factors identified upon treatment with the viral vectors. In addition, subcellular localization, post-translational modifications and protein interactions known to be critical for p53/ARF or IFN-beta will be evaluated after viral treatment. We hope that elucidation of molecular mechanisms involved in the response of melanoma cells to the combined p19Arf and IFN-beta treatments could be useful for understanding tumor biology and, possibly, shape new therapeutic interventions.

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Scientific publications (10)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VIEIRA MEDRANO, RUAN FELIPE; PORTELA CATANI, JOAO PAULO; RIBEIRO, ALINE HUNGER; TOMAZ, SAMANTA LOPES; MERKEL, CHRISTIAN A.; COSTANZI-STRAUSS, EUGENIA; STRAUSS, BRYAN E.. Vaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapy. CANCER IMMUNOLOGY IMMUNOTHERAPY, v. 65, n. 4, p. 371-382, . (11/10656-5, 13/09474-5, 14/11524-3, 13/25167-5)
MEDRANO, RUAN F. V.; HUNGER, ALINE; MENDONCA, SAMIR ANDRADE; BARBUTO, JOSE ALEXANDRE M.; STRAUSS, BRYAN E.. Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy. ONCOTARGET, v. 8, n. 41, p. 71249-71284, . (11/10656-5, 15/26580-9, 13/09474-5, 13/25167-5)
DA-COSTA, R. C.; VIEIRA, I. L.; HUNGER, A.; TAMURA, R. E.; STRAUSS, B. E.. p19Arf sensitizes B16 melanoma cells to interferon-beta delivered via mesenchymal stem cells in vitro. Brazilian Journal of Medical and Biological Research, v. 53, n. 3, . (13/25167-5, 11/10656-5, 16/18197-3, 11/21256-8, 15/26580-9)
DAVID, TAYNAH I. P.; CERQUEIRA, OTTO L. D.; LANA, MARLOUS G.; MEDRANO, V, RUAN F.; HUNGER, ALINE; STRAUSS, BRYAN E.. Response of human melanoma cell lines to interferon-beta gene transfer mediated by a modified adenoviral vector. SCIENTIFIC REPORTS, v. 10, n. 1, . (17/23068-0, 10/15025-0, 12/05066-7, 11/10656-5, 15/26580-9, 13/09474-5)
VIEIRA, IGOR DE LUNA; TAMURA, RODRIGO ESAKI; HUNGER, ALINE; STRAUSS, BRYAN E.. Distinct Roles of Direct Transduction Versus Exposure to the Tumor Secretome on Murine Endothelial Cells After Melanoma Gene Therapy with Interferon-beta and p19Arf. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, v. 39, n. 4, p. 246-258, . (13/25167-5, 11/10656-5, 11/21256-8, 15/26580-9)
HUNGER, ALINE; MEDRANO, V, RUAN F.; ZANATTA, DANIELA B.; DEL VALLE, PAULO R.; MERKEL, CHRISTIAN A.; SALLES, THIAGO DE ALMEIDA; FERRARI, DANIEL G.; FURUYA, TATIANE K.; BUSTOS, SILVINA O.; SAITO, RENATA DE FREITAS; et al. Reestablishment of p53/Arf and interferon-beta pathways mediated by a novel adenoviral vector potentiates antiviral response and immunogenic cell death. CELL DEATH DISCOVERY, v. 3, . (11/10656-5, 13/09474-5, 13/25167-5)
MEDRANO, RUAN F., V; SALLES, THIAGO A.; DARIOLLI, RAFAEL; ANTUNES, FERNANDA; FEITOSA, VALKER A.; HUNGER, ALINE; CATANI, JOAO P. P.; MENDONCA, SAMIR A.; TAMURA, RODRIGO E.; LANA, MARLOUS G.; et al. Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy. SCIENTIFIC REPORTS, v. 12, n. 1, p. 14-pg., . (18/04800-5, 13/09474-5, 15/26580-9, 11/10656-5, 11/21256-8, 14/11524-3, 12/05066-7)
HUNGER, ALINE; MEDRANO, RUAN F. V.; STRAUSS, BRYAN E.. Harnessing combined p19Arf and interferon-beta gene transfer as an inducer of immunogenic cell death and mediator of cancer immunotherapy. CELL DEATH & DISEASE, v. 8, p. 3-pg., . (13/09474-5, 11/10656-5, 13/25167-5)
PORTELA CATANI, JOAO PAULO; MEDRANO, RUAN F. V.; HUNGER, ALINE; DEL VALLE, PAULO; ADJEMIAN, SANDY; ZANATTA, DANIELA BERTOLINI; KROEMER, GUIDO; COSTANZI-STRAUSS, EUGENIA; STRAUSS, BRYAN E.. Intratumoral Immunization by p19Arf and Interferon-beta Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma. TRANSLATIONAL ONCOLOGY, v. 9, n. 6, p. 565-574, . (11/10656-5, 12/25380-8, 13/09474-5, 14/11524-3, 13/25167-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RIBEIRO, Aline Hunger. Evaluation of molecular mechanisms of p53/ARF and IFNbeta pathways involved int the response of molecuar cells to treatment with p19Arf and IFNbeta transgenes. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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