| Grant number: | 16/07463-4 |
| Support Opportunities: | Regular Research Grants |
| Start date: | September 01, 2016 |
| End date: | February 28, 2019 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Erico Tosoni Costa |
| Grantee: | Erico Tosoni Costa |
| Host Institution: | Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil |
| Associated researchers: | Anamaria Aranha Camargo ; Marilene Hohmuth Lopes ; Paula Fontes Asprino ; Pedro Alexandre Favoretto Galante ; Suely Kazue Nagahashi Marie |
Abstract
Diffuse gliomas are the most common malignant primary brain tumors of adults and are highly therapy resistant. The most frequent and highly lethal variants are referred to as glioblastoma (GBM), which have a highly invasive and aggressive nature, making this class hardly treatable. Neurosurgical cure is an unattainable goal for GBM and, unfortunately, GBM continues to be uniformly fatal, regardless of treatment.Recent molecular advances, focusing on clinically relevant biomarkers and on potential molecular targets for further drug development, have contributed to a better understanding of GBM pathophysiology and disease stratification. Together, these insightful works seek to put order to the heterogeneity of GBM to give hope to the possibility of making the therapeutic approach more specific, based on the classification of gliomas into molecular subtypes. Added to this, the identification of functionally associated genes with the development and progression of gliomas, associate them with molecular classes and demonstrate its clinical relevance consist of essential challenges for the understanding of the disease and its translation into therapeutic approach. This is the general purpose of this project and the focus of study is the gene called ADAM23.The ADAM23 gene is found highly expressed in normal brain and exhibit a gradually reduced expression during glioma progression. The ADAM23 gene encodes a catalytically inactive family member of ADAM family (The Disintegrin And Metalloproteinase Family) and is often found silenced in several types of cancer. In this project we aim to study the role, the mechanisms and clinical relevance of the ADAM23 gene in the progression of gliomas by analyzing ADAM23 expression levels in primary samples of diffuse gliomas and by using small hairpin RNA (shRNA) in cellular neurospheres models of GBM and use them in vitro and in vivo assays. (AU)
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