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https://www.readbyqxmd.com/read/28427194/alternative-rna-splicing-of-the-meaf6-gene-facilitates-neuroendocrine-prostate-cancer-progression
#1
Ahn R Lee, Yinan Li, Ning Xie, Martin E Gleave, Michael E Cox, Colin C Collins, Xuesen Dong
Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423762/predicting-the-pathogenic-impact-of-sequence-variation-in-the-human-genome
#2
Mark F Rogers, Hashem A Shihab, Michael Ferlaino, Tom R Gaunt, Colin Campbell
Sequencing data will become widely available in clinical practice within the near future. Uptake of sequence data is currently being stimulated within the UK through the government-funded 100,000 genomes project (Genomics England), with many similar initiatives being planned and supported internationally. The analysis of the large volumes of data derived from sequencing programmes poses a major challenge for data analysis. In this paper we outline progress we have made in the development of predictors for estimating the pathogenic impact of single nucleotide variants, indels and haploinsufficiency in the human genome...
2017: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/28423296/eltrombopag-added-to-standard-immunosuppression-for-aplastic-anemia
#3
Danielle M Townsley, Phillip Scheinberg, Thomas Winkler, Ronan Desmond, Bogdan Dumitriu, Olga Rios, Barbara Weinstein, Janet Valdez, Jennifer Lotter, Xingmin Feng, Marie Desierto, Harshraj Leuva, Margaret Bevans, Colin Wu, Andre Larochelle, Katherine R Calvo, Cynthia E Dunbar, Neal S Young
Background Acquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia...
April 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28422152/towards-automatic-pulmonary-nodule-management-in-lung-cancer-screening-with-deep-learning
#4
Francesco Ciompi, Kaman Chung, Sarah J van Riel, Arnaud Arindra Adiyoso Setio, Paul K Gerke, Colin Jacobs, Ernst Th Scholten, Cornelia Schaefer-Prokop, Mathilde M W Wille, Alfonso Marchianò, Ugo Pastorino, Mathias Prokop, Bram van Ginneken
The introduction of lung cancer screening programs will produce an unprecedented amount of chest CT scans in the near future, which radiologists will have to read in order to decide on a patient follow-up strategy. According to the current guidelines, the workup of screen-detected nodules strongly relies on nodule size and nodule type. In this paper, we present a deep learning system based on multi-stream multi-scale convolutional networks, which automatically classifies all nodule types relevant for nodule workup...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419548/detection-of-prostate-cancer-specific-transcripts-in-extracellular-vesicles-isolated-from-post-dre-urine
#5
Kathryn L Pellegrini, Dattatraya Patil, Kristen J S Douglas, Grace Lee, Kathryn Wehrmeyer, Mersiha Torlak, Jeremy Clark, Colin S Cooper, Carlos S Moreno, Martin G Sanda
BACKGROUND: The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder-specific transcripts and known prostate cancer biomarkers in urine EVs...
April 17, 2017: Prostate
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#6
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414188/a-case-of-splenomegaly-in-cbl-syndrome
#7
Rachel R Coe, Margaret L McKinnon, Maja Tarailo-Graovac, Colin J Ross, Wyeth W Wasserman, Jan M Friedman, Paul C Rogers, Clara D M van Karnebeek
INTRODUCTION: We present a child with unexplained splenomegaly to highlight this feature as a presenting sign of the RASopathy CBL syndrome and to draw attention to the power and utility of next generation genomic sequencing for providing rapid diagnosis and critical information to guide care in the pediatric clinical setting. CLINICAL REPORT: A 7-year-old boy presented with unexplained splenomegaly, attention deficit hyperactivity disorder, mild learning difficulties, easy bruising, mild thrombocytopenia, and subtle dysmorphic features...
April 13, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28412271/impact-of-a-new-distal-attachment-on-colonoscopy-performance-in-an-academic-screening-center
#8
Zacharias P Tsiamoulos, Ravi Misra, Rajaratanam Rameshshanker, Timothy R Elliott, Iosif Beintaris, Siwan Thomas-Gibson, Adam Haycock, Noriko Suzuki, Colin Rees, Brian P Saunders
BACKGROUND AND AIMS: Distal attachments placed on the colonoscope tip may positively affect performance by assisting insertion and polyp detection. The Endocuff-original appears to improve adenoma detection rate, but there are no data assessing the performance of the second generation Endocuff-vision. METHODS: A pilot service evaluation study (April-2013/September-2014) was conducted on patients with positive faecal occult blood tests within the National Bowel Cancer Programme during 3 consecutive periods: pre-cuff/no device used, during-cuff/device used and post-cuff/no device used...
April 12, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28409857/asbestos-asbestosis-and-cancer-the-helsinki-criteria-for-diagnosis-and-attribution-critical-need-for-revision-of-the-2014-update
#9
Xaver Baur, Hans-Joachim Woitowitz, Lygia T Budnik, David Egilman, Christine Oliver, Arthur Frank, Colin L Soskolne, Philip J Landrigan, Richard A Lemen
No abstract text is available yet for this article.
May 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/28408976/when-tads-go-bad-chromatin-structure-and-nuclear-organisation-in-human-disease
#10
REVIEW
Vera B Kaiser, Colin A Semple
Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains...
2017: F1000Research
https://www.readbyqxmd.com/read/28404010/risk-stratification-of-barrett-s-oesophagus-using-a-non-endoscopic-sampling-method-coupled-with-a-biomarker-panel-a-cohort-study
#11
Caryn S Ross-Innes, Hamza Chettouh, Achilleas Achilleos, Nuria Galeano-Dalmau, Irene Debiram-Beecham, Shona MacRae, Petros Fessas, Elaine Walker, Sibu Varghese, Theodore Evan, Pierre S Lao-Sirieix, Maria O'Donovan, Shalini Malhotra, Marco Novelli, Babett Disep, Phillip V Kaye, Laurence B Lovat, Rehan Haidry, Michael Griffin, Krish Ragunath, Pradeep Bhandari, Adam Haycock, Danielle Morris, Stephen Attwood, Anjan Dhar, Colin Rees, Matt D Rutter, Richard Ostler, Benoit Aigret, Peter D Sasieni, Rebecca C Fitzgerald
BACKGROUND: Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up. METHODS: In this multicentre cohort study (BEST2), patients with Barrett's oesophagus underwent the Cytosponge test before their surveillance endoscopy...
January 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28401142/comprehensive-survey-of-household-radon-gas-levels-and-risk-factors-in-southern-alberta
#12
Fintan K T Stanley, Siavash Zarezadeh, Colin D Dumais, Karin Dumais, Renata MacQueen, Fiona Clement, Aaron A Goodarzi
BACKGROUND: The inhalation of naturally occurring radon (222Rn) gas from indoor air exposes lung tissue to α-particle bombardment, a highly mutagenic form of ionizing radiation that damages DNA and increases the lifetime risk of lung cancer. We analyzed household radon concentrations and risk factors in southern Alberta, including Calgary, the third-largest Canadian metropolis. METHODS: A total of 2382 residential homes (2018 in Calgary and 364 in surrounding townships) from an area encompassing 82% of the southern Alberta population were tested for radon, per Health Canada guidelines, for at least 90 days (median 103 d) between 2013 and 2016...
January 2017: CMAJ Open
https://www.readbyqxmd.com/read/28362549/cd8-t-cell-mediated-anti-malaria-protection-induced-by-malaria-vaccines-assessment-of-hepatic-cd8-t-cells-by-scbc-assay
#13
Jing Zhou, Alaina Kaiser, Colin Ng, Rachel Karcher, Tim McConnell, Patrick Paczkowski, Cristina Fernandez, Min Zhang, Sean Mackay, Moriya Tsuji
Malaria is a severe infectious disease with relatively high mortality, thus having been a scourge of humanity. There are a few candidate malaria vaccines that have shown a protective efficacy in humans against malaria. One of the candidate human malaria vaccines, which is based on human malaria sporozoites and called PfSPZ Vaccine, has been shown to protect a significant proportion of vaccine recipients from getting malaria. PfSPZ Vaccine elicits a potent response of hepatic CD8+ T cells that are specific for malaria antigens in non-human primates...
March 31, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28348409/inhibiting-the-system-xc-glutathione-axis-selectively-targets-cancers-with-mutant-p53-accumulation
#14
David S Liu, Cuong P Duong, Sue Haupt, Karen G Montgomery, Colin M House, Walid J Azar, Helen B Pearson, Oliver M Fisher, Matthew Read, Glen R Guerra, Ygal Haupt, Carleen Cullinane, Klas G Wiman, Lars Abrahmsen, Wayne A Phillips, Nicholas J Clemons
TP53, a critical tumour suppressor gene, is mutated in over half of all cancers resulting in mutant-p53 protein accumulation and poor patient survival. Therapeutic strategies to target mutant-p53 cancers are urgently needed. We show that accumulated mutant-p53 protein suppresses the expression of SLC7A11, a component of the cystine/glutamate antiporter, system xC(-), through binding to the master antioxidant transcription factor NRF2. This diminishes glutathione synthesis, rendering mutant-p53 tumours susceptible to oxidative damage...
March 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28344874/high-baseline-levels-of-interleukin-8-in-leukocytes-and-urine-predict-tumor-recurrence-in-non-muscle-invasive-bladder-cancer-patients-receiving-bacillus-calmette-guerin-therapy-a-long-term-survival-analysis
#15
Kai Qu, Jian Gu, Yuanqing Ye, Stephen B Williams, Colin P Dinney, Xifeng Wu, Ashish Kamat
Bacillus Calmette-Guerin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC) can significantly reduce the risk of recurrence and progression. However, BCG therapy may fail in up to a half of treated patients and may also cause toxicities. Biomarkers to predict the effectiveness of BCG therapy are desired to pre-select patients for BCG therapy to maximize efficacy while avoid unnecessary toxicity. Twelve cytokines were measured in 100 blood and 112 urine samples using cytokine antibody array and correlated with recurrence-free survival in overall and BCG-treated NMIBC patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28339311/lung-rads-category-4x-does-it-improve-prediction-of-malignancy-in-subsolid-nodules
#16
Kaman Chung, Colin Jacobs, Ernst T Scholten, Jin Mo Goo, Helmut Prosch, Nicola Sverzellati, Francesco Ciompi, Onno M Mets, Paul K Gerke, Mathias Prokop, Bram van Ginneken, Cornelia M Schaefer-Prokop
Purpose To evaluate the added value of Lung CT Screening Reporting and Data System (Lung-RADS) assessment category 4X over categories 3, 4A, and 4B for differentiating between benign and malignant subsolid nodules (SSNs). Materials and Methods SSNs on all baseline computed tomographic (CT) scans from the National Lung Cancer Trial that would have been classified as Lung-RADS category 3 or higher were identified, resulting in 374 SSNs for analysis. An experienced screening radiologist volumetrically segmented all solid cores and located all malignant SSNs visible on baseline scans...
March 24, 2017: Radiology
https://www.readbyqxmd.com/read/28334730/examining-the-common-aetiology-of-serous-ovarian-cancers-and-basal-like-breast-cancers-using-double-primaries
#17
Colin B Begg, Megan S Rice, Emily C Zabor, Shelley S Tworoger
BACKGROUND: The somatic molecular profiles of basal-like breast cancers and high-grade serous ovarian cancers share many similarities, leading to the hypothesis that they have similar aetiologies, in which case they should occur together in the same patient more often than expected. METHODS: We identified 545 women with double independent primary cancers of the breast and ovary reported to the California Cancer Registry from 1999 to 2013 and examined the coincidence of subtype combinations...
April 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28330676/stromal-gene-expression-is-predictive-for-metastatic-primary-prostate-cancer
#18
Fan Mo, Dong Lin, Mandeep Takhar, Varune Rohan Ramnarine, Xin Dong, Robert H Bell, Stanislav V Volik, Kendric Wang, Hui Xue, Yuwei Wang, Anne Haegert, Shawn Anderson, Sonal Brahmbhatt, Nicholas Erho, Xinya Wang, Peter W Gout, James Morris, R Jeffrey Karnes, Robert B Den, Eric A Klein, Edward M Schaeffer, Ashley Ross, Shancheng Ren, S Cenk Sahinalp, Yingrui Li, Xun Xu, Jun Wang, Jian Wang, Martin E Gleave, Elai Davicioni, Yinghao Sun, Yuzhuo Wang, Colin C Collins
BACKGROUND: Clinical grading systems using clinical features alongside nomograms lack precision in guiding treatment decisions in prostate cancer (PCa). There is a critical need for identification of biomarkers that can more accurately stratify patients with primary PCa. OBJECTIVE: To identify a robust prognostic signature to better distinguish indolent from aggressive prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: To develop the signature, whole-genome and whole-transcriptome sequencing was conducted on five PCa patient-derived xenograft (PDX) models collected from independent foci of a single primary tumor and exhibiting variable metastatic phenotypes...
March 19, 2017: European Urology
https://www.readbyqxmd.com/read/28329761/somatic-mutations-reveal-asymmetric-cellular-dynamics-in-the-early-human-embryo
#19
Young Seok Ju, Inigo Martincorena, Moritz Gerstung, Mia Petljak, Ludmil B Alexandrov, Raheleh Rahbari, David C Wedge, Helen R Davies, Manasa Ramakrishna, Anthony Fullam, Sancha Martin, Christopher Alder, Nikita Patel, Steve Gamble, Sarah O'Meara, Dilip D Giri, Torril Sauer, Sarah E Pinder, Colin A Purdie, Åke Borg, Henk Stunnenberg, Marc van de Vijver, Benita K T Tan, Carlos Caldas, Andrew Tutt, Naoto T Ueno, Laura J van 't Veer, John W M Martens, Christos Sotiriou, Stian Knappskog, Paul N Span, Sunil R Lakhani, Jórunn Erla Eyfjörd, Anne-Lise Børresen-Dale, Andrea Richardson, Alastair M Thompson, Alain Viari, Matthew E Hurles, Serena Nik-Zainal, Peter J Campbell, Michael R Stratton
Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28325079/dietary-guidelines-for-the-asia-pacific-region
#20
Colin W Binns, Mi Kyung Lee, Masaharu Kagawa, Wah Yun Low, Qiu Liqian, Georgia S Guldan, Tomiko Hokama, Keiko Nanishi, Sreymom Oy, Li Tang, Alfred Zerfas
Nutrition is a major determinant of health throughout all stages of life and together with smoking is the most important risk factor for morbidity and mortality in the Asia Pacific Region. The workshop participants examined Dietary Guidelines and Food Guides that are in use in our region, together with additional materials from the World Health Organization, UNICEF and the World Cancer Research Foundation. The resulting set of guidelines is meant as a reminder of the main issues to be covered in a general public health education program...
March 2017: Asia-Pacific Journal of Public Health
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