Anti-cancer effect of metabotropic glutamate receptor 1 inhibition in human glioma U87 cells: involvement of PI3K/Akt/mTOR pathway.

BACKGROUND: Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors that mediate neuronal excitability and synaptic plasticity in the central nervous system, and emerging evidence suggests a role of mGluRs in the biology of cancer. Previous studies showed that mGluR1 was a potential therapeutic target for the treatment of breast cancer and melanoma, but its role in human glioma has not been determined. METHODS: In the present study, we investigated the effects of mGluR1 inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA) or selective antagonists Riluzole and BAY36-7620. The anti-cancer effects of mGluR1 inhibition were measured by cell viability, lactate dehydrogenase (LDH) release, TUNEL staining, cell cycle assay, cell invasion and migration assays in vitro, and also examined in a U87 xenograft model in vivo. RESULTS: Inhibition of mGluR1 significantly decreased the cell viability but increased the LDH release in a dose-dependent fashion in U87 cells. These effects were accompanied with the induction of caspase-dependent apoptosis and G0/G1 cell cycle arrest. In addition, the results of Matrigel invasion and cell tracking assays showed that inhibition of mGluR1 apparently attenuated cell invasion and migration in U87 cells. All these anti-cancer effects were ablated by the mGluR1 agonist L-quisqualic acid. The results of western blot analysis showed that mGluR1 inhibition overtly decreased the phosphorylation of PI3K, Akt, mTOR and P70S6K, indicating the mitigated activation of PI3K/Akt/mTOR pathway. Moreover, the anti-tumor activity of mGluR1 inhibition in vivo was also demonstrated in a U87 xenograft glioma model in athymic nude mice. CONCLUSION: The remarkable efficiency of mGluR1 inhibition to induce cell death in U87 cells may find therapeutic application for the treatment of glioma patients.

Downregualtion of dynamin-related protein 1 attenuates glutamate-induced excitotoxicity via regulating mitochondrial function in a calcium dependent manner in HT22 cells.

Glutamate-mediated excitotoxicity is involved in many acute and chronic brain diseases. Dynamin related protein 1 (Drp-1), one of the GTPase family of proteins that regulate mitochondrial fission and fusion balance, is associated with apoptotic cell death in cancer and neurodegenerative diseases. Here we investigated the effect of downregulating Drp-1 on glutamate excitotoxicity-induced neuronal injury in HT22 cells. We found that downregulation of Drp-1 with specific small interfering RNA (siRNA) increased cell viability and inhibited lactate dehydrogenase (LDH) release after glutamate treatment. Downregulation of Drp-1 also inhibited an increase in the Bax/Bcl-2 ratio and cleavage of caspase-9 and caspase-3. Drp-1 siRNA transfection preserved the mitochondrial membrane potential (MMP), reduced cytochrome c release, enhanced ATP production, and partly prevented mitochondrial swelling. In addition, Drp-1 knockdown attenuated glutamate-induced increases of cytoplasmic and mitochondrial Ca(2+), and preserved the mitochondrial Ca(2+) buffering capacity after excitotoxicity. Taken together, these results suggest that downregulation of Drp-1 protects HT22 cells against glutamate-induced excitatory damage, and this neuroprotection may be dependent at least in part on the preservation of mitochondrial function through regulating intracellular calcium homeostasis.

Relationship between postoperative hypothalamic injury and water and sodium disturbance in patients with craniopharyngioma: A retrospective study of 178 cases.

Objective: To investigate the relationship between postoperative hypothalamo-hypophyseal injury (HHI) and postoperative water and sodium disturbances in patients with craniopharyngioma. Methods: The medical records, radiological data, and laboratory results of 178 patients (44 children and 134 adults) who underwent microsurgery for craniopharyngioma in a single center were reviewed. Postoperative HHI was assessed using magnetic resonance imaging. Structural defects of the hypothalamo-hypophyseal system (pituitary, pituitary stalk, floor and lateral wall of the third ventricle) were assessed in four standard T1-weighted images. The defect of each structure was assigned 1 score (0.5 for the unilateral injury of the third ventricle wall), and a HHI score was calculated. Results: The number of patients with HHI scores of 0-1, 2, 2.5-3, and >3 was 35, 49, 61, and 33, respectively. Diabetes insipidus (DI) worsened in 56 (31.5%) patients with preoperative DI, while 119 (66.9%) patients were diagnosed with new-onset DI. Hypernatremia and hyponatremia developed in 127 (71.3%) and 128 (71.9%) patients after surgery, respectively. Syndrome of inappropriate antidiuresis occurred in 97(54.5%) patients. During hospitalization, hypernatremia recurred in 33 (18.5%) patients and in 54 (35.7%) during follow-up, of which 18 (11.9%) were severe. DI persisted in 140 (78.7%) patients before discharge. No relationship was found between the HHI score and incidence of early DI, hyponatremia, syndrome of inappropriate diuretic hormone, or prolonged DI. Compared with patients with a score of 0-1, those with scores =2.5-3 (OR = 5.289, 95% CI:1.098-25.477, P = 0.038) and >3 (OR = 10.815, 95% CI:2.148-54.457, P = 0.004) had higher risk of developing recurrent hypernatremia. Patients with a score >3 had higher risk of developing severe hypernatremia during hospitalization (OR = 15.487, 95% CI:1.852-129.539, P = 0.011) and at follow-up (OR = 28.637, 95% CI:3.060-267.981, P = 0.003). Conclusions: The neuroimaging scoring scale is a simple tool to semi-quantify HHI after surgery. Recurrent and severe hypernatremia should be considered in patients with a high HHI score (>2.5). An HHI score >3 is a potential predictor of adipsic DI development. Preventive efforts should be implemented in the perioperative period to reduce the incidence of potentially catastrophic complications.

[Facial nerve preservation following microsurgical removal of large and huge acoustic neuroma].

OBJECTIVES: To evaluate the long-term facial nerve function of patients following microsurgical removal of large and huge acoustic neuroma, and to identify the factors that influence these outcomes. METHODS: A retrospective review was performed which included 176 consecutive patients with a large acoustic neuroma (≥ 30 mm) underwent a retrosigmoid craniotomy for tumor resection between January 2002 to November 2009. House-Brackmann (HB) Scale was used preoperatively and in a long-term follow-up after surgery. Test for linear trend was applied for statistic analysis. RESULTS: Complete resection was achieved in 168 (95.5%) of these 176 patients with a mortality of 1.7%. Anatomic preservation of the facial nerve was attained in 96.0% of the patients. In the series of 96 patients who had at least 1-year follow-up (mean 3.0 years) the facial nerve function preservation (HB grade 1 - 2) was totally attained in 79 patients (82.3%), and 40 of 55 patients (72.7%) who presented huge tumors (diameter > 40 mm) among the 96 patients had facial nerve function preserved. Analysis showed that facial nerve function correlated linearly with tumor sizes (χ(2) = 14.114, ν = 1, P < 0.05). CONCLUSIONS: Complete removal of large and giant acoustic neuroma may be obtained via retrosigmoid approach with facial nerve preservation. Excellent long-term facial function can be expected in the majority of patients who undergo microsurgical removal of vestibular schwannoma via the suboccipital retrosigmoid approach. Tumor size is a significant prognostic parameter for facial nerve function following vestibular schwannoma surgery.

[Surgical outcomes of pediatric symptomatic epilepsy and their influencing factors].

OBJECTIVE: To investigate the surgical outcomes of pediatric symptomatic epilepsy and the influencing factors for postoperative outcomes. METHODS: A cohort of 48 children with symptomatic epilepsy received surgical treatment from October 2004 to September 2008. The surgical outcomes were followed up. RESULTS: A 27.3 months (range 12-51 months) follow-up was performed in 43 cases. Engel classification for evaluating postoperative epileptic outcomes showed that class I in 32 cases (74%), class II in 4 cases (9%), class III in 4 cases (9%) and class IV in 3 cases (7%). Preoperative seizure frequency is an independent predictor of postoperative epileptic outcomes (P<0.05). CONCLUSIONS: Operative treatment can lead to a favorable result in children with symptomatic epilepsy. Preoperative seizure frequency is an independent influencing factor for postoperative outcomes.

[Surgical treatment of childhood craniopharyngioma: clinical analysis of 31 cases].

OBJECTIVE: To study the diagnosis, surgical treatment and outcome of craniopharyngioma in 31 children. METHODS: The clinical data of 31 children (aged 7-14 years) with craniopharyngioma were studied retrospectively. RESULTS: Headache, visual disorder and growth retardation were main manifestations in the 31 children. The 31 children were definitely diagnosed with craniopharyngioma by CT and MRI. In the 31 cases, 19 (61.3%) underwent total tumor removal, 5 (16.1%) subtotal removal, and 7 (22.6%) partial removal. After tumor removal, transient diabetes insipidus occurred in 19 cases (61.3%) and long-term diabetes insipidus in 3 cases. Six cases (19.4%) presented hypothalamic injuries after surgery. No patient died after surgery. Five patients (16.1%) had recurrent tumor in a mean follow-up of 32.5 months. CONCLUSIONS: The diagnosis of childhood craniopharyngioma may be based on clinical manifestations and CT/MRI examinations. Craniotomy is a preferred surgical treatment. Proper extent of tumor resection should be determined in order to reduce the tumor recurrence and the incidence of postoperative complications.

[Neuroendoscopy for treatment of multilocular brain abscess in children].

OBJECTIVE: Multilocular brain abscess in children is a serious neurosurgical emergency and remains a serious, life-threatening disease. This study evaluated the role of neuroendoscopy in treating multilocular brain abscess in children. METHODS: Between January 2002 and June 2007, 16 children with multilocular brain abscess underwent an operation using a pure endoscopic procedure. RESULTS: Increased intracranial pressure was relieved after operation in the 16 patients. CT/MRI after operation showed the abscess cavities disappeared and only the residual abscess walls existed in the 16 patients. Fourteen patients were followed up for 6 months to 5 years after surgery. Abscess walls disappeared in 13 patients and abscess recurred only in 1 patient. CONCLUSIONS: Neuroendoscopy for treatment of multilocular brain abscess is safe and effective in children.

[Endoscopic anatomy involving the extended transsphenoidal approach].

OBJECTIVE: To provide pertinent anatomic data and details for the clinical application of the extended transsphenoidal approach; to probe the anatomic characteristic and method under endoscope; METHODS: 25 adult cadaver heads fixed in formalin were used to dissect, observe, measure and photograph the relationship between the neural and vascular structure and the important anatomic landmarks related to the extended transsphenoidal approach under endoscope. RESULTS: The posterior and lateral wall of sphenoidal sinus could be well exposed by bilateral approach under endoscope. The clinical application of endoscope could improve the illumination of the operative field, magnify the objects and provide two-dimensional images. The distortion of the images under endoscope depended upon the distance between the lens and the object as well as the angle of the lens. To establish the anatomic vertical compartment under the endoscope might be helpful to the operation. The midline vertical compartment consisted of the planum sphenoidale, tuberculum sella, sella and clival indentation. The paramedian vertical compartment was composed of the medial third of the optic canal and the carotid artery protuberance. The lateral vertical compartment contained four bony protuberances (optic, cavernous sinus apex, maxillary, and mandibular). Endoscopic surgical maneuvering was under non-midline direction. Precise surgical landmarks are essential for a successful operation. These landmarks allowed the surgeon to recognize and approach the surgical target without confusion. The nasopharynx, middle turbinate, and inferior turbinate were some of the landmarks in the nasal cavity. Once the sphenoidal sinus was entered, the anatomic structures of the sphenoidal sinus posterior wall, which were described above, were the unique landmarks that will guide the surgeon to the surgical target. CONCLUSION: The anatomic characteristics under endoscope were different from those under microscope. The application of the extended transsphenoidal approach under endoscope could provide more extensive vision and satisfied exposure to reach the area of the central skull base.

[Quantitative analysis of the exposure of suboccipital far-lateral approach and postauricular transtemporal approach to the jugular foramen region].

OBJECTIVE: To study the exposure of suboccipital far-lateral approach and postauricular transtemporal approach to the jugular foramen region based on quantitative measurements, and provide reliable anatomic data for selecting surgical approach individually and protecting the function of important structures. METHODS: The complete approach of the suboccipital far-lateral approach and the postauricular transtemporal approach were reproduced in twelve (twenty-four sides) head-neck specimens of adults be fixed in 10% formalin. The exposure area to the jugular foramen region was obtained using a stereotactic device, and the length of exposure of the clivus and the trigeminal nerve were measured using a vernier caliper. RESULTS: In the suboccipital far-lateral approach, the significant increase in exposure was noted after removal of the jugular process and partial resection of occipital condyle. In the postauricular transtemporal approach, the exposure increased significantly after complete retrolabyrinthine approach, partial labyrinthectomy and transcochlear approach. CONCLUSIONS: Resection of jugular process is the key to expose the jugular foramen through the far-lateral approach. The infralabyrinthine approach and the partial labyrinthectomy approach are ideal approaches to expose the jugular foramen region laterally.

[Clinical significance of the expression of the RCAS1 mRNA and protein in astrocytic tumors].

OBJECTIVE: To determine the mRNA and protein expressions of RCAS1 in human astrocytic tumors, and to explore the relation between their expression and the genesis and development of tumor. METHODS: The RCAS1 mRNA expression in human astrocytic tumors was evaluated by RT-PCR, and the RCAS1 protein expression was studied by immunohistochemical staining. RESULTS: The quantities of RCAS1 mRNA expression between diffusive astrocytoma(Grade II) and anaplastic astrocytoma(Grade III), anaplastic astrocytoma and glioblastoma(Grade IV) were significantly different(P<0.05), while the expression scores of RCAS1 protein were different only between the anaplastic astrocytoma and glioblastoma(P<0.01). RCAS1 protein expression was positively correlated with the tumor grade (r=0.573,P<0.001). The RCAS1 protein was not detected in normal brain tissues by immunohistochemical staining. CONCLUSION: The RCAS1 expression is related to the histological grade of astrocytic tumor. In astrocytic tumors, the RCAS1 expression is regulated transcriptionally and posttranscriptionally.

Solitary Fibrous Tumor of Central Nervous System: Clinical and Prognostic Study of 24 Cases.

BACKGROUND: Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that occasionally occur in the central nervous system (CNS). It is difficult to fully understand their clinical characteristics, partly due to a limited number of reported cases. METHODS: We reviewed 24 patients admitted to our institution between 2009 and 2016 with CNS solitary fibrous tumors. We reviewed and analyzed patient profiles, such as demographics, presentations, imaging studies, extent of resection, and adjuvant treatment. Differences between malignant and benign SFTs were assessed using the χ2 test or Student's t-test. Kaplan-Meier analysis was used to estimate the disease-free survival (DFS) rate. The multivariate Cox regression analysis was performed to evaluate the possible predictive value of the DFS rate of the previously mentioned covariates. RESULTS: A total of 13 men and 11 women were enrolled in the study (the average age was 43). The median follow-up time was 58 months. Twenty-one patients underwent gross total resection (GTR), and 3 patients received a subtotal resection (STR). The tumors in 15 patients (62.5%) were atypical or malignant. One patient (4.2%) suffered SFT-related death (multiple organ failure by tumor metastasis), and 3 patients (12.5%) experienced tumor recurrence. We found that a large tumor size (≥10 cm, P < 0.001) and STR (P < 0.001) were negatively associated with the DFS rate. CONCLUSION: CNS SFTs are rare, slow-growing, less aggressive, and recrudescent tumors. Complete resection is the most effective therapy. Large tumor size and STRs might shorten DFS time.

[Mononostril-septum-transsphenoidal approach for pituitary adenoma].

OBJECTIVE: To summarize the mononostril-septum-transsphenoidal approach for pituitary adenoma. METHODS: The clinical features, operative techniques, and outcome of 36 patients with pituitary adenoma were analyzed retrospectively. RESULTS: Tumors were totally removed in 28 cases, and subtotally resected in 8 patients. No patient died after the operation. Endocrine symptom of 31 patients returned to the normal level, the symptom of the other 5 cases were improved. Thirty patients with visual field defects recovered after the operation. Cerebrospinal fluid leakage occurred in one patient, and was cured with conservative treatment in 2 weeks. CONCLUSION: Mononostril-septum-transsphenoidal approach can make use of the natural space of the nasal cavity, which has many advantages, such as direct approach, short operative time, minimal invasion, and few complications. It is a effective transsphenoidal surgical approach.

Microsurgical Management of Craniopharyngiomas via a Unilateral Subfrontal Approach: A Retrospective Study of 177 Continuous Cases.

OBJECTIVE: To evaluate the outcomes of 177 cases of craniopharyngioma (CP) treated via a unilateral subfrontal approach. METHODS: A total of 177 continuous microscopic surgeries were performed by the senior author (Y.X.). The tumors were divided into 6 groups using the diaphragm sellae and the third ventricle floor as the anatomic references. The preoperative, postoperative, and long-term follow-up data were analyzed to evaluate the extent of tumor resection, recurrence, and functional status. RESULTS: The subfrontal-basal approach was used in 169 (91.4%) cases. Total resection was achieved in 167 (94.4%) cases. A total of 158 patients were followed from 6 to 130 months. There were 3 perioperative and 23 delayed deaths. Twenty-two patients had tumor recurrence (12.7%). The progression-free survival was 80% at 5 years and 72% at 10 years. The overall survival was 84.0% at 2.5 years and 83.2% at 10 years. There was a significant increase of pituitary dysfunction after total resection. Neurologic function was stable in most patients. Rate of hypothalamic dysfunction and mortality were higher in patients with intraventricular CPs. Of the surviving patients, 91.8% were living independently with acceptable morbidities at the end of the study. CONCLUSIONS: Most CPs extend along the intrasellar-suprasellar-third ventricle axis. A subfrontal-basal approach is a simple, safe, and effective approach to resecting CPs extending along the vertical axis. A translamina terminalis approach is an ideal corridor to resect intraventricular CP. The benefit of radical resection remains controversial, especially for CPs involving the infundibulotuberal region.

Effect of ATorvastatin On Chronic subdural Hematoma (ATOCH): a study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH. METHODS/DESIGN: We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4(th), 12(th), and 24(th) weeks; 2) Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life-the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight. DISCUSSION: Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier--NCT02024373 The date of trial registration: 7 August 2013.

Aetiology of epilepsy in surgically treated patients in China.

The aim of this retrospective, multicenter clinical study was to evaluate the aetiology of epilepsy in surgically treated patients in China. The detailed clinical records of all intractable partial epilepsy (IPE) were reviewed in five tertiary referral centres from June 1991 to June 2000. 1650 patients (927 males, 723 females) were recruited. 41.4% had aetiological factors, including the histories of major brain trauma (20.9%), febrile seizure (6.5%), meningitis (5.4%), encephalitis (5.0%), prenatal distress (2.1%), birth trauma (0.8%) and family history of seizure (0.7%). The pathological lesions were divided into eight groups according to the nature of the lesion: scar (19.2%), vascular malformations (VM) (17.7%), hippocampal sclerosis (HS) (16.2%), tumours (15.0%), gliosis (12.1%), neuronal migration disorders (NMDs) (7.4%), intracranial infection (4.5%), and other lesions (7.9%). In conclusion, effective management of these aetiological factors and pathological lesions may be essential to deal with IPE. Scar, HS, VM, NMDs are the most likely consequences of antecedent morbid events.

[Microsurgical treatment for craniopharyngioma combined transorbital-subfrontal and temporal craniotomy].

OBJECTIVE: To summarize the experience in microsurgical removal of craniopharyngioma using combined transorbital-subfrontal and temporal craniotomy. METHODS: Eighteen patients with craniopharyngioma varied from 3.1 cm to 6.2 cm in diameter. The tumor was located in the suprasellar region in 7 patients, extended to the third ventricle in 6, and down to the intrasellar from the suprasellar region in 4, and in the third ventricle in 1. Complete or partial cystic tumor was seen in 13 patients, and solid tumor in 5, and calcified tumor in 12. All the patients were operated on via combined transorbital subfrontal and temporal approach. The tumor was dissected in the spaces I, II and IV with great attention to the preservation of the perforating arteries from the carotid, posterior communication and anterior choroidal arteries to the structure of the hypothalamus. The solid portion of the tumor was removed by piecemeal. RESULTS: The tumor was totally removed in 14 patients and subtotally in 4. Postoperation, follow-up for 8 to 41 months showed no change in 3 residual tumors and one lost to follow-up. All patients Postoperative Karnofsky scales showed 80 - 90, in 12 patients, 60 - 70 in 5 patients, and 50 in 1. CONCLUSIONS: Combined transorbital-subfrontal and temporal approach can provide an excellent exposure to the sellar region, craniopharyngioma and its surrounding structures. This approach ensures less cerebral retraction for easy access to craniopharyngioma, including other large neoplasm of the middle cranial base with ventricle or posterior cranial base extension. Microsurgical techniques play an important role in removing tumor and preserving hypothalamic function.

[Clinical and neuroimage characteristics of primary central nervous system lymphoma].

OBJECTIVE: To analyze the clinical and neuroimage characteristics of primary central nervous system lymphoma and explore the methods of treatment. METHODS: The clinical data of 28 cases of primary central nervous system lymphoma were analyzed retrospectively. RESULTS: All the 28 patients with lyphoma were proved by craniotomy and pathologic study. The survival periods were 5 days to 40 months after the craniotomy. Eighteen patients received radiotherapy after the operation. Sixteen recurrent cases were proved by neuroimage and the minimum recurrent time was the 29th day after the operation. CONCLUSION: The duration of primary lymphoma in the central nervous system is short and the clinical symptom is serious. The neuroimage of primary lymphoma in the central nervous system has some characteristic changes. The recurrence may occur over a brief time after the operation even though the tumor has been totally removed under the microscope. The majority of lymphomas are sensitive to radiotherapy.

miR-124a restoration inhibits glioma cell proliferation and invasion by suppressing IQGAP1 and ß-catenin.

A number of microRNAs have been identified to be important regulators of tumorigenesis. Previous research has shown that miR-124 is abundantly expressed in normal brain tissue; however, only a few reports have focused on the biological impact of miR-124 on glioma cells, and the underlying mechanisms need to be elucidated. Therefore, we investigated the effect of miR-124a on glioma cell proliferation and invasion; furthermore, the underlying molecular mechanism was examined. The present study demonstrated that miR-124a expression was downregulated in human glioma tissues, and its expression level was negatively correlated with the pathological grade of the glioma. Restoration of miR-124a inhibited glioma cell proliferation and invasion in vitro. Furthermore, we found that miR-124a directly targeted and suppressed IQ motif containing GTPase activating protein 1 (IQGAP1), a well-known regulator of actin dynamics and cell motility. RNA interference assay showed that IQGAP1 knockdown led to downregulation of ß-catenin and downstream cyclin D1. Taken together, our study revealed that miR-124a could inhibit glioma cell proliferation and invasion by blocking the expression of the IQGAP1 gene and downstream ß-catenin and cyclin D1. This research may provide a useful molecular therapy for gliomas.

Expression and functional significance of ezrin in human brain astrocytoma.

Ezrin is overexpressed in a variety of neoplastic cells and is involved in the later stages of tumor progression and metastasis. The present study investigated the expression and functional significance of ezrin in human brain astrocytoma. Ezrin expression was examined in specimens from healthy human brains (10 autopsies) or human astrocytoma (107 cases) by immunohistochemistry. All healthy specimens were negative for ezrin expression, while this expression was positive in a great majority of human astrocytoma tissues (96/107; 89.7%; p < 0.05 vs. healthy). Ezrin expression was positively correlated with tumor grade (r = 0.551, p < 0.01). Analysis of clinicopathologic data revealed that the post-operation disease-free survival times were significantly (p < 0.001) different between those with a strong positive ezrin expression and those with a weak or negative expression. Specifically, median DFS in patients with a strongly positive ezrin expression was 13 months (range 2-46 months), while it was significantly (p < 0.001) longer in patients with weakly positive or negative expression (median of 28 months, range 6-56 months). In conclusion, there is a strong association between ezrin expression and increased malignancy in astrocytoma. Thus, enhanced ezrin expression may play an important role in the development of astrocytoma. Our results further indicate that ezrin may be useful for grading of astrocytoma and as a molecular marker for the prognosis.