IMPORTANCE Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH.OBJECTIVE To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. DESIGN, SETTING, AND PARTICIPANTSThe Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified.INTERVENTIONS Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week.RESULTS One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported.CONCLUSIONS AND RELEVANCE Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH.
Abstract. Glioblastoma is the most common type of primary brain tumor in adults, and is usually fatal in a short duration. Acquiring a better understanding of the pathogenic mechanisms of glioblastoma is essential to the design of effective therapeutic strategies. Grb2-associated binding protein 2 (GAB2) is a member of the daughter of sevenless/Gab family of scaffolding adapters, and has been reported to be important in the development and progression of human cancer. Previously, it has been reported that GAB2 is expressed at high levels in glioma, and may serve as a useful prognostic marker for glioma and a novel therapeutic target for glioma invasion intervention. Elucidating why GAB2 is overexpressed in glioma, and investigating how to downregulate it will assist in further understanding the pathogenesis and progression of the disease, and to offer novel targets for therapy. The present study used in situ hybridization to detect microRNA (miR)-197 expression levels and Targetscan to predict that the 3'-UTR of GAB2 was targeted by miR-197. Northern blotting and reverse transcription-quantitative polymerase chain reaction were also conducted in the current study. miR-197 is downregulated in glioblastoma tissues, compared with adjacent normal tissues, however it involvement continues to be detected in the disease. The results of the present study demonstrated that miR-197, as a tumor suppressor gene, inhibited proliferation by regulating GAB2 in glioblastoma cells. Furthermore, GAB2 was not only upregulated in glioma, but its expression levels were also associated with the grades of glioma severity. In addition, overexpression of GAB2 suppressed the expression of miR-197 in glioblastoma cells. Therefore, restoration of miR-197 and targeting GAB2 may be used, in conjunction with other therapies, to prevent the progression of glioblastoma. IntroductionMicroRNAs (miRNAs; miRs) are short, non-coding RNAs, which regulate target mRNA by binding predominantly to the 3'-untranslated region (3'-UTR), inducing either translational repression or the degradation of the mRNA target (1-3). Previously, the involvement of miRNAs in the phenotypic modulation of human glioma has been reported. For example, miRNA-21 knockdown disrupts glioma growth in vivo and exhibits synergistic cytotoxicity with neural precursor cell-delivered secretable tumor necrosis factor-related apoptosis-inducing ligand in human glioma (4); miRNA-34a acts as a tumor suppressor in brain tumors and glioma stem cells (5); and miRNA-181a sensitizes human U87MG malignant glioma cells to radiation by targeting B cell lymphoma 2 (6). Although miR-197 is downregulated in glioblastoma, its roles in malignant tumor progression remain to be elucidated (7).Grb2-associated binding protein (GAB)2 belongs to a family of evolutionarily conserved proteins consisting of three mammalian paralogues: GAB1, GAB2 and GAB3; Drosophila melanogaster homolog daughter of sevenless; and Caenorhabditis elegans homolog suppressor of clear. Family members exhibit 40-50% sequence homolog...
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