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Nie Q.-M.,Shanghai JiaoTong University | Lin Y.-Y.,Shanghai Institute of Head Trauma | Yang X.,Shanghai JiaoTong University | Shen L.,Shanghai JiaoTong University | And 8 more authors.
Molecular Medicine Reports | Year: 2015

Mutations in isocitrate dehydrogenase 1 (IDH1) are found in >70% of secondary glioblastomas and lower-grade gliomas (grades II-III). Among the numerous phenotypic differences between IDH1 mutant and wild-type glioma patients, the most salient is an improved survival rate for patients with a mutation. MicroRNAs (miRNAs) are a class of small, non-coding, single-stranded RNAs that can negatively regulate gene expression at the post-transcriptional level, predominantly by binding to the 3'-untranslated region of their target mRNAs. The dysregulated expression of several miRNAs has been reported to modulate glioma progression; however, it is unclear whether mutations in IDH1 regulate glioma cell proliferation through miRNA dysregulation. In the present study, stable overexpression of IDH1WT or IDHR132H was established in the U87 glioma cell line. It was found that IDH1R132H decreased cell proliferation of U87 glioma cells by inducing the expression of the miRNA miR-128a. This process was dependent on the transcription factor hypoxia inducible factor-1α (HIF-1α), which binds to a hypoxia response element in the promoter of miR-128a. Furthermore, miR-128a negatively regulated the expression of B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1), which is involved in suppressing cell proliferation. These findings suggest that the IDH1R132H-HIF-1α-miR-128a-Bmi-1 pathway is involved in glioma cell proliferation. Source


Lei J.,Shanghai Institute of Head Trauma | Lei J.,Shanghai JiaoTong University | Gao G.,Shanghai Institute of Head Trauma | Gao G.,Shanghai JiaoTong University | And 5 more authors.
Contemporary Clinical Trials | Year: 2015

Background: Traumatic brain injury (TBI) is a major public health problem recently, however, no intervention showing convincing efficacy. Therapeutic hypothermia with a relatively long duration (more than 48. h), as a promising treatment measure, might improve the patient outcome following severe TBI. Methods/design: The LTH-1 trial is a prospective, nationwide multicenter, randomized, controlled clinical trial to examine the efficacy and safety of long-term mild hypothermia in adult patients after severe traumatic brain injury. A total of 300 consecutive patients will be recruited from 15 large neurosurgical centers in China. The eligible patient will be randomized to receive either long-term mild hypothermia (34-35. °C) for 5. days, or normothermia (36-37. °C). Additionally, a standardized management protocol will be used in all patients. The primary end point is the neurological outcome 6. months post-injury on the Glasgow Outcome Scale. The secondary outcomes include GOS score at one month post-injury, mortality during six months after injury, length of ICU and hospital stay, intracranial pressure control and Glasgow Coma Scale score during the hospital stay and frequency of complications during the six-month follow-up period. Discussion: Long-term hypothermia is recommended by most recent studies and its efficacy urgently needs to be established in randomized controlled settings. The LTH-1 trial, together with other ongoing studies, will present more evidence for optimal use of hypothermia in severe TBI patients. © 2014 Elsevier Inc. Source


Guo P.,Shanghai JiaoTong University | Lan J.,Shanghai JiaoTong University | Ge J.,Shanghai JiaoTong University | Nie Q.,Shanghai JiaoTong University | And 5 more authors.
Experimental Cell Research | Year: 2014

Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new radiosensitizers are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance radiosensitivity and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3'UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new radiosensitizer of GBM. © 2013 Elsevier Inc. Source


Guo P.,Shanghai JiaoTong University | Nie Q.,Shanghai JiaoTong University | Lan J.,Shanghai JiaoTong University | Ge J.,Shanghai JiaoTong University | And 4 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc-miR-26a-PTEN signaling pathway. This may be of clinical relevance. © 2013 Elsevier Inc. All rights reserved. Source


Lei J.,Shanghai JiaoTong University | Lei J.,Shanghai Institute of Head Trauma | Gao G.,Shanghai JiaoTong University | Gao G.,Shanghai Institute of Head Trauma | And 2 more authors.
Journal of Neurotrauma | Year: 2013

Traumatic brain injury (TBI) is a major health and socioeconomic problem worldwide with a high rate of death and long-term disability. Previous studies have summarized evidence from large-scale randomized trials, finding no intervention showing convincing efficacy for acute TBI management. The present empirical study set out to assess another crucial component of evidence base-systematic review, which contributes a lot to evidence-based health care, in terms of clinical issues, methodological aspects, and implication for practice and research. A total of 44 systematic reviews pertaining to therapeutic interventions for acute TBI were identified through electronic database searching, clinical guideline retrieval, and expert consultation, of which 21 were published in Cochrane Library and 23 in peer-reviewed journals. Their methodological quality was generally satisfactory, with the median Overview Quality Assessment Questionnaire score of 5.5 (interquartile range 2-7). Cochrane reviews are of better quality than regular journal reviews. Twenty-nine high-quality reviews provided no conclusive evidence for the investigated 22 interventions except for an adverse effect of corticosteroids. Less than one-third of the component trials were reported with adequate allocation concealment. Additionally other methodological flaws in design-for example, ignoring heterogeneity among the TBI population-also contributed to the failure of past clinical research. Based on the above findings, evidence from both systematic reviews and clinical trials does not fully support current management of acute TBI. Translating from laboratory success to clinical effect remains an unique challenge. Accordingly it may be the time to rethink the way in future practice and clinical research in TBI. © 2013, Mary Ann Liebert, Inc. Source

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