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https://www.readbyqxmd.com/read/28433252/nrasq61r-immunohistochemistry-detects-both-nrasq61r-and-krasq61r-mutations-in-colorectal-cancer
#1
Jie-Yang Jhuang, Chang-Tsu Yuan, Yu-Lin Lin, Mei-Ling Cheng, Jau-Yu Liau, Jia-Huei Tsai
The NRASQ61R monoclonal antibody (clone sp174) is a mutation-specific antibody that is increasingly being used to detect the NRAS(Q61R) mutation in melanomas. This antibody has been reported to be highly correlated with the NRAS(Q61R) mutation status in melanomas and follicular neoplasms of the thyroid gland. However, its utility in colorectal carcinoma (CRC) has remained largely unknown. In this study, we assessed the sensitivity, specificity, and diagnostic utility of NRASQ61R immunohistochemistry in a cohort consisting of tissue sections of 113 CRCs, which were molecularly profiled for the KRAS, NRAS, and BRAF mutations...
April 19, 2017: Pathology
https://www.readbyqxmd.com/read/28431513/functional-characterization-of-cucumber-cucumis-sativus-l-clade-v-mlo-genes
#2
Jeroen A Berg, Michela Appiano, Gerard Bijsterbosch, Richard G F Visser, Henk J Schouten, Yuling Bai
BACKGROUND: Powdery mildew (PM) causing fungi are well-known pathogens, infecting over 10.000 plant species, including the economically important crop cucumber (Cucumis sativus L.). Loss-of-function mutations in clade V MLO genes have previously been shown to lead to recessively inherited broad-spectrum resistance to PM in several species. In cucumber, one clade V MLO homolog (CsaMLO8) was previously identified as being a susceptibility factor to PM. Two other closely related homologs (CsaMLO1 and CsaMLO11) were found, but their function was not yet unravelled...
April 21, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28431268/assessment-of-mutagenicity-of-water-from-lake-sevan-armenia-with-application-of-tradescantia-clone-02
#3
R E Avalyan, E A Aghajanyan, A Khosrovyan, A L Atoyants, A E Simonyan, R M Aroutiounian
For many decades water resources in Armenia have been affected by anthropogenic activity, therefore, a regular bioindication of genotoxic effects of the water bodies is desirable. The genotoxicity of water samples collected from different parts of Lake Sevan were assessed by means of Trad-SHM (stamen hair mutation) assay using Tradescantia (clone 02). Here we report a significant increase in the frequency of somatic mutations and morphological changes in the Tradescantia inflorescences exposed to the water samples compared to the control...
March 31, 2017: Mutation Research
https://www.readbyqxmd.com/read/28429795/cd200-positive-cancer-associated-fibroblasts-augment-the-sensitivity-of-epidermal-growth-factor-receptor-mutation-positive-lung-adenocarcinomas-to-egfr-tyrosine-kinase-inhibitors
#4
Masayuki Ishibashi, Shinya Neri, Hiroko Hashimoto, Tomoyuki Miyashita, Tatsuya Yoshida, Yuka Nakamura, Hibiki Udagawa, Keisuke Kirita, Shingo Matsumoto, Shigeki Umemura, Kiyotaka Yoh, Seiji Niho, Masahiro Tsuboi, Kenkichi Masutomi, Koichi Goto, Atsushi Ochiai, Genichiro Ishii
Cancer associated fibroblasts (CAFs) play important roles in the chemotherapeutic process, especially through influencing the resistance of tumor cells to molecular targeted therapy. Here we report the existence of a special subpopulation of patient-specific-CAFs that augment the sensitivity of EGFR gene mutation-positive lung cancer to the EGFR-tyrosine kinase inhibitor (EGFR-TKI), gefitinib. When cocultured with EGFR mutation positive lung cancer cells, these CAFs increased the apoptic effect of gefitinib on cancer cells, whereas, in the absence of gefitinib, they did not affect cancer cell viability...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429735/phylogenetic-analysis-of-metastatic-progression-in-breast-cancer-using-somatic-mutations-and-copy-number-aberrations
#5
David Brown, Dominiek Smeets, Borbála Székely, Denis Larsimont, A Marcell Szász, Pierre-Yves Adnet, Françoise Rothé, Ghizlane Rouas, Zsófia I Nagy, Zsófia Faragó, Anna-Mária Tőkés, Magdolna Dank, Gyöngyvér Szentmártoni, Nóra Udvarhelyi, Gabriele Zoppoli, Lajos Pusztai, Martine Piccart, Janina Kulka, Diether Lambrechts, Christos Sotiriou, Christine Desmedt
Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429724/clonal-evolution-in-myelodysplastic-syndromes
#6
Pedro da Silva-Coelho, Leonie I Kroeze, Kenichi Yoshida, Theresia N Koorenhof-Scheele, Ruth Knops, Louis T van de Locht, Aniek O de Graaf, Marion Massop, Sarah Sandmann, Martin Dugas, Marian J Stevens-Kroef, Jaroslav Cermak, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Theo de Witte, Nicole M A Blijlevens, Petra Muus, Gerwin Huls, Bert A van der Reijden, Seishi Ogawa, Joop H Jansen
Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429680/the-inhibitory-effects-of-hydamtiq-a-novel-parp-inhibitor-on-growth-in-human-tumor-cell-lines-with-defective-dna-damage-response-pathways
#7
Enrico Mini, Ida Landini, Laura Lucarini, Andrea Lapucci, Cristina Napoli, Gabriele Perrone, Renato Tassi, Emanuela Masini, Flavio Moroni, Stefania Nobili
The poly(ADP-ribose) polymerase (PARP) enzymes play key roles in the regulation of cellular processes (e.g. DNA damagerepair, genomic stability). It has been shown that PARP inhibitors (PARPIs) are selectively cytotoxic against cells with dysfunctions in genes involved in DNA repair mechanisms (synthetic lethality). Drug induced PARP inhibition potentiates the activity of anticancer drugs such as 5-fluorouracil in enhancing DNA damage, whose repair involves PARP1 activity.The aim of this study was to evaluate the growth inhibitory effects of a novel PARPI, HYDAMTIQ, on human tumor cell lines characterized by different features with regard to DNA damage response pathways (BRCA mutational status, microsatellite status and ATM expression level) and degree of sensitivity/resistance to 5-fluorouracil...
April 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28426879/acute-exposure-to-dehp-metabolite-mehp-cause-genotoxicity-mutagenesis-and-carcinogenicity-in-mammalian-chinese-hamster-ovary-cells
#8
Yu-Jung Chang, Chia-Yi Tseng, Pei-Ying Lin, Yu-Chen Chuang, Ming-Wei Chao
Di-(2-ethylhexyl) phthalate (DEHP), the common plasticizer used in the production of polyvinyl chloride, can be converted to the more potent metabolite mono-ethylhexyl phthalate (MEHP). Epidemiological studies have shown an association with elevated induction of rat hepatic cancer and reproductive toxicity in response to MEHP exposure. However, the mechanism of genotoxicity and carcinogenicity induced by MEHP treatment remains unclear. As a means to elucidate the mechanisms of action, lethality and mutagenicity in the adenine phosphoribosyltransferase (aprt+/-) gene induced in several CHO cell types by MEHP were assessed...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28424234/braf-v600-mutation-detection-in-melanoma-a-comparison-of-two-laboratory-testing-methods
#9
Odharnaith O'Brien, Tomas Lyons, Sandra Murphy, Linda Feeley, Derek Power, Cynthia C B B Heffron
AIMS: The assessment of B-raf proto-oncogene, serine/threonine kinase (BRAF) gene status is now standard practice in patients diagnosed with metastatic melanoma with its presence predicting a clinical response to treatment with BRAF inhibitors. The gold standard in determining BRAF status is currently by DNA-based methods. More recently, a BRAF V600E antibody has been developed. We aim to investigate whether immunohistochemical detection of BRAF mutation is a suitable alternative to molecular testing by polymerase chain reaction (PCR)...
April 19, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28423700/hla-class-i-loss-in-metachronous-metastases-prevents-continuous-t-cell-recognition-of-mutated-neoantigens-in-a-human-melanoma-model
#10
Barbara Schrörs, Silke Lübcke, Volker Lennerz, Martina Fatho, Anne Bicker, Catherine Wölfel, Patrick Derigs, Thomas Hankeln, Dirk Schadendorf, Annette Paschen, Thomas Wölfel
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#11
Lijun Shi, Yang Zhang, Lin Feng, Liming Wang, Weiqi Rong, Fan Wu, Jianxiong Wu, Kaitai Zhang, Shujun Cheng
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422737/generation-of-lung-cancer-cell-lines-harboring-egfr-t790m-mutation-by-crispr-cas9-mediated-genome-editing
#12
Mi-Young Park, Min Hee Jung, Eun Young Eo, Seokjoong Kim, Sang Hoon Lee, Yeon Joo Lee, Jong Sun Park, Young Jae Cho, Jin Haeng Chung, Cheol Hyeon Kim, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee
Tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are effective against lung adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations. However, cancer cells can develop resistance to these agents with prolonged exposure; in over 50% of cases, this is attributable to the EGFR T790M mutation. Moreover, additional resistance mutations can arise with the use of new drugs. Cancer cell lines with specific mutations can enable the study of resistance mechanisms. In this study, we introduced the EGFR T790M mutation into the PC9 human lung cancer cell line-which has a deletion in exon 19 of the EGFR gene-by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)9-mediated genome editing...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422729/the-relevance-of-a-low-jak2v617f-allele-burden-in-clinical-practice-a-monocentric-study
#13
Margherita Perricone, Nicola Polverelli, Giovanni Martinelli, Lucia Catani, Emanuela Ottaviani, Elisa Zuffa, Eugenia Franchini, Arbana Dizdari, Dorian Forte, Elena Sabattini, Michele Cavo, Nicola Vianelli, Francesca Palandri
Since low JAK2V617F allele burden (AB) has been detected also in healthy subjects, its clinical interpretation may be challenging in patients with chronic myeloproliferative neoplasms (MPNs). We tested 1087 subjects for JAK2V617F mutation on suspicion of hematological malignancy. Only 497 (45.7%) patients were positive. Here we present clinical and laboratory parameters of a cohort of 35/497 patients with an AB ≤ 3%.Overall, 22/35 (62.9%) received a WHO-defined diagnosis of MPN and in 14/35 cases (40%) diagnosis was supported by bone marrow (BM) histology (''Histology-based'' diagnosis)...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421415/a-tyrosine-residue-along-with-a-glutamic-acid-of-the-omega-like-loop-governs-the-beta-lactamase-activity-of-msmeg_4455-in-mycobacterium-smegmatis
#14
Ankita Bansal, Debasish Kar, Satya Deo Pandey, Ashok Matcha, N Ganesh Kumar, Soshina Nathan, Anindya S Ghosh
Mycobacterial beta-lactamases are involved in exerting beta-lactam resistance, though many of these proteins remain uncharacterized. Here, we have characterized MSMEG_4455 of Mycobacterium smegmatis as a beta-lactamase using molecular, biochemical and mutational techniques. To elucidate its nature in vivo and in vitro, and to predict its structure-function relationship in silico analysis is done. The MSMEG_4455 is cloned and expressed ectopically in a beta-lactamase deficient Escherichia coli mutant to establish the in vivo beta-lactamase like nature via minimum inhibitory concentration (MIC) determination...
April 19, 2017: Protein Journal
https://www.readbyqxmd.com/read/28421066/unveiling-the-hybrid-genome-structure-of-escherichia-coli-rr1-hb101-reca
#15
Haeyoung Jeong, Young Mi Sim, Hyun Ju Kim, Sang Jun Lee
There have been extensive genome sequencing studies for Escherichia coli strains, particularly for pathogenic isolates, because fast determination of pathogenic potential and/or drug resistance and their propagation routes is crucial. For laboratory E. coli strains, however, genome sequence information is limited except for several well-known strains. We determined the complete genome sequence of laboratory E. coli strain RR1 (HB101 RecA(+)), which has long been used as a general cloning host. A hybrid genome sequence of K-12 MG1655 and B BL21(DE3) was constructed based on the initial mapping of Illumina HiSeq reads to each reference, and iterative rounds of read mapping, variant detection, and consensus extraction were carried out...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28420613/genetic-analysis-and-identification-of-candidate-genes-for-two-spotted-leaf-mutants-spl101-and-spl102-in-rice
#16
Han Xiaobin, Xu Ran, Duan Penggen, Yu Haiyue, Luo Yuehua, Li Yunhai
Spotted-leaf mutants form spots in leaves or leaf sheaths under normal condition. The spotted-leaf phenotypes are similar to hypersensitive reaction of plants attacked by pathogen. Identification and characterization of the spotted-leaf mutants are helpful for understanding the mechanisms of resistance to plant diseases. Here, we identify two spotted-leaf mutants spl101 and spl102 from an EMS-treated elite japonica cultivar KYJ (Kuanyejing). spl101 and spl102 form serious spots at the late heading stage. Genetic analyses show that the spotted-leaf phenotypes of both spl101 and spl102 are caused by a single recessive mutation, respectively...
April 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28419091/multidrug-resistant-bacteria-compensate-for-the-epistasis-between-resistances
#17
Jorge Moura de Sousa, Roberto Balbontín, Paulo Durão, Isabel Gordo
Mutations conferring resistance to antibiotics are typically costly in the absence of the drug, but bacteria can reduce this cost by acquiring compensatory mutations. Thus, the rate of acquisition of compensatory mutations and their effects are key for the maintenance and dissemination of antibiotic resistances. While compensation for single resistances has been extensively studied, compensatory evolution of multiresistant bacteria remains unexplored. Importantly, since resistance mutations often interact epistatically, compensation of multiresistant bacteria may significantly differ from that of single-resistant strains...
April 2017: PLoS Biology
https://www.readbyqxmd.com/read/28418922/novel-impact-of-the-dnmt3a-r882h-mutation-on-gsh-metabolism-in-a-k562-cell-model-established-by-talens
#18
Li Yang, Ya'Nan Liu, Na Zhang, Xiao'Yi Ding, Wei Zhang, Ke'Feng Shen, Liang Huang, Jian'Feng Zhou, Sen Cui, Zun'Min Zhu, Zheng Hu, Min Xiao
DNA methyltransferase 3A (DNMT3A) mutations occurred in 18%~23% of acute myeloid leukemia (AML) patients, and were considered to be an adverse prognostic factor for adult de novo AML cases. However, the relevant molecular mechanism of the mutation in AML pathogenesis remains obscure. In this study, we established K562 and SKM1 cell model carrying the DNMT3A R882H mutation via transcription activator-like effector nuclease (TALEN) and Clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, and discovered that mutated DNMT3A could promote the proliferative capability of malignant cell clones...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418909/pathogenesis-of-etv6-runx1-positive-childhood-acute-lymphoblastic-leukemia-and-mechanisms-underlying-its-relapse
#19
REVIEW
Congcong Sun, Lixian Chang, Xiaofan Zhu
ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL). Multiple lines of evidence imply a "two-hit" model for the molecular pathogenesis of E/R-positive ALL, whereby E/R rearrangement is followed by a series of secondary mutations that trigger overt leukemia. The cellular framework in which E/R arises and the maintenance of a pre-leukemic condition by E/R are fundamental to the mechanism that underlies leukemogenesis. Accordingly, a variety of studies have focused on the relationship between the clones giving rise to the primary and recurrent E/R-positive ALL...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418900/therapeutic-inhibition-of-usp7-pten-network-in-chronic-lymphocytic-leukemia-a-strategy-to-overcome-tp53-mutated-deleted-clones
#20
Giovanna Carrà, Cristina Panuzzo, Davide Torti, Guido Parvis, Sabrina Crivellaro, Ubaldo Familiari, Marco Volante, Deborah Morena, Marcello Francesco Lingua, Mara Brancaccio, Angelo Guerrasio, Pier Paolo Pandolfi, Giuseppe Saglio, Riccardo Taulli, Alessandro Morotti
Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder with either indolent or aggressive clinical course. Current treatment regiments have significantly improved the overall outcomes even if higher risk subgroups - those harboring TP53 mutations or deletions of the short arm of chromosome 17 (del17p) - remain highly challenging. In the present work, we identified USP7, a known de-ubiquitinase with multiple roles in cellular homeostasis, as a potential therapeutic target in CLL. We demonstrated that in primary CLL samples and in CLL cell lines USP7 is: i) over-expressed through a mechanism involving miR-338-3p and miR-181b deregulation; ii) functionally activated by Casein Kinase 2 (CK2), an upstream interactor known to be deregulated in CLL; iii) effectively targeted by the USP7 inhibitor P5091...
March 17, 2017: Oncotarget
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