INFLAMMATORY AND NITROSATIVE STRESS EVALUATION DURING TUMOR DEVELOPMENT IN HYPERGLICEMIC ENVIRONMENT

• Grant number: 16/06539-7
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2016 - April 30, 2019
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Elaine Guadelupe Rodrigues
• Grantee: Elaine Guadelupe Rodrigues
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Hugo Pequeno Monteiro

Abstract

Epidemiological studies suggest a strong correlation between the occurrence of diabetes and cancer development. Aging, obesity, diet, and a sedentary lifestyle are risk factors associated with both diseases. Hyperglycemia and inflammation have been implicated in the association of diabetes and cancer. However, how these factors influence this association is not known. With this proposal we aim to verify the effects of hyperglycemia on in vitro and in vivo development of murine breast carcinoma 4T1 and murine melanoma B16F10-Nex2. In vitro, tumor cells will be cultivated in the presence of increasing concentrations of glucose. Several parameters, namely proliferation, glucose receptors expression, cytokines secretion, and nitrosative stress factors, will be determined in tumor cells cultivated in normoglycemic and hyperglycemic conditions. Nitrosative stress factors include characterization of the main isoform of nitric oxide synthase expressed in these cells and estimation of endogenous nitric oxide levels. In preliminary studies we showed that in vivo, the hyperglycemic environment interferes with the development of both tumor models, as we observed increased tumor growth and mortality in streptozotocin-treated animals (diabetes experimental model) with increased serum glucose concentrations. Primary tumors will be collected and the same parameters described above for the in vitro studies will be determined. Furthermore, we will perform the identification and quantification of infiltrating inflammatory cells. Systemic inflammatory response will be evaluated by the identification and quantification of cell populations in spleen and draining lymph nodes. In addition, we will perform the quantification of pro- and anti-inflammatory cytokines in both sites and in sera. Finally, the effects of metformin and NOS inhibitors, isolated or in combination, as well as the silencing of the predominantly expressed NOS isoform on tumor development in vivo will be verified. (AU)

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)

CARDOSO AMORIM REIS, ADRIANA KARLA; STERN, ARNOLD; MONTEIRO, HUGO PEQUENO. S-nitrosothiols and H2S donors: Potential chemo-therapeutic agents in cancer. REDOX BIOLOGY, v. 27, n. SI, OCT 2019. (16/06539-7, 12/10470-1)

MONTEIRO, HUGO P.; RODRIGUES, ELAINE G.; AMORIM REIS, ADRIANA K. C.; LONGO, JR., LUIZ S.; OGATA, FERNANDO T.; MORETTI, ANA I. S.; DA COSTA, PAULO E.; TEODORO, ANA C. S.; TOLEDO, MAYTE S.; STERN, ARNOLD. Nitric oxide and interactions with reactive oxygen species in the development of melanoma, breast, and colon cancer: A redox signaling perspective. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 89, p. 1-13, AUG 1 2019. (16/06539-7, 13/16644-4, 12/10470-1)

CARDOSO AMORIM REIS, ADRIANA KARLA; STERN, ARNOLD; MONTEIRO, HUGO PEQUENO. S-nitrosothiols and H2S donors: Potential chemo-therapeutic agents in cancer. REDOX BIOLOGY, v. 27, p. 8-pg., 2019-10-01. (12/10470-1, 16/06539-7)