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https://www.readbyqxmd.com/read/29777945/patterns-of-care-and-outcomes-of-chemoradiation-versus-radiation-alone-for-mgmt-promoter-unmethylated-glioblastoma
#1
Anna Lee, Nikita Malakhov, Niki Sheth, Arthur Wang, Peter Han, David Schreiber
OBJECTIVE: The recommended treatment for O6 -methylguanine-DNA methyltransferase (MGMT) promoter unmethylated glioblastoma (GBM) is radiation therapy with concurrent/adjuvant temozolomide (TMZ). However, it is well known that the clinical benefit from TMZ is lower in these patients. We sought to analyze patterns of care and outcomes of chemoradiation versus radiation alone in this cohort using a large, hospital database. PATIENTS AND METHODS: Patients diagnosed with MGMT promoter unmethylated GBM from 2010 to 2012 who received radiation (RT) or chemoradiation (CRT) were identified in the National Cancer Database...
May 16, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29774877/-analysis-of-prognostic-factors-for-survival-in-elderly-patients-with-glioma
#2
Jinghui Liu, Miao Lou, Peigang Ji, Chen Li, Fuqiang Feng, Baofu Li, Meng Xu, Guodong Gao, Yan Qu, Liang Wang
To analyze the prognostic factors for survival in elderly patients with glioma.
 Methods: We performed a retrospective analysis of prognostic factors for elderly patients with glioma, who were treated by the same attending doctor during June 2014 and June 2016, to investigate the correlations of the age, dimension of pathology, histological grade, extent of resection, adjuvant therapy, preoperative Karnofsky Performance Scale (KPS) score, postoperative KPS score, molecular markers [isocitrate dehydrogenase-1 (IDH-1), O6-methylguanine DNA-transferase (MGMT), epidermal growth factor receptor (EGFR), Ki-67] with the prognosis...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29770368/multi-label-inductive-matrix-completion-for-joint-mgmt-and-idh1-status-prediction-for-glioma-patients
#3
Lei Chen, Han Zhang, Kim-Han Thung, Luyan Liu, Junfeng Lu, Jinsong Wu, Qian Wang, Dinggang Shen
MGMT promoter methylation and IDH1 mutation in high-grade gliomas (HGG) have proven to be the two important molecular indicators associated with better prognosis. Traditionally, the statuses of MGMT and IDH1 are obtained via surgical biopsy, which is laborious, invasive and time-consuming. Accurate presurgical prediction of their statuses based on preoperative imaging data is of great clinical value towards better treatment plan. In this paper, we propose a novel Multi-label Inductive Matrix Completion (MIMC) model, highlighted by the online inductive learning strategy, to jointly predict both MGMT and IDH1 statuses...
September 2017: Medical Image Computing and Computer-assisted Intervention: MICCAI ..
https://www.readbyqxmd.com/read/29761922/fm19g11-inhibits-o-6-methylguanine-dna-methyltransferase-expression-under-both-hypoxic-and-normoxic-conditions
#4
Chao-Guo You, Han-Song Sheng, Chao-Ran Xie, Nu Zhang, Xue-Sheng Zheng
FM19G11 is a small molecular agent that inhibits hypoxia-inducible factor-1-alpha (HIF-1α) and other signaling pathways. In this study, we characterized the modulating effects of FM19G11 on O6 -methylguanine DNA-methyltransferase (MGMT), the main regulator of temozolomide (TMZ) resistance in glioblastomas. This study included 2 MGMT-positive cell lines (GBM-XD and T98G). MGMT promoter methylation status, mRNA abundance, and protein levels were determined before and after FM19G11 treatment, and the roles of various signaling pathways were characterized...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29761860/hypermethylation-of-cpg-islands-is-associated-with-increasing-chromosomal-damage-in-chinese-lead-exposed-workers
#5
Li-Bo Yu, Yu-Ting Tu, Jing-Wen Huang, Ya-Nan Zhang, Guo-Qiao Zheng, Xiao-Wen Xu, Jin-Wei Wang, Jean Qin Xiao, David C Christiani, Zhao-Lin Xia
Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B-Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppressor genes (TSGs) post lead exposure. In the study, 147 lead-exposed workers were divided into two groups according to their B-Pb P50 value, with other 50 lead-unexposed workers as a control group...
May 15, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29748206/deep-learning-convolutional-neural-networks-accurately-classify-genetic-mutations-in-gliomas
#6
P Chang, J Grinband, B D Weinberg, M Bardis, M Khy, G Cadena, M-Y Su, S Cha, C G Filippi, D Bota, P Baldi, L M Poisson, R Jain, D Chow
BACKGROUND AND PURPOSE: The World Health Organization has recently placed new emphasis on the integration of genetic information for gliomas. While tissue sampling remains the criterion standard, noninvasive imaging techniques may provide complimentary insight into clinically relevant genetic mutations. Our aim was to train a convolutional neural network to independently predict underlying molecular genetic mutation status in gliomas with high accuracy and identify the most predictive imaging features for each mutation...
May 10, 2018: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29747595/the-search-for-a-melanoma-tailored-chemotherapy-in-the-new-era-of-personalized-therapy-a-phase-ii-study-of-chemo-modulating-temozolomide-followed-by-fotemustine-and-a-cooperative-study-of-goim-gruppo-oncologico-italia-meridionale
#7
Michele Guida, Stefania Tommasi, Sabino Strippoli, Maria Iole Natalicchio, Simona De Summa, Rosamaria Pinto, Antonio Cramarossa, Anna Albano, Salvatore Pisconti, Michele Aieta, Ruggiero Ridolfi, Amalia Azzariti, Gabriella Guida, Vito Lorusso, Giusepe Colucci
BACKGROUND: It is frequently asked whether chemotherapy can still play a role in metastatic melanoma considering the effectiveness of the available drugs today, including antiCTLA4/antiPD1 immunotherapy and antiBRAF/antiMEK inhibitors. However, only approximately half of patients respond to these drugs, and the majority progress after 6-11 months. Therefore, a need for other therapeutic options is still very much apparent. We report the first large trial of a sequential full dose of fotemustine (FM) preceded by a low dose of temozolomide (TMZ) as a chemo-modulator in order to inactivate the DNA repair action of O(6)-methylguanine DNA-methyltransferase (MGMT)...
May 10, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29744991/rapid-electrochemical-assessment-of-tumor-suppressor-gene-methylations-in-raw-human-serum-and-tumor-cells-and-tissues-using-immuno-magnetic-beads-and-selective-dna-hybridization
#8
Eloy Povedano, Alejandro Valverde, Víctor Ruiz-Valdepeñas Montiel, María Pedrero, Paloma Yáñez-Sedeño, Rodrigo Barderas, Pablo San Segundo-Acosta, Alberto Peláez-García, Marta Mendiola, David Hardisson, Susana Campuzano, José Manuel Pingarron
We report a rapid and sensitive electrochemical strategy for the detection of gene-specific 5-methylcytosine DNA methylation. Magnetic beads (MBs) modified with an antibody specific for 5-methylcytosines (5-mC) are employed for the selective capture of any 5-mC methylated single-stranded (ss)DNA sequence. A flanking region next to the 5-mCs of the captured methylated ssDNA is recognized by selective hybridization with a synthetic biotinylated DNA sequence, further labeled with an HRP streptavidin conjugate...
May 9, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29741745/prospective-feasibility-and-safety-assessment-of-surgical-biopsy-for-patients-with-newly-diagnosed-diffuse-intrinsic-pontine-glioma
#9
Nalin Gupta, Liliana C Goumnerova, Peter Manley, Susan N Chi, Donna Neuberg, Maneka Puligandla, Jason Fangusaro, Stewart Goldman, Tadanori Tomita, Tord Alden, Arthur DiPatri, Joshua B Rubin, Karen Gauvain, David Limbrick, Jeffrey Leonard, J Russel Geyer, Sarah Leary, Samuel Browd, Zhihong Wang, Sandeep Sood, Anne Bendel, Mahmoud Nagib, Sharon Gardner, Matthias A Karajannis, David Harter, Kanyalakshmi Ayyanar, William Gump, Daniel C Bowers, Bradley Weprin, Tobey J MacDonald, Dolly Aguilera, Barunashish Brahma, Nathan J Robison, Erin Kiehna, Mark Krieger, Eric Sandler, Philipp Aldana, Ziad Khatib, John Ragheb, Sanjiv Bhatia, Sabine Mueller, Anu Banerjee, Amy-Lee Bredlau, Sri Gururangan, Herbert Fuchs, Kenneth J Cohen, George Jallo, Kathleen Dorris, Michael Handler, Melanie Comito, Mark Dias, Kellie Nazemi, Lissa Baird, Jeff Murray, Neal Lindeman, Jason L Hornick, Hayley Malkin, Claire Sinai, Lianne Greenspan, Karen D Wright, Michael Prados, Pratiti Bandopadhayay, Keith L Ligon, Mark W Kieran
Background: Diagnosis of diffuse intrinsic pontine gliomas (DIPG) has relied on imaging studies since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods: Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG...
May 5, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29735403/proteins-of-the-retinoblastoma-pathway-fen1-and-mgmt-are-novel-potential-prognostic-biomarkers-in-pancreatic-adenocarcinoma
#10
Joel Isohookana, Kirsi-Maria Haapasaari, Ylermi Soini, Joni Leppänen, Peeter Karihtala
BACKGROUND: We studied the expression of some major proteins involved in cell-cycle regulation and DNA repair, the roles of which are not well known in pancreatic ductal adenocarcinoma (PDAC), but which have a significant impact on carcinogenesis of many other cancers. METHODS: We immunohistochemically assessed expression levels of the cell-cycle regulators Rb1, p16 and cyclin-dependent kinase 4 (CDK4), and the DNA repair enzymes O6-methylguanine-DNA-alkyltransferase (MGMT) and flap endonuclease-1 (FEN1) separately in malignant tissue and benign tissue from resection margins in 102 cases of PDAC...
May 1, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29733378/assessing-the-predictability-of-idh-mutation-and-mgmt-methylation-status-in-glioma-patients-using-relaxation-compensated-multi-pool-cest-mri-at-7-0-tesla
#11
Daniel Paech, Johannes Windschuh, Johanna Oberhollenzer, Constantin Dreher, Felix Sahm, Jan-Eric Meissner, Steffen Goerke, Patrick Schuenke, Moritz Zaiss, Sebastian Regnery, Sebastian Bickelhaupt, Philipp Bäumer, Martin Bendszus, Wolfgang Wick, Andreas Unterberg, Peter Bachert, Mark Edward Ladd, Heinz-Peter Schlemmer, Alexander Radbruch
Background: Early identification of prognostic superior characteristics in glioma patients such as Isocitrate dehydrogenase(IDH)-mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promotor methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH-mutation status, MGMT promotor methylation, and differentiation of lower versus higher grade glioma (LGG vs. HGG) in newly-diagnosed patients employing relaxation-compensated multi-pool Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) at 7...
May 4, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29730791/distinct-demographic-profile-and-molecular-markers-of-primary-cns-tumor-in-1873-adolescent-and-young-adult-patient-population
#12
Rohit Vadgaonkar, Sridhar Epari, Girish Chinnaswamy, Rahul Krishnatry, Raees Tonse, Tejpal Gupta, Rakesh Jalali
INTRODUCTION: We present detailed demographic profile, tumor types, and their molecular markers in adolescent and young adult (AYA) patients of age group between 15 and 39 years with primary central nervous system (PCNS) tumors, and compare with pediatric and adult patient populations. METHODOLOGY: Demographic- and disease-related information of 1873 PCNS tumor patients of age 15-39 years registered between 1 January 2011 and 31 December 2015 at our institution was analyzed with respect to their demographics and tumor subtypes...
May 5, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29726772/mgmt-promoter-methylation-in-patients-with-glioblastoma-is-methylation-sensitive-high-resolution-melting-superior-to-methylation-sensitive-polymerase-chain-reaction-assay
#13
Shinji Yamashita, Kiyotaka Yokogami, Fumitaka Matsumoto, Kiyotaka Saito, Asako Mizuguchi, Hajime Ohta, Hideo Takeshima
OBJECTIVE The methylation status of the O6-methylguanine-DNA methyltransferase ( MGMT) gene promoter is a prognostic factor in adults with glioblastoma (GBM); it also yields information that is useful for clinical decision-making in elderly GBM patients. While pyrosequencing is the gold standard for the evaluation of the methylation status of MGMT, methylation-sensitive polymerase chain reaction (MS-PCR) assay continues to be used widely. Although MS-PCR results exhibited a good correlation with the prognosis of patients with GBM treated under the Stupp protocol, interpretation of the bands is based on subjective judgment, and the assay cannot be used to analyze heterogeneously methylated samples...
May 4, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29725463/quantitative-assessment-of-gene-promoter-methylation-in-non-small-cell-lung-cancer-using-methylation-sensitive-high-resolution-melting
#14
Fangming Liu, Honglian Zhang, Shaohua Lu, Zhenhua Wu, Lin Zhou, Zule Cheng, Yanan Bai, Jianlong Zhao, Qiqing Zhang, Hongju Mao
DNA methylation is closely associated with aberrant epigenetic changes. Previous studies have identified various genes associated with non-small cell lung cancer (NSCLC), but the precise combination responsible for its etiology is still debated. The aim of the present study was to select a new set of NSCLC-related genes using methylation-sensitive high-resolution melting. The promoter methylation status of six selected genes, consisting of protocadherin γ subfamily B, 6 (PCDHGB6), homeobox A9 (HOXA9), O6 -methylguanine-DNA methyltransferase (MGMT), microRNA (miR)-126, suppressor of cytokine signaling 3 (SOCS3) and Ras association domain family member 5, also termed NORE1A, was evaluated in 54 NSCLC patients...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29722661/phase-2-study-of-bortezomib-combined-with-temozolomide-and-regional-radiation-therapy-for-upfront-treatment-of-patients-with-newly-diagnosed-glioblastoma-multiforme-safety-and-efficacy-assessment
#15
Xiao-Tang Kong, Nhung T Nguyen, Yoon J Choi, Guicheng Zhang, HuyTram N Nguyen, Emese Filka, Stacey Green, William H Yong, Linda M Liau, Richard M Green, Tania Kaprealian, Whitney B Pope, P Leia Nghiemphu, Timothy Cloughesy, Andrew Lassman, Albert Lai
PURPOSE: To assess the safety and efficacy of upfront treatment using bortezomib combined with standard radiation therapy (RT) and temozolomide (TMZ), followed by adjuvant bortezomib and TMZ for ≤24 cycles, in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: Twenty-four patients with newly diagnosed GBM were enrolled. The patients received standard external beam regional RT with concurrent TMZ beginning 3 to 6 weeks after surgery, followed by adjuvant TMZ and bortezomib for ≤24 cycles or until tumor progression...
April 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29720885/successful-second-line-metronomic-temozolomide-in-metastatic-paraganglioma-case-reports-and-review-of-the-literature
#16
Isabel Tena, Garima Gupta, Marcos Tajahuerce, Marta Benavent, Manuel Cifrián, Alejandro Falcon, María Fonfria, Maribel Del Olmo, Rosa Reboll, Antonio Conde, Francisca Moreno, Julia Balaguer, Adela Cañete, Rosana Palasí, Pilar Bello, Alfredo Marco, José Luis Ponce, Juan Francisco Merino, Antonio Llombart, Alfredo Sanchez, Karel Pacak
Metastatic pheochromocytoma and paraganglioma (mPHEO/PGL) are frequently associated with succinate dehydrogenase B ( SDHB ) mutations. Cyclophosphamide-dacarbazine-vincristine (CVD) regimen is recommended as standard chemotherapy for advanced mPHEO/PGL. There is limited evidence to support the role of metronomic schemes (MS) of chemotherapy in mPHEO/PGL treatment. We report 2 patients with SDHB -related mPGL who received a regimen consisting of MS temozolomide (TMZ) and high-dose lanreotide after progression on both CVD chemotherapy and high-dose lanreotide...
2018: Clinical Medicine Insights. Oncology
https://www.readbyqxmd.com/read/29712977/concordant-association-validates-mgmt-methylation-and-protein-expression-as-favorable-prognostic-factors-in-glioma-patients-on-alkylating-chemotherapy-temozolomide
#17
Arshad A Pandith, Iqbal Qasim, Wani Zahoor, Parveen Shah, Abdul R Bhat, Dheera Sanadhya, Zafar A Shah, Niyaz A Naikoo
O6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29709748/correlation-between-the-residual-tumor-volume-extent-of-tumor-resection-and-mgmt-status-in-patients-with-glioblastoma-gbm
#18
Mayur Sharma, Sushma Bellamkonda, Suryanarayan Mohapatra, Antonio Meola, Xuefei Jia, Alireza Mohammadi, Lilyana Angelov, Gene H Barnett, Michael Vogelbaum, Manmeet S Ahluwalia
INTRODUCTION: There is limited information on O6 -methylguanine DNA methyltransferase (MGMT) status, extent of surgical resection and its impact on overall outcomes in patients with Glioblastoma (GBM). METHODS: Following IRB approval, 233 newly diagnosed GBM patients with known MGMT status (2009-2015) were included in our analysis. Clinical, imaging and follow-up data were collected from the database. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary end points respectively...
April 27, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29705182/inhibition-of-nf-%C3%AE%C2%BAb-results-in-anti-glioma-activity-and-reduces-temozolomide-induced-chemoresistance-by-down-regulating-mgmt-gene-expression
#19
Zhiyun Yu, Yong Chen, Shiqiang Wang, Pengliang Li, Guangtong Zhou, Yongjie Yuan
The introduction of temozolomide (TMZ) has improved chemotherapy for malignant gliomas. However, many gliomas are refractory to TMZ, so there is a pressing need for more effective therapeutic options. Here we demonstrated that glioma specimens and cell lines have constitutively high levels of nuclear factor κB (NF-κB) activity. Notably, the expression levels of this transcription factor correlated with malignant grades in glioblastoma multiforme (GBM) and inversely correlated with overall survival. Conversely, knockdown of NF-κB inhibits glioma cell proliferation and treating a panel of established glioma cell lines with pharmacological NF-κB inhibitors markedly decreased glioma viability, led to S cell cycle arrest, and induced apoptosis...
April 26, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29700705/imaging-scoring-systems-for-preoperative-molecular-diagnoses-of-lower-grade-gliomas
#20
Tokunori Kanazawa, Hirokazu Fujiwara, Hidenori Takahashi, Yuya Nishiyama, Yuichi Hirose, Saeko Tanaka, Kazunari Yoshida, Hikaru Sasaki
Recent advance in molecular characterization of gliomas showed that patient prognosis and/or tumor chemosensitivity correlate with certain molecular signatures; however, this information is available only after tumor resection. If molecular information is available by routine radiological examinations, surgical strategy as well as overall treatment strategy could be designed preoperatively.With the aim to establish an imaging scoring system for preoperative diagnosis of molecular status in lower-grade gliomas (WHO grade 2 or 3, LrGGs), we investigated 8 imaging features available on routine CT and MRI in 45 LGGs (discovery cohort) and compared them with the status of 1p/19q codeletion, IDH mutations, and MGMT promoter methylation...
April 26, 2018: Neurosurgical Review
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