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The link between cathepsin, HIV, apoptosis and cancer in HIV infected patiens on HAART
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A infeção pelo vírus da imunodeficiência humana (HIV) está associada ao aparecimento de diversos cancros, denominados de AIDS-defining cancers (ADCs). A terapêutica antirretroviral altamente ativa (HAART) veio mudar profundamente o cenário dos problemas oncológicos em indivíduos seropositivos, diminuindo o número de casos de ADCs e aumentando o número de non-AIDS-defining cancers (NADCs). As catepsinas são proteases que aparecem sobre-expressas em muitos cancros. Essas proteases podem induzir morte celular por apoptose dependente ou independente de caspases. O HIV altera vias apoptóticas na célula hospedeira, e parece alterar a atividade e expressão de catepsinas. Tentámos compreender se os cancros que surgem em indivíduos seropositivos a fazer HAART, têm alguma relação com as catepsinas. A revisão aponta no sentido de existir uma relação entre as catepsinas e a carcinogénese nesses indivíduos, antes e após o consumo de HAART. A HAART pode alterar a atividade e expressão das catepsinas, uma vez que parece fazê-lo para outras cisteínas. No então,
não há certezas de que estas relações existam. Entre outros estudos, sugerimos que sejam estudadas as concentrações de algumas catepsinas – nomeadamente D e B – e seus inibidores, no meio intra- e extracelular, em indivíduos infetados com HIV em diferentes fases da infeção.
The human immunodeficiency virus (HIV) is related to the appearance of several cancers, called AIDS-defining cancers (ADCs). The highly active antiretroviral therapy (HAART) has deeply changed the landscape of cancer problems in HIV-positive individuals, decreasing the number of cases of ADCs and increasing the number of non- AIDS-defining cancers (NADCs). Cathepsins are proteases that appear overexpressed in many cancers. These proteases can induce cell death by caspase-dependent or -independent apoptosis. HIV alters apoptotic pathways in the host cell and seems to alter the activity and expression of cathepsins. We tried to understand whether cancers that arise in HIV-positive individuals on HAART, are in some way related to the cathepsins. The review suggests that there is a relationship between cathepsins and carcinogenesis in HIV-infected individuals, before and after consumption of HAART. HAART can alter the activity and expression of cathepsins, since it seems to do it for other cysteines. However, there is no certainty that these relationships exist. Among other studies, we suggest that some of cathepsins concentrations - D and B -, and their inhibitors, are studied, intra- and extracellularly, in HIV infected individuals at various stages of infection.
The human immunodeficiency virus (HIV) is related to the appearance of several cancers, called AIDS-defining cancers (ADCs). The highly active antiretroviral therapy (HAART) has deeply changed the landscape of cancer problems in HIV-positive individuals, decreasing the number of cases of ADCs and increasing the number of non- AIDS-defining cancers (NADCs). Cathepsins are proteases that appear overexpressed in many cancers. These proteases can induce cell death by caspase-dependent or -independent apoptosis. HIV alters apoptotic pathways in the host cell and seems to alter the activity and expression of cathepsins. We tried to understand whether cancers that arise in HIV-positive individuals on HAART, are in some way related to the cathepsins. The review suggests that there is a relationship between cathepsins and carcinogenesis in HIV-infected individuals, before and after consumption of HAART. HAART can alter the activity and expression of cathepsins, since it seems to do it for other cysteines. However, there is no certainty that these relationships exist. Among other studies, we suggest that some of cathepsins concentrations - D and B -, and their inhibitors, are studied, intra- and extracellularly, in HIV infected individuals at various stages of infection.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014
Palavras-chave
Mestrado Integrado - 2014