| Grant number: | 14/06428-5 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | February 01, 2015 |
| End date: | January 31, 2019 |
| Field of knowledge: | Biological Sciences - Genetics - Mutagenesis |
| Principal Investigator: | Vinicius Kannen Cardoso |
| Grantee: | Vinicius Kannen Cardoso |
| Host Institution: | Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| City of the host institution: | Ribeirão Preto |
| Associated 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 - 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)
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