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Association of Immunotherapy with OncoTherad® (MRB-CFI-1) and Platelet-Rich Plasma in the Treatment of Chemically Induced Ovarian Cancer in Rats: Toll-like Receptor Signaling Pathway and Immune Response Profile

Grant number: 20/07898-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2021
Effective date (End): January 31, 2022
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal researcher:Wagner José Fávaro
Grantee:Daniel Henrique da Silva Santos
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Among gynecological tumors, ovarian cancer (OC) is the most lethal, responsible for the highest mortality among cancers of the female reproductive system and the fifth neoplasm that causes more deaths in women. Conventional chemotherapy drugs such as platinum / paclitaxel have several toxic effects in addition to acquired resistance to the drug during treatment. Considering the importance of the development of drugs that act as modulators of the immune system, our research group developed a nanostructured synthetic compound called OncoTherad® (MRB-CFI-1) with anti-tumor and immunological properties reported in bladder cancer of animals and humans, involving the signaling pathway for interferon mediated by Toll-like receptors (TLRs) 2 and 4. The tumor microenvironment of OC involves a complex immunosuppressive network of leukocytes and immunosuppressive mediators that favor the establishment of the tumor and its escape from the host's immune system. Given the importance of modulating immune system receptors by phosphate species and their relationship to activated platelets, our research group investigated the importance of Platelet Rich Plasma (PRP) in modulating these receptors and found that PRP exerts antitumor effects mediated by imune system. PRP still has cytoprotective effects and improves ovarian function in humans. Thus, the objective of the project is to evaluate the effects of immunotherapy with OncoTherad® and the administration of PRP, alone or in combination, in the treatment of chemically induced ovarian cancer in Fischer 344 rats. For this purpose, the possible mechanisms of action of this therapeutic association in the signaling pathway of Toll-like receptors (TLR2, TLR4, MyD88 and IRF-3) will be investigated in addition to the evaluation of the inflammatory response profile with mediators and cytokines (IL-1², TNF±, IL-6 and TGF-²). The combination of OncoTherad® and PRP can support the development of a new drug and thus another therapeutic alternative for OC.

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