tbuckley/cabot-search huggingface dataset:
Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial
Authors: H-J Aubin, A Bobak, J R Britton, C Oncken, C B Billing, J Gong, K E Williams, K R Reeves
Journal: Thorax (2008)

<h3>Background:</h3> Varenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). A study was undertaken to compare a 12-week standard regimen of varenicline with a 10-week standard regimen of transdermal nicotine replacement therapy (NRT) for smoking cessation. <h3>Methods:</h3> In this 52-week, open-label, randomised, multicentre, phase 3 trial conducted in Belgium, France, the Netherlands, UK and USA, participants were randomly assigned (1:1) to receive varenicline uptitrated to 1 mg twice daily for 12 weeks or transdermal NRT (21 mg/day reducing to 7 mg/day) for 10 weeks. Non-treatment follow-up continued to week 52. The primary outcome was the biochemically confirmed (exhaled carbon monoxide ⩽10 ppm) self-reported continuous abstinence rate (CAR) for the last 4 weeks of the treatment period in participants who had taken at least one dose of treatment. Secondary outcomes included CAR from the last 4 weeks of treatment through weeks 24 and 52, and measures of craving, withdrawal and smoking satisfaction. <h3>Results:</h3> A total of 376 and 370 participants assigned to varenicline and NRT, respectively, were eligible for analysis. The CAR for the last 4 weeks of treatment was significantly greater for varenicline (55.9%) than NRT (43.2%; OR 1.70, 95% CI 1.26 to 2.28, p&lt;0.001). The week 52 CAR (NRT, weeks 8–52; varenicline, weeks 9–52) was 26.1% for varenicline and 20.3% for NRT (OR 1.40, 95% CI 0.99 to 1.99, p = 0.056). Varenicline significantly reduced craving (p&lt;0.001), withdrawal symptoms (p&lt;0.001) and smoking satisfaction (p&lt;0.001) compared with NRT. The most frequent adverse event was nausea (varenicline, 37.2%; NRT, 9.7%). <h3>Conclusions:</h3> The outcomes of this trial established that abstinence from smoking was greater and craving, withdrawal symptoms and smoking satisfaction were less at the end of treatment with varenicline than with transdermal NRT. <h3>Trial registration number:</h3> NCT00143325.
Mutational landscapes of tongue carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance
Authors: Andre Luiz Vettore, Kalpana Ramnarayanan, Gregory Poore, Kevin Lim, Choon Kiat Ong, Kie Kyon Huang, Hui Sun Leong, Fui Teen Chong, Tony Kiat-Hon Lim, Weng Khong Lim, Ioana Cutcutache, John R. Mcpherson, Yuka Suzuki, Shenli Zhang, Thakshayeni Skanthakumar, Weining Wang, Daniel SW Tan, Byoung Chul Cho, Bin Tean Teh, Steve Rozen, Patrick Tan, N. Gopalakrishna Iyer
Journal: Genome Medicine (2015)

Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. Here, we sought to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention. Seventy-eight cases were subjected to whole-exome (n = 18) and targeted deep sequencing (n = 60). While the most common mutation was in TP53, the OTSCC genetic landscape differed from previously described cohorts of patients with head and neck tumors: OTSCCs demonstrated frequent mutations in DST and RNF213, while alterations in CDKN2A and NOTCH1 were significantly less frequent. Despite a lack of previously reported NOTCH1 mutations, integrated analysis showed enrichments of alterations affecting Notch signaling in OTSCC. Importantly, these Notch pathway alterations were prognostic on multivariate analyses. A high proportion of OTSCCs also presented with alterations in drug targetable and chromatin remodeling genes. Patients harboring mutations in actionable pathways were more likely to succumb from recurrent disease compared with those who did not, suggesting that the former should be considered for treatment with targeted compounds in future trials. Our study defines the Asian OTSCC mutational landscape, highlighting the key role of Notch signaling in oral tongue tumorigenesis. We also observed somatic mutations in multiple therapeutically relevant genes, which may represent candidate drug targets in this highly lethal tumor type.
Human Endothelial Cells of the Placental Barrier Efficiently Deliver Cholesterol to the Fetal Circulation via ABCA1 and ABCG1
Authors: Jasminka Stefulj, Ute Panzenboeck, Tatjana Becker, Birgit Hirschmugl, Cornelia Schweinzer, Ingrid Lang, Gunther Marsche, Anton Sadjak, Uwe Lang, Gernot Desoye, Christian Wadsack
Journal: Circulation Research (2009)

Although maternal-fetal cholesterol transfer may serve to compensate for insufficient fetal cholesterol biosynthesis under pathological conditions, it may have detrimental consequences under conditions of maternal hypercholesterolemia leading to preatherosclerotic lesion development in fetal aortas. Maternal cholesterol may enter fetal circulation by traversing syncytiotrophoblast and endothelial layers of the placenta. We hypothesized that endothelial cells (ECs) of the fetoplacental vasculature display a high and tightly regulated capacity for cholesterol release. Using ECs isolated from human term placenta (HPECs), we investigated cholesterol release capacity and examined transporters involved in cholesterol efflux pathways controlled by liver-X-receptors (LXRs). HPECs demonstrated 2.5-fold higher cholesterol release to lipid-free apolipoprotein (apo)A-I than human umbilical vein ECs (HUVECs), whereas both cell types showed similar cholesterol efflux to high-density lipoproteins (HDLs). Interestingly, treatment of HPECs with LXR activators increased cholesterol efflux to both types of acceptors, whereas no such response could be observed for HUVECs. In line with enhanced cholesterol efflux, LXR activation in HPECs increased expression of ATP-binding cassette transporters ABCA1 and ABCG1, while not altering expression of ABCG4 and scavenger receptor class B type I (SR-BI). Inhibition of ABCA1 or silencing of ABCG1 decreased cholesterol efflux to apoA-I (-70%) and HDL(3) (-57%), respectively. Immunohistochemistry localized both transporters predominantly to the apical membranes of placental ECs in situ. Thus, ECs of human term placenta exhibit unique, efficient and LXR-regulated cholesterol efflux mechanisms. We propose a sequential pathway mediated by ABCA1 and ABCG1, respectively, by which HPECs participate in forming mature HDL in the fetal blood.
Renin-angiotensin-aldosterone system in cirrhosis.
Authors: S P Wilkinson, R Williams
Journal: Gut (1980)

According to traditional concepts, ascites formation and portal hypertension in cirrhosis lead to a deficit in the 'effective' extracellular fluid (ECF) and blood volumes respectively. The renin-angiotensin-aldosterone (RAA) system is thus stimulated and the kidneys retain fluid as a homeostatic mechanism to restore the ECF and blood volumes. Recent studies, however, show that approximately two-thirds of patients with ascites do not have a stimulated RAA system and in those without clinical evidence of fluid retention the RAA system is actually suppressed. These findings are incompatible with the concepts of reduced effective ECF and blood volumes. Despite the fact that most patients retaining sodim and accumulating ascites have a normal plasma aldosterone concentration, other evidence strongly suggests a dominant role for aldosterone in the regulation of renal sodium excretion. There might therefore be an increased renal tubular sensitivity to aldosterone in cirrhosis. For the one-third of patients with ascites who do have a stimulated RAA system this may well be a response to reduced effective ECF and/or blood volumes in accord with traditional concepts.
Characteristics of Triple-Negative Breast Cancer in Patients With a <i>BRCA1</i> Mutation: Results From a Population-Based Study of Young Women
Authors: Eunjung Lee, Roberta McKean-Cowdin, Huiyan Ma, Darcy V. Spicer, David Van Den Berg, Leslie Bernstein, Giske Ursin
Journal: Journal of Clinical Oncology (2011)

Purpose Triple-negative breast cancers (TNBCs) are tumors with low or no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. These tumors have a poor prognosis, remain a clinical challenge, and are more common among women with BRCA1 mutations. We tested whether there are distinguishing features of TNBC after BRCA1 mutation status has been taken into account. Patients and Methods We sequenced BRCA1 and BRCA2 genes in a population-based sample of 1,469 patients with incident breast cancer age 20 to 49 years from Los Angeles County (California). Information on tumor receptor status was available for 1,167 women. Clinical, pathologic, and hormone-related lifestyle characteristics were compared across patient subgroups defined by BRCA1 mutation status and triple-negative receptor status. Results Forty-eight percent of BRCA1 mutation carriers had TNBC compared with only 12% of noncarriers. Within BRCA1 mutation carriers, as well as within noncarriers, triple-negative receptor status was associated with younger age at diagnosis and higher tumor grade. Among women without a BRCA1 mutation, we observed that women with TNBC had higher premenopausal body mass index and earlier age at first full-term pregnancy than those with non-TNBC. Age at menarche and other reproductive factors were not associated with triple-negative status regardless of BRCA1 mutation status. Within BRCA1 mutation carriers, Ashkenazi Jewish women were about five times more likely to have TNBC than non–Ashkenazi Jewish women. Conclusion Our results suggest that among BRCA1 mutation carriers, as among noncarriers, there are unique characteristics associated with the triple-negative subtype. The findings in Ashkenazi Jewish BRCA1 mutation carriers should be confirmed.
Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes) predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92
Authors: TM Calero Moreno, G Gustafsson, S Garwicz, D Grandér, GK Jonmundsson, B-M Frost, A Mäkipernaa, O Rasool, E-R Savolainen, K Schmiegelow, S Söderhäll, K Vettenranta, F Wesenberg, S Einhorn, M Heyman
Journal: Leukemia (2002)
Acyl-CoA Metabolism and Partitioning
Authors: Trisha J. Grevengoed, Eric L. Klett, Rosalind A. Coleman
Journal: Annual Review of Nutrition (2014)

Long-chain fatty acyl-coenzyme As (CoAs) are critical regulatory molecules and metabolic intermediates. The initial step in their synthesis is the activation of fatty acids by one of 13 long-chain acyl-CoA synthetase isoforms. These isoforms are regulated independently and have different tissue expression patterns and subcellular locations. Their acyl-CoA products regulate metabolic enzymes and signaling pathways, become oxidized to provide cellular energy, and are incorporated into acylated proteins and complex lipids such as triacylglycerol, phospholipids, and cholesterol esters. Their differing metabolic fates are determined by a network of proteins that channel the acyl-CoAs toward or away from specific metabolic pathways and serve as the basis for partitioning. This review evaluates the evidence for acyl-CoA partitioning by reviewing experimental data on proteins that are believed to contribute to acyl-CoA channeling, the metabolic consequences of loss of these proteins, and the potential role of maladaptive acyl-CoA partitioning in the pathogenesis of metabolic disease and carcinogenesis.
Diverse Origin and Function of Cells With Endothelial Phenotype Obtained From Adult Human Blood
Authors: Rajiv Gulati, Dragan Jevremovic, Timothy E. Peterson, Suvro Chatterjee, Vijay Shah, Richard G. Vile, Robert D. Simari
Journal: Circulation Research (2003)

Cells with endothelial phenotype generated from adult peripheral blood have emerging diagnostic and therapeutic potential. This study examined the lineage relationship between, and angiogenic function of, early endothelial progenitor cells (EPCs) and late outgrowth endothelial cells (OECs) in culture. Culture conditions were established to support the generation of both EPCs and OECs from the same starting population of peripheral blood mononuclear cells (PBMCs). Utilizing differences in expression of the surface endotoxin receptor CD14, it was determined that the vast majority of EPCs arose from a CD14+ subpopulation of PBMCs but OECs developed exclusively from the CD14- fraction. Human OECs, but not EPCs, expressed key regulatory proteins endothelial nitric oxide synthase (eNOS) and caveolin-1. Moreover, OECs exhibited a markedly greater capacity for capillary morphogenesis in in vitro and in vivo matrigel models, tube formation by OECs being in part dependent on eNOS function. Collectively, these data indicate lineage and functional heterogeneity in the population of circulating cells capable of assuming an endothelial phenotype and provide rationale for the investigation of new cell-therapeutic approaches to ischemic cardiovascular disease.
High-dose thiotepa and melphalan with hemopoietic progenitor support following induction therapy with epirubicin-paclitaxel-containing regimens in metastatic breast cancer (MBC)
Authors: C. Bengala, I. Pazzagli, F. Innocenti, S. Donati, C. Favre, M.C. Menconi, F. Greco, R. Danesi, C. Orlandini, V. Guarneri, M. Del Tacca, P.F. Conte
Journal: Annals of Oncology (2001)

Background-Preliminary data from phase III randomized studies have failed to show benefit of HDC given as consolidation after anthracychne and alkylating-based chemotherapy in metastatic breast cancer (MBC) Moderate activity of induction regimens and selection of chemoresistant clones are among the possible reasons for these disappointing results We therefore have designed a phase II study where high-dose alkylating agents are given as consolidation after an induction treatment including the most active agents (epirubicin and pachtaxel) without alkylating agents.Patients and methods Patients with MBC not previously treated with chemotherapy for metastatic disease were eligible After six courses of epirubicin-pachtaxel ± gemcitabine patients received a course of thiotepa 600 mg/m 2 + melphalan 160 mg/m 2 with hemopoietic support Pharmacokinetic parameters of thiotepa and melphalan were measured and related to treatment outcomes The L-VEF of the patients was monitored before and after treatment Results Forty-eight patients have been treated.Before HDC 14 patients were in CR, and 34 in PR A median of 6 92 x 10 6 (range 1 53-16 6) CD34+ cells/kg were reinfused after HDC.Median days (range) to neutrophils >0.5 x 10 9 /l and platelets > 20,000 x 10 9 /l were 9.5 (9-33) and 10 days (9-32), respectively Symptomatic CHF was observed in two patients (4 1%) C mnx and AUC of thiotepa showed a linear relationship with time to progression (TTP) and overall survival (OS)' r 2 = 0 6.After HDC the conversion rate from PR to CR was 44 1% At five years progression-free and overall survival rates are 37 5% and 65%, respectively A treatment-related death was observed Conclusions High-dose thiotepa and melphalan after an epirubicin-pachtaxel-containing treatment is feasible, devoid of significant cardiotoxicity and very active.Pharmacokinetic parameters of high-dose thiotepa might be linked to treatment outcome Key words high-dose chemotherapy
REGULATION OF IMMUNE RESPONSES BY TGF-β
Authors: John J. Letterio, Anita B. Roberts
Journal: Annual Review of Immunology (1998)

▪ Abstract The transforming growth factor β (TGF-β) family of proteins are a set of pleiotropic secreted signaling molecules with unique and potent immunoregulatory properties. TGF-β1 is produced by every leukocyte lineage, including lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to control the differentiation, proliferation, and state of activation of these immune cells. TGF-β can modulate expression of adhesion molecules, provide a chemotactic gradient for leukocytes and other cells participating in an inflammatory response, and inhibit them once they have become activated. Increased production and activation of latent TGF-β have been linked to immune defects associated with malignancy and autoimmune disorders, to susceptibility to opportunistic infection, and to the fibrotic complications associated with chronic inflammatory conditions. In addition to these roles in disease pathogenesis, TGF-β is now established as a principal mediator of oral tolerance and can be recognized as the sine qua non of a unique subset of effector cells that are induced in this process. The accumulated knowledge gained through extensive in vitro functional analyses and from in vivo animal models, including newly established TGF-β gene knockout and transgenic mice, supports the concept that clinical therapies based on modulation of this cytokine represent an important new approach to the treatment of disorders of immune function.
A double-blind study of the effect of zinc and oxytetracycline in acne vulgaris
Authors: GERD MICHAELSSON, L. JUHLIN, KERSTIN LJUNGHALL
Journal: British Journal of Dermatology (1977)

Journal Article A double‐blind study of the effect of zinc and oxytetracycline in acne vulgaris Get access GERD MICHAËLSSON, GERD MICHAËLSSON Department of Dermatology, University Hospital, 750 14 Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar L. JUHLIN, L. JUHLIN Department of Dermatology, University Hospital, 750 14 Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar KERSTIN LJUNGHALL KERSTIN LJUNGHALL Department of Dermatology, University Hospital, 750 14 Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue 5, 1 May 1977, Pages 561–566, https://doi.org/10.1111/j.1365-2133.1977.tb14136.x Published: 01 May 1977
THE IMPACT OF RENAL FUNCTION AND HEMODIALYSIS ON TARGET LESION REVASCULARIZATION FOR THE LESIONS WITH SIROLIMUS-ELUTING STENT AND PACLITAXEL-ELUTING STENT
Authors: Ren Kawaguchi, Yusuke Miyaishi, Hakuken Kan, Shinya Kogure, Eiji Yamashita, Hiroshi Hoshizaki, Shigeru Oshima
Journal: Journal of the American College of Cardiology (2011)
Increased Vascularity of the Bronchial Mucosa in Mild Asthma
Authors: XUN LI, JOHN W. WILSON
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Airway-wall remodeling leading to thickening of the bronchial wall in asthma has been invoked to account for airflow obstruction and increased bronchial reactivity to provocative stimuli. Bronchial-wall changes characteristic of asthma are thought to include increased vascularity with vasodilatation. The contention that inflammatory mediators cause bronchial vasodilatation and that growth factors may induce increased vascularity is based on little structural evidence. We took bronchoscopic biopsies from the major airways of 12 subjects with mild asthma and 11 control subjects, and evaluated bronchial vessel numbers and size, using computerized image analysis after staining for type IV collagen in vessel walls. The airways of asthmatic subjects were significantly more vascular (17.2 ± 4.2 versus 10.3 ± 1.9%, p < 0.001), with more vessels (738 ± 150 versus 539 ± 276 vessels/mm2 [mean ± SD], p < 0.05) than those of the controls. There were significantly more asthmatic bronchial than control vessels with a cross-sectional area greater than 300 μ m2 (19.4 versus 12.7%, p < 0.05). These findings provide the first confirmatory evidence that bronchial biopsies from patients with mild asthma are more vascular than those of normal controls, that there are more vessels in asthmatic airways, and that asthmatic bronchial vessels are larger than controls.
Biomechanics of Cardiovascular Development
Authors: Larry A. Taber
Journal: Annual Review of Biomedical Engineering (2001)

▪ Abstract It long has been known that mechanical forces play a role in the development of the cardiovascular system, but only recently have biomechanical engineers begun to explore this field. This paper reviews some of this work. First, an overview of the relevant biology is discussed. Next, a mechanical theory is presented that can be used to model developmental processes. The theory includes the effects of finite volumetric growth and active contractile forces. Finally, applications of this and other theories to problems of cardiovascular development are discussed, and some future directions are suggested. The intent is to stimulate further interest among engineers in this important area of research.
Antioxidant Vitamins C and E Improve Endothelial Function in Children With Hyperlipidemia
Authors: Marguerite M. Engler, Mary B. Engler, Mary J. Malloy, Elisa Y. Chiu, Monique C. Schloetter, Steven M. Paul, Markus Stuehlinger, Ken Y. Lin, John P. Cooke, Jason D. Morrow, Paul M Ridker, Nader Rifai, Elizabeth Miller, Joseph L. Witztum, Michele Mietus-Snyder
Journal: Circulation (2003)

Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children.In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (P<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide.Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.
Expression Profiling of Purified Normal Human Luminal and Myoepithelial Breast Cells
Authors: Chris Jones, Alan Mackay, Anita Grigoriadis, Antonio Cossu, Jorge S. Reis-Filho, Laura Fulford, Tim Dexter, Susan Davies, Karen Bulmer, Emily Ford, Suzanne Parry, Mario Budroni, Giuseppe Palmieri, A. Munro Neville, Michael J. O’Hare, Sunil R. Lakhani
Journal: Cancer Research (2004)

Abstract The normal duct-lobular system of the breast is lined by two epithelial cell types, inner luminal secretory cells and outer contractile myoepithelial cells. We have generated comprehensive expression profiles of the two normal cell types, using immunomagnetic cell separation and gene expression microarray analysis. The cell-type specificity was confirmed at the protein level by immunohistochemistry in normal breast tissue. New prognostic markers for survival were identified when the luminal- and myoepithelial-specific molecules were evaluated on breast tumor tissue microarrays. Nuclear expression of luminal epithelial marker galectin 3 correlated with a shorter overall survival in these patients, and the expression of SPARC (osteonectin), a myoepithelial marker, was an independent marker of poor prognosis in breast cancers as a whole. These data provide a framework for the interpretation of breast cancer molecular profiling experiments, the identification of potential new diagnostic markers, and development of novel indicators of prognosis.