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Effects of pituitary adenylate cyclase activating peptide (PACAP) and related peptides on human retinoblastoma Y79 cells

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Resumo(s)

Retinoblastoma is an aggressive neuroblastic tumour and, although rare, it is the most common primary intraocular malignancy of infancy and childhood. If untreated, retinoblastoma will grow and produce seeding in the eye, leading to retinal detachment, necrosis and invasion of the orbit, optic nerve, and central nervous system. Numerous clinical data indicate that retinoblastoma may be fatal. The Y79 line is the most prominent retinoblastoma cell line. It has been demonstrated that PACAP38, a neuropeptide belonging to the secretin superfamily of peptides exerts cytotoxic activity against Y79 retinoblastoma cells. In this work effects of PACAP38 and PACAP6-38 (an antagonist of mammalian PAC1 receptors) on survival of Y79 cells were compared to the action of other peptides from the secretin family, namely GLP7-36, GLP7-37 and its stable analogue, exendin-4. MTT cell viability assay and BrdU cell proliferation assay were performed to assess cytotoxic and/or antiproliferative activity for the peptides and their combinations. In some experiments the action of peptides was evaluated in the presence of sitagliptin, an inhibitor of DPP4. Moreover, for the first time, DPP4 expression at mRNA level in Y79 retinoblastoma cells was demonstrated.

Descrição

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014

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Retinoblastoma PACAP GLP Exendin Sitagliptin DPP4 MTT assay BrdU assay PCR

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