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https://www.readbyqxmd.com/read/28425046/mir-198-enhances-temozolomide-sensitivity-in-glioblastoma-by-targeting-mgmt
#1
Er Nie, Xin Jin, Weining Wu, Tianfu Yu, Xu Zhou, Zhumei Shi, Junxia Zhang, Ning Liu, Yongping You
Glioblastoma is one of the most frequent and aggressive brain tumors. Accumulating evidence indicates that microRNAs are involved in glioma proliferation, invasion and drug resistance. Previous studies showed that miR-198 is downregulated in glioblastoma. However, the function of miR-198 in glioblastoma is still unclear. In this study, we report that miR-198 levels were greatly downregulated in glioblastoma specimens and decreased expression of miR-198 was associated with poor prognosis in patients with glioblastoma...
April 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28409559/correlations-of-mgmt-genetic-polymorphisms-with-temozolomide-resistance-and-prognosis-of-patients-with-malignant-gliomas-a-population-based-study-in-china
#2
H-W Wang, Z-K Xu, Y Song, Y-G Liu
This study aims to investigate the associations of O(6)-methylguanine-DNA methyltransferase (MGMT) genetic polymorphisms (Leu84Phe and Ile143Val) with temozolomide (TMZ) resistance and prognosis of patients with malignant gliomas. A total of 212 patients diagnosed with malignant gliomas were enrolled in this study as the case group. All of these patients took oral TMZ and were assigned into the TMZ-sensitive (complete response+partial response) and the TMZ-resistant (stable disease+progressive disease) groups based on the clinical response after chemotherapy...
April 14, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28371614/hypermutations-in-gliomas-a-potential-immunotherapy-target
#3
Gaetano Finocchiaro, Tiziana Langella, Cristina Corbetta, Serena Pellegatta
Checkpoint inhibitors, like ipilimumab, nivolumab, and pembrolizumab, have provided a breakthrough in cancer immunotherapy, such as in the treatment of melanoma and colorectal and lung cancer. The close relationship between the number of mutations (mutational load) and the response to checkpoint immunotherapy has been convincingly demonstrated in these cancers. Hypermutations in tumors are caused by environmental factors, like UV radiations or cigarette smoking, or by germinal mutations affecting genes of the Mismatch Repair (MMR) machinery, as in the Lynch syndrome...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28314286/safety-and-tolerance-of-d-l-methadone-in-combination-with-chemotherapy-in-patients-with-glioma
#4
Julia Onken, Claudia Friesen, Peter Vajkoczy, Martin Misch
BACKGROUND/AIM: D,L-Methadone increases sensitivity toward chemotherapy of different tumor cell populations. We evaluated the safety and tolerance of additional use of D,L-methadone in patients with glioma in combination with chemotherapy. PATIENTS AND METHODS: The dosage, duration of therapy and side-effects related to D,L-methadone were recorded in 27 patients. Toxicity was assessed accordingly to the Common Toxicity Criteria (CTC) of the National Cancer Institute...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303493/the-effect-of-molecular-diagnostics-on-the-treatment-of-glioma
#5
REVIEW
Nancy Ann Oberheim Bush, Nicholas Butowski
PURPOSE OF REVIEW: This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. RECENT FINDINGS: Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28298550/limited-role-for-extended-maintenance-temozolomide-for-newly-diagnosed-glioblastoma
#6
Dorothee Gramatzki, Philipp Kickingereder, Bettina Hentschel, Jörg Felsberg, Ulrich Herrlinger, Gabriele Schackert, Jörg-Christian Tonn, Manfred Westphal, Michael Sabel, Uwe Schlegel, Wolfgang Wick, Torsten Pietsch, Guido Reifenberger, Markus Loeffler, Martin Bendszus, Michael Weller
OBJECTIVE: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. METHODS: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression...
March 15, 2017: Neurology
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#7
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28195901/prognostic-molecular-and-imaging-biomarkers-in-primary-glioblastoma
#8
Edit Bosnyák, Sharon K Michelhaugh, Neil V Klinger, David O Kamson, Geoffrey R Barger, Sandeep Mittal, Csaba Juhász
PURPOSE: Several molecular glioma markers (including isocitrate dehydrogenase 1 [IDH1] mutation, amplification of the epidermal growth factor receptor [EGFR], and methylation of the O6-methylguanine-DNA methyltransferase [MGMT] promoter) have been associated with glioblastoma survival. In this study, we examined the association between tumoral amino acid uptake, molecular markers, and overall survival in patients with IDH1 wild-type (primary) glioblastoma. PATIENTS AND METHODS: Twenty-one patients with newly diagnosed IDH1 wild-type glioblastomas underwent presurgical MRI and PET scanning with alpha[C-11]-L-methyl-tryptophan (AMT)...
May 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28185110/foxm1-mediated-rfc5-expression-promotes-temozolomide-resistance
#9
Wan-Xin Peng, Xiu Han, Chun-Li Zhang, Lu Ge, Feng-Yi Du, Jie Jin, Ai-Hua Gong
Although methylguanine-DNA-methyltransferase (MGMT) plays an important role in resistance to temozolomide (TMZ) in glioma, 40% of gliomas with MGMT inactivation are still resistant to TMZ. The underlying mechanism is not clear. Here, we report that forkhead box M1 (FoxM1) transcriptionally activates the expression of DNA repair gene replication factor C5 (RFC5) to promote TMZ resistance in glioma cells independent of MGMT activation. We showed that RFC5 expression is positively correlated with FoxM1 expression in human glioma cells and FoxM1 is able to transcriptionally activate RFC expression by interaction with the RFC5 promoter...
February 9, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28148826/prognostic-relevance-of-tumor-purity-and-tert-promoter-mutations-on-mgmt-promoter-methylation-in-glioblastoma
#10
Eva Schulze Heuling, Felix Knab, Josefine Radke, Eskil Eskilsson, Emmanuel Martinez-Ledesma, Arend Koch, Marcus Czabanka, Christoph Dieterich, Roel G Verhaak, Christoph Harms, Philipp Euskirchen
Promoter methylation status of O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, is a critical biomarker in glioblastoma multiforme (GBM) as treatment decisions and clinical trial inclusion rely on its accurate assessment. However, interpretation of results is complicated by poor inter-assay reproducibility as well as weak a correlation between methylation status and expression levels of MGMT. The present study systematically investigates the influence of tumor purity on tissue subjected to MGMT analysis...
February 1, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28147244/the-pi3k-inhibitor-gdc-0941-enhances-radiosensitization-and-reduces-chemoresistance-to-temozolomide-in-gbm-cell-lines
#11
Fei Shi, Hongchuan Guo, Rong Zhang, Hongyu Liu, Liangliang Wu, Qiyan Wu, Jialin Liu, Tianyi Liu, Qiuhang Zhang
Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). However, GBM has a dismal prognosis, and survivors have compromised quality of life owing to the adverse effects of radiation. GBM is characterized by overt activity of the phosphoinositide 3-kinase (PI3K) signaling pathway...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28143714/chloroethylating-nitrosoureas-in-cancer-therapy-dna-damage-repair-and-cell-death-signaling
#12
REVIEW
Teodora Nikolova, Wynand P Roos, Oliver H Krämer, Herwig M Strik, Bernd Kaina
Chloroethylating nitrosoureas (CNU), such as lomustine, nimustine, semustine, carmustine and fotemustine are used for the treatment of malignant gliomas, brain metastases of different origin, melanomas and Hodgkin disease. They alkylate the DNA bases and give rise to the formation of monoadducts and subsequently interstrand crosslinks (ICL). ICL are critical cytotoxic DNA lesions that link the DNA strands covalently and block DNA replication and transcription. As a result, S phase progression is inhibited and cells are triggered to undergo apoptosis and necrosis, which both contribute to the effectiveness of CNU-based cancer therapy...
January 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28110346/prognostic-value-of-molecular-and-imaging-biomarkers-in-patients-with-supratentorial-glioma
#13
Egesta Lopci, Marco Riva, Laura Olivari, Fabio Raneri, Riccardo Soffietti, Arnoldo Piccardo, Alberto Bizzi, Pierina Navarria, Anna Maria Ascolese, Roberta Rudà, Bethania Fernandes, Federico Pessina, Marco Grimaldi, Matteo Simonelli, Marco Rossi, Tommaso Alfieri, Paolo Andrea Zucali, Marta Scorsetti, Lorenzo Bello, Arturo Chiti
PURPOSE: We evaluated the relationship between (11)C-methionine PET ((11)C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. METHODS: A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative (11)C-METH PET were analysed. Semiquantitative evaluation of the (11)C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV)...
January 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28107674/mitochondrial-serine-hydroxymethyltransferase-2-is-a-potential-diagnostic-and-prognostic-biomarker-for-human-glioma
#14
Bo Wang, Wei Wang, ZhiZhong Zhu, XueBin Zhang, Fan Tang, Dong Wang, Xi Liu, XiaoLing Yan, Hao Zhuang
OBJECTIVE: Scholars have gradually come to appreciate the relevance of serine and glycine metabolism. Recently, researchers have discovered that mitochondrial serine hydroxymethyltransferase 2 (SHMT2) is overexpressed in various types of cancer. However, the function of SHMT2 in glioma is not clear. In this study, we sought to examine the expression of SHMT2 in glioma, the association between SHMT2 expression and clinicopathological characteristics, and the association of SHMT2 expression with prognosis in glioma patients...
March 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28025770/molecular-genetic-and-clinicopathological-prognostic-factors-in-patients-with-gliomas-showing-total-1p19q-loss-gain-of-chromosome-19p-and-histological-grade-iii-negatively-correlate-with-patient-s-prognosis
#15
Saeko Hayashi, Yohei Kitamura, Yuichi Hirose, Kazunari Yoshida, Hikaru Sasaki
Although 1p19q codeleted gliomas are the most favorable molecular subgroup of lower-grade gliomas, there are cases with early recurrence or short survival. The objective of this study was to elucidate molecular-genetic and clinicopathological prognostic factors in patients with gliomas showing total 1p19q loss. The study included 57 consecutive patients with codeleted gliomas who were operated at Keio University Hospital between 1990 and 2010. These patients were assessed for chromosomal copy number aberrations, promoter methylation status of the O6-methylguanine-DNA methyltransferase gene (MGMT), and demographic and clinicopathological prognostic factors in diffuse gliomas...
December 26, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27979804/correction-ifn-%C3%AE-down-regulates-the-expression-of-dna-repair-gene-mgmt-and-sensitizes-resistant-glioma-cells-to-temozolomide
#16
(no author information available yet)
No abstract text is available yet for this article.
December 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27966427/patterns-of-diagnostic-marker-assessment-in-adult-diffuse-glioma-a-survey-of-the-european-confederation-of-neuropathological-societies-euro-cns
#17
Adelheid Woehrer, Bjarne W Kristensen, Anne Vital, Johannes A Hainfellner
The 2016 update of the WHO classification has introduced an integrated diagnostic approach that incorporates both tumor morphology and molecular information. This conceptual change has far-reaching implications, especially for neuropathologists who are in the forefront of translating molecular markers to routine diagnostic use. Adult diffuse glioma is a prototypic example for a group of tumors that underwent substantial regrouping, and it represents a major workload for surgical neuropathologists. Hence, we conducted a survey among members of the European Confederation of Neuropathological Societies (Euro-CNS) in order to assess 1) the extent to which molecular markers have already been incorporated in glioma diagnoses, 2) which molecular techniques are in daily use, and 3) to set a baseline for future surveys in this field...
January 2017: Clinical Neuropathology
https://www.readbyqxmd.com/read/27915062/rosette-forming-glioneuronal-tumor-originating-from-the-spinal-cord-report-of-2-cases-and-literature-review
#18
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. RGNT was first described as a new entity for the distinct clinicopathologic features by Komori et.al. in 2002. Histologically, it is composed of 2 distinct features: a glial component, resembling pilocytic astrocytoma, and a neurocytic component forming neurocytic rosettes and/or perivascular rosettes. We report 2 extremely rare cases of RGNT arising from the spinal cord, which were misdiagnosed as ependymoma and astrocytoma preoperatively...
February 2017: World Neurosurgery
https://www.readbyqxmd.com/read/27894350/gant61-a-gli-inhibitor-sensitizes-glioma-cells-to-the-temozolomide-treatment
#19
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
https://www.readbyqxmd.com/read/27834917/potential-role-of-methylation-marker-in-glioma-supporting-clinical-decisions
#20
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
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