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Rhiannon E. Lloyd Kathleen Keatley D. Timothy J. Littlewood Brigitte Meunier William V. Holt Qian An Samantha C. Higgins Stavros Polyzoidis Katie F. Stephenson Keyoumars Ashkan Helen L. Fillmore Geoffrey J. Pilkington John E. McGeehan 《Neuro-oncology》2015,17(7):942-952
BackgroundGlioblastoma (GBM) is the most common primary brain tumor in adults, with a dismal prognosis. Treatment is hampered by GBM''s unique biology, including differential cell response to therapy. Although several mitochondrial abnormalities have been identified, how mitochondrial DNA (mtDNA) mutations contribute to GBM biology and therapeutic response remains poorly described. We sought to determine the spectrum of functional complex III and IV mtDNA mutations in GBM.MethodsThe complete mitochondrial genomes of 10 GBM cell lines were obtained using next-generation sequencing and combined with another set obtained from 32 GBM tissues. Three-dimensional structural mapping and analysis of all the nonsynonymous mutations identified in complex III and IV proteins was then performed to investigate functional importance.ResultsOver 200 mutations were identified in the mtDNAs, including a significant proportion with very low mutational loads. Twenty-five were nonsynonymous mutations in complex III and IV, 9 of which were predicted to be functional and affect mitochondrial respiratory chain activity. Most of the functional candidates were GBM specific and not found in the general population, and 2 were present in the germ-line. Patient-specific maps reveal that 43% of tumors carry at least one functional candidate.ConclusionsWe reveal that the spectrum of GBM-associated mtDNA mutations is wider than previously thought, as well as novel structural-functional links between specific mtDNA mutations, abnormal mitochondria, and the biology of GBM. These results could provide tangible new prognostic indicators as well as targets with which to guide the development of patient-specific mitochondrially mediated chemotherapeutic approaches. 相似文献
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Xavier Etienne Keller Piotr Kardas Claudio Acevedo Giovanni Sais Cédric Poyet Irina Banzola Ashkan Mortezavi Burkhardt Seifert Tullio Sulser Hans H. Hirsch Maurizio Provenzano 《Oncotarget》2015,6(8):6459-6469
Infectious agents, including the BK polyomavirus (BKPyV), have been proposed as important inflammatory pathogens in prostate cancer. Here, we evaluated whether the preoperative antibody response to BKPyV large T antigen (LTag) and viral capsid protein 1 (VP1) was associated with the risk of biochemical recurrence in 226 patients undergoing radical prostatectomy for primary prostate cancer. Essentially, the multivariate Cox regression analysis revealed that preoperative seropositivity to BKPyV LTag significantly reduced the risk of biochemical recurrence, independently of established predictors of biochemical recurrence such as tumor stage, Gleason score and surgical margin status. The predictive accuracy of the regression model was denotatively increased by the inclusion of the BKPyV LTag serostatus. In contrast, the VP1 serostatus was of no prognostic value. Finally, the BKPyV LTag serostatus was associated with a peculiar cytokine gene expression profile upon assessment of the cellular immune response elicited by LTag. Taken together, our findings suggest that the BKPyV LTag serology may serve as a prognostic factor in prostate cancer. If validated in additional studies, this biomarker may allow for better treatment decisions after radical prostatectomy. Finally, the favorable outcome of LTag seropositive patients may provide a potential opportunity for novel therapeutic approaches targeting a viral antigen. 相似文献
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Mahdi Fakhar Zakaria Zakariaei Ali Sharifpour Mostafa Soleymani Ashkan Zakariaei 《Clinical Case Reports》2022,10(1)
Anaphylactic shock is an unexpected, life‐threatening, and sometimes fatal occurrence that affects patients in 75% of instances without a prior history of allergies. The severity of the reaction can vary among individuals. We report a case who died suddenly after being stung by bees in various parts of his body. 相似文献
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Ain MC Shirley ED Pirouzmanesh A Skolasky RL Leet AI 《Journal of pediatric orthopedics》2006,26(3):375-379
The etiology of genu varum in achondroplasia is the subject of much speculation. The purpose of the current study was to investigate the association between fibular overgrowth and genu varum in achondroplasia. A retrospective analysis was performed on the long-leg radiographs of 48 pediatric patients with achondroplasia. All patients were skeletally immature, and the average age was 7.7 years (range, 3-16 years). Boys were significantly more likely to have varus mechanical tibiofemoral angles than girls (Fisher exact test, P=0.038 for the right leg and P=0.008 for the left leg). The distance from the proximal and distal fibula to the proximal tibia knee and ankle joint orientation lines, respectively, was not associated with the alignment of the lower extremity. We conclude that fibular overgrowth does not correlate with the severity of genu varum. 相似文献