Cholangiocarcinoma in association with MicroRNAs Involved in Tumorigenesis in Patients and their Relation to the Effect of Radiotherapy with Iodine131 on in vitro and in vivo Models

• Grant number: 18/00356-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2018
• End date: August 31, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Dorotéia Rossi Silva Souza
• Grantee: Maria Clara Jessica Calastri
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Introduction - Cholangiocarcinoma (CC) is the second most common type of primary liver cancer. Sodium and iodine pump (NIS) is the subject of research for the treatment of cancer, including CC presenting endogenous suppression of this transporter. In this context, metabolic radiotherapy using Iodine 131 (I131) may be an option for the treatment of CC, which needs clarification. Objectives: To evaluate the expression of microRNAs involved in oncogenesis (NIS, vascular endothelial growth factor A (VEGF-A), hypoxia-induced factor (HIF), phosphatidylinositol-4-5 biphosphate 3-kinase (PIK3CA), and phosphatase And PTEN) in patients with CC and its relation to radiotherapy with I131 in in vitro and in vivo models. Methodology - We will study 60 patients with CHD (30 intra and 30 extra hepatic) and 60 control subjects without clinical and biochemical signs of the disease, both groups will be submitted to a questionnaire for anthropometric, clinical and biochemical profile, as well as blood sample collection peripheral. Expression of said miRNAs will be analyzed in peripheral blood of patients with CC and controls, as well as intrahepatic and extrahepatic human CC cell lines and cholangiocytes before and after 5, 30, 60, 90 and 120 minutes of incubation with I131, in addition to tumor tissue from 20 DC RNU mice, including those exposed to I131 and controls. Expression analyzes of miRNAs will be performed by reverse transcription polymerase chain reaction (RT-qPCR). The data will be analyzed statistically, according to the characteristics of the variables, assuming a level of significance for P value <0.05.

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)

CALASTRI, M.; FERREIRA, R.; JORDAO, P.; JUNIOR, S.; SPINOLA, L.; TENANI, G.; VIEIRA, G.; NAPOLI, L.; ZANOVELO, E.; DE SOUZA, D.; et al. Overexpression of mir-224-3p in extrahepatic cholangiocarcinoma associated with increased dose of I131 radiotherapy: An in vitro study. Annals of Oncology, v. 33, p. 1-pg., 2022-06-01. (18/00356-3)

JORDAO, P.; FERREIRA, R.; CALASTRI, M.; JUNIOR, S.; SPINOLA, L.; TENANI, G.; VIEIRA, G.; NAPOLI, L.; ZANOVELO, E.; DE SOUZA, D.; et al. miR-145-3p subexpression, life habits and comorbidities in cholangiocarcinoma carcinogenesis pathway. Annals of Oncology, v. 33, p. 2-pg., 2022-06-01. (18/00356-3)