tbuckley/cabot-search huggingface dataset:
Resveratrol Selectively Induces DNA Damage, Independent of <i>Smad4</i> Expression, in Its Efficacy against Human Head and Neck Squamous Cell Carcinoma
Authors: Alpna Tyagi, Mallikarjuna Gu, Takenori Takahata, Barbara Frederick, Chapla Agarwal, Sunitha Siriwardana, Rajesh Agarwal, Robert A. Sclafani
Journal: Clinical Cancer Research (2011)

Alterations in Smad4 signaling and its loss cause genomic instability and head and neck squamous cell carcinoma (HNSCC), suggesting that agents that target both Smad4-dependent and -independent pathways could control HNSCC.Resveratrol efficacy was evaluated against the HNSCC cells FaDu, Cal27, Det562, and Cal27-Smad4 for viability, DNA damage, cell-cycle progression, and apoptosis, as well as γ-H2AX expression, and focus formation (γ-H2AX and Brca1). Resveratrol efficacy was also examined in nude mice for FaDu xenograft growth. Xenografts were analyzed for γ-H2AX and cleaved caspase-3.Resveratrol (5-50 μmol/L) suppressed viability and induced DNA damage in FaDu and Cal27 cells but not in normal human epidermal keratinocytes and human foreskin fibroblasts, showing its selectivity toward HNSCC cells; however, Det562 cells were resistant to resveratrol even at 100 μmol/L. Cal27 cells stably transfected with Smad4 showed similar resveratrol effects as parental Cal27, indicating that a lack of resveratrol effect in Det562 cells was independent of Smad4 status in these cells. Furthermore, resveratrol caused S-phase arrest and apoptotic death of FaDu and Cal27 cells together with induction of Brca1 and γ-H2AX foci. Resveratrol (50 mg/kg body weight) treatment also inhibited FaDu tumor growth in nude mice, and γ-H2AX and cleaved caspase-3 were strongly increased in xenografts from resveratrol-treated mice compared with controls.Our findings for the first time showed antiproliferative, DNA damaging, and apoptotic effects of resveratrol in HNSCC cells independent of Smad4 status, both in vitro and in vivo, suggesting that more studies are needed to establish its potential usefulness against HNSCC.
Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial
Authors: Marc S Sabatine, Elliott M Antman, Petr Widimsky, Iftikhar O Ebrahim, Robert G Kiss, André Saaiman, Rostislav Polasek, Charles F Contant, Carolyn H McCabe, Eugene Braunwald
Journal: The Lancet (2009)
A Prospective Study of Serum C-Reactive Protein and Colorectal Cancer Risk in Men
Authors: Marc J. Gunter, Rachael Stolzenberg-Solomon, Amanda J. Cross, Michael F. Leitzmann, Stephanie Weinstein, Richard J. Wood, Jarmo Virtamo, Philip R. Taylor, Demetrius Albanes, Rashmi Sinha
Journal: Cancer Research (2006)

Abstract Chronic inflammation has been implicated in the etiology of colorectal cancer. C-reactive protein (CRP), a sensitive marker of inflammation, has been investigated with regard to colorectal cancer in only three previous studies, and the results from these investigations were inconsistent. We examined serum CRP levels in relation to colorectal cancer incidence in a nested case-control study within the Alpha Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 Finnish males enrolled from 1985 to 1988 with follow-up through April 2002. Colorectal cancer cases were ascertained by the Finnish Cancer Registry; this analysis included 130 cases of colorectal cancer (with available blood), which occurred between 1990 and April 30, 2002, and 260 matched controls. Baseline median CRP levels were ∼25% higher among colorectal cancer cases (3.4 mg/L) than controls (2.6 mg/L; P = 0.04). Relative to men in the lowest quartile of CRP concentration, men in the highest quartile had an odds ratio of 2.9 (95% confidence interval, 1.4-6.0) for developing colorectal cancer with a dose-response relationship supported (Ptrend = 0.006). The relation between CRP and incident colorectal cancer was modified by body mass index such that the association was stronger among lean individuals than in heavier individuals (Pinteraction = 0.018). These results support the notion that chronic low-grade inflammation is a marker for increased risk of colorectal cancer. (Cancer Res 2006; 66(4): 2483-7)
GnRH antagonists in ovarian stimulation for IVF
Authors: B C Tarlatzis, B C Fauser, E M Kolibianakis, K Diedrich, Luk Rombauts, P Devroey
Journal: Human Reproduction Update (2006)

The present review describes, on the basis of the currently available evidence, the consensus reached by a group of experts on the use of gonadotropin-releasing hormone (GnRH) antagonists in ovarian stimulation for IVF. The single or multiple low-dose administration of GnRH antagonist during the late-follicular phase effectively prevents a premature rise in serum luteinizing hormone (LH) levels in most women. Although controversy remains, most comparative studies suggest a slight, not significant reduction in the probability of pregnancy after IVF using GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest that this slight difference in pregnancy rates is not attributed to chance. Further studies applying varying treatment regimens and outcome measures are required. Data are not in favour of a need to modify the starting dose of gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH antagonist initiation. The addition of LH from the initiation of ovarian stimulation or from GnRH antagonist administration does not appear to be necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for triggering final oocyte maturation is associated with a lower probability of pregnancy. The optimal timing for HCG administration needs to be explored further. GnRH antagonist initiation on day 6 of stimulation appears to be superior to flexible initiation by a follicle of 14–16 mm, although earlier GnRH antagonist administration is worth further evaluation. Luteal phase supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation syndrome remains uncertain, although a trend is present in favour of the GnRH antagonists. The role of GnRH antagonists in ovarian stimulation for IVF appears to be promising, although many questions regarding preferred dose regimens and effects on clinical outcomes remain.
Intermittent Subglottic Secretion Drainage and Ventilator-associated Pneumonia
Authors: Jean-Claude Lacherade, Bernard De Jonghe, Pierre Guezennec, Karim Debbat, Jan Hayon, Antoine Monsel, Pascal Fangio, Corinne Appere de Vecchi, Cédric Ramaut, Hervé Outin, Sylvie Bastuji-Garin
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Ventilator-associated pneumonia (VAP) causes substantial morbidity and mortality. The influence of subglottic secretion drainage (SSD) in preventing VAP remains controversial.Objectives: To determine whether SSD reduces the overall incidence of microbiologically confirmed VAP.Methods: Randomized controlled clinical trial conducted at four French centers. A total of 333 adult patients intubated with a tracheal tube allowing drainage of subglottic secretions and expected to require mechanical ventilation for ≥48 hours was included. Patients were randomly assigned to undergo intermittent SSD (n = 169) or not (n = 164).Measurements and Main Results: Primary outcome was the overall incidence of VAP based on quantitative culture of distal pulmonary samplings performed after each clinical suspicion. Other outcomes included incidence of early- and late-onset VAP, duration of mechanical ventilation, and hospital mortality. Microbiologically confirmed VAP occurred in 67 patients, 25 of 169 (14.8%) in the SSD group and 42 of 164 (25.6%) in the control group (P = 0.02), yielding a relative risk reduction of 42.2% (95% confidential interval, 10.4–63.1%). Using the Day 5 threshold, the beneficial effect of SSD in reducing VAP was observed in both early-onset VAP (2 of 169 [1.2%] patients undergoing SSD vs. 10 of 164 [6.1%] control patients; P = 0.02) and late-onset VAP (23 of 126 [18.6%] patients undergoing SSD vs. 32 of 97 [33.0%] control patients; P = 0.01). VAP was clinically suspected at least once in 51 of 169 (30.2%) patients undergoing SSD and 60 of 164 (36.6%) control patients (P = 0.25). No significant between-group differences were observed in duration of mechanical ventilation and hospital mortality.Conclusions: Subglottic secretion drainage during mechanical ventilation results in a significant reduction in VAP, including late-onset VAP.Clinical trial registered with www.clinicaltrials.gov (NCT00219661).
Telemedical Artificial Pancreas
Authors: Alberto de Leiva, María Elena Hernando
Journal: Diabetes Care (2009)

The integration of continuous subcutaneous insulin infusion (CSII) (insulin pump therapy) and continuous interstitial glucose monitoring (CGM) appears to be an excellent solution for obtaining the desirable metabolic control for most insulin-treated subjects (1–4). Several studies have suggested that CGM with readings in real-time (CGM-RT) further improves blood glucose control (5–9). The introduction of CGM and CSII into clinical practice has generated an inevitable increase in the amount of data to be managed and interpreted. Telemedicine facilitates data management and preprocessing to optimize therapy. Among other potential benefits, telemedicine improves communication among patients and health care providers, improves quantity and quality of data collection, and eases decision-making and therapy adjustment (10–12). DIABTel, a web-based telemedicine system, is a good example for a solution designed to supply these needs (13).

PARIS (Pancreas Artificial Telemedico Inteligente) is a coordinated research project to develop and validate a telemedical artificial pancreas (TAP), a multi-access telemedicine system that integrates CGM-RT, insulin pump, a smart assistant (SA), and close-loop control algorithms. SA is a personal intelligent assistant based on a handheld digital device to provide both personal and remote loop strategies, using CGM, CSII, and mobile general packet radio service (GPRS) communication with a telemedicine central server (TMCS).

This review summarizes acquired experiences with TAP, integrating these new technologies with the objective to improve glycemic control of type 1 diabetic patients.

### Description of the DIABTel telemedicine system

The telemedicine architecture consists of two components: the medical unit (a telemedical central server) and the patient unit (a smart assistant).

The TMCS at the diabetes center of the hospital continuously runs, receiving and processing patients' monitoring data, messages, and requests for professional advice. A previous publication already reported the benefits of DIABTel, allowing the implementation of an easy-to-use, user-tailored telemedicine system with a technological platform allowing tight …
Frequency and clinical characteristics of rapid-onset fatal and near-fatal asthma
Authors: V. Plaza, J. Serrano, C. Picado, J. Sanchis
Journal: European Respiratory Journal (2002)

The onset of fatal and near-fatal asthma attacks can be rapid. The objective of this study was to determine the frequency and clinical characteristics of rapid-onset asthma (ROA) in patients suffering fatal and near-fatal crises. Two-hundred and twenty patients with fatal or near-fatal attacks were enrolled in a multicentre, prospective study. ROA was defined as a crisis developing in ≤2 h. Data on patient and clinical characteristics were collected, and spirometric and allergy studies were performed when the patients were in a stable condition. Forty-five attacks (20%) were ROA and 175 (80%) were slow-onset asthma (SOA). The triggers for SOA and ROA attacks were different, with the ROA group having a significantly lower rate of suspected respiratory infection (7% <i>versus</i> 38%), higher rates of fume/irritant inhalation (9% <i>versus</i> 1%) and a higher intake of nonsteroidal anti-inflammatory drugs (14% <i>versus</i> 3%). The ROA group exhibited significantly higher rates of impaired consciousness (63% <i>versus</i> 44%), absence of lung sounds upon admission (68% <i>versus</i> 42%), fewer hours of mechanical ventilation (13 h <i>versus</i> 28 h) and fewer days of hospitalization (8 days <i>versus</i> 9.5 days) than the SOA group. The 20% frequency of rapid-onset fatal and near-fatal attacks in this study suggests that rapidly developing attacks may not be rare. These findings also support a distinct clinical profile for rapid-onset asthma marked by differences in triggers, severity of exacerbation and clinical course.
Antitumor Activity of Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone in Prostate Cancer Cells
Authors: Vinata B. Lokeshwar, Luis E. Lopez, Daniel Munoz, Andrew Chi, Samir P. Shirodkar, Soum D. Lokeshwar, Diogo O. Escudero, Neetika Dhir, Norman Altman
Journal: Cancer Research (2010)

4-Methylumbelliferone (4-MU) is a hyaluronic acid (HA) synthesis inhibitor with anticancer properties; the mechanism of its anticancer effects is unknown. We evaluated the effects of 4-MU on prostate cancer cells. 4-MU inhibited proliferation, motility, and invasion of DU145, PC3-ML, LNCaP, C4-2B, and/or LAPC-4 cells. At IC(50) for HA synthesis (0.4 mmol/L), 4-MU induced >3-fold apoptosis in prostate cancer cells, which could be prevented by the addition of HA. 4-MU induced caspase-8, caspase-9, and caspase-3 activation, PARP cleavage, upregulation of Fas-L, Fas, FADD and DR4, and downregulation of bcl-2, phosphorylated bad, bcl-XL, phosphorylated Akt, phosphorylated IKB, phosphorylated ErbB2, and phosphorylated epidermal growth factor receptor. At IC(50), 4-MU also caused >90% inhibition of NF-kappaB reporter activity, which was prevented partially by the addition of HA. With the exception of caveolin-1, HA reversed the 4-MU-induced downregulation of HA receptors (CD44 and RHAMM), matrix-degrading enzymes (MMP-2 and MMP-9), interleukin-8, and chemokine receptors (CXCR1, CXCR4, and CXCR7) at the protein and mRNA levels. Expression of myristoylated-Akt rescued 4-MU-induced apoptosis and inhibition of cell growth and interleukin-8, RHAMM, HAS2, CD44, and MMP-9 expression. Oral administration of 4-MU significantly decreased PC3-ML tumor growth (>3-fold) when treatment was started either on the day of tumor cell injection or after the tumors became palpable, without organ toxicity, changes in serum chemistry, or body weight. Tumors from 4-MU-treated animals showed reduced microvessel density ( approximately 3-fold) and HA expression but increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells and expression of apoptosis-related molecules. Therefore, the anticancer effects of 4-MU, an orally bioavailable and relatively nontoxic agent, are primarily mediated by inhibition of HA signaling.
Sleep apnoea attenuates the effects of a lifestyle intervention programme in men with visceral obesity
Authors: Anne-Laure Borel, Xavier Leblanc, Natalie Alméras, Angelo Tremblay, Jean Bergeron, Paul Poirier, Jean-Pierre Després, Frédéric Series
Journal: Thorax (2012)

Excess visceral adiposity and sleep apnoea are two conditions independently associated with cardiovascular diseases. The two conditions are often combined and are believed to interact in a vicious circle.To compare the response of men with visceral obesity with or without sleep apnoea syndrome to a 1-year healthy eating, physical activity/exercise intervention programme.77 men, selected on the basis of increased waist circumference (≥90 cm) and dyslipidaemia (triglycerides ≥1.69 and/or high-density lipoprotein (HDL) cholesterol <1.03 mmol/litre), participated in this study. Body composition and fat distribution were assessed by dual-emission X-ray absorptiometry or CT and sleep breathing disorders by home-based polygraphic recording. Cardiorespiratory fitness, plasma adipokines, plasma inflammatory markers, fasting lipoprotein-lipid profile and oral glucose tolerance test were assessed.After the 1-year lifestyle intervention, the mean oxygen desaturation index (ODI) of the whole sample decreased (-3±13 events/h, p<0.05). Men with sleep apnoea syndrome at baseline (ODI ≥10 events/h, n=28) showed smaller reductions in body mass index, waist circumference, triglycerides and smaller increases in HDL cholesterol and adiponectin than men without sleep apnoea (ODI <10 events/h, n=49), despite similar compliance to the programme. The higher the baseline ODI and the time spent under 90% saturation, the lower the reductions in fat mass and visceral adiposity, and the smaller the improvement in glucose/insulin homeostasis indices after 1 year.Men with sleep apnoea syndrome at baseline had smaller reduction in body weight and less metabolic improvements associated with the lifestyle intervention programme than men without sleep apnoea syndrome.
Reactivation of Androgen Receptor–Regulated <i>TMPRSS2:ERG</i> Gene Expression in Castration-Resistant Prostate Cancer
Authors: Changmeng Cai, Hongyun Wang, Youyuan Xu, Shaoyong Chen, Steven P. Balk
Journal: Cancer Research (2009)

It seems clear that androgen receptor (AR)-regulated expression of the TMPRSS2:ERG fusion gene plays an early role in prostate cancer (PC) development or progression, but the extent to which TMPRSS2:ERG is down-regulated in response to androgen deprivation therapy (ADT) and whether AR reactivates TMPRSS2:ERG expression in castration-resistant PC (CRPC) have not been determined. We show that ERG message levels in TMPRSS2:ERG fusion-positive CRPC are comparable with the levels in fusion gene-positive primary PC, consistent with the conclusion that the TMPRSS2:ERG expression is reactivated by AR in CRPC. To further assess whether TMPRSS2:ERG expression is initially down-regulated in response to ADT, we examined VCaP cells, which express the TMPRSS2:ERG fusion gene, and xenografts. ERG message and protein rapidly declined in response to removal of androgen in vitro and castration in vivo. Moreover, as observed in the clinical samples, ERG expression was fully restored in the VCaP xenografts that relapsed after castration, coincident with AR reactivation. AR reactivation in the relapsed xenografts was also associated with marked increases in mRNA encoding AR and androgen synthetic enzymes. These results show that expression of TMPRSS2:ERG, similarly to other AR-regulated genes, is restored in CRPC and may contribute to tumor progression.
Study on cellular events in post-thymectomy autoimmune oophoritis in mice. II. Requirement of Lyt-1 cells in normal female mice for the prevention of oophoritis.
Authors: S Sakaguchi, T Takahashi, Y Nishizuka
Journal: The Journal of Experimental Medicine (1982)

Autoimmune oophoritis that develops in A/J mice after neonatally thymectomy (NTx) was prevented by a single intraperitoneal injection of spleen cells or thymocytes from normal adult female mice. Prevention of oophoritis was achieved when spleen cells were given within 2 wk after Tx. When spleen cells were obtained from neonatally oophorectomized mice, four times more cells were required for the prevention of oophoritis, but those from the mice oophorectomized on day 7 after birth had equivalent capacity to prevent oophoritis to those from normal female mice. The spleen cells from normal A/J mice that prevented the development of oophoritis in NTx A/J mice were Thy-1+, Lyt-1+,23-, Ia-, Qa-1-, sensitive to in vitro irradiation with 400 rad, resistant to administration of cyclophosphamide or anti-thymocyte serum, and were not eliminated by adult thymectomy. Thymocytes with oophoritis-preventing capacity were also found to be Lyt-1+,23- and TL-1,2,3-. These results seem to correlate well with the finding that the Lyt-1 subpopulation is substantially decreased in NTx mice. The results suggest that, in this post-thymectomy autoimmune oophoritis, NTx abrogates the Lyt-1 T cell subpopulation that serves as suppressive or regulatory cells over developing self-reactive cells directed toward ovarian antigens, and eventually may cause autoimmune oophoritis.
Acid secretion and sensitivity to gastrin in patients with duodenal ulcer: effect of eradication of Helicobacter pylori.
Authors: S F Moss, J Calam
Journal: Gut (1993)

The effect of ulcer healing with eradication of Helicobacter pylori (H pylori) on gastric function was investigated in nine patients with duodenal ulcer disease. One month after eradication there were significant reductions in both basal plasma gastrin concentration, from a median (range) of 19 (1-22) to 6 (2-15) pmol/l (p &lt; 0.05), and of basal acid secretion from 8.3 (2.4-24) to 2.6 (1.4-8.1) mM H+/h, (p &lt; 0.01). The peak acid secretion rate was unchanged from 37 (16-59) to 37 (21-59) mM H+/h. After treatment there was no change in the parietal cell sensitivity to stepped infusions of gastrin heptadecapeptide: the median concentration of gastrin required for 50% of maximal acid secretion (EC50) was 41 (14.8-126) before and 33 (23-125) pmol/l after eradication of H pylori. The metabolic clearance rate of gastrin was also unaffected by the eradication of H pylori. Thus eradication of H pylori infection from patients with active duodenal ulcers is accompanied by falls in both basal gastrin release and basal acid secretion without a change in the parietal cell sensitivity to gastrin. Cyclical changes in H pylori infection may cause the variations in basal acid secretion that are seen in duodenal ulcer disease.
Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Christian Confavreux, Paul O'Connor, Giancarlo Comi, Mark S Freedman, Aaron E Miller, Tomas P Olsson, Jerry S Wolinsky, Teresa Bagulho, Jean-Luc Delhay, Deborah Dukovic, Philippe Truffinet, Ludwig Kappos
Journal: The Lancet Neurology (2014)
p27-p16 Fusion Gene Inhibits Angioplasty-Induced Neointimal Hyperplasia and Coronary Artery Occlusion
Authors: Lisa V. Tsui, Allan Camrud, Jean Mondesire, Paula Carlson, Nathalie Zayek, LaDonna Camrud, Brian Donahue, Scott Bauer, Andy Lin, David Frey, Marianne Rivkin, Ajit Subramanian, Robert Falotico, Jeno Gyuris, Robert Schwartz, James G. McArthur
Journal: Circulation Research (2001)

Inhibition of proliferative neointima formed by vascular smooth muscle cells is a potential target in preventing angioplasty-induced restenosis. We have created a potent antiproliferative by fusing the active regions of the p27 and p16 cell cycle inhibitors. Intravascular delivery of a replication-deficient adenoviral vector (AV) encoding this p27-p16 fusion protein, named W9, inhibited balloon injury-induced neointimal hyperplasia in rabbit carotid arteries. In a therapeutically more relevant model, AV-W9 was delivered to balloon-injured porcine coronary arteries in vivo using an infusion catheter. Of the three coronary arteries, two were injured with a 15-mm balloon catheter and either were left untreated or were treated with 10(12) viral particles of either AV-W9 or a control null virus. AV-W9 treatment significantly inhibited neointimal hyperplasia in this porcine arterial balloon injury model compared with untreated or control virus-treated vessels. The average intimal area of the AV-W9-treated group 10 days after balloon injury and treatment was 0.42+/-0.36 mm(2), whereas the AV-null group demonstrated an intimal area of 0.70+/-0.52 mm(2). At day 10 the average intimal thickness of the AV-W9-treated vessels was 9.1 microm (n=5, x 20 magnification) compared with 21.2 microm (n=5, x 20 magnification) in control virus-treated vessels. This trend was also observed at 28 days after balloon injury and gene transfer during which AV-W9-treated vessels demonstrated an average intimal thickness of 4.7 microm (n=8, x 20 magnification) compared with 13.3 microm (n=3, x 20 magnification) in control virus-treated vessels and 7.3 microm (n=5, x 20 magnification) in the sham-treated vessels. The AV-W9 treatment was safe and well tolerated. These data suggest that AV-W9 gene therapy may be useful in preventing angioplasty-induced intimal hyperplasia in the coronary artery.