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cancer colin

Jun Hao, Xinpei Ci, Hui Xue, Rebecca Wu, Xin Dong, Stephen Yiu Chuen Choi, Haiqing He, Yu Wang, Fang Zhang, Sifeng Qu, Fan Zhang, Anne M Haegert, Peter W Gout, Amina Zoubeidi, Colin Collins, Martin E Gleave, Dong Lin, Yuzhuo Wang
BACKGROUND: Although androgen deprivation therapy is initially effective in controlling growth of hormone-naive prostate cancers (HNPCs) in patients, currently incurable castration-resistant prostate cancer (CRPC) inevitably develops. OBJECTIVE: To identify CRPC driver genes that may provide new targets to enhance CRPC therapy. DESIGN, SETTING, AND PARTICIPANTS: Patient-derived xenografts (PDXs) of HNPCs that develop CRPC following host castration were examined for changes in expression of genes at various time points after castration using transcriptome profiling analysis; particular attention was given to pre-CRPC changes in expression indicative of genes acting as potential CRPC drivers...
March 12, 2018: European Urology
Vincent Plagnol, Samuel Woodhouse, Karen Howarth, Stefanie Lensing, Matt Smith, Michael Epstein, Mikidache Madi, Sarah Smalley, Catherine Leroy, Jonathan Hinton, Frank de Kievit, Esther Musgrave-Brown, Colin Herd, Katherine Baker-Neblett, Will Brennan, Peter Dimitrov, Nathan Campbell, Clive Morris, Nitzan Rosenfeld, James Clark, Davina Gale, Jamie Platt, John Calaway, Greg Jones, Tim Forshew
Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA...
2018: PloS One
Mario Silva, Cornelia M Schaefer-Prokop, Colin Jacobs, Giovanni Capretti, Francesco Ciompi, Bram van Ginneken, Ugo Pastorino, Nicola Sverzellati
OBJECTIVES: The aim of this study was to compare computer-aided diagnosis (CAD) and visual reading for the detection of subsolid nodules (SSNs) in volumetrl measuremic low-dose computed tomography (LDCT) for lung cancer screening. MATERIALS AND METHODS: Prospective visual detection (VD) and manuaent of SSN were performed in the 2303 baseline volumetric LDCTs of the Multicenter Italian Lung Detection trial. Baseline and 2- and 4-year LDCTs underwent retrospective CAD analysis, subsequently reviewed by 2 experienced thoracic radiologists...
March 14, 2018: Investigative Radiology
Maeva Dufies, Damien Ambrosetti, Sonia Boulakirba, Anne Calleja, Coline Savy, Nathan Furstoss, Marwa Zerhouni, Julien Parola, Lazaro Aira-Diaz, Sandrine Marchetti, Francois Orange, Sandra Lacas-Gervais, Frederic Luciano, Arnaud Jacquel, Guillaume Robert, Gilles Pagès, Patrick Auberger
Polo-like kinases (Plks) define a highly conserved family of Ser/Thr kinases with crucial roles in the regulation of cell division. Here we show that Plk1 is cleaved by caspase 3, but not by other caspases in different hematopoietic cell lines treated with competitive inhibitors of the ATP-binding pocket of Plk1. Intriguingly, Plk1 was not cleaved in cells treated with Rigosertib, a non-competitive inhibitor of Plk1, suggesting that binding of the inhibitor to the ATP binding pocket of Plk1 triggers a conformational change and unmasks a cryptic caspase 3 cleavage site on the protein...
February 16, 2018: Oncotarget
Reinier Snetselaar, Matthijs F M van Oosterhout, Jan C Grutters, Coline H M van Moorsel
The enzyme telomerase reverse transcriptase (TERT) is essential for telomere maintenance. In replicating cells, maintenance of telomere length is important for the preservation of vital genetic information and prevention of genomic instability. A common genetic variant in TERT , rs2736100 C/A, is associated with both telomere length and multiple diseases. Carriage of the C allele is associated with longer telomere length, while carriage of the A allele is associated with shorter telomere length. Furthermore, some diseases have a positive association with the C and some with the A allele...
2018: Frontiers in Medicine
Dong-Wook Kim, Keun-Cheol Kim, Kee-Beom Kim, Colin T Dunn, Kwon-Sik Park
The discovery of recurrent alterations in genes encoding transcription regulators and chromatin modifiers is one of the most important recent developments in the study of the small cell lung cancer (SCLC) genome. With advances in models and analytical methods, the field of SCLC biology has seen remarkable progress in understanding the deregulated transcription networks linked to the tumor development and malignant progression. This review will discuss recent discoveries on the roles of RB and P53 family of tumor suppressors and MYC family of oncogenes in tumor initiation and development...
February 2018: Translational Lung Cancer Research
Peter V Deraska, Colin O'Leary, Hunter D Reavis, Shelby Labe, Tru-Khang Dinh, Jean-Bernard Lazaro, Christopher Sweeney, Alan D D'Andrea, David Kozono
Despite optimal chemotherapy, radiotherapy (RT), and/or surgery, non-small-cell lung carcinoma (NSCLC) remains the leading cause of cancer-related death in the US and worldwide. Thoracic RT, a mainstay in the treatment of locally advanced NSCLC, is often restricted in efficacy by a therapeutic index limited by sensitivity of tissues surrounding the malignancy. Therefore, radiosensitizers that can improve the therapeutic index are a vital unmet need. Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization...
December 2018: Cell Death Discovery
Huakang Tu, Colin P Dinney, Yuanqing Ye, H Barton Grossman, Seth P Lerner, Xifeng Wu
Background: Patients with cancer are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification can lead to accumulation of unmetabolized folic acid in the systemic circulation and urine and may promote cancer growth, especially among those with neoplastic alterations. Objective: We investigated the prospective association between synthetic compared with natural folate intake and clinical outcomes in non-muscle-invasive bladder cancer (NMIBC), which is a highly recurrent disease...
February 1, 2018: American Journal of Clinical Nutrition
Coline H M van Moorsel
PURPOSE OF REVIEW: The process of aging involves biological changes that increases susceptibility for disease. In the aging lung disease IPF, GWAS studies identified genes associated with risk for disease. Recently, several of these genes were also found to be involved in risk for COPD or lung cancer. This review describes GWAS-derived risk genes for IPF that overlap with risk genes for lung cancer or COPD. RECENT FINDINGS: Risk genes that overlap between aging lung diseases, include FAM13A, DSP and TERT...
March 6, 2018: Current Opinion in Pulmonary Medicine
Kah Poh Loh, Colin McHugh, Supriya G Mohile, Karen Mustian, Marie Flannery, Heidi Klepin, Rebecca Schnall, Eva Culakova, Erika Ramsdale
PURPOSE OF REVIEW: Older adults with cancer have complex medical needs and often experience higher rates of treatment-related toxicities compared to their younger counterparts. The advent of health information technologies can address multiple gaps in the care of this population. We review the role of existing and emerging technologies in facilitating the use of comprehensive geriatric assessment (CGA) in routine clinics, promoting symptom reporting, and monitoring medication adherence...
March 6, 2018: Current Oncology Reports
Catherine S Grasso, Marios Giannakis, Daniel K Wells, Tsuyoshi Hamada, Xinmeng Jasmine Mu, Michael Quist, Jonathan A Nowak, Reiko Nishihara, Zhi Rong Qian, Kentaro Inamura, Teppei Morikawa, Katsuhiko Nosho, Gabriel Abril-Rodriguez, Charles Connolly, Helena Escuin-Ordinas, Milan S Geybels, William M Grady, Li Hsu, Siwen Hu-Lieskovan, Jeroen R Huyghe, Yeon Joo Kim, Paige E Krystofinski, Mark Dm Leiserson, Dennis J Montoya, Brian B Nadel, Matteo Pellegrini, Colin C Pritchard, Cristina Puig-Saus, Elleanor H Quist, Benjamin J Raphael, Stephen J Salipante, Daniel Sanghoon Shin, Eve Shinbrot, Brian Shirts, Sachet Shukla, Janet L Stanford, Wei Sun, Jennifer Tsoi, Alexander Upfill-Brown, David A Wheeler, Catherine J Wu, Ming Yu, Syed H Zaidi, Jesse M Zaretsky, Stacey B Gabriel, Eric S Lander, Levi A Garraway, Thomas J Hudson, Charles S Fuchs, Antoni Ribas, Shuji Ogino, Ulrike Peters
To understand the genetic drivers of immune recognition and evasion in colorectal cancer (CRC), we analyzed 1,211 CRC primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas CRC cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of CRC, had a high rate of significantly mutated genes in important immune modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy number alterations and copy-neutral loss of heterozygosity (CN-LOH)...
March 6, 2018: Cancer Discovery
Nick A Iarrobino, Beant Gill, Mark E Bernard, Mark V Mishra, Colin E Champ
INTRODUCTION: A growing body of preclinical data suggests that statins may exert potent antitumor effects, yet the interactions of these medications with standard therapies and clinical outcomes in this population is less clear. We assessed the impact of statin use on outcomes in patients with advanced-stage pancreatic adenocarcinoma undergoing various treatments. MATERIALS AND METHODS: After institutional review board approval, we conducted a retrospective-cohort study consisting of 303 newly diagnosed advanced-stage pancreatic adenocarcinoma patients to determine the impact of statin use on outcomes...
March 5, 2018: American Journal of Clinical Oncology
Kah Poh Loh, Jason Zittel, Sindhuja Kadambi, Chintan Pandya, Huiwen Xu, Marie Flannery, Allison Magnuson, Javier Bautista, Colin McHugh, Karen Mustian, William Dale, Paul Duberstein, Supriya G Mohile
OBJECTIVES: Sleep disturbance is prevalent and often coexists with depression, fatigue, and pain in the cancer population. The aim of this study was to describe the prevalence of sleep disturbance with co-existing depression, fatigue, and pain in older patients with cancer. We also examined the associations of several socio-demographic and clinical variables with sleep disturbance. METHODS: This cross-sectional study consisted of 389 older patients with solid and hematologic malignancies who were referred to the Specialized Oncology Care & Research in the Elderly (SOCARE) clinics at the Universities of Rochester and Chicago between May 2011 and October 2015 and completed a sleep and geriatric assessment (that inquires about fatigue, pain, and depression)...
March 2, 2018: Journal of Geriatric Oncology
Manraj N Kaur, Feng Xie, Andrea Shiwcharan, Lisa Patterson, Yaron Shargall, Christian Finley, Colin Schieman, Terry Dalimonte, Christine Fahim, Waël C Hanna
BACKGROUND: The objective of this study is to compare robotic portal (RP) to video-assisted thoracoscopic surgery (VATS) pulmonary resections for early stage non-small cell lung cancer with respect to health care resource utilization during the first year of a robotic surgery program in thoracic oncology. METHODS: Patients who underwent anatomic lung resections using RP (n = 42) or VATS (n = 96) for early stage non-small cell lung cancer between April 2014 and March 2015 at a single institution were identified...
March 2, 2018: Annals of Thoracic Surgery
Li Tang, Nitin Shivappa, James R Hebert, Andy H Lee, Fenglian Xu, Colin W Binns
Diet has been shown to have an effect on both inflammation and oesophageal cancer. This study investigated the association between the dietary inflammatory index (DII®) and the risk of oesophageal cancer in Xinjiang Uyghur Autonomous Region, China. A case-control study was conducted during 2008-2009 in Urumqi and Shihezi. DII scores were calculated based on dietary intake assessed by a validated FFQ administered to 359 incident oesophageal cancer patients and 380 hospital-based controls. Higher DII scores indicate more pro-inflammatory diets...
March 5, 2018: British Journal of Nutrition
Jennifer L F Port, Nathiya Muthalagu, Meera Raja, Fatih Ceteci, Tiziana Monteverde, Bjorn Kruspig, Ann Hedley, Gabriela Kalna, Sergio Lilla, Lisa Neilson, Martina Brucoli, Katarina Gyuraszova, Jacqueline Tait-Mulder, Mokdad Mezna, Silvija Svambaryte, Amy Bryson, David Sumpton, Allan McVie, Colin Nixon, Martin Drysdale, Hiroyasu Esumi, Graeme I Murray, Owen J Sansom, Sara Zanivan, Daniel J Murphy
Exploiting oxidative stress has recently emerged as a plausible strategy for treatment of human Cancer and anti-oxidant defences are implicated in resistance to chemo- and radiotherapy. Targeted suppression of anti-oxidant defences could thus broadly improve therapeutic outcomes. Here we identify the AMPK-related kinase NUAK1 as a key component of the anti-oxidant stress response pathway and reveal a specific requirement for this role of NUAK1 in colorectal cancer. We show that NUAK1 is activated by oxidative stress and that this activation is required to facilitate nuclear import of the anti-oxidant master regulator NRF2: Activation of NUAK1 coordinates PP1β inhibition with AKT activation in order to suppress GSK3β-dependent inhibition of NRF2 nuclear import...
March 2, 2018: Cancer Discovery
Xinpei Ci, Jun Hao, Xin Dong, Stephen Y C Choi, Hui Xue, Rebecca Wu, Sifeng Qu, Peter W Gout, Fang Zhang, Anne M Haegert, Ladan Fazil, Francesco Crea, Christopher J Ong, Amina Zoubedi, Housheng H He, Martin E Gleave, Colin C Collins, Dong Lin, Yuzhuo Wang
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer (PCa) arising mostly from adenocarcinoma via NE transdifferentiation following androgen deprivation therapy. Mechanisms contributing to both NEPC development and its aggressiveness remain elusive. In light of the fact that hyperchromatic nuclei are a distinguishing histopathological feature of NEPC, we utilized transcriptomic analyses of our patient-derived xenograft (PDX) models, multiple clinical cohorts, and genetically engineered mouse models to identify 36 heterochromatin-related genes that are significantly enriched in NEPC...
February 27, 2018: Cancer Research
Richard W Smith, Richard D Moccia, Colin B Seymour, Carmel E Mothersill
Exposure to a single 0.5 Gy X-ray dose of eggs at 48 h after fertilisation (48 h egg), eyed eggs, yolk sac larvae (YSL) and first feeders induces a legacy effect in adult rainbow trout. This includes the transmission of a bystander effect to non-irradiated adult trout which had swam with the irradiated fish. The aim of this study was to investigate this legacy by analysing the gill proteome of these irradiated and bystander fish. Irradiation at all of the early life stages resulted in changes to proteins which play a key role in development but are also known to be anti-tumorigenic and anti-oxidant: upregulation of haemoglobin subunit beta (48 h egg), haemoglobin, serum albumin 1 precursor (eyed eggs), clathrin heavy chain 1 isoform X10 (eyed eggs and first feeders), and actin-related protein 2/3 complex subunit 4 (first feeders), downregulation of pyruvate dehydrogenase, histone 1 (48 h egg), triosephosphate isomerase (TPI), collagen alpha-1(1) chain like proteins (YSL), pyruvate kinase PKM-like protein (YSL and first feeders), ubiquitin-40S ribosomal proteins S27 and eukaryotic translation initiation factor 4 A isoform 1B (first feeders)...
February 17, 2018: Environmental Research
Colin Hockings, Amber E Alsop, Stephanie C Fennell, Erinna F Lee, W Douglas Fairlie, Grant Dewson, Ruth M Kluck
The prosurvival Bcl-2 family proteins Mcl-1 and Bcl-xL inhibit apoptosis by sequestering BH3-only proteins such as Bid and Bim (MODE 1) or the effector proteins Bak and Bax (MODE 2). To better understand the contributions of MODE 1 and MODE 2 in blocking cell death, and thus how to bypass resistance to cell death, we examined prescribed mixtures of Bcl-2 family proteins. In a Bim and Bak mixture, Bcl-xL and Mcl-1 each sequestered not only Bim but also Bak as it became activated by Bim. In contrast, in a Bid and Bak mixture, Bcl-xL preferentially sequestered Bid while Mcl-1 preferentially sequestered Bak...
February 19, 2018: Cell Death and Differentiation
Dong Van Hoang, Andy H Lee, Ngoc Minh Pham, Colin W Binns
Increasing prostate cancer incidence in the Asia-Pacific region may be related to a more sedentary lifestyle resulted from economic growth and rapid urbanization. The present case-control study of 640 men aged 64 to 75 years was conducted in Vietnam between 2013 and 2015 to ascertain the relationship between physical activity and prostate cancer risk, accounting for the duration of sitting time. Reduced prostate cancer risks were found for men engaging in medium (15.8-47.3 metabolic equivalent task [MET]-h/week) and high (>47...
February 1, 2018: Asia-Pacific Journal of Public Health
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