tbuckley/cabot-search huggingface dataset:
Abstract 3019: TGFβ3 is a less potent inducer of TGFβ signaling than TGFβ1 in non-small cell lung cancer cells
Authors: Sarah Elizabeth Anne McLean, Gianni M. Di Guglielmo
Journal: Cancer Research (2012)

Abstract Transforming growth factor beta (TGFβ) is an essential cytokine for tissue homeostasis. Its signalling pathway is under intense study as it is commonly dysregulated in many cancers, including pancreatic cancer, non-small cell lung cancer, and colorectal cancer. The TGFβ signalling cascade is propagated by the binding of ligand to cell-surface serine-threonine kinase receptors, which leads to the phosphorylation of receptor regulated Smad (R-Smad) proteins. There are three main ligands capable of activating the classical TGFβ pathway: TGFβ1, TGFβ2 and TGFβ3. These ligands show distinct spatial and temporal expression patterns and have non-overlapping functions in vivo. Extensive studies have been conducted on the role of TGFβ1 in the tumour microenvironment, and the role of TGFβ3 has largely been thought to be the same as TGFβ1 though there are few studies to support this claim. Interestingly in the wound microenvironment, TGFβ1 and TGFβ3 have vastly different signalling outcomes: TGFβ1 promotes the formation of a scar while TGFβ3 induces scar-free wound resolution. The objective of the present study was to evaluate the signalling capacity of TGFβ1 and TGFβ3 in non-small cell lung cancer cells. Our studies show that TGFβ3 is less potent at initiating Smad2 phosphorylation than TGFβ1, resulting in reduced transcriptional activity, as assessed by microarray analysis. We also observed that TGFβ3 is less effective than TGFβ1 at altering cell-cell adhesions. In order to assess the differences in signalling potential, we investigated TGFβ receptor engagement at the cell surface using radiolabelled TGFβ ligands. We observed that the ratio of activated receptors in signalling complexes is altered in the presence of TGFβ3, which may lead to a decreased signalling capacity. Future studies will evaluate the capacity of TGFβ3 to induce cancer cell migration and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3019. doi:1538-7445.AM2012-3019
Abstract 1775: Characterization of new highly selective and potent PARP-1 inhibitors
Authors: Alessia Montagnoli, Gianluca Papeo, Sonia Rainoldi, Antonella Ciavolella, Francesco Sola, Rosita Lupi, Marina Ciomei, Alessandra Cirla, Alessandra Scolaro, Helena Posteri, Daniele Donati, Eduard Felder, Antonella Isacchi, Enrico Pesenti, Arturo Galvani
Journal: Cancer Research (2012)

Abstract Poly (ADP-ribose) polymerase 1 (PARP-1) is a key nuclear enzyme that is activated by DNA-strand breaks; activation of PARP-1 protects DNA breaks and chromatin structure and recruits DNA repair and checkpoint proteins to the sites of damage, by modification with poly(ADP-ribose) (PAR) polymers. PARP-2, another nuclear member of the PARP family with largely unknown functions, shares homology with PARP-1 and is also activated by DNA breaks. Embryonic knock out of either PARP-1 or PARP-2 is well tolerated; however, double knockout is embryonic lethal suggesting that inhibiting both PARPs could enhance toxicity. PARP inhibitors in clinical development generally inhibit more than one PARP isoforms. These compounds are synthetic lethal with defects in homologous recombination (HR), and are currently being tested in combination as well as in monotherapy for hereditable cancers deficient in the BRCA1 or BRCA2 genes. Here we describe the in vitro and in vivo properties of a novel class of potent and selective PARP-1 small molecule inhibitors. Starting from a series of derivatives that were found to be active against PARP-1 and PARP-2, an expansion and optimization program was undertaken. This led to the identification of inhibitors with single digit nM affinity for PARP-1 and negligible crossreactivity against PARP-2. Members of this sub-series display single agent cytotoxicity with IC50s below 1 μM in cell lines harboring BRCA mutations, or in cells stably transfected with BRCA-1 short harpin RNA, and more than 100 times selectivity against BRCA wild-type tumor cell lines. Furthermore, these compounds are highly active in other repair deficient backgrounds such as ATM and Mre11 mutated acute leukemias and lymphomas and they compared favorably with reference PARP inhibitors which are in clinical development. Expected mechanism of action was confirmed by observed modulation of PAR induction, in vitro and in vivo. These compounds show high oral bioavailability, good ADME properties and high tolerability. Selection of the candidate most suitable for further development is underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1775. doi:1538-7445.AM2012-1775
INTRAMYOCARDIAL HEMORRHAGE AFTER REPERFUSED MYOCARDIAL INFARCTION IS RELATED TO ANATOMIC LOCATION OF THE CULPRIT AND ANTI-COAGULANT THERAPY
Authors: Ruben Tijssen, Paul Teunissen, Rodrigo Fernandez-Jimenez, Gonzalo Pizarro, Ines Garcia-Lunar, Peter van de Ven, Aernout Beek, Martijn Smulders, Sebastiaan Bekkers, Niels Van Royen, Borja Ibanez, Robin Nijveldt
Journal: Journal of the American College of Cardiology (2016)
Filling Buckets
Authors: Matthew J. Press, Timothy J. Judson, Allan S. Detsky
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
PMO-001 The role of the specialist screening practitioner within the bowel screening wales programme
Authors: R Kyte
Journal: Gut (2012)

<h3>Introduction</h3> Bowel Screening Wales (BSW) was launched nationally in October 2008. With its launch came the introduction of a unique, autonomous nursing role which is placed at the interface of secondary and primary care. <h3>Methods</h3> Specialist Screening Practitioners (SSPs) are based at all BSW Local Assessment Centres (LACs) throughout Wales. The original sixteen SSPs employed prior to the inception of the BSW programme had diverse clinical backgrounds and all underwent a 4-week induction programme. On returning to their local areas, SSPs were supported by a programme of clinical induction which incorporated an understanding of agreed competencies. During the initial induction phase SSPs were mentored by the Regional Nurses and Lead Screening Colonoscopists. The role of the SSP is multi faceted. They apply advanced expert clinical knowledge and experience alongside evidence based decision making skills to support participants who have received a positive faecal occult blood test and have consented to speak to a SSP. Each practitioner has their own participant caseload for which they are accountable. They assess participants9 fitness to undergo a colonoscopy, arrange the colonoscopy, consent the participants prior to the colonoscopy and are present during the colonoscopy. They also give results, ensure that the participants are placed on the routine recall or surveillance pathway, refer to and attend Multi Disciplinary Team meetings following a participant9s diagnosis of cancer. Many participants require considerable support from their SSP due to their medical history which may include mental health issues, the presence of co-morbidity and social problems. As the role of SSP is an advanced nursing role all practitioners are required to posses or be working towards a Degree. BSW has collaborated with Cardiff University to develop a MSc module. All Wales SSP network meetings are held twice per year and offer educational and peer support. SSPs employed since the autumn of 2008 undergo a programme of induction based on their educational needs. <h3>Results</h3> As a result of the support given by SSPs, participants are well informed about the procedure. Compliance with bowel preparation is high as is evidenced by the low numbers of incomplete colonoscopy. There is a very low rate of participants who do not attend for colonoscopy. <h3>Conclusion</h3> Over the last 3 years the role of the SSP has continually evolved. The role can be further developed by sharing knowledge and good practice on a UK wide basis. <h3>Competing interests</h3> None declared.
338 NK CELL SECRETED IFN-g BLOCKS HCV REPLICATION AND MAY PROMOTE SPONTANEOUS CLEARANCE OF ACUTE HEPATITIS C IN HIV(+) PATIENTS
Authors: P. Kokordelis, B. Krämer, C. Boesecke, C. Körner, E. Voigt, P. Ingiliz, M. Eisenhardt, A. Glässner, F. Wolter, C.P. Strassburg, U. Spengler, J.K. Rockstroh, J. Nattermann
Journal: Journal of Hepatology (2013)
Carcinogenicity studies on vinylidene chloride.
Authors: P L Viola, A Caputo
Journal: Environmental Health Perspectives (1977)

Results of a study on Wistar rats regarding a possible carcinogenic effect of vinylidene chloride (VDC) were presented previously by one of the authors. Due to the unclear character of these results, a second inhalation study was initiated with Sprague-Dawley rats. Groups of 60 animals were exposed to 100 and 75 ppm VDC, along with one control group. A final report on the pathological results must await completion of the microscopic examination of the tissues and organs from all the animals. Nevertheless, it seems clear that there is no grossly observable interrelation between tumor production and VDC inhalation.
FRI0071 Self-reported patterns of job loss and social security benefits claims in early rheumatoid arthritis: The eran cohort:
Authors: D.F. Mcwilliams, A. Young, P. Kiely, D.A. Walsh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> RA is an important cause of disability and job loss, and financial pressures attributed to RA may increase applications and eligibility for social security benefits. Better understanding of these social impacts of early RA may help develop and target interventions. <h3>Objectives</h3> This study assessed the rate of job loss and new social security benefits claims in a cohort of early RA. <h3>Methods</h3> ERAN is an inception cohort of patients with early RA, given standard care in the UK and Eire. At baseline, and during each annual study visit, participants (n=1235) were asked to report employment, job loss, retirement and whether they were claiming social security benefits due to RA. Associations of patient and disease characteristics with baseline employment and benefit status were determined by logistic regression. Survival analyses of the time to first self-reported job loss and benefits claim were by Cox regression. <h3>Results</h3> Participants at baseline had median age of 58 years and 66% were female. At baseline, 47% reported they were employed and 52% were not (mostly retired); also 17% reported claiming benefits due to RA and 79% did not. At baseline, non-workers were older, and had more females, disease activity and disability. Baseline benefits claimants had higher pain, disability and symptom duration, and more fulfilled 1987 ACR criteria. The median (IQR) follow up period was 3 (1 – 4) years. Due to RA, 10% (49/475) of working participants lost their employment and 20% (179/905) began to claim benefits. Most loss of employment or new benefits claims were within 2 years of baseline assessment. Univariate Cox regression found baseline disability, pain, poorer mental health, low vitality, smoking history and disease activity were all associated with shorter time to job loss or benefits claim. Independent baseline predictors of earlier job loss were bodily pain and low vitality (see Table 1). In contrast disability and extra-articular disease predicted early benefits claim (Table 1). <h3>Conclusions</h3> Peak onset of RA is around retirement age, which was younger for females at the time. Job loss due to RA, however, was not predicted by age or gender. Benefits claims due to RA target the economic burden of disability, probably explaining associations with HAQ. Job loss due to RA was predicted by high pain and low vitality, rather than disease activity. Further research should investigate whether interventions targeting these symptoms can help job retention. <h3>Disclosure of Interest</h3> D. Mcwilliams Grant/Research support from: Pfizer Ltd, A. Young: None Declared, P. Kiely: None Declared, D. Walsh Grant/Research support from: Pfizer Ltd, Consultant for: Pfizer Ltd
Violations of the Embargo and a New Policy on Early Publicity
Authors: Jerome P. Kassirer, Marcia Angell
Journal: New England Journal of Medicine (1994)

Given the public's interest in the possibility of preventing illness or forestalling death by taking vitamins, it probably was inevitable that the paper entitled “The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers” in the April 14 issue of the Journal1 would receive wide attention. The study failed to demonstrate a protective effect of those antioxidant vitamins on the risk of lung cancer and even suggested that beta carotene might increase the risk. Our subscribers, most of whom do not receive the Journal until Thursday, the day of publication, . . .
P153 The effect of body mass index on outcomes of acute non-invasive ventilation (NIV) in a district general hospital
Authors: H. Liddicoat, C. Zammitt, J. Loft, I. Moonsie, H. Makker
Journal: Thorax (2010)

<h3>Introduction</h3> The increasing prevalence of obesity is likely to affect the caseload of Non-invasive Ventilation (NIV) units. We hypothesised that outcomes in the obese and morbidly obese population would differ from patients with a normal Body Mass Index (BMI) on the NIV unit. <h3>Method</h3> We audited all patients admitted to the NIV unit from January 2007 to December 2009. Patient demographics, admitting diagnosis, baseline arterial blood gases (ABG), duration on NIV, length of stay and outcome were recorded on BTS NIV audit proformas. BMI was obtained from GP records. Data were analysed using Prism 5. <h3>Results</h3> A total of 176 patients (46% male, median age 74), were managed on the NIV unit. The admitting diagnosis was COPD (59%), Obesity hypoventilation syndrome (OHS) (13%), Cardiac failure (13%), Neuromuscular disorders (2%) or “other” diagnoses (13%). The median BMI was 27 (IQR 22.7–35.0); 6% of patients were underweight, 33% normal weight, 18% overweight, 26% obese and 17% morbidly obese. An increasing proportion of females were found in the obese and morbidly obese population (χ<sup>2</sup> p=0.003). No statistical differences were found in baseline ABG and NIV duration between different BMI categories. Compared to patients with a normal weight, obese and morbidly obese individuals had significantly longer lengths of hospital stay (Mann–Whitney U test p=0.004 and p=0.001, respectively). Outcomes did not differ between normal weight, underweight, or overweight patients. However, obese and morbidly obese patients were significantly more likely to survive admission compared to patients with a normal BMI (Abstract P153 Figure 1; χ<sup>2</sup> p=0.035 and p=0.0008, respectively). Similarly, there was no significant difference in age, gender, ABG parameters, NIV duration or length of stay between COPD and OHS patients. However, OHS patients were significantly more likely to survive admission (χ<sup>2</sup> p=0.0042). <h3>Conclusion</h3> The outcomes for obese and morbidly obese patients were significantly better than patients with a normal BMI, although the length of stay was higher. Despite similar demographic features and metabolic disturbance of COPD and OHS patients, OHS patients were more likely to survive admission.
AB0171 Muscle atrophy in murine model of arthritis is related to disease score
Authors: L. Filippin, V. de Oliveira Nunes Teixeira, P.S. Lora, P.R. Viacava, L.D.L. Xavier, M. Romero, R.M. Xavier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology, affecting the joint and also other tissues [Altindag, 2007]. RA patients usually present weakness and muscle atrophy, non-articular manifestation of the disease [Mirό, 1996]. Although causing great impact, the development of muscle atrophy and mechanisms involved is still very limited. <h3>Objectives</h3> To evaluate the development of muscle atrophy in skeletal muscle of murine model of arthritis. <h3>Methods</h3> We used the experimental murine model of collagen induced arthritis (CIA) conform Brand <i>et al</i> [2007]. Experimental animals were randomly divided into three groups (n=79): control (CO), sham arthritis (SA) and arthritis (CIA), analyzed in different time-points: 25, 35 and 45 days after induction of the arthritis. The arthritis development was followed by clinical scores three times a week and weight was evaluated weekly. Cytokine analysis was evaluated by CBA in serum collected before the death of the animals. Cross-sectional area of the myofiberof skeletal muscle (tibialis anterior - TA, gastrocnemius - GA) was measured. Significance was considered p&lt;0.05. <h3>Results</h3> Disease scores of arthritis groups were always different from their controls in all times, also in 45 days CIA group was different from other times and SA was different from CO (Table 1). There were no differences in myofiber cross-sectional area among groups in 25 and 35 days, however in 45 days CIA had reduced myofiber area (Table 1). Myofiber area did not differed among times on all experimental groups. There was no correlation between myofiber area and disease score when analyzing paws separately (left and right), however using a paw mean, this correlation was significant and inverse in 45 days (TA: -0.68 p=0.029 and GA: -0.71 p=0.021). CBA analysis showed IL-6 significantly inhanced in CIA. <h3>Conclusions</h3> Disease score is inversely correlated with myofiber area in 45 days, demonstrating that muscle atrophy was clearly presented when arthritis is established. Furthermore, this correlation is not symmetric. These observations are relevant to understand the development of muscle loss, as well as for the design of future studies trying to understand the mechanisms involved. As far as we concern, this is the first study to evaluate the relation between disease score and muscle atrophy in a model of arthritis. <h3>Disclosure of Interest</h3> None Declared
Risk Factors for Gastrointestinal Bleeding in Critically Ill Patients
Authors: Deborah J. Cook, Hugh D. Fuller, Gordon H. Guyatt, John C. Marshall, David Leasa, Richard Hall, Timothy L. Winton, Frank Rutledge, Thomas Todd, Peter Roy, Jacques Lacroix, Lauren Griffith, Andrew Willan
Journal: New England Journal of Medicine (1994)

The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit.
Histopathology of Breast Lesions Induced in BUF Rats of Varying Ages by Ingestion of N-4-(4'-Fluorobiphenyl)acetamide
Authors: Kurt Stromberg, Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1975)

Inbred BUF male and female rats 4, 12, 24, and 52 weeks old ingested 0.04 percent N-4-(4'fluorobiphenyl)-acetamide in a semisynthetic diet for 36 weeks. They were killed 12 weeks later. Susceptibility to mammary carcinogenesis was related to the age and sex of the animals. Younger female rats developed more mammary tumors. Approximately half of these mammary tumors were well-differentiated adenocarcinomas; the remainder were either poorly differentiated or anaplastic adenocarcinomas.
Reducing Health Care Costs by Reducing the Need and Demand for Medical Services
Authors: James F. Fries, C. Everett Koop, Carson E. Beadle, Paul P. Cooper, Mary Jane England, Roger F. Greaves, Jacque J. Sokolov, Daniel Wright
Journal: New England Journal of Medicine (1993)

Health care costs in the United States exceed 14 percent of the gross domestic product, far more than in any other nation. Overall costs were $838 billion in 1992, or over $3,000 per person1. Well over 30 million Americans are uninsured, partly because of rising premium costs2,3. We propose an approach to part of this problem that has been neglected, one that focuses on systematically reducing the need and thus the demand for medical services. This approach requires expanding the definitions of “health promotion” and “preventive care,” paying selective attention to strategies that have been found to . . .
Fdg Pet/Ct in Patients Treated with Neoadjuvant Chemotherapy for Localized Bone Sarcomas
Authors: E. Palmerini, C. Nanni, M. Colangeli, A. Paioli, S. Fanti, M. Gambarotti, P. Picci, D. Donati, S. Ferrari
Journal: Annals of Oncology (2014)