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Project: Diagnostic and prognostic value of the dioxin receptor pathway in the progression of melanoma and glioma in Cuba

Global Noncommunicable Diseases Intiatives

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Public Universities
The dioxin receptor AhR is a transcription factor of the bHLH family that mediates toxicity and carcinogenesis. However, studies carried out in recent years in both in vitro and in vivo systems have shown that AhR plays an important role in cellular homeostasis. Thus, AhR participates in the control of cell proliferation and differentiation, in the regulation of TGF activity and in vascular development. AhR also modulates cell migration and recent data from our group show its role in adhesion, migration, epithelial-mesenchymal transition (EMT) and in tumor metastasis. This project is based on three basic premises: (i) AhR has a tumor suppressive role in melanoma cells and in acute lymphoblastic leukemia (ALL); (ii) However, stromal AhR promotes and maintains growth and metastasis in melanoma models; (iii) Human melanomas express reduced levels of AhR with respect to Nevus; (iv) Human glioblastomas show hypermethylation of the AhR promoter and, in general, reduced levels of this protein. In this project we set out to investigate the AhR-dependent pathway in the progression of melanoma in a sample of the Cuban population, in which this tumor type shows a significant incidence. At the same time we will analyze its relevance in glioma given that AhR also exerts suppressive function. The objectives of this project are: (1) To study the expression patterns of AhR in biopsies of melanoma patients with respect to nevus and glioma with respect to astrocytoma; (2) Study changes in the levels of Slug / Snail co-regulators and functionally related proteins HIF-1 and HIF-1, caveolin1 and integrin 1; (3) Analyze epigenetic changes in the promoter region of AhR and genes of its route involved in the progression of these tumors (MGMT, MDM2, MAPK13, miR-18b); (4) Determine the association between metastatic phenotype and the expression of pluripotency genes (Sox2, Oct4, Klf4, c-Myc); (5) Obtaining a profile of molecular alterations in the Cuban population that serves to design a protocol of diagnostic and prognostic utility.. This project was identified by RTI International for their own research purposes and some fields do not align with The GO Map categories. End dates were estimated as one year after the start date. The Project Type "Research, Clinical" may not accurately describe this project's focus but was used for all RTI International's Global Noncommunicable Diseases Initiative projects added in June 2018. Specialties were not analyzed. All project funding was valued in 2015 USD.

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