Histophatological and Molecular Analysis of P-MAPA Immunotherapy with Tamoxifen in Chemically Induced Breast Cancer Progression in Sprague-Dawley Rats.

• Grant number: 13/15060-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2013
• End date: November 30, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Luís Fernando Barbisan
• Grantee: Joyce Regina Zapaterini Rossi
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The breast cancer has diverse natural history, complex histology, and its incidence has been increased in the last decades. Actually, there are few treatments against hormone-dependent breast cancer and the drugs commonly used generate serious side effects. The immunotherapy represents a new perspective to cancer treatment and researches about the role of toll-like receptors in carcinogenesis have been increased. In this context, P-MAPA is an important immunomodulatory, which has effectively demonstrated antitumor activity by increasing cytokines expression and by stimulating lymphocytes and toll-like receptors.This study aims to characterize and compare the histophatological, molecular and biochemical effects of P-MAPA immunotherapy with estrogenic receptor blockade (Tamoxifen) in the treatment of breast cancer mouse model. For this purpose, female mouse Sprague-Dawley will be distributed in six experimental groups: the groups 1-4 will receive a single dose i.p of N-metil-N-nitrosoureia (MNU) (50 mg/kg) carcinogen in the first experimental week, while the groups 5 and 6 will receive a single dose i.p of MNU (NaCl 0,9%) vehicle. Then, the groups 1 and 6 will receive the P-MAPA and Tamoxifen vehicles, while the groups 2 and 5 will receive P-MAPA doses i.p (5,0 mg/kg, 3x/week) and vehicle doses of Tamoxifen (5x/week) during the fifteen experimental weeks. The group 3 will receive Tamoxifen doses s.c (5,0 mg/kg, 5x/week) and P-MAPA vehicle (3x/week) and the group 4 will receive P-MAPA doses i.p (5,0 mg/kg, 3x/week) and Tamoxifen doses (5x/week) during the fifteen experimental weeks.The animals will be euthanized at the end of the 15th. week. The normal mamary and tumoral tissues, spleen, liver and kidneys will be removed and subjected to histophatological, immunohistochemical, biochemical and molecular analysis (MALDI-Imaging and Western Blotting). The present study aims to contribute to the achievement of advanced and fundamental researches as well as to provide integration between researches from different areas and institutions.

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)

DA SILVAA, FLAVIA R. M.; GRASSI, TONY F.; ZAPATERINI, JOYCE R.; BIDINOTTO, LUCAS T.; BARBISAN, LUIS F.. Early-in-life dietary zinc deficiency and supplementation and mammary tumor development in adulthood female rats. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 44, p. 71-79, JUN 2017. (12/13004-1, 13/15060-9)

Academic Publications

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

ROSSI, Joyce Regina Zapaterini. Histophatological and molecular analysis of P-MAPA immunotherapy with tamoxifen in chemically induced breast cancer progression in Sprague-Dawley rats. 2017. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.