Medulloblastoma is considered one of the most threatening malignant brain tumors with an extremely high mortality rate in children. In the medulloblastoma, there are several genes and mutations found to work in an unregulated manner that works together to push the cells into a cancerous state. With the discovery of non-coding RNAs such as microRNAs (miRNAs), it has been shown that a different layer of gene regulations may be disrupted which would cause cancer. This fact led scientists to put their focus on the role of miRNAs in cancer. A mature miRNA contains a seed sequence which gives the miRNA to identify and attach to the interest mRNA; this attachment may lead degradation of mRNA or suppress of translation of the mRNA. The expression of miRNAs in medulloblastoma shows that some of these non-coding RNAs are overexpressed (OncomiRs) which help cells to proliferate and keep their stemness features. On the other hand, there are other forms of these miRNAs which normally inhibit cell proliferation and promote cell differentiation (tumor suppressor). These are down-regulated during cancer progression. In this systematic review, we attempted to gather several important studies on miRNAs’ role in medulloblastoma tumors and the importance of these non-coding RNAs in the future study of cancer.
Brain Neoplasms ; Cell Differentiation ; Cell Proliferation ; Child ; Genes, Tumor Suppressor ; Hand ; Humans ; Medulloblastoma ; MicroRNAs ; Mortality ; Oncogenes ; RNA, Messenger ; RNA, Untranslated ; Social Control, Formal

Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.
Arm ; Brain Neoplasms ; Child ; Classification ; Computational Biology ; Drug Therapy ; Hedgehogs ; Humans ; Medulloblastoma ; Mortality ; Neurosurgery ; Pediatrics ; Population Characteristics ; Recurrence

The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates +/-95% confidence intervals (CI) were 33.3+/-12.2% and 26.7% +/-11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates +/-95% CI was 40.0+/-15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.
Adolescent ; Cerebellar Neoplasms/drug therapy/mortality/*therapy ; Child ; Child, Preschool ; Combined Modality Therapy ; Disease-Free Survival ; Female ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Medulloblastoma/drug therapy/mortality/*therapy ; Neoplasm Recurrence, Local/drug therapy/mortality/*therapy ; Republic of Korea ; Salvage Therapy ; Transplantation, Autologous ; Young Adult

OBJECTIVETo investigate the diagnostic method and analyze the result of microneurosurgical treatment for tumors of the fourth cerebral ventricle.

METHODSTumor of the fourth ventricle was clinically diagnosed in 86 patients basing on the preliminary assessment of symptom and CT or MRI findings. Of these 86 patients treated with micro-neurosurgery, the tumors in 62 were totally removed, subtotally in 19, and partially in 5. Forty-two patients received postoperative radiotherapy.

RESULTSThree patients died postoperatively within ten days, and symptoms in 83 were improved after treatment. The average survival period was over 3 years. The pathology included 32 medulloblastomas, 23 ependymoma, 15 astrocytoma, 10 hemangiblastomas, 2 choroid plexus papillomas, and 4 epidermoid cysts.

CONCLUSIONMedulloblastoma, astrocytoma and hemangiblastoma are suggested to be removed totally whenever technically possible according to the site, character and volume of the tumor. For ependymoma, if close to the brain stem, is recommended to be subtotally removed. Postoperative radiotherapy may be beneficial for malignant types.

Adolescent ; Adult ; Aged ; Astrocytoma ; diagnosis ; diagnostic imaging ; surgery ; Cerebral Ventricle Neoplasms ; diagnosis ; radiotherapy ; surgery ; Child ; Child, Preschool ; Combined Modality Therapy ; Ependymoma ; diagnosis ; diagnostic imaging ; surgery ; Female ; Follow-Up Studies ; Fourth Ventricle ; pathology ; radiation effects ; surgery ; Hemangioblastoma ; diagnosis ; diagnostic imaging ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Medulloblastoma ; diagnosis ; diagnostic imaging ; surgery ; Microsurgery ; methods ; mortality ; Middle Aged ; Neoplasm Recurrence, Local ; Survival Analysis ; Survival Rate ; Tomography, X-Ray Computed

Child ; Child Welfare ; Humans ; Medulloblastoma ; drug therapy ; epidemiology ; surgery ; Mortality ; Radiotherapy ; Singapore ; epidemiology ; Treatment Outcome

OBJECTIVETo study the potential relationship between the expressions of c-jun and c-fos oncogenes and the prognosis of medulloblastoma.

METHODSThe specimens from 70 cases of medulloblastoma of the posterior fossa and 10 cases of normal cerebellar tissues were collected to determine c-jun and c-fos expressions by immunohistochemical staining in formalin fixed paraffin-embedded sections.

RESULTS(1) It showed that c-fos and c-jun protein expression was negative in 10 normal cerebellar tissue, while positive c-fos, c-jun immunoreactivity was found in 70 medulloblastoma specimens. The positive rate of c-jun and c-fos was 80% and 77%, respectively. There was high expression of c-jun and c-fos protein in medulloblastoma tissues. (2) There were positive correlations and strong co-operativity between c-jun and c-fos expression (r = 0.493, P < 0.01). (3) Correlative analysis indicated that expression of c-jun, c-fos were significantly correlated with survival time (c-jun: r = -0.447, P < 0.01; c-fos: r = -0.590, P < 0.01). The higher the expression level of c-jun and c-fos protein was, the worse the prognosis was in medulloblastoma patients.

CONCLUSIONSHigh expression of c-jun and c-fos protein could be noted in medulloblastoma tissues. The two transcription factors show positive correlation and strong co-existence between c-jun and c-fos expressions. The expression levels of c-jun as well as c-fos are negatively correlated with the mortality rate and life expectancy of patients with medulloblastoma. In addition, the co-expression of c-jun and c-fos could serve as an indicator for judging the prognosis of medulloblastoma.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Immunohistochemistry ; Infant ; Male ; Medulloblastoma ; metabolism ; mortality ; pathology ; Proto-Oncogene Proteins c-fos ; analysis ; Proto-Oncogene Proteins c-jun ; analysis ; Survival Analysis ; Survival Rate

PURPOSE: Medulloblastoma is the most common malignant brain tumor in childhood. The standard treatments are composed of tumor resection, irradiation and chemotherapy. In this study, we analysed the outcome of high risk medulloblastoma patients who were treated with surgical resection followed by craniospinal irradiation and chemotherapy utilizing cisplatin, vincristine, cyclophosphamide and etoposide. METHODS: We conducted a retrospective analysis of medical record of twenty-five patients with high risk medulloblastoma, treated from January 1998 to April 2004 in the Department of Pediatrics, Neurosurgery and Radiation Oncology at Asan Medical Center. RESULTS: The median age at diagnosis was 9 years and 10 month. The 2-year overall survival rate was 80%, and 2-year progression-free survival rate was 71%. Degree of surgical resections or residual tumor did not show statistically significant differences of survival rate, but there was difference depending on metastasis staging. The side effects of chemotherapy were grade IV hematologic toxicity (n=20), SIADH (n=2), and severe paralytic ileus (n=1). The long-term sequelae were endocrinopathy (n=6) that include growth failure, precocious puberty and hypothyroidism. Neurological complications such as mild mental retardation and ataxia occurred in seven patients. There was no treatment-related mortality. Four patients died of tumor progression. CONCLUSION: Patients with high risk medulloblastoma treated with surgical resection followed by radiation and chemotherapy as described here show satisfactory outcome. In this high risk group, metastasis staging correlated with outcome but the degree of surgical resection and presence or absence of residual tumor at primary site did not correlate with outcome.
Ataxia ; Brain Neoplasms ; Child ; Chungcheongnam-do ; Cisplatin ; Craniospinal Irradiation ; Cyclophosphamide ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Etoposide ; Humans ; Hypothyroidism ; Inappropriate ADH Syndrome ; Intellectual Disability ; Intestinal Pseudo-Obstruction ; Medical Records ; Medulloblastoma* ; Mortality ; Neoplasm Metastasis ; Neoplasm, Residual ; Neurosurgery ; Pediatrics ; Puberty, Precocious ; Radiation Oncology ; Retrospective Studies ; Survival Rate ; Vincristine

Medulloblastoma accounts for 20 to 25+ACU- of all intracranial neoplasms in children. The significance of the presence of isochromosome 17q (i(17q)), proliferative potential, apoptotic activity, and expression of c-erbB-2, bd-2, and p53 proteins in predicting long-term survival of patients with medulloblastomas was investigated. Twenty children were divided into two groups (favorable and poor outcome groups). Ten children with favorable outcome (FO) were disease-free during the follow-up period (median: 61.5 months). The other ten children with poor outcome (PO) died of disease progression, having a median survival of 18 months. Fluorescent in situ hybridization (FISH) for i(17q), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and immunohistochemistry for Ki-67, c-erbB-2, bcl-2, and p53 proteins was performed in these patients. Nine out of 17 children showed i(17q). There was no difference in the rate of positive i(17q) between the FO and PO groups. The presence of i(17q) was not significantly related to biological factors that we investigated. Unlike the prominent presence of the proliferative potential and p53 expression in children with PO, apoptotic activity and expression of c-erbB-2 and bcl-2 had no correlation with the outcome.
Adolescence ; Apoptosis ; Brain Neoplasms/pathology ; Brain Neoplasms/mortality ; Brain Neoplasms/genetics+ACo- ; Cell Division ; Child ; Child, Preschool ; Chromosomes, Human, Pair 17/ultrastructure+ACo- ; Chromosomes, Human, Pair 17/genetics ; Comparative Study ; Disease-Free Survival ; Female ; Follow-Up Studies ; Genes, bcl-2+ACo- ; Genes, erbB-2+ACo- ; Genes, p53+ACo- ; Human ; In Situ Hybridization, Fluorescence ; In Situ Nick-End Labeling ; Infant ; Ki-67 Antigen/analysis ; Male ; Medulloblastoma/pathology ; Medulloblastoma/mortality ; Medulloblastoma/genetics+ACo- ; Neoplasm Proteins/analysis ; Prognosis ; Retrospective Studies ; Survival Analysis ; Treatment Outcome

Medulloblastoma accounts for 20 to 25+ACU- of all intracranial neoplasms in children. The significance of the presence of isochromosome 17q (i(17q)), proliferative potential, apoptotic activity, and expression of c-erbB-2, bd-2, and p53 proteins in predicting long-term survival of patients with medulloblastomas was investigated. Twenty children were divided into two groups (favorable and poor outcome groups). Ten children with favorable outcome (FO) were disease-free during the follow-up period (median: 61.5 months). The other ten children with poor outcome (PO) died of disease progression, having a median survival of 18 months. Fluorescent in situ hybridization (FISH) for i(17q), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and immunohistochemistry for Ki-67, c-erbB-2, bcl-2, and p53 proteins was performed in these patients. Nine out of 17 children showed i(17q). There was no difference in the rate of positive i(17q) between the FO and PO groups. The presence of i(17q) was not significantly related to biological factors that we investigated. Unlike the prominent presence of the proliferative potential and p53 expression in children with PO, apoptotic activity and expression of c-erbB-2 and bcl-2 had no correlation with the outcome.
Adolescence ; Apoptosis ; Brain Neoplasms/pathology ; Brain Neoplasms/mortality ; Brain Neoplasms/genetics+ACo- ; Cell Division ; Child ; Child, Preschool ; Chromosomes, Human, Pair 17/ultrastructure+ACo- ; Chromosomes, Human, Pair 17/genetics ; Comparative Study ; Disease-Free Survival ; Female ; Follow-Up Studies ; Genes, bcl-2+ACo- ; Genes, erbB-2+ACo- ; Genes, p53+ACo- ; Human ; In Situ Hybridization, Fluorescence ; In Situ Nick-End Labeling ; Infant ; Ki-67 Antigen/analysis ; Male ; Medulloblastoma/pathology ; Medulloblastoma/mortality ; Medulloblastoma/genetics+ACo- ; Neoplasm Proteins/analysis ; Prognosis ; Retrospective Studies ; Survival Analysis ; Treatment Outcome

Medulloblastoma, once a tumor with a dismal prognosis, is one of the most common primary brain tumors of childhood. As the methods of treatment have been continuously refined, the outcome has improved remarkably during the last few decades. The outcome of 78 medulloblastoma patients, which were managed from 1972 to 1992 at the Department of Neurosurgery of Seoul National University Hospital, were analyzed to calculate the 3-year and 5-year survival rates (3yS and 5yS). Of those, 52 cases which were treated after July 1982 were studied 1) to calculate the 3yS and 5yS, 2) to figure out the prognostic factors of survival, and 3) to investigate the role of adjuvant chemotherapy ('8-drugs-in-a-day' protocol: CCNU, cisplatin, vincristine, hydroxyurea, procarbazine, cytosine arabinoside, methylprednisolone and cyclophosphamide). The 3yS and 5yS of the 78 patients were 57.4% and 47.3%, respectively. Of the 52 patients treated after July 1982, the 3yS and 5yS were 67.8% and 64.1%, respectively. The latest recurrence was at 56 months after surgery. All the recurrences were within the risk period of Collins' rule. Of the prognostic factors studied by univariate analysis (age, sex, Chang's classification T- and M-stages, extent of surgical removal, and chemotherapy), Chang's classification M-stage and sex were the statistically significant factors (p = 0.028 and 0.024 respectively). On multivariate analysis, only the M-stage was statistically significant (p = 0.004). Adjuvant chemotherapy had different influences in different patient groups. Only in the 'poor risk' group, did adjuvant chemotherapy have a strong tendency to better outcome (p = 0.069). Further data collection and analysis will lead to better treatment modalities and better outcome for this most common primary malignant brain tumor in childhood.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cerebellar Neoplasms/*drug therapy/mortality/radiotherapy ; Chemotherapy, Adjuvant ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Medulloblastoma/*drug therapy/mortality/radiotherapy ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Survival Rate ; Treatment Outcome