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Effect of Amblyomin-X at interface of the immune system and hemostasis during progression RENCA tumor (murine renal cell carcinoma): in vivo and in vitro

Grant number: 12/06944-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2012
Effective date (End): December 31, 2015
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Ana Marisa Chudzinski-Tavassi
Grantee:Jean Gabriel de Souza
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated scholarship(s):14/23493-5 - Immunogenic activity by Amblyomin-X in human t lymphocytes, BE.EP.DR


Cancer cells are from a normal cell that has changed in their gene expression may lead to the development of the malignant phenotype. The tumor microenvironment, composed of tumor cells, extracellular matrix, fibroblasts, immune cells and endothelial cells has a decisive role in the genesis and progression of cancers, making it essential to understand the signaling pathways involved for this disease process.Described in the literature is the importance of mediators and cellular effectors of inflammation in the tumor microenvironment, favoring or inhibiting tumor development. This inflammatory process, it is known that macrophages and B-1 cells present in the peritoneal cavity have a major activity on tumor formation. Therefore, depending on the context, inflammatory cells may have beneficial role and / or harmful, being involved in the pathogenesis of several diseases, including cancer.Moreover, the presence of an inflammatory microenvironment, production of aberrant proteins and necrosis associated with tumorigenesis, can trigger disturbances in the hemostatic system, triggering changes in coagulation and inducing a prothrombotic phenotype.The tumor immunogenicity RENCA has low to moderate and can be injected into the orthotopic site, making it highly vascularized during its growth, can locally invade and form metastases in regional lymph nodes, lungs and liver. This tumor is progressive development, similar to that described for human renal cancer, allowing it to be considered one of the main models for evaluation of chemical and immunotherapeutic approaches to the treatment of kidney cancer.Recently, our laboratory was obtained in a recombinant protein originating from the salivary gland of the tick Amblyomma cajennense, designated Amblyomin-X. Our data showed that this protein induces apoptosis in various tumor cells. In addition, the protein possesses anticoagulant activity by inhibiting blood coagulation FXa.Compared to the results shown by the action of Amblyomin-X suggests that the protein may somehow be modulating the immune response in the "clearance" of the tumor microenvironment and helping to reduce the formation of metastases.Thus, objectives of this project are: a) characterize the action of Amblyomin-X in the population profile of peritoneal cells of mice with metastasis of Renca tumor and secretory activity b) investigating the secretory activity of adherent peritoneal cells co-cultured with tumor cell line differences, c) characterize survival and pattern of tumor metastases after nephrectomy and RENCA 10 days of treatment with Amblyomin-X d) evaluate the effect of Amblyomin-X on various coagulation parameters in the model in vivo, and e) Determine the pattern of immune response against the tumor, and treatment with Amblyomin-X, emphasizing the role of dendritic cells, macrophages and subpopulations of T lymphocytes

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Scientific publications
(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)
DE SOUZA, JEAN GABRIEL; MORAIS, KATIA L. P.; ANGLES-CANO, EDUARDO; BOUFLEUR, PAMELA; DE MELLO, EVANDRO SOBROZA; MARIA, DURVANEI AUGUSTO; TAEMI ORIGASSA, CLARICE SILVIA; ZAMPOLLI, HAMILTON DE CAMPOS; SARAIVA CAMARA, NIELS OLSEN; BERRA, CAROLINA MARIA; et al. Promising pharmacological profile of a Kunitz-type inhibitor in murine renal cell carcinoma model. ONCOTARGET, v. 7, n. 38, p. 62255-62266, . (13/07467-1, 15/50040-4, 12/02270-2, 12/06944-8, 10/07958-7)
PAVON, LORENA FAVARO; CAPPER, DAVID; SIBOV, TATIANA TAIS; CAMINADA DE TOLEDO, SILVIA REGINA; THOMALE, ULRICH-W.; DE SOUZA, JEAN GABRIEL; CABRAL, FRANCISCO ROMERO; BERRA, CAROLINA MARIA; SILVA DA COSTA, MARCOS DEVANIR; NICACIO, JARDEL MENDONCA; et al. New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X. SCIENTIFIC REPORTS, v. 9, . (12/06944-8)
DREWES, C. C.; DIAS, R. Y.; BRANCO, V. G.; CAVALCANTE, M. F.; SOUZA, J. G.; ABDALLA, D. S. P.; CHUDZINSKI-TAVASSI, A. M.; FARSKY, S. H. P.. Post-transcriptional control of Amblyomin-X on secretion of vascular endothelial growth factor and expression of adhesion molecules in endothelial cells. Toxicon, v. 101, p. 1-10, . (09/08584-6, 13/07467-1, 12/06944-8, 10/19802-1)

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