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Evaluation of the potential therapeutic effects of immunotherapy of the biological response modifier: inorganic phosphat complex - 1 (BRM- IPC-1) in rats with colorectal cancer chemically induced

Grant number: 17/18755-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2018
Effective date (End): April 30, 2019
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Wagner José Fávaro
Grantee:Stephanie Kussik de Almeida Leite
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Colorectal Cancer (CRC) is pointed as a global health problem, affecting 1 million people each year as well as being the second largest cause of death in women and the third in men. The carcinogenic processes are complex and multiphasic involving cellular, molecular and morphological changes, supported by changes in gene expression related to cell proliferation, differentiation and apoptosis. The chronic inflammation in the gastrointestinal tract is characterized by abnormal functioning of the epithelial barrier, with irregular increase of the absorptive capacity of the tissue and an increase in recognition of components of the microflora and their metabolic products. These events result in overstimulation of the immune system, with the consequent increase in cell recruitment, increased proliferation rate, and genetic alterations with subsequent abnormality in the immune response. Because of the different signaling pathways activated during the carcinogenic process in the CRC and the anatomical and histopathological features of the tumor (tumor infiltration level, angiogenesis, the involvement of nerves and the presence of lymph node metastases) the therapies of first choice are colectomy, radiotherapy and chemotherapy with 5-fluorouracil (5-FU). 5-FU is a chemotherapeutic of high toxicity to bone marrow and gastrointestinal (GI) tract, resulting in anemia, leukopenia, neutropenia, nausea, vomiting, mucositis and diarrhea as adverse effects. In this context, the search for new therapeutics, more effective and with reduction of adverse effects is of big importance. Among the possible therapeutic approaches, this project pretend to evaluate the modulation of imunlogical response by the Biological Response Modulator - Inorganic Phosphate Complex - 1 (BRM-IPC-1), an sintetic compound developed by the research group of Professor Wagner José Fávaro (IB - Unicamp) and Professor Nelson Eduardo Durán Caballero (IQ - Unicamp). Initial studies with this BRM-IPC-1 in non-invasive muscle bladder cancer (NIMBC) chemically induced in female Fisher 344 rats showed significative regression of tumoral lesions, indicating an important antitumoral effect of BRM-IPC-1, through interferon singalling by toll-like receptors (TLR). So, this work has the main objective to evaluate the action mechanisms of BRM-IPC-1 compound, through histopatologial and immunohistochemmical evaluation in colorectal cancer (CRC) chemically induced by 1,2- Dimethylhydrazine in male Fisher 344 lineage rats.