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https://www.readbyqxmd.com/read/29156686/crosstalk-between-mismatch-repair-and-base-excision-repair-in-human-gastric-cancer
#1
Valeria Simonelli, Giuseppe Leuzzi, Giorgia Basile, Mariarosaria D'Errico, Paola Fortini, Annapaola Franchitto, Valentina Viti, Ashley R Brown, Eleonora Parlanti, Barbara Pascucci, Domenico Palli, Alessandro Giuliani, Fabio Palombo, Robert W Sobol, Eugenia Dogliotti
DNA repair gene expression in a set of gastric cancers suggested an inverse association between the expression of the mismatch repair (MMR) gene MLH1 and that of the base excision repair (BER) gene DNA polymerase β (Polβ). To gain insight into possible crosstalk of these two repair pathways in cancer, we analysed human gastric adenocarcinoma AGS cells over-expressing Polβ or Polβ active site mutants, alone or in combination with MLH1 silencing. Next, we investigated the cellular response to the alkylating agent methyl methanesulfonate (MMS) and the purine analogue 6-thioguanine (6-TG), agents that induce lesions that are substrates for BER and/or MMR...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152101/functional-network-analysis-of-gene-phenotype-connectivity-associated-with-temozolomide
#2
Jia Shi, Bo Dong, Peng Zhou, Wei Guan, Ya Peng
Rationale: Glioma has a poor survival rate in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for treating glioma, but TMZ treatment consistently leads to high resistance. Aim: To investigate the underlying mechanisms of TMZ action with new therapeutic regimens in glioma. Methods and results: The biological effects of TMZ mainly depend on the three following DNA repair systems: methylguanine methyltransferase (MGMT), mismatch repair (MMR) and base excision repair (BER)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151909/bkm120-sensitizes-c6-glioma-cells-to-temozolomide-via-suppression-of-the-pi3k-akt-nf-%C3%AE%C2%BAb-mgmt-signaling-pathway
#3
Mao Li, Ruo Fei Liang, Xiang Wang, Qing Mao, Yan Hui Liu
Glioblastoma is the most common type of malignant intracranial tumor in adults. Temozolomide (TMZ), as the first-line chemotherapy agent used in patients with glioblastoma, has demonstrated different effects in patients due to the expression of O6-methylguanine-DNA methyltransferase (MGMT) which is able to repair the DNA lesions induced by TMZ. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is over-activated in glioblastoma and has been revealed to be potentially implicated in resistance to TMZ...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29150792/correlation-between-mgmt-promoter-methylation-and-response-to-temozolomide-based-therapy-in-neuroendocrine-neoplasms-an-observational-retrospective-multicenter-study
#4
Davide Campana, Thomas Walter, Sara Pusceddu, Fabio Gelsomino, Emmanuelle Graillot, Natalie Prinzi, Andrea Spallanzani, Michelangelo Fiorentino, Marc Barritault, Filippo Dall'Olio, Nicole Brighi, Guido Biasco
PURPOSE: Temozolomide (TEM) based therapy has been reported being effective in the treatment of metastatic neuroendocrine neoplasms (NEN), with response rates ranging from 30 to 70%. Among patients affected by advanced glioblastoma or melanoma and treated with TEM, loss of tumoral O6-methylguanine DNA methyltransferase (MGMT) is correlated with improved survival. In NEN patients, the role of MGMT deficiency in predicting clinical outcomes of TEM treatment is still under debate. METHODS: In this study we evaluated 95 patients with advanced NENs undergoing treatment with TEM-based therapy...
November 17, 2017: Endocrine
https://www.readbyqxmd.com/read/29147863/prognostic-relevance-of-programmed-cell-death-ligand-1-expression-in-glioblastoma
#5
Kyu Sang Lee, Kyoungyul Lee, Sumi Yun, Seyoung Moon, Yujun Park, Jung Ho Han, Chae-Yong Kim, Hye Seung Lee, Gheeyoung Choe
The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29143344/down-regulation-of-p16-and-mgmt-promotes-the-anti-proliferative-and-pro-apoptotic-effects-of-5-aza-dc-and-radiation-on-cervical-cancer-cells
#6
Guan-di Chen, De-Ying Qian, Zhi-Gang Li, Ge-Ying Fan, Ke-Li You, Yi-Long Wu
Cervical cancer is one of the most common malignancies of the female reproductive system. Therefore, it is critical to investigate the molecular mechanisms involved in the development and progression of cervical cancer. In this study, we stimulated cervical cancer cells with 5-aza-2'-deoxycytidine (5-Aza-dC) and found that this treatment inhibited cell proliferation and induced apoptosis; additionally, methylation of p16 and O-6-methylguanine-DNA methyltransferase (MGMT) was reversed, although their expression was suppressed...
November 15, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29141164/lomustine-and-bevacizumab-in-progressive-glioblastoma
#7
Wolfgang Wick, Thierry Gorlia, Martin Bendszus, Martin Taphoorn, Felix Sahm, Inga Harting, Alba A Brandes, Walter Taal, Julien Domont, Ahmed Idbaih, Mario Campone, Paul M Clement, Roger Stupp, Michel Fabbro, Emilie Le Rhun, Francois Dubois, Michael Weller, Andreas von Deimling, Vassilis Golfinopoulos, Jacoline C Bromberg, Michael Platten, Martin Klein, Martin J van den Bent
BACKGROUND: Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma. METHODS: We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients)...
November 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29137285/genetic-and-immune-features-of-resectable-malignant-brainstem-gliomas
#8
Yang Zhang, Changcun Pan, Junmei Wang, Jingli Cao, Yuhan Liu, Yajie Wang, Liwei Zhang
We surveyed common genetic mutations (IDH1, H3F3A, PPM1D, and TP53) and immune features (PD-L1 expression and CD8(+) T cell tumor infiltration) in a series of 62 malignant brainstem gliomas that were resected via microsurgery. IDH1 mutations were mutually exclusive with H3F3A mutations. IDH1 mutations appeared only in adults and occurred more frequently in tumors larger than 10cm(3) (8/29 vs 1/32, Fisher's exact test, p=0.010). H3F3A mutations occurred more frequently in children and adolescent patients (19/24 vs 18/38, chi-square test, p=0...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136645/a-4-mirna-signature-to-predict-survival-in-glioblastomas
#9
Simon K Hermansen, Mia D Sørensen, Anker Hansen, Steen Knudsen, Alvaro G Alvarado, Justin D Lathia, Bjarne W Kristensen
Glioblastomas are among the most lethal cancers; however, recent advances in survival have increased the need for better prognostic markers. microRNAs (miRNAs) hold great prognostic potential being deregulated in glioblastomas and highly stable in stored tissue specimens. Moreover, miRNAs control multiple genes representing an additional level of gene regulation possibly more prognostically powerful than a single gene. The aim of the study was to identify a novel miRNA signature with the ability to separate patients into prognostic subgroups...
2017: PloS One
https://www.readbyqxmd.com/read/29126203/a-randomized-phase-ii-study-of-everolimus-in-combination-with-chemoradiation-in-newly-diagnosed-glioblastoma-results-of-nrg-oncology-rtog-0913
#10
Prakash Chinnaiyan, Minhee Won, Patrick Y Wen, Amyn M Rojiani, Maria Werner-Wasik, Helen A Shih, Lynn S Ashby, Hsiang-Hsuan Michael Yu, Volker W Stieber, Shawn C Malone, John B Fiveash, Nimish A Mohile, Manmeet S Ahluwalia, Merideth M Wendland, Philip J Stella, Andrew Y Kee, Minesh P Mehta
Background: This Phase II study was designed to determine the efficacy of the mTOR inhibitor everolimus administered daily with conventional radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma. Methods: Patients were randomized to radiation therapy with concurrent and adjuvant temozolomide with or without daily everolimus (10 mg). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS) and treatment-related toxicities...
November 6, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29121274/quality-of-life-in-the-glarius-trial-randomizing-bevacizumab-irinotecan-versus-temozolomide-in-newly-diagnosed-mgmt-nonmethylated-glioblastoma
#11
Niklas Schäfer, Martin Proescholdt, Joachim P Steinbach, Astrid Weyerbrock, Peter Hau, Oliver Grauer, Roland Goldbrunner, Franziska Friedrich, Veit Rohde, Florian Ringel, Uwe Schlegel, Michael Sabel, Michael W Ronellenfitsch, Martin Uhl, Stefan Grau, Mathias Hänel, Oliver Schnell, Dietmar Krex, Peter Vajkoczy, Ghazaleh Tabatabai, Frederic Mack, Christina Schaub, Theophilos Tzaridis, Michael Nießen, Sied Kebir, Barbara Leutgeb, Horst Urbach, Claus Belka, Walter Stummer, Martin Glas, Ulrich Herrlinger
Background: The GLARIUS trial which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) as compared to standard temozolomide (TMZ) in the first-line therapy of MGMT-nonmethylated glioblastoma showed that progression-free survival was significantly prolonged by BEV/IRI while overall survival was similar in both arms. The present report focusses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease. Patients and methods: Patients (n=170) received standard radiotherapy and were randomized (2:1) for BEV/IRI or standard TMZ...
November 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29116491/prognostic-and-predictive-value-of-o-6-methylguanine-methyltransferase-for-chemotherapy-in-patients-with-muscle-invasive-bladder-cancer
#12
Junyu Zhang, Yu Zhu, Yiwei Wang, Qiang Fu, Huyang Xie, Zheng Liu, Hangcheng Fu, Yifan Cao, Jiejie Xu, Bo Dai
PURPOSE: DNA repair genes are potential biomarkers for chemotherapy in muscle-invasive bladder cancer (MIBC). O(6)-methylguanine methyltransferase (MGMT) is involved in DNA repair and is found to affect the efficacy of platinum-based chemotherapy. However, the prognostic or predictive value of MGMT expression in chemotherapy for MIBC is unknown. MATERIALS AND METHODS: Immunohistochemical staining for MGMT was performed in paraffin-embedded tumor tissue of high-grade MIBC patients who underwent cystectomy in two independent cohorts [n = 74 for Fudan University Shanghai Cancer Center (FUSCC) cohort and n = 115 for Zhongshan Hospital (ZS) cohort]...
November 7, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29113851/impact-of-academic-facility-type-and-volume-on-post-surgical-outcomes-following-diagnosis-of-glioblastoma
#13
Alan Hauser, Sunil W Dutta, Timothy N Showalter, Jason P Sheehan, Surbhi Grover, Daniel M Trifiletti
OBJECTIVE: To identify if facility type and/or facility volume impact overall survival (OS) following diagnosis of glioblastoma (GBM). We also sought to compare early post-surgical outcomes based on these factors. METHODS: The National Cancer Database was queried for patients with GBM diagnosed from 2004 to 2013 with known survival. Patients were grouped based on facility type and facility volume. Multivariable analyses were performed to investigate factors associated OS following diagnosis and Chi-square tests were used to compare early post-surgical outcomes...
November 4, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29110584/microrna-target-cross-talks-key-players-in-glioblastoma-multiforme
#14
Eman Ali Toraih, Nagwa Mahmoud Aly, Hoda Y Abdallah, Saeed Awad Al-Qahtani, Aly Am Shaalan, Mohammad Hosny Hussein, Manal Said Fawzy
The role of microRNAs in brain cancer is still naive. Some act as oncogene and others as tumor suppressors. Discovery of efficient biomarkers is mandatory to debate that aggressive disease. Bioinformatically selected microRNAs and their targets were investigated to evaluate their putative signature as diagnostic and prognostic biomarkers in primary glioblastoma multiforme. Expression of a panel of seven microRNAs (hsa-miR-34a, hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, hsa-miR-326, and hsa-miR-375) and seven target genes ( E2F3, PI3KCA, TOM34, WNT5A, PDCD4, DFFA, and EGFR) in 43 glioblastoma multiforme specimens were profiled compared to non-cancer tissues via quantitative reverse transcription-polymerase chain reaction...
November 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29107723/results-of-a-policy-of-fast-tapering-of-steroids-after-resection-surgery-in-glioblastoma
#15
Ricardo Díez Valle, Victoria Becerra Castro, Miguel Marigil Sánchez, Jaime Gállego Pérez de Larraya, Jorge M Núñez-Córdoba, Sonia Tejada Solis
BACKGROUND: Corticosteroids are routinely used to treat brain tumors. While steroids have an immediate clinical benefit, their use can lead to a number of relevant complications, and a negative association with overall survival (OS) has been shown in glioblastoma (GBM) patients. There is no evidence in the literature regarding the ideal dose. We assessed the use of steroids in patients with GBM after resection surgery. METHODS: This is a cohort study of 131 newly diagnosed GBM patients that underwent tumor resection surgery...
October 28, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29105360/pseudoprogression-as-an-adverse-event-of-glioblastoma-therapy
#16
Carmen Balaña, Jaume Capellades, Estela Pineda, Anna Estival, Josep Puig, Sira Domenech, Eugenia Verger, Teresa Pujol, Maria Martinez-García, Laura Oleaga, JoseMaria Velarde, Carlos Mesia, Rafael Fuentes, Jordi Marruecos, Sonia Del Barco, Salvador Villà, Cristina Carrato, Oscar Gallego, Miguel Gil-Gil, Jordi Craven-Bartle, Francesc Alameda
We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) as well as the relationship between PFS and PPS in the three groups. Of the 256 patients studied, 56 (21...
November 3, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29103769/comparative-assessment-of-three-methods-to-analyze-mgmt-methylation-status-in-a-series-of-350-gliomas-and-gangliogliomas
#17
Leiming Wang, Zhuo Li, Cuicui Liu, Li Chen, Li Liu, Zeliang Hu, Lihong Zhao, Dehong Lu, Lianghong Teng
MGMT promoter methylation is considered as a prognostic and predictive biomarker indicating response to chemotherapy and radiotherapy in glioblastoma. A number of different methods and platforms including pyrosequencing (PSQ), quantitative methylation-specific PCR (qMSP) and immunohistochemistry (IHC), methylation-sensitive high resolution melting (MS-HRM) and NGS (Next Generation Sequencing) have been used to detect MGMT promoter methylation in gliomas. However, controversy remains about the most appropriate method to use for analyzing MGMT status...
October 10, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29103024/long-term-survivors-of-pancreatic-adenocarcinoma-show-low-rates-of-genetic-alterations-in-kras-tp53-and-smad4
#18
Michele Masetti, Giorgia Acquaviva, Michela Visani, Giovanni Tallini, Adele Fornelli, Moira Ragazzi, Francesco Vasuri, Daniela Grifoni, Simone Di Giacomo, Sirio Fiorino, Raffaele Lombardi, David Tuminati, Matteo Ravaioli, Carlo Fabbri, Maria Letizia Bacchi-Reggiani, Annalisa Pession, Elio Jovine, Dario de Biase
BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. OBJECTIVE: The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing...
October 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29100425/promoter-methylation-of-tumor-related-genes-as-a-potential-biomarker-using-blood-samples-for-gastric-cancer-detection
#19
Jinfeng Wen, Tuo Zheng, Kefeng Hu, Chunxia Zhu, Lihua Guo, Guoliang Ye
Gene promoter methylation has been reported in gastric cancer (GC). However, the potential applications of blood-based gene promoter methylation as a noninvasive biomarker for GC detection remain to be evaluated. Hence, we performed this analysis to determine whether promoter methylation of 11 tumor-related genes could become a promising biomarker in blood samples in GC. We found that the cyclin-dependent kinase inhibitor 2A (p16), E-cadherin (CDH1), runt-related transcription factor 3 (RUNX3), human mutL homolog 1 (MLH1), RAS association domain family protein 1A (RASSF1A), cyclin-dependent kinase inhibitor 2B (p15), adenomatous polyposis coli (APC), Glutathione S-transferase P1 (GSTP1), TP53 dependent G2 arrest mediator candidate (Reprimo), and O6-methylguanine-DNAmethyl-transferase (MGMT) promoter methylation was notably higher in blood samples of patients with GC compared with non-tumor controls...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100349/alu-hypomethylation-and-mgmt-hypermethylation-in-serum-as-biomarkers-of-glioma
#20
Mingjie Gong, Wei Shi, Jing Qi, Guoping Shao, Zhenghua Shi, Junxiang Wang, Jian Chen, Rongtao Chu
In order to improve prognosis of glioma patients, better tools are required for early diagnosis and treatment. Serum cell-free DNA methylation levels of Alu, MGMT, P16, RASSF1A from 124 glioma patients and 58 healthy controls were detected by the bisulfite sequencing. The median methylation level of Alu was 46.15% (IQR, 36.57%-54.00%) and 60.85% (IQR, 57.23%-65.68%) in glioma patients and healthy controls respectively. The median methylation level of MGMT in glioma samples was 64.65% (IQR, 54.87%-74.37%) compared to 38...
September 29, 2017: Oncotarget
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