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Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Julie J Miller, Wolfgang Wick
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH- mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients...
February 2018: Seminars in Neurology
Jiang He, Yuzu Zhao, Erhu Zhao, Xianxing Wang, Zhen Dong, Yibiao Chen, Liqun Yang, Hongjuan Cui
Background: The cancer-testis specific gene Opa interacting protein 5 (OIP5) is a testis-specific gene that is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time. Methods: An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5...
March 14, 2018: Neuro-oncology
Michael Karsy, Jian Guan, L Eric Huang
OBJECTIVE Gliomas are one of the most common types of primary brain tumors. Recent studies have supported the importance of key genetic alterations, including isocitrate dehydrogenase (IDH) mutations and 1p19q codeletion, in glioma prognosis. Mutant IDH produces 2-hydroxyglutarate from α-ketoglutarate, a key metabolite of the Krebs cycle. The mitochondrial pyruvate carrier (MPC) is composed of MPC1 and MPC2 subunits and is functionally essential for the Krebs cycle. The authors sought to explore the impact of MPC1 and MPC2 expression on patient prognosis...
March 16, 2018: Journal of Neurosurgery
C Lavanya, Manjunatha M Venkataswamy, M K Sibin, M M Srinivas Bharath, G K Chetan
Increased telomerase activity can be blocked by targeting the hTERT activity at both RNA and catalytic subunits. Various inhibitors had been used to regulate hTERT activity in glioblastoma cell lines and showed promising results. The present study hypothesized that the telomerase specific inhibitor BIBR1532 can effectively down-regulate the telomerase activity in LN18 glioblastoma cell line. LN18 glioblastoma cell line was treated with various concentrations of BIBR1532 at different time intervals. MTT assay was performed to determine cell viability after BIBR1532 treatment...
March 15, 2018: Cytotechnology
Brent D Weinberg, Lauren Boreta, Steve Braunstein, Soonmee Cha
Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospective review of 50 patients diagnosed with glioblastoma and treated with surgery, radiation, and concurrent temozolomide from January 2012 to June 2013 was performed. Tumors were classified based on location, size, and cortical and subventricular zone involvement...
March 15, 2018: Journal of Neuro-oncology
Aldo Berti, Michelle Granville, Robert E Jacobson
A case of an extremely healthy, active, 96-year-old patient, nonsmoker, is reviewed. He was initially treated for left V1, V2, and V3 trigeminal neuralgia in 2001, at age 80, with stereotactic radiosurgery (SRS) with a dose of 80 Gy to the left retrogasserian trigeminal nerve. He remained asymptomatic for nine years until his trigeminal pain recurred in 2010. He was first treated medically but was intolerant to increasing doses of carbamazepine and gabapentin. He underwent a second SRS in 2012 with a dose of 65...
January 12, 2018: Curēus
Muhammad Khairi Ahmad, Nur Ainina Abdollah, Nurul Husna Shafie, Narazah Mohd Yusof, Siti Razila Abdul Razak
Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells...
February 2018: Cancer Biology & Medicine
IlKyoo Koh, Junghwa Cha, Junseong Park, Junjeong Choi, Seok-Gu Kang, Pilnam Kim
Glioblastoma multiforme (GBM) is the most common brain tumor with very aggressive and infiltrative. Extracellular matrix (ECM) plays pivotal roles in the infiltrative characteristics of GBM. To understand the invasive characteristic of GBM, it is necessary to study cell-ECM interaction in the physiologically relevant biomimetic model that recapitulates the GBM-specific ECM microenvironment. Here, we propose biomimetic GBM-specific ECM microenvironment for studying mode and dynamics of glioblastoma cell invasion...
March 15, 2018: Scientific Reports
Joydeep Mukherjee, Tor-Christian Aase Johannessen, Shigeo Ohba, Tracy T Chow, Lindsey E Jones, Ajay Pandita, Russell O Pieper
A subset of tumors use a recombination-based alternative lengthening of telomere (ALT) pathway to resolve telomeric dysfunction in the absence of TERT. Loss-of-function mutations in the chromatin remodeling factor ATRX are associated with ALT but are insufficient to drive the process. Because many ALT tumors express the mutant isocitrate dehydrogenase IDH1 R132H, including all lower-grade astrocytomas (LGA) and secondary glioblastoma, we examined an hypothesized role for IDH1 R132H in driving the ALT phenotype during gliomagenesis...
March 15, 2018: Cancer Research
Carmen J Zamora-Sánchez, Aylin Del Moral-Morales, Ana M Hernández-Vega, Valeria Hansberg-Pastor, Ivan Salido-Guadarrama, Mauricio Rodríguez-Dorantes, Ignacio Camacho-Arroyo
Glioblastomas (GBM) are the most frequent and aggressive brain tumors. In these malignancies, progesterone (P4) promotes proliferation, migration, and invasion. The P4 metabolite allopregnanolone (3α-THP) similarly promotes cell proliferation in the U87 human GBM cell line. Here, we evaluated global changes in gene expression of U87 cells treated with 3α-THP, P4, and the 5α-reductase inhibitor, finasteride (F). 3α-THP modified the expression of 137 genes, while F changed 90. Besides, both steroids regulated the expression of 69 genes...
March 15, 2018: International Journal of Molecular Sciences
Seyed A Dehghan Manshadi, SeyedAhmad SeyedAlinaghi, Seyed A Mousavi, Mohammad R Salehi, Ali Asadollahi-Amin, Hossein Keyvani
No abstract text is available yet for this article.
March 27, 2018: AIDS
Bárbara da Silva, Ryan K Mathew, Euan S Polson, Jennifer Williams, Heiko Wurdak
Organoid methodology provides a platform for the ex vivo investigation of the cellular and molecular mechanisms underlying brain development and disease. The high-grade brain tumor glioblastoma multiforme (GBM) is considered a cancer of unmet clinical need, in part due to GBM cell infiltration into healthy brain parenchyma, making complete surgical resection improbable. Modeling the process of GBM invasion in real time is challenging as it requires both tumor and neural tissue compartments. Here, we demonstrate that human GBM spheroids possess the ability to spontaneously infiltrate early-stage cerebral organoids (eCOs)...
March 1, 2018: SLAS Discovery
Amit Shivajirao Waghmare, Shivaji Sandu Pandit, Dayanand M Suryawanshi
AIM AND OBJECTIVE: 4H-pyran is one of the most well-known groups of synthetic heterocyclic compounds and it has attracted considerable attention of chemists in recent years because of their extensive range of biological and pharmaceutical activities. These compounds are used as antibacterial, anticancer agents, anti-coagulants, spasmolytics and anti-anaphylactic. 4H-pyran derivatives are utilized in cosmetics, pigments, biodegradable agrochemicals as well as photoactive materials. In addition, 4H-pyrans are also helpful as cognitive enhancers for the treatment of neuro degenerative diseases, including Alzheimer's disease, as well as for the treatment of schizophrenia and myoclonus...
March 14, 2018: Combinatorial Chemistry & High Throughput Screening
Manijeh Beigi, Kevan Ghasemi, Parvin Mirzaghavami, Mohammadreza Khanmohammadi, Hamidreza SalighehRad
The main aim of this study was to propose a new statistical method for evaluation of spatial malignancy distribution within Magnetic Resonance Spectroscopy (MRS) grid in Glioblastoma Multiforme patients. Voxels with different malignancy probabilities were presented as a novel MRS-based Malignancy Probability Map (MPM). For this purpose, a predictive probability-based clustering approach was developed, including the two following steps: (1) Gaussian Mixture Model, (2) Quadratic Discriminate Analysis coupled with Genetic Algorithm...
March 14, 2018: Journal of Neuro-oncology
Koji Omoto, Ryosuke Matsuda, Ichiro Nakagawa, Yasushi Motoyama, Hiroyuki Nakase
Background: 5-aminolevulinic acid (5-ALA)-guided surgery is one of the gold standard perioperative modalities for maximum resection of malignant gliomas. However, it should be noted that 5-ALA fluorescence does not definitively indicate the presence of malignant tumor cells. Case Description: We report a rare case of false-positive lesion mimicking glioblastoma multiforme (GBM) under 5-ALA-guided surgery. A 44-year-old woman presented with persistent headache and flickering in her eyes...
2018: Surgical Neurology International
Toni Rose Jue, Emily S Sena, Malcolm R Macleod, Kerrie L McDonald, Theodore C Hirst
Malignant glioma is a devastating disease affecting both adults and children with limited treatment strategies. Pre-clinical animal studies are critical to the development and planning of novel treatment designs for human clinical trials. Topoisomerases has been a target of interest in the treatment of high grade gliomas, such as glioblastoma, in the past years. Here we assess pre-clinical glioma literature with the aim to identify predictive variables that favour treatment outcomes from topoisomerase inhibition...
February 16, 2018: Oncotarget
Leland J Dunwoodie, William L Poehlman, Stephen P Ficklin, Frank Alexander Feltus
Tumors exhibit complex patterns of aberrant gene expression. Using a knowledge-independent, noise-reducing gene co-expression network construction software called KINC, we created multiple RNAseq-based gene co-expression networks relevant to brain and glioblastoma biology. In this report, we describe the discovery and validation of a glioblastoma-specific gene module that contains 22 co-expressed genes. The genes are upregulated in glioblastoma relative to normal brain and lower grade glioma samples; they are also hypo-methylated in glioblastoma relative to lower grade glioma tumors...
February 16, 2018: Oncotarget
Stefanie Bette, Melanie Barz, Thomas Huber, Christoph Straube, Friederike Schmidt-Graf, Stephanie E Combs, Claire Delbridge, Julia Gerhardt, Claus Zimmer, Bernhard Meyer, Jan S Kirschke, Tobias Boeckh-Behrens, Benedikt Wiestler, Jens Gempt
Recent studies suggested that postoperative hypoxia might trigger invasive tumor growth, resulting in diffuse/multifocal recurrence patterns. Aim of this study was to analyze distinct recurrence patterns and their association to postoperative infarct volume and outcome. 526 consecutive glioblastoma patients were analyzed, of which 129 met our inclusion criteria: initial tumor diagnosis, surgery, postoperative diffusion-weighted imaging and tumor recurrence during follow-up. Distinct patterns of contrast-enhancement at initial diagnosis and at first tumor recurrence (multifocal growth/progression, contact to dura/ventricle, ependymal spread, local/distant recurrence) were recorded by two blinded neuroradiologists...
March 14, 2018: Scientific Reports
Robert A Fenstermaker, Sheila A Figel, Jing-Xin Qiu, Tara A Barone, Sanam Sahjram Dharma, Evan K Winograd, Phillip M Galbo, Laura M Wiltsie, Michael J Ciesielski
PURPOSE: Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in many cancers and represents an attractive molecule for targeted cancer therapy. Although primarily regarded as an intracellular protein with diverse actions, survivin has also been identified in association with circulating tumor exosomes. EXPERIMENTAL DESIGN: We have reported that active specific vaccination with a long peptide surviving immunogen leads to the development of survivin-specific CD8-mediated tumor cell lysis and prolongation of survival in tumor-bearing mice...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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