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https://www.readbyqxmd.com/read/28445279/promoter-hypermethylation-of-mgmt-gene-may-contribute-to-the-pathogenesis-of-gastric-cancer-a-prisma-compliant-meta-analysis
#1
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
#2
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
https://www.readbyqxmd.com/read/28434963/recurrence-pattern-analysis-of-primary-glioblastoma
#3
Marion Rapp, Jessica Baernreuther, Bernd Turowski, Hans-Jakob Steiger, Michael Sabel, Marcel A Kamp
OBJECTIVE: The typical recurrence of a glioblastoma occurs locally, usually within 2 cm from the original lesion. With the improvement of surgery techniques, more aggressive surgical strategies have become feasible, resulting in a significantly increased rate of complete resection. Therefore, we were interested, if these improvements are also reflected by the tumor recurrence pattern. PATIENTS AND METHODS: Inclusion criteria were: first diagnosis of glioblastoma, followed by standard adjuvant radio-chemotherapy and histologically proven tumor recurrence...
April 18, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28430038/prognostic-implications-of-the-subcellular-localization-of-survivin-in-glioblastomas-treated-with-radiotherapy-plus-concomitant-and-adjuvant-temozolomide
#4
Taiichi Saito, Kazuhiko Sugiyama, Yukio Takeshima, Vishwa Jeet Amatya, Fumiyuki Yamasaki, Takeshi Takayasu, Ryo Nosaka, Yoshihiro Muragaki, Takakazu Kawamata, Kaoru Kurisu
OBJECTIVE Currently, the standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been described, including survivin expression. The aim of this study was to determine whether the subcellular localization of survivin correlates with GBM prognosis in patients who received the standard treatment protocol. METHODS The authors retrospectively examined the subcellular localization of survivin (nuclear, cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had received the standard treatment...
April 21, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28429715/mapping-clinicopathological-entities-within-colorectal-mucinous-adenocarcinomas-a-hierarchical-clustering-approach
#5
Charly Liddell, Laure Droy-Dupré, Sylvie Métairie, Fabrice Airaud, Christelle Volteau, Stéphane Bezieau, Christian L Laboisse, Jean-François Mosnier
The aim of this study was to interrogate the heterogeneity of colorectal mucinous adenocarcinomas. This study is based on hierarchical clustering approach combining clinicopathological and molecular patterns known to be relevant to oncogenesis and therapeutic management of patients with colorectal carcinoma, ie, microsatellite instability, O6-methylguanine-DNA methyltransferase (MGMT) status, KRAS, and BRAF mutations and wnt signaling pathway activation. Comparison of the study group of 60 mucinous adenocarcinomas defined according to World Health Organization classification with control group of 136 colorectal adenocarcinomas successively removed shows higher frequency of BRAF and KRAS mutations and microsatellite instability-high status and lower frequency of wnt signaling pathway activation in mucinous adenocarcinomas...
April 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28427986/prognostic-implications-of-extent-of-resection-in-glioblastoma-analysis-from-a-large-database
#6
Daniel M Trifiletti, Clayton Alonso, Surbhi Grover, Camilo E Fadul, Jason P Sheehan, Timothy N Showalter
OBJECTIVE: To analyze the predictors for and clinical impact of gross total resection (GTR) in patients with glioblastoma (GBM). METHODS AND MATERIALS: The National Cancer Database was queried for patients with GBM diagnosed from 2004-2013 with known survival and extent of resection. Patients were grouped based on extent of resection into biopsy alone, subtotal resection (STR), and GTR. Univariable and multivariable (MVA) analyses were performed to investigate factors associated with the likelihood of GTR and overall survival (OS) following diagnosis...
April 17, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28427088/a-phase-2-study-of-temozolomide-in-pretreated-metastatic-colorectal-cancer-with-mgmt-promoter-methylation
#7
M A Calegari, A Inno, S Monterisi, A Orlandi, D Santini, M Basso, A Cassano, M Martini, T Cenci, I de Pascalis, F Camarda, B Barbaro, L M Larocca, S Gori, G Tonini, C Barone
BACKGROUND: Presently, few options are available for refractory colorectal cancer (CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a frequent and early event in CRC tumourigenesis. This epigenetic silencing is a predictor of response to the alkylating drug temozolomide in glioblastoma. Preclinical evidences and some case reports showed temozolomide activity in CRC with MGMT silencing, but the available data from clinical trials are inconsistent. METHODS: This was a multicentre, phase 2 trial, planned according to a two-stage Simon's optimal design to investigate activity and safety of temozolomide in refractory CRC harbouring MGMT promoter methylation...
April 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28425046/mir-198-enhances-temozolomide-sensitivity-in-glioblastoma-by-targeting-mgmt
#8
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/28421382/relationship-between-the-expression-of-o-6-methylguanine-dna-methyltransferase-mgmt-and-p53-and-the-clinical-response-in-metastatic-pancreatic-adenocarcinoma-treated-with-folfirinox
#9
Carole Vitellius, Caroline Eymerit-Morin, Dominique Luet, Lionel Fizanne, Fanny Foubert, Sandrine Bertrais, Marie-Christine Rousselet, François-Xavier Caroli-Bosc
BACKGROUND: To date, no predictive biomarker for the efficacy of FOLFIRINOX in metastatic pancreatic adenocarcinoma has been demonstrated. Deficiency in O(6)-methylguanine-DNA methyltransferase (MGMT) has been associated with a therapeutic response in endocrine tumors of the pancreas and the lack of expression of protein 53 (p53) could interfere with the action of MGMT. OBJECTIVE: The aim of our study was to assess the prevalence of MGMT and p53 in patients with metastatic pancreatic adenocarcinoma treated with FOLFIRINOX as a first-line treatment and to investigate their association with therapeutic response and survival...
April 18, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28421310/comparison-of-selected-protein-levels-in-tumour-and-surgical-margin-in-a-group-of-patients-with-oral-cavity-cancer
#10
Joanna Katarzyna Strzelczyk, Karolina Gołąbek, Piotr Cuber, Łukasz Krakowczyk, Aleksander Jerzy Owczarek, Martyna Fronczek, Piotr Choręża, Edyta Hudziec, Zofia Ostrowska
Oral cavity cancer belongs to head-and-neck squamous cell carcinoma group. The purpose of the study was to assess the levels of certain proteins in a tumour and surgical margin in a group of patients with oral cavity cancer. The levels of DAPK1, MGMT, CDH1, SFRP1, SFRP2, RORA, TIMP3, p16, APC and RASSF1 proteins were measured by ELISA in tissue homogenates. The protein levels of DAPK1, MGMT, CDH1, SFRP2 and RASSF1 were significantly higher in tumour tissue than in the margin, contrary to TIMP3 which was lower in the tumour itself...
April 18, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/28411277/long-term-survival-in-glioblastoma-with-cytomegalovirus-pp65-targeted-vaccination
#11
Kristen A Batich, Elizabeth A Reap, Gary E Archer, Luis Sanchez-Perez, Smita K Nair, Robert J Schmittling, Pam Norberg, Weihua Xie, James E Herndon, Patrick Healy, Roger E McLendon, Allan H Friedman, Henry S Friedman, Darell Bigner, Gordana Vlahovic, Duane A Mitchell, John H Sampson
Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival (PFS) and overall survival (OS)...
April 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#12
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/28405827/mgmt-promoter-methylation-status-in-merkel-cell-carcinoma-in-vitro-versus-invivo
#13
Giuseppina Improta, Cathrin Ritter, Angela Pettinato, Valeria Vasta, David Schrama, Filippo Fraggetta, Jürgen C Becker
PURPOSE: Expression of O6-methylguanine-DNA methyltransferase (MGMT) in Merkel cell carcinoma (MCC) is very variable; thus, we tested whether this may be due to differential methylation of the MGMT gene promoter. METHODS: Quantitative analysis of MGMT mRNA and protein expression, as well as MGMT promoter methylation status, was performed in a series of tissue samples of MCC tumors, representing both primary and metastatic lesions, as well as in six MCC cell lines...
April 12, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28404957/gene-methylation-as-a-powerful-biomarker-for-detection-and-screening-of-non-small-cell-lung-cancer-in-blood
#14
Bao-Hua Wang, Yan-Yu Li, Jin-Zhu Han, Lian-Ya Zhou, Ying-Qian Lv, He-Lin Zhang, Li Zhao
DNA methylation has been reported to become a potential powerful tool for cancer detection and diagnosis. However, the possibilities for the application of blood-based gene methylation as a biomarker for non-small cell lung cancer (NSCLC) detection and screening remain unclear. Hence, we performed this meta-analysis to evaluate the value of gene methylation detected in blood samples as a noninvasive biomarker in NSCLC. A total of 28 genes were analyzed from 37 case-control studies. In the genes with more than three studies, we found that the methylation of P16, RASSF1A, APC, RARβ, DAPK, CDH13, and MGMT was significantly associated with risks of NSCLC...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28395288/safety-and-effectiveness-of-bis-chloroethylnitrosourea-wafer-chemotherapy-in-elderly-patients-with-recurrent-glioblastoma
#15
Johann Klein, Tareq A Juratli, Yordan Radev, Dirk Daubner, Silke Soucek, Gabriele Schackert, Dietmar Krex
OBJECTIVE: To assess the safety and effectiveness of bis-chloroethylnitrosourea (BCNU) wafers in elderly patients with recurrent glioblastoma (GBM). METHODS: Patients with recurrent GBM operated on between 2007 and 2014 were divided into 3 groups: >65 years with BCNU wafer implantation, >65 years without BCNU wafer implantation, and ≤65 years with BCNU wafer implantation. We compared survival and complications. RESULTS: A total of 79 patients were identified: 24 in the older BCNU group (median age 68...
April 11, 2017: Oncology
https://www.readbyqxmd.com/read/28386459/pathogenesis-of-warthin-s-tumors
#16
REVIEW
Yevhen V Kuzenko, Anatoly M Romanuk, Olena Olegivna Dyachenko, Olena Hudymenko
INTRODUCTION: Warthin's tumor, also known as papillary cystadenoma lymphomatosum, monomorphic adenoma, or adenolymphoma, is a benign cystic tumor of the salivary glands containing abundant lymphocytes and lymph node-like stroma. It is named after the pathologist Aldred Scott Warthin, who described two cases in 1929. OBJECTIVE: The aim of this study is to analyze the pathogenesis of Warthin's tumor. METHODS: A total of 15 patients with Warthin's tumor were studied...
June 1, 2016: Interventional Medicine & Applied Science
https://www.readbyqxmd.com/read/28384044/the-association-between-mgmt-promoter-methylation-and-patients-with-gastric-cancer-a-meta-analysis
#17
Xiaolong Yuan, Jifei Xu, Weiyang Fang, Zhenfeng Zhao, Fan Wang, Zhuting Tong
AIMS: Several previous studies have suggested that MGMT promoter methylation is significantly associated with gastric cancer, but the results were not consistent. Hence, we conducted a systematic meta-analysis to explore the potential correlation of MGMT promoter methylation with gastric cancer and its clinicopathologic characteristics. MATERIALS AND METHODS: Searches of PubMed, EMBASE, Web of Science, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) literature databases were conducted to identify relevant studies published in English or Chinese before July 1, 2016...
April 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28373576/dual-bioluminescence-and-near-infrared-fluorescence-monitoring-to-evaluate-spherical-nucleic-acid-nanoconjugate-activity-in-vivo
#18
Timothy L Sita, Fotini M Kouri, Lisa A Hurley, Timothy J Merkel, Alexandra Chalastanis, Jasmine L May, Serena T Ghelfi, Lisa E Cole, Thomas C Cayton, Stacey N Barnaby, Anthony J Sprangers, Nikunjkumar Savalia, Charles David James, Andrew Lee, Chad A Mirkin, Alexander H Stegh
RNA interference (RNAi)-based gene regulation platforms have shown promise as a novel class of therapeutics for the precision treatment of cancer. Techniques in preclinical evaluation of RNAi-based nanoconjugates have yet to allow for optimization of their gene regulatory activity. We have developed spherical nucleic acids (SNAs) as a blood-brain barrier-/blood-tumor barrier-penetrating nanoconjugate to deliver small interfering (si) and micro (mi)RNAs to intracranial glioblastoma (GBM) tumor sites. To identify high-activity SNA conjugates and to determine optimal SNA treatment regimens, we developed a reporter xenograft model to evaluate SNA efficacy in vivo...
April 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28371907/is-more-better-the-impact-of-extended-adjuvant-temozolomide-in-newly-diagnosed-glioblastoma-a-secondary-analysis-of-eortc-and-nrg-oncology-rtog
#19
Deborah T Blumenthal, Thierry Gorlia, Mark R Gilbert, Michelle M Kim, L Burt Nabors, Warren P Mason, Monika E Hegi, Peixin Zhang, Vassilis Golfinopoulos, James R Perry, Do Hyun Nam, Sara C Erridge, Benjamin W Corn, René O Mirimanoff, Paul D Brown, Brigitta G Baumert, Minesh P Mehta, Martin J van den Bent, David A Reardon, Michael Weller, Roger Stupp
Background: Radiation with concurrent and adjuvant (6 cycles) temozolomide (TMZ) is the established standard of postsurgical care for newly diagnosed glioblastoma (GBM). This regimen has been adopted with variations, including extending TMZ beyond 6 cycles. The optimal duration of maintenance therapy remains controversial. Methods: We performed pooled analysis of individual patient data from 4 randomized trials for newly diagnosed GBM. All patients who were progression free 28 days after cycle 6 were included...
March 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28371614/hypermutations-in-gliomas-a-potential-immunotherapy-target
#20
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
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