Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 78
Filter
1.
Front Endocrinol (Lausanne) ; 13: 958295, 2022.
Article in English | MEDLINE | ID: mdl-36120435

ABSTRACT

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.


Subject(s)
Brain Injuries, Traumatic , Craniopharyngioma , Diabetes Insipidus , Hypernatremia , Hyponatremia , Pituitary Neoplasms , Adult , Brain Injuries, Traumatic/complications , Child , Craniopharyngioma/complications , Craniopharyngioma/surgery , Diabetes Insipidus/complications , Diuretics , Hormones , Humans , Hypernatremia/epidemiology , Hypernatremia/etiology , Hyponatremia/epidemiology , Hyponatremia/etiology , Pituitary Neoplasms/complications , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Sodium , Water
2.
Cancer Cell Int ; 21(1): 456, 2021 Aug 28.
Article in English | MEDLINE | ID: mdl-34454479

ABSTRACT

BACKGROUND: The regulatory roles of long non-coding RNA (lncRNA) CRNDE in temozolomide (TMZ) chemoresistance to glioblastoma multiforme (GBM) are still poorly understood. Therefore, the function, characteristics, and possible mechanism of CRNDE in TMZ-induced chemoresistance to GBM were explored. METHODS: Firstly, the expression level of CRNDE in 58 cases of glioma tissue specimens and 30 cases of normal brain tissues were tested by qRT-PCR. Meanwhile, the correlation between CRNDE expression level, the clinicopathological characteristics, and survival time of patients with glioma were analyzed. Then, the CRNDE expression in various glioma cell lines was detected, and CRNDE knockdown cell models were constructed. Subsequently, to explore the effect of CRNDE on chemosensitivity to TMZ, cell viability was detected by the CCK-8 assay and IC50 values, and cell proliferation was detected by cell clone assay and EdU assay, as well as cell survival was detected by apoptosis with flow cytometry under TMZ treatment. Further, the expression of drug-resistance protein ABCG2, autophagy related proteins, and PI3K/Akt/mTOR pathway were measured by western blot or qRT-PCR in TMZ-treated glioma cells. Finally, the mouse tumor xenograft model was established and the tumor volume and weight were measured, and ABCG2 expression was conducted by immunohistochemistry assay. RESULTS: The integrated results demonstrated lncRNA CRNDE was a poor prognosis factor for GBM patient, which was upregulated in patients who were resistant to TMZ, and closely associated with chemotherapeutic response status to TMZ treatment. Further, functional assays revealed that knockdown of CRNDE could notably reduce glioma cell viability and proliferation, and elevate cell apoptosis to enhance the chemosensitivity to TMZ in vitro and in vivo. Mechanistically, the depression of CRNDE could diminish the expression of LC3 II/I, Beclin1 and Atg5 and increase the p62 expression level to inhibit autophagy due to the activation of PI3K/Akt/mTOR pathway as well as highly correlated with ABCG2 expression. CONCLUSIONS: Overall, the study provided that lncRNA CRNDE is a reliable clinical predictor of outcome and prognosis and a potential biomarker for predicting TMZ treatment response in GBM by modulating the autophagy through PI3K/Akt/mTOR pathway and ABCG2 expression which may be a novel therapeutic target for regulating TMZ sensitivity to GBM.

3.
Int J Oncol ; 59(3)2021 Sep.
Article in English | MEDLINE | ID: mdl-34278467

ABSTRACT

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the scratch-wound assay data shown in Fig. 3A and Transwell cell migration data shown in Figs. 3B and 6B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 48: 541-550, 2016; DOI: 10.3892/ijo.2015.3267].

5.
Genome Biol ; 22(1): 125, 2021 04 29.
Article in English | MEDLINE | ID: mdl-33926529

ABSTRACT

BACKGROUND: Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes. RESULTS: We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes. CONCLUSIONS: These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.


Subject(s)
Disease Susceptibility , Medulloblastoma/etiology , Medulloblastoma/metabolism , Mixed Function Oxygenases/genetics , Mixed Function Oxygenases/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , 5-Methylcytosine/analogs & derivatives , Animals , Biomarkers, Tumor , Computational Biology/methods , CpG Islands , DNA Methylation , Databases, Nucleic Acid , Disease Models, Animal , Disease Progression , Epigenesis, Genetic , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Medulloblastoma/mortality , Medulloblastoma/pathology , Mice , Mice, Transgenic , Nucleotide Motifs , Prognosis
6.
Sci Rep ; 10(1): 4655, 2020 03 13.
Article in English | MEDLINE | ID: mdl-32170139

ABSTRACT

Petroclival meningiomas (PCMs) are regarded as one of the most formidable challenges in neurosurgery. We retrospectively assessed the surgical outcomes of PCMs based on a tumor classification to evaluate the long-term outcomes. A series of 168 patients with PCMs from July 1996 to January 2017. On the basis of the difference in the origin of dural attachment and patterns of growth, the PCMs were classified into 4 different types. The clinical characteristics, surgical record, and follow-up data of each type were reviewed. The study included 138 females (82.1%) with an average age of 49.9 ± 16.2 years. And 138 cases (82.1%) had developed neurological deficits preoperatively with the average tumor size of 44.0 ± 10.6 mm. Specific surgical approaches were applied depended on the tumor classification. Gross total resection (GTR) was achieved in 119 cases (70.8%) with the complications of 46 cases (27.7%). With a median follow-up of 86.5 months, there were 41 cases of recurrence/progress (25.7%) and 39 cases of morbidity (26.4%). Compared with the non-GTR group, the GTR significantly decreased the R/P rate (P = 0.001), prolonged the R/P-FS time (P = 0.032) and improved the follow-up neurological status (P = 0.026). Favorable outcomes and acceptable morbidity were achieved with the treatment strategy of the choice of specific approaches for each type. Meanwhile, the differences of each type in diverse clinical characteristic were verified. Individualized assessment and suitable approach choice should be based on the tumor classification to improved the GTR and quality of life for patients.


Subject(s)
Meningeal Neoplasms/pathology , Meningeal Neoplasms/surgery , Meningioma/pathology , Meningioma/surgery , Adolescent , Adult , Aged , Female , Humans , Male , Meningeal Neoplasms/diagnostic imaging , Meningioma/diagnostic imaging , Middle Aged , Neurosurgical Procedures , Quality of Life , Retrospective Studies , Survival Analysis , Treatment Outcome , Tumor Burden , Young Adult
7.
Front Oncol ; 10: 609056, 2020.
Article in English | MEDLINE | ID: mdl-33552981

ABSTRACT

BACKGROUND: Management of tentorial notch meningiomas (TNM) remains a challenge for neurosurgeons. We demonstrate the clinical characteristics and surgical experiences of TNM based on our cases according to a proposed further classification. METHODS: We retrospectively analyzed clinical and follow-up data in a consecutive series of 53 TNM patients who underwent microsurgical operation from 2011 to 2019 in our institution. The operations were performed using various approaches. Clinical history, preoperative and postoperative neurofunction, imaging results, and surgical outcomes were collected for further classification of TNM. RESULTS: All TNM cases were divided into anterior (T1), middle (T2), and posterior notch (T3). According to the direction of tumor extension and correlation with the neurovascular structures, detailed subtypes of anterior TNMs were identified as the central (T1a), posterior (T1b), and medial type (T1c). The middle TNMs were divided into the infratentorial (T2a), supratentorial (T2b), and supra-infratentorial type (T2c). The posterior TNMs were divided into superior (T3a), inferior (T3b), lateral (T3c), and straight sinus type (T3d) in reference to Bassiouni's classification. Total removal of the tumor was achieved in 46 cases, with five cases of subtotal and two cases of partial removal without any recorded deaths in our series. In total, five subtotal resected cases underwent gamma-knife treatment and achieved stable disease. Postoperative aggravation or new onset cranial nerve dysfunction occurred in some individual cases, with incidences ranging from 3.77 to 15.10% and improved preoperative neurological deficits ranging from 0 to 100%. CONCLUSION: Further, TNM classification based on the intracranial location, extension direction, relationship with brainstem, and neurovascular structures guides preoperative evaluation, rational surgical approach selection, and surgical strategy formulation. Taking microsurgery as the main body, a satisfactory outcome of TNM treatment can be achieved for complicated tumors by combining stereotactic radiotherapy. This study demonstrates the surgical outcomes and complications in detail. Further classification might be helpful for treatment decisions in the future.

9.
JAMA Neurol ; 75(11): 1338-1346, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30073290

ABSTRACT

Importance: Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH. Objective: To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. Design, Setting, and Participants: The Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified. Interventions: Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. Main Outcomes and Measures: The primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week. Results: One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported. Conclusions and Relevance: Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH. Trial Registration: ClinicalTrials.gov Identifier: NCT02024373.


Subject(s)
Atorvastatin/pharmacology , Hematoma, Subdural, Chronic/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Outcome Assessment, Health Care , Aged , Atorvastatin/administration & dosage , Atorvastatin/adverse effects , China , Double-Blind Method , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Male , Middle Aged
10.
BMC Cancer ; 18(1): 773, 2018 Jul 31.
Article in English | MEDLINE | ID: mdl-30064493

ABSTRACT

BACKGROUND: High-grade gliomas (HGGs) exhibit marked heterogeneity in clinical behavior. The purpose of this study was to identify a novel biomarker that predicts patient outcome, which is helpful in HGG patient management. METHODS: We analyzed gene expression profiles of 833 HGG cases, representing the largest patient population ever reported. Using the data set from the Cancer Genome Atlas (TCGA) and random partitioning approach, we performed Cox proportional hazards model analysis to identify novel prognostic mRNAs in HGG. The predictive capability was further assessed via multivariate analysis and validated in 4 additional data sets. The Kaplan-Meier method was used to evaluate survival difference between dichotomic groups of patients. Correlation of gene expression and DNA methylation was evaluated via Student's t-test. RESULTS: Patients with elevated FBXO17 expression had a significantly shorter overall survival (OS) (P = 0.0011). After adjustment by IDH1 mutation, sex, and patient age, FBXO17 gene expression was significantly associated with OS (HR = 1.29, 95% CI =1.04-1.59, P = 0.018). In addition, FBXO17 expression can significantly distinguish patients by OS not only among patients who received temozolomide chemotherapy (HR 1.35, 95% CI =1.12-1.64, P = 0.002) but also among those who did not (HR = 1.48, 95% CI =1.20-1.82, P < 0.0001). The significant association of FBXO17 gene expression with OS was further validated in four external data sets. We further found that FBXO17 endogenous expression is significantly contributable from its promoter methylation. CONCLUSION: Epigenetically modulated FBXO17 has a potential as a stratification factor for clinical decision-making in HGG.


Subject(s)
Brain Neoplasms/metabolism , Brain Neoplasms/mortality , F-Box Proteins/metabolism , Glioma/metabolism , Glioma/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/genetics , Child , Cohort Studies , DNA Methylation , Epigenesis, Genetic , F-Box Proteins/genetics , Female , Glioma/genetics , Humans , Male , Middle Aged , Mutation/genetics , Prognosis , Young Adult
11.
Exp Ther Med ; 15(6): 4798-4804, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29805498

ABSTRACT

Temozolomide (TMZ) is one of the most commonly used drugs for the clinical treatment of glioblastomas. However, it has been reported that treatment with TMZ can induce autophagy, which leads to tumor resistance and increases the survival of tumor cells. MicroRNA-30a (miR-30a) has been found to have inhibitory effects on autophagy by directly targeting beclin 1. However, the exact role of miR-30a in TMZ-treated glioblastoma cells has not been studied previously. The present study aimed to investigate whether miR-30a increased the cytotoxicity of TMZ to glioblastoma U251 cells, as well as the underlying mechanism. MTT and flow cytometry assay results showed that treatment with TMZ inhibited the proliferation of U251 cells while inducing cell apoptosis in a dose-dependent manner. Western blotting data showed that the expression levels of LC3-II and beclin 1 as well as the ratio of LC3-II to LC3-I were markedly increased in TMZ-treated U251 cells compared with the untreated control cells, indicating that treatment with TMZ induced autophagy. Moreover, reverse transcription-quantitative polymerase chain reaction data showed that treatment with TMZ led to a significant reduction in miR-30a levels in a dose-dependent manner in U251 cells. Elevation of the miR-30a level significantly inhibited TMZ-induced autophagy, demonstrated by the decreased LC3-II and beclin 1 levels and ratio of LC3-II to LC3-I, accompanied by the reduced proliferation and increased apoptosis in TMZ-treated U251 cells. Furthermore, luciferase reporter assay data indicated that beclin 1 was a direct target of miR-30a in U251 cells. In summary, this study demonstrated that miR-30a increases the chemosensitivity of glioblastoma U251 cells to temozolomide by directly targeting beclin 1 and inhibiting autophagy. Therefore, autophagy may be a promising target for the treatment of TMZ-resistant tumors.

12.
Invest New Drugs ; 36(6): 961-969, 2018 12.
Article in English | MEDLINE | ID: mdl-29508248

ABSTRACT

Genomic studies have established a set of three core-signaling pathways, receptor tyrosine kinase (RTK), p53 and retinoblastoma (Rb) signaling pathways, contributing glioblastoma (GBM) and revealed that dysregulation of at least two pathways is required for GBM progression. In the present study, we investigate efficacy of combination of palbociclib, cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and erlotinib, epidermal growth factor receptor (EGFR) inhibitor in GBM cell systems with different p53 status. Cell proliferation and colony formation assays showed that the combination treatment synergistically suppressed GBM cell proliferation. LN229 cells with mutant p53 and wild-type PTEN were more sensitive to the combination treatment. Further studies indicated that the synergetic anti-GBM effects were due to cell apoptosis induction and cell cycle arrest at G1 phase. Signaling examination indicated that levels of p-Rb and p-4E-BP1 significantly decreased by the combination treatment; however, Akt and MAPK signaling were differentially suppressed among the three GBM cell lines. Hence, our data demonstrate that palbociclib and erlotinib exert synergistic anti-GBM activity, providing pre-clinical evidence and a proof-ofconcept that usage of the combination of EGFR and CDK4/6 inhibitors for GBM treatment.


Subject(s)
Antineoplastic Agents/pharmacology , Erlotinib Hydrochloride/pharmacology , Glioblastoma/metabolism , Glioblastoma/pathology , Piperazines/pharmacology , Pyridines/pharmacology , Retinoblastoma Protein/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Erlotinib Hydrochloride/therapeutic use , Glioblastoma/drug therapy , Humans , Piperazines/therapeutic use , Pyridines/therapeutic use , Signal Transduction/drug effects , Tumor Stem Cell Assay
13.
Biosci Rep ; 38(6)2018 12 21.
Article in English | MEDLINE | ID: mdl-29133459

ABSTRACT

In certain surgical procedures, sacrificing the superior petrosal vein (SPV) is required. Previous studies have reported transient cerebellar edema, venous infarction, or hemorrhage that might occur after sectioning of the SPV. The present study investigated the pathophysiological changes in cerebellum and brain stem after SPV sacrifice. Rabbits were divided into the operation group where the SPV was sacrificed and the control group where the SPV remained intact. Each group was further subdivided into 4, 8, 12, 24, 48, and 72 h groups which represented the time period from sacrificing of the SPV to killing of the rabbits. The water content (WC), Na+ content, K+ content, and pathophysiological changes in cerebellum and brain stem tissue were measured. In comparison with the control, the WC and Na+ content of cerebellar tissue were increased in the 4, 8, 12, and 24 h operation subgroups (P<0.05), but only increased in the 4-h subgroup of the brain stem tissue (P<0.05). The K+ content of the cerebellar tissue decreased in the 4, 8, 12, and 24 h operation subgroups (P<0.05) but only decreased in the 4-h subgroup of brain stem tissue (P<0.05). Nissl staining and TEM demonstrated that cerebellar edema occurred in the 4, 8, 12, and 24 h operation subgroups but not in the 48- and 72-h subgroups. Brain stem edema occurred in the 4-h operation subgroup. In summary, cerebellum and brain stem edema can be observed at different time points after sacrificing of the SPV in the rabbit model.


Subject(s)
Brain Edema/physiopathology , Brain Stem/physiopathology , Cerebellum/physiopathology , Cerebral Veins/physiopathology , Animals , Brain Edema/metabolism , Brain Stem/blood supply , Brain Stem/metabolism , Cerebellum/blood supply , Cerebellum/metabolism , Cerebral Veins/metabolism , Disease Models, Animal , Humans , Nissl Bodies/metabolism , Nissl Bodies/pathology , Rabbits
14.
J Cancer ; 8(15): 2924-2932, 2017.
Article in English | MEDLINE | ID: mdl-28928883

ABSTRACT

PURPOSE: AHNAK is originally identified as a giant protein based on the estimated size of approximately 700 kDa. The aim of this study is to identify the role of AHNAK in the pathogenesis of glioma. METHODS: We tested AHNAK mRNA level in a panel of six human glioma cell lines, and in 30 cases of normal brain tissues and 73 cases of glioma tissue samples using a qRT-PCR method. Further, we analyzed the relationship of AHNAK expression with clinicopathological characteristics in glioma patients. Meanwhile, we analyzed the relationship of expression of AHNAK and survival of glioma patients in survival analyses. Then, in vitro, we analyzed the biological effects of AHNAK in glioma cell lines (U87 and U251) including proliferation assay, cell transwell assay, and apoptosis. And in vivo, we examined the effects of AHNAK on tumor growth using xenograft model of human glioma cells in nude mice. Then we examined the expression of Ki-67-positive cells in these tumors. RESULTS: We found that the mRNA levels of AHNAK were down-regulated in 4 of 6 human glioma cell lines, especially in U87 and U251 cell lines. Meanwhile, in glioma patients, a negative correlation was found between the expression of AHNAK and the glioma histopathology. And a low expression of AHNAK was a significant and independent prognostic factor for poor survival of glioma patients. Through over expression of AHNAK in both of U87 and U251, we demonstrated that overexpression of AHNAK could inhibit glioma cell proliferation and invasion, induce apoptosis, and inhibit in vivo glioma tumor growth and ki-67 expression. CONCLUSIONS: The AHNAK acts as a potential tumor suppressor. Our study provides a preclinical basis for developing AHNAK as a reliable clinical prognostic indicator for glioma patients, and a new biomarker for treatment response, and a potentially therapeutic target in glioma management options.

15.
Exp Ther Med ; 13(3): 1011-1016, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28450934

ABSTRACT

Surgery is the primary treatment of choice for all symptomatic pituitary adenomas except prolactinomas. Common postoperative complications include endocrinopathies, vision impairment and cerebrospinal fluid leak. The present study assessed 153 continuous microscopic surgeries for pituitary adenomas performed by an author of the present study between 2010 to 2014. Patients underwent either transphenoidal or transcranial surgery depending on their individual tumor characteristics. Five typical cases are presented in the present study and intraoperative identification and preservation of the gland and stalk were discussed. Postoperative complications were analyzed and compared with the literature. In the present analysis, 90.2% patients received transphenoidal surgery, and the rest underwent transcranial operation. Gross total resection was achieved in 81.2% patients in the transphenoidal group and 46.7% patients in the transcranial group. No new hypopituitarism or worsening of the pre-existing pituitary dysfunctions was detected. The most common postoperative endocrinopathy was diabetes insipidus (transphenoidal group, 4.3%; transcranial group, 26.7%). All patients were fully recovered prior to discharge. The findings indicated the importance of pituitary gland and stalk preservation during the microscopic surgery to minimize postoperative morbidity and mortality, without compromising the extent of tumor resection. Based on preoperative imaging characteristics and intraoperative observations, surgeons should try all possible means to preserve the pituitary stalk and gland during surgery in order to minimize postoperative endocrinopathies and improve quality of life.

16.
Biomed Res Int ; 2017: 8124501, 2017.
Article in English | MEDLINE | ID: mdl-28421199

ABSTRACT

Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson's disease (PD). The goal of the present study was to confirm VPA's dose-dependent neuroprotective propensities in the MPP+ model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors. VPA reversed MPP+-induced mitochondrial apoptosis and counteracted MPP+-induced extracellular signal-regulated kinase (ERK) and Akt repression and inhibited glycogen synthase kinase 3ß (GSK3ß) activation through induction of GSK3ß phosphorylation. Moreover, inhibitors of the PI3K and MAPK pathways abolished GSK3ß phosphorylation and diminished the VPA-induced neuroprotective effect. These findings indicated that VPA's neuroprotective effect in the MPP+-model of PD is associated with GSK3ß phosphorylation via Akt and ERK activation in the mitochondrial intrinsic apoptotic pathway. Thus, VPA may be a promising therapeutic candidate for clinical treatment of PD.


Subject(s)
Apoptosis/drug effects , Dopaminergic Neurons/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , MAP Kinase Signaling System/drug effects , MPTP Poisoning/prevention & control , Mitochondria/metabolism , Neuroprotective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Valproic Acid/pharmacology , Animals , Dopaminergic Neurons/pathology , Female , MPTP Poisoning/metabolism , MPTP Poisoning/pathology , Mice , Mice, Inbred BALB C , Mitochondria/pathology
17.
World Neurosurg ; 101: 457-465, 2017 May.
Article in English | MEDLINE | ID: mdl-28192265

ABSTRACT

OBJECTIVES: To compare and analyze the differences in clinical manifestations and surgical outcomes after gross total resection (GTR) for vestibular schwannoma between elderly and younger patients. METHODS: We conducted a retrospective study of 40 elderly (≥65 years) and 40 younger (<65 years) patients, and matched operation dates and tumor size in the 2 groups were matched. All 80 patients underwent microsurgical resection though the sigmoid approach, by the same surgeon (X.Y.). We then summarized clinical manifestations, image data, perioperative complications, tumor recurrence, and functional outcomes and assessed the differences between the 2 groups. RESULTS: The mean follow-up time was 52.64 months. Elderly patients had a poorer preoperative American Society of Anesthesiology physical status scores than younger patients (62.5% vs. 30%, P = 0.004) and were more likely to have balance disorders (72.5% vs. 25%, P < 0.01), without other preoperative differences. Both groups of patients achieved GTR. The incidence of infection was slightly but not significantly greater in elderly patients (P > 0.05). There were also no significant differences in perioperative complications, recurrence rate, facial nerve function, hearing level, or Karnofsky Performance Status Scale scores between younger and older patients. CONCLUSIONS: Elderly patients tended to suffer from poorer health (American Society of Anesthesiology score) and poor balance before the operation; however, they did not experience more complications, worse nerve function, or worse quality of life in the perioperative or follow-up times. We conclude that GTR of vestibular schwannomas, even large or giant ones, is a safe and effective option for elderly patients.


Subject(s)
Microsurgery/trends , Neuroma, Acoustic/diagnostic imaging , Neuroma, Acoustic/surgery , Postoperative Complications/diagnostic imaging , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Microsurgery/adverse effects , Middle Aged , Neuroma, Acoustic/epidemiology , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome
18.
World Neurosurg ; 99: 584-592, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28017751

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/metabolism , Central Nervous System Neoplasms/surgery , Solitary Fibrous Tumors/surgery , Adult , Aged , Central Nervous System Neoplasms/diagnostic imaging , Central Nervous System Neoplasms/metabolism , Central Nervous System Neoplasms/pathology , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/epidemiology , Prognosis , Proportional Hazards Models , Radiosurgery , Radiotherapy, Adjuvant , Retrospective Studies , Solitary Fibrous Tumors/diagnostic imaging , Solitary Fibrous Tumors/metabolism , Solitary Fibrous Tumors/pathology , Tomography, X-Ray Computed , Tumor Burden , Young Adult
19.
Cell Physiol Biochem ; 39(6): 2173-2185, 2016.
Article in English | MEDLINE | ID: mdl-27802437

ABSTRACT

BACKGROUND: Valproic acid (VPA), an established antiepileptic drug, was assessed for antitumor activity, including its effects on glioblastoma, but its role has not been determined. METHODS: In the present study, we investigated VPA-induced apoptosis effects on human U87 cells by cell viability, lactate dehydrogenase (LDH) release, TUNEL/Hoechst staining and flow cytometric in vitro, then we further explored the underlying molecular mechanisms using the selective antagonists PD98059, LY294002 and SB216763. RESULTS: The data showed that VPA dose-dependent induction of glioma U87 cells to undergo apoptosis through the mitochondria-dependent pathway in vitro. VPA activated the ERK/Akt pathways by increasing their protein phosphorylation and in turn inhibited GKS3ß activation by the induction of GKS3ß phosphorylation. However, the MAPK inhibitor PD98059 and/or PI3K inhibitor LY294002 were able to antagonize the effects of VPA by abolishing ERK/Akt activations and cancelling GSK3ß suppression, thus it impaired VPA apoptosis-inducing effects on glioma cells. Furthermore, the GSK3ß inhibitor SB216763 caused a strong suppression of GSK3ß activity, which showed similar effects of VPA on regulation of protein expression and apoptosis. CONCLUSION: These findings suggest that GSK3ß may be the central hub for VPA-induced apoptosis and VPA can be further evaluated as a novel agent for glioma therapy.


Subject(s)
Apoptosis/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Glioma/enzymology , Glioma/pathology , Glycogen Synthase Kinase 3 beta/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Valproic Acid/pharmacology , Brain Neoplasms/enzymology , Brain Neoplasms/pathology , Cell Line, Tumor , Enzyme Activation/drug effects , Flow Cytometry , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Models, Biological , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 41(10): 1058-1063, 2016 Oct 28.
Article in Chinese | MEDLINE | ID: mdl-27807328

ABSTRACT

OBJECTIVE: To explore the influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma.
 Methods: The data of 83 patients, who underwent unilateral sub-frontal approach resection of craniopharyngioma between 2010 and 2014 by the same senior neurosurgeon, were retrospectively analyzed. The patients were divided into a vasopressin tannate group (used group) and a control group. The diabetes insipidus and serum sodium changes were compared between the two groups.
 Results: Compared with the control group, the incidence of diabetes insipidus decreased at the early postoperation in the vasopressin tannate group (P<0.05). There was high incidence of diabetes insipidus in patients with pituitary stalk excision and tumor close adhesion to the third ventricle floor at the early postoperation (P<0.05). Under such conditions, the incidence of diabetes insipidus in the vasopressin tannate group was decreased compared with the control group (P<0.05). Postoperative hypernatremia occurred in 37 patients (44.6%), and hyponatremia occurred in 60 patients (72.3%), the average time of the occurrence of hpernatremia and hyponatremia was 1.4 and 3.7 days after surgery. Postoperative high serum sodium and low serum sodium appeared alternately in 19 patients (22.9%). There was significant difference in the serum sodium distribution in the first day after surgery in both groups (P<0.05), and the percent of hpernatremia in the vasopressin tannate group was significantly less than that in the control group (P<0.05).
 Conclusion: Preventive use of vasopressin tannate can effectively reduce diabetes insipidus and hypernatremia incidence at the early postoperative stage after microsurgery for craniopharyngioma.


Subject(s)
Arginine Vasopressin/therapeutic use , Craniopharyngioma/complications , Diabetes Insipidus/prevention & control , Hypernatremia/prevention & control , Microsurgery/adverse effects , Postoperative Complications/prevention & control , Craniopharyngioma/surgery , Female , Humans , Hypernatremia/epidemiology , Hyponatremia/epidemiology , Incidence , Male , Pituitary Gland/surgery , Pituitary Neoplasms , Postoperative Period , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL
...