Adult ; Humans ; Rhabdoid Tumor/surgery* ; Teratoma/pathology* ; Medulloblastoma ; Central Nervous System Neoplasms ; Cerebellar Neoplasms ; Brain Neoplasms/pathology*

OBJECTIVETo investigate the apoptosis and proliferation effect of matrine on human medulloblastoma cell line D341 in vitro and the effect of the expression of the related caspase 3 and caspase 9 proteins.

METHODSThe D341 cells were cultivated successfully in vitro. Then the cells were divided into 5 groups according to the concentration of matrine (0.5 mg/mI group, 1.0 mg/ml group, 1.5 mg/ml group, 2.0 mg/ml group and the control group was 0 mg/ml). All the experiments were repeated three times. The cell morphologic and structure change was observed with the optical microscope and the transmission electron microscope. The proliferation of D341 cell was analyzed using Cell Counting Kit-8 assay. Apoptosis was detected by Annexin V-FITC/PI double staining. The expression of Caspase3 and Caspase9 was detected by Western blot.

RESULTSWith the effect of matrine, the proliferation inhibition rate gradually increased with drug concentrations increasing, and there was a significant difference (P < 0.01). The inhibitory effect of matrine on cell proliferation was different with the different treatment time, there was a significant difference between the 24 h to 72 h groups (P < 0.01). The apoptotic rate increased with matrine concentrations increasing. There were significant differences between the group of 0.5 mg/mI or 1.0 mg/mI to the group of 1.5 mg/mI or 2.0 mg/mI (P < 0.05). The apoptotic rate increased with the prolonged treatment time. There were significant differences between the group of 24 h or 48 h to the group of 72 h ( P < 0.05). With the increase of matrine concentration, the expression of Caspase 3 and Caspase 9 increased (P < 0.01).

CONCLUSIONMatrine induces the apoptosis, and inhibits the proliferation of human medulloblastoma D341 cells in vitro by up-regulation of the expression level of Caspase3, Caspase9.

Alkaloids ; pharmacology ; Apoptosis ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cerebellar Neoplasms ; metabolism ; pathology ; Humans ; Medulloblastoma ; metabolism ; pathology ; Quinolizines ; pharmacology ; Up-Regulation

OBJECTIVETo identify novel lncRNAs involved in cerebellar neurogenesis using neuronal specific Nbs1-deficient (Nbs1(CNS-del)) mouse model.

METHODSMicroarray analysis was performed to identify differentially expressed lncRNAs between Nbs1(CNS-ctr) and Nbs1(CNS-del) mice. Expression profiles of lncRNA Gm15577 and coding gene Negr1 in mice, primary cerebellar culture and cell lines were measured using RT-qPCR. Subcellular fractionation was performed to determine the subcellular localization of Gm15577.

RESULTSGm15577 was specifically expressed in mice cerebellum in a developmentally regulated manner, which could be abolished upon Nbs1-deficiency. Gm15577 was located in the intronic region of Negr1 in a reversed orientation. Gm15577 modulated the RNA expression of Negr1, Shh and β-catenin. NEGR1 had a distinct expression pattern between normal and medulloblastoma patients.

CONCLUSIONGm15577 may modulate cerebellar granule cell proliferation and differentiation by targeting Negr1, and their dysfunctions or abnormal expression may be related to tumorigenesis of medulloblastoma.

Animals ; Cell Differentiation ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cerebellar Neoplasms ; pathology ; Cerebellum ; cytology ; physiology ; Disease Models, Animal ; Humans ; Introns ; Medulloblastoma ; pathology ; Mice ; Mice, Knockout ; Neurogenesis ; Neurons ; physiology ; RNA, Long Noncoding ; metabolism

OBJECTIVETo study the pathologic characteristics and prognosis in different subtypes of adult medulloblastoma (MB).

METHODSThe clinical information, imaging findings and pathologic characteristics of 151 cases of adult medulloblastomas were retrospectively reviewed and analyzed by chi-square test. The survival data were assessed using the Kaplan-Meier method.

RESULTSAmongst the 151 MB cases studied, there were 73 cases of classic MB, 36 cases of desmoplastic/nodular MB, 39 cases of anaplastic MB and 3 cases of large cell MB. The primary tumors were more frequently located in cerebral hemisphere in desmoplastic/nodular MB than in other subtypes (P=0.000).On the other hand, large cell/anaplastic MB were associated with more frequently local recurrence and distant metastasis (P=0.003). The post-operative overall survival time ranged from 6 to 150 months, with median survival being (103.3±5.7) months (95%CI, 92.52 to 115.09). The median survival of classic MB, desmoplastic/nodular MB and large cell/anaplastic MB was (110.7±7.8) months, (125.5±7.6) months and (57.6±7.6) months, respectively. The differences were statistically significant (P=0.000).

CONCLUSIONSThe three variants of MB show different biologic behavior. Large cell/anaplastic MB represents an independent poor prognostic indicator in adults.

Adolescent ; Adult ; Cerebellar Neoplasms ; classification ; metabolism ; pathology ; radiotherapy ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen ; metabolism ; Male ; Medulloblastoma ; classification ; metabolism ; pathology ; radiotherapy ; surgery ; Middle Aged ; Neoplasm Recurrence, Local ; Phosphopyruvate Hydratase ; metabolism ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Synaptophysin ; metabolism ; Young Adult

OBJECTIVETo study the clinicopathologic features, immunohistochemical findings, diagnosis and differential diagnosis of atypical teratoid/rhabdoid tumors (AT/RT) of central nervous system in childhood.

METHODSThe clinicopathologic data, morphologic features and immunophenotypes were reviewed in 6 cases of AT/RT. EnVision method was applied. Antibodies include cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, smooth muscle actin (SMA), muscle specific actin (MSA), glial fibrinary acid protein (GFAP), desmin, placental alkaline phosphatase (PLAP) and INI1.

RESULTSFive of the six cases of AT/RT occurred in infancy and early childhood. Histologically, the predominant component was rhabdoid cells. Cytoplasmic inclusions were present in all cases. Primitive neuroectodermal tumor (PNET) component was also identified in 5 of the 6 cases studied. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen and vimentin. The staining for INI1, desmin and PLAP was negative. Smooth muscle actin was expressed in 2 cases and glial fibrillary acidic protein in 5 cases. The proliferative index as demonstrated by Ki-67 staining was high.

CONCLUSIONSAT/RT is not a particularly uncommon malignancy in childhood. The histologic hallmark is the presence of rhabdoid cells with cytoplasmic inclusions. The tumor cells are positive for cytokeratin, epithelial membrane antigen and vimentin, and negative for INI1. Differential diagnosis includes PNET, medulloblastoma and medullomyoblastoma.

Brain Neoplasms ; metabolism ; pathology ; surgery ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Infant ; Keratins ; metabolism ; Male ; Medulloblastoma ; metabolism ; pathology ; Mucin-1 ; metabolism ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; Rhabdoid Tumor ; metabolism ; pathology ; surgery ; Teratoma ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

OBJECTIVETo study the expression of β-catenin protein and the status of loss of heterozygosity (LOH) on chromsome 10q in medulloblastoma, with clinical correlation.

METHODSImmunohistochemical study for β-catenin protein was carried out in 50 cases of medulloblastoma encountered in the First Affiliated Hospital of Xinjiang Medical University during the period from 2002 to 2011, including 32 cases of classic medulloblastoma, 13 cases of desmoplastic medulloblastoma and 5 cases of medulloblastoma with extensive nodularity. The status of LOH on 10q was also detected by fluorescence in-situ hybridization. The clinicopathologic characteristics and prognostic parameters were studied by Kaplan-Meien and Cox analysis.

RESULTSThe rates of expression of β-catenin protein in classic medulloblastoma, desmoplastic medulloblastoma and medulloblastoma with extensive nodularity were 53.1% (17/32), 4/13 and 1/5, respectively. The rate of LOH on 10q was 33.3% (8/24) in classic medulloblastoma and 2/11 in desmoplastic medulloblastoma. There was no statistically significant difference between the two tumor types. Univariate analysis showed that the expression of β-catenin protein (P = 0.022), lack of LOH on 10q (P = 0.020), extensiveness of tumor resection (P < 0.01), radiotherapy (P = 0.002) and chemotherapy (P < 0.01) represented important prognostic factors.

CONCLUSIONSMedulloblastoma with expression of β-catenin protein and without LOH on 10q carries a better prognosis. Assessment of these parameters is helpful in evaluating prognosis and subsequent patient management.

Adolescent ; Adult ; Cerebellar Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Child ; Child, Preschool ; Chromosomes, Human, Pair 10 ; genetics ; Female ; Follow-Up Studies ; Humans ; Infant ; Loss of Heterozygosity ; Male ; Medulloblastoma ; genetics ; metabolism ; pathology ; surgery ; Proportional Hazards Models ; Survival Rate ; Young Adult ; beta Catenin ; metabolism

OBJECTIVETo investigate the effects of microRNA-383 (miR-383) on PRDX3 gene expression, cell proliferation and apoptosis of human medulloblastma.

METHODSPRDX3 and miR-383 RNA expression was detected by real-time quantitative RT-PCR in human medulloblastoma tumor tissue samples, Daoy cell line and normal brain tissue samples. Western blot was used to detect protein expression of PRDX3. Synthetic miR-383 mimics were transfected into Daoy cells by lipofectamine. Using Cell Counting Kit-8 (CCK-8) method, flow cytometry was used to investigate the cell proliferation and apoptosis, cells reactive oxgen species(ROS), mitochondrial membrane potential changes in each experimental groups.

RESULTSOf 15 cases of human medulloblastoma tumor, 13 cases had miR-383 expression levels significantly lower than that of normal brain tissue, and 14 had PRDX3 mRNA expression levels significantly higher than that of normal brain tissue. The expression levels of miR-383 and PRDX3 in Daoy cells were 0.353 and 1.315 times than those of normal brain tissue, respectively. The protein expression levels of PRDX3 were higher in human medulloblatoma tumors and Daoy cells than that of normal brain tissue. Transfected miR-383 mimics increased the expression level of miR-383 after 24 h and 48 h was significantly higher than that of the control. In contrast, PRDX3 gene mRNA and protein expression levels were significantly decreased at 48 h compared with the control group. Using CCK-8 assay, the cell proliferation rate in the experimental group was significantly lower than that of the control group (P < 0.05). Annexin V-FITC assay demonstrated that early apoptosis rate of the experimental group (11.60 ± 0.30)% was significantly higher than those of the control group (2.3 ± 0.20)% and negative control group (10.37 ± 0.25)% (P = 0.000) after 48 h of transfection. The intracellular ROS levels after transfection at 24 and 48 h significantly increased than those of the control group. Mitochondrial membrane potential level at 24 h after transfection significantly decreased, comparing with the blank control group and the negative control group.

CONCLUSIONSCompared with normal brain tissue, decreased expression of miR-383 but elevated expression of PRDX3 are medulloblastoma tumour and Daoy cell lines. Up-regulation of miR-383 knockdowns the expression of PRDX3, inhibits proliferation and promotes apoptosis of Daoy cells, leading to increased intracellular ROS and decreased levels of mitochondrial membrane potential.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cerebellar Neoplasms ; genetics ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Medulloblastoma ; genetics ; metabolism ; pathology ; Membrane Potential, Mitochondrial ; MicroRNAs ; genetics ; metabolism ; Peroxiredoxin III ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Reactive Oxygen Species ; metabolism ; Transfection

Medulloblastoma is the most common malignant pediatric brain tumor. Despite its prevalence and importance in pediatric neuro-oncology, the genes and pathways responsible for its initiation, maintenance, and progression remain poorly understood. Genetically engineered mouse models are an essential tool for uncovering the molecular and cellular basis of human diseases, including cancer, and serve a valuable role as preclinical models for testing targeted therapies. In this review, we summarize how such models have been successfully applied to the study of medulloblastoma over the past decade and what we might expect in the coming years.
Animals ; Cerebellar Neoplasms ; genetics ; metabolism ; pathology ; Disease Models, Animal ; Genetic Engineering ; Hedgehog Proteins ; metabolism ; Humans ; Medulloblastoma ; genetics ; metabolism ; pathology ; Mice ; Mice, Transgenic ; Mutation ; Patched Receptors ; RNA Interference ; RNA, Small Interfering ; genetics ; Receptors, Cell Surface ; genetics ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Signal Transduction ; Smoothened Receptor ; Tumor Suppressor Protein p53 ; genetics ; metabolism

Astrocytoma ; genetics ; metabolism ; pathology ; Brain Neoplasms ; classification ; genetics ; metabolism ; pathology ; Child ; Child, Preschool ; Chromosomal Proteins, Non-Histone ; genetics ; metabolism ; Chromosome Deletion ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Ependymoma ; genetics ; metabolism ; pathology ; Hedgehog Proteins ; genetics ; metabolism ; Humans ; Medulloblastoma ; classification ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Rhabdoid Tumor ; genetics ; metabolism ; pathology ; SMARCB1 Protein ; Signal Transduction ; Transcription Factors ; genetics ; metabolism ; Wnt Proteins ; metabolism ; beta Catenin ; genetics ; metabolism

Adult ; Diagnosis, Differential ; Humans ; MART-1 Antigen ; metabolism ; Magnetic Resonance Imaging ; Male ; Medulloblastoma ; metabolism ; pathology ; Melanocytes ; pathology ; Melanoma ; diagnosis ; metabolism ; pathology ; surgery ; Melanoma-Specific Antigens ; metabolism ; Meningeal Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Neoplasms, Multiple Primary ; diagnosis ; metabolism ; pathology ; surgery ; Neurilemmoma ; metabolism ; pathology ; Nevus of Ota ; diagnosis ; metabolism ; pathology ; surgery ; S100 Proteins ; metabolism ; Skin Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Vimentin ; metabolism