Despite recent advances in the understanding of high-grade gliomas, they are among the most malignant of all cancers, with dismal patient outcomes. The classification of gliomas follows the World Health Organization (WHO) classification, which is based on knowledge of cytologic features and degrees of malignancy. The most aggressive form of glioma, the glioblastoma (GBM), represents 29% of primary brain tumors and about 55% of all gliomas 1,2,3 . In spite of standard treatment with surgery, chemotherapy with temozolomide, and radiotherapy, glioblastomas are always fatal with a median survival rate of less than a year and a five-year survival rate of less than 10% of the cases 4,5,6,7 . The glioblastomas are characterized by complex heterogeneity. A new definition of this heterogeneity was recently proposed based on genomic, transcriptomic and epigenomic studies carried out by The Cancer Genome Atlas Network. Through the latter's analyses, the GBMs were clustered into four subgroups: proneural, neural, classical and mesenchymal, which correlate with biological properties of the tumors and measures of clinical outcome 8,9 . ABSTRACT Glioblastoma (GBM) is the most malignant glioma and represents 29% of all brain tumors. Tumorigenesis is intimately connected with characteristics acquired in the physiologic pathway of cellular death. Objective: In the present study, the expression of anti-apoptotic (XIAP and Bcl-2) and apoptotic (cytochrome C, caspase 9, APAF-1), caspase 3 and the Smac/DIABLO genes related to the apoptosis pathway were evaluated in 30 samples of glioblastoma. Methods: The gene expression was evaluated in 30 glioblastomas (WHO grade IV) and compared to 10 white matter control samples with real-time PCR. Results and Conclusion: There were higher expressions of XIAP (p = 0.0032) and Bcl-2 (p = 0.0351) in the glioblastoma samples compared to the control samples of normal brain. These results raise the question of whether Bcl-2 and XIAP genes can be responsible for the inhibition of programmed cell death in glioblastomas. Moreover, they provide additional information capable of allowing the development of new target therapy strategies.Keywords: glioblastoma; apoptosis; X-linked inhibitor of apoptosis protein; B-cell lymphoma 2. RESUMOO glioblastoma (GBM) é o glioma mais maligno e representa 29% de todos os tumores cerebrais. A tumorigênese está intimamente ligada à características adquiridas na via fisiológica de morte celular. Objetivo: Avaliar a expressão de genes anti-apoptóticos (XIAP e Bcl-2) e apoptóticos (citocromo C, a caspase 9, APAF-1), caspase 3 e SMAC/DIABLO, relacionados à apoptose, em 30 amostras de tecido de pacientes com glioblastoma. Métodos: A expressão gênica foi avaliada em trinta glioblastomas e comparada a dez amostras controles de substância branca por PCR em tempo real. Resultados e Conclusão: Houve maior nível de expressão de XIAP (p = 0,0032) e Bcl-2 (p = 0,0351) em comparação com as amostras controle, de cérebro normal. Estes resultados levantam a questão de que os genes Bcl-2 e...

One of the different genetic mechanisms involved in the carcinogenesis of meningiomas is influenced by interactions between proteins that induce and inhibit apoptosis. Objective: To evaluate the expression of c-FLIP, XIAP, Bcl-2, caspase 3, 8 and 9, cytochrome c, APAF 1 and Smac/DIABLO genes related to apoptosis pathways. Methods: The gene expression was evaluated in 30 meningiomas (WHO grades I and II) and in 10 normal samples (from arachnoid tissue) through PCR-RT. Results: The results showed higher expression of anti-apoptotic genes in meningiomas when compared to the control group, which had a low expression of pro-apoptotic genes. Conclusion: There is a possible block in the activation of caspases through the intrinsic apoptosis pathway in meningiomas. c-FLIP modulates caspase 8 and, by inhibiting its activation due to the lack of connection with the receiver, there is a block to the FAS activation of apoptosis by its extrinsic pathway.Keywords: meningioma; carcinogenesis; apoptosis; gene expression. RESUMOUm dos diferentes mecanismos genéticos envolvidos na carcinogênese de meningiomas é influenciado por interações entre proteínas que induzem e inibem a apoptose. Objetivos: Avaliar a expressão de c-FLIP, XIAP, Bcl-2, caspase 3, 8 e 9, citocromo C, APAF 1 e Smac/DIABLO, genes relacionados com as vias da apoptose. Métodos: A expressão gênica foi avaliada em trinta amostras de meningiomas (OMS grau I e II) e em dez amostras normais (de aracnóide) por PCR em tempo real. Resultados: Os resultados mostraram maior expressão de genes antiapoptóticos em meningiomas quando comparados com controle, em contraste com a menor expressão de genes próapoptóticos. Conclusão: Há um possível bloqueio na ativação de caspases através da via intrínseca da apoptose em meningiomas. O c-FLIP modula a caspase 8 e, desse modo, inibindo a sua ativação pela ausência de ligação com o receptor, há um bloqueio na ativação de FAS pela via extrínseca da apoptose.Palavras-chave: meningioma; carcinogênese; apoptose; expressão gênica.Meningioma is the most frequent primary intracranial tumor in adults 1 . They arise from the meninges and are composed of neoplastic arachnoid (meningothelial) cells. They generally grow slowly and rarely show an aggressive behavior 2,3,4,5 . According to the current World Health Organization histological grade system, meningiomas are classified into three grades: grade I or benign (90%), generally following a benign clinical course; grade II or atypical (5-7%) are associated with increased risk of recurrence; and grade III, or anaplastic (1-2%), defined as meningiomas that have obvious malignant histology or high mitotic rates that frequently present with local and brain invasion, recurrence and even metastases 3,4 . Currently, the curative treatment option is complete surgical resection 6 , and there is no established chemotherapy regimen for unresectable meningiomas 7 . Despite being benign, meningiomas have a significant rate of recurrence after surgery. While recurrence rates of benign meningiomas ran...

The epitranscriptomic modification N6-methyladenosine (m6A) is a ubiquitous feature of the mammalian transcriptome. It modulates mRNA fate and dynamics to exert regulatory control over numerous cellular processes and disease pathways, including viral infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) reactivation from the latent phase leads to the redistribution of m6A topology upon both viral and cellular mRNAs within infected cells. Here we investigate the role of m6A in cellular transcripts upregulated during KSHV lytic replication. Our results show that m6A is crucial for the stability of the GPRC5A mRNA, whose expression is induced by the KSHV latent–lytic switch master regulator, the replication and transcription activator (RTA) protein. Moreover, we demonstrate that GPRC5A is essential for efficient KSHV lytic replication by directly regulating NFκB signalling. Overall, this work highlights the central importance of m6A in modulating cellular gene expression to influence viral infection.