Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups.

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling.

Systematic comparison of MRI findings in pediatric ependymoblastoma with ependymoma and CNS primitive neuroectodermal tumor not otherwise specified.

Background: Ependymoblastoma (EBL), ependymoma (EP), and primitive neuroectodermal tumors of the central nervous system not otherwise specified (CNS-PNET NOS) are pediatric brain tumors that can be differentiated by histopathology in the clinical setting. Recently, we described specific MRI features of EBL. In this study, we compare standardized MRI characteristics of EBL with EP and CNS-PNET NOS in a series comprising 22 patients in each group.

Molecular heterogeneity characterizes glioblastoma with lipoblast/adipocyte-like cytology.

Glioblastoma, the most common primary brain tumor in adults, may rarely show among unusual histological patterns lipoblast/adipocyte-like features. The genetic features of such cases are not yet well characterized, and molecular data are available for only few cases. In order to further expand our knowledge about their molecular profile, we analyzed four cases of glioblastoma with adipocyte-like features.

Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis.

Background: Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours.

Prognostic impact of B-cell lymphoma 6 in primary CNS lymphoma.

Background: We investigated the prognostic significance of B-cell differentiation status and common B-cell differentiation markers in a post hoc analysis of 119 patients with primary CNS lymphoma (PCNSL) homogeneously receiving high-dose methotrexate (HDMTX)-based chemotherapy within the prospective G-PCNSL-SG1 trial.

Methods: We evaluated protein expression of B-cell lymphoma 2 (BCL2), BCL6, CD10, and multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) by immunohistochemistry and analyzed the association with survival.

Results: The median follow-up of all patients was 67.

Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups.

Cerebral gliomas of World Health Organization (WHO) grade II and III represent a major challenge in terms of histological classification and clinical management. Here, we asked whether large-scale genomic and transcriptomic profiling improves the definition of prognostically distinct entities. We performed microarray-based genome- and transcriptome-wide analyses of primary tumor samples from a prospective German Glioma Network cohort of 137 patients with cerebral gliomas, including 61 WHO grade II and 76 WHO grade III tumors.

Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma.

Objective: This is the final report of a phase III randomized study to evaluate whole-brain radiotherapy (WBRT) in primary therapy of primary CNS lymphoma (PCNSL) after a median follow-up of 81.2 months.

Methods: Patients with newly diagnosed PCNSL were randomized to high-dose methotrexate (HDMTX)-based chemotherapy alone or followed by WBRT.

Disseminated oligodendroglial-like leptomeningeal tumors: preliminary diagnostic and therapeutic results for a novel tumor entity [corrected].

Pediatric tumors of the central nervous system composed of oligoid tumor cells showing diffuse leptomeningeal spread without a primary mass lesion seem to represent a novel tumor entity. The terms "diffuse leptomeningeal glioneural tumor" or-preferably-"disseminated oligodendroglial-like leptomeningeal tumor of childhood" (DOGLT) were proposed. Four patients were identified with clinico-neuropathologic findings compatible with DOGLT and a mean follow-up time of 54 months was determined.

Differential imaging characteristics and dissemination potential of pilomyxoid astrocytomas versus pilocytic astrocytomas.

Introduction: Pilomyxoid astrocytoma (PMA) is a rare WHO grade II tumor occurring most often in young children. PMA is associated with worse outcome as compared to the pathologically related pilocytic astrocytoma (PA). The radiological differentiation of PMAs from PAs is challenging.

Emerging magnetic order in platinum atomic contacts and chains.

The development of atomic-scale structures revealing novel transport phenomena is a major goal of nanotechnology. Examples include chains of atoms that form while stretching a transition metal contact or the predicted formation of magnetic order in these chains, the existence of which is still debated. Here we report an experimental study of the magneto-conductance (MC) and anisotropic MC with atomic-size contacts and mono-atomic chains of the nonmagnetic metal platinum.

Nanoporous Thin Films and Binary Nanoparticle Superlattices Created by Directed Self-Assembly of Block Copolymer Hybrid Materials.

The design and development of well-defined, functional nanostructures via self-assembly is one of the key objectives in current nanotechnology. Block copolymer-based hybrid materials are attractive candidates for the fabrication of multifunctional nanostructures, which provide the building blocks for more complex nanoarchitectures and nanodevices. However, one of the major challenges lies in controlling the structure formation in these hybrid materials by guiding the self-assembly of the block copolymer.

A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma.

Purpose: A randomised, open label phase III trial was conducted to evaluate efficacy of nimotuzumab, a monoclonal antibody against epidermal growth factor receptor (EGF-R) added to standard therapy for newly diagnosed glioblastoma.

Patients And Methods: 149 glioblastoma patients stratified as with or without residual tumour were randomly assigned to receive either intravenous nimotuzumab 400mg weekly added to standard radiochemotherapy followed by 400mg biweekly after twelve weeks or standard radiochemotherapy. Progression status after 52 weeks (12moPFS) and progression-free survival (PFS) based on Macdonald criteria were co-primary and overall survival (OS), toxicity and quality of life secondary end-points.

The PI3K inhibitor GDC-0941 displays promising in vitro and in vivo efficacy for targeted medulloblastoma therapy.

Deregulation of the Phosphoinositide 3-kinase (PI3K)/AKT signalling network is a hallmark of oncogenesis. Also medulloblastoma, the most common malignant brain tumor in children, is characterized by high levels of AKT phosphorylation and activated PI3K signalling in medulloblastoma is associated with enhanced cellular motility, survival and chemoresistency underscoring its role of as a potential therapeutic target. Here we demonstrate that GDC-0941, a highly specific PI3K inhibitor with good clinical tolerability and promising anti-neoplastic activity in adult cancer, also displays anti-proliferative and pro-apoptotic effects in pediatric human medulloblastoma cell lines.

High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors.

Choroid plexus tumors are rare neoplasms that mainly affect children. They include papillomas, atypical papillomas, and carcinomas. Detailed genetic studies are rare, and information about their molecular pathogenesis is limited.

Primitive neuroectodermal tumors of the brainstem in children treated according to the HIT trials: clinical findings of a rare disease.

Object: Primitive neuroectodermal tumors of the central nervous system (CNS-PNET) arising in the brainstem are extremely rare, and knowledge about them is limited. The few existing case series report fatal outcomes. The purpose of this study was to analyze clinical characteristics of and outcome for brainstem CNS-PNET patients treated according to the consecutive, population-based HIT studies covering a 19-year time period.

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation.

Magnetotransport in atomic-size bismuth contacts.

We report low-temperature transport experiments on atomic-size contacts of bismuth that are fabricated using the mechanically controlled break-junction technique at low temperatures. We observe stable contacts with conductance values at fractions of one conductance quantum G0 = 2e(2)/h, as is expected for systems with long Fermi wavelength. We defer two preferred conductance scales: the lower one is in the order of 0.

Genetic Analysis of Diffuse High-Grade Astrocytomas in Infancy Defines a Novel Molecular Entity.

Pediatric high-grade gliomas are considered to be different when compared to adult high-grade gliomas in their pathogenesis and biological behavior. Recently, common genetic alterations, including mutations in the H3F3A/ATRX/DAXX pathway, have been described in approximately 30% of the pediatric cases. However, only few cases of infant high-grade gliomas have been analyzed so far.

In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy.

Regardless of the recent advances in cytotoxic therapies, 30% of children diagnosed with medulloblastoma. succumb to the disease. Therefore, novel therapeutic approaches are warranted.

Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas.

Studies in pediatric high-grade astrocytomas (HGA) by our group and others have uncovered recurrent somatic mutations affecting highly conserved residues in histone 3 (H3) variants. One of these mutations leads to analogous p.Lys27Met (K27M) mutations in both H3.

Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial.

Early studies with high-dose chemotherapy for treatment of relapsed cerebral PNET had shown modest efficacy but considerable toxicity. The HIT97 national trial tested a nonrandomized but stratified relapse protocol using either intensive chemotherapy, potentially high dose, or oral chemotherapy. 72 patients (59 disseminated) whose primary treatment had been surgery (97 %), radiotherapy (88 %), and/or chemotherapy (95 %) were enrolled in the intensive chemotherapy arm at diagnosis of relapse or resistance.

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.

Background: Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter.