microRNA-181d associated with the methylation status of the MGMT gene in Glioblastoma multiforme cancer stem cells submitted to treatments with ionizing radiation and temozolomide.

Despite the increased understanding of the oncological mechanisms underlying Glioblastoma multiforme (GBM) pathophysiology, and recent advances in therapeutic strategies such as maximal surgical resection and post-operative radiotherapy with concomitant and adjuvant temozolomide chemotherapy, the prognosis for patients with brain tumors remains limited. Evidences indicate that the assessment of DNA methylation status in cancer stem cells would allow identifying molecules expressed in these cells, to lead to targeted elimination of this critical population from brain tumors, making the glioblastoma treatment more effective. This study aimed to analyze the role of microRNA-181d associated with the methylation status of the O6-methylguanine methyl transferase (MGMT) gene in Glioblastoma multiforme cancer stem cells subjected to treatment with temozolomide and ionizing radiation. Such responses were analyzed in terms of cell survival, evaluation of the MGMT gene methylation status by MS-HRM (Methylation-Sensitive High Resolution Melting), and analysis of miRNA-181d and MGMT gene expression by relative quantification of mRNA levels in cancer stem cells subjected to treatment with temozolomide and ionizing radiation, isolated or combined. We showed that ionizing radiation and temozolomide reduced the viability of cancer stem cells from GBM patients, as well as modified MGMT gene and miRNA-181d expression in cancer stem cells, suggesting that miRNA-181d interferes in the glioblastoma cancer stem cell response to treatment with temozolomide and ionizing radiation.

Extra and intradural spinal Hemangioblastoma / Hemangioblastoma espinhal extra e intradural / Hemangioblastoma espinal extra e intradural

Hemangioblastomas of the central nervous system (CNS) are low-grade highly vascularized tumors that may be sporadic or associated with Von Hippel-Lindau disease. Extradural hemangioblastomas are uncommon and those located extra and intradurally are even rarer. This study uses an illustrative case and literature review to discuss the difficulties to consider the correct diagnosis and to select the best surgical approach. A 57 years-old white male patient presented with myelopathy and right C5 radiculopathy. The images showed a lobulated, hourglass shaped, highly enhanced extra/intradural lesion that occupied the spinal canal and widened the C4-C5 right intervertebral foramen. Total resection of the intradural lesion was achieved through a posterior approach, but the extradural part could only be partially removed. Complete improvement was observed after four months of follow-up and the residual tumor has been followed up clinically and radiologically. Even though the preoperative impression was of a spinal schwannoma, the histopathological examination revealed grade I hemangioblastoma as per WHO. Despite their rarity, current complementary exams allow considering the diagnosis of hemangioblastoma preoperatively. That is essential to a better surgical planning in view of the particular surgical features of this lesion.

Hemangioblastomas do sistema nervoso central são lesões de baixo grau de malignidade, altamente vascularizadas, que podem se apresentar esporadicamente ou associadas com a doença de Von Hippel-Lindau. Hemangioblastomas extradurais são incomuns e os extra e intradurais são ainda mais raros. Este estudo usa um caso ilustrativo e revisão da literatura para discutir as dificuldades de considerar o diagnóstico correto e selecionar a melhor abordagem cirúrgica. Um paciente do sexo masculino, branco, com 57 anos de idade apresentou-se com mielopatia e radiculopatia de C5 à direita. As imagens mostraram lesão extra-intradural lobulada, em forma de ampulheta, com alta impregnação após contraste, que ocupava o canal vertebral e estreitava o forame intervertebral de C4-C5 à direita. A ressecção total da lesão intradural foi alcançada através de abordagem posterior, mas a porção extradural só pôde ser parcialmente removida. Melhora total dos sintomas foi observada após quatro meses e o tumor residual tem sido seguido clínica e radiologicamente. Embora a impressão pré-operatória tenha sido de um schwannoma espinal, o exame histopatológico revelou hemangioblastoma grau I, segundo a OMS. Apesar de sua raridade, exames complementares atuais permitem o correto diagnóstico pré-operatório. Isto é essencial para melhor programação cirúrgica, tendo em vista as características particulares desta lesão.

Hemangioblastomas del sistema nervioso central (SNC) son tumores altamente vascularizados, de grado bajo, que pueden ser esporádicos o vinculados a la enfermedad de Von Hippel-Lindau. Hemangioblastomas extradurales no son comunes, y aquellos localizados extra e intraduralmente son aún más raros. Este estudio usa un caso ilustrativo y la revisión de la literatura para analizar las dificultades cuanto a considerar el diagnóstico correcto y para seleccionar el mejor abordaje quirúrgico. Un paciente, hombre blanco de 57 años de edad, presentaba mielopatía con radiculopatía C5 derecha. Las imágenes mostraban lesión extra/intradural, muy acrecentada, con forma de ampolla y lobulada, la cual ocupaba el conducto espinal y ensanchaba el agujero intervertebral derecho C4-C5. La resección de la lesión intradural fue conseguida mediante un abordaje posterior, pero la parte extradural solamente pudo ser removida parcialmente. La mejoría completa fue observada después de cuatro meses de seguimiento y el tumor residual ha sido acompañado clínica y radiológicamente. Aunque la impresión preoperatoria era de schwannoma espinal, el examen histopatológico reveló hemangioblastoma grado I según la Organización Mundial de la Salud. A pesar de su rareza, los actuales exámenes complementarios permiten considerar, preoperativamente, el diagnóstico de hemangioblastoma. Esto es esencial para hacer un mejor planeamiento quirúrgico, teniendo en cuenta los aspectos quirúrgicos peculiares de esta lesión.