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https://www.readbyqxmd.com/read/28516344/defining-optimal-cutoff-value-of-mgmt-promoter-methylation-by-roc-analysis-for-clinical-setting-in-glioblastoma-patients
#1
Guoqiang Yuan, Liang Niu, Yinian Zhang, Xiaoqing Wang, Kejun Ma, Hang Yin, Junqiang Dai, Wangning Zhou, Yawen Pan
Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in the treatment of glioblastoma (GBM). Hypermethylation in O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is thought to play a critical role in this resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for MGMT promoter methylation testing. The unresolved issue is the determination of a cut-off value for dichotomization of quantitative MGMT PSQ results into "MGMT methylated" and "MGMT unmethylated" patient subgroups as a basis for further treatment decisions...
May 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28510787/a-phase-ii-trial-of-arsenic-trioxide-and-temozolomide-in-combination-with-radiation-therapy-for-patients-with-malignant-gliomas
#2
Priya Kumthekar, Sean Grimm, James Chandler, Minesh Mehta, Maryanne Marymont, Robert Levy, Kenji Muro, Irene Helenowski, Katie McCarthy, Leanne Fountas, Jeffrey Raizer
Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic trioxide (ATO) is synergistic with RT based on several mechanisms of action previously identified, however not tested herein. The MTD of ATO, RT and TMZ was determined in a Phase I trial. We now present the combined Phase I/II data. Patients with newly diagnosed malignant gliomas were eligible for treatment. Patients were treated with RT (60 GY), TMZ (75 mg/m(2) daily × 42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week ×5 weeks, after completing RT they were treated with TMZ 5/28 for up to 12 months...
May 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28508327/assessment-of-molecular-markers-demonstrates-concordance-between-samples-acquired-via-stereotactic-biopsy-and-open-craniotomy-in-both-anaplastic-astrocytomas-and-glioblastomas
#3
Florian Gessler, Peter Baumgarten, Joshua D Bernstock, Patrick Harter, Stephanie Lescher, Christian Senft, Volker Seifert, Gerhard Marquardt, Lutz Weise
The classification, treatment and prognosis of high-grade gliomas has been shown to correlate with the expression of molecular markers (e.g. MGMT promotor methylation and IDH1 mutations). Acquisition of tumor samples may be obtained via stereotactic biopsy or open craniotomy. Between the years 2009 and 2013, 22 patients initially diagnosed with HGGs via stereotactic biopsy, that ultimately underwent open craniotomy for resection of their tumor were prospectively included in an institutional glioma database...
May 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28500786/dovitinib-enhances-temozolomide-efficacy-in-glioblastoma-cells
#4
Thatchawan Thanasupawat, Suchitra Natarajan, Amy Rommel, Aleksandra Glogowska, Hugo Bergen, Jerry Krcek, Marshall Pitz, Jason Beiko, Sherry Krawitz, Inder M Verma, Saeid Ghavami, Thomas Klonisch, Sabine Hombach-Klonisch
The multikinase inhibitor and FDA-approved drug Dovitinib (Dov) crosses the blood-brain-barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target High Mobility Group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3(Tyr705) phosphorylation demonstrated that Dov negatively affects the STAT3-LIN28-Let-7-HMGA2 regulatory axis in GB cells...
May 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28499389/a-phase-ii-trial-of-autologous-dendritic-cell-vaccination-and-radiochemotherapy-following-fluorescence-guided-surgery-in-newly-diagnosed-glioblastoma-patients
#5
Susana Inogés, Sonia Tejada, Ascensión López-Díaz de Cerio, Jaime Gállego Pérez-Larraya, Jaime Espinós, Miguel Angel Idoate, Pablo Daniel Domínguez, Reyes García de Eulate, Javier Aristu, Maurizio Bendandi, Fernando Pastor, Marta Alonso, Enrique Andreu, Felipe Prósper Cardoso, Ricardo Díez Valle
BACKGROUND: Prognosis of patients with glioblastoma multiforme (GBM) remains dismal, with median overall survival (OS) of about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained with conventional treatments. In this context, immunotherapy seems to be a promising therapeutic option. We hypothesized that the addition of tumor lysate-pulsed autologous dendritic cells (DCs) vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide could improve patients' survival...
May 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28499365/investigation-of-dna-repair-related-snps-underlying-susceptibility-to-papillary-thyroid-carcinoma-reveals-mgmt-as-a-novel-candidate-gene-in-belarusian-children-exposed-to-radiation
#6
Christine Lonjou, Francesca Damiola, Monika Moissonnier, Geoffroy Durand, Irina Malakhova, Vladimir Masyakin, Florence Le Calvez-Kelm, Elisabeth Cardis, Graham Byrnes, Ausrele Kesminiene, Fabienne Lesueur
BACKGROUND: Genetic factors may influence an individual's sensitivity to ionising radiation and therefore modify his/her risk of developing papillary thyroid carcinoma (PTC). Previously, we reported that common single nucleotide polymorphisms (SNPs) within the DNA damage recognition gene ATM contribute to PTC risk in Belarusian children exposed to fallout from the Chernobyl power plant accident. Here we explored in the same population the contribution of a panel of DNA repair-related SNPs in genes acting downstream of ATM...
May 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28498475/targeting-hexokinase-2-inhibition-promotes-radiosensitization-in-hpv16%C3%A2-e7-induced-cervical-cancer-and-suppresses-tumor-growth
#7
Yuan Liu, Tracy Murray-Stewart, Robert A Casero, Ioannis Kagiampakis, Lihua Jin, Jiawen Zhang, Huihui Wang, Qi Che, Huan Tong, Jieqi Ke, Feizhou Jiang, Fangyuan Wang, Xiaoping Wan
In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells. We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3. HK2 inhibition also induced much inferior proliferation of cervical cancer cells both in vitro and in vivo with diminishing expression of mTOR, MIB and MGMT...
May 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28497669/mapping-seizure-foci-and-tumor-genetic-factors-in-glioma-associated-seizure-patients
#8
Mao Yunhe, Yang Yuan, Wang Xiang, Liu Yanhui, Mao Qing
BACKGROUND: Epilepsy, which is the most common symptom accompanying gliomas, was reported as an independent favorable prognosis factor for glioma patients. However, the correlation between glioma location and epilepsy prognosis, genesis and genetic phenotypes of the glioma associated seizure (GAS) patients is far from clear, the purpose of the current study was to provide probabilistic radiographic atlases reflecting seizure susceptible regions, relationship between tumor associated biomarkers and seizure initiation and poor epilepsy prognosis areas...
May 11, 2017: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/28496000/stratification-according-to-recursive-partitioning-analysis-predicts-outcome-in-newly-diagnosed-glioblastomas
#9
Fan Yang, Pei Yang, Chuanbao Zhang, Yongzhi Wang, Wei Zhang, Huimin Hu, Zhiliang Wang, Xiaoguang Qiu, Tao Jiang
Glioblastoma accounts for more than half of diffuse gliomas. The prognosis of patients with glioblastoma remains poor despite comprehensive and intensive treatments. Furthermore, the clinical significance of molecular parameters and routinely available clinical variables for the prognosis prediction of glioblastomas remains limited. The authors describe a novel model may help in prognosis prediction and clinical management of glioblastoma patients. We performed a recursive partitioning analysis to generate three independent prognostic classes of 103 glioblastomas patients from TCGA dataset...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28494176/comparative-analysis-of-the-effects-of-a-sphingosine-kinase-inhibitor-to-temozolomide-and-radiation-treatment-on-glioblastoma-cell-lines
#10
Liliana R Oancea-Castillo, Carmen Klein, Amir Abdollahi, Klaus-Josef Weber, Anne Régnier-Vigouroux, Ivana Dokic
Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28486243/mgmt-methylation-correlates-with-melphalan-pelvic-perfusion-survival-in-stage-iii-melanoma-patients-a-pilot-study
#11
Stefano Guadagni, Giammaria Fiorentini, Marco Clementi, Giancarlo Palumbo, Francesco Masedu, Marcello Deraco, Giovanni De Manzoni, Alessandro Chiominto, Marco Valenti, Cristina Pellegrini
Approximately 25% of melanoma patients with locoregional metastases are nonresponsive to new molecular target therapy and immunotherapy. When metastases are located in the pelvis, melphalan hypoxic perfusion can be an optional treatment. Because methylation of MGMT promoter increases the efficacy of alkylating agents, studies on melanoma outcome of patients treated with melphalan regional chemotherapy should consider this epigenetic change. This study aims to evaluate whether the survival of stage III melanoma patients treated with melphalan regional chemotherapy may be correlated with MGMT methylation status...
May 10, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28484518/importance-of-biomarkers-in-glioblastomas-patients-receiving-local-bcnu-wafer-chemotherapy
#12
Steffi Urbschat, Christoph Sippl, Jana Engelhardt, Kai Kammers, Joachim Oertel, Ralf Ketter
BACKGROUND: To assess the influence of molecular markers with potential prognostic value to groups of patients with newly diagnosed glioblastoma patients were examined: group A with 36 patients (surgical resection plus standard combined chemoradiotherapy) and group B with 36 patients (surgical resection, standard combined chemoradiotherapy plus carmustine wafer implantation). Our aim was to determine chromosomal alterations, methylation status of MGMT, p15, and p16 (CDKN2A) in order to analyse the influence on patient survival time as well as radio- and chemotherapy responses...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28468586/alteration-in-the-expression-of-mgmt-and-runx3-due-to-non-cpg-promoter-methylation-and-their-correlation-with-different-risk-factors-in-esophageal-cancer-patients
#13
Snigdha Saikia, Asad Ur Rehman, Prajjalendra Barooah, Preeti Sarmah, Mallika Bhattacharyya, Muktanjalee Deka, Manab Deka, Bhabadev Goswami, Syed Akhtar Husain, Subhash Medhi
Promoter methylation reflects in the inactivation of different genes like O(6)-methylguanine-DNA methyltransferase DNA repair gene and runt-related transcription factor 3, a known tumor suppressor gene in various cancers such as esophageal cancer. The promoter methylation was evaluated for O(6)-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in CpG, CHH, and CHG context (where H is A, T, or C) by next-generation sequencing. The methylation status was correlated with quantitative messenger RNA expression...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28458179/promoter-methylation-of-mgmt-in-oral-carcinoma-a-population-based-study-and-meta-analysis
#14
Chinchu Jayaprakash, Raghu Radhakrishnan, Satadru Ray, Kapaettu Satyamoorthy
INTRODUCTION: The relevance of DNA methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) in relation to several cancers and other disorders has been extensively explored in several cancer types. AIMS: To ascertain the significance of DNA methylation of MGMT promoter in oral squamous cell carcinoma (OSCC), we undertook a study to a) analyse the methylation patterns of MGMT gene promoter in afflicted and normal population of coastal Karnataka, b) determine the expression status of MGMT in oral cancer cell lines (CAL-27 and SCC-4) and its relationship to DNA methylation and c) performed a meta-analysis of the published data...
April 23, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28454549/does-age-really-matter-radiotherapy-in-elderly-patients-with-glioblastoma-the-munich-experience
#15
Christoph Straube, Hagen Scherb, Jens Gempt, Stefanie Bette, Claus Zimmer, Friederike Schmidt-Graf, Jürgen Schlegel, Bernhard Meyer, Stephanie E Combs
BACKGROUND: Glioblastoma is usually diagnosed around the age of 60-70 years. Patients older than 65 years are frequently described as "elderly". Several trials with monotherapy have established treatment regimens that offer therapies with reduced side effects but reduced efficacy. We analysed the outcome of elderly glioblastoma patients treated at our facility. METHODS: We performed a retrospective analysis of 62 consecutive patients older than 65 years treated for a primary glioblastoma at our facility from 2009 to 2015...
April 28, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28453749/an-independently-validated-nomogram-for-individualized-estimation-of-survival-among-patients-with-newly-diagnosed-glioblastoma-nrg-oncology-rtog-0525-and-0825
#16
Haley Gittleman, Daniel Lim, Michael W Kattan, Arnab Chakravarti, Mark R Gilbert, Andrew B Lassman, Simon S Lo, Mitchell Machtay, Andrew E Sloan, Erik P Sulman, Devin Tian, Michael A Vogelbaum, Tony J C Wang, Marta Penas-Prado, Emad Youssef, Deborah T Blumenthal, Peixin Zhang, Minesh P Mehta, Jill S Barnholtz-Sloan
Background.: Glioblastoma (GBM) is the most common primary malignant brain tumor. Nomograms are often used for individualized estimation of prognosis. This study aimed to build and independently validate a nomogram to estimate individualized survival probabilities for patients with newly diagnosed GBM, using data from 2 independent NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials. Methods.: This analysis included information on 799 (RTOG 0525) and 555 (RTOG 0825) eligible and randomized patients with newly diagnosed GBM and contained the following variables: age at diagnosis, race, gender, Karnofsky performance status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) methylation status, and survival (in months)...
May 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28451581/effect-of-exposure-to-900-mhz-gsm-mobile-phone-radiofrequency-radiation-on-estrogen-receptor-methylation-status-in-colon-cells-of-male-sprague-dawley-rats
#17
P Mokarram, M Sheikhi, S M J Mortazavi, S Saeb, N Shokrpour
BACKGROUND: Over the past several years, the rapidly increasing use of mobile phones has raised global concerns about the biological effects of exposure to radiofrequency (RF) radiation. Numerous studies have shown that exposure to electromagnetic fields (EMFs) can be associated with effects on the nervous, endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of genetic diversity, the onset and progression of cancer can be controlled by epigenetic mechanisms such as gene promoter methylation...
March 2017: Journal of Biomedical Physics & Engineering
https://www.readbyqxmd.com/read/28450824/identification-of-novel-biomarker-and-therapeutic-target-candidates-for-acute-intracerebral-hemorrhage-by-quantitative-plasma-proteomics
#18
Guo-Chun Li, Lina Zhang, Ming Yu, Haiyu Jia, Ting Tian, Junqin Wang, Fuqiang Wang, Ling Zhou
BACKGROUND: The systematic mechanisms of acute intracerebral hemorrhage are still unknown and unverified, although many recent researches have indicated the secondary insults. This study was aimed to disclose the pathological mechanism and identify novel biomarker and therapeutic target candidates by plasma proteome. METHODS: Patients with AICH (n = 8) who demographically matched healthy controls (n = 4) were prospectively enrolled, and their plasma samples were obtained...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28445279/promoter-hypermethylation-of-mgmt-gene-may-contribute-to-the-pathogenesis-of-gastric-cancer-a-prisma-compliant-meta-analysis
#19
Zongxin Zhang, Shaojun Xin, Min Gao, Yunxiang Cai
BECKGROUND: The association of MGMT (O-methyguanine deoxyribonucleic acid methyltransferase) promoter hypermethylation with gastric cancer (GC) risk has been studied extensively, but the results remained unclear. Here, we performed a meta-analysis to evaluate whether promoter hypermethylation of the MGMT gene contributed to gastric pathogenesis. METHODS: Relevant studies were identified by retrieving the PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28436299/mgmt-gene-variants-temozolomide-myelotoxicity-and-glioma-risk-a-concise-literature-survey-including-an-illustrative-case
#20
Meric A Altinoz, Ilhan Elmaci, Fatih Han Bolukbasi, Cumhur Gokhan Ekmekci, Guven Yenmis, Ramazan Sari, Aydin Sav
Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma patients, respectively. However, pancytopenia is rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA mutations and associates both with antitumour efficacy and myelosuppression. Many studies on the effects of MGMT gene-methylation on temozolomide's effects exist, but much fewer publications concerning MGMT variants were documented. A full sequencing of the MGMT gene was performed in a female glioblastoma patient, who developed pancytopenia following temozolomide treatment...
April 23, 2017: Journal of Chemotherapy
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