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https://www.readbyqxmd.com/read/29243509/loss-of-mtap-expression-is-a-negative-prognostic-marker-in-ewing-sarcoma-family-of-tumors
#1
Lucas Faria Abrahao-Machado, Bruno Antunes, Renee Zon Filippi, Sahlua Volc, Erica Boldrini, Weder P Menezes, Rui M Reis, Olavo Pires de Camargo
AIM: The Ewing sarcoma family of tumors (ESFT) is a group of malignant small round cell neoplasms of bones and soft tissues closely histogenetically related. Methylthioadenosine phosphorylase (MTAP) deficiency has been recently associated with increased tumor aggressiveness and poor outcomes in different types of neoplasms. However, the expression of this biomarker and its biological role in ESFT remain largely unknown. METHODS: Immunohistochemical expression of MTAP was accessed in 112 patients with ESFT in a tissue microarray platform and associated with clinicopathological parameters and overall survival (OS)...
December 15, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/29100284/exosomes-containing-differential-expression-of-microrna-and-mrna-in-osteosarcoma-that-can-predict-response-to-chemotherapy
#2
Ji-Feng Xu, Ya-Ping Wang, Shui-Jun Zhang, Yu Chen, Hai-Feng Gu, Xiao-Fan Dou, Bing Xia, Qing Bi, Shun-Wu Fan
A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29053210/a-combination-of-mtap-and-bap1-immunohistochemistry-in-pleural-effusion-cytology-for-the-diagnosis-of-mesothelioma
#3
Yoshiaki Kinoshita, Tomoyuki Hida, Makoto Hamasaki, Shinji Matsumoto, Ayuko Sato, Tohru Tsujimura, Kunimitsu Kawahara, Kenzo Hiroshima, Yoshinao Oda, Kazuki Nabeshima
BACKGROUND: Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The authors previously described that IHC expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM tissues...
October 20, 2017: Cancer
https://www.readbyqxmd.com/read/29022512/schistosoma-mansoni-purine-and-pyrimidine-biosynthesis-structures-and-kinetic-experiments-in-the-search-for-the-best-therapeutic-target
#4
Vitor Hugo Balasco Serrão, Humberto D'Muniz Pereira, Juliana Roberta Torini de Souza, Larissa Romanello
BACKGROUND: Schistosoma mansoni is the etiological agent of schistosomiasis, a debilitating treatment neglected tropical disease that affects approximately 218 million people worldwide. Despite its importance, the treatment of schistosomiasis relies on a single drug, praziquantel. Some reports on the resistance of S. mansoni to this drug have stimulated efforts to develop new drugs to treat this disease. S. mansoni possesses all the same pyrimidine pathways (de novo, salvage and thymidylate cycles) as those of its host...
October 11, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28988007/chromosome-copy-number-variation-in-telomerized-human-bone-marrow-stromal-cells-insights-for-monitoring-safe-ex-vivo-expansion-of-adult-stem-cells
#5
Jorge S Burns, Linda Harkness, Abdullah Aldahmash, Laurent Gautier, Moustapha Kassem
Adult human bone marrow stromal cells (hBMSC) cultured for cell therapy require evaluation of potency and stability for safe use. Chromosomal aberrations upsetting genomic integrity in such cells have been contrastingly described as "Limited" or "Significant". Previously reported stepwise acquisition of a spontaneous neoplastic phenotype during three-year continuous culture of telomerized cells (hBMSC-TERT20) didn't alter a diploid karyotype measured by spectral karyotype analysis (SKY). Such screening may not adequately monitor abnormal and potentially tumorigenic hBMSC in clinical scenarios...
September 25, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28880543/the-transition-state-structure-for-human-mat2a-from-isotope-effects
#6
Ross S Firestone, Vern L Schramm
Human methionine S-adenosyltransferase (MAT2A) catalyzes the formation of S-adenosylmethionine (SAM) from ATP and methionine. Synthetic lethal genetic analysis has identified MAT2A as an anticancer target in tumor cells lacking expression of 5'-methylthioadenosine phosphorylase (MTAP). Approximately 15% of human cancers are MTAP(-/-). The remainder can be rendered MTAP(-) through MTAP inhibitors. We used kinetic isotope effect (KIE), commitment factor (Cf), and binding isotope effect (BIE) measurements combined with quantum mechanical (QM) calculations to solve the transition state structure of human MAT2A...
October 4, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28720843/clinical-study-of-genomic-drivers-in-pancreatic-ductal-adenocarcinoma
#7
Michael T Barrett, Ray Deiotte, Elizabeth Lenkiewicz, Smriti Malasi, Tara Holley, Lisa Evers, Richard G Posner, Timothy Jones, Haiyong Han, Mark Sausen, Victor E Velculescu, Jeffrey Drebin, Peter O'Dwyer, Gayle Jameson, Ramesh K Ramanathan, Daniel D Von Hoff
BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer with complex genomes and dense fibrotic stroma. This study was designed to identify clinically relevant somatic aberrations in pancreatic cancer genomes of patients with primary and metastatic disease enrolled and treated in two clinical trials. METHODS: Tumour nuclei were flow sorted prior to whole genome copy number variant (CNV) analysis. Targeted or whole exome sequencing was performed on most samples...
August 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28620131/exosomes-containing-differential-expression-of-microrna-and-mrna-in-osteosarcoma-that-can-predict-response-to-chemotherapy
#8
Ji-Feng Xu, Ya-Ping Wang, Shui-Jun Zhang, Yu Chen, Hai-Feng Gu, Xiao-Fan Dou, Bing Xia, Qing Bi, Shun-Wu Fan
A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28213009/immunohistochemical-detection-of-mtap-and-bap1-protein-loss-for-mesothelioma-diagnosis-comparison-with-9p21-fish-and-bap1-immunohistochemistry
#9
COMPARATIVE STUDY
Tomoyuki Hida, Makoto Hamasaki, Shinji Matsumoto, Ayuko Sato, Tohru Tsujimura, Kunimitsu Kawahara, Akinori Iwasaki, Tatsuro Okamoto, Yoshinao Oda, Hiroshi Honda, Kazuki Nabeshima
OBJECTIVES: Differentiating malignant pleural mesothelioma (MPM) from reactive mesothelial hyperplasia (RMH) is still challenging. Detection of homozygous deletion (HD) of 9p21 region including p16(INK4A) (p16) by fluorescence in situ hybridization (FISH) and immunohistochemical detection of loss of BRCA1 associated protein 1 (BAP1), are reliable markers for MPM diagnosis. However, not all laboratories are equipped to perform 9p21 FISH; immunohistochemistry (IHC) is a more common and feasible technique...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28026167/heat-capacity-changes-for-transition-state-analogue-binding-and-catalysis-with-human-5-methylthioadenosine-phosphorylase
#10
Ross S Firestone, Scott A Cameron, Jerome M Karp, Vickery L Arcus, Vern L Schramm
Human 5'-methylthioadenosine phosphorylase (MTAP) catalyzes the phosphorolysis of 5'-methylthioadenosine (MTA). Its action regulates cellular MTA and links polyamine synthesis to S-adenosylmethionine (AdoMet) salvage. Transition state analogues with picomolar dissociation constants bind to MTAP in an entropically driven process at physiological temperatures, suggesting increased hydrophobic character or dynamic structure for the complexes. Inhibitor binding exhibits a negative heat capacity change (-ΔCp), and thus the changes in enthalpy and entropy upon binding are strongly temperature-dependent...
February 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/27994653/association-of-common-variants-in-mtap-with-susceptibility-and-overall-survival-of-osteosarcoma-a-two-stage-population-based-study-in-han-chinese
#11
Liqiang Zhi, Dan Liu, Stephen G Wu, Tianqing Li, Guanghui Zhao, Bo Zhao, Meng Li
Osteosarcoma (OS) is a common malignant tumor, which exists widely in the bone of children and adolescents, and genetic factors may influence its susceptibility. Recently, the gene MTAP has been reported to be associated with OS in a Caucasian population. To investigate the association of common variants in MTAP with OS risk in Han Chinese individuals, we designed a two-stage case-control study with 392 OS patients and 1,578 unrelated healthy controls of Han Chinese individuals. A total of 17 tagging single nucleotide polymorphisms (SNPs) were firstly genotyped in the discovery stage, and single-SNP association and haplotypic association analyses have been performed...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27960044/genetic-variants-at-9p21-3-are-associated-with-risk-of-esophageal-squamous-cell-carcinoma-in-a-chinese-population
#12
Xiaoming Lin, Caiwang Yan, Yong Gao, Jiangbo Du, Xun Zhu, Fei Yu, Tongtong Huang, Juncheng Dai, Hongxia Ma, Yue Jiang, Rong Yin, Zhibin Hu, Guangfu Jin, Lin Xu, Hongbing Shen
Genome-wide association studies have linked genetic variants at 9p21.3 to the risk of multiple cancers. However, the roles of genetic variants at 9p21.3 in esophageal squamous cell carcinoma (ESCC) development are largely unknown. We evaluated the genetic variants at 9p21.3 reported in cancer genome-wide association studies with a case-control study including 2139 ESCC cases and 2273 controls in a Chinese population, and measured the mRNA expression levels of MTAP, CDKN2A, CDKN2B, and CDKN2B-AS1 in paired ESCC tumor and adjacent normal tissues...
February 2017: Cancer Science
https://www.readbyqxmd.com/read/27935959/crystal-structure-of-schistosoma-mansoni-adenosine-phosphorylase-5-methylthioadenosine-phosphorylase-and-its-importance-on-adenosine-salvage-pathway
#13
Juliana Roberta Torini, José Brandão-Neto, Ricardo DeMarco, Humberto D'Muniz Pereira
Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27929028/concordance-between-somatic-copy-number-loss-and-down-regulated-expression-a-pan-cancer-study-of-cancer-predisposition-genes
#14
Ran Wei, Ming Zhao, Chun-Hou Zheng, Min Zhao, Junfeng Xia
Cancer predisposition genes (CPGs) are a class of cancer genes in which germline variants lead to increased risk of cancer. Research has revealed that copy number variation (CNV) may be linked to cancer susceptibility in CPGs. In this pan-cancer analysis, we explored the relationship between somatic CNV and gene expression changes in CPGs. Based on curated 827 human CPGs from literature, we firstly identified 729 CPGs with precise CNV information from 5067 tumor samples using TCGA CNV data. Among them, 128 CPGs tended to have more frequent copy number losses (CNLs) compared with copy number gains (CNGs)...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27851804/experimentally-assessed-reactive-aggression-in-borderline-personality-disorder
#15
Olga Kogan-Goloborodko, Elisabeth Brügmann, Jonathan Repple, Ute Habel, Benjamin Clemens
Approximately 73% of patients suffering from Borderline personality disorder (BPD) exhibit aggressive behaviour, which severely hinders therapeutic work and clinical improvement. Because the underlying mechanisms of aggression in BPD are not yet completely understood, additional research in this domain has a high clinical and scientific relevance. We employed a modified version of the Taylor Aggression Paradigm (mTAP), in order to examine for the first time whether this task can be used to differentiate between BPD patients and healthy controls with regard to reactive aggression...
2016: PloS One
https://www.readbyqxmd.com/read/27779859/continuous-fluorescence-assays-for-reactions-involving-adenine
#16
Ross S Firestone, Scott A Cameron, Peter C Tyler, Rodrigo G Ducati, Adam Z Spitz, Vern L Schramm
5'-Methylthioadenosine phosphorylase (MTAP) and 5'-methylthioadenosine nucleosidase (MTAN) catalyze the phosphorolysis and hydrolysis of 5'-methylthioadenosine (MTA), respectively. Both enzymes have low KM values for their substrates. Kinetic assays for these enzymes are challenging, as the ultraviolet absorbance spectra for reactant MTA and product adenine are similar. We report a new assay using 2-amino-5'-methylthioadenosine (2AMTA) as an alternative substrate for MTAP and MTAN enzymes. Hydrolysis or phosphorolysis of 2AMTA forms 2,6-diaminopurine, a fluorescent and easily quantitated product...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27775850/clinicopathological-characteristics-and-genomic-profile-of-primary-sinonasal-tract-diffuse-large-b-cell-lymphoma-dlbcl-reveals-gain-at-1q31-and-rgs1-encoding-protein-high-rgs1-immunohistochemical-expression-associates-with-poor-overall-survival-in-dlbcl-not
#17
Joaquim Carreras, Yara Y Kikuti, Sílvia Beà, Masashi Miyaoka, Shinichiro Hiraiwa, Haruka Ikoma, Ryoko Nagao, Sakura Tomita, David Martin-Garcia, Itziar Salaverria, Ai Sato, Akifumi Ichiki, Giovanna Roncador, Juan F Garcia, Kiyoshi Ando, Elias Campo, Naoya Nakamura
AIMS: We aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large B cell lymphoma (DLBCL(sn) ) in a series of 240 cases of DLBCL not otherwise specified [DLBCL(all ()(NOS)()) ], including DLBCL(sn) training set (n = 11) and validation set (n = 18), and DLBCL(non-sn) (n = 211). METHODS AND RESULTS: In the training set, 82% had a non-germinal center B-cell-like (Hans' Classifier) (non-GCB) phenotype and 18% were Epstein-Barr virus-encoded small RNAs (EBER)(+) ...
March 2017: Histopathology
https://www.readbyqxmd.com/read/27761950/melanoma-risk-alleles-are-associated-with-downregulation-of-the-mtap-gene-and-hypermethylation-of-a-cpg-island-upstream-of-the-gene-in-dermal-fibroblasts
#18
LETTER
Antonella Sangalli, Giovanni Malerba, Gianpaolo Tessari, Monica Rodolfo, Macarena Gomez-Lira
Several association studies and GWAS on melanoma skin cancer risk have reported statistically significant signals on 9p21.3 region, where MTAP gene maps. None of the associated SNPs identified in these studies lie in the coding region of the gene and the causative relation of risk alleles with melanoma predisposition has not been elucidated. MTAP has a tumor suppressor activity and epigenetic silencing has been described in melanoma cell lines. In the present study, we show that melanoma risk alleles correlate with a MTAP allele-specific hyper-methylation and down-regulation of gene expression...
August 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/27622058/suppressive-effects-of-tumor-cell-derived-5-deoxy-5-methylthioadenosine-on-human-t-cells
#19
Frederik C Henrich, Katrin Singer, Kerstin Poller, Luise Bernhardt, Carolin D Strobl, Katharina Limm, Axel P Ritter, Eva Gottfried, Simon Völkl, Benedikt Jacobs, Katrin Peter, Dimitrios Mougiakakos, Katja Dettmer, Peter J Oefner, Anja-Katrin Bosserhoff, Marina P Kreutz, Michael Aigner, Andreas Mackensen
The immunosuppressive tumor microenvironment represents one of the main obstacles for immunotherapy of cancer. The tumor milieu is among others shaped by tumor metabolites such as 5'-deoxy-5'-methylthioadenosine (MTA). Increased intratumoral MTA levels result from a lack of the MTA-catabolizing enzyme methylthioadenosine phosphorylase (MTAP) in tumor cells and are found in various tumor entities. Here, we demonstrate that MTA suppresses proliferation, activation, differentiation, and effector function of antigen-specific T cells without eliciting cell death...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27556634/concordance-of-copy-number-loss-and-down-regulation-of-tumor-suppressor-genes-a-pan-cancer-study
#20
Min Zhao, Zhongming Zhao
BACKGROUND: Tumor suppressor genes (TSGs) encode the guardian molecules to control cell growth. The genomic alteration of TSGs may cause tumorigenesis and promote cancer progression. So far, investigators have mainly studied the functional effects of somatic single nucleotide variants in TSGs. Copy number variation (CNV) is another important form of genetic variation, and is often involved in cancer biology and drug treatment, but studies of CNV in TSGs are less represented in literature...
August 22, 2016: BMC Genomics
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