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Investigation of the direct and paracrine angiogenic effects after gene transfer mediated by adenoviral vectors carrying the Interferon-beta in murine melanoma

Grant number: 16/18197-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2016
Effective date (End): January 31, 2021
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Bryan Eric Strauss
Grantee:Igor de Luna Vieira
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

Melanoma has high mortality and significant impact on society. Tumors are not simply masses of cancer cells, they are complex "organs" with a variety of cell types and structures that cooperate with tumor progression. Alternative therapies, such as gene therapy, are showing promising results in preclinical and clinical research. Our laboratory developed viral vectors carrying INF-² that offer anti-cancer activity. IFN-² is an immunomodulatory cytokine with anti-tumor and anti-angiogenic effects. Results from the group have shown that the use of Ad-IFN² slowed tumor growth in a murine melanoma model. During the master's project of this student, we demonstrated that the Ad-IFN vector had no effect when endothelial cells (tEnd) were directly transduced, however a paracrine test where tEnd cells were cultured with transduced melanoma cells (B16), resulted in the death of tEnd cells. This result demonstrates an effect that is dependent on the transductional target of the INF-² adenovirus. Given these data in combination with additional results from our group, we seek to explore the mechanisms involved in the death or survival of endothelial cells in the presence of IFN-². With this project, we will deepen our understanding of the potential anti-angiogenic effect promoted by IFN-²gene transfer in a mouse model of melanoma.

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Scientific publications (5)
(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)
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)
TAMURA, RODRIGO ESAKI; DE LUNA, IGOR VIEIRA; LANA, MARLOUS GOMES; STRAUSS, BRYAN E.. Improving adenoviral vectors and strategies for prostate cancer gene therapy. Clinics, v. 73, n. 1, . (11/21256-8, 15/26580-9, 12/05066-7, 16/18197-3, 13/25167-5)
STRAUSS, BRYAN E.; OLIVEIRA SILVA, GISSELE ROLEMBERG; VIEIRA, IGOR DE LUNA; DUTRA CERQUEIRA, OTTO LUIZ; DEL VALLE, PAULO ROBERTO; VIEIRA MEDRANO, RUAN FELIPE; MENDONCA, SAMIR ANDRADE. Perspectives for cancer immunotherapy mediated by p19Arf plus interferon-beta gene transfer. Clinics, v. 73, n. 1, . (12/05066-7, 16/18197-3, 13/09474-5, 13/25167-5, 13/16074-3, 15/26580-9)
TAMURA, RODRIGO ESAKI; DE LUNA, IGOR VIEIRA; LANA, MARLOUS GOMES; STRAUSS, BRYAN E.. Improving adenoviral vectors and strategies for prostate cancer gene therapy. Clinics, v. 73, p. 7-pg., . (12/05066-7, 11/21256-8, 16/18197-3, 13/25167-5, 15/26580-9)
STRAUSS, BRYAN E.; OLIVEIRA SILVA, GISSELE ROLEMBERG; VIEIRA, IGOR DE LUNA; DUTRA CERQUEIRA, OTTO LUIZ; DEL VALLE, PAULO ROBERTO; VIEIRA MEDRANO, RUAN FELIPE; MENDONCA, SAMIR ANDRADE. Perspectives for cancer immunotherapy mediated by p19Arf plus interferon-beta gene transfer. Clinics, v. 73, p. 11-pg., . (12/05066-7, 16/18197-3, 13/09474-5, 13/25167-5, 13/16074-3, 15/26580-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
VIEIRA, Igor de Luna. Evaluation of the autocrine and paracrine effects of IFN gene therapy with adenovirus and its relationship with IFNAR1 in melanoma and microenvironment of the murine model. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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