3,775,929 results match your criteria Cancer Associated and Related Autoimmune Retinopathies


Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. An alternative pathway for ATR activation has been proposed to occur via stalled RNA polymerase II (RNAPII). However, how RNAPII might signal to activate ATR remains unknown. Read More

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December 2018

Predictive Value of Preoperative Magnetic Resonance Imaging Findings for Survival and Local Recurrence in Patients Undergoing En Bloc Resection of Sacral Chordomas.

Neurosurgery 2018 Dec 12. Epub 2018 Dec 12.

Department of Neurological Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Few studies have assessed the prognostic importance of preoperative magnetic resonance imaging (MRI) scan findings in patients undergoing en bloc resection of sacral chordomas.

Objective: To (1) report in-depth imaging characteristics of sacral chordomas, (2) describe the patterns of local and distant recurrence, and (3) determine imaging predictors of overall survival (OS) and local recurrence (LR).

Methods: This retrospective case series was obtained from a prospectively maintained spine database from 1995 to 2016. Read More

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December 2018

Altered sleep architecture, rapid eye movement (REM) sleep, and neural oscillation in a mouse model of human chromosome 16p11.2 microdeletion.

Sleep 2018 Dec 12. Epub 2018 Dec 12.

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA.

Sleep abnormalities are common among children with neurodevelopmental disorders. The human chr16p11.2 microdeletion is associated with a range of neurological and neurobehavioral abnormalities. Read More

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December 2018
2 Reads

A population-based cohort study to evaluate the effectiveness of lung cancer screening using low-dose CT in Hitachi city, Japan.

Jpn J Clin Oncol 2018 Dec 12. Epub 2018 Dec 12.

Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.

Objectives: To evaluate the effectiveness of lung cancer screening using low-dose computed tomography for the general population, we conducted a retrospective cohort study of screening for participants among Hitachi residents.

Materials And Methods: Citizens aged 50-74 who underwent low-dose computed tomography screening at least once during 1998-2006 were defined as the computed tomography group, and those who underwent X-ray screening at least once during the same period, but did not receive low-dose computed tomography screening throughout the follow-up period, were defined as the XP group. We investigated the lung cancer incidence rate, mortality rate and all-cause mortality rate for both groups from the first lung cancer screening to the end of 2012. Read More

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December 2018

Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.

Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m1A) and 3-methylcytidine (m3C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. Read More

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December 2018

Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial.

Am J Clin Nutr 2018 Dec;108(6):1249-1258

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, School of Medicine, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.

Background: Previous in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium dependent. Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality. According to NHANES, 79% of US adults do not meet their Recommended Dietary Allowance of magnesium. Read More

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December 2018

In Vivo Imaging With Confirmation by Histopathology for Increased Rigor and Reproducibility in Translational Research: A Review of Examples, Options, and Resources.

ILAR J 2018 Dec 12. Epub 2018 Dec 12.

Department of Radiology, Miller Research Building Molecular Imaging Service Center, Johns Hopkins University, Baltimore, Maryland.

Preclinical noninvasive imaging can be an indispensable tool for studying animal models of disease. In vivo imaging to assess anatomical, functional, and molecular features requires verification by a comparison to the macroscopic and microscopic morphological features, since all noninvasive in vivo imaging methods have much lower resolution than standard histopathology. Comprehensive pathological evaluation of the animal model is underutilized; yet, many institutions have veterinary or human pathologists with necessary comparative pathology expertise. Read More

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December 2018

Associations between general practice characteristics with use of urgent referrals for suspected cancer and endoscopies: a cross-sectional ecological study.

Fam Pract 2018 Dec 12. Epub 2018 Dec 12.

The Health Improvement Institute (THIS), University of Cambridge, Cambridge, UK.

Background: Large variation in measures of diagnostic activity has been described previously between English general practices, but related predictors remain understudied.

Objective: To examine associations between general practice population and characteristics, with the use of urgent referrals for suspected cancer, and use of endoscopy.

Methods: Cross-sectional observational study of English general practices. Read More

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December 2018

Targeting cervical cancer campaigns on teenage high schoolers in resource-limited economies: lessons from an intervention study of Nigerian senior secondary school girls.

Fam Pract 2018 Dec 12. Epub 2018 Dec 12.

Department of Community Medicine and Primary Healthcare, Chukwuemeka Odumegwu Ojukwu University/University Teaching Hospital, Awka, Nigeria.

Background: Given the dearth of government-sponsored programmes, preventive lifestyles and practices are the realistic hopes for millions of women in developing countries against cervical cancer. Early interventions for teenage high school girls have been advocated recently, but evidence-base for sustainable activities at this demographic is lacking. This article reduces this gap by determining the impact of two cervical cancer education techniques. Read More

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December 2018

Cancer stem cells in relation to treatment.

Jpn J Clin Oncol 2018 Dec 12. Epub 2018 Dec 12.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

The classical cancer therapies, including chemotherapy and radiation therapy, can initially show good results and tumor shrinkage; however, for most cancer patients disease recurrence is a common event. This tumor regrowth following therapy is now thought to depend on a small population of cancer stem cells (CSCs), which, similar to other stem cells, have the capacity for self-renewal and multipotent differentiation. Cancer stem cells have been identified based on cell surface protein expression in many tumor types, and for all diseases studied, this specific cell population is required for serial transplantation in animal models. Read More

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December 2018

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.

Authors:
Naomi Walsh Han Zhang Paula L Hyland Qi Yang Evelina Mocci Mingfeng Zhang Erica J Childs Irene Collins Zhaoming Wang Alan A Arslan Laura Beane-Freeman Paige M Bracci Paul Brennan Federico Canzian Eric J Duell Steven Gallinger Graham G Giles Michael Goggins Gary E Goodman Phyllis J Goodman Rayjean J Hung Charles Kooperberg Robert C Kurtz Núria Malats Loic LeMarchand Rachel E Neale Sara H Olson Ghislaine Scelo Xiao O Shu Stephen K Van Den Eeden Kala Visvanathan Emily White Wei Zheng Demetrius Albanes Gabriella Andreotti Ana Babic William R Bamlet Sonja I Berndt Ayelet Borgida Marie-Christine Boutron-Ruault Lauren Brais Paul Brennan Bas Bueno-de-Mesquita Julie Buring Kari G Chaffee Stephen Chanock Sean Cleary Michelle Cotterchio Lenka Foretova Charles Fuchs J Michael M Gaziano Edward Giovannucci Michael Goggins Thilo Hackert Christopher Haiman Patricia Hartge Manal Hasan Kathy J Helzlsouer Joseph Herman Ivana Holcatova Elizabeth A Holly Robert Hoover Rayjean J Hung Vladimir Janout Eric A Klein Robert C Kurtz Daniel Laheru I-Min Lee Lingeng Lu Núria Malats Satu Mannisto Roger L Milne Ann L Oberg Irene Orlow Alpa V Patel Ulrike Peters Miquel Porta Francisco X Real Nathaniel Rothman Howard D Sesso Gianluca Severi Debra Silverman Oliver Strobel Malin Sund Mark D Thornquist Geoffrey S Tobias Jean Wactawski-Wende Nick Wareham Elisabete Weiderpass Nicolas Wentzensen William Wheeler Herbert Yu Anne Zeleniuch-Jacquotte Peter Kraft Donghui Li Eric J Jacobs Gloria M Petersen Brian M Wolpin Harvey A Risch Laufey T Amundadottir Kai Yu Alison P Klein Rachael Z Stolzenberg-Solomon

J Natl Cancer Inst 2018 Dec 12. Epub 2018 Dec 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.

Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. Read More

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December 2018

Multicenter experience with large panel next-generation sequencing in patients with advanced solid cancers in Japan.

Jpn J Clin Oncol 2018 Dec 12. Epub 2018 Dec 12.

Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan.

Background: Application of next-generation DNA sequencing (NGS) has recently become increasingly common in the field of clinical oncology in several countries around the world. In Japan also, a system for applying NGS to routine clinical practice is gradually being established. During this process, we introduced in Japan the tumor-profiling MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) assay. Read More

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December 2018

TNM classification of malignant tumors (Breast Cancer Study Group).

Jpn J Clin Oncol 2018 Dec 12. Epub 2018 Dec 12.

Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

The eighth editions of the primary tumor, lymph node and metastasis classifications for breast cancer issued by the American Joint Commission of Cancer and the Union for International Cancer Control were revised in 2017. The major change made by the American Joint Commission of Cancer is to incorporate biological factors such as estrogen and progesterone receptor, human epidermal growth factor receptor 2, histological grade and multigene prognostic assays, into the staging system. Tumor biomarkers and low recurrence scores confirmed by multigene prognostic assays change the staging. Read More

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December 2018

A robust pipeline with high replication rate for detection of somatic variants in the adaptive immune system as a source of common genetic variation in autoimmune disease.

Hum Mol Genet 2018 Dec 12. Epub 2018 Dec 12.

KU Leuven - Department of Neurosciences, Laboratory for Neuroimmunology, B-3000 Leuven, Belgium.

The role of somatic variants in diseases beyond cancer is increasingly being recognized, with potential roles in autoinflammatory and autoimmune diseases. However, as mutation rates and allele fractions are lower, studies in these diseases are substantially less tolerant of false positives and bio-informatics algorithms require high replication rates. We developed a pipeline combining two variant callers, MuTect2 and VarScan2, with technical filtering and prioritization. Read More

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December 2018

Safety Considerations When Working with Humanized Animals.

ILAR J 2018 Dec 12. Epub 2018 Dec 12.

Unit for Laboratory Animal Medicine, University of Michigan Medical School in Ann Arbor, Michigan.

Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized mice like those injected with human CD34+ hematopoietic stem cells and patient-derived xenografts. Read More

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December 2018

Thyroid Sequelae of Pediatric Cancer Therapy.

Horm Res Paediatr 2018 Dec 12:1-14. Epub 2018 Dec 12.

The hypothalamic-pituitary-thyroid axis is a common site of unintended, acquired disease either during or after the treatment of cancer. Children treated with external radiation therapy are at the highest risk for developing a thyroid-related late effect, but thyroid dysfunction and second primary thyroid neoplasms can also occur after treatment with radiopharmaceutical agents such as 131I-metaiodobenzylguanidine. Increasingly recognized is the development of early thyroid dysfunction as an off-target consequence of the more novel cancer therapeutics such as the tyrosine kinase inhibitors and immune checkpoint inhibitors. Read More

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December 2018
1 Read

Influence of Nutritional Management and Rehabilitation on Physical Outcome in Japanese Intensive Care Unit Patients: A Multicenter Observational Study.

Ann Nutr Metab 2018 Dec 12;74(1):35-43. Epub 2018 Dec 12.

Emergency and Critical Care Medicine, Tokushima University Graduate School, Tokushima, Japan.

Background: There is lack of evidence regarding nutritional management among intensive care unit (ICU) patients in a population with relatively low body mass index. Therefore, we conducted an observational study to assess the nutritional management in Japanese ICUs. Also, we investigated the impact of nutritional management and rehabilitation on physical outcome. Read More

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December 2018

The Actual Prevalence of Symptoms in Pancreatic Cystic Neoplasms: A Prospective Propensity Matched Cohort Analysis.

Dig Surg 2018 Dec 12:1-8. Epub 2018 Dec 12.

Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona,

Background: The prevalence of symptoms in pancreatic cystic neoplasms (PCNs) is mainly based on retrospective surgical series. The aim of this study is to describe the actual prevalence of symptoms in PCNs under surveillance.

Methods: Patients with PCNs under surveillance observed from 2015 to 2017 were submitted to magnetic resonance imaging (MRI) and a specific interview. Read More

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December 2018

Accuracy and Pitfalls in the Assessment of Early Gastrointestinal Lesions.

Dig Dis 2018 Dec 12:1-10. Epub 2018 Dec 12.

Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.

Superficial neoplastic lesions of the digestive tract are usually asymptomatic, and often represent incidental findings on endoscopy. The Paris Classification was developed for the systematic evaluation of superficial lesions of the oesophagus, stomach and colon. The significance of this classification in clinical practice is that it allows the depth of invasion to be estimated. Read More

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December 2018
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A Matched Analysis on the Prognostic Impact of Race on Survival Endpoints of Women with Early-Stage Endometrial Cancer.

Gynecol Obstet Invest 2018 Dec 12:1-7. Epub 2018 Dec 12.

Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan,

Objective: To compare survival endpoints between African American (AA) and non-AA (NAA) women with endometrial carcinoma (EC) stage I-II using a robust matching analysis.

Methods And Materials: Patients were matched by stage, grade, adjuvant management (surveillance, vaginal brachytherapy or pelvic radiation treatment), age, and year of hysterectomy. Recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were calculated. Read More

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December 2018

CpG Island Methylator Phenotype May Predict Poor Overall Survival of Patients with Stage IV Colorectal Cancer.

Oncology 2018 Dec 12:1-8. Epub 2018 Dec 12.

Department of Oncology, National Taiwan University Hospital, Taipei City,

Objective: We aimed to study the prognostic role of CpG island methylator phenotype (CIMP) in patients with different stages of colorectal cancer (CRC).

Material And Methods: We analyzed CIMP in stage I-IV CRC specimens from patients who were diagnosed between 2005 and 2013. CIMP status was determined using a 5-gene MethyLight-based assay. Read More

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December 2018

How Online Family History Tool Design and Message Content Impact User Perceptions: An Examination of Family HealthLink.

Public Health Genomics 2018 Dec 12:1-14. Epub 2018 Dec 12.

Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.

Background: Family health history tools have the ability to improve health outcomes and promote patient-provider communication, but some research suggests their effectiveness is limited. Tool design features may heavily influence users' perceptions of the tools.

Aims: This study provides a summative evaluation of the Family HealthLink tool, which assesses cancer and coronary heart disease risk based on personal and family health history, to better understand how tool design and message content impact user perceptions. Read More

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December 2018

A recursive ensemble organ segmentation (REOS) framework: application in brain radiotherapy.

Phys Med Biol 2018 Dec 12. Epub 2018 Dec 12.

Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, TX 75235, Dallas, Texas, 75205, UNITED STATES.

The aim of this work is to develop a novel recursive ensemble OARs segmentation (REOS) framework for accurate organs-at-risk (OARs) automatic segmentation. The REOS recursively segment individual OARs by ensembling images features extracted from an organ localization module and a contour detection module. Both modules are based on a 3D U-Net architecture. Read More

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December 2018
1 Read

Self-assembled CpG oligodeoxynucleotides conjugated hollow gold nanospheres to enhance cancer-associated immunostimulation.

Colloids Surf B Biointerfaces 2018 Dec 3;175:248-255. Epub 2018 Dec 3.

Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, PR China. Electronic address:

To realize efficiently cellular uptake and enhance the immunostimulation, thiolated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) were self-assembled on hollow gold nanospheres (HGNs) to form CpG-HGNs. The cellular uptake of CpG-HGNs in immune cells was studied in RAW 264.7 cells. Read More

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December 2018

Photothermally controlled drug release system with high dose loading for synergistic chemo-photothermal therapy of multidrug resistance cancer.

Colloids Surf B Biointerfaces 2018 Dec 5;175:239-247. Epub 2018 Dec 5.

Laboratory of Environmental Sciences and Technology, Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, Urumqi, Xinjiang 830011, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address:

Chemotherapy is an important first-line strategy for tumor therapy in cancer treatment, but multidrug resistance (MDR) is a major problem that reduces the efficacy of chemotherapeutics. Herein, we report a novel photothermally controlled intelligent drug release system (AuNP@mSiO-DOX-FA) with a large amount of drugs loading for synergistic chemo-photothermal therapy of MDR in breast cancer. The nanoplatform utilized gold nanoparticles as a hyperthermia core, and large-mesoporous silica as a shell for doxorubicin (DOX) loading. Read More

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December 2018

A Renewable Source of Human Beige Adipocytes for Development of Therapies to Treat Metabolic Syndrome.

Cell Rep 2018 Dec;25(11):3215-3228.e9

Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA; School of Biomedical Sciences and Engineering, The University of Maine, Orono, ME 04469, USA; Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA. Electronic address:

Molecular- and cellular-based therapies have the potential to reduce obesity-associated disease. In response to cold, beige adipocytes form in subcutaneous white adipose tissue and convert energy stored in metabolic substrates to heat, making them an attractive therapeutic target. We developed a robust method to generate a renewable source of human beige adipocytes from induced pluripotent stem cells (iPSCs). Read More

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December 2018
1 Read

Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells.

Cell Rep 2018 Dec;25(11):3047-3058.e4

Biozentrum, University of Basel, 4056 Basel, Switzerland. Electronic address:

Highly glycolytic cancer cells prevent intracellular acidification by excreting the glycolytic end-products lactate and H via the monocarboxylate transporters 1 (MCT1) and 4 (MCT4). We report that syrosingopine, an anti-hypertensive drug, is a dual MCT1 and MCT4 inhibitor (with 60-fold higher potency on MCT4) that prevents lactate and H efflux. Syrosingopine elicits synthetic lethality with metformin, an inhibitor of mitochondrial NADH dehydrogenase. Read More

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December 2018

Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis.

Cell Rep 2018 Dec;25(11):3036-3046.e6

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA. Electronic address:

IL-10 functions as a suppressor of colitis and colitis-associated colon cancer, but it is also a risk locus associated with ulcerative colitis. The mechanism underlying the contrasting roles of IL-10 in inflammation and colon cancer is unknown. We report here that inflammation induces the accumulation of CD11bGr1 myeloid-derived suppressor cells (MDSCs) that express high levels of IL-10 in colon tissue. Read More

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December 2018

IGFBP7 Induces Differentiation and Loss of Survival of Human Acute Myeloid Leukemia Stem Cells without Affecting Normal Hematopoiesis.

Cell Rep 2018 Dec;25(11):3021-3035.e5

Department of Hematology, Cancer Center Amsterdam (CCA), Amsterdam UMC, VU Medical Center, Amsterdam, the Netherlands. Electronic address:

Leukemic stem cells (LSCs) are thought to be the major cause of the recurrence of acute myeloid leukemia (AML) due to their potential for self-renewal. To identify therapeutic strategies targeting LSCs, while sparing healthy hematopoietic stem cells (HSCs), we performed gene expression profiling of LSCs, HSCs, and leukemic progenitors all residing within the same AML bone marrow and identified insulin-like growth factor-binding protein 7 (IGFBP7) as differentially expressed. Low IGFBP7 is a feature of LSCs and is associated with reduced chemotherapy sensitivity. Read More

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December 2018
2 Reads

KLF4, A Gene Regulating Prostate Stem Cell Homeostasis, Is a Barrier to Malignant Progression and Predictor of Good Prognosis in Prostate Cancer.

Cell Rep 2018 Dec;25(11):3006-3020.e7

Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA; Department of Urology, NYU School of Medicine, New York, NY 10016, USA. Electronic address:

There is a considerable need to identify those individuals with prostate cancer who have indolent disease. We propose that genes that control adult stem cell homeostasis in organs with slow turnover, such as the prostate, control cancer fate. One such gene, KLF4, overexpressed in murine prostate stem cells, regulates their homeostasis, blocks malignant transformation, and controls the self-renewal of tumor-initiating cells. Read More

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December 2018

Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli Are Altered with Age.

Cell Rep 2018 Dec;25(11):2992-3005.e5

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address:

Long-term hematopoietic stem cells (LT-HSCs) maintain hematopoietic output throughout an animal's lifespan. However, with age, the balance is disrupted, and LT-HSCs produce a myeloid-biased output, resulting in poor immune responses to infectious challenge and the development of myeloid leukemias. Here, we show that young and aged LT-HSCs respond differently to inflammatory stress, such that aged LT-HSCs produce a cell-intrinsic, myeloid-biased expression program. Read More

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December 2018

PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.

Cell Rep 2018 Dec;25(11):2972-2980.e5

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

PARP inhibitors have shown promising clinical activities for patients with BRCA mutations and are changing the landscape of ovarian cancer treatment. However, the therapeutic mechanisms of action for PARP inhibition in the interaction of tumors with the tumor microenvironment and the host immune system remain unclear. We find that PARP inhibition by olaparib triggers robust local and systemic antitumor immunity involving both adaptive and innate immune responses through a STING-dependent antitumor immune response in mice bearing Brca1-deficient ovarian tumors. Read More

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December 2018
1 Read

Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA.

Cell Rep 2018 Dec;25(11):2955-2962.e3

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Double homeobox (DUX) transcription factors are unique to eutherian mammals. DUX4 regulates expression of repetitive elements during early embryogenesis, but misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and translocations overexpressing the DUX4 double homeodomain cause B cell leukemia. Here, we report the crystal structure of the tandem homeodomains of DUX4 bound to DNA. Read More

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December 2018
2 Reads

SIRT7-Dependent Deacetylation of Fibrillarin Controls Histone H2A Methylation and rRNA Synthesis during the Cell Cycle.

Cell Rep 2018 Dec;25(11):2946-2954.e5

Molecular Biology of the Cell II, German Cancer Research Centre (DKFZ), DKFZ-Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH) Alliance, 69120 Heidelberg, Germany. Electronic address:

Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2'-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7. Read More

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December 2018

Phosphatidyl Inositol 3-Kinase (PI3K)-mTOR Inhibitor PKI-402 Inhibits Breast Cancer Induced Osteolysis.

Cancer Lett 2018 Dec 9. Epub 2018 Dec 9.

Department of Orthopedics, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China, 515041. Electronic address:

Bone metastasis causes bone pain and pathological bone fracture in breast cancer patients with a serious complication. Previous studies have demonstrated that a novel phosphatidyl inositol 3-kinase (PI3K)-mTOR inhibitor PKI-402 suppressed the growth of breast cancer cells. However, the role of PKI-402 involved in osteolysis induced by breast cancer remains unclear. Read More

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December 2018

Conformational stability and dynamics of the cancer-associated isoform Δ133p53β are modulated by p53 peptides and p53-specific DNA.

FASEB J 2018 Dec 12:fj201801973R. Epub 2018 Dec 12.

Basic Science Program, Leidos Biomedical Research, Inc., Cancer and Inflammation Program, National Cancer Institute, Frederick, Maryland, USA; and.

p53 is a tumor suppressor protein that maintains genome stability, but its Δ133p53β and Δ160p53β isoforms promote breast cancer cell invasion. The sequence truncations in the p53 core domain raise key questions related to their physicochemical properties, including structural stabilities, interaction mechanisms, and DNA-binding abilities. Herein, we investigated the conformational dynamics of Δ133p53β and Δ160p53β with and without binding to p53-specific DNA by using molecular dynamics simulations. Read More

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December 2018

An unusual presentation of papillary thyroid carcinoma in a pediatric patient: A case report.

Ear Nose Throat J 2018 Dec;97(12):E7-E10

University of Arizona College of Medicine - Tucson, 1501 N. Campbell Ave., PO Box 245017, Tucson, AZ 85724, USA.

Cystic neck masses in the pediatric population are common but rarely concerning for malignancy. Given this typically benign nature, they are frequently managed conservatively. Here we present an unusual case of a waxing and waning cystic neck mass in a pediatric patient. Read More

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December 2018
1 Read

[Oral contraception and the risk of breast cancer. Review of the literature].

Magy Onkol 2018 Dec 10;62(4):258-263. Epub 2018 Sep 10.

Uzsoki Utcai Kórház, Fõvárosi Onkoradiológiai Központ, Budapest, Hungary.

At present an estimated hundred millions of women worldwide use oral contraception, but the influence of hormonal contraception on carcinogenesis of breast is not fully understood. Previous studies of breast cancer risk show inconsistent findings - from zero elevation to approximately 30%-40% increase in risk. The beneficial effect on ovarian and endometrial cancer risk is apparent. Read More

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December 2018

[Clinical results of combined intracavitary-interstitial image-guided adaptive brachytherapy in locally advanced cervical cancer].

Magy Onkol 2018 Dec 10;62(4):249-257. Epub 2018 Aug 10.

Onkológiai Tanszék, Semmelweis Egyetem, Általános Orvostudományi Kar, Budapest, Hungary.

We present the early clinical results achieved with image-guided adaptive brachytherapy (IGABT) with combined intracavitary-interstitial (IC-IS) technique recently implemented in Hungary in the treatment of locally advanced cervical cancer (LACC). Twenty-one patients were treated with radio-chemotherapy (RCT) followed by combined IC-IS BT. At the end of the RCT we assessed the residual tumour with pelvic MRI. Read More

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December 2018

[Dosimetric evaluation of intracavitary-interstitial image-guided adaptive brachytherapy of cervical cancer and comparison with conventional treatment techniques].

Magy Onkol 2018 Dec 31;62(4):242-248. Epub 2018 Aug 31.

Onkológiai Tanszék, Semmelweis Egyetem, Általános Orvostudományi Kar, Budapest, Hungary.

Our aim was the dosimetric evaluation of intracavitary-interstitial high-dose-rate image-guided adaptive cervix brachytherapy, implemented in Hungary. Between 2016 and 2018, 21 patients with cervical cancer were treated with overall 72 fractions. Graphical optimized treatment plans were compared to inverse optimized plans, 3D optimized plans (without needles) and conventional intracavitary 2D plans. Read More

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December 2018

Improved multilineage human hematopoietic reconstitution and function in NSGS mice.

PLoS One 2018 12;13(12):e0209034. Epub 2018 Dec 12.

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.

Genetic manipulation of NOD/SCID (NS) mice has yielded numerous sub-strains with specific traits useful for the study of human hematopoietic xenografts, each with unique characteristics. Here, we have compared the engraftment and output of umbilical cord blood (UCB) CD34+ cells in four immune-deficient strains: NS, NS with additional IL2RG knockout (NSG), NS with transgenic expression of human myeloid promoting cytokines SCF, GM-CSF, and IL-3 (NSS), and NS with both IL2RG knockout and transgenic cytokine expression (NSGS). Overall engraftment of human hematopoietic cells was highest in the IL2RG knockout strains (NSG and NSGS), while myeloid cell output was notably enhanced in the two strains with transgenic cytokine expression (NSS and NSGS). Read More

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December 2018
2 Reads

Clinical outcomes of bortezomib-based therapy in myeloma.

PLoS One 2018 12;13(12):e0208920. Epub 2018 Dec 12.

Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.

Bortezomib, a first generation proteasome inhibitor, is used in both newly diagnosed and relapsed myeloma settings. Considerable differences exist in the usage of bortezomib therapy in the clinical practice setting in comparison to clinical trial setting as well manufacturer's recommendations. These differences include route of administration (intravenous (iv) vs. Read More

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December 2018

Different clinical features according to the anastomotic leakage subtypes after rectal cancer surgeries: contained vs. free leakages.

PLoS One 2018 12;13(12):e0208572. Epub 2018 Dec 12.

Division of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Anastomotic leakage can be classified by free and contained leakage according to clinical manifestations. The risk factors and their comparison between these leakage subtypes are uncertain. This study aims to evaluate anastomotic leakage patterns and to compare clinical features between free and contained leakages after low anterior resection for rectal cancer. Read More

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December 2018
1 Read

Anti-smoking social norms are associated with increased cessation behaviours among lower and higher socioeconomic status smokers: A population-based cohort study.

PLoS One 2018 12;13(12):e0208950. Epub 2018 Dec 12.

Centre for Behavioural Research in Cancer, Cancer Council Victoria, Melbourne, Australia.

Background: Social denormalisation of smoking can provide an environment that helps smokers to quit. This study examined which of three measures of anti-smoking social norms have the greatest influence on quitting-related cognitions and behaviours, and if this influence differs according to socioeconomic status (SES).

Methods: The Victorian Tracking Survey measured social norms among 1,348 (n(weighted) = 1,373) Australian adult smokers (aged 18-59) between 2012 and 2014, who were followed-up one week later. Read More

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December 2018

Genome-wide identification and characterization of gene family for RWP-RK transcription factors in wheat (Triticum aestivum L.).

PLoS One 2018 12;13(12):e0208409. Epub 2018 Dec 12.

Department of Genetics and Plant Breeding, CCS University, Meerut, India.

RWP-RKs represent a small family of transcription factors (TFs) that are unique to plants and function particularly under conditions of nitrogen starvation. These RWP-RKs have been classified in two sub-families, NLPs (NIN-like proteins) and RKDs (RWP-RK domain proteins). NLPs regulate tissue-specific expression of genes involved in nitrogen use efficiency (NUE) and RKDs regulate expression of genes involved in gametogenesis/embryogenesis. Read More

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December 2018
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The National Institutes of Health measure of Healing Experience of All Life Stressors (NIH-HEALS): Factor analysis and validation.

PLoS One 2018 12;13(12):e0207820. Epub 2018 Dec 12.

Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.

Two hundred patients with severe and/or life-threatening disease were recruited form the NIH Clinical Center and participated in the validation of the NIH-HEALS, which included exploratory factor analysis, principal component analysis, reliability, convergent validity, and divergent validity analyses. Item-reducing principal components analysis and internal consistency and split-half reliability demonstrated excellent internal consistency and split-half reliability (Cronbach's alpha = 0.89, split-half reliability = 0. Read More

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December 2018

Multiplexed CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility.

PLoS Genet 2018 Dec 12;14(12):e1007821. Epub 2018 Dec 12.

Cancer Genomics Unit, Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Fanconi Anemia (FA) is a genomic instability syndrome resulting in aplastic anemia, developmental abnormalities, and predisposition to hematological and other solid organ malignancies. Mutations in genes that encode proteins of the FA pathway fail to orchestrate the repair of DNA damage caused by DNA interstrand crosslinks. Zebrafish harbor homologs for nearly all known FA genes. Read More

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December 2018
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Decomposing the subclonal structure of tumors with two-way mixture models on copy number aberrations.

PLoS One 2018 12;13(12):e0206579. Epub 2018 Dec 12.

Institute of Statistics, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.

Multistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Read More

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December 2018

Screen for modulators of atonal homolog 1 gene expression using notch pathway-relevant gene transcription based cellular assays.

PLoS One 2018 12;13(12):e0207140. Epub 2018 Dec 12.

R&D Alternative Discovery and Development, GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom.

Atonal homolog 1 (Atoh1) is a basic helix-loop-helix 9 (bHLH) transcription factor acting downstream of Notch and is required for the differentiation of sensory hair cells in the inner ear and the specification of secretory cells during the intestinal crypt cell regeneration. Motivated by the observations that the upregulation of Atoh1 gene expression, through genetic manipulation or pharmacological inhibition of Notch signaling (e.g. Read More

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December 2018
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