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charles sawyers

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https://www.readbyqxmd.com/read/29121144/positron-emission-tomography-computed-tomography-based-assessments-of-androgen-receptor-expression-and-glycolytic-activity-as-a-prognostic-biomarker-for-metastatic-castration-resistant-prostate-cancer
#1
Josef J Fox, Somali C Gavane, Estelle Blanc-Autran, Sadek Nehmeh, Mithat Gönen, Brad Beattie, Hebert A Vargas, Heiko Schöder, John L Humm, Samson W Fine, Jason S Lewis, Stephen B Solomon, Joseph R Osborne, Darren Veach, Charles L Sawyers, Wolfgang A Weber, Howard I Scher, Michael J Morris, Steven M Larson
Importance: Androgen receptor-signaling inhibitor (ARSi) drugs prolong life in metastatic castration-resistant prostate cancer (mCRPC), but such tumors eventually become resistant and progress. Comprehensive positron emission tomography/computed tomography (PET/CT) imaging using fluoro-2-D-deoxyglucose F 18 ([18F]-FDG) for glycolysis (Glyc) and fluorodihydrotestosterone F 18 ([18F]-FDHT) for androgen receptor (AR) expression determine heterogeneity of imaging phenotypes, which may be useful in distinguishing patients who will benefit from ARSi drugs from those who need alternative treatments...
November 9, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29067575/inguinal-hernia-repair-is-there-a-benefit-to-using-the-robot
#2
Eric J Charles, J Hunter Mehaffey, Carlos A Tache-Leon, Peter T Hallowell, Robert G Sawyer, Zequan Yang
BACKGROUND: The number of robotic surgical procedures performed yearly is constantly rising, due to improved dexterity and visualization capabilities compared with conventional methods. We hypothesized that outcomes after robotic-assisted inguinal hernia repair would not be significantly different from outcomes after laparoscopic or open repair. METHODS: All patients undergoing inguinal hernia repair between 2012 and 2016 were identified using institutional American College of Surgeons National Surgical Quality Improvement Program data...
October 24, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/29057879/deletion-of-3p13-14-locus-spanning-foxp1-to-shq1-cooperates-with-pten-loss-in-prostate-oncogenesis
#3
Haley Hieronymus, Phillip J Iaquinta, John Wongvipat, Anuradha Gopalan, Rajmohan Murali, Ninghui Mao, Brett S Carver, Charles L Sawyers
A multigenic locus at 3p13-14, spanning FOXP1 to SHQ1, is commonly deleted in prostate cancer and lost broadly in a range of cancers but has unknown significance to oncogenesis or prognosis. Here, we report that FOXP1-SHQ1 deletion cooperates with PTEN loss to accelerate prostate oncogenesis and that loss of component genes correlates with prostate, breast, and head and neck cancer recurrence. We demonstrate that Foxp1-Shq1 deletion accelerates prostate tumorigenesis in mice in combination with Pten loss, consistent with the association of FOXP1-SHQ1 and PTEN loss observed in human cancers...
October 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29020201/novel-method-suggests-global-superiority-of-short-duration-antibiotics-for-intra-abdominal-infections
#4
Arthur R Celestin, Stephen R Odom, Konstantia Angelidou, Scott R Evans, Raul Coimbra, Christopher A Guidry, Joseph Cuschieri, Kaysie L Banton, Patrick J O'Neill, Reza Askari, Nicholas Namias, Therèse M Duane, Jeffrey A Claridge, E Patchen Dellinger, Robert A Sawyer, Charles H Cook
Desirability of outcome ranking and response adjusted for duration of antibiotic risk (DOOR/RADAR) are novel and innovative methods of evaluating data in antibiotic trials. We analyzed data from a noninferiority trial of short-course antimicrobial therapy for intra-abdominal infection (STOP-IT), and results suggest global superiority of short-duration therapy for intra-abdominal infections.
October 16, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28994635/does-isolation-of-enterococcus-affect-outcomes-in-intra-abdominal-infections
#5
James M Sanders, Jeffrey M Tessier, Robert Sawyer, E P Dellinger, Preston R Miller, Nicholas Namias, Michaela West, Charles H Cook, P J O'Neill, Lena Napolitano, Rishi Rattan, Joseph Cuschieri, Jeffrey A Claridge, Chris A Guidry, Reza Askari, Kaysie Banton, Ori Rotstein, Billy J Moore, Therese M Duane
BACKGROUND: Enterococci are isolated frequently as pathogens in patients with intra-abdominal infections (IAIs) and may predict poor clinical outcomes. It remains controversial whether enterococci warrant an altered treatment approach with regard to antimicrobial treatment. PATIENTS AND METHODS: The study population was derived from the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial database. Through post hoc analysis subjects were stratified into two groups based on isolation of Enterococcus...
October 10, 2017: Surgical Infections
https://www.readbyqxmd.com/read/28891793/regulation-of-the-glucocorticoid-receptor-via-a-bet-dependent-enhancer-drives-antiandrogen-resistance-in-prostate-cancer
#6
Neel Shah, Ping Wang, John Wongvipat, Wouter R Karthaus, Wassim Abida, Joshua Armenia, Shira Rockowitz, Yotam Drier, Bradley E Bernstein, Henry W Long, Matthew L Freedman, Vivek K Arora, Deyou Zheng, Charles L Sawyers
In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals...
September 11, 2017: ELife
https://www.readbyqxmd.com/read/28873162/mutation-detection-in-patients-with-advanced-cancer-by-universal-sequencing-of-cancer-related-genes-in-tumor-and-normal-dna-vs-guideline-based-germline-testing
#7
Diana Mandelker, Liying Zhang, Yelena Kemel, Zsofia K Stadler, Vijai Joseph, Ahmet Zehir, Nisha Pradhan, Angela Arnold, Michael F Walsh, Yirong Li, Anoop R Balakrishnan, Aijazuddin Syed, Meera Prasad, Khedoudja Nafa, Maria I Carlo, Karen A Cadoo, Meg Sheehan, Megan H Fleischut, Erin Salo-Mullen, Magan Trottier, Steven M Lipkin, Anne Lincoln, Semanti Mukherjee, Vignesh Ravichandran, Roy Cambria, Jesse Galle, Wassim Abida, Marcia E Arcila, Ryma Benayed, Ronak Shah, Kenneth Yu, Dean F Bajorin, Jonathan A Coleman, Steven D Leach, Maeve A Lowery, Julio Garcia-Aguilar, Philip W Kantoff, Charles L Sawyers, Maura N Dickler, Leonard Saltz, Robert J Motzer, Eileen M O'Reilly, Howard I Scher, Jose Baselga, David S Klimstra, David B Solit, David M Hyman, Michael F Berger, Marc Ladanyi, Mark E Robson, Kenneth Offit
Importance: Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. Objective: To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. Design, Setting, and Participants: From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing...
September 5, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28815210/lpxk-is-essential-for-growth-of-acinetobacter-baumannii-atcc-19606-relationship-to-toxic-accumulation-of-lipid-a-pathway-intermediates
#8
Jun-Rong Wei, Daryl L Richie, Mina Mostafavi, Louis E Metzger, Christopher M Rath, William S Sawyer, Kenneth T Takeoka, Charles R Dean
Acinetobacter baumannii ATCC 19606 can grow without lipid A, the major component of lipooligosaccharide. However, we previously reported that depletion of LpxH (the fourth enzyme in the lipid A biosynthetic pathway) prevented growth of this strain due to toxic accumulation of lipid A pathway intermediates. Here, we explored whether a similar phenomenon occurred with depletion of LpxK, a kinase that phosphorylates disaccharide 1-monophosphate (DSMP) at the 4' position to yield lipid IVA. An A. baumannii ATCC 19606 derivative with LpxK expression under the control of an isopropyl β-d-1-thiogalactopyranoside (IPTG)-regulated expression system failed to grow without induction, indicating that LpxK is essential for growth...
July 2017: MSphere
https://www.readbyqxmd.com/read/28688647/effect-of-hypothermia-on-splenic-leukocyte-modulation-and-survival-duration-in-severely-septic-rats
#9
Rhett N Willis, Eric J Charles, Christopher A Guidry, Mahendra D Chordia, Stephen W Davies, Zequan Yang, Robert G Sawyer
BACKGROUND: Therapeutic hypothermia (HT) in severe septic shock is associated with prolonged survival. We hypothesized that moderate HT would prolong survival and modulate the inflammatory response in rats with septic shock by exerting its therapeutic effect on splenic leukocytes. MATERIALS AND METHODS: Severe septic shock was created in rats by cecal ligation and incision (CLI). One hour after CLI or laparotomy, rats were randomized to sham, normothermia (NT), or 4 h of HT followed by 2 h of rewarming...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28650745/longer-duration-antimicrobial-therapy-does-not-prevent-treatment-failure-in-high-risk-patients-with-complicated-intra-abdominal-infections
#10
Taryn E Hassinger, Christopher A Guidry, Ori D Rotstein, Therese M Duane, Heather L Evans, Charles H Cook, Patrick J O'Neill, John E Mazuski, Reza Askari, Lena M Napolitano, Nicholas Namias, Preston R Miller, E Patchen Dellinger, Raul Coimbra, Christine S Cocanour, Kaysie L Banton, Joseph Cuschieri, Kimberley Popovsky, Robert G Sawyer
BACKGROUND: Recent studies have suggested the length of treatment of intra-abdominal infections (IAIs) can be shortened without detrimental effects on patient outcomes. However, data from high-risk patient populations are lacking. We hypothesized that patients at high risk for treatment failure will benefit from a longer course of antimicrobial therapy. METHODS: Patients enrolled in the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated retrospectively to identify risk factors associated with treatment failure, which was defined as the composite outcome of recurrent IAI, surgical site infection, or death...
August 2017: Surgical Infections
https://www.readbyqxmd.com/read/28614298/erf-mutations-reveal-a-balance-of-ets-factors-controlling-prostate-oncogenesis
#11
Rohit Bose, Wouter R Karthaus, Joshua Armenia, Wassim Abida, Phillip J Iaquinta, Zeda Zhang, John Wongvipat, Elizabeth V Wasmuth, Neel Shah, Patrick S Sullivan, Michael G Doran, Ping Wang, Anna Patruno, Yilin Zhao, Deyou Zheng, Nikolaus Schultz, Charles L Sawyers
Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens to drive expression of the normally silent E26 transformation-specific (ETS) transcription factor ERG in prostate cells. Recent genomic landscape studies of such cancers have reported recurrent point mutations and focal deletions of another ETS member, the ETS2 repressor factor ERF. Here we show these ERF mutations cause decreased protein stability and mostly occur in tumours without ERG upregulation. ERF loss recapitulates the morphological and phenotypic features of ERG gain in normal mouse prostate cells, including expansion of the androgen receptor transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of Pten loss that yields oncogenic activity by ERG...
June 29, 2017: Nature
https://www.readbyqxmd.com/read/28486022/wound-concerns-and-healthcare-consumption-of-resources-after-colorectal-surgery-an-opportunity-for-innovation
#12
Puja M Shah, Heather L Evans, Amy Harrigan, Robert G Sawyer, Charles M Friel, Traci L Hedrick
BACKGROUND: Significant portions of patients undergoing colorectal surgical procedures have minor incision disturbances, yet very few meet definitions for surgical site infection (SSI). We sought to investigate the natural history of incision disturbances with a focus on the patient experience and resource utilization. We hypothesize that patients who have an incision disturbance consume frequent healthcare resources in the post-operative period despite the fact that most never receive a diagnosis of SSI...
July 2017: Surgical Infections
https://www.readbyqxmd.com/read/28130854/isotope-labelling-by-reduction-of-nitriles-application-to-the-synthesis-of-isotopologues-of-tolmetin-and-celecoxib
#13
Kate Ellis-Sawyer, Ryan A Bragg, Nick Bushby, Charles S Elmore, Michael J Hickey
The aryl methyl group is found in many drug-like compounds, but there are limited ways of preparing compounds with an isotope label in this methyl position. The process of cyanation of an aryl halide followed by complete reduction of the nitrile to a methyl group was investigated as a route for preparing stable and radiolabelled isotopologues of drug-like compounds. Using this methodology, carbon-13, deuterium, carbon-14, and tritium labelled isotopologues of the nonsteroidal anti-inflammatory drug tolmetin were produced, as well as carbon-13, deuterium, and carbon-14 labelled isotopologues of another nonsteroidal anti-inflammatory drug, celecoxib...
January 28, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28059768/sox2-promotes-lineage-plasticity-and-antiandrogen-resistance-in-tp53-and-rb1-deficient-prostate-cancer
#14
Ping Mu, Zeda Zhang, Matteo Benelli, Wouter R Karthaus, Elizabeth Hoover, Chi-Chao Chen, John Wongvipat, Sheng-Yu Ku, Dong Gao, Zhen Cao, Neel Shah, Elizabeth J Adams, Wassim Abida, Philip A Watson, Davide Prandi, Chun-Hao Huang, Elisa de Stanchina, Scott W Lowe, Leigh Ellis, Himisha Beltran, Mark A Rubin, David W Goodrich, Francesca Demichelis, Charles L Sawyers
Some cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. We use in vitro and in vivo human prostate cancer models to show that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR)-dependent luminal epithelial cells to AR-independent basal-like cells. This lineage plasticity is enabled by the loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2, and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression...
January 6, 2017: Science
https://www.readbyqxmd.com/read/28059767/rb1-and-trp53-cooperate-to-suppress-prostate-cancer-lineage-plasticity-metastasis-and-antiandrogen-resistance
#15
Sheng Yu Ku, Spencer Rosario, Yanqing Wang, Ping Mu, Mukund Seshadri, Zachary W Goodrich, Maxwell M Goodrich, David P Labbé, Eduardo Cortes Gomez, Jianmin Wang, Henry W Long, Bo Xu, Myles Brown, Massimo Loda, Charles L Sawyers, Leigh Ellis, David W Goodrich
Prostate cancer relapsing from antiandrogen therapies can exhibit variant histology with altered lineage marker expression, suggesting that lineage plasticity facilitates therapeutic resistance. The mechanisms underlying prostate cancer lineage plasticity are incompletely understood. Studying mouse models, we demonstrate that Rb1 loss facilitates lineage plasticity and metastasis of prostate adenocarcinoma initiated by Pten mutation. Additional loss of Trp53 causes resistance to antiandrogen therapy. Gene expression profiling indicates that mouse tumors resemble human prostate cancer neuroendocrine variants; both mouse and human tumors exhibit increased expression of epigenetic reprogramming factors such as Ezh2 and Sox2...
January 6, 2017: Science
https://www.readbyqxmd.com/read/28005468/age-and-its-impact-on-outcomes-with-intra-abdominal-infection
#16
Drew Farmer, Jeffrey M Tessier, James M Sanders, Robert G Sawyer, Ori D Rotstein, E P Dellinger, Pamela A Lipsett, Joseph Cuschieri, Preston Miller, Charles H Cook, Christopher A Guidry, Reza Askari, Billy J Moore, Therese M Duane
BACKGROUND: Age has been shown to play a significant role in the etiology of complicated intra-abdominal infections (cIAIs), but the correlation between age and outcomes after therapy was not investigated in the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial. PATIENTS AND METHODS: Data were obtained by post hoc analysis of the STOP-IT trial database. Patients were stratified by age <65 or ≥65 years. Primary outcomes were surgical site infection (SSI), recurrent IAI (recIAI), and death...
February 2017: Surgical Infections
https://www.readbyqxmd.com/read/27932611/kaposi-s-sarcoma-associated-herpesvirus-infection-of-neurons-in-hiv-positive-patients
#17
For Yue Tso, Ashley Sawyer, Eun Hee Kwon, Victor Mudenda, Dianne Langford, You Zhou, John West, Charles Wood
Background: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), one of the leading cancers in human immunodeficiency virus (HIV)-infected patients in Zambia. KSHV was detected in the human central nervous system (CNS) by polymerase chain reaction (PCR) analysis, but tissue location and cell tropism for KSHV infection has not been established. Given the neurotropism exhibited by other herpesviruses and the frequent coinfection of HIV-positive individuals by KSHV, we sought to determine whether the central nervous system (CNS) can be infected by KSHV in HIV-positive Zambian individuals...
June 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27926864/low-cd38-identifies-progenitor-like-inflammation-associated-luminal-cells-that-can-initiate-human-prostate-cancer-and-predict-poor-outcome
#18
Xian Liu, Tristan R Grogan, Haley Hieronymus, Takao Hashimoto, Jack Mottahedeh, Donghui Cheng, Lijun Zhang, Kevin Huang, Tanya Stoyanova, Jung Wook Park, Ruzanna O Shkhyan, Behdokht Nowroozizadeh, Matthew B Rettig, Charles L Sawyers, David Elashoff, Steve Horvath, Jiaoti Huang, Owen N Witte, Andrew S Goldstein
Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38(lo) luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38(lo) luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27556229/fine-mapping-of-the-1p11-2-breast-cancer-susceptibility-locus
#19
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
#20
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
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