ABSTRACT
High-grade gliomas are relatively frequent in adults, and consist of the most malignant kind of primary brain tumor. Being resistant to standard treatment modalities such as surgery, radiation, and chemotherapy, it is fatal within 1 to 2 years of onset of symptoms. Although several gene therapy systems proved to be efficient in controlling or eradicating these tumors in animal models, the clinical studies performed so far were not equally successful. Most clinical studies showed that methodologies that increase tumor infection/transduction and, consequently confer more permanent activity against the tumor, will lead to enhanced therapeutic results. Due to the promising practical clinical benefits that can be expected for the near future, an exposition to the practicing neurosurgeon about the basic issues in genetic therapy of gliomas seems convenient. Among the main topics, we shall discuss anti-tumoral mechanisms of various genes that can be transfected, the advantages and drawbacks of the different vectors utilized, the possibilities of tumor targeting by modifications in the native tropism of virus vectors, as well as the different physical methods for vector delivery to the tumors. Along with the exposition we will also review of the history of the genetic therapy for gliomas, with special focus on the main problems found during the advancement of scientific discoveries in this area. A general analysis is also made of the present state of this promising therapeutic modality, with reference to the problems that still must be solved and the new paradigms for future research in this area.
Subject(s)
Animals , Brain Neoplasms/history , Genetic Therapy/history , Genetic Vectors/history , Glioma/history , History, 20th Century , History, 21st Century , HumansABSTRACT
O astrocitoma de células gigantes é uma variante rara das neoplasias gliais, oscilando ao redor de 2 por cento dos tumores astrocitários e frequentemente associado à esclerose tuberosa, doença hamartomatosa de caráter genético autossômico dominante. Afeta ambos os sexos de maneira semelhante, sendo mais encontrado na primeira e na segunda décadas de vida, principalmente nos ventrículos laterias e por vezes ocluindo o forame de Monro. É um tumor de crescimento lento e sobrevida longa após ressecção cirúrgica. Microscopicamente, mostrou-se composto por células grandes, globóides, de citoplasma amplo com núcleos vesiculosos e arranjo perivascular. Os autores relatam seis casos de pacientes portadores de astrocitoma de células gigantes, sendo quatro pacientes portadores de astrocitoma de células gigantes, sendo quatro pacientes portadores de esclerose tuberosa diagnosticados e registrados no Banco de Patologia Tumoral do Sistema Nervoso Central de Curitiba. Os casos estudados correspondem aos dados da literatura, auxiliando na compreesão do comportamento biológico e na correlação clínica desta neoplasia.