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https://www.readbyqxmd.com/read/28433605/stability-of-patient-specific-features-of-altered-dna-replication-timing-in-xenografts-of-primary-human-acute-lymphoblastic-leukemia
#1
Takayo Sasaki, Juan Carlos Rivera-Mulia, Daniel Vera, Jared Zimmerman, Sunny Das, Michelle Padget, Naoto Nakamichi, Bill H Chang, Jeff Tyner, Brian J Druker, Andrew P Weng, Curt I Civin, Connie J Eaves, David M Gilbert
Genome-wide DNA replication timing (RT) profiles reflect the global 3D chromosome architecture of cells. They also provide a comprehensive and unique megabase-scale picture of the cellular epigenetic state. Thus normal differentiation involves reproducible changes in RT and transformation generally perturbs these, although the potential effects of altered RT on the properties of transformed cells remain largely unknown. A major challenge to interrogating these issues in human acute lymphoid leukemia (ALL) is the low proliferative activity of most of the cells, which may be further reduced in cryopreserved samples and difficult to overcome in vitro...
April 19, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28431544/strategies-for-monitoring-and-combating-resistance-to-combination-kinase-inhibitors-for-cancer-therapy
#2
REVIEW
Leanne G Ahronian, Ryan B Corcoran
Targeted therapies such as kinase inhibitors and monoclonal antibodies have dramatically altered cancer care in recent decades. Although these targeted therapies have improved patient outcomes in several cancer types, resistance ultimately develops to these agents. One potential strategy proposed to overcome acquired resistance involves taking repeat tumor biopsies at the time of disease progression, to identify the specific molecular mechanism driving resistance in an individual patient and to select a new agent or combination of agents capable of surmounting that specific resistance mechanism...
April 21, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28431016/somatic-transposition-and-meiotically-driven-elimination-of-an-active-helitron-family-in-pleurotus-ostreatus
#3
Alessandra Borgognone, Raúl Castanera, Elaia Muguerza, Antonio G Pisabarro, Lucía Ramírez
Helitrons constitute a superfamily of DNA transposons that were discovered in silico and are widespread in most eukaryotic genomes. They are postulated to mobilize through a "rolling-circle" mechanism, but the experimental evidence of their transposition has been described only recently. Here, we present the inheritance patterns of HELPO1 and HELPO2 helitron families in meiotically derived progeny of the basidiomycete Pleurotus ostreatus. We found distorted segregation patterns of HELPO2 helitrons that led to a strong under-representation of these elements in the progeny...
April 1, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28430777/correction-the-subclonal-architecture-of-metastatic-breast-cancer-results-from-a-prospective-community-based-rapid-autopsy-program-cascade
#4
Peter Savas, Zhi Ling Teo, Christophe Lefevre, Christoffer Flensburg, Franco Caramia, Kathryn Alsop, Mariam Mansour, Prudence A Francis, Heather A Thorne, Maria Joao Silva, Nnennaya Kanu, Michelle Dietzen, Andrew Rowan, Maik Kschischo, Stephen Fox, David D Bowtell, Sarah-Jane Dawson, Terence P Speed, Charles Swanton, Sherene Loi
[This corrects the article DOI: 10.1371/journal.pmed.1002204.].
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28429724/clonal-evolution-in-myelodysplastic-syndromes
#5
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/28426879/acute-exposure-to-dehp-metabolite-mehp-cause-genotoxicity-mutagenesis-and-carcinogenicity-in-mammalian-chinese-hamster-ovary-cells
#6
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/28425268/efficient-production-of-nanobodies-against-urease-activity-ofhelicobacter-pylori-in-pichia-pastoris
#7
Shahrbanoo Pourasadi, Seyed Latif Mousavi Gargari, Masoumeh Rajabibazl, Shahram Nazarian
BACKGROUND/AIM: Helicobacter pylori is a major health problem. One of the therapeutic approaches is administration of antibody against H. pylori. The methylotrophic Pichia pastoris is a suitable host for expression of recombinant antibody fragments. The aims of this study were the expression and the evaluation of camelid nanobody in the yeast Pichia pastoris. MATERIALS AND METHODS: The camelid-derived heavy-chain antibody (nanobody) against the UreC subunit of urease from H...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28424524/hqia-a-novel-quorum-quenching-enzyme-which-expands-the-ahl-lactonase-family
#8
Marta Torres, Stéphane Uroz, Rafael Salto, Laure Fauchery, Emilia Quesada, Inmaculada Llamas
The screening of a metagenomic library of 250,000 clones generated from a hypersaline soil (Spain) allowed us to identify a single positive clone which confers the ability to degrade N-acyl homoserine lactones (AHLs). The sequencing of the fosmid revealed a 42,318 bp environmental insert characterized by 46 ORFs. The subcloning of these ORFs demonstrated that a single gene (hqiA) allowed AHL degradation. Enzymatic analysis using purified HqiA and HPLC/MS revealed that this protein has lactonase activity on a broad range of AHLs...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28417598/genetic-analysis-of-a-morphologically-heterogeneous-ovarian-endometrioid-carcinoma
#9
Felipe C Geyer, Fresia Pareja, Kathleen A Burke, Anne M Schultheis, Yaser R Hussein, Jiqing Ye, Maria R De Filippo, Caterina Marchio, Gabriel S Macedo, Salvatore Piscuoglio, Raymond S Lim, Eugene Toy, Rajmohan Murali, Achim A Jungbluth, Jorge S Reis-Filho, Robert A Soslow, Britta Weigelt
AIMS: Low-grade ovarian endometrioid carcinomas may be associated with high-grade components. Whether the latter are clonally-related to and originate from the low-grade endometrioid carcinoma remains unclear. Here we employed massively parallel sequencing to characterize the genomic landscape and clonal relatedness of an ovarian endometrioid carcinoma containing low- and high-grade components. METHODS AND RESULTS: DNA samples extracted from each tumor component (low-grade endometrioid, high-grade anaplastic, high-grade squamous) and matched normal tissue were subjected to targeted massively parallel sequencing using the 410 gene Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay...
April 18, 2017: Histopathology
https://www.readbyqxmd.com/read/28412380/colonization-by-multidrug-resistant-organisms-in-long-term-care-facilities-in-italy-a-point-prevalence-study
#10
Maria Giufrè, Enrico Ricchizzi, Marisa Accogli, Fabrizio Barbanti, Monica Monaco, Fernanda Pimentel de Araujo, Claudio Farina, Paolo Fazii, Romano Mattei, Mario Sarti, Agostino Barozzi, Rossella Buttazzi, Marina Cosentino, Maria Nardone, Vincenzo Savini, Patrizia Spigaglia, Annalisa Pantosti, Maria Luisa Moro, Marina Cerquetti
OBJECTIVES: This study aimed to determine prevalence and risk factors for colonization by multidrug-resistant organisms (MDROs) in long-term care facility (LTCF) residents in Italy. Genotypes of MDRO isolates were investigated. METHODS: A point-prevalence study was conducted at 12 LTCFs located in 4 Italian cities (2 February-14 March 2015). Rectal swabs, faeces and nasal/auxiliary swabs were cultured for extended-spectrum β-lactamase (ESBL)- and/or carbapenemase-producing Enterobacteriaceae, Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA), respectively...
April 12, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28410227/subcloning-and-characterization-of-highly-metastatic-cells-derived-from-human-esophageal-squamous-cell-carcinoma-kyse150-cells-by-in-vivo-selection
#11
Masafumi Okuda, Jun Inoue, Naoto Fujiwara, Tatsuyuki Kawano, Johji Inazawa
Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer-related deaths worldwide. Despite the research progress in understanding the disease, the mechanism underlying the metastasis is still unclear. Here, we successfully generated a highly metastatic cell subline, designated as KYSE150-LuM, derived from an esophageal squamous cell carcinoma cell line (KYSE150) by in vivo selection. To elucidate the mechanisms driving metastasis, we characterized the gene expression differences between LuM cells and parent KYSE150 cells...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403382/molecular-profiling-of-multiple-primary-merkel-cell-carcinoma-to-distinguish-genetically-distinct-tumors-from-clonally-related-metastases
#12
Kelly L Harms, Lorena Lazo de la Vega, Daniel H Hovelson, Samantha Rahrig, Andi K Cani, Chia-Jen Liu, Douglas R Fullen, Min Wang, Aleodor A Andea, Christopher K Bichakjian, Timothy M Johnson, Scott A Tomlins, Paul W Harms
Importance: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. In rare cases, the development of an additional cutaneous MCC tumor is clinically consistent with a second primary MCC tumor rather than a cutaneous metastasis, which has important treatment and prognostic implications. Objective: To evaluate genetic relatedness in 4 cases with the clinical diagnosis of multiple primary MCCs. Design, Setting, and Participants: In this case series, 7 cases of clinically designated multiple primary MCC were identified; 4 cases met inclusion criteria for next-generation sequencing (NGS) analysis...
April 12, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28400153/spatiotemporal-diversification-of-intrapatient-genomic-clones-and-early-drug-development-concepts-realize-the-roadmap-of-precision-cancer-medicine
#13
REVIEW
Dimitrios H Roukos
The unmet clinical needs of high relapse and cancer-related death rates are reflected by the poor understanding of the genome-wide mutational landscape and molecular mechanisms orchestrating therapeutic resistance. Emerging potential solutions to this challenge include the exploration of cancer genome dynamic evolution in time and space. Breakthrough next-generation sequencing (NGS) applications including multiregional NGS for intratumor heterogeneity identification, repeated cell-free DNA/circulating tumor DNA-NGS for detecting circulating genomic subclones and their comparison to reveal intrapatient heterogeneity (IPH) could identify the dynamic emergence of resistant subclones in the neoadjuvant, adjuvant and metastatic setting...
April 8, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28382524/characterization-of-a-metagenome-derived-protease-from-contaminated-agricultural-soil-microorganisms-and-its-random-mutagenesis
#14
Chengjian Jiang, Liang Zhang, Fajia Li, Can Meng, Rong Zeng, Jie Deng, Peihong Shen, Qian Ou, Bo Wu
Proteases are typical key enzymes that hydrolyze proteins into amino acids and peptides. Numerous proteases have been studied, but the discovery of metagenome-derived proteases is still significant for both commercial applications and basic research. An unexplored protease gene sep1A was identified by function-based screening from a plasmid metagenomic library derived from uncultured contaminated agricultural soil microorganisms. The putative protease gene was subcloned into pET-32a (+) vector and overexpressed in E...
April 5, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28380360/the-mutational-landscape-of-circulating-tumor-cells-in-multiple-myeloma
#15
Yuji Mishima, Bruno Paiva, Jiantao Shi, Jihye Park, Salomon Manier, Satoshi Takagi, Mira Massoud, Adriana Perilla-Glen, Yosra Aljawai, Daisy Huynh, Aldo M Roccaro, Antonio Sacco, Marzia Capelletti, Alexandre Detappe, Diego Alignani, Kenneth C Anderson, Nikhil C Munshi, Felipe Prosper, Jens G Lohr, Gavin Ha, Samuel S Freeman, Eliezer M Van Allen, Viktor A Adalsteinsson, Franziska Michor, Jesus F San Miguel, Irene M Ghobrial
The development of sensitive and non-invasive "liquid biopsies" presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs) is prognostic in multiple myeloma (MM), but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28369958/isolation-and-characterization-of-rice-cesium-transporter-genes-from-a-rice-transporter-enriched-yeast-expression-library
#16
Tomohiro Yamaki, Masahiro Otani, Kohei Ono, Takuro Mimura, Koshiro Oda, Takeshi Minamii, Shingo Matsumoto, Yuzy Matsuo, Makoto Kawamukai, Takashi Akihiro
A considerable portion of agricultural land in central-east Japan has been contaminated by radioactive material, particularly radioactive Cs, due to the industrial accident at the Fukushima Daiichi nuclear power plant. Understanding the mechanism of absorption, translocation, and accumulation of Cs(+) in plants will greatly assist in developing approaches to help reduce the radioactive contamination of agricultural products. At present, however, little is known regarding the Cs(+) transporters in rice. A transporter-enriched yeast expression library was constructed and the library was screened for Cs(+) transporter genes...
March 28, 2017: Physiologia Plantarum
https://www.readbyqxmd.com/read/28368392/met-amplification-and-epithelial-to-mesenchymal-transition-exist-as-parallel-resistance-mechanisms-in-erlotinib-resistant-egfr-mutated-nsclc-hcc827-cells
#17
K R Jakobsen, C Demuth, A T Madsen, D Hussmann, J Vad-Nielsen, A L Nielsen, B S Sorensen
Although many epidermal growth factor receptor (EGFR)-mutated lung cancer patients initially benefit from the EGFR-inhibitor erlotinib, all acquire resistance. So far, several mechanisms implicated in resistance have been identified, but the existence of multiple resistance mechanisms in parallel have only been sparsely investigated. In this study, we investigated parallel resistance mechanisms acquired by HCC827, an EGFR-mutated adenocarcinoma cell line dependent on EGFR activity and sensitive to erlotinib...
April 3, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28366542/key-biological-processes-driving-metastatic-spread-of-pancreatic-cancer-as-identified-by-multi-omics-studies
#18
REVIEW
T Y S Le Large, M F Bijlsma, G Kazemier, H M W van Laarhoven, E Giovannetti, C R Jimenez
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood...
March 30, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28363898/there-is-still-a-role-for-cytology-in-the-liquid-biopsy-era-a-lesson-from-a-tki-treated-patient-showing-adenocarcinoma-to-squamous-cell-carcinoma-transition-during-disease-progression
#19
Eduardo Clery, Pasquale Pisapia, Salvatore Feliciano, Elena Vigliar, Antonio Marano, Caterina De Luca, Umberto Malapelle, Giancarlo Troncone, Claudio Bellevicine
Non-small cell lung carcinoma harbouring epidermal growth factor receptor (EGFR) mutation, usually progress after an initial response to tyrosine-kinase inhibitors (TKI). Liquid biopsy enables with a simple blood draw the accurate detection of EGFR p.T790M mutation, the most common resistance mechanism, avoiding the more invasive tissue re-biopsy. However, in a subset of cases, resistance mechanisms are more complex featuring both genetic and morphological changes. Here we report the case of a 67 years-old woman, affected by an EGFR mutated lung adenocarcinoma and treated by TKI...
March 31, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28361688/pysim-sv-a-package-for-simulating-structural-variation-data-with-gc-biases
#20
Yuchao Xia, Yun Liu, Minghua Deng, Ruibin Xi
BACKGROUND: Structural variations (SVs) are wide-spread in human genomes and may have important implications in disease-related and evolutionary studies. High-throughput sequencing (HTS) has become a major platform for SV detection and simulation serves as a powerful and cost-effective approach for benchmarking SV detection algorithms. Accurate performance assessment by simulation requires the simulator capable of generating simulation data with all important features of real data, such GC biases in HTS data and various complexities in tumor data...
March 14, 2017: BMC Bioinformatics
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