Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with extremely poor prognostic outcome despite intensive treatment. All chemotherapeutic agents currently used have no greater than 30–40% response rate, many fall into the range of 10–20%, with delivery across the blood brain barrier (BBB) or chemoresistance contributing to the extremely poor outcomes despite treatment. Increased expression of the multidrug resistance protein 1(MRP1) in high grade glioma, and it's role in BBB active transport, highlights this member of the ABC transporter family as a target for improving drug responses in GBM. In this study we show that small molecule inhibitors and gene silencing of MRP1 had a significant effect on GBM cell response to temozolomide (150 μM), vincristine (100 nM), and etoposide (2 μM). Pre-treatment with Reversan (inhibitor of MRP1 and P-glycoprotein) led to a significantly improved response to cell death in the presence of all three chemotherapeutics, in both primary and recurrent GBM cells. The presence of MK571 (inhibitor of MRP1 and multidrug resistance protein 4 (MRP4) led to an enhanced effect of vincristine and etoposide in reducing cell viability over a 72 h period. Specific MRP1 inhibition led to a significant increase in vincristine and etoposide-induced cell death in all three cell lines assessed. Treatment with MK571, or specific MRP1 knockdown, did not have any effect on temozolomide drug response in these cells. These findings have significant implications in providing researchers an opportunity to improve currently used chemotherapeutics for the initial treatment of primary GBM, and improved treatment for recurrent GBM patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19) is a highly transmissible virus and has become pandemic. Part of the prevention of disease spread by the Malaysian government is by getting COVID-19 vaccine. Using the mRNA technology, the Pfizer/BioNTech vaccine is one of the vaccines been approved by the Drug Control Authority in Malaysia. Herein, we report an immediate complication of cerebral VST after the first dose of the Pfizer/BioNTech vaccine.

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OBJECTIVEThe aim of this study was to assess the outcome of neurosurgical treatment in children with bleeding diathesis and also to evaluate the current management plan applied in the authors’ service.METHODSThe authors retrospectively analyzed all cases in which neurosurgical procedures were performed in pediatric patients presenting with intracranial hematoma due to an underlying bleeding tendency over a 5-year period at their institution. They evaluated the patients’ neurological symptoms from the initial referral, hematological abnormalities, surgical treatment, neurological outcome, and scores on the Pediatric Glasgow Outcome Scale–Extended (GOS-E Peds) obtained 1 year after the last operation.RESULTSFive patients with a bleeding diathesis who underwent surgery for intracranial hematoma were identified; the diagnosis was hemophilia A in 3 cases, idiopathic thrombocytopenic purpura in 1 case, and severe aplastic anemia in 1 case. Intracerebral hematoma (ICH) (n = 4) and acute subdural hematoma (n = 1) were confirmed on radiological investigations. In 2 of the 4 patients with ICH, the diagnosis of bleeding diathesis was made for the first time on presentation. Four patients (all male) were younger than 2 years; the patient with severe aplastic anemia and spontaneous ICH was 15 years old and female. The duration of symptoms varied from 24 hours to 5 days. Neurological examination at 1 year’s follow-up showed complete recovery (GOS-E Peds score of 1) in 3 cases and mild weakness (GOS-E Peds score of 2) in 2 cases.CONCLUSIONSNeurosurgical management of patients with bleeding diathesis should be carried out in a tertiary-care setting with multidisciplinary team management, including members with expertise in neuroimaging and hematology, in addition to neurosurgery. Early diagnosis and prompt treatment of a bleeding diathesis is crucial for full neurological recovery.

BackgroundThe evasion of apoptosis is a hallmark of cancer. Understanding this process holistically and overcoming apoptosis resistance is a goal of many research teams in order to develop better treatment options for cancer patients. Efforts are also ongoing to personalize the treatment of patients. Strategies to confirm the therapeutic efficacy of current treatments or indeed to identify potential novel additional options would be extremely beneficial to both clinicians and patients. In the past few years, system medicine approaches have been developed that model the biochemical pathways of apoptosis. These systems tools incorporate and analyse the complex biological networks involved. For their successful integration into clinical practice, it is mandatory to integrate systems approaches with routine clinical and histopathological practice to deliver personalized care for patients.ResultsWe review here the development of system medicine approaches that model apoptosis for the treatment of cancer with a specific emphasis on the aggressive brain cancer, glioblastoma.ConclusionsWe discuss the current understanding in the field and present new approaches that highlight the potential of system medicine approaches to influence how glioblastoma is diagnosed and treated in the future.