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Abstract(s)
A presente dissertação encontra-se divida em 3 capítulos que compreendem
respetivamente a minha experiência profissionalizante nas vertentes de investigação,
farmácia hospitalar e farmácia comunitária, respetivamente.
O primeiro capítulo intitula-se “Efeito do silenciamento do gene STEAP1 em células
LNCaP submetidas ao tratamento com apalutamida e paclitaxel” e foi realizado no
âmbito da componente de investigação, sob orientação do Professor Doutor Cláudio
Jorge Maia Baptista e da Doutora Sandra Catarina Moreira Rocha. O Six
Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) é um oncogene
associado à progressão e agressividade do cancro da próstata (CaP), embora a sua
relação com a sinalização do recetor de androgénio ainda não tenha sido elucidada. Os
fármacos anti-androgénios, como a apalutamida, são as terapias farmacológicas padrão
para o tratamento do CaP não-metastático. Por outro lado, os fármacos antineoplásicos à base de taxano, como o paclitaxel, têm sido investigados no tratamento
do CaP, nomeadamente para o desenvolvimento de terapias combinadas para melhoria
da eficácia terapêutica. O presente estudo teve como objetivo avaliar se o silenciamento
do gene STEAP1 pode tornar as células de CaP mais sensíveis a estes fármacos. Para a
concretização do objetivo, as células LNCaP -Wild Type (LNCaP-WT) e as células
LNCaP -STEAP1 knockdown foram expostas a apalutamida e paclitaxel, tendo sido
avaliada a viabilidade e proliferação celular, bem como a apoptose. Os resultados
obtidos mostraram que o fármaco apalutamida diminui a proliferação celular e,
aumentou a apoptose quer nas células LNCaP -WT quer nas células LNCaP -STEAP1
knockdown. Os resultados com o fármaco paclitaxel, mostraram que as células LNCaP -
WT apresentaram uma proliferação reduzida, e a apoptose aumentada. No entanto, o
efeito do tratamento com paclitaxel foi invertido quando combinado com o
silenciamento do STEAP1. Para além disso, o paclitaxel parece estimular o crescimento
celular das células de CaP com silenciamento para o STEAP1. Em conclusão, este
estudo demonstrou que os níveis de expressão de STEAP1 podem influenciar a resposta
das células de CaP a fármacos quimioterápicos, indicando que o uso de utilização de
paclitaxel pode ser menos benéfico em células de CaP que apresentem níveis reduzidos
da STEAP1. O segundo capítulo é relativo ao estágio curricular em farmácia hospitalar, decorrido
no período compreendido entre 22 de fevereiro a 22 de abril de 2022 no Hospital Nossa
Senhora da Assunção de Seia sob orientação da Dra. Carmo Teixeira, e no Hospital
Sousa Martins, sob orientação do Professor Dr. Jorge Aperta. Este capítulo tem como
objetivo descrever o funcionamento, a estrutura e áreas de ação desta área da profissão
farmacêutica. Este estágio permitiu-me integrar uma equipa multidisciplinar e ter
contacto direto com a prática real.
O terceiro capítulo descreve a minha experiência durante o período de estágio
curricular em farmácia comunitária. Este estágio decorreu de 26 de abril a 19 de julho,
na Farmácia Moderna (FM), situada no concelho da Guarda, sob a orientação da
Diretora Técnica Drª. Ana Raquel Sá Morais Videira Lopes Andrade. Este capítulo visa
descriminar as diferentes atividades desenvolvidas em contexto de farmácia
comunitária, com base no enquadramento ético, legal e financeiro, assim como,
sublinhar a importância do papel do farmacêutico comunitário na prática real.
This dissertation is divided into three chapters, which cover my professional experience in research, hospital pharmacy and community pharmacy, respectively. The first chapter is entitled "Effect of STEAP1 gene silencing in LNCaP cells treated with apalutamide and paclitaxel" and was carried out as part of the research component, under the supervision of Professor Cláudio Jorge Maia Baptista and Doctor Sandra Catarina Moreira Rocha. The Six Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is an oncogene associated with the progression and aggressiveness of prostate cancer (PCa), although its relationship with androgen receptor signalling remains to be elucidated. Anti-androgen drugs, such as apalutamide, are the standard pharmacological therapies for the treatment of non-metastatic PCa. On the other hand, taxane-based antineoplastic drugs, such as paclitaxel, have been investigated in the treatment of PCa, particularly for the development of combined therapies with improved therapeutic efficacy. The aim of this study was to evaluate whether silencing STEAP1 can make PCa cells more sensitive to these drugs. To this end, LNCaP -Wild Type (LNCaP-WT) cells and LNCaP -STEAP1 knockdown cells were exposed to apalutamide and paclitaxel, and cell viability, proliferation and apoptosis were assessed. The results showed that the apalutamide drug decreased cell proliferation and increased apoptosis of LNCaP -WT and LNCaP -STEAP1 knockdown cells. The results with the paclitaxel drug showed that LNCaP -WT cells showed reduced proliferation, while apoptosis increased. However, the effect of paclitaxel treatment was reversed when combined with STEAP1 silencing. Furthermore, paclitaxel can stimulate cell growth in STEAP1-silenced PCa cells. In conclusion, this study has shown that STEAP1 expression levels can influence the response of PCa cells to chemotherapeutic drugs, indicating that the use of paclitaxel may have harmful effects on PCa cells. The second chapter relates to the curricular internship in hospital pharmacy, which took place between 22 February and 22 April 2022 at Nossa Senhora da Assunção Hospital in Seia, under the supervision of Dr Carmo Teixeira, and at Sousa Martins Hospital, under the supervision of Professor Dr Jorge Aperta. The aim of this chapter is to describe the functioning, structure and areas of action of this pharmaceutical area. This internship allowed me to join a multidisciplinary team and have direct contact with real practice. The third chapter describes my experience during my curricular internship in community pharmacy. This internship took place from 26 April to 19 July at Farmácia Moderna (FM), located in Guarda, under the supervision of Technical Director Dr Ana Raquel Sá Morais Videira Lopes Andrade. This chapter aims to describe the different activities carried out in a community pharmacy context, based on the ethical, legal and financial framework, as well as emphasising the importance of the community pharmacist's role in real-life practice.
This dissertation is divided into three chapters, which cover my professional experience in research, hospital pharmacy and community pharmacy, respectively. The first chapter is entitled "Effect of STEAP1 gene silencing in LNCaP cells treated with apalutamide and paclitaxel" and was carried out as part of the research component, under the supervision of Professor Cláudio Jorge Maia Baptista and Doctor Sandra Catarina Moreira Rocha. The Six Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is an oncogene associated with the progression and aggressiveness of prostate cancer (PCa), although its relationship with androgen receptor signalling remains to be elucidated. Anti-androgen drugs, such as apalutamide, are the standard pharmacological therapies for the treatment of non-metastatic PCa. On the other hand, taxane-based antineoplastic drugs, such as paclitaxel, have been investigated in the treatment of PCa, particularly for the development of combined therapies with improved therapeutic efficacy. The aim of this study was to evaluate whether silencing STEAP1 can make PCa cells more sensitive to these drugs. To this end, LNCaP -Wild Type (LNCaP-WT) cells and LNCaP -STEAP1 knockdown cells were exposed to apalutamide and paclitaxel, and cell viability, proliferation and apoptosis were assessed. The results showed that the apalutamide drug decreased cell proliferation and increased apoptosis of LNCaP -WT and LNCaP -STEAP1 knockdown cells. The results with the paclitaxel drug showed that LNCaP -WT cells showed reduced proliferation, while apoptosis increased. However, the effect of paclitaxel treatment was reversed when combined with STEAP1 silencing. Furthermore, paclitaxel can stimulate cell growth in STEAP1-silenced PCa cells. In conclusion, this study has shown that STEAP1 expression levels can influence the response of PCa cells to chemotherapeutic drugs, indicating that the use of paclitaxel may have harmful effects on PCa cells. The second chapter relates to the curricular internship in hospital pharmacy, which took place between 22 February and 22 April 2022 at Nossa Senhora da Assunção Hospital in Seia, under the supervision of Dr Carmo Teixeira, and at Sousa Martins Hospital, under the supervision of Professor Dr Jorge Aperta. The aim of this chapter is to describe the functioning, structure and areas of action of this pharmaceutical area. This internship allowed me to join a multidisciplinary team and have direct contact with real practice. The third chapter describes my experience during my curricular internship in community pharmacy. This internship took place from 26 April to 19 July at Farmácia Moderna (FM), located in Guarda, under the supervision of Technical Director Dr Ana Raquel Sá Morais Videira Lopes Andrade. This chapter aims to describe the different activities carried out in a community pharmacy context, based on the ethical, legal and financial framework, as well as emphasising the importance of the community pharmacist's role in real-life practice.
Description
Keywords
Apalutamida Cancro da Próstata Farmácia Comunitária Farmácia Hospitalar Lncap Paclitaxel Steap1