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https://www.readbyqxmd.com/read/27921166/outcome-in-unresectable-glioblastoma-mgmt-promoter-methylation-makes-the-difference
#1
Niklas Thon, Jun Thorsteinsdottir, Sabina Eigenbrod, Ulrich Schüller, Jürgen Lutz, Simone Kreth, Claus Belka, Jörg-Christian Tonn, Maximilian Niyazi, Friedrich Wilhelm Kreth
In 2011, we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival (PFS) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide (RTX/TMZ → TMZ). We, here, present the final results of this prospective study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification. Overall, 56 adult patients with unresectable, biopsy proven glioblastoma were prospectively assigned to upfront RTX/TMZ → TMZ treatment between March 2006 and August 2008...
December 5, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27915062/rosette-forming-glioneuronal-tumor-originating-from-the-spinal-cord-report-of-two-cases-and-literature-review
#2
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
https://www.readbyqxmd.com/read/27904447/long-term-survival-in-glioblastoma-methyl-guanine-methyl-transferase-mgmt-promoter-methylation-as-independent-favourable-prognostic-factor
#3
Uros Smrdel, Mara Popovic, Matjaz Zwitter, Emanuela Bostjancic, Andrej Zupan, Viljem Kovac, Damjan Glavac, Drago Bokal, Janja Jerebic
BACKGROUND: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. PATIENTS AND METHODS: Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27903892/methylation-sensitive-enrichment-of-minor-dna-alleles-using-a-double-strand-dna-specific-nuclease
#4
Yibin Liu, Chen Song, Ioannis Ladas, Mariana Fitarelli-Kiehl, G Mike Makrigiorgos
Aberrant methylation changes, often present in a minor allelic fraction in clinical samples such as plasma-circulating DNA (cfDNA), are potentially powerful prognostic and predictive biomarkers in human disease including cancer. We report on a novel, highly-multiplexed approach to facilitate analysis of clinically useful methylation changes in minor DNA populations. Methylation Specific Nuclease-assisted Minor-allele Enrichment (MS-NaME) employs a double-strand-specific DNA nuclease (DSN) to remove excess DNA with normal methylation patterns...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27896979/genome-wide-interaction-with-selected-type-2-diabetes-loci-reveals-novel-loci-for-type-2-diabetes-in-african-americans
#5
Jacob M Keaton, Jacklyn N Hellwege, Maggie C Y Ng, Nicholette D Palmer, James S Pankow, Myriam Fornage, James G Wilson, Adolfo Correa, Laura J Rasmussen-Torvik, Jerome I Rotter, Yii-DER I Chen, Kent D Taylor, Stephen S Rich, Lynne E Wagenknecht, Barry I Freedman, Donald W Bowden
Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, and previously associated with T2D in genome-wide association studies (GWAS) were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n=492 subjects)...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27894350/gant61-a-gli-inhibitor-sensitizes-glioma-cells-to-the-temozolomide-treatment
#6
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/27888622/quantification-and-expert-evaluation-of-evidence-for-chemopredictive-biomarkers-to-personalize-cancer-treatment
#7
Shruti Rao, Robert A Beckman, Shahla Riazi, Cinthya S Yabar, Simina M Boca, John L Marshall, Michael J Pishvaian, Jonathan R Brody, Subha Madhavan
Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27872185/the-major-replicative-histone-chaperone-caf-1-suppresses-the-activity-of-the-dna-mismatch-repair-system-in-the-cytotoxic-response-to-a-dna-methylating-agent
#8
Lyudmila Y Kadyrova, Basanta K Dahal, Farid A Kadyrov
The DNA mismatch repair (MMR) system corrects DNA mismatches in the genome. It is also required for the cytotoxic response of O(6)-methylguanine-DNA methyltransferase (MGMT)-deficient mammalian cells and yeast mgt1Δ rad52Δ cells to treatment with Sn1-type methylating agents, which produce cytotoxic O(6)-methylguanine (O(6)-mG) DNA lesions. Specifically, processing of irreparable O(6)-mG-containing mispairs by the MMR system causes DNA degradation, triggering cell death; this process forms the basis of treatments of MGMT-deficient cancers with Sn1-type methylating drugs...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27865821/the-effects-of-tumor-treating-fields-and-temozolomide-in-mgmt-expressing-and-non-expressing-patient-derived-glioblastoma-cells
#9
Paul A Clark, Jordan T Gaal, Joslyn K Strebe, Cheri A Pasch, Dustin A Deming, John S Kuo, H Ian Robins
A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12...
November 16, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27864689/epstein-barr-virus-infection-and-gene-promoter-hypermethylation-in-rheumatoid-arthritis-patients-with-methotrexate-associated-b-cell-lymphoproliferative-disorders
#10
Kozue Ejima-Yamada, Yumi Oshiro, Seiichi Okamura, Tomoaki Fujisaki, Yasuhito Mihashi, Kazuo Tamura, Tomoko Fukushige, Masaru Kojima, Kazutoshi Shibuya, Morishige Takeshita
We analyzed CpG-island hypermethylation status in 12 genes of paraffin-embedded tissues from 38 rheumatoid arthritis (RA) patients with methotrexate (MTX)-associated large B cell lymphoproliferative disorder (BLPD), 11 RA patients with non-MTX-associated BLPD (non-MTX-BLPD), 22 controls with diffuse large B cell lymphoma (DLBCL), and 10 controls with Epstein-Barr virus (EBV)(+) DLBCL. Among them, tumor cells from EBV(+) MTX-BLPD patients and control EBV(+) DLBCL patients had significantly lower median incidence of CpG island methylator phenotype (CIMP) than those from non-MTX-BLPD and control DLBCL groups (2...
November 18, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27845303/new-insights-into-estrogenic-regulation-of-o-6-methylguanine-dna-methyltransferase-mgmt-in-human-breast-cancer-cells-co-degradation-of-er-%C3%AE-and-mgmt-proteins-by-fulvestrant-or-o-6-benzylguanine-indicates-fresh-avenues-for-therapy
#11
Ameya Paranjpe, Nathan I Bailey, Santhi Konduri, George C Bobustuc, Francis Ali-Osman, Mohd A Yusuf, Surendra R Punganuru, Hanumantha Rao Madala, Debasish Basak, Agm Mostofa, Kalkunte S Srivenugopal
Endocrine therapy using estrogen receptor-α (ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated the functional and physical interactions of ER-α with O(6)-methylguanine DNA methyltransferase (MGMT), a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents. The ER-α -positive breast cancer cell lines (MCF-7, T47D) and ER- negative cell lines (MDAMB-468, MDAMB-231), and established inhibitors of ER-α and MGMT, namely, ICI-182,780 (Faslodex) and O(6)-benzylguanine, respectively, were used to study MGMT- ER interactions...
September 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27835605/meta-analysis-of-dna-methylation-biomarkers-in-hepatocellular-carcinoma
#12
Cheng Zhang, Jinyun Li, Tao Huang, Shiwei Duan, Dongjun Dai, Danjie Jiang, Xinbing Sui, Da Li, Yidan Chen, Fei Ding, Changxin Huang, Gongying Chen, Kaifeng Wang
DNA methylation is an epigenetic mechanism in the pathogenesis of hepatocellular carcinoma (HCC). Here, we conducted a systematic meta-analysis to evaluate the contribution of DNA methylation to the risk of HCC. A total of 2109 publications were initially retrieved from PubMed, Web of Science, Cochrane Library, Embase, CNKI and Wanfang literature database. After a four-step filtration, we harvested 144 case-control articles in the meta-analysis. Our results revealed that 24 genes (carcinoma tissues vs adjacent tissues), 17 genes (carcinoma tissues vs normal tissues) and six genes (carcinoma serums vs normal serums) were significantly hypermethylated in HCC...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834917/potential-role-of-methylation-marker-in-glioma-supporting-clinical-decisions
#13
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
https://www.readbyqxmd.com/read/27824946/the-correlation-of-mgmt-promoter-methylation-and-clinicopathological-features-in-gastric-cancer-a-systematic-review-and-meta-analysis
#14
Yong Ding, Qihua Yang, Bojun Wang, Guoliang Ye, Xiaoqiong Tong
The silencing of the tumor suppressor gene O-6-methylguanine-DNA methyltransferase (MGMT) by promoter methylation commonly occurs in human cancers. The relationship between MGMT promoter methylation and gastric cancer (GC) remains inconsistent. This study aimed to evaluate the potential value of MGMT promoter methylation in GC patients. Electronic databases were searched to identify eligible studies. The pooled odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were used to evaluate the effects of MGMT methylation on GC risk and clinicopathological characteristics...
2016: PloS One
https://www.readbyqxmd.com/read/27802200/modern-molecular-biomarkers-of-head-and-neck-cancer-part-i-epigenetic-diagnostics-and-prognostics-systematic-review
#15
Gintaras Juodzbalys, David Kasradze, Marco Cicciù, Aurimas Sudeikis, Laurynas Banys, Pablo Galindo-Moreno, Zygimantas Guobis
INTRODUCTION: Nearly half of the head and neck cancer cases are diagnosed in late stages. Traditional screening modalities have many disadvantages. The aim of the present article was to review the scientific literature about novel head and neck cancer diagnostics - epigenetic biomarkers. EVIDENCE ACQUISITION: A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in English language published from 2004 to 2015...
September 30, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27800031/long-term-survival-in-a-patient-with-glioblastoma-on-antipsychotic-therapy-for-schizophrenia-a-case-report-and-literature-review
#16
REVIEW
Shahdabul Faraz, Susan Pannullo, Marc Rosenblum, Andrew Smith, A Gabriella Wernicke
Glioblastoma is not only the most common primary brain tumor, but also the most aggressive. Currently, the most effective treatment of surgery, chemotherapy and radiation therapy allows for a modest median survival of 15 months. Here, we report a case of a 57-year-old male with histologically confirmed glioblastoma with unfavorable prognostic characteristics (poor performance status and persistent neurological symptoms after surgery), whose expected 5-year survival is 0%. Further genetic analysis offered a mixed prognostic picture with positive methylation of 0-6-methylguinine-DNA (deoxyribonucleic acid) methyltransferase (MGMT; favorable prognosis) and wild-type isocitrate dehydrogenase 1 (IDH-1; unfavorable prognosis)...
November 2016: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/27798894/kras-mutant-status-p16-and-%C3%AE-catenin-expression-may-predict-local-recurrence-in-patients-who-underwent-transanal-endoscopic-microsurgery-tems-for-stage-i-rectal-cancer
#17
Michail Sideris, Jane Moorhead, Salvador Diaz-Cano, Ingvar Bjarnason, Amyn Haji, Savvas Papagrigoriadis
BACKGROUND/AIM: Transanal endoscopic microsurgery (TEMS) is emerging as an alternative treatment for rectal cancer Stage I. There remains a risk of local recurrence. The Aim of the study was to study the effect of biomarkers in local recurrence for Stage I rectal cancer following TEMS plus or minus radiotherapy. MATERIALS AND METHODS: This is a case control study where we compared 10 early rectal cancers that had recurred, against 19 cases with no recurrence, total 29 patients (age=28...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27793847/dna-repair-capacity-in-multiple-pathways-predicts-chemoresistance-in-glioblastoma-multiforme
#18
Zachary D Nagel, Gaspar J Kitange, Shiv K Gupta, Brian A Joughin, Isaac A Chaim, Patrizia Mazzucato, Douglas A Lauffenburger, Jann N Sarkaria, Leona D Samson
Cancer cells can resist the effects of DNA-damaging therapeutic agents via utilization of DNA repair pathways, suggesting that DNA repair capacity (DRC) measurements in cancer cells could be used to identify patients most likely to respond to treatment. However, the limitations of available technologies have so far precluded adoption of this approach in the clinic. We recently developed fluorescence-based multiplexed host cell reactivation (FM-HCR) assays to measure DRC in multiple pathways. Here we apply a mathematical model that uses DRC in multiple pathways to predict cellular resistance to killing by DNA-damaging agents...
October 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27792996/microrna-101-reverses-temozolomide-resistance-by-inhibition-of-gsk3%C3%AE-in-glioblastoma
#19
Tian Tian, Ma Mingyi, Xia Qiu, Yang Qiu
Glioblastoma multiforme (GBM) is a chemotherapy-resistant brain tumor with limited treatment options. Temozolomide (TMZ), an alkylating agent, is a front-line chemotherapeutic drug currently employed in GBM. Although it is currently the most promising chemotherapy for GBM, resistance to TMZ is also common and accounts for many treatment failures. Therefore, understanding the underlying mechanisms that generate resistance is essential to develop more effective chemotherapies. Here, we show that microRNA-101 (miR-101) was significantly downregulated in TMZ-resistant GBM cells and human specimens...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27785051/relationships-between-mgmt-promoter-methylation-and-gastric-cancer-a-meta-analysis
#20
Dan Yu, Tao Cao, Ya-Di Han, Fu-Sheng Huang
A DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT), plays an important role in the development of gastric cancers. However, the role of MGMT promoter methylation in the occurrence of gastric cancer and its relationships with clinicopathologic characteristics has not been fully clarified. Thus, we performed a meta-analysis to evaluate the associations between MGMT promoter methylation and gastric cancer. Electronic databases, including PubMed and Web of Science, were used to systematically search related clinical studies published in English until April 1, 2016...
2016: OncoTargets and Therapy
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