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https://www.readbyqxmd.com/read/27556229/fine-mapping-of-the-1p11-2-breast-cancer-susceptibility-locus
#1
Hisani N Horne, Charles C Chung, Han Zhang, Kai Yu, Ludmila Prokunina-Olsson, Kyriaki Michailidou, Manjeet K Bolla, Qin Wang, Joe Dennis, John L Hopper, Melissa C Southey, Marjanka K Schmidt, Annegien Broeks, Kenneth Muir, Artitaya Lophatananon, Peter A Fasching, Matthias W Beckmann, Olivia Fletcher, Nichola Johnson, Elinor J Sawyer, Ian Tomlinson, Barbara Burwinkel, Frederik Marme, Pascal Guénel, Thérèse Truong, Stig E Bojesen, Henrik Flyger, Javier Benitez, Anna González-Neira, Hoda Anton-Culver, Susan L Neuhausen, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K Schmutzler, Hiltrud Brauch, Ute Hamann, Heli Nevanlinna, Sofia Khan, Keitaro Matsuo, Hiroji Iwata, Thilo Dörk, Natalia V Bogdanova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Georgia Chenevix-Trench, Anna H Wu, David Ven den Berg, Ann Smeets, Hui Zhao, Jenny Chang-Claude, Anja Rudolph, Paolo Radice, Monica Barile, Fergus J Couch, Celine Vachon, Graham G Giles, Roger L Milne, Christopher A Haiman, Loic Le Marchand, Mark S Goldberg, Soo H Teo, Nur A M Taib, Vessela Kristensen, Anne-Lise Borresen-Dale, Wei Zheng, Martha Shrubsole, Robert Winqvist, Arja Jukkola-Vuorinen, Irene L Andrulis, Julia A Knight, Peter Devilee, Caroline Seynaeve, Montserrat García-Closas, Kamila Czene, Hatef Darabi, Antoinette Hollestelle, John W M Martens, Jingmei Li, Wei Lu, Xiao-Ou Shu, Angela Cox, Simon S Cross, William Blot, Qiuyin Cai, Mitul Shah, Craig Luccarini, Caroline Baynes, Patricia Harrington, Daehee Kang, Ji-Yeob Choi, Mikael Hartman, Kee Seng Chia, Maria Kabisch, Diana Torres, Anna Jakubowska, Jan Lubinski, Suleeporn Sangrajrang, Paul Brennan, Susan Slager, Drakoulis Yannoukakos, Chen-Yang Shen, Ming-Feng Hou, Anthony Swerdlow, Nick Orr, Jacques Simard, Per Hall, Paul D P Pharoah, Douglas F Easton, Stephen J Chanock, Alison M Dunning, Jonine D Figueroa
The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array...
2016: PloS One
https://www.readbyqxmd.com/read/27536883/a-tmprss2-creert2-knock-in-mouse-model-for-cancer-genetic-studies-on-prostate-and-colon
#2
Dong Gao, Yu Zhan, Wei Di, Amanda R Moore, Jessica J Sher, Youxin Guan, Shangqian Wang, Zeda Zhang, Devan A Murphy, Charles L Sawyers, Ping Chi, Yu Chen
Fusion between TMPRSS2 and ERG, placing ERG under the control of the TMPRSS2 promoter, is the most frequent genetic alteration in prostate cancer, present in 40-50% of cases. The fusion event is an early, if not initiating, event in prostate cancer, implicating the TMPRSS2-positive prostate epithelial cell as the cancer cell of origin in fusion-positive prostate cancer. To introduce genetic alterations into Tmprss2-positive cells in mice in a temporal-specific manner, we generated a Tmprss2-CreERT2 knock-in mouse...
2016: PloS One
https://www.readbyqxmd.com/read/27526195/toxic-accumulation-of-lps-pathway-intermediates-underlies-the-requirement-of-lpxh-for-growth-of-acinetobacter-baumannii-atcc-19606
#3
Daryl L Richie, Kenneth T Takeoka, Jade Bojkovic, Louis E Metzger, Christopher M Rath, William S Sawyer, Jun-Rong Wei, Charles R Dean
The lipid A moiety of lipopolysaccharide (LPS) is the main constituent of the outer leaflet of the Gram-negative bacterial outer membrane (OM) and is essential in many Gram-negative pathogens. An exception is Acinetobacter baumannii ATCC 19606, where mutants lacking enzymes occurring early in lipid A biosynthesis (LpxA, LpxC or LpxD), and correspondingly lacking LPS, can grow. In contrast, we show here that LpxH, an enzyme that occurs downstream of LpxD in the lipid A biosynthetic pathway, is essential for growth in this strain...
2016: PloS One
https://www.readbyqxmd.com/read/27459855/identification-of-independent-association-signals-and-putative-functional-variants-for-breast-cancer-risk-through-fine-scale-mapping-of-the-12p11-locus
#4
Chenjie Zeng, Xingyi Guo, Jirong Long, Karoline B Kuchenbaecker, Arnaud Droit, Kyriaki Michailidou, Maya Ghoussaini, Siddhartha Kar, Adam Freeman, John L Hopper, Roger L Milne, Manjeet K Bolla, Qin Wang, Joe Dennis, Simona Agata, Shahana Ahmed, Kristiina Aittomäki, Irene L Andrulis, Hoda Anton-Culver, Natalia N Antonenkova, Adalgeir Arason, Volker Arndt, Banu K Arun, Brita Arver, Francois Bacot, Daniel Barrowdale, Caroline Baynes, Alicia Beeghly-Fadiel, Javier Benitez, Marina Bermisheva, Carl Blomqvist, William J Blot, Natalia V Bogdanova, Stig E Bojesen, Bernardo Bonanni, Anne-Lise Borresen-Dale, Judith S Brand, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Saundra S Buys, Qiuyin Cai, Trinidad Caldes, Ian Campbell, Jane Carpenter, Jenny Chang-Claude, Ji-Yeob Choi, Kathleen B M Claes, Christine Clarke, Angela Cox, Simon S Cross, Kamila Czene, Mary B Daly, Miguel de la Hoya, Kim De Leeneer, Peter Devilee, Orland Diez, Susan M Domchek, Michele Doody, Cecilia M Dorfling, Thilo Dörk, Isabel Dos-Santos-Silva, Martine Dumont, Miriam Dwek, Bernd Dworniczak, Kathleen Egan, Ursula Eilber, Zakaria Einbeigi, Bent Ejlertsen, Steve Ellis, Debra Frost, Fiona Lalloo, Peter A Fasching, Jonine Figueroa, Henrik Flyger, Michael Friedlander, Eitan Friedman, Gaetana Gambino, Yu-Tang Gao, Judy Garber, Montserrat García-Closas, Andrea Gehrig, Francesca Damiola, Fabienne Lesueur, Sylvie Mazoyer, Dominique Stoppa-Lyonnet, Graham G Giles, Andrew K Godwin, David E Goldgar, Anna González-Neira, Mark H Greene, Pascal Guénel, Lothar Haeberle, Christopher A Haiman, Emily Hallberg, Ute Hamann, Thomas V O Hansen, Steven Hart, Jaana M Hartikainen, Mikael Hartman, Norhashimah Hassan, Sue Healey, Frans B L Hogervorst, Senno Verhoef, Carolyn B Hendricks, Peter Hillemanns, Antoinette Hollestelle, Peter J Hulick, David J Hunter, Evgeny N Imyanitov, Claudine Isaacs, Hidemi Ito, Anna Jakubowska, Ramunas Janavicius, Katarzyna Jaworska-Bieniek, Uffe Birk Jensen, Esther M John, Charles Joly Beauparlant, Michael Jones, Maria Kabisch, Daehee Kang, Beth Y Karlan, Saila Kauppila, Michael J Kerin, Sofia Khan, Elza Khusnutdinova, Julia A Knight, Irene Konstantopoulou, Peter Kraft, Ava Kwong, Yael Laitman, Diether Lambrechts, Conxi Lazaro, Loic Le Marchand, Chuen Neng Lee, Min Hyuk Lee, Jenny Lester, Jingmei Li, Annelie Liljegren, Annika Lindblom, Artitaya Lophatananon, Jan Lubinski, Phuong L Mai, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Frederik Marme, Keitaro Matsuo, Lesley McGuffog, Alfons Meindl, Florence Menegaux, Marco Montagna, Kenneth Muir, Anna Marie Mulligan, Katherine L Nathanson, Susan L Neuhausen, Heli Nevanlinna, Polly A Newcomb, Silje Nord, Robert L Nussbaum, Kenneth Offit, Edith Olah, Olufunmilayo I Olopade, Curtis Olswold, Ana Osorio, Laura Papi, Tjoung-Won Park-Simon, Ylva Paulsson-Karlsson, Stephanie Peeters, Bernard Peissel, Paolo Peterlongo, Julian Peto, Georg Pfeiler, Catherine M Phelan, Nadege Presneau, Paolo Radice, Nazneen Rahman, Susan J Ramus, Muhammad Usman Rashid, Gad Rennert, Kerstin Rhiem, Anja Rudolph, Ritu Salani, Suleeporn Sangrajrang, Elinor J Sawyer, Marjanka K Schmidt, Rita K Schmutzler, Minouk J Schoemaker, Peter Schürmann, Caroline Seynaeve, Chen-Yang Shen, Martha J Shrubsole, Xiao-Ou Shu, Alice Sigurdson, Christian F Singer, Susan Slager, Penny Soucy, Melissa Southey, Doris Steinemann, Anthony Swerdlow, Csilla I Szabo, Sandrine Tchatchou, Manuel R Teixeira, Soo H Teo, Mary Beth Terry, Daniel C Tessier, Alex Teulé, Mads Thomassen, Laima Tihomirova, Marc Tischkowitz, Amanda E Toland, Nadine Tung, Clare Turnbull, Ans M W van den Ouweland, Elizabeth J van Rensburg, David Ven den Berg, Joseph Vijai, Shan Wang-Gohrke, Jeffrey N Weitzel, Alice S Whittemore, Robert Winqvist, Tien Y Wong, Anna H Wu, Drakoulis Yannoukakos, Jyh-Cherng Yu, Paul D P Pharoah, Per Hall, Georgia Chenevix-Trench, Alison M Dunning, Jacques Simard, Fergus J Couch, Antonis C Antoniou, Douglas F Easton, Wei Zheng
BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac...
June 21, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27433846/inherited-dna-repair-gene-mutations-in-men-with-metastatic-prostate-cancer
#5
MULTICENTER STUDY
Colin C Pritchard, Joaquin Mateo, Michael F Walsh, Navonil De Sarkar, Wassim Abida, Himisha Beltran, Andrea Garofalo, Roman Gulati, Suzanne Carreira, Rosalind Eeles, Olivier Elemento, Mark A Rubin, Dan Robinson, Robert Lonigro, Maha Hussain, Arul Chinnaiyan, Jake Vinson, Julie Filipenko, Levi Garraway, Mary-Ellen Taplin, Saud AlDubayan, G Celine Han, Mallory Beightol, Colm Morrissey, Belinda Nghiem, Heather H Cheng, Bruce Montgomery, Tom Walsh, Silvia Casadei, Michael Berger, Liying Zhang, Ahmet Zehir, Joseph Vijai, Howard I Scher, Charles Sawyers, Nikolaus Schultz, Philip W Kantoff, David Solit, Mark Robson, Eliezer M Van Allen, Kenneth Offit, Johann de Bono, Peter S Nelson
BACKGROUND: Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. METHODS: We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis...
August 4, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27149219/facilitating-a-culture-of-responsible-and-effective-sharing-of-cancer-genome-data
#6
Lillian L Siu, Mark Lawler, David Haussler, Bartha Maria Knoppers, Jeremy Lewin, Daniel J Vis, Rachel G Liao, Fabrice Andre, Ian Banks, J Carl Barrett, Carlos Caldas, Anamaria Aranha Camargo, Rebecca C Fitzgerald, Mao Mao, John E Mattison, William Pao, William R Sellers, Patrick Sullivan, Bin Tean Teh, Robyn L Ward, Jean Claude ZenKlusen, Charles L Sawyers, Emile E Voest
Rapid and affordable tumor molecular profiling has led to an explosion of clinical and genomic data poised to enhance the diagnosis, prognostication and treatment of cancer. A critical point has now been reached at which the analysis and storage of annotated clinical and genomic information in unconnected silos will stall the advancement of precision cancer care. Information systems must be harmonized to overcome the multiple technical and logistical barriers to data sharing. Against this backdrop, the Global Alliance for Genomic Health (GA4GH) was established in 2013 to create a common framework that enables responsible, voluntary and secure sharing of clinical and genomic data...
May 5, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27027416/obesity-is-not-associated-with-antimicrobial-treatment-failure-for-intra-abdominal-infection
#7
Zachary C Dietch, Therese M Duane, Charles H Cook, Patrick J O'Neill, Reza Askari, Lena M Napolitano, Nicholas Namias, Christopher M Watson, Daniel L Dent, Brandy L Edwards, Puja M Shah, Christopher A Guidry, Stephen W Davies, Rhett N Willis, Robert G Sawyer
BACKGROUND: Obesity and commonly associated comorbidities are known risk factors for the development of infections. However, the intensity and duration of antimicrobial treatment are rarely conditioned on body mass index (BMI). In particular, the influence of obesity on failure of antimicrobial treatment for intra-abdominal infection (IAI) remains unknown. We hypothesized that obesity is associated with recurrent infectious complications in patients treated for IAI. METHODS: Five hundred eighteen patients randomized to treatment in the Surgical Infection Society Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated...
August 2016: Surgical Infections
https://www.readbyqxmd.com/read/26953758/percutaneously-drained-intra-abdominal-infections-do-not-require-longer-duration-of-antimicrobial-therapy
#8
Rishi Rattan, Casey J Allen, Robert G Sawyer, Reza Askari, Kaysie L Banton, Raul Coimbra, Charles H Cook, Therese M Duane, Patrick J OʼNeill, Ori D Rotstein, Nicholas Namias
BACKGROUND: The length of antimicrobial therapy in complicated intra-abdominal infections (CIAIs) is controversial. A recent prospective, multicenter, randomized controlled trial found that 4 days of antimicrobial therapy after source control of CIAI resulted in similar outcomes when compared with longer duration. We sought to examine whether outcomes remain similar in the subpopulation who received percutaneous drainage for source control of CIAI. METHODS: With the use of the STOP-IT database, patients with a CIAI who received percutaneous drainage were analyzed...
July 2016: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/26920994/patients-with-complicated-intra-abdominal-infection-presenting-with-sepsis-do-not-require-longer-duration-of-antimicrobial-therapy
#9
RANDOMIZED CONTROLLED TRIAL
Rishi Rattan, Casey J Allen, Robert G Sawyer, Reza Askari, Kaysie L Banton, Jeffrey A Claridge, Christine S Cocanour, Raul Coimbra, Charles H Cook, Joseph Cuschieri, E Patchen Dellinger, Therese M Duane, Heather L Evans, Pamela A Lipsett, John E Mazuski, Preston R Miller, Patrick J O'Neill, Ori D Rotstein, Nicholas Namias
BACKGROUND: A recent prospective, multicenter, randomized controlled trial found that 4 days of antibiotics after source control of complicated intra-abdominal infections resulted in similar outcomes when compared with longer duration. We hypothesized that the subset of patients presenting with sepsis have similar outcomes when treated with the shorter course of antibiotics. STUDY DESIGN: Patients from the STOP-IT (Study to Optimize Peritoneal Infection Therapy) trial database meeting criteria for sepsis (ie, temperature <36°C or >38°C and a WBC count <4000 cells/mm(3) or >12,000 cells/mm(3)) were analyzed...
April 2016: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/26797458/organoid-culture-systems-for-prostate-epithelial-and-cancer-tissue
#10
Jarno Drost, Wouter R Karthaus, Dong Gao, Else Driehuis, Charles L Sawyers, Yu Chen, Hans Clevers
This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumor. We explain how to establish these cultures in the fully defined serum-free conditioned medium that is required to sustain organoid growth...
February 2016: Nature Protocols
https://www.readbyqxmd.com/read/26794662/development-of-a-human-physiologically-based-pharmacokinetic-pbpk-model-for-dermal-permeability-for-lindane
#11
Megan E Sawyer, Marina V Evans, Charles A Wilson, Lauren J Beesley, Lider S Leon, Chris R Eklund, Edward L Croom, Rex A Pegram
Lindane is a neurotoxicant used for the treatment of lice and scabies present on human skin. Due to its pharmaceutical application, an extensive pharmacokinetic database exists in humans. Mathematical diffusion models allow for calculation of lindane skin permeability coefficients using human kinetic data obtained from in vitro and in vivo experimentation as well as a default compound-specific calculation based on physicochemical characteristics used in the absence of kinetic data. A dermal model was developed to describe lindane diffusion into the skin, where the skin compartment consisted of homogeneous dermal tissue...
March 14, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/26725682/applying-%C3%A2-%C3%A2-zr-transferrin-to-study-the-pharmacology-of-inhibitors-to-bet-bromodomain-containing-proteins
#12
Michael G Doran, Kathryn E Carnazza, Jeffrey M Steckler, Daniel E Spratt, Charles Truillet, John Wongvipat, Charles L Sawyers, Jason S Lewis, Michael J Evans
Chromatin modifying proteins are attractive drug targets in oncology, given the fundamental reliance of cancer on altered transcriptional activity. Multiple transcription factors can be impacted downstream of primary target inhibition, thus making it challenging to understand the driving mechanism of action of pharmacologic inhibition of chromatin modifying proteins. This in turn makes it difficult to identify biomarkers predictive of response and pharmacodynamic tools to optimize drug dosing. In this report, we show that (89)Zr-transferrin, an imaging tool we developed to measure MYC activity in cancer, can be used to identify cancer models that respond to broad spectrum inhibitors of transcription primarily due to MYC inhibition...
February 1, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/26668262/characterization-of-an-acinetobacter-baumannii-lptd-deletion-strain-permeability-defects-and-response-to-inhibition-of-lipopolysaccharide-and-fatty-acid-biosynthesis
#13
Jade Bojkovic, Daryl L Richie, David A Six, Christopher M Rath, William S Sawyer, Qijun Hu, Charles R Dean
UNLABELLED: Lipid A on the Gram-negative outer membrane (OM) is synthesized in the cytoplasm by the Lpx pathway and translocated to the OM by the Lpt pathway. Some Acinetobacter baumannii strains can tolerate the complete loss of lipopolysaccharide (LPS) resulting from the inactivation of early LPS pathway genes such as lpxC. Here, we characterized a mutant deleted for lptD, which encodes an OM protein that mediates the final translocation of fully synthesized LPS to the OM. Cells lacking lptD had a growth defect comparable to that of an lpxC deletion mutant under the growth conditions tested but were more sensitive to hydrophobic antibiotics, revealing a more significant impact on cell permeability from impaired LPS translocation than from the loss of LPS synthesis...
December 14, 2015: Journal of Bacteriology
https://www.readbyqxmd.com/read/26628377/identification-of-different-classes-of-luminal-progenitor-cells-within-prostate-tumors
#14
Supreet Agarwal, Paul G Hynes, Heather S Tillman, Ross Lake, Wassim G Abou-Kheir, Lei Fang, Orla M Casey, Amir H Ameri, Philip L Martin, Juan Juan Yin, Phillip J Iaquinta, Wouter R Karthaus, Hans C Clevers, Charles L Sawyers, Kathleen Kelly
Primary prostate cancer almost always has a luminal phenotype. However, little is known about the stem/progenitor properties of transformed cells within tumors. Using the aggressive Pten/Tp53-null mouse model of prostate cancer, we show that two classes of luminal progenitors exist within a tumor. Not only did tumors contain previously described multipotent progenitors, but also a major population of committed luminal progenitors. Luminal cells, sorted directly from tumors or grown as organoids, initiated tumors of adenocarcinoma or multilineage histological phenotypes, which is consistent with luminal and multipotent differentiation potentials, respectively...
December 15, 2015: Cell Reports
https://www.readbyqxmd.com/read/26563462/emerging-mechanisms-of-resistance-to-androgen-receptor-inhibitors-in-prostate-cancer
#15
REVIEW
Philip A Watson, Vivek K Arora, Charles L Sawyers
During the past 10 years, preclinical studies implicating sustained androgen receptor (AR) signalling as the primary driver of castration-resistant prostate cancer (CRPC) have led to the development of novel agents targeting the AR pathway that are now in widespread clinical use. These drugs prolong the survival of patients with late-stage prostate cancer but are not curative. In this Review, we highlight emerging mechanisms of acquired resistance to these contemporary therapies, which fall into the three broad categories of restored AR signalling, AR bypass signalling and complete AR independence...
December 2015: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/26554403/aacr-precision-medicine-series-highlights-of-the-integrating-clinical-genomics-and-cancer-therapy-meeting
#16
Elaine Maggi, Cristina Montagna
The American Association for Cancer Research (AACR) Precision Medicine Series "Integrating Clinical Genomics and Cancer Therapy" took place June 13-16, 2015 in Salt Lake City, Utah. The conference was co-chaired by Charles L. Sawyers form Memorial Sloan Kettering Cancer Center in New York, Elaine R. Mardis form Washington University School of Medicine in St. Louis, and Arul M. Chinnaiyan from University of Michigan in Ann Arbor. About 500 clinicians, basic science investigators, bioinformaticians, and postdoctoral fellows joined together to discuss the current state of Clinical Genomics and the advances and challenges of integrating Next Generation Sequencing (NGS) technologies into clinical practice...
December 2015: Mutation Research
https://www.readbyqxmd.com/read/26526696/all-the-world-s-a-stage-facilitating-discovery-science-and-improved-cancer-care-through-the-global-alliance-for-genomics-and-health
#17
LETTER
Mark Lawler, Lillian L Siu, Heidi L Rehm, Stephen J Chanock, Gil Alterovitz, John Burn, Fabien Calvo, Denis Lacombe, Bin Tean Teh, Kathryn N North, Charles L Sawyers
The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages "team science" and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients...
November 2015: Cancer Discovery
https://www.readbyqxmd.com/read/26484571/a-novel-approach-to-high-quality-postmortem-tissue-procurement-the-gtex-project
#18
Latarsha J Carithers, Kristin Ardlie, Mary Barcus, Philip A Branton, Angela Britton, Stephen A Buia, Carolyn C Compton, David S DeLuca, Joanne Peter-Demchok, Ellen T Gelfand, Ping Guan, Greg E Korzeniewski, Nicole C Lockhart, Chana A Rabiner, Abhi K Rao, Karna L Robinson, Nancy V Roche, Sherilyn J Sawyer, Ayellet V Segrè, Charles E Shive, Anna M Smith, Leslie H Sobin, Anita H Undale, Kimberly M Valentino, Jim Vaught, Taylor R Young, Helen M Moore
The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project...
October 2015: Biopreservation and Biobanking
https://www.readbyqxmd.com/read/26445180/defining-surgical-site-infection-in-colorectal-surgery-an-objective-analysis-using-serial-photographic-documentation
#19
Traci L Hedrick, Amy M Harrigan, Robert G Sawyer, Florence E Turrentine, George J Stukenborg, Bindu A Umapathi, Charles M Friel
BACKGROUND: Surgical site infection is common following colorectal surgery, yet the incidence varies widely. CDC criteria include "diagnosis by attending physician," which can be subjective. Alternatively, the ASEPSIS score is an objective scoring system based on the presence of clinical findings. OBJECTIVE: The aim of this study is to compare the interrater reliability of the ASEPSIS score vs CDC definitions in identifying surgical site infection. DESIGN: This 24-month prospective study used serial photography of the wound...
November 2015: Diseases of the Colon and Rectum
https://www.readbyqxmd.com/read/26432404/androgen-receptor-upregulation-mediates-radioresistance-after-ionizing-radiation
#20
Daniel E Spratt, Michael J Evans, Brian J Davis, Michael G Doran, Man Xia Lee, Neel Shah, John Wongvipat, Kathryn E Carnazza, George G Klee, William Polkinghorn, Donald J Tindall, Jason S Lewis, Charles L Sawyers
Clinical trials have established the benefit of androgen deprivation therapy (ADT) combined with radiotherapy in prostate cancer. ADT sensitizes prostate cancer to radiotherapy-induced death at least in part through inhibition of DNA repair machinery, but for unknown reasons, adjuvant ADT provides further survival benefits. Here, we show that androgen receptor (AR) expression and activity are durably upregulated following radiotherapy in multiple human prostate cancer models in vitro and in vivo. Moreover, the degree of AR upregulation correlates with survival in vitro and time to tumor progression in animal models...
November 15, 2015: Cancer Research
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