-
Bang-Bao Tao,
Hua He,
Xiu-Hua Shi,
Chun-Lin Wang,
Wei-Qing Li,
Bing Li,
Yan Dong,
Guo-Han Hu,
Li-Jun Hou,
Chun Luo, Ju-Xiang Chen,
Huai-Rui Chen,
Yu-Hong Yu,
Qing-Fang Sun,
Yi-Cheng Lu
[show abstract]
[hide abstract]
ABSTRACT: Gliomas are the most common neoplasms in the central nervous system. The lack of efficacy of glioma therapies necessitates in-depth studies of glioma pathology, especially of the underlying molecular mechanisms that transform normal glial cells into tumor cells. Here we report that a deubiquitinating enzyme, ubiquitin-specific protease 2a (USP2a), and its substrate, fatty acid synthase (FASN), are over-expressed in glioma tissue. Using real-time quantitative polymerase chain reaction (PCR), Western blot and immunohistochemistry, we examined the expression and cellular distribution of USP2a and FASN in human glioma tissues. The expression patterns of USP2a and FASN correlated with the pathologic and clinical characteristics of the patients. Real-time PCR analysis showed that the expression levels of USP2a and its substrate FASN were higher in high-grade (World Health Organization [WHO] grades III and IV) glioma tissues than in low-grade (WHO grades I and II) glioma tissues. Western blot analysis indicated that the average optical densitometry ratio of USP2a and its substrate FASN in high-grade gliomas was higher than in low-grade gliomas. Moreover, statistical analysis of grade-classified glioma samples showed that the level of USP2a and FASN expression increased with the elevation of the WHO grade of glioma. USP2a protein expression was detected in the nucleus of glioma tissues and an increase in expression was significantly associated with the elevation of the WHO grade of glioma by immunohistochemistry. These findings expand our understanding of the molecular profiling of glioma and could shed light on new diagnostic criteria for gliomas.
Journal of Clinical Neuroscience 02/2013; · 1.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The GTPase-activating protein RLIP76 is overexpressed in many malignant tumor cells, but it is unclear if RLIP76 overexpression contributes to the high proliferative potential of glioma cells. We demonstrate that RLIP76 mRNA and protein expression are positively correlated with glioma grade and that higher RLIP76 expression correlates with shorter patient survival.Immunohistochemical staining revealed that RLIP76 expression was positively correlated with the expression of Ki-67, a biomarker for cell proliferation. Inhibition of RLIP76 expression in U87 and U251 glioma cell lines by stable transfection of a targeted siRNA suppressed anchorage-independent growth and enhanced apoptosis in vitro. Conversely, overexpression of RLIP76 in SW1088 and U251 lines enhanced proliferation and reduced apoptosis. Inhibition of RLIP76 in U251 cells also significantly suppressed tumorigenicity and induced apoptosis in an endotopic xenograft mouse model. Moreover, we demostrate that knockdown of RLIP76 increases apoptosis in different human gliomas independently of p53 status. In addition, a constitutively active Rac1 reversed both the suppression of proliferation and the promotion of apoptosis induced by the RLIP76-targeted siRNA, indicating that RLIP76 is an upstream activator of Rac1. Rac1-mediated suppression of apoptosis and promotion of proliferation were dependent on intact JNK signaling. Furthermore, we demonstrate that RLIP76 promotes proliferation and suppresses glioma cell apoptosis through a RhoGAP-independent mechanism. Instead, we found that the ATPase function of Rlip76 modulates Rac1 activity by regulating Rac1 protein ubiquitylation and degradation. These data demonstrate that RLIP76 may suppress apoptosis and promote the proliferation of glioma cells by direct ATP-dependent xenobiotic transport and by activating the Rac1-JNK signaling pathway. Inhibition of RLIP76 signaling is a potential treatment for malignant glioma.
Carcinogenesis 12/2012; · 5.70 Impact Factor
-
Bing Li,
Hua He,
Bang-Bao Tao,
Zhen-Yu Zhao,
Guo-Han Hu,
Chun Luo, Ju-Xiang Chen,
Xue-Hua Ding,
Ping Sheng,
Yan Dong,
Ling Zhang,
Yi-Cheng Lu
[show abstract]
[hide abstract]
ABSTRACT: Chemotherapy is widely used for the treatment of glioma. Given the high resistance of brain neoplasm tissues to chemotherapy, it is important to find new methods to improve the effects of chemotherapy. However, the molecular mechanisms underlying glioma resistance to chemotherapy are largely unknown. Here, we demonstrate that CDK6, a cell cycle regulator, is significantly upregulated in glioma cells, and the increasing expression of CDK6 correlates well with the grades of glioma malignancy. Using shRNA-mediated CDK6 knockdown, we found that the proliferation and survival of tumor cells were dramatically inhibited. Moreover, CDK6 knockdown in the U251 glioma cell line caused significant increase in the apoptosis of U251 cells treated with temozolomide (TMZ). Furthermore, CDK6 knockdown reduced the expression level of drug resistance genes such as MRP and MDR. These data indicate that CDK6 is an important mediator of glioma resistance to chemotherapy. Our findings provide a new strategy for the development of chemotherapy sensitizer.
Oncology Reports 06/2012; 28(3):909-14. · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Dysautonomia after severe traumatic brain injury (TBI) is a clinical syndrome affecting a subgroup of survivors and is characterized by episodes of autonomic dysregulation and muscle overactivity. The purpose of this study was to determine the incidence of dysautonomia after severe TBI in an intensive care unit setting and analyze the risk factors for developing dysautonomia.
A consecutive series of 101 patients with severe TBI admitted in a major trauma hospital during a 2-year period were prospectively observed to determine the effects of age, sex, mode of injury, hypertension history, admission systolic blood pressure, fracture, lung injury, admission Glasgow Coma Scale (GCS) score, injury severity score, emergency craniotomy, sedation or analgesia, diffuse axonal injury (DAI), magnetic resonance imaging (MRI) scales, and hydrocephalus on the development of dysautonomia. Risk factors for dysautonomia were evaluated by using logistic regression analysis.
Seventy-nine of the 101 patients met inclusion criteria, and dysautonomia was observed in 16 (20.3%) of these patients. Univariate analysis revealed significant correlations between the occurrence of dysautonomia and patient age, admission GCS score, DAI, MRI scales, and hydrocephalus. Sex, mode of injury, hypertension history, admission systolic blood pressure, fracture, lung injury, injury severity score, sedation or analgesia, and emergency craniotomy did not influence the development of dysautonomia. Multivariate logistic regression revealed that patient age and DAI were two independent predictors of dysautonomia. There was no independent association between dysautonomia and admission GCS score, MRI scales, or hydrocephalus.
Dysautonomia frequently occurs in patients with severe TBI. A younger age and DAI could be risk factors for facilitating the development of dysautonomia.
The Journal of trauma 03/2011; 71(3):538-42. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: GABA and enkephalin (ENK) are principle inhibitory transmitters in the rostral portion of the nucleus tractus solitarius (rNTS) for regulating the gustatory information. Although the existence of GABA- and ENK-immunoreactive (ir) profiles in the rNTS has been demonstrated, there are no morphological data revealing the connections between them. In the present study, using immunofluorescent and electron microscopic methods, we examined their relationship in the rNTS of rat. Results showed the following: (1) dense ENK-ir fibers and terminals and GABA-ir cell bodies, fibers, and terminals were observed in the rNTS; (2) ENK-ir terminals mainly make symmetric synapses with GABA-ir and immunonegative somas and dendrites; (3) co-existence of ENK/GABA-ir axon terminals and convergence of ENK- and GABA-ir terminals on one immunonegative soma or dendrite can also be observed. These results suggest that ENK should inhibit directly or excite indirectly (by blocking the inhibition of the GABAergic neurons) the gustatory neurons in the rNTS.
Neurological Sciences 02/2011; 32(1):53-8. · 1.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ventriculo-peritoneal (VP) shunt is the most common form of treatment for hydrocephalus and rejection to the shunt hardware is very rare. Also, in ventricul-atrial (VA) shunt thrombi and embolism are possible but rare complications. For the first time, we present a case of rejection and thrombosis following VP and VA shunt in the same patient.
British Journal of Neurosurgery 12/2010; 25(2):300-2. · 0.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Paroxysmal sympathetic hyperactivity (PSH) is a clinical syndrome affecting a subgroup of survivors of severe brain injury. In this study, the prevalence, magnetic resonance imaging (MRI) presentation, influence on the clinical course in the intensive care unit (ICU), and effect on neurological recovery of PSH were prospectively surveyed in 87 patients with severe traumatic brain injury (TBI). Cranial MRI was performed during the first 30 days after injury. The outcome was assessed according to the Glasgow Outcome Scale (GOS). PSH occurred in 18.4% of patients, with a greater incidence among younger patients and those with lower Glasgow Coma Scale (GCS) scores. Patients with PSH had more deep lesions as shown on cranial MRI, significantly longer ICU stays, and worse outcomes. PSH was shown to be common among patients with severe TBI who also had deep intraparenchymal lesions. The mechanism by which PSH influences patient outcomes has yet to be defined, but we believe that it may be mediated by diencephalic-mesencephalic dysfunction or disconnection.
Journal of neurotrauma 10/2010; 27(11):1945-50. · 4.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Haemophilic pseudotumor is a rare complication of haemophilia occurring in 1-2% of patients and is more frequently located is in the long bones of the lower extremities and in the pelvis. We present the first case of an intracranial haemophilic pseudotumor in a patient with factor VIII deficiency.
British Journal of Neurosurgery 09/2009; 23(4):455-7. · 0.88 Impact Factor
-
Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society 07/2009; 29(2):156-7. · 1.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare the effects of treatment of spasmodic torticollis (ST) by neurovascular decompression, myotomy, and botulinum toxin type A and to investigate the mechanism of ST.
Nine ST patients who failed to respond to other conservative treatment methods underwent neurovascular decompression of accessory nerve. The effect of decompression was compared with that by botulinum toxin in 22 patients and that by myotomy in 13 patients.
The symptoms and signs were improved to a certain degree by botulinum toxin treatment at first, but recurred and gradually worsened in several months. None of the 22 patients had reached a real cure by botulinum toxin type A treatment. Four of 13 patients undergoing myotomy improved a lot in the symptoms and 9 improved only a bit. However, weakness in neck movement was found in all patients after myotomy. Neurovascular decompression was performed on 9 patients, 5 of which had botulinum toxin treatment and 1 had undergone myotomy, and found that all of them had severe vascular compression in the accessory nerve. Obvious alleviation of symptoms was achieved 2 - 14 days after the operation in 8 patients, and 3 months later in 1 patient. All of the 9 patients resumed their nonenal work and life 6 months after the operation. No complication, such as nerve damage, infection, hemorrhage, leakage of cerebrospinal fluid, and weakness of neck, was found.
Neurovascular compression may be the most important cause of ST. Microneurovascular decompression is effective for some patients. However, it is still difficult to judge its indication.
Zhonghua yi xue za zhi 02/2009; 89(1):21-4.
-
Ju-xiang Chen,
Yi-cheng Lu,
Chun-lin Wang,
Ke-hua Sun,
Xue-hua Ding,
Gao-han Hu,
Chun Luo,
Mei-qing Lou,
Tao Xu,
Xiao-jun Wu,
Xiao-xin Chen
[show abstract]
[hide abstract]
ABSTRACT: To investigate the microsurgical strategies of glioma located in lateral fissure area.
The clinical data of 123 patients with glioma located in lateral fissure area confirmed by pathology, 76 males and 47 females, aged 46.2 (4-75), were retrospectively analyzed. The optimal surgical approach and comprehensive therapeutic strategies were selected according to the imaging features and pathological properties of tumors. Resections were performed by the pterion approach in all cases to remove the tumors, navigational orientation was used in 17 cases, and supervision by B mode ultrasonography was used in 12 cases. The branches of middle cerebral artery and fissure vein were protected carefully. The patients with tumors above grade U, confirmed pathologically after resection, underwent chemotherapy ( teniposide + semustine or temozolomide) and radiotherapy that was designated individually according to the pathological grade and distribution of the tumors. Follow-up was conducted by telephone, mail or outpatient department visit on 102 of the 133 patients (82.9%).
82 patients (66.7%) underwent total resection, 18 (14.6%) underwent subtotal resection, 16 (13.0%) underwent major resection, and 7 (5.7%) underwent partial resection. Postoperatively cerebral vasospasm in 8 cases, brief aphasia and reaction clumsily in 4 cases, muscle strength decline in 3 cases, and epilepsy in 1 case, these patients were submitted to symptomatic treatment with progressive improvement of the above-mentioned signs and symptoms. One patient died of malignant intracranial hypertension. The follow-up showed that 97 patients survived over 1 year, the 5-year survival rate was 25.6%, and the average survival time was 21.7 months.
The lateral fissure area glioma can be treated through proficient microsurgical technique after the anatomic training. It is the key in the surgery on the lateral fissure glioma to protect the main branches of middle cerebral artery, trunk of middle cerebral vein, and important brain functional areas.
Zhonghua yi xue za zhi 02/2009; 89(3):151-5.
-
[show abstract]
[hide abstract]
ABSTRACT: This study was conducted to evaluate the effect of 3D-RA on the treatment of SCVMs.
Twelve patients with SCVM were retrospectively reviewed for details of 2D and 3D-RA findings. Pretherapeutic 2D and 3D-RA angiograms were compared with respect to 4 critical categories of parameters: (1) the exact anatomic location, size, and extent; (2) the definitive diagnosis; (3) the precise angioarchitectural configuration; and (4) the contribution to further intervention.
Overall, 2D and 3D-RA were equally effective in demonstrating the exact anatomic location, size, and extent, and establishing the definitive diagnosis of SCVM in all 12 cases. 3-Dimensional rotational angiography demonstrated precise angioarchitectural configuration in 8 (8/12) cases, facilitated treatment in 6 (6/12) cases, and modified therapeutic strategies in 2 (2/12) cases via information not available from 2D-DSA images. Both 2D and 3D-RA contributed equally to the therapeutic intervention in 4 (4/12) patients. No complications occurred as a result of 3D-RA.
3-Dimensional rotational angiography may enhance our ability to treat SCVMs with complex angioarchitecture and is an ideal addition to conventional 2D angiography in the management of these vascular lesions.
Surgical Neurology 05/2008; 69(4):369-73; discussion 373-4. · 1.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: UbcH10 is one of the key regulators of cell cycle progression through the mitotic spindle assembly checkpoint pathway. Recently, aberrantly high UbcH10 expression has been demonstrated in a variety of malignancies. However, its role in astrocytic carcinogenesis is not well defined. This study investigated the splice pattern of the UbcH10 gene and its expression status in astrocytomas of different grades. Consequently, UbcH10 splice variant 1 (GenBank accession nos. NM_007019) was detected in astrocytomas and normal brain tissues by RT-PCR and sequence analysis. Expression levels of UbcH10 mRNA were elevated in high- versus low-grade astrocytomas (64.33+/-60.98 vs 8.36+/-8.15, respectively; p=0.000) or normal controls (64.33+/-60.98 vs 1.00+/-1.57, respectively; p=0.000), as determined by quantitative real time PCR analysis. Similarly, immunohistochemistry study showed increased UbcH10 labelling index in high-grade astrocytomas versus low-grade tumors (10.53+/-5.79% vs 4.23+/-2.85%, respectively; p=0.000) or normal controls (10.53+/-5.79% vs 0.0+/-0.0%, respectively; p=0.000) and, a positive correlation between UbcH10 immunoreactivity and Ki-67 immunostaining was also noted (Spearman r=0.63, p<0.001). These data suggest that overexpression of UbcH10 may serve as one important molecular mechanism that underlies the astrocytic carcinogenesis.
Brain Research 03/2008; 1201:161-6. · 2.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To clone and identify expression pattern of the novel LNX gene, and characterize its molecular mechanism in all grades of human gliomas.
From a fetal brain cDNA library, we isolated the novel human LNX gene. The expression pattern of LNX gene in 16 normal tissues was examined by MTC panel (Clontech). Microarray were adopted and hybridized with LNX probes to examine the expression of novel gene in gliomas. Northern hybridization was used for verifying expression of LNX gene in gliomas. Two-hybrid screen in yeast was used to identify human LNX interacting proteins. Pull-down assays and Co-immunoprecipitation were transfected in HEK293 cells according to the lipofectAMINE protocol.
We isolated a 3.7 kb cDNA containing an open reading frame (ORF) of 1,899 bp and a putative 632 amino acids protein, which was located on 4q12. cDNA microarray showed LNX was down-regulated in all 18 glioma samples and it was testified by Northern-blot. The MTC panel showed a ubiquitous expression pattern which highly expressed in adult brain, kidney and pancreas, while weak expression in heart, lung, etc. The two-hybrid screen in yeast revealed that LNX interacted with SKIP (Ski interacting protein) via PDZ domains. The co-immunoprecipation suggested that LNX interacted with SKIP in HEK293 cells and could affect the subcellular localization of Numb, which indicated that LNX might function as a molecular anchor that localized Numb to the subcellular site of its interaction with Notch.
cDNA microarray technology is a powerful technique in screening and locking differentially expressed genes in gliomas, LNX was closely related to human gliomas and suggested playing an important role in gliomas by notch signal approach.
Zhonghua yi xue za zhi 11/2005; 85(38):2704-10.
-
[show abstract]
[hide abstract]
ABSTRACT: To screen differentially expressed genes in the development of human glioma and establish molecular classification of glioma preliminary based on gene expression using cDNA microarray.
Brain specimens were obtained from 18 patients with glioma, 10 males and 8 females, aged 14 approximately 62 with an average age of 44.4. The total RNAs of these glioma specimens and 2 specimens of donated brain of normal adults were extracted. BioStarH140S microarray (including 8347 old genes and 5592 novel genes) were adopted and hybridized with probes which were prepared from the total RNAs. Differentially expressed genes between the normal tissues and glioma tissues were assayed after scanning cDNA microarray with ScanArray 4000. Northern hybridization, and in situ hybridization (ISH) were used to identify the functions of novel genes. Those differentially expressed genes were studied with Hierarchical method and molecular classification of glioma was preliminarily carried out.
Among the 13 939 target genes, there were 1200 (8.61%) differentially expressed genes and 395 (2.83%) novel genes. 348 genes were up-regulated and 852 genes were down-regulated in glioma. The results of bioinformatical analysis, Northern hybridization and ISH revealed that those novel genes were highly associated with glioma. There were multiple genes which were relevance to classification by Hierarchical method, such as MAP gene, cytoskeleton and matrix motility genes, etc. Molecular classification of glioma with Hierarchical cluster was in accordance with pathology and revealed internal essence in tumorigenesis and development.
Multiple genes play important roles in development of glioma. cDNA microarray technology is a powerful technique in screening for differentially expressed genes between two different kinds of tissues.
Zhonghua yi xue za zhi 05/2004; 84(8):622-7.
