Shanghai Institute of Head Trauma

Shanghai, China

Shanghai Institute of Head Trauma

Shanghai, China
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Xu C.,Ruijin Hospital | Cao L.,Ruijin Hospital | Liu J.,Shanghai JiaoTong University | Qian Z.,Shanghai JiaoTong University | And 5 more authors.
Oncology Research | Year: 2017

Elevated circulating asparaginyl endopeptidase (AEP), a novel lysosomal protease, has been found in breast cancer, and AEP is thus considered to be a prognostic factor in this disease. However, the pathological functions of circulating AEP in the development of breast cancer and the potential of AEP-targeted therapy remain unclear. We used MMTV-PyVmT transgenic mice, which spontaneously develop mammary tumors. Western blotting showed overexpression of AEP in both primary tumor tissue and lung metastases compared to their normal counterparts. Moreover, the concentration of circulating AEP gradually increased in the serum during the development of mammary tumors. Purified AEP protein injected through the tail vein promoted tumor growth and mammary tumor metastasis and shortened survival, whereas AEP-specific small compound inhibitors (AEPIs) effectively suppressed tumor progression and prolonged host survival. Further analysis of the molecular mechanism revealed that AEP was important for PI3K/AKT pathway activation. Thus, an elevated serum AEP level was closely related to mammary cancer progression and metastasis, and AEP is a potential target for breast cancer therapy in the clinic. Copyright © 2017 Cognizant, LLC.

Feng J.-F.,University of California at Davis | Feng J.-F.,Shanghai JiaoTong University | Feng J.-F.,Shanghai Institute of Head Trauma | Liu J.,University of California at Davis | And 7 more authors.
Stem Cell Reports | Year: 2017

Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies. © 2017 The Author(s)

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.

Lei J.,Shanghai JiaoTong University | Lei J.,Shanghai Institute of Head Trauma | Wang L.,Shanghai JiaoTong University | Wang L.,Shanghai Institute of Head Trauma | And 5 more authors.
Journal of Neurotrauma | Year: 2015

The right median nerve as a peripheral portal to the central nervous system can be electrically stimulated to help coma arousal after traumatic brain injury (TBI). The present study set out to examine the efficacy and safety of right median nerve electrical stimulation (RMNS) in a cohort of 437 comatose patients after severe TBI from August 2005 to December 2011. The patients were enrolled 2 weeks after their injury and assigned to the RMNS group (n=221) receiving electrical stimulation for 2 weeks or the control group (n=216) treated by standard management according to the date of birth in the month. The baseline data were similar. After the 2-week treatment, the RMNS-treated patients demonstrated a more rapid increase of the mean Glasgow Coma Score, although statistical significance was not reached (8.43±4.98 vs. 7.47±5.37, p=0.0532). The follow-up data at 6-month post-injury showed a significantly higher proportion of patients who regained consciousness (59.8% vs. 46.2%, p=0.0073). There was a lower proportion of vegetative persons in the RMNS group than in the control group (17.6% vs. 22.0%, p=0.0012). For persons regaining consciousness, the functional independence measurement (FIM) score was higher among the RMNS group patients (91.45±8.65 vs. 76.23±11.02, p<0.001). There were no unique complications associated with the RMNS treatment. The current study, although with some limitations, showed that RMNS may serve as an easy, effective, and noninvasive technique to promote the recovery of traumatic coma in the early phase. © Mary Ann Liebert, Inc. 2015.

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.

Guo P.,Shanghai JiaoTong University | Lan J.,Shanghai JiaoTong University | Ge J.,Shanghai JiaoTong University | Nie Q.,Shanghai JiaoTong University | And 4 more authors.
Oncology Reports | Year: 2013

Glioblastoma (GBM) is one of the most lethal forms of human cancer, and new clinical biomarkers and therapeutic targets are urgently required. microRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding the 3′ untranslated regions (3′ UTRs) of target mRNAs. The dysregulated expression of several miRNAs has been reported to modulate glioma progression. In the present study, we defined the expression and function of miR-708, which, based on real-time PCR analysis, were downregulated in GBM cells. The overexpression of miR-708 inhibited cell proliferation and invasion and induced apoptosis in the human GBM cell lines A172 and T98G. Furthermore, the overexpression of miR-708 reduced the expression of Akt1, CCND1, MMP2, EZH2, Parp-1 and Bcl2 in A172 and T98G cells. Taken together, our study suggests that miR-708 affects GBM cell proliferation and invasion, and induces apoptosis. It is suggested that miR-708 may play an important role as a tumor suppressor in GBM and it may be an attractive target for therapeutic intervention in GBM.

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.

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.

Guo P.,Shanghai JiaoTong University | Lan J.,Shanghai JiaoTong University | Ge J.,Shanghai JiaoTong University | Mao Q.,Shanghai JiaoTong University | And 3 more authors.
Oncology Letters | Year: 2013

Despite therapeutic advances, the prognosis of patients diagnosed with malignant glioma has not improved in recent years. In particular, the molecular mechanisms that mediate glioma invasion remain poorly understood. The importance of ID1 in promoting tumor invasion and metastasis has recently emerged and a role for ID1 as a possible molecular marker of tumor aggressiveness has been proposed. To investigate the biological function of ID1 in glioblastomas, ID1-silenced U87 glioblastoma multiforme (GBM) cells were constructed using a small hairpin RNA (shRNA) sequence. The effect of the knockdown of ID1 on proliferation and invasion in these cells was analyzed using the 5-bromo-2'-deoxy-uridine cell proliferation, Transwell invasion, scratch and cell adhesion assays. Compared with the controls, the U87 cells expressing ID1-shRNA exhibited a significantly decreased proliferation and invasion capacity (P<0.05), as well as increased cell adhesion. Furthermore, silencing ID1 reduced the expression of c-Myc, cyclin D1 and β-catenin, while increasing E-cadherin expression in U87 cells. This study showed that ID1 regulates the metastatic potential of GBM cells by controlling the epithelial-mesenchymal transition. Therefore, ID1 is a potential prognostic indicator and therapeutic target in glioblastomas.

PubMed | Shanghai Institute of Head Trauma, Fujian Medical University, Shanghai JiaoTong University and Qingdao University
Type: Journal Article | Journal: 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, noncoding, singlestranded RNAs that can negatively regulate gene expression at the posttranscriptional level, predominantly by binding to the 3untranslated 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 IDH1R132H 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 miR128a. This process was dependent on the transcription factor hypoxia inducible factor1 (HIF1), which binds to a hypoxia response element in the promoter of miR128a. Furthermore, miR128a negatively regulated the expression of Bcellspecific Moloney murine leukemia virus integration site 1 protein (Bmi1), which is involved in suppressing cell proliferation. These findings suggest that the IDH1R132HHIF1miR128aBmi1 pathway is involved in glioma cell proliferation.

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