Scholarship 23/17908-7 - Carcinoma medular de tiroide, Resposta imune - BV FAPESP
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TRANSCRIPTOMIC PROFILE ANALYSIS OF THE IMMUNOLOGICAL MICROENVIRONMENT IN PATIENTS WITH MEDULLARY THYROID CARCINOMA: FROM THE LABORATORY TO CLINICAL APPLICATION.

Grant number: 23/17908-7
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date until: May 01, 2024
End date until: April 30, 2025
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Lucas Leite Cunha
Grantee:Kauê Ramon Gandolphi
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:21/02752-6 - Multiple Endocrine Neoplasia type 2 (MEN 2) and Medullary Thyroid Carcinoma (TCM): new issues in developmental biology, genetics, immunology, epidemiology, mechanisms of disease and clinical management, AP.TEM

Abstract

This project is part of the Thematic Project contemplated by FAPESP (2021/02752-6). Medullary thyroid carcinoma (MTC) is a tumor originated from calcitonin-secreting C cells. When associated with Multiple Endocrine Neoplasia type 2 (MEN2) results from germline mutations in proto-oncogene RET, located on chromosome 10q11.2. Some characteristics observed in individuals with MTC and MEN2 may predict the aggressiveness of the clinical picture and assist in determining the prognosis. However, the clinical and molecular repertoire still lack more accurate predictors of clinical prognosis. The aim of this project is to evaluate the gene expression profile of tumor infiltrating lymphocytes present in different topographies of the tumor microenvironment of patients with MTC. This study is a translational study that aims to unravel the mechanisms by which immune cells interact in the composition of the tumor microenvironment of MTC. Therefore, we will study a few patients, but each of them more deeply. We will include 50 patients with MTC. Samples of these 50 patients will be obtained including tissues preserved in paraffin. From this material, we will make a critical evaluation of the tumor microenvironment. The investigation of the immunological profile of the microenvironment will be made by immunohistochemical techniques, according to preliminary data. We will complement the phenotypic evaluation of immune cells through the GeoMx Digital Spatial Profiling (GeoMx DSP) spatial transcriptomic analysis technique. Tissue analysis will be made from biological materials collected from selected patients. The samples fixed in formalin and embedded in paraffin (FFPE) will be subjected to analysis by means of tests using NanoString technology GeoMx DSP in the Multidisciplinary Laboratory of Spatial Multiomics (LMME) located at EPM-UNIFESP contemplated by FAPESP (2022/11571-8). We believe that this may bring new prognostic markers that help in the individualization of the clinical management of patients with MTC, in addition to being able to bring up therapeutic targets in patients with MTC.

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