tbuckley/cabot-search huggingface dataset:
ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death
Authors: Sannula Kesavardhana, Teneema Kuriakose, Clifford S. Guy, Parimal Samir, R.K. Subbarao Malireddi, Ashutosh Mishra, Thirumala-Devi Kanneganti
Journal: The Journal of Experimental Medicine (2017)

Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA-binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I-MAVS-IFN-β signaling axis. IAV infection induces ubiquitination of ZBP1, suggesting potential regulation of ZBP1 function through posttranslational modifications. We further demonstrate that ZBP1 senses viral ribonucleoprotein (vRNP) complexes of IAV to trigger cell death. These findings collectively indicate that ZBP1 activation requires RIG-I signaling, ubiquitination, and vRNP sensing to trigger activation of programmed cell death pathways during IAV infection. The mechanism of ZBP1 activation described here may have broader implications in the context of virus-induced cell death.
DNA replication biomarkers as functional markers of folate status in colon cells
Authors: AP McGlynn, GR Wasson, SL O'Reilly, A Molloy, I Bradbury, JJ Strain, JM Scott, CS Downes, H McNulty, DG Weir
Journal: Endoscopy (2005)

Aims: To develop new methods based on modifications of Comet assay to investigate DNA biomarkers (uracil misincorporation and DNA hypomethylation) as putative functional markers of folate status in colonocytes.
Les biopsies systématiques sont elles encore utiles pour détecter la dysplasie chez les patients atteints de rectocolite hémorragique à l'ère de la chromoendoscopie?
Authors: C Stefanescu, M Driffa, JM Gornet, S Nancey, A Attar, X Treton, F Berger, D Cazals-Hatem, P Bertheau, A Lavergne Slove, JF Flejou, M Allez, M Lémann, Y Bouhnik, B Flourié
Journal: Endoscopy (2009)

Introduction: La coloscopie avec chromoendoscopie (CE) est supérieure à la coloscopie classique dans la détection de la dysplasie (DYS) en cas de rectocolite hémorragique (RCH). Le but de cette étude était d'évaluer la rentabilité des biopsies systématiques pratiquées selon les Recommandations en plus des biopsies ciblées sur les lésions suspectes mises en évidence par CE pour détecter la DYS en cas de RCH.
Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation
Authors: CJ O'Malley, JE Rasko, RL Basser, KM McGrath, J Cebon, AP Grigg, W Hopkins, B Cohen, J O'Byrne, MD Green, RM Fox, MC Berndt, CG Begley
Journal: Blood (1996)
PET imaging drugs for cancer diagnostics and therapeutics
Authors: Ashot Khanamiryan
Journal: Clinical Cancer Research (2007)

A16  Background: Labeled thymidine and thymidine closest analogs have become preferred radiopharmaceuticals as they easily incorporate into DNA through the enzyme catalyzed thymidine kinase-1-mono-phosporilation reaction and sensitively indicate the cellular proliferation. Our primary objective is to demonstrate a reliable method to synthesize 18[F]-FXAU family analog nucleosides and apply them as PET imaging drugs.  Method: We have modified the 18[F]-FMAU synthesis procedure reported by Mangner et al, developed a dynamic version and applied for the 18[F]-FEAU/18[F]-FXAU drugs9 synthesis. The separated 18[F]-FEAU a/b-isomers, as independent isoforms, were compared to 3[H]-FEAU, 3[H]-PCV (Pencyclovir) and 18[F]-FHBG by their cytoplasm accumulation & relative mono-phosphorilation constants in C6 & C6Sr39-tk rat cells9 uptake studies.  Results: The b-isomer of 18[F]-FEAU applied in different concentrations in cell uptake studies demonstrated high accumulation in C6 HSV1-sr39-tk cells.  Conclusion: The alternative-high accumulation of b-18[F]-FEAU in mutant C6 HSV1-sr39-tk cells proves 18[F]-FXAU family drugs huge potential as PET imaging radio-tracers which will operate in animal models and humans.
Abstract 13974: Hospital-Level Variation in Delays to Clopidogrel Filling Following Stent Implantation and Short-Term Cardiovascular Outcomes: Insights from the National VA Clinical Assessment, Reporting, and Tracking (CART) Program
Authors: James B Byrd, Thomas M Maddox, Colin O'Donnell, Deepak L Bhatt, Thomas T Tsai, John S Rumsfeld, P. M Ho
Journal: Circulation (2011)

Background: A prior study found ∼16% of patients delay filling clopidogrel after hospital discharge following coronary artery stent implantation and this delay was associated with adverse outcomes....
A meta-analysis of randomzied controlled trials comparing the effect of neoadjuvant chemotherapy with or without bevacizumab (Bev) in the treatment of breast cancer (BC).
Authors: Zeina A. Nahleh, Christopher Dodoo, Alok kumar Dwivedi, Gehan Botrus
Journal: Journal of Clinical Oncology (2016)

577 Background: There is currently no defined role of Bev in the treatment of BC, despite several studies suggesting activity in early and advanced BC. The achievement of PCR after neoadjuvant chemotherapy has been associated with improved long-term prognosis in BC Methods: We carried out meta-analysis to compare the effect of adding Bev to neoadjuvant chemotehrapy on pathological complete response (PCR) rates compared to chemotherapy without Bev in BC. The data were extracted from published randomized clinical trials. We found 4 published manuscripts and one study presented as a poster . Random effects models were used as final model for estimating the relative risk (RR) of outcomes in Bev compared to without Bev and 95% confidence interval (CI). The effect size was summarized using relative risk measure. Results: 5 randomized studies involving 4526 patients (2268 treated with Bev & 2278 without Bev) were included in the meta-analysis and were evaluated on the rate of PCR in breast + lymph nodes overall and by Estrogen receptor (ER) /Progesterone receptor (PGR) and HER2 neu status, and adverse events. Overall incidence of PCR was obtained as 35% with Bev while 27% without Bev (RR = 1.26, 95%CI: 1.15-1.38, p < 0.001). Addition of Bev to chemotherapy significantly increased the rate of PCR (breast and lymph nodes) (RR: 1.22, 95%CI: 1.10-1.36, p < 0.001) compared to treatment without Bev. In triple negative BC (TNBC), there was a 30% increase in PCR (RR 1. 30, 95% CI: 1.16-1.45, P < 0.001) in patients treated with Bev versus no Bev. Also, in ER/ PGR + cases, there was a 26% increase in PCR rates (RR 1.26, 95% CI: 1.08-1.26, P < 0.003) in patients treated with Bev compared to patients treated without Bev. There were no significant differences in the incidence of grade 1-3 adverse events between the Bev and non-Bev groups. Conclusions: Adding Bev to neoadjuvant chemotherapy improves the achievement of PCR in both ER/PGR + and TNBC without increasing the incidence of toxicity. The benefit was more pronounced in TNBC. The role of Bev combined with neoadjuvant chemotherapy warrants further investigation in the treatment of BC.
Maîtrise de la qualité microbiologique des endoscopes: évaluation sur site de l'intérêt d'une armoire de séchage/stockage des endoscopes
Authors: L Pineau, B La Scola, A Desjeux, B Marchetti, M Barthet, JC Grimaud
Journal: Endoscopy (2005)

Les conditions de séchage et de stockage des endoscopes ont fait l'objet de nombreuses recommandations. L'objectif de ce travail est d'évaluer l'intérêt d'une armoire de séchage/stockage des endoscopes digestifs en terme de maîtrise d'une éventuelle contamination résiduelle persistant après application d'une procédure de nettoyage/désinfection.
Quit Early, Quit Often
Authors: Susan E. Bates
Journal: Clinical Cancer Research (2015)

The American Cancer Society estimates that, in 2015, 86,380 men and 71,660 women will die of lung cancer (1). This number represents almost 27% of all cancer deaths. Although rates have been declining due to the reduced prevalence of smoking, 18% of U.S. adults still smoke cigarettes, and smoking causes about 85% to 90% of lung cancer deaths (1). Given that lung cancer from smoking is a preventable disease, these numbers have to temper the excitement over new therapies and new therapeutic targets discussed in the following pages of this CCR Focus section.Guest Editors Roy S. Herbst and Katerina Politi have assembled experts in the field to discuss progress and challenges in lung cancer, with articles discussing genomic targets and immunotherapy in squamous cell lung cancer, the unmet need in small cell lung cancer, and the validated genomic targets—epidermal growth factor receptor and anaplastic lymphoma kinase—both potential and limitations. Together, these articles represent a comprehensive look at a field in which the discovery of new targets has become the norm.However, the elephant in the room is addiction to cigarettes. I overheard someone say recently, as an aside, “Quit early, quit often”; it seems an apt concept. Every year, according to the Surgeon General's 2010 Report on tobacco (2), only 5% of daily smokers stop smoking, although half try to do so. For those who do quit, multiple attempts are the norm. The phrase “Quit early, quit often” was coined by Harvard professor Deepak Malhotra in his 2012 speech on choosing a career path, given to graduating master of business administration (MBA) students at Harvard Business School (3). He said, “Quit early and quit often” to find the career that is right for you. Had he been an oncologist, “Quit early, quit often” would have had a very different meaning. Because so many lung cancer deaths are related to smoking, the imperative is clear. Quitting smoking decreases the risk of dying not only from lung cancer but also from other tobacco-related illnesses.As always, this CCR Focus is meant to inspire and challenge those working in the field, and to interest and inform the academic nonexpert. And let's not forget to encourage those who smoke to “Quit early and quit often”…until it sticks.Susan E. BatesDeputy Editor, CCR FocusNational Cancer InstituteSee all articles in this CCR Focus section, “Progress in Lung Cancer.”
Determinants of adjuvant chemotherapy use in small luminal-like breast cancer.
Authors: Marta Bonotto, Lorenzo Gerratana, Alessandro Bettini, Marika Cinausero, Debora Basile, Giacomo Pelizzari, Maria Grazia Vitale, Claudia Bozza, Camilla Lisanti, Valentina Fanotto, Michele Bartoletti, Claudia Andreetta, Stefania Russo, Elena Poletto, Donatella Iacono, Mauro Mansutti, Alessandro Marco Minisini, Gianpiero Fasola, Fabio Puglisi
Journal: Journal of Clinical Oncology (2017)

e12010 Background: The use of adjuvant chemotherapy (CT) in small luminal-like breast cancer (BC) is still heavily debated. International guidelines identify endocrine therapy as the backbone of adjuvant treatment for these patients (pts), while the addition of CT should be limited to high risk cases. The aim of this study was to evaluate the association between patient- or disease-related factors with the prescription of adjuvant CT. Methods: This retrospective study reviewed data from 559 consecutive pts with pT1 ( &lt; 2 cm) luminal-like BC treated between 2004 and 2015 at the Department of Oncology of Udine (Italy). No restrictions were applied regarding lymph node status. The cut-off point of 1% was used to define ER and/or PgR positivity. Factors influencing the prescription of CT were investigated through uni- and multivariate logistic regression with odds ratio (OR) calculation. Prognosis was explored through Cox regression. Results: About thirty percent (173/559) of pts received adjuvant CT. By multivariate analysis, lymph node involvement was highly associated with CT prescription (OR 16.94, 95% CI 7.86-36.50, P &lt; 0.001 for pN1; OR 3.92, 95% CI 1.45-10.58, P = 0.007 for pNmi). Tumor size drove towards the use of CT among pts with pT1c tumors (OR 12.87, 95% CI 1.49-110.88, P = 0.020) but not in pts with pT1b BC (OR 2.38, 95% CI 0.26-21.38, P = 0.437). In addition, a higher CT use was observed in pts with luminal B-like disease (OR 3.79, 95% CI 2.16-6.65, P &lt; 0.001) or in presence of a Ki67 &gt; 14% (OR 1.05, 95% CI 1.03-1.07, P &lt; 0.001). On the contrary, pts with age &gt; 60 years had a very low chance of receiving adjuvant CT (OR 0.09, 95% CI 0.04-0.20, P &lt; 0.001). Notably, the use of CT was not associated with Disease Free Survival or Overall Survival (HR 1.3, 95% CI 0.77-2.17, P = 0.320; HR 1.05, 95% CI 0.56-2, P = 0.866; respectively). Conclusions: Nodal status, tumor size, disease sub-type, Ki67 expression and age are determinants of adjuvant CT prescription in pts with small luminal-like BC. Prospective studies are needed to identify which pts could safely avoid CT without influencing prognosis.
Targeting CDC20 via small interfering RNA shows anti-proliferative effects on human pancreatic carcinoma cells
Authors: Koichi Taniguchi, Nobuyoshi Momiyama, Michio Ueda, Ryusei Matsuyama, Takashi Chishima, Yasushi Ichikawa, Shinji Togo, Hiroshi Shimada
Journal: Cancer Research (2005)

5421  CDC20 (Cell Division Cycle 20 homologue) is thought to play a key role in cell division during M phase of the cell cycle. Our previous study using cDNA microarray showed CDC20 is highly expressed in pancreatic carcinoma compared to normal tissue. [Aim]To evaluate inhibitory effects of siRNA targeting CDC20, a 21-mer synthesized double strand RNA, on the growth of human pancreatic carcinoma cells in combination with cytotoxic drugs and irradiation in vitro. [Methods]Gene expression was examined by real-time PCR and Western blot analysis in four pancreatic carcinoma cell lines; PANC-1, MIAPaCa-2, BxPC-3 and AsPC-1. Cell proliferation was measured by MTT assay. DNA histogram was examined by flow cytometry to analyze the cell cycle.[Results]Real-time PCR and Western blot analysis demonstrated that the siRNA inhibited CDC20 expression at both mRNA and protein levels in each cell lines. Cells treated with 100nM of CDC20 siRNA showed marked decrease in growth rate compared to control non-targeting siRNA (p
Genome-wide association study (GWAS) of response to androgen deprivation therapy (ADT) and survival in metastatic prostate cancer (PCa).
Authors: Mark Pomerantz, Xin Victoria Wang, Philip W. Kantoff, Wanling Xie, Manish Kohli, Gwo-Shu Mary Lee, Elaine Wang, Yu-Hui Chen, Noah M. Hahn, David Frazier Jarrard, Glenn Liu, Jorge A. Garcia, Michael Anthony Carducci, Robert S. DiPaola, Matthew L Freedman, Christopher Sweeney
Journal: Journal of Clinical Oncology (2016)

1540 Background: Inherited genetic factors are among the variables influencing PCa outcome and response to treatment. We conducted a GWAS to identify germline genetic polymorphisms associated with time to ADT resistance and overall survival (OS). Methods: DNA isolated from blood from 1,048 subjects with metastatic hormone-sensitive PCa were genotyped for approximately one million single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05 (1,037 samples with call rate > 85%). Among these, 687 patients were treated with ADT alone and were included in this study. An additional 80 million SNPs per sample were imputed using data from the 1000 Genomes Project. Time to castration-resistant prostate cancer (CRPC) was defined as duration between ADT start and either i) the first of two documented rises in PSA, or ii) start of medication for CRPC. Time to CRPC and OS were treated as time-to-event data in the analysis. Results: Median time to CRPC from start of ADT was 13.3 months. Median OS from ADT start was 4.5 years. The SNPs most highly associated with time to CRPC were polymorphisms residing in intronic regions of the genes FHIT (p-value, 1.73x10-7), PSD3 (p-value, 1.70x10-6), SARDH (p-value, 2.18x10-6). The SNPs most highly associated with OS resided in intergenic regions approximately 70 kilobases (kb) upstream of ETV6 (p-value, 2.99x10-7) and 500 kb from GUSBP4 (p-value, 1.51x10-6), and in an intronic region of HEATR5B (p-value, 1.46x10-6). Conclusions: This study is among the most extensive interrogations of the germline genetic underpinnings of PCa hormone responsiveness and lethality. Reproducibility is being assessed in an independent cohort. Proven associations with ADT response will provide novel insights into ADT resistance as well as potential clinical biomarkers.
Trends in quantitative cancer risk assessment.
Authors: S C Morris
Journal: Environmental Health Perspectives (1991)

Quantitative cancer risk assessment is a dynamic field, more closely coupled to rapidly advancing biomedical research than ever before. Six areas of change and growth are identified: expansion from models of cancer initiation to a more complete picture of the total carcinogenic process; trend from curve-fitting to biologically based models; movement from upperbound estimates to best estimates, with a more complete treatment of uncertainty; increased consideration of the role of susceptibility; growing development of expert systems and decision support systems; and emerging importance of risk communication.
Incident Cardiovascular Disease Among Adults With Blood Pressure &lt;140/90 mm Hg
Authors: Gabriel S. Tajeu, John N. Booth, Lisandro D. Colantonio, Rebecca F. Gottesman, George Howard, Daniel T. Lackland, Emily C. O’Brien, Suzanne Oparil, Joseph Ravenell, Monika M. Safford, Samantha R. Seals, Daichi Shimbo, Steven Shea, Tanya M. Spruill, Rikki M. Tanner, Paul Muntner
Journal: Circulation (2017)

Background: Data from before the 2000s indicate that the majority of incident cardiovascular disease (CVD) events occur among US adults with systolic and diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg. Over the past several decades, BP has declined and hypertension control has improved. Methods: We estimated the percentage of incident CVD events that occur at SBP/DBP &lt;140/90 mm Hg in a pooled analysis of 3 contemporary US cohorts: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), the MESA (Multi-Ethnic Study of Atherosclerosis), and the JHS (Jackson Heart Study) (n=31 856; REGARDS=21 208; MESA=6779; JHS=3869). Baseline study visits were conducted in 2003 to 2007 for REGARDS, 2000 to 2002 for MESA, and 2000 to 2004 for JHS. BP was measured by trained staff using standardized methods. Antihypertensive medication use was self-reported. The primary outcome was incident CVD, defined by the first occurrence of fatal or nonfatal stroke, nonfatal myocardial infarction, fatal coronary heart disease, or heart failure. Events were adjudicated in each study. Results: Over a mean follow-up of 7.7 years, 2584 participants had incident CVD events. Overall, 63.0% (95% confidence interval [CI], 54.9−71.1) of events occurred in participants with SBP/DBP &lt;140/90 mm Hg; 58.4% (95% CI, 47.7−69.2) and 68.1% (95% CI, 60.1−76.0) among those taking and not taking antihypertensive medication, respectively. The majority of events occurred in participants with SBP/DBP &lt;140/90 mm Hg among those &lt;65 years of age (66.7%; 95% CI, 60.5−73.0) and ≥65 years of age (60.3%; 95% CI, 51.0−69.5), women (61.4%; 95% CI, 49.9−72.9) and men (63.8%; 95% CI, 58.4−69.1), and for whites (68.7%; 95% CI, 66.1−71.3), blacks (59.0%; 95% CI, 49.5−68.6), Hispanics (52.7%; 95% CI, 45.1−60.4), and Chinese-Americans (58.5%; 95% CI, 45.2−71.8). Among participants taking antihypertensive medication with SBP/DBP &lt;140/90 mm Hg, 76.6% (95% CI, 75.8−77.5) were eligible for statin treatment, but only 33.2% (95% CI, 32.1−34.3) were taking one, and 19.5% (95% CI, 18.5−20.5) met the SPRINT (Systolic Blood Pressure Intervention Trial) eligibility criteria and may benefit from a SBP target goal of 120 mm Hg. Conclusions: Although higher BP levels are associated with increased CVD risk, in the modern era, the majority of incident CVD events occur in US adults with SBP/DBP &lt;140/90 mm Hg. While absolute risk and cost-effectiveness should be considered, additional CVD risk-reduction measures for adults with SBP/DBP &lt;140/90 mm Hg at high risk for CVD may be warranted.
Probiotic-induced immunomodulation in lymphoid compartments of IL-10 knock-out mice prior to onset of inflammation
Authors: B Sheil, J MacSharry, L O'Callaghan, A O'Riordan, A Waters, L O'Mahony, JK Collins, F Shanahan
Journal: Endoscopy (2006)

Aims: Prophylactic efficacy against colitis following Bifidobacterium infantis consumption in IL-10 knockout (KO) mice has been demonstrated. This study investigated the effect of B. infantis consumption on cytokine responses of IL-10KO mice in early inflammation compared to wild-type (WT) C57Bl/6 mice.
Medulloblastoma: From Myth to Molecular
Authors: Vijay Ramaswamy, Michael D. Taylor
Journal: Journal of Clinical Oncology (2017)

Current therapies for medulloblastoma were introduced primarily in the 1980s and consist of predominantly cytotoxic, nontargeted approaches. Mortality from medulloblastoma remains significant. In addition, many survivors suffer from severe treatment-related effects of radiation and cytotoxic chemotherapy. Further intensification of nonspecific therapy is unlikely to offer additional benefits, because survival rates have reached a plateau. Recent publications in medulloblastoma have revolved largely around the recognition that medulloblastoma per se does not exist, but rather, that there are a group of histologically similar but clinically and molecularly distinct entities that have been grouped under that rubric. Distinguishing the four molecular subgroups of medulloblastoma-wingless (WNT), sonic hedgehog (SHH), group 3, and group 4-in the daily treatment of patients, as well in the setting of clinical trials, is an important challenge in the near term for the pediatric neuro-oncology community. The preponderance of morbidity in treating patients with medulloblastoma is secondary to the treatment or prophylaxis of leptomeningeal metastases, and the cause of most deaths is leptomeningeal metastases. Recurrence of medulloblastoma is a nearly universally fatal event, with no significant salvage rate. The extent of spatial and temporal intratumoral heterogeneity as medulloblastoma metastasizes to leptomeninges and as it evolves in the face of radiation and cytotoxic chemotherapy is just beginning to be understood as a major barrier to therapeutic success. Pediatric neuro-oncology clinicians and scientists must now determine how best to incorporate rapid changes in our biologic understanding of medulloblastoma into the next generation of upfront clinical trials, with the goal of both improving survival for the highest-risk patients and improving quality of life for survivors.