Most intramedullary spinal cord tumors need operative treatment as early as possible. The outcome of aggressive surgery now is much better than it has been in the past, and the results are acceptable. For malignant tumors and those where total removal has not been possible radiation therapy is necessary.
The coiled coil is a superhelical structural protein motif involved in a diverse array of biological functions, and the abnormal expression of the coiled-coil domain containing proteins has a direct link with the phenotype of tumor cell migration, invasion and metastasis. The aim of this study was to investigate the critical role of Coiled-coil domain-containing protein 34 (CCDC34) in bladder carcinogenesis, which has never been reported to date. Here, we found CCDC34 expression was elevated in bladder cancer tissues and cell lines. The knockdown of CCDC34 via lentivirus-mediated siRNA significantly suppressed bladder cancer cells proliferation and migration, and induced cell cycle arrest at G2/M phase and increased apoptosis in vitro. In addition, CCDC34 knockdown suppressed bladder tumor growth in nude mice. Moreover, CCDC34 silencing decreased the phosphorylation of MEK, ERK1/2, JNK, p38 and Akt, and the expressions of c-Raf and c-Jun, indicating MAPK and AKT pathways (ERK/MAPK, p38/MAPK, JNK/MAPK and PI3K/Akt) might be involved in CCDC34 regulation of bladder cancer cell proliferation and migration. Our findings revealed for the first time a potential oncogenic role for CCDC34 in bladder carcinoma pathogenesis and it may serve as a biomarker or even a therapeutic target for bladder cancer.
BackgroundThe incidence of tuberculosis (TB), especially multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), continues to increase alarmingly worldwide. Molecular line probe assays (LPAs) are endorsed by the World Health Organization for the fast detection of MDR-TB and XDR-TB. The aim of this study was to evaluate the performance of LPAs in China.MethodsWe analyzed MDR-TB and XDR-TB in 96 isolates from Beijing by using culture-based drug susceptibility testing (DST) and LPAs to compare the detection rate of the two methods.ResultsCompared to phenotypic DST, the GenoType® MTBDRplus and MTBDRsl, respectively, showed a sensitivity of 98.7% and a specificity of 88.9% for detection of rifampicin resistance, 82.1% and 94.4% for isoniazid, 89.7% and 94.4% for levofloxacin, 60.0% and 98.7% for amikacin/capreomycin, and 57.5% and 98.2% for ethambutol. The sensitivity and specificity of LPAs, respectively, were 80.8% and 100% for MDR-TB and 50.0% and 97.6% for XDR-TB. Mutations in codon S531L of the rpoB gene and S315T1 of the KatG gene were dominated in MDR-TB strains. The most frequently observed mutations were in codon A90V of the gyrA gene, A1401G of the rrs gene, and M306V of the embB gene, according to the MTBDRsl results.ConclusionOur study showed that, in combination with phenotypic DST, application of the LPAs might be an efficient and reliable supplementary DST assay for rapid susceptibility screening of MDR-TB and XDR-TB. Using LPAs in countries with high MDR/XDR burden allows for appropriate and timely treatment, which will reduce transmission rates and morbidity, and improve treatment outcomes in patients.
Stent-assisted coiling of paraclinoid aneurysms did not add significantly to morbidity; overall effectiveness was comparable to that of bare coiling of paraclinoid aneurysms. These results require confirmation by a prospective controlled trial.
Background
Intracranial Aneurysm (IA) is usually a late-onset disease, affecting 1-3% of the general population and leading to life-threatening subarachnoid hemorrhage (SAH). Genetic susceptibility has been implicated in IAs but the causative genes remain elusive.
Methods
We performed next-generation sequencing (NGS) in a discovery cohort of 20 Chinese IA patients. Bioinformatics filters were exploited to search for candidate deleterious variants with rare and low allele frequency. We further examined the candidate variants in a multi-ethnic sample collection of 86 whole-exome sequenced unsolved familial IA cases from three previously published studies.
Results
We identified that the low-frequency variant c.4394C>A_p.Ala1465Asp (rs2298808) of ARHGEF17 was significantly associated with IA in our Chinese discovery cohort (P =7.3×10−4; OR=7.34). It was subsequently replicated in Japanese familial IA patients (P=0.039; OR=4.00; 95% CI = 0.832-14.8) and was associated with IA in the large Chinese sample collection comprising 832 sporadic IA-affected and 599 control individuals (P=0.041; OR =1.51; 95% CI = 1.02-Inf). When combining the sequencing data of all familial IA patients from four different ethnicities (i.e. Chinese, Japanese, European American, and French-Canadian), we identified a significantly increased mutation burden for ARHGEF17 (21/106 versus 11/306; P = 8.1×10−7; OR=6.6; 95% CI = 2.9-15.8) in cases as compared to controls. In zebrafish, arhgef17 was highly expressed in the brain blood vessel. arhgef17 knockdown caused blood extravasation in the brain region. Endothelial lesions were identified exclusively on cerebral blood vessels in the arhgef17-deficient zebrafish.
Conclusions
Our results provide compelling evidence that ARHGEF17 is a risk gene for IA.
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