ffects of P-MAPA Immunotherapy Associated with Gemcitabine on Chemically-Induced Pancreatic Cancer in Animal Model: New Therapeutic Perspective

Author(s)

Favaro, Wagner J. ^[1] ; dos Santos, Mariana M. ^[1] ; Pereira, Maisa M. ^[1] ; Garcia, V, Patrick ; Duran, Nelson ^{[2, 3]}

Affiliation

^[1] Univ Campinas UNICAMP, Dept Struct & Funct Biol, Lab Urogenital Carcinogenesis & Immunotherapy, Campinas, SP - Brazil

^[2] Fed Univ ABC UFABC, Nanomed Res Unit NANOMED, Santo Andre, SP - Brazil

^[3] Garcia, Patrick, V, Univ Campinas UNICAMP, Dept Struct & Funct Biol, Lab Urogenital Carcinogenesis & Immunotherapy, Campinas, SP - Brazil

• Document type: Journal article
• Source: BIOINTERFACE RESEARCH IN APPLIED CHEMISTRY; v. 12, n. 6, p. 7540-7555, DEC 2021.
• Web of Science Citations: 0

Abstract

Pancreatic cancer is one of the most aggressive tumors since it accounts for approximately 5% of cancer-related deaths worldwide. Immunotherapy based on compounds capable of acting as toll-like receptor (TLRs) agonists may be a valuable strategy to treat cancer, either alone or in association with prevailing therapies. Thus, P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) has emerged as a likely candidate to treat some cancer types, such as pancreatic cancer (PC). The current study reports the effects of an emerging alternative therapy against PC, which lies in associating P-MAPA immunotherapy with gemcitabine-based chemotherapy to treat PC in murine models. Besides, the study reports the potential mechanisms of action of this new therapeutic association involving the TLR4 signaling pathway. PC chemically induced in animal model based on 7,12-dimethylbenz(a)anthracene carcinogen administered by thermosensitive copolymer effectively induced pancreatic tumors in 100% of the investigated rats. P-MAPA-based immunotherapy application alone has shown histopathological repair in 40% of rats, whereas those only treated with gemcitabine have shown 100% of malignant tumors. P-MAPA/Gemcitabine-associated treatment was highly effective in reducing neoplastic lesion progression and enabling histopathological improvement in 80% of the investigated rats. P-MAPA and P-MAPA/Gemcitabine treatments led to increased TLR4 protein contents, which led to increased interferon signaling pathways and positive antitumor effectiveness due to suppressed abnormal cell proliferation. Thus, it is a possible conclusion that the P-MAPA immunotherapy/gemcitabine association had a positive effect on murine models with PC and that it may be a valuable alternative to treat this tumor type. (AU)

• FAPESP's process: 12/20706-2 - New therapeutic strategies for non-muscle invasive bladder cancer: effects of BCG and P-mapa immunotherapies on the steroid hormone receptors and reactive oxygen species
• Grantee: Wagner José Fávaro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/05726-4 - Oxidative Stress, Antioxidant Enzyme Activities and Toll-Like Receptors 2 and 4 Signaling Pathway in Urinary Bladder Cancer Progression of Rats Submitted to Bacillus Calmette-Guerin and P-MAPA Intravesical Immunotherapies.
• Grantee: Fábio Rodrigues Ferreira Seiva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/11866-1 - Mechanisms and effects of the immunomodulator P-MAPA in the treatment of prostate cancer and non-muscle invasive bladder cancer: interfaces between energy metabolism, oxidative balance, angiogenesis and signaling pathway of toll-like receptors
• Grantee: Petra Karla Böckelmann
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/13585-4 - EFFECTS OF INTRAVESICAL IMMUNOTHERAPIES WITH BCG AND P-MAPA ON SEXUAL STEROID HORMONES RECEPTORS AND REACTIVE OXYGEN SPECIES: POTENTIAL THERAPEUTIC STRATEGIES FOR URINARY BLADDER CANCER
• Grantee: Patrick Vianna Garcia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral