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Estágio de natureza profissional: neuropatia periférica induzida por quimioterapia
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Abstract(s)
O cancro é um dos principais responsáveis pelo número de óbitos nos países desenvolvidos, a deteção precoce é imprescindível para aumentar as probabilidades de tratamento e sobrevida. As células cancerígenas têm um elevado potencial metabólico e de sobrevida, afetando por vezes os tecidos e órgãos nas proximidades, à medida que a doença progride ocorrem mutações que originam uma heterogeneidade tumoral, sendo necessário haver várias abordagens terapêuticas para auxiliar todos os doentes. Até ao momento, a quimioterapia continua a ser o modelo standard. Os fármacos quimioterapêuticos são agentes citotóxicos, causando efeitos colaterais, sendo o Paclitaxel (PTX) o anticancerígeno mais utilizado para tumores sólidos. O PTX provoca degeneração axonal, manifestando-se em forma de dor neuropática, conhecida Neuropatia Periférica Induzida por Quimioterapia (CIPN), manifestando-se com sintomas sensoriais como sensibilidade em relação à pressão, dor, temperatura, toque e sensação de formigueiro nos pés e mãos. A CIPN afeta quase 70% dos indivíduos ao fim de um mês de quimioterapia e perdura em 1/3 após 6 meses. Infelizmente, ainda não existe um tratamento nem um coadjuvante para a quimioterapia que seja neuroprotetor e impeça que este processo se inicie. Assim, a proposta científica do presente estágio tem por base a comparação de compostos S4UR1 e S4UR2 à baseline terapêutica do PTX com o intuito de verificar a possibilidade destas moléculas serem coadjuvantes para a quimioterapia, com o objetivo de mitigar e/ou prevenir o desenvolvimento da CIPN. Recorrendo a uma abordagem técnica multidisciplinar de cultura de células, com células cancerígenas (MCF-7) e fibroblastos dérmicos humanos adultos e técnicas de biologia molecular (western-blotting), é possível a validação da adequação dos compostos, assegurando a eficácia do tratamento anticancerígeno basal. Através da análise dos resultados de citotoxicidade é possível comprovar que os compostos não afetam a baseline terapêutica do PTX e que podem ser co-adjuvantes para a quimioterapia, no entanto será necessário aumentar a complexidade do estudo e avaliar a citotoxicidade dos compostos em co-culturas. Para uma maior validação através das técnicas de Western-blotting, será necessário aumentar o N do nosso estudo e fazer a análise completa dos canais de sódio dependentes da voltagem (Nav) que estão associados ao processo de dor neuropática, tal como o Nav 1.7, Nav 1.8 e Nav 1.9.
ABSTRACT: Cancer is one of the main causes of death in developed countries and early detection is essential to increase the chances of treatment and survival. Cancer cells have a high metabolic and survival potential, sometimes affecting nearby tissues and organs. As the disease progresses, mutations occur that give rise to tumor heterogeneity, requiring various therapeutic approaches to help all patients. To date, chemotherapy remains the standard model. Chemotherapeutic drugs are cytotoxic agents, that cause side effects, with Paclitaxel being the most widely used anticancer drug for solid tumors. PTX causes axonal degeneration, manifesting itself in the form of neuropathic pain, known as Chemotherapy-Induced Peripheral Neuropathy (CIPN), manifesting itself with sensory symptoms such as sensitivity to pressure, pain, temperature, touch and tingling sensations in the feet and hands. CIPN affects almost 70% of individuals after one month of chemotherapy and persists in 1/3 after 6 months. Unfortunately, there is still no treatment or adjunct to chemotherapy that is neuroprotective and prevents this process from starting. Thus, the scientific proposal of this internship is based on the formulation of compounds S4UR1 and S4UR2 as coadjuvants for chemotherapy and to mitigate and prevent the development of CIPN. Using a multidisciplinary technical approach of cell culture with cancer cells (MCF-7) and adult human dermal fibroblasts and molecular biology techniques (western blotting), it is possible to validate the suitability of the compounds, ensuring the efficacy of the baseline anticancer treatment. By analyzing the cytotoxicity results, it is possible to prove that the compounds do not affect the therapeutic baseline of PTX and that they can be co-adjuvants for chemotherapy. However, it will be necessary to increase the complexity of the study and evaluate the cytotoxicity of the compounds in cocultures. For further validation using molecular biology techniques, it will be necessary to increase the N of our study and carry out a complete analysis of the voltage-dependent sodium channels (Nav) that are associated with the neuropathic pain process, such as Nav 1.7, Nav 1.8, and Nav 1.9.
ABSTRACT: Cancer is one of the main causes of death in developed countries and early detection is essential to increase the chances of treatment and survival. Cancer cells have a high metabolic and survival potential, sometimes affecting nearby tissues and organs. As the disease progresses, mutations occur that give rise to tumor heterogeneity, requiring various therapeutic approaches to help all patients. To date, chemotherapy remains the standard model. Chemotherapeutic drugs are cytotoxic agents, that cause side effects, with Paclitaxel being the most widely used anticancer drug for solid tumors. PTX causes axonal degeneration, manifesting itself in the form of neuropathic pain, known as Chemotherapy-Induced Peripheral Neuropathy (CIPN), manifesting itself with sensory symptoms such as sensitivity to pressure, pain, temperature, touch and tingling sensations in the feet and hands. CIPN affects almost 70% of individuals after one month of chemotherapy and persists in 1/3 after 6 months. Unfortunately, there is still no treatment or adjunct to chemotherapy that is neuroprotective and prevents this process from starting. Thus, the scientific proposal of this internship is based on the formulation of compounds S4UR1 and S4UR2 as coadjuvants for chemotherapy and to mitigate and prevent the development of CIPN. Using a multidisciplinary technical approach of cell culture with cancer cells (MCF-7) and adult human dermal fibroblasts and molecular biology techniques (western blotting), it is possible to validate the suitability of the compounds, ensuring the efficacy of the baseline anticancer treatment. By analyzing the cytotoxicity results, it is possible to prove that the compounds do not affect the therapeutic baseline of PTX and that they can be co-adjuvants for chemotherapy. However, it will be necessary to increase the complexity of the study and evaluate the cytotoxicity of the compounds in cocultures. For further validation using molecular biology techniques, it will be necessary to increase the N of our study and carry out a complete analysis of the voltage-dependent sodium channels (Nav) that are associated with the neuropathic pain process, such as Nav 1.7, Nav 1.8, and Nav 1.9.
Description
Mestrado em Tecnologias Clínico-Laboratoriais
Keywords
Neuropatia periférica Quimioterapia CIPN Paclitaxel S4UR1 S4UR2 Peripheral neuropathy Chemotherapy MTCL
Citation
Borralho MS. Estágio de natureza profissional: neuropatia periférica induzida por quimioterapia [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2024.
Publisher
Instituto Politécnico de Lisboa