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mgmt glioma

Lian Duan, Yunkun Zhang, Weilun Fu, Sumin Geng
Rosette-forming glioneuronal tumor (RGNT) is a recently recognized and rarely encountered tumor occurring in the fourth ventricle. Histologically, it is composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a neurocytic component forming neurocytic rosettes and/or perivascular rosettes. The authors describe two extremely rare cases of RGNT arising from the spinal cord, which were misdiagnosed as ependymoma and astrocytoma preoperatively. Symptoms included dissociated sensory disturbance, episodic pain and fatigue, as well as motor disturbance, had been presented for two years and two months, respectively...
November 30, 2016: World Neurosurgery
Jianlong Li, Jinquan Cai, Shihong Zhao, Kun Yao, Ying Sun, Yongli Li, Lingchao Chen, Ruiyan Li, Xiuwei Zhai, Junhe Zhang, Chuanlu Jiang
BACKGROUND: The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms. METHODS: The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively...
November 28, 2016: Journal of Experimental & Clinical Cancer Research: CR
Krzysztof Roszkowski, Jacek Furtak, Bogdan Zurawski, Tadeusz Szylberg, Marzena A Lewandowska
The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses...
November 10, 2016: International Journal of Molecular Sciences
Eugene J Vaios, Brian V Nahed, Alona Muzikansky, Amir T Fathi, Jorg Dietrich
OBJECTIVE Glioblastoma (GBM) is a highly aggressive malignancy that requires a multidisciplinary therapeutic approach of surgery, chemotherapy, and radiation therapy, but therapy is frequently limited by side effects. The most common adverse effect of chemotherapy with temozolomide (TMZ) is myelosuppression. It remains unclear whether the degree of bone-marrow suppression might serve as a biomarker for treatment outcome. The aim of the current study was to investigate whether the degree of bone-marrow toxicity in patients treated with TMZ correlates with overall survival (OS) and MRI-based time to progression (progression-free survival [PFS])...
October 14, 2016: Journal of Neurosurgery
Brigitta G Baumert, Monika E Hegi, Martin J van den Bent, Andreas von Deimling, Thierry Gorlia, Khê Hoang-Xuan, Alba A Brandes, Guy Kantor, Martin J B Taphoorn, Mohamed Ben Hassel, Christian Hartmann, Gail Ryan, David Capper, Johan M Kros, Sebastian Kurscheid, Wolfgang Wick, Roelien Enting, Michele Reni, Brian Thiessen, Frederic Dhermain, Jacoline E Bromberg, Loic Feuvret, Jaap C Reijneveld, Olivier Chinot, Johanna M M Gijtenbeek, John P Rossiter, Nicolas Dif, Carmen Balana, Jose Bravo-Marques, Paul M Clement, Christine Marosi, Tzahala Tzuk-Shina, Robert A Nordal, Jeremy Rees, Denis Lacombe, Warren P Mason, Roger Stupp
BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration...
November 2016: Lancet Oncology
Yang Yuan, Mao Yunhe, Wang Xiang, Liu Yanhui, Liang Ruofei, Luo Jiewen, Mao Qing
BACKGROUND: Tumor location, which serves as a prognostic factor for high-grade gliomas, may reflect the molecular and genetic phenotype of tumor initiate cells and thus predict tumor origin. Therefore, the purpose of this study was to combine radiographic atlases and tumor biomarkers through a voxel-based neuroimaging approach. METHODS: Preoperative MRIs were collected from 65 newly diagnosed patients with histologically confirmed high-grades gliomas. These samples were analyzed for TP53 mutations and MMP-9...
November 2016: Clinical Neurology and Neurosurgery
Johann-Martin Hempel, Sotirios Bisdas, Jens Schittenhelm, Cornelia Brendle, Benjamin Bender, Henk Wassmann, Marco Skardelly, Ghazaleh Tabatabai, Salvador Castaneda Vega, Ulrike Ernemann, Uwe Klose
The purpose of this study is to assess the diagnostic performance of diffusion kurtosis imaging (DKI) for in vivo molecular profiling of human glioma. Normalized mean kurtosis (MKn) and mean diffusivity (MDn) metrics from DKI were assessed in 50 patients with histopathologically confirmed glioma. The results were compared in regard to the WHO-based histological findings and molecular characteristics leading to integrated diagnosis (Haarlem Consensus): isocitrate-dehydrogenase (IDH1/2) mutation status, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression, chromosome 1p/19q loss of heterozygosity (LOH), and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status...
September 7, 2016: Journal of Neuro-oncology
Wen Wang, Lu Zhang, Zheng Wang, Fan Yang, Haoyuan Wang, Tingyu Liang, Fan Wu, Qing Lan, Jiangfei Wang, Jizong Zhao
Glioblastoma is the most malignant tumor and has high mortality rate. The methylated prompter of MGMT results in chemotherapy sensitivity for these patients. However, there are still other factors that affected the prognosis for the glioblastoma patients with similar MGMT methylation status. We developed a signature with three genes screened from the whole genome mRNA expression profile from Chinese Glioma Genome Atlas (CGGA) and RNAseq data from The Cancer Genome Atlas (TCGA). Patients with MGMT methylation in low risk group had longer survival than those in high risk group (median overall survival 1074 vs...
August 31, 2016: Oncotarget
Zhongling Zhu, Shuangshuang Du, Fengxia Ding, Shanshan Guo, Guoguang Ying, Zhao Yan
The DNA-alkylating agent temozolomide (TMZ) is an effective chemotherapeutic agent against malignant glioma, including glioblastoma multiforme (GBM). However, the clinical efficacy of TMZ is limited in many patients because of O(6)-methylguanine-DNA methyltransferase (MGMT)-driven resistance. Thus, new strategies to overcome TMZ resistance are urgently needed. Ursolic acid (UA) is a naturally derived pentacyclic triterpene acid that exerts broad anticancer effects, and shows capability to cross the blood-brain barrier...
2016: American Journal of Translational Research
Hideyuki Arita, Kai Yamasaki, Yuko Matsushita, Taishi Nakamura, Asanao Shimokawa, Hirokazu Takami, Shota Tanaka, Akitake Mukasa, Mitsuaki Shirahata, Saki Shimizu, Kaori Suzuki, Kuniaki Saito, Keiichi Kobayashi, Fumi Higuchi, Takeo Uzuka, Ryohei Otani, Kaoru Tamura, Kazutaka Sumita, Makoto Ohno, Yasuji Miyakita, Naoki Kagawa, Naoya Hashimoto, Ryusuke Hatae, Koji Yoshimoto, Naoki Shinojima, Hideo Nakamura, Yonehiro Kanemura, Yoshiko Okita, Manabu Kinoshita, Kenichi Ishibashi, Tomoko Shofuda, Yoshinori Kodama, Kanji Mori, Yusuke Tomogane, Junya Fukai, Koji Fujita, Yuzo Terakawa, Naohiro Tsuyuguchi, Shusuke Moriuchi, Masahiro Nonaka, Hiroyoshi Suzuki, Makoto Shibuya, Taketoshi Maehara, Nobuhito Saito, Motoo Nagane, Nobutaka Kawahara, Keisuke Ueki, Toshiki Yoshimine, Etsuo Miyaoka, Ryo Nishikawa, Takashi Komori, Yoshitaka Narita, Koichi Ichimura
The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients' treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status...
2016: Acta Neuropathologica Communications
Donglai Lv, Shi-Cang Yu, Yi-Fang Ping, Haibo Wu, Xilong Zhao, Huarong Zhang, Youhong Cui, Bing Chen, Xia Zhang, Jianwu Dai, Xiu-Wu Bian, Xiao-Hong Yao
Three-dimensional (3D) culture, which can simulate in vivo microenvironments, has been increasingly used to study tumor cell biology. Since most preclinical anti-glioma drug tests still rely on conventional 2D cell culture, we established a collagen scaffold for 3D glioma cell culture. Glioma cells cultured on these 3D scaffolds showed greater degree of dedifferentiation and quiescence than cells in 2D culture. 3D-cultured cells also exhibited enhanced resistance to chemotherapeutic alkylating agents, with a much higher proportion of glioma stem cells and upregulation of O6-methylguanine DNA methyltransferase (MGMT)...
July 28, 2016: Oncotarget
Jie Zhang, Jian-Hui Yang, Jia Quan, Xing Kang, Hui-Juan Wang, Peng-Gao Dai
O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation was reported to be an independent prognostic and predictive factor in glioma patients who received temozolomide treatment. However, the predictive value of MGMT methylation was recently questioned by several large clinical studies. The purpose of this study is to identify MGMT gene promoter CpG sites or region whose methylation were closely correlated with its gene expression to elucidate this contradictory clinical observations. The methylation status for all CpG dinucleotides in MGMT promoter and first exon region were determined in 42 Chinese glioma patients, which were then correlated with MGMT gene expression, IDH1 mutation, and tumor grade...
July 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Fausto J Rodriguez, M Adelita Vizcaino, Ming-Tseh Lin
Gliomas represent the most common primary intraparenchymal tumors of the central nervous system in adults and children and are a genetic and phenotypic heterogeneous group. Large multi-institutional studies and The Cancer Genome Atlas have provided firm insights into the basic genetic drivers in gliomas. The main molecular biomarkers routinely applied to evaluate diffuse gliomas include MGMT promoter methylation, EGFR alterations (eg, EGFRvIII), IDH1 or IDH2 mutations, and 1p19q co-deletion. Many of these markers have become standard of care for molecular testing and prerequisites for clinical trial enrollment...
September 2016: Journal of Molecular Diagnostics: JMD
Guo-Zhong Yi, Ya-Wei Liu, Wei Xiang, Hai Wang, Zi-Yang Chen, Si-di Xie, Song-Tao Qi
Glioblastoma is one of the most lethal cancers in central nervous system, and some individual cells that cannot be isolated for surgical resection and also show treatment-resistance induce poor prognosis. Hence, in order to research these cells, we treated temozolomide (TMZ)-sensitive U87MG cells with 400μM TMZ in culture media for over 6months and established TMZ-resistant cell line designated as U87/TR. We detected the MGMT status through pyrosequencing and western blotting, and we also assessed the proliferation, migration, EMT-like changes and possible activated signaling pathways in U87/TR cells...
August 15, 2016: Journal of the Neurological Sciences
Quinn T Ostrom, Haley Gittleman, Carol Kruchko, David N Louis, Daniel J Brat, Mark R Gilbert, Valentina I Petkov, Jill S Barnholtz-Sloan
Cancer registries are an important source of population-level information on brain tumor incidence and survival. Surveillance, Epidemiology, and End Results (SEER) registries currently collect data on specific required factors related to brain tumors as defined by the American Joint Commission on Cancer, including World Health Organization (WHO) grade, MGMT methylation and 1p/19q codeletion status. We assessed 'completeness', defined as having valid values over the time periods that they have been collected, overall, by year, histology, and registry...
October 2016: Journal of Neuro-oncology
Norman L Lehman, Eyas M Hattab, Bret C Mobley, Aisulu Usubalieva, Matthew J Schniederjan, Roger E McLendon, Werner Paulus, Elisabeth J Rushing, Maria-Magdalena Georgescu, Marta Couce, Mohanpal S Dulai, Mark L Cohen, Christopher R Pierson, Jack M Raisanen, Sarah E Martin, Trang D Lehman, Eric S Lipp, Jose M Bonnin, Mousa A Al-Abbadi, Kara Kenworthy, Kevin Zhao, Nehad Mohamed, Guojuan Zhang, Weiqiang Zhao
BACKGROUND: Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. METHODS: We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan-Meier methods. RESULTS: Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive...
July 14, 2016: Neuro-oncology
Songhua Xiao, Zhen Yang, Xingsheng Qiu, Ruiyan Lv, Jun Liu, Ming Wu, Yiwei Liao, Qing Liu
Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However growing resistance to TMZ remains a major challenge to clinicians. The DNA repair protein O6-methylguanine-DNA methytransferase (MGMT) plays critical roles in TMZ resistance. Promoter methylation can inhibit MGMT expression and increase chemosensitivity. Here, we described a novel mechanism regulating MGMT expression. We showed that miR-29c suppressed MGMT expression indirectly via targeting specificity protein 1 (Sp1)...
July 1, 2016: Oncotarget
Sarah T Garber, Yuuri Hashimoto, Shiao-Pei Weathers, Joanne Xiu, Zoran Gatalica, Roel G W Verhaak, Shouhao Zhou, Gregory N Fuller, Mustafa Khasraw, John de Groot, Sandeep K Reddy, David Spetzler, Amy B Heimberger
BACKGROUND: Expression of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) across glioma grades is undocumented, and their interactions with commonly expressed genetic and epigenetic alterations are undefined but nonetheless highly relevant to combinatorial treatments. METHODS: Patients with CNS malignancies were profiled by Caris Life Sciences from 2009 to 2016. Immunohistochemistry findings for PD-1 on tumor-infiltrating lymphocytes (TIL) and PD-L1 on tumor cells were available for 347 cases...
October 2016: Neuro-oncology
Wolfgang Wick, Patrick Roth, Christian Hartmann, Peter Hau, Makoto Nakamura, Florian Stockhammer, Michael C Sabel, Antje Wick, Susanne Koeppen, Ralf Ketter, Peter Vajkoczy, Ilker Eyupoglu, Rolf Kalff, Torsten Pietsch, Caroline Happold, Norbert Galldiks, Friederike Schmidt-Graf, Michael Bamberg, Guido Reifenberger, Michael Platten, Andreas von Deimling, Christoph Meisner, Benedikt Wiestler, Michael Weller
BACKGROUND: Optimal treatment and precise classification for anaplastic glioma are needed. METHODS: The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). RESULTS: Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered...
November 2016: Neuro-oncology
Laura Fontana, Silvia Tabano, Eleonora Bonaparte, Giovanni Marfia, Chiara Pesenti, Rossella Falcone, Claudia Augello, Nicole Carlessi, Rosamaria Silipigni, Silvana Guerneri, Rolando Campanella, Manuela Caroli, Silvia Maria Sirchia, Silvano Bosari, Monica Miozzo
Several molecular markers drive diagnostic classification, prognostic stratification, and/or prediction of response to therapy in patients with gliomas. Among them, IDH gene mutations are valuable markers for defining subtypes and are strongly associated with epigenetic silencing of the methylguanine DNA methyltransferase (MGMT) gene. However, little is known about the percentage of MGMT-methylated alleles in IDH-mutated cells or the potential association between MGMT methylation and deletion of chromosome 10q, which encompasses the MGMT locus...
June 26, 2016: Journal of Neuropathology and Experimental Neurology
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