Molecular characterization of human gliomas and identification of neoplasms responsible for new biopharmaceuticals obtained from animal venom: a translational approach

• Grant number: 19/10003-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2020
• End date: October 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Catarina Raposo Dias Carneiro
• Grantee: Natália Barreto dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Gliomas correspond to approximately 80% of primary malignant brain tumors in adults. Until recently, these tumors were classified mainly on the basis of histopathological criteria; however, associating these aspects to the identification of the molecular profile of the neoplasias has been shown to be a more accurate strategy in relation to the prediction of the tumor's behavior and its responsiveness to the treatments. However, while private centers use molecular diagnostics, patients from the Sistema Único de Saúde (SUS) do not have access to these high cost exams. Added to this is the need to develop new treatments; some Gliomas, such as Glioblastoma (GBM), are highly infiltrating and aggressive and the average survival of patients is 14 to 17 months after diagnosis. Studies have increasingly shown the potential of using biopharmaceuticals in the fight against cancer. Our research group has recently shown that the poison of the spider Phoneutria nigriventer (PnV) contains molecules that reduced the survival and migration of human GBM cell lines in vitro, as well as tumor growth in a pre-clinical murine model study xenogeneic. Therefore, the present project consists in a proposal of a translational study, whose objective is to characterize, as regards molecular identity, Glioma samples collected from patients submitted to the surgical procedure at the Santa Casa de Misericórdia Hospital of São Paulo, in order to improve diagnostic methods and prognostic predictions, as well as contribute to the development of new drugs. As a result of data collection, epidemiological statistics will also be generated that will contribute to the mapping of cases of brain Cancer in the SUS, considering the capacity of this medical center to capture national cases. For the development of the study, after consent of the patients, samples of the tumors clinically diagnosed as Glioma will be collected during the surgical procedure. The material will be evaluated for the expression and detection of biomarkers already related to staging of Gliomas: the IDH1, IDH2 and ATRX proteins will be analyzed by immunohistochemistry; the molecular markers EGFR, NF1 and PDGFRA, and the O6-methylguanine-DNA methyltransferase (MGMT) repair enzyme, through the Polymerase Chain Reaction (PCR) technique; the 1p/19q codeletion will be detected by in situ hybridization (FISH). The PI3K/AKT/mTOR and RhoA/ROCK signaling pathways (both target PnV and mutated in many Gliomas) will also be analyzed by PCR. To establish new diagnostic methods, samples of Gliomas, as well as saliva collected from patients, will be analyzed by high-resolution mass spectrometry and their results will be incorporated into a database to rank the samples through Machine Learning. In parallel, part of the collected tumor will be establish by cell culture techniques to analyze its responsiveness to PnV and its purified peptides; a correlation will be made between the tumor response to the treatment and its molecular profile. Finally, once patients' information will be collected through interviews and analysis of medical records, a cross-sectional epidemiological study will be done, correlating these findings with the molecular profile of the neoplasia; it is expected to contribute with epidemiological data to clarify the profile of SUS patients diagnosed with Glioma, as well as to establish a relationship between this profile and the molecular characteristics of the tumor. (AU)

Scientific publications

(4)

(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)

BARRETO, NATALIA; RAMOS DA SILVA, MONIZE VALERIA; ALVES DA ROCHA-E-SILVA, THOMAZ AUGUSTO; SUTTI, RAFAEL; SCIANI, JULIANA MOZER; ESTEVES VEIGA, JOSE CARLOS; VERINAUD, LIANA; VITORINO ARAUJO, JOAO LUIZ; RAPOSO, CATARINA. SPIDER VENOM MOLECULES IMPAIR HUMAN GLIOMA CELLS MIGRATION: POTENTIAL APPLICATION IN CANCER THERAPY. NEURO-ONCOLOGY, v. 24, p. 2-pg., 2022-11-01. (19/10003-3)

BARRETO, NATALIA; CABALLERO, MARCUS; BONFANTI, AMANDA PIRES; PINHEIRO DE MATO, FELIPE CEZAR; MUNHOZ, JAQUELINE; DA ROCHA-E-SILVA, THOMAZ A. A.; SUTTI, RAFAEL; VITORINO-ARAUJO, JOAO LUIZ; VERINAUD, LIANA; RAPOSO, CATARINA. Spider venom components decrease glioblastoma cell migration and invasion through RhoA-ROCK and Na+/K+-ATPase beta 2: potential molecular entities to treat invasive brain cancer. CANCER CELL INTERNATIONAL, v. 20, n. 1, DEC 17 2020. (15/04194-0, 15/06134-4, 17/05402-0, 17/16196-2, 17/24331-7, 19/10003-3, 18/23559-7)

MUNHOZ, JAQUELINE; PERON, GABRIELA; BONFANTI, AMANDA PIRES; OLIVEIRA, JANINE; DA ROCHA-E-SILVA, THOMAZ A. A.; SUTTI, RAFAEL; THOME, RODOLFO; BOMBEIRO, ANDRE LUIS; BARRETO, NATALIA; CHALBATANI, GHANBAR MAHMOODI; et al. Components from spider venom activate macrophages against glioblastoma cells: new potential adjuvants for anticancer immunotherapy. JOURNAL OF BIOCHEMISTRY, v. 170, n. 1, p. 51-68, JUL 2021. (15/04194-0, 15/06134-4, 18/23559-7, 18/03051-9, 19/10003-3)

DE MATO, FELIPE CEZAR; BARRETO, NATALIA; CORDEIRO, GABRIEL; MUNHOZ, JAQUELINE; BONFANTI, AMANDA PIRES; DA ROCHA-E-SILVA, THOMAZ A. A.; SUTTI, RAFAEL; CRUZ, PRISCILLA B. M.; SANCHES, LIVIA R.; BOMBEIRO, ANDRE LUIS; et al. Isolated Peptide from Spider Venom Modulates Dendritic Cells In Vitro: A Possible Application in Oncoimmunotherapy for Glioblastoma. CELLS, v. 12, n. 7, p. 19-pg., 2023-04-01. (15/04194-0, 22/03543-4, 18/03051-9, 18/23559-7, 19/10003-3)