Effect of P-MAPA immunomodulator associated to Interleukin-12 on ovarian cancer: in vivo approaches involving the inflammatory process and immune system

• Grant number: 17/03441-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2019
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Luiz Gustavo de Almeida Chuffa
• Grantee: Henrique Spaulonci Silveira
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Ovarian cancer (OC) has the highest incidence in post-menopausal women and, due to its late diagnosis and poor prognosis, is the fifth most common cause of cancer death worldwide. OC responds initially to conventional chemotherapy, which control tumor growth and progression; however, many women develop chemoresistance linked to the inflammatory process and the disease relapse. Interleukin (IL)-12 has been administered in patients with solid tumors, including OC, in an attempt to stimulate the polarized Th1-type inflammatory response, increasing interferon-gamma (IFN-³) production. However, the impact of its anti-tumor effects is still limited to OC. The P-MAPA immunomodulator (polymeric aggregate of magnesium phospholinoleate-palmitoleate and proteinaceous ammonium - Farmabrasilis) is a biopolymer that has shown significant effects on components of the immune system, being able to stimulate Toll-like receptors (TLR2 and TLR4), production of T cells secreting cytokines (IL-2 and IFN-³) as well as promotion of increased activity of natural killer (NK) cells. Therefore, this study aim to verify the effects of P-MAPA and IL-12 as functional treatments on inflammatory process and immune system associated to OC in Fischer 344 rats. To achieve the objectives, all animals will be chemically induced for OC using the 7,12 dimetilbenzoantraceno (DMBA) as carcinogen and the combined effects of P-MAPA and IL-12 studied with the following parameters: frequency and characterization of tumor subtypes based on histopathological analysis, immunolocalization and quantification of TLR2 and TLR4 as well as immunological factors through western blot: myeloid differentiation factor (MyD88), IFN-³ inducing factor associated TIR domain (TRIF), nuclear factor related to interferon (IRF3) and nuclear factor kappaB (NF-k²) involved in the inflammatory process, measurement of the mediators of inflammatory process (pro- and anti-inflammatory cytokines, and others) in the animals's serum with OC through multiplexed assay and quantification of cells of the immune system (TCD3 +, TCD4 +, TCD8 + and Tregs) present in the OC draining lymph nodes by flow cytometry. These results may contribute to the understanding of the combined effects of P-MAPA and IL-12 on the different biological responses from the inflammatory process and OC-associated immune system. (AU)

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)

SILVEIRA, HENRIQUE SPAULONCI; LUPI, LUIZ ANTONIO; ROMAGNOLI, GRAZIELA GORETE; KANENO, RAMON; NUNES, ISEU DA SILVA; FAVARO, WAGNER JOSE; DE ALMEIDA CHUFFA, LUIZ GUSTAVO. P-MAPA activates TLR2 and TLR4 signaling while its combination with IL-12 stimulates CD4+and CD8+effector T cells in ovarian cancer. Life Sciences, v. 254, AUG 1 2020. (17/03441-9, 16/03993-9, 19/00906-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVEIRA, Henrique Spaulonci. Effect of the P-MAPA immunomodulator associated with interleukin-12 in the ovarian carcinoma of Fischer 344 rats: approach of the inflammatory process and immune system. 2020. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.