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https://read.qxmd.com/read/31593885/towards-breast-cancer-targeting-synthesis-of-tetrahydroindolocarbazoles-antibreast-cancer-evaluation-upa-inhibition-molecular-genetic-and-molecular-modelling-studies
#21
Entesar M Ahmed, Alaadin E Sarhan, Dina H El-Naggar, Reham R Khattab, Mohamed El-Naggar, Shahenda M El-Messery, Ghada S Hassan, Marwa M Mounier, Khaled Mahmoud, Neama I Ali, Karima F Mahrous, Mamdouh M Ali, Mardia T El Sayed
A series of some new tetrahydroindolocarbazole derivatives has been synthesized. The structure of the synthesized compounds has been confirmed by different spectroscopic techniques such as IR, NMR, elemental analysis and mass spectrometry. The target compounds were evaluated for their antitumor activity against breast cancer cell line MCF-7, their GI% and their LC50 have been determined. Six of the synthesized compounds exhibited GI% values against MCF-7 cell lines exceeding 70% ranging from 71.9 to 85.0% in addition that compound 11 expressed GI% values of 99...
October 1, 2019: Bioorganic Chemistry
https://read.qxmd.com/read/31572674/rapid-identification-of-key-copy-number-alterations-in-b-and-t-cell-acute-lymphoblastic-leukemia-by-digital-multiplex-ligation-dependent-probe-amplification
#22
Deepshi Thakral, Gurvinder Kaur, Ritu Gupta, Anne Benard-Slagter, Suvi Savola, Indresh Kumar, Rajni Anand, Lata Rani, Pramod Verma, Sangeeta Joshi, Lalit Kumar, Atul Sharma, Sameer Bakhshi, Rachna Seth, Vivek Singh
Recurrent clonal genetic alterations are the hallmark of Acute Lymphoblastic Leukemia (ALL) and govern the risk stratification, response to treatment and clinical outcome. In this retrospective study conducted on ALL patient samples, the purpose was to estimate the copy number alterations (CNAs) in ALL by digitalMLPA (dMLPA), validation of the dMLPA data by conventional MLPA and RT-PCR, and correlation of CNAs with Minimal Residual Disease (MRD) status. The ALL patient samples ( n = 151; B-ALL, n = 124 cases and T-ALL, n = 27 cases) were assessed for CNAs by dMLPA for detection of sub-microscopic CNAs and ploidy status...
2019: Frontiers in Oncology
https://read.qxmd.com/read/31570769/fluorescence-in-situ-hybridization-fish-provides-estimates-of-minute-and-interstitial-bap1-cdkn2a-and-nf2-gene-deletions-in-peritoneal-mesothelioma
#23
Silvia Brich, Fabio Bozzi, Federica Perrone, Elena Tamborini, Antonello Domenico Cabras, Marcello Deraco, Silvia Stacchiotti, Gian Paolo Dagrada, Silvana Pilotti
The aim of this study was to assess the performance of fluorescence in situ hybridization (FISH) in identifying the copy number profiles of the three key peritoneal mesothelioma tumor suppressor genes BAP1, CDKN2A, and NF2, with particular emphasis on minute homozygous deletions, a copy number abnormality recently unveiled at the 3p21 (BAP1) chromosomal region using high-throughput methods. FISH was performed on 75 formalin-fixed-paraffin-embedded peritoneal mesotheliomas and recognized two types of monoallelic loss (monosomy, and hemizygous deletion) and two types of biallelic loss (canonical homozygous deletion with a complete loss of FISH signal and homozygous deletion with diminished signal)...
September 30, 2019: Modern Pathology
https://read.qxmd.com/read/31533041/a-prmt5-rnf168-smurf2-axis-controls-h2ax-proteostasis
#24
Changzheng Du, Landon J Hansen, Simranjit X Singh, Feiyifan Wang, Ran Sun, Casey J Moure, Kristen Roso, Paula K Greer, Hai Yan, Yiping He
H2AX safeguards genomic stability in a dose-dependent manner; however, mechanisms governing its proteostasis are poorly understood. Here, we identify a PRMT5-RNF168-SMURF2 cascade that regulates H2AX proteostasis. We show that PRMT5 sustains the expression of RNF168, an E3 ubiquitin ligase essential for DNA damage response (DDR). Suppression of PRMT5 occurs in methylthioadenosine phosphorylase (MTAP)-deficient glioblastoma cells and attenuates the expression of RNF168, leading to destabilization of H2AX by E3 ubiquitin ligase SMURF2...
September 17, 2019: Cell Reports
https://read.qxmd.com/read/31495751/proceedings-of-the-american-society-of-cytopathology-companion-session-at-the-2019-united-states-and-canadian-academy-of-pathology-annual-meeting-part-2-effusion-cytology-with-focus-on-theranostics-and-diagnosis-of-malignant-mesothelioma
#25
REVIEW
Momin T Siddiqui, Fernando Schmitt, Andrew Churg
We live in the "era" of minimally invasive procedures, molecular testing, and personalized care. Effusions have a high sensitivity and will often yield diagnostic cytological material. The companion session presented by the American Society of Cytopathology at the 2019 United States and Canadian Academy of Pathology meeting outlined our current and future projected practices in characterizing, managing, and diagnosing serous cavity fluids. In this second part, the role of theranostics and the diagnosis of malignant mesothelioma, as was discussed at the meeting, have been highlighted...
August 8, 2019: Journal of the American Society of Cytopathology
https://read.qxmd.com/read/31403758/body-site-specific-genetic-effects-influence-naevus-count-distribution-in-women
#26
Alessia Visconti, Simone Ribero, Marianna Sanna, Timothy D Spector, Veronique Bataille, Mario Falchi
Body site is highly relevant for melanoma: it affects prognosis and varies according to the patient's sex. The distribution of naevi, a major risk factor for melanoma, at different body sites also varies according to sex in childhood. Using naevus counts at different body sites in 492 unrelated adults from both sexes, we observed that women have an increased number of naevi on the lower limbs compared to men (P=8.5x10-5 ), showing that a high naevus count on this site persists from childhood throughout life...
August 12, 2019: Pigment Cell & Melanoma Research
https://read.qxmd.com/read/31267186/genomic-profile-of-a-primary-squamous-cell-carcinoma-arising-from-malignant-transformation-of-a-pineal-epidermoid-cyst
#27
Mina M Gerges, Saniya S Godil, Kavelin Rumalla, Benjamin Liechty, David J Pisapia, Rajiv S Magge, Theodore H Schwartz
Malignant transformation of intracranial epidermoid cysts is a rare occurrence. We present the second case of such an event occurring in the pineal region and the first case sent for detailed genomic profiling. MRI demonstrated two lesions: a cyst in a quadrigeminal cistern with restricted diffusion on DWI-weighted images and an adjacent, peripherally enhancing tumor with cerebellar infiltration. Both the lesions were completely resected with a small residual of the epidermoid cyst. The final pathology of both lesions was consistent with epidermoid cyst and squamous cell carcinoma (SCC), respectively...
July 2, 2019: Acta Neurochirurgica
https://read.qxmd.com/read/31257072/anti-tumor-activity-of-the-type-i-prmt-inhibitor-gsk3368715-synergizes-with-prmt5-inhibition-through-mtap-loss
#28
Andrew Fedoriw, Satyajit R Rajapurkar, Shane O'Brien, Sarah V Gerhart, Lorna H Mitchell, Nicholas D Adams, Nathalie Rioux, Trupti Lingaraj, Scott A Ribich, Melissa B Pappalardi, Niyant Shah, Jenny Laraio, Yan Liu, Michael Butticello, Chris L Carpenter, Caretha Creasy, Susan Korenchuk, Michael T McCabe, Charles F McHugh, Raman Nagarajan, Craig Wagner, Francesca Zappacosta, Roland Annan, Nestor O Concha, Roberta A Thomas, Timothy K Hart, Jesse J Smith, Robert A Copeland, Mikel P Moyer, John Campbell, Kim Stickland, James Mills, Suzanne Jacques-O'Hagan, Christina Allain, Danielle Johnston, Alejandra Raimondi, Margaret Porter Scott, Nigel Waters, Kerren Swinger, Ann Boriack-Sjodin, Tom Riera, Gideon Shapiro, Richard Chesworth, Rabinder K Prinjha, Ryan G Kruger, Olena Barbash, Helai P Mohammad
Type I protein arginine methyltransferases (PRMTs) catalyze asymmetric dimethylation of arginines on proteins. Type I PRMTs and their substrates have been implicated in human cancers, suggesting inhibition of type I PRMTs may offer a therapeutic approach for oncology. The current report describes GSK3368715 (EPZ019997), a potent, reversible type I PRMT inhibitor with anti-tumor effects in human cancer models. Inhibition of PRMT5, the predominant type II PRMT, produces synergistic cancer cell growth inhibition when combined with GSK3368715...
July 8, 2019: Cancer Cell
https://read.qxmd.com/read/31249865/nutrient-availability-shapes-methionine-metabolism-in-p16-mtap-deleted-cells
#29
Sydney M Sanderson, Peter G Mikhael, Vijyendra Ramesh, Ziwei Dai, Jason W Locasale
Codeletions of gene loci containing tumor suppressors and neighboring metabolic enzymes present an attractive synthetic dependency in cancers. However, the impact that these genetic events have on metabolic processes, which are also dependent on nutrient availability and other environmental factors, is unknown. As a proof of concept, we considered panels of cancer cells with homozygous codeletions in CDKN2a and MTAP , genes respectively encoding the commonly-deleted tumor suppressor p16 and an enzyme involved in methionine metabolism...
June 2019: Science Advances
https://read.qxmd.com/read/31231129/hemizygous-loss-of-nf2-detected-by-fluorescence-in-situ-hybridization-is-useful-for-the-diagnosis-of-malignant-pleural-mesothelioma
#30
Yoshiaki Kinoshita, Makoto Hamasaki, Masayo Yoshimura, Shinji Matsumoto, Akinori Iwasaki, Kazuki Nabeshima
Neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene located on chromosome 22q12.2, is frequently abnormal in mesothelioma. Recent studies have revealed the effectiveness of diagnostic assays for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia. These include detection of homozygous deletion of the 9p21 locus by fluorescence in situ hybridization (FISH) (9p21 FISH), loss of expression of BAP1 as detected by immunohistochemistry, and loss of expression of methylthioadenosine phosphorylase (MTAP) as detected by immunohistochemistry...
June 23, 2019: Modern Pathology
https://read.qxmd.com/read/31231127/mtap-immunohistochemistry-is-an-accurate-and-reproducible-surrogate-for-cdkn2a-fluorescence-in-situ-hybridization-in-diagnosis-of-malignant-pleural-mesothelioma
#31
David B Chapel, Jefree J Schulte, Kyra Berg, Andrew Churg, Sanja Dacic, Carrie Fitzpatrick, Francoise Galateau-Salle, Kenzo Hiroshima, Thomas Krausz, Nolwenn Le Stang, Stephanie McGregor, Kazuki Nabeshima, Aliya N Husain
Ancillary studies facilitate accurate diagnosis of morphologically challenging mesothelial proliferations. The current diagnostic algorithm proceeds from BAP1 immunohistochemistry to CDKN2A fluorescence in situ hybridization. While MTAP immunohistochemistry has recently shown promise as a surrogate for CDKN2A fluorescence in situ hybridization, it has been examined in only a few single-institution studies. Furthermore, there are no published reports on interobserver agreement or interlaboratory reproducibility for MTAP immunohistochemistry...
June 23, 2019: Modern Pathology
https://read.qxmd.com/read/31201594/validity-of-the-multidimensional-task-ability-profile
#32
Joe L Verna, Leonard N Matheson, Sharon Scherer, John M Mayer
Background The Multidimensional Task Ability Profile (MTAP) is a patient-reported outcome (PRO) measure that provides a global score linked to the physical demand characteristics of work, but needs to be validated against established measures. Purpose To assess the concurrent validity of the MTAP compared with the Oswestry Disability Index (ODI), Neck Disability Index (NDI), Disabilities of the Arm, Shoulder, and Hand (DASH), Lower Extremity Functional Scale (LEFS), and Short Form 12 Health-Related Quality of Life (SF-12) questionnaires...
June 14, 2019: Journal of Occupational Rehabilitation
https://read.qxmd.com/read/31096160/frequent-homozygous-deletions-of-the-cdkn2a-locus-in-somatic-cancer-tissues
#33
Abdulaziz Hamid Beniamin Petreaca, Ruben Petreaca
Here we present and describe data on homozygous deletions (HD) of human CDKN2 A and neighboring regions on the p arm of Chromosome 9 from cancer genome sequences deposited on the online Catalogue of Somatic Mutations in Cancer (COSMIC) database. Although CDKN2 A HDs have been previously described in many cancers, this is a pan-cancer report of these aberrations with the aim to map the distribution of the breakpoints. We find that HDs of this locus have a median range of 1,255,650bps. When the deletion breakpoints were mapped on both the telomere and centromere proximal sides of CDKN2A, most of the telomere proximal breakpoints concentrate to a narrow region of the chromosome which includes the gene MTAP...
April 25, 2019: Mutation Research
https://read.qxmd.com/read/31040154/mtap-loss-promotes-stemness-in-glioblastoma-and-confers-unique-susceptibility-to-purine-starvation
#34
Landon J Hansen, Ran Sun, Rui Yang, Simranjit X Singh, Lee H Chen, Christopher J Pirozzi, Casey J Moure, Carlee Hemphill, Austin B Carpenter, Patrick Healy, Ryan C Ruger, Chin-Pu J Chen, Paula K Greer, Fangping Zhao, Ivan Spasojevic, Carole Grenier, Zhiqing Huang, Susan K Murphy, Roger E McLendon, Henry S Friedman, Allan H Friedman, James E Herndon, John H Sampson, Stephen T Keir, Darell D Bigner, Hai Yan, Yiping He
Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastoma (GBM), but its pathologic consequences remain unclear. In this study, we report that loss of MTAP results in profound epigenetic reprogramming characterized by hypomethylation of PROM1/CD133-associated stem cell regulatory pathways. MTAP deficiency promotes glioma stem-like cell (GSC) formation with increased expression of PROM1/CD133 and enhanced tumorigenicity of glioblastoma cells and is associated with poor prognosis in GBM patients...
April 30, 2019: Cancer Research
https://read.qxmd.com/read/30994774/root-canal-dressings-for-revascularization-influence-in-vitro-mineralization-of-apical-papilla-cells
#35
Juliana Garuba Rahhal, Emanuel da Silva Rovai, Marinella Holzhausen, Celso Luiz Caldeira, Carlos Ferreira Dos Santos, Carla Renata Sipert
Endodontic revascularization is based on cell recruitment into the necrotic root canal of immature teeth after chemical disinfection. The clinical outcome depends on the ability of surviving cells from the apical tissue to differentiate and promote hard tissue deposition inside the dentinal walls. OBJECTIVE: To investigate the effect of calcium hydroxide (CH) and modified triple antibiotic paste (mTAP - ciprofloxacin, metronidazole and cefaclor) on the viability and mineralization potential of apical papilla cells (APC) in vitro ...
2019: Journal of Applied Oral Science: Revista FOB
https://read.qxmd.com/read/30994044/chromatin-conformation-links-putative-enhancers-in-intracranial-aneurysm-associated-regions-to-potential-candidate-genes
#36
Melanie D Laarman, Geert Geeven, Phil Barnett, Gabriël J E Rinkel, Wouter de Laat, Ynte M Ruigrok, Jeroen Bakkers
Background We previously showed that intracranial aneurysm ( IA )-associated single-nucleotide polymorphisms are enriched in promoters and putative enhancers identified in the human circle of Willis, on which IA s develop, suggesting a role for promoters and enhancers in IAs . We further investigated the role of putative enhancers in the pathogenesis of IA by identifying their potential target genes and validating their regulatory activity. Methods and Results Using our previously published circle of Willis chromatin immunoprecipitation and sequencing data, we selected 34 putative enhancers in IA -associated regions from genome-wide association studies...
May 7, 2019: Journal of the American Heart Association
https://read.qxmd.com/read/30916320/prmt1-loss-sensitizes-cells-to-prmt5-inhibition
#37
Guozhen Gao, Liang Zhang, Oscar D Villarreal, Wei He, Dan Su, Ella Bedford, Phoebe Moh, Jianjun Shen, Xiaobing Shi, Mark T Bedford, Han Xu
PRMT5 is an arginine methyltransferase that accounts for the vast majority of the symmetric methylation in cells. PRMT5 exerts its function when complexed with MEP50/WDR77. This activity is often elevated in cancer cells and correlates with poor prognosis, making PRMT5 a therapeutic target. To investigate the PRMT5 signaling pathway and to identify genes whose loss-of-function sensitizes cancer cells to PRMT5 inhibition, we performed a CRISPR/Cas9 genetic screen in the presence of a PRMT5 inhibitor. We identified known components of the PRMT5 writer/reader pathway including PRMT5 itself, MEP50/WDR77, PPP4C, SMNDC1 and SRSF3...
March 27, 2019: Nucleic Acids Research
https://read.qxmd.com/read/30885343/highly-expressed-ezh2-in-combination-with-bap1-and-mtap-loss-as-detected-by-immunohistochemistry-is-useful-for-differentiating-malignant-pleural-mesothelioma-from-reactive-mesothelial-hyperplasia
#38
Masayo Yoshimura, Yoshiaki Kinoshita, Makoto Hamasaki, Shinji Matsumoto, Tomoyuki Hida, Yoshinao Oda, Akinori Iwasaki, Kazuki Nabeshima
OBJECTIVE: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with poor prognosis. Loss of BRCA-associated protein 1 (BAP1) protein expression as detected by immunohistochemistry (IHC) and homozygous deletion (HD) of the 9p21 locus as detected by fluorescence in situ hybridization (FISH) permits differentiation of MPM from reactive mesothelial hyperplasia (RMH). We have previously reported that detecting the loss of methylthioadenosine phosphorylase (MTAP) using IHC is a surrogate assay for 9p21 FISH...
April 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://read.qxmd.com/read/30860833/-selective-inhibitors-of-h-pylori-methylthioadenosine-nucleosidase-and-human-methylthioadenosine-phosphorylase
#39
Rajesh K Harijan, Oskar Hoff, Rodrigo G Ducati, Ross S Firestone, Brett M Hirsch, Gary B Evans, Vern L Schramm, Peter C Tyler
Bacterial 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes the hydrolysis of adenine from S-methyl-5'-thioadenosine (MTA) and S-adenosyl L-homocysteine (SAH) to form S-methyl-5'-thioribose (MTR) and S-ribosyl-L-homocysteine (SRH), respectively. The MTANs are involved in quorum sensing pathways and hydrolyze MTA to metabolites for recycling to S-adenosylmethionine (SAM). A few bacterial species use the futalosine pathway for menaquinone synthesis and in these, MTAN catalyzes an essential step, making it a candidate for species-specific antibiotic development...
March 12, 2019: Journal of Medicinal Chemistry
https://read.qxmd.com/read/30810637/cytotoxicity-of-intracanal-dressings-on-apical-papilla-cells-differ-upon-activation-with-e-faecalis-lta
#40
Carla Renata Sipert, Aline Pereira Oliveira, Celso Luiz Caldeira
OBJECTIVE: The aim of this study was to investigate the cytotoxic effects of modified triple antibiotic paste and an experimental composition using calcium hydroxide on lipoteichoic acid (LTA)-primed apical papilla cells (APC). MATERIAL AND METHODS: Human APC were tested for in vitro cytotoxicity of modified Triple Antibiotic Paste (mTAP - Ciprofloxacin, Metronidazole and Cefaclor at 1:1:1) and of a paste of Ciprofloxacin, Metronidazole and Calcium hydroxide (CMC - 1:1:2) and modified CMC (mCMC - 2:2:1) by using MTT assay...
February 21, 2019: Journal of Applied Oral Science: Revista FOB
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