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Abstract(s)
Os gliomas sĂŁo os tumores cerebrais primĂĄrios mais frequentes, representando mais de 70% de todas as neoplasias do Sistema Nervoso Central. Tanto o diagnĂłstico como a classificação destes tumores sĂŁo baseados nas caracterĂsticas histopatolĂłgicas que, por vezes, sĂŁo difĂceis de definir. Apesar dos avanços na neurocirurgia, quimioterapia e radioterapia, o prognĂłstico dos doentes com gliomas continua muito reservado.
Nos Ășltimos anos, diversos estudos em gliomas identificaram marcadores moleculares de diagnĂłstico e prognĂłstico, Ășteis na definição da classificação histolĂłgica. A codeleção 1p/19q, a presença de mutaçÔes somĂĄticas em genes que codificam isocitrato desidrogenase e a hipermetilação da regiĂŁo promotora do gene MGMT sĂŁo os trĂȘs marcadores com maior relevĂąncia na atualidade.
Nas Ășltimas duas dĂ©cadas, o tratamento para os gliomas de alto grau envolveu uma abordagem multidisciplinar, que se baseava em resseção cirĂșrgica mĂĄxima, quando possĂvel, seguida de radioterapia e quimioterapia. Esta constitui a abordagem terapĂȘutica convencional, com um grande nĂșmero de ensaios clĂnicos que revelaram na sua maioria pequenas melhorias que nĂŁo sĂŁo satisfatĂłrias. Com a evolução da nanotecnologia em plena expansĂŁo, surgiram agora os primeiros estudos sobre a aplicação desta tecnologia inovadora na abordagem terapĂȘutica dos gliomas de alto grau. Novas tĂ©cnicas de diagnĂłstico e terapĂȘuticas baseadas em nanomateriais oferecem opçÔes promissoras no tratamento de gliomas malignos. No entanto, a entrega de nanopartĂculas para tumores cerebrais malignos representa um desafio devido Ă presença da barreira hemato-encefĂĄlica e Ă s cĂ©lulas tumorais infiltradas no cĂ©rebro normal que nĂŁo sĂŁo facilmente detetadas.
As nanopartĂculas magnĂ©ticas representam o nanomaterial mais promissor para direcionar a terapĂȘutica Ă s cĂ©lulas tumorais e simultaneamente obter imagens em tempo real, devido Ă s suas propriedades paramagnĂ©ticas, permitindo localizar o tumor. A conjugação de pĂ©ptidos ou anticorpos na superfĂcie destas nanopartĂculas permite o direcionamento direto Ă superfĂcie da cĂ©lula tumoral e potencial rutura das vias de sinalização ativas presentes nas cĂ©lulas tumorais. Esta conjugação de pĂ©ptidos ou anticorpos serĂĄ fulcral para permitir atingir todas as cĂ©lulas tumorais, inclusive as que nĂŁo sĂŁo detetadas nos meios convencionais de diagnĂłstico. Neste momento, encontram-se em curso numerosos estudos para permitir compreender o impacto destas nanopartĂculas magnĂ©ticas no tratamento de tumores cerebrais malignos, com especial interesse nos gliomas cerebrais de alto grau.
Gliomas are the most frequent primary brain tumors, accounting for over 70% of all neoplasms of the central nervous system. Diagnosis and classification of these tumors are based on the histopathological characteristics that are sometimes difficult to define. Despite advances in neurosurgery, chemotherapy and radiotherapy, the prognosis of patients with gliomas remains very poor. In recent years, various studies in gliomas identified molecular markers for diagnostic and prognostic, useful in defining the histological classification. The co-deletion 1p/19q, the presence of somatic mutations in genes encoding isocitrate dehydrogenase and hypermethylation of the promoter region of the MGMT gene are the three markers with greater relevance today. In the last two decades, treatment for high-grade gliomas involved a multidisciplinary approach, which was based on maximum surgical resection, when possible, followed by radiotherapy and chemotherapy. This is the conventional therapeutic approach, with a large number of clinical trials that showed mostly small improvements that are unsatisfactory. With the development of nanotechnology in full expansion, the first studies on the application of this innovative technology in the management of high-grade gliomas have emerged. Novel diagnostic and therapeutic techniques based on nanomaterials provide promising options in the treatment of malignant gliomas. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the bloodâbrain barrier and infiltrating cancer cells in the normal brain. The magnetic nanoparticles are the most promising nanomaterial to direct therapy to tumor cells and simultaneously obtain images in real time, due to its paramagnetic properties, enabling you to locate the tumor. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. This conjugation of peptides or antibodies will be crucial to enable reach all tumor cells, including those that are not detected in conventional diagnostics. At the moment, there are numerous ongoing studies to enable understanding of the impact of magnetic nanoparticles in the treatment of malignant brain tumors, with special interest in cerebral high-grade gliomas.
Gliomas are the most frequent primary brain tumors, accounting for over 70% of all neoplasms of the central nervous system. Diagnosis and classification of these tumors are based on the histopathological characteristics that are sometimes difficult to define. Despite advances in neurosurgery, chemotherapy and radiotherapy, the prognosis of patients with gliomas remains very poor. In recent years, various studies in gliomas identified molecular markers for diagnostic and prognostic, useful in defining the histological classification. The co-deletion 1p/19q, the presence of somatic mutations in genes encoding isocitrate dehydrogenase and hypermethylation of the promoter region of the MGMT gene are the three markers with greater relevance today. In the last two decades, treatment for high-grade gliomas involved a multidisciplinary approach, which was based on maximum surgical resection, when possible, followed by radiotherapy and chemotherapy. This is the conventional therapeutic approach, with a large number of clinical trials that showed mostly small improvements that are unsatisfactory. With the development of nanotechnology in full expansion, the first studies on the application of this innovative technology in the management of high-grade gliomas have emerged. Novel diagnostic and therapeutic techniques based on nanomaterials provide promising options in the treatment of malignant gliomas. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the bloodâbrain barrier and infiltrating cancer cells in the normal brain. The magnetic nanoparticles are the most promising nanomaterial to direct therapy to tumor cells and simultaneously obtain images in real time, due to its paramagnetic properties, enabling you to locate the tumor. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. This conjugation of peptides or antibodies will be crucial to enable reach all tumor cells, including those that are not detected in conventional diagnostics. At the moment, there are numerous ongoing studies to enable understanding of the impact of magnetic nanoparticles in the treatment of malignant brain tumors, with special interest in cerebral high-grade gliomas.
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Keywords
Abordagem TerapĂȘutica Gliomas de Alto Grau Marcadores Moleculares NanopartĂculas Neurocirurgia Radioterapia Temozolamida