Measuring Cancer Hallmark Mediation of the TET1 Glioma Survival Effect with Linked Neural-Network Based Mediation Experiments.

This paper examines the effect of TET1 expression on survival in glioma patients using open-access data from the Genomic Data Commons. A neural network-based survival model was built on expression data from a selection of genes most affected by TET1 knockdown with a median cross-validated survival concordance of 82.5%.

Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage.

Purpose: Reirradiation for recurrent glioma remains controversial without knowledge of optimal patient selection, dose, fractionation, and normal tissue tolerances. We retrospectively evaluated outcomes and toxicity after conventionally fractionated reirradiation for recurrent high-grade glioma, along with the impact of concurrent chemotherapy.

Methods And Materials: We conducted a retrospective review of patients reirradiated for high-grade glioma recurrence between 2007 and 2016 (including patients with initial low-grade glioma).

INSM1 Expression Is Frequent in Primary Central Nervous System Neoplasms but Not in the Adult Brain Parenchyma.

Tumors with a neuronal component comprise a small percentage of central nervous system (CNS) neoplasms overall, but the presence of neuronal differentiation has important diagnostic, prognostic, and therapeutic implications. Insulinoma-associated protein 1 (INSM1) is a transcription factor with strong nuclear immunostaining in neuroendocrine cells and neoplasms of neuroendocrine origin; however, its expression in the CNS in normal brain and in neoplastic cells has not been fully explored. Here, we present immunostaining results from a large number of archival CNS tissue specimens, including 416 tumors.

Prostate-Specific Membrane Antigen-Targeted Imaging With [18F]DCFPyL in High-Grade Gliomas.

High-grade gliomas (World Health Organization grade III-IV) are highly lethal primary brain tumors. Imaging modalities, including MRI and FDG PET, provide a limited ability to differentiate treatment effects (such as radiation necrosis) from recurrent or residual tumor. As the first step in validating the applicability of prostate-specific membrane antigen (PSMA)-targeted imaging in high-grade gliomas, we evaluated the ability of the PSMA-targeted small molecule [F]DCFPyL (2-(3-(1carboxy-5-(6-[F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid) to image high-grade gliomas in a series of 3 prospectively recruited patients.

Updates from the Neuro-Oncology Section of the 2015 American Neurological Association Annual Meeting.

American Neurological Association Annual Meeting, Chicago, IL, USA, 27-29 September 2015 The American Neurological Association (ANA) held its annual meeting in Chicago, IL, USA on 27-29 September 2015. The Scientific Programming Advisory Committee was chaired by Dr. S Pleasure from the University of California-San Francisco (CA, USA).

Antiangiogenic Therapies and Extracranial Metastasis in Glioblastoma: A Case Report and Review of the Literature.

We present a case report of a patient with glioblastoma multiforme (GBM) complicated by extracranial metastasis (ECM) whose survival of nearly four years surpassed the anticipated life expectancy given numerous negative prognostic factors including EGFRvIII-mutation, unmethylated MGMT promoter status, and ECM. Interestingly, while this patient suffered from locally aggressive disease with multiple intracranial recurrences, the proximal cause of death was progressive extracranial disease and complications related to pulmonary metastases. Herein, we review potential mechanisms of ECM with an emphasis upon glioblastoma molecular and genetic profiles and the potential implications of targeted agents such as bevacizumab.

Scatter factor protects tumor cells against apoptosis caused by TRAIL.

Scatter factor (SF) and its receptor c-Met are overexpressed in various tumor types, and their expression often correlates with a poor prognosis. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), is a proposed tumor-specific chemotherapy agent, but its clinical usage is limited by acquisition of TRAIL resistance by tumors. The goals of this study were to determine whether and how SF protects tumor cells against TRAIL and whether SF-induced TRAIL resistance could be reversed.

Role of Src signal transduction pathways in scatter factor-mediated cellular protection.

Scatter factor (SF) (hepatocyte growth factor) is a pleiotrophic cytokine that accumulates in tumors, where it may induce invasion, angiogenesis, and chemoresistance. We have studied the mechanisms by which SF and its receptor (c-Met) protect cells against the DNA-damaging agent adriamycin (ADR) as a model for chemoresistance of SF/c-Met-overexpressing tumors. Previous studies identified a phosphatidylinositol 3-kinase/c-Akt/Pak1/NF-kappaB cell survival pathway in DU-145 prostate cancer and Madin-Darby canine kidney epithelial cells.

Identification of genes that modulate sensitivity of U373MG glioblastoma cells to cis-platinum.

Scatter factor (hepatocyte growth factor) and its receptor c-Met are increasingly expressed during progression from low-grade to high-grade gliomas. Scatter factor/c-Met signaling induces glioma cell motility, invasion, angiogenesis and resistance to DNA-damaging agents. The latter is relevant to the understanding of the resistance of human gliomas to chemotherapy and radiotherapy.

Role of NF-kappaB signaling in hepatocyte growth factor/scatter factor-mediated cell protection.

The cytokine scatter factor/hepatocyte growth factor (HGF/SF) protects epithelial, carcinoma, and other cell types against cytotoxicity and apoptosis induced by DNA-damaging agents such as ionizing radiation and adriamycin (ADR, a topoisomerase IIalpha inhibitor). We investigated the role of nuclear factor kappa B (NF-kappaB) signaling in HGF/SF-mediated protection of human prostate cancer (DU-145) and Madin-Darby canine kidney (MDCK) epithelial cells against ADR. HGF/SF caused the rapid nuclear translocation of the p65 (RelA) subunit of NF-kappaB associated with the transient loss of the inhibitory subunit IkappaB-alpha.

Suramin and radiotherapy in newly diagnosed glioblastoma: phase 2 NABTT CNS Consortium study.

Suramin is a polysulfonated naphthylurea that inhibits the function of growth factors and growth factor receptors implicated in glioma progression, angiogenesis, and radioresistance. The safety and benefits of combining inhibitors of angiogenesis and growth factors with cytotoxic therapies in patients with neoplasms of the central nervous system remain unclear. The objectives of this phase 2 study were to determine the safety of administering suramin with standard cranial radiotherapy (RT) and to estimate survival using this approach in patients with newly diagnosed glioblastoma multiforme (GBM).