tbuckley/cabot-search huggingface dataset:
Gene copy number alterations and differential gene expression in the acquired resistance of ovarian cancer cells to taxanes
Authors: Dejan Juric, Yan C. Wang, Ron X. Yu, George E. Duran, E. Brian Francisco, Branimir I. Sikic
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1252 

Ovarian cancer is the most common cause of death among women with gynecologic malignancies. Close to 75% of the patients have advanced-stage disease at diagnosis and are often characterized by rapid development of resistance to chemotherapy. In order to understand biological mechanisms underlying this behavior, we have developed a set of taxane-resistance models consisting of six parental ovarian cancer cell lines (A2780/1A9, ES-2, MES-OV, OVCA429, OVCA433 and OVCAR3) and 24 resistant variants exhibiting at least 10-fold resistance to either paclitaxel or docetaxel, selected with or without PSC, a modulator of P-glycoprotein. We hypothesized that the drug resistance phenotype depends on multiple changes in the transcriptional programs of resistant variants and the accumulation of numerous chromosomal alterations conferring selective advantages under drug pressure. High-resolution gene copy number and gene expression profiling were performed using a 42,000-element cDNA microarray platform. Parallel measures of gene copy number variation and gene expression were obtained for a total of 12,480 unique UniGene clusters. Gene copy number profiles were first transformed into regions of consistent gene copy number level using a recently developed circular binary segmentation algorithm (CBS) and deemed changed based on the reference distribution of multiple self-to-self hybridizations. The profiled cell lines exhibited numerous complex gene copy number aberrations, which is consistent with a high degree of aneuploidy in these tumors. The most common alterations include 1q, 3q, 8q, 17q and 20q. The global impact of gene copy number alterations on gene expression was first estimated using a linear regression model which indicated that at least 10% of all variation in gene expression among the analyzed cell lines is directly attributable to underlying variation in gene copy number. Since this relationship is likely to be much larger for a selected number of genes with higher biological importance, gene copy number and gene expression data were also integrated on a gene-by-gene level using signal-to-noise computation coupled with permutation testing. Gene expression profiles of 1,266 clones were found to be significantly associated with gene copy number alterations (q<0.05). These genes were then correlated with the taxane resistance phenotype using Significance Analysis of Microarrays (SAM), and 36 and 38 clones were found to be associated with P-gp and non-P-gp mediated drug resistance phenotypes, respectively (q<0.05). Finally, molecular interactions and potential functional relevance of identified genes were investigated using pathway analysis tools. Collectively, these observations provide a framework for future studies on the roles of genome instability and the accumulated genetic alterations in the development of chemoresistance.
Abstract 16489: Cardiovascular Disease Risk Reduction in Socioeconomically Austere Rural Environments: A Randomized, Controlled Efficacy Trial of a Self-Care Intervention Followed by an Effectiveness Study
Authors: Debra K Moser, Martha J Biddle, Gia Mudd-Martin, Alison L Bailey, Barretta Casey, Michale J Novak, Misook L Chung, Mary Kay Rayens, Susan Westneat, Terry A Lennie
Journal: Circulation (2013)

Background: Cardiovascular disease (CVD) risk is extraordinarily high in austere, rural environments in Kentucky. Although this risk is increasing and affects millions, no interventions focusing on...
Chemotherapy for Hepatocellular Carcinoma
Authors: Dennie V. Jones
Journal: Liver Cancer (1998)

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with approximately one million new cases recorded annually.1 The Pacific rim of Asia and sub-Saharan Africa are regions of exceptionally high HCC prevalence secondary to chronic liver disease and cirrhosis, in turn secondary to hepatitis B or C (or both) viral infections and the ingestion of aflatoxin B.2–4 HCC is relatively uncommon in North America and western Europe. However, with approximately 13,600 cases diagnosed annually in the United States and a 2:1 male predominance, it is estimated that HCC will be one of the top 10 causes of cancer death in American men in 1997.5 Cirrhosis from virtually any cause may place a patient at risk for developing HCC. At present, only complete surgical resection with either partial hepatectomy or a liver transplant is potentially curative, but this procedure is possible in only a small subset of patients. Within the limits of the chemotherapeutic agents currently available, an increasing number of approaches are being investigated in an effort to increase patient survival and the quality of life.
Ongoing rubella outbreak in Austria, 2008-2009
Authors: D Schmid, S Kasper, HW Kuo, S Aberle, H Holzmann, E Daghofer, M Wassermann-Neuhold, O Feenstra, C Krischka, F Allerberger
Journal: Eurosurveillance (2009)

Since October 2008, a total of 143 cases of rubella have affected the two Austrian provinces Styria and Burgenland. The index case occurred in mid-October 2008, but was not notified to the public health authorities until February 2009, when the Austrian Agency for Health and Food Safety was asked to investigate a cluster of 32 rubella cases (24 laboratory-confirmed and eight clinically suspected cases). No case of rubella had been reported in the two affected provinces between February 2007 - when statutory notification for rubella was implemented - and mid-October 2008. 113 of the 143 cases (79%) were confirmed: 101 (89.3% of the 113 cases) clinical-laboratory confirmed and 12 clinical-epidemiological confirmed. Thirty cases fulfilled the criteria of a probable outbreak case only (laboratory results or data on epidemiological link are pending). For 140 outbreak cases data on age was known; the median age was 19 years (range: 2-60 years). 20 cases occurred in soldiers in seven military camps in the area. 55 cases (38.5 %) were female. One case of a laboratory-confirmed rubella infection, affecting an unvaccinated pregnant 18-years old native Austrian in the early first trimenon of pregnancy, led to voluntary abortion
Abstract 16008: FoxO3 Triggers Robust Cardiac Atrophy via BNIP3-dependent Myocyte Autophagy
Authors: Dian J Cao, Nan Jiang, Janet L Johnstone, Misook Oh, Xiang Luo, Kai-chun Yang, Beverly A Rothermel, Joseph A Hill
Journal: Circulation (2010)

Introduction: FoxO transcription factors antagonize cardiac hypertrophy induced by load stress and evidence points to FoxO activation in heart disease. However, underlying mechanisms are unknown. I...
Abstract 3657: Cell-Specific Delivery and Monitoring of Antiangiogenic Therapy in Experimental Aortic Valve Disease with Theranostic Integrin-Targeted 19F Nanobeacons
Authors: Emily A Waters, Junjie Chen, John S Allen, Huiying Zhang, Ralph Fuhrhop, Gregory M Lanza, Samuel A Wickline
Journal: Circulation (2008)

Although angiogenesis plays a critical role in the development of atherosclerosis, its participation in early valvular disease remains speculative. To delineate the presence of angiogenesis and its potential responsiveness to medical therapy in experimental valve disease, we used unique signaling ( 19 F), background-free molecular MR nanobeacons as simultaneous diagnostic and therapeutic (theranostic) tools to quantify valvular angiogenesis in 24 cholesterol-fed NZW rabbits (0.25% cholesterol, 6 mo.) and its response to nanoparticle-borne antiangiogenic therapy with an aminopeptidase-2 inhibitor, fumagillin. Perfluorocarbon nanobeacons (~250 nm) targeted to neovascular α v β 3 integrins and loaded with 0.2% fumagillin were given i.v. at 1 mL/kg for 4 weekly doses (n=8; 30 μg/kg fumagillin/dose). Controls included treatment with nontargeted drug-bearing nanoparticles (n=7) and saline (n=9). MR spectroscopy (470 MHz) for detection of 19 F signal from bound nanoparticles was performed after valve excision. Immunocytochemistry confirmed angiogenesis in all valves. In the targeted drug treatment group, both 50% fewer vessels and 50% lower 19 F signal were observed vs nontargeted or saline groups (p&lt;0.01, p&lt;0.001), confirming efficacy of the theranostic agent in limited dosing (Figure 1 ). Across all animals, cholesterol levels exerted a strong linear effect on the extent of angiogenesis (r=0.52; p&lt;0.01). We speculate that targeted therapy of angiogenesis with theranostic nanoparticles could offer an alternative or conjunctive approach for rational medical management of valvular disease. Figure 1: (Left) Least squares means of 19 F signal from the saline (S), targeted fumagillin (TF), and untargeted fumagillin (UF) treated groups, normalized to the saline control. Note 50% reduction of 19 F signal in the group treated with targeted fumagillin nanoparticles compared to the untreated and untargeted controls. (Right) LS means of vessel count on stained valve sections. Note 50% fewer vessels in targeted fumagillin group corresponding to reduction in 19 F signal. (* p&lt;0.01, ** p&lt;0.001)
Abstract 13814: Clinical and Hemodynamic Outcomes of Transapical Aortic Valve Implantation: Two Years Experience in 155 Patients
Authors: Augusto D'Onofrio, Melissa Fusari, Nicola Abbiate, Chiara Zanchettin, Roberto Bianco, Alessandro Fabbri, Loris Salvador, Elvio Polesel, Paolo Biglioli, Gino Gerosa
Journal: Circulation (2010)

Trans-apical aortic valve implantation (TA-TAVI) is a good alternative in patients with severe aortic valve stenosis (AS) who are inoperable or have a high surgical risk. Few data exist about hemod...
Abstract 3237: The Economic Impact of Same-Day Discharge after Transradial Percutaneous Coronary Intervention and a Single Bolus of Abciximab; an Analysis from the EASY Trial
Authors: Stéphane Rinfret, Wendy Kennedy, Jean Lachaine, Anne Lemay, Josep Rodés-Cabau, Olivier F Bertrand
Journal: Circulation (2008)

Background: In patients presenting with an acute coronary syndrome, same-day home discharge (SDD) after an uncomplicated transradial percutaneous coronary intervention (PCI) performed under a single bolus of abciximab was found clinically non-inferior to the usual overnight hospitalization (OH) and an abciximab bolus followed by a 12h infusion. Objective: To estimate post-PCI health resources cost of trial subjects, and, using cost-minimization, immediate and short-term economic impact of same-day home discharge. Method: A total of 1005 patients were randomized to either the SDD group (n =504) or the OH (n = 501). As randomization was post-procedure, and PCI resource use showed minimal and non-significant differences, a post-PCI cost analysis was conducted. A hospital-based perspective was used. Detailed per patient information of healthcare resources used immediately post-PCI up to hospital discharge were prospectively collected. Costs were estimated based on 2006 Laval Hospital unit prices, and 2006 costs from the Centre Hospitalier de l’université de Montréal (CHUM) hospital costing system (direct and indirect costs). In addition, patient-reported resources for a period of 30 days post-discharge were examined. Results: Per hour post-PCI hospital costs were estimated as $113, based on average 2006 cost for all patients hospitalized for angioplasty plus stent (DRG 112) at the CHUM ($5716), net of estimated PCI-related cost ($1131), and divided by average post PCI length-of-stay of subjects. SDD patients stayed an average of 8.9 hours (95%CI from 8.2 to 9.5) post-PCI, compared to 26.5 hours (25.2–27.8) for OH patients. Mean estimated post-PCI hospital costs (including abciximab infusion when used, other medications, nursing time, meals, etc..) were $1004 ($929–$1079) in the SDD group versus $3117 ($2975–$3260) in the OH group, saving, on average, $2113 per patient (p&lt;0.001). Within 30 days of discharge, only 50 patients were rehospitalized, 29 after SD discharge and 21 after OH (p=0.26). Conclusion: Same-day home discharge after an uncomplicated transradial PCI and a single bolus of abciximab resulted in a 68% relative saving in post PCI costs. In our trial, SDD of 504 patients saved over 1 million dollars to the hospital.
Prevention of vertical transmission of HIV in South Africa
Authors: C. Gunneberg, K Rotchford, S S A. Karim, N Rollins, K. Zwi, N. Soderlund
Journal: BMJ (1999)

Editor-Bero's editorial on commercial sponsorship for research is important 1 because commercial interests can bias the conduct and reporting of research. 2It may, however, leave the impression that pressure on research is an issue only in relation to commercial sponsorship.I used to believe that public sponsors would allow the independent conduct of research, but experiences have taught me otherwise.Recent stories in the Norwegian mass media indicate that public sponsors may also breach ethical codes for research sponsorship.Newspapers have told their readers that the ministry of education tried to influence research into the effects of an educational reform, 3 while a trade union tried to keep secret a report on privatisation of municipal services. 4 The National Council of Tobacco and Health asked a research team to change its methods for analysing the economic consequences of smoking: the methods had been agreed on before the project started, but the council later asked the team to switch to a method that would make smoking seem more "costly" to society. 5 In the end, the funding was stopped.For all three cases, the sponsors denied any unethical conduct.Industry's motive for influencing research is obvious (profit), but the motives of public sponsors may be obscure.The perceived benefits from getting the "right" results are probably related more to organisations or interest groups than to individuals.Conceivably, civil servants or other parties see themselves as agents for public interests that entitle them to influence research.In the commercial sector agents are more used to criticism for biased research and may be better aware of the ethical rules.Interestingly, some researchers say they feel less pressure when undertaking research for the pharmaceutical industry than for government.
Diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm By Using 10-Colour Flow Cytometry and Achievement of Remission By Hypercvad Therapy
Authors: Uday Deotare, Elizabeth Hyjek, Anna Porwit, Rumina Musani, David Barth, Emina Torlakovic, Anne Tierens, Aaron D Schimmer, Andre C Schuh, Mark D. Minden, Vikas Gupta, Matthew D. Seftel, Naheed Alam, Karen W.L. Yee
Journal: Blood (2014)
Abstract 1805: Chromosome 9p21.3 Genetic Variation is Associated with Angiographic CAD but not with CAD Disease Burden
Authors: Chrissa P Mower, Jeffrey L Anderson, Benjamin D Horne, James J Park, Jesse L Coleman, Heidi T May, Mona S Jahromi, John F Carlquist
Journal: Circulation (2008)

Genetic variation at the 9p21.3 locus rs2383206 is associated with coronary heart disease (CHD) phenotypes. In a comparison of patients with and without angiographically confirmed CHD, the G allele of rs2383206 was present more frequently in diseased vs controls (normal angiograms). However, the pathophysiologic impact, whether it affects initiation, severity, or triggers an event, of the 9p21.3 locus remains unknown. We sought to determine whether 9p21.3 variation affects disease severity (promotion) by assessing its association with CAD burden. Methods: Genotyping for rs2383206 using 5′exonuclease chemistry (Taqman) was performed on 1759 subjects. Subjects were grouped as homozygous wild-type (low risk), heterozygous (intermediate risk) or homozygous risk-associated genotype (high risk). Disease burden was assessed by 1, 2, or 3 vessels; ≥70% stenosis and the validated Duke CAD Index (DCI). Comparison used a chi-square test (single vs multivessel disease) and analysis of variance (ANOVA) for the DCI comparison. Results: Average age 51.1± 7.4 years, 64.0% male. Frequency of the CAD risk allele did not differ among groups with 1, 2, or 3 vessel disease. There was no difference among groups with respect to the DCI. After adjustment for standard cardiac risk factors, the rs2383206 genotype was associated with CAD compared to controls (OR (CI)=1.73(1.26–1.85), p=0.001). Conclusion: The rs2383206 polymorphism was not associated with CAD disease burden. Findings suggest the rs2383206 polymorphism, although associated with disease onset is not likely involved in its progression. These findings will aid in refining the application of 9p21.3 for risk assessment and developing novel preventive and therapeutic strategies.
Abstract 17979: A Subset of Patients with Isolated Transposition of the Great Arteries and Double Outlet Right Ventricle Fall Within the Spectrum of Heterotaxy Syndrome
Authors: Lisa C D'Alessandro, Brande C Latney, Prasuna C Paluru, Elizabeth Goldmuntz
Journal: Circulation (2011)

Background: Heterotaxy is a rare disorder of laterality. ZIC3 was the first gene in which human disease-causing mutations were identified. Mutations typically result in males with situs ambiguus and complex congenital heart disease; however affected females and one male with isolated transposition of the great arteries (TGA) have been reported. We hypothesized that a subset of patients with heart defects common to heterotaxy but without laterality defects would have ZIC3 mutations. We also sought to estimate the prevalence of ZIC3 mutations in sporadic heterotaxy. Methods and Results: Patients with TGA (n=169), double outlet right ventricle (DORV) (n=90), complete atrioventricular canal (n= 41) and heterotaxy (n=53) underwent sequencing of the ZIC3 open reading frame. We tested 90 patients with tetralogy of Fallot (TOF) to correlate genotype with phenotype. Three mutations were detected: 1 female with isolated DORV [c.49G&gt;T (Gly17Cys)], 1 male with isolated TGA [c.98C&gt;T (Ala33Val)], and 1 female with sporadic heterotaxy [841C&gt;T (His280Tyr)] that were absent in 100 Caucasian and 100 African American control patients. We also identified a novel insertional mutation (CPFP333ins) in a family with heterotaxy. No mutations were found in cases with TOF. Transcriptional activation studies demonstrated significantly reduced transcription of the ZIC3 His280Tyr mutant construct. Conclusions: Isolated TGA and DORV, like heterotaxy, can arise from mutations in ZIC3, confirming a spectrum of disease that includes isolated cardiac malformations. ZIC3 mutations were found in 2% of patients with sporadic heterotaxy, therefore routine testing should be considered in patients with heterotaxy.
Abstract 17738: CRP Predicting Locus at 6q22 Modulates Risk of Ventricular Fibrillation in Acute Myocardial Infarction
Authors: Raha Pazoki, Michael W Tanck, Darshan Dalal, Jonas S de Jong, Arthur A Wilde, Connie R Bezzina
Journal: Circulation (2011)

Sudden cardiac death is a leading mode of death in adults in the Western world and is largely caused by ventricular fibrillation (VF) during acute myocardial ischemia-infarction (MI). A genetic component in risk of VF in the setting of MI is recognized. However, the underlying genetic factors remain largely unknown. Plasma concentration of C-reactive protein (CRP) is a predictor of sudden cardiac death. Recently, several single nucleotide polymorphisms (SNPs) have been revealed to be associated with CRP levels in genome-wide association studies (GWAS). In this study we investigated the effect of CRP-predicting SNPs in modulation of risk of VF in acute MI. Methods: Patients studied were from the Arrhythmia Genetics in the NEtherlands Study (AGNES), consisting of patients with a first acute MI, with those suffering VF classified as cases (n=515) and those not suffering VF classified as controls (n=457). Twenty independent SNPs (r2&lt;0.75) previously found to be associated with CRP levels at genome-wide significant p-values (P&lt;5e-08) in previous GWAS were identified. Genotypes were obtained by direct genotyping (Illumina 610) or were imputed using HapMap. A Bonferroni-corrected threshold of P&lt;0.002 was used to define statistical significance in testing of individual SNPs. We also generated a genetic risk score based on the number of CRP-increasing alleles. Logistic regression modeling was used to test for association with VF. Results: SNP rs6901250 in GPRC6A was strongly associated with VF in acute MI (OR:1.39;95%CI:1.14,1.69;P=9.6e-04), with the CRP-increasing allele being associated with increased risk for VF. Analysis of SNPs in a 50 Kb region around rs6901250 identified a stronger signal at SNP rs633420 (P=9.7e-05) which was in high linkage disequilibrium (r2=0.73) with rs6901250. The CRP genetic risk score generated based on the number of CRP-increasing alleles was associated with risk of VF after MI (OR: 1.07; 95%CI: 1.01,1.12; P=0.01). Conclusions: CRP-predicting loci in aggregate and rs6901250 individually are associated with risk of VF in MI. Our study highlights the role of inflammatory loci on risk of VF after acute MI.
Abstract 17600: Membrane Trafficking of Large Conductance, Ca2+-and Voltage-Activated K+ (bk) Channels is Modulated by Rab4GTPase
Authors: Xiaoli Wang, Tong Lu, Hon-Chi Lee
Journal: Circulation (2012)

The large-conductance Ca2+-activated K+ (BK) channels are important ion channels, linking the metabolic state and cellular Ca2+ homeostasis with cellular excitability. The BK channel provides an im...
Abstract 1750: Collateral Flow and Early Reperfusion Reduce Infarct Transmurality and Prevent Left Ventricular Remodeling After ST-Segment Elevation Acute Myocardial Infarction
Authors: Jose T Ortiz, Sheridan N Meyers, Charles J Davidson, Thomas A Holly, Francis J Klocke, Robert O Bonow, Edwin Wu
Journal: Circulation (2006)

The presence of left ventricular (LV) remodeling following an acute ST-segment elevation myocardial infarction (STEMI) is associated with adverse outcomes. We hypothesized that early reperfusion an...