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Differentiating the effects of epithelial from the neural serotoninergic signalling during inflammation-related colon cancer

Grant number: 14/06428-5
Support type:Research Grants - Young Investigators Grants
Duration: February 01, 2015 - January 31, 2019
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Vinicius Kannen Cardoso
Grantee:Vinicius Kannen Cardoso
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers:Sergio Akira Uyemura
Associated scholarship(s):18/03668-6 - Development of transgenic mouse strains to study neuroendocrine changes and colon tumors, BP.TT
17/09432-1 - Intestinal serotoninergic activity modulates the intensity of DNA damage, BP.IC
17/01260-7 - Effects of colonic serotonergic activity on DNA damage inducing carcinogenesis colon, BP.MS
+ associated scholarships 16/12619-3 - Serotonin epithelial synthesis impacts on the development of colon carcinogenesis, BP.MS
15/08767-4 - Modulating the serotonin synthesis with a carcinogen during the colon carcinogenesis, BP.IC
15/01723-1 - Differentiating the effects of epithelial from the neural serotonergic signalling during the development of colon carcinogenesis, BP.JP - associated scholarships

Abstract

Serotonin is a neurohormone with one of the most complex activity in humans and other animals. It modulates apetite, peristalsis, sleep, learning, memory, mood, growth, aging, reproduction, among many other events. Novel evidence suggests that the source of serotonin (5-HT; either epithelial or neural) expression is most important for the establishment of inflammatory bowel disease. Although 5-HT is generally thought to promote colon tumors, recent evidence argues that suppressing the colonic 5-HT levels enhances preneoplastic lesions in carcinogenic models, whereas the endogenous upregulation of its levels reduces such events in the colon. Moreover, inflammation is one of the leading events driving colon carcinogenesis. Of paramount importance is establishing how the 5-HT signaling, as differentiated by its either epithelial or neural synthesis, acts on colon carcinogenesis. This will be explored in mecanistic experiments in carcinogen exposed or unexposed mice together with pharmacological treatments. Kknockout mouse models will be used to explore effects of epithelial or neural 5-HT synthesis on colon carcinogenesis. Molecular biology will be applied to investigate DNA damage-related events, such as activation or silencing of DNA-repair mechanisms. Our different experimental conditions will be further explored to uncover specific gene mutations from preneoplastic lesions to tumor manifestation. Then, pathological studies will bring together all molecular data collected throughout our study. This will mechanistically provide new insights on how the serotoninergic system modulates molecular signaling cascades driving the colon carcinogenesis. Our results will shed light on new mechanisms and potential therapeutical targets in colon cancer. (AU)

Scientific publications (6)
(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)
SAKITA, JULIANA Y.; BADER, MICHAEL; SANTOS, EMERSON S.; GARCIA, SERGIO B.; MINTO, STEFANIA B.; ALENINA, NATALIA; BRUNALDI, MARIANGELA O.; CARVALHO, MILENE C.; VIDOTTO, THIAGO; GASPAROTTO, BIANCA; MARTINS, RONALDO B.; SILVA, JR., WILSON A.; BRANDAO, MARCUS L.; LEITE, CAIO A.; CUNHA, FERNANDO Q.; KARSENTY, GERARD; SQUIRE, JEREMY A.; UYEMURA, SERGIO A.; KANNEN, VINICIUS. Serotonin synthesis protects the mouse colonic crypt from DNA damage and colorectal tumorigenesis. JOURNAL OF PATHOLOGY, v. 249, n. 1, p. 102-113, SEP 2019. Web of Science Citations: 0.
SOARES, PAULO VICTORIA; KANNEN, VINICIUS; JORDAO JUNIOR, ALCEU AFONSO; GARCIA, SERGIO BRITTO. Coffee, but Neither Decaffeinated Coffee nor Caffeine, Elicits Chemoprotection Against a Direct Carcinogen in the Colon of Wistar Rats. NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, v. 71, n. 4, p. 615-623, MAY 19 2019. Web of Science Citations: 2.
MARTIN, FRANCIS L.; MARTINEZ, EDSON Z.; STOPPER, HELGA; GARCIA, SERGIO BRITTO; UYEMURA, SERGIO AKIRA; KANNEN, VINICIUS. Increased exposure to pesticides and colon cancer: Early evidence in Brazil. Chemosphere, v. 209, p. 623-631, OCT 2018. Web of Science Citations: 2.
KANNEN, VINICIUS; SAKITA, JULIANA Y.; CARNEIRO, ZUMIRA A.; BADER, MICHAEL; ALENINA, NATALIA; TEIXEIRA, REGINA R.; DE OLIVEIRA, ENIO C.; BRUNALDI, MARIANGELA O.; GASPAROTTO, BIANCA; SARTORI, DANIELA C.; FERNANDES, CLEVERSON R.; SILVA, JOAO S.; ANDRADE, MARCUS V.; SILVA, WILSON A.; UYEMURA, SERGIO A.; GARCIA, SERGIO B. Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence. Digestive Diseases and Sciences, v. 63, n. 6, p. 1473-1484, JUN 2018. Web of Science Citations: 1.
UYEMURA, SERGIO AKIRA; STOPPER, HELGA; MARTIN, FRANCIS L.; KANNEN, VINICIUS. A Perspective Discussion on Rising Pesticide Levels and Colon Cancer Burden in Brazil. FRONTIERS IN PUBLIC HEALTH, v. 5, OCT 16 2017. Web of Science Citations: 3.
SAKITA, JULIANA YUMI; GASPAROTTO, BIANCA; GARCIA, SERGIO BRITTO; UYEMURA, SERGIO AKIRA; KANNEN, VINICIUS. A critical discussion on diet, genomic mutations and repair mechanisms in colon carcinogenesis. Toxicology Letters, v. 265, p. 106-116, JAN 4 2017. Web of Science Citations: 7.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.