Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity.

Comparative analysis of somatostatin analog uptake between successfully irradiated and non-irradiated meningiomas.

Objective: To evaluate whether there is a significant difference in somatostatin analog uptake in meningiomas treated or not with radiation therapy.

Methods: A cross-sectional study was performed comparing measurements of somatostatin analog (68Ga-DOTATATE) uptake in two independent groups of ten patients each - one consisting of patients with meningiomas previously treated with radiation therapy and another comprising patients who had never been submitted to radiation therapy. All patients underwent PET/CT and MRI scans in an interval shorter than 24 hours between exams.

Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study.

Purpose: Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay.

Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma Subgroup.

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MB, MB, MB, or MB). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology.

RIPK3 is a novel prognostic marker for lower grade glioma and further enriches IDH mutational status subgrouping.

Purpose: Necroptosis is a necrotic-like cell death pathway in which Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) plays a central role and may induce inflammation and immunity. Lower RIPK3 levels have been correlated with a poor prognosis in breast and colorectal cancer patients. Instead, in gliomas, the most prevalent among central nervous system cancers, necrosis concurs with a more aggressive and lethal outcome, suggesting that, in these cases, necrotic-like pathways may be linked to worse prognoses.

Lack of KBTBD4 Mutations in Molecularly Classified Brazilian Medulloblastomas.

Medulloblastoma is the most frequent malignant brain tumor in children, representing 20% of all childhood brain tumors. Currently, medulloblastomas are molecularly classified in 4 subgroups that are associated with distinctive clinicopathological features. KBTBD4 mutations were recently described in a subset of MBGRP3 and MBGRP4 medulloblastomas subgroups.

New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X.

EPNs comprise a heterogeneous group of neuroepithelial tumors, accounting for about 10% of all intracranial tumors in children and up to 30% of brain tumors in those younger than 3 years. Actually, the pattern therapy for low-grade EPNs includes complete surgical resection followed by radiation therapy. Total surgical excision is often not possible due to tumor location.

Intravenous Grafts of Human Amniotic Fluid-Derived Stem Cells Reduce Behavioral Deficits in Experimental Ischemic Stroke.

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia-reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats.

Tropism of mesenchymal stem cell toward CD133 stem cell of glioblastoma in vitro and promote tumor proliferation in vivo.

Background: Previous studies have demonstrated remarkable tropism of mesenchymal stem cells (MSCs) toward malignant gliomas, making these cells a potential vehicle for delivery of therapeutic agents to disseminated glioblastoma (GBM) cells. However, the potential contribution of MSCs to tumor progression is a matter of concern. It has been suggested that CD133 GBM stem cells secrete a variety of chemokines, including monocytes chemoattractant protein-1 (MCP-1/CCL2) and stromal cell-derived factor-1(SDF-1/CXCL12), which could act in this tropism.

Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma.

Medulloblastoma is the most frequent malignant brain tumor in children. Four medulloblastoma molecular subgroups, MB , MB , MB and MB , have been identified by integrated high-throughput platforms. Recently, a 22-gene panel NanoString-based assay was developed for medulloblastoma molecular subgrouping, but the robustness of this assay has not been widely evaluated.

Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology.

Background: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs.

Performance of adjuvant treatment correlates with survival in reoperated glioblastomas.

Objective: To analyze cases of recurrent glioblastoma subjected to reoperation at a Brazilian public healthcare service.

Methods: A total of 39 patients subjected to reoperation for recurrent glioblastoma at the Department of Neurosurgery, São Paulo Hospital, Federal University of São Paulo, from January 2000 to December 2013 were retrospectively analyzed.

Results: The median overall survival was 20 months (95% confidence interval - CI = 14.

Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells.

Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells.

Minimizing the uncertainties regarding the effects of delaying radiotherapy for Glioblastoma: A systematic review and meta-analysis.

Background And Purpose: Previous studies have provided no clear conclusions regarding the effects of delaying radiotherapy (RT) in GBM patients. We present a systematic review and meta-analysis to address the effect of delayed RT on the overall survival (OS) of GBM patients.

Methods: A systematic search retrieved 19 retrospective studies published between 1975 and 2014 reporting on the waiting time (WT) to RT for GBM patients.

Waiting time to radiotherapy as a prognostic factor for glioblastoma patients in a scenario of medical disparities.

Objective: To evaluate the effect of waiting time (WT) to radiotherapy (RT) on overall survival (OS) of glioblastoma (GBM) patients as a reliable prognostic variable in Brazil, a scenario of medical disparities.

Method: Retrospective study of 115 GBM patients from two different health-care institutions (one public and one private) in Brazil who underwent post-operative RT.

Results: Median WT to RT was 6 weeks (range, 1.

Fas, FasL, and cleaved caspases 8 and 3 in glioblastomas: a tissue microarray-based study.

This investigation analyzed the immunoexpression of FasL, Fas, cleaved caspase-8, and cleaved caspase-3 in glioblastomas. Formalin-fixed and paraffin-embedded glioblastoma tissues and control brain tissues from 97 patients were analyzed by tissue microarrays and immunohistochemistry. Patients with glioblastomas that were negative or weakly stained (<50% of cells positive) for cleaved caspase-8 had worse cancer-specific overall survival (median=8.

Patterns of care and outcomes in elderly patients with glioblastoma in Sao Paulo, Brazil: a retrospective study.

Objective: To analyze how elderly patients with glioblastoma are managed in Brazil.

Material And Methods: We identified 30 patients aged ≥ 65 years treated between 2003 and 2011 at Albert Einstein Hospital in Sao Paulo. We retrospectively reviewed medical records to obtain data on clinical variables, treatment and outcomes.

Initial care and outcome of glioblastoma multiforme patients in 2 diverse health care scenarios in Brazil: does public versus private health care matter?

Background: The aim of this study was to describe the epidemiological and survival features of patients with glioblastoma multiforme treated in 2 health care scenarios--public and private--in Brazil.

Methods: We retrospectively analyzed clinical, treatment, and outcome characteristics of glioblastoma multiforme patients from 2003 to 2011 at 2 institutions.

Results: The median age of the 171 patients (117 public and 54 private) was 59.

In vitro Analysis of Neurospheres Derived from Glioblastoma Primary Culture: A Novel Methodology Paradigm.

Glioblastomas are the most lethal primary brain tumor that frequently relapse or progress as focal masses after radiation, suggesting that a fraction of tumor cells are responsible for the tumor regrowth. The identification of a brain tumor cell subpopulation with potent tumorigenic activity supports the cancer stem cell hypothesis in solid tumors. The goal of this study is to determine a methodology for the establishment of primary human glioblastoma cell lines.

Glioblastoma: approach to treat elderly patients.

Treating elderly cancer patients is a challenge for oncologists, especially considering the several therapeutic modalities in glioblastoma. Extensive tumor resection offers the best chance of local control. Adequate radiotherapy should always be given to elderly patients if they have undergone gross total resection and have maintained a good performance status.