tbuckley/cabot-search huggingface dataset:
Prognostic Significance of Nodal and PgR Status on Early Relapse in Operable HER-2 Positive Breast Cancer from the Pre-Trastuzumab Era.
Authors: H. Cho, V. Van Belle, T. Vandorpe, H. Wildiers, H. Janssen, K. Leunen, F. Amant, I. Vergote, P. Berteloot, A. Smeets, E. Van Limbergen, C. Weltens, R. Paridaens, S. Van Huffel, M. Christiaens, P. Neven
Journal: Cancer Research (2009)

Abstract Background: Over the last decade, trastuzumab has become a standard adjuvant treatment option in HER-2 positive breast cancers. However, with a mainly 'on-treatment' effect only, the economic burden and adverse effects incurred from its routine use for 1 year following completion of chemotherapy, there emerges a need to identify a group of HER-2 positive breast cancers at low-risk for relapse. We, therefore, investigated potential prognostic factors in a cohort of HER-2 positive breast cancers in the era before trastuzumab, especially focusing on hormonal status.Methods: We retrospectively reviewed the data of 240 trastuzumab-naïve patients with a HER-2 FISH-positive breast cancer who had primary surgery at University Hospitals Leuven between January 2000 and December 2005. We collected data including age at diagnosis, menopausal status, histologic type, tumor size, grade, lymph node involvement, estrogen receptor (ER) /progesterone receptor (PgR) status, and disease-free survival (DFS) outcome. A multivariate Cox hazard model was used to identify prognostic factors and the cumulative DFS rate was determined using the Kaplan-Meier method.Results: After a median follow-up of 57.5 months there were 50 breast cancer related events meaning that 5-year DFS rate was 78.4% for the entire cohort. Median time to first event was 20 months and ranged from 4 to 96 months. Cox model revealed that only PgR status and lymph node involvement were independent prognostic factors for disease relapse. (p = 0.03 and p &amp;lt; 0.01 respectively). In Kaplan-Meier analysis, patients with PgR+ showed better DFS rate than those with PgR- (figure 1; 83.8% vs. 73.1%, p = 0.02) while ER status didn't reach statistical significance (p = 0.154).Nodal involvement ≥4 was strongly associated with poor DFS rate compared with node negativity. (p = 0.00). Of note, a subgroup of patients with PgR+ and LN-. presented no relapse within the first two years after surgery (figure 2).Conclusions: In this series of HER-2 positive breast cancers, PgR and nodal status were strong prognostic factors for early breast cancer relapse. Patients with a PgR+/LN- phenotype were unlikely to relapse within the first two years of surgery. We propose to evaluate the added benefit of adjuvant trastuzumab to chemotherapy in women with this phenotype as such data are yet not available from the major adjuvant trastuzumab trials. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6046.
Pathological analysis and endoscopic ultrasonography in diagnosis of submucosal tumors of esophagus
Authors: Xin Xu, Bangmao Wang, Yixiang Chang, Qingxiang Yu, Chao Sun, Wentian Liu
Journal: Endoscopy (2011)

Submucosal tumours (SMTs) are relatively common findings in patients undergoing endoscopy, especially in upper gastrointestinal (GI) tract. This term includes various non-neoplastic and neoplastic conditions. Endoscopic ultrasonography (EUS) is the best imaging procedure to characterise SMT and to determine the need for further explorations. In this review, the following issues will be addressed: the endosonographic features of SMT; the diagnostic accuracy of EUS; the ability of EUS to distinguish benign and malignant SMTs.
DIABETES MELLITUS DOES NOT WORSEN LONG-TERM SURVIVAL FOLLOWING ISOLATED SURGICAL AORTIC VALVE REPLACEMENT: A PROPENSITY MATCHED ANALYSIS
Authors: Benjamin van Boxtel, Robert Sorabella, Nathaniel Langer, Nathaniel Kheysin, Andres Gomez, Sanatkumar Patel, Catherine Wang, Koji Takeda, Takayama Hiroo, Yoshifumi Naka, Michael Borger, Michael Argenziano, Craig Smith, Isaac George
Journal: Journal of the American College of Cardiology (2016)
P70 Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV Treatment-Naive patients: final results of phase 3 ADVANCE Study
Authors: G. M. Dusheiko, L. Bengtsson, N. Adda, R. Kauffman, I. M. Jacobson
Journal: Gut (2011)

<h3>Aim</h3> The ADVANCE study is a 3-arm double-blind, randomised, placebo-controlled Phase 3 study assessing efficacy and safety of two telaprevir (TVR, T)-based response-guided regimens compared with peginterferon alfa-2a 180 _g/week and ribavirin 1000–1200 mg/day (PR) in treatment-naive patients with chronic genotype 1 HCV infection. <h3>Method</h3> Treatment arms were (a) T 750 mg q8 h in combination with PR for 8 weeks, followed by additional weeks of PR; (b) T 750 mg q8 h in combination with PR for 12 weeks, followed by additional weeks of PR; (c) PR for 48 weeks (control arm). Patients in T arms achieving an extended rapid viral response (eRVR, undetectable HCV RNA at weeks 4 and 12) received a total of 24 weeks of therapy while those who did not received a total of 48 weeks of therapy. Randomisation was 1:1:1 and patients were stratified by HCV RNA (&lt;800 000 IU/ml, ≥800 000 IU/ml), and genotype 1a vs. 1b. The primary endpoint was SVR (undetectable HCV RNA 24 weeks after last planned dose of treatment). The primary analysis was based on the Full Analysis (intention-to-treat) dataset. Safety is presented for TVR/Placebo duration phase. <h3>Results</h3> Of 1088 patients, 839 (77%) had HCV RNA ≥800 000 IU/ml, 631 (58%) were genotype 1a, 636 (58%) male, 94 (9%) black, 117 (11%) Latino/Hispanic, 231 (21%) had bridging fibrosis or compensated cirrhosis. The most common (&gt;25%) AEs in the T arms were fatigue, pruritus, nausea, headache, anaemia, rash, influenza-like illness, insomnia, fever, and diarrhoea. Discontinuation of treatment due to AEs occurred in 8% in T8PR, 7% in T12PR and 4% in PR48; due to rash occurred in 0.5%, 1.4% and 0.0% and due to anaemia occurred in 3.3%, 0.8% and 0.6% in T8PR, T12PR and control arms, respectively. <h3>Conclusion</h3> A significantly greater proportion of patients achieved SVR with 12-week and 8-week telaprevir-based combination regimens (75% and 69%, respectively), compared with PR48 control arm (44%, p&lt;0.0001). The safety and tolerability profile of telaprevir in the ADVANCE trial was consistent with the profile previously reported, with an improvement in treatment discontinuation rates due to adverse events, including rash and anaemia. These first Phase 3 results confirm the clinical benefit previously reported in Phase 2.
Ineffective Treatment of Muscular Dystrophy with an Anabolic Steroid and Other Measures
Authors: William M. Fowler, Carl M. Pearson, Glen H. Egstrom, Gerald W. Gardner
Journal: New England Journal of Medicine (1965)

THROUGHOUT the years many agents have been tested for their therapeutic benefit in muscular dystrophy, a relentlessly progressive disease. Eventually, all have been found to be ineffective after careful evaluation, including a variety of anabolic hormones.1 2 3 4 5 6 7 8 More recently Dowben9 has presented preliminary evidence that patients with muscular dystrophy showed significant "improvement" when treated by a program consisting of the anabolic steroid, 1-methyl-Δ1 androstenolone acetate,ǁ digitoxin and exercise.The purpose of this report is to re-evaluate such a therapeutic program in muscular dystrophy when the drugs are used singly, in combination and with or without exercise. Objective serial measurements were made . . .
Extensive dabigatran-induced exfoliative esophagitis harboring squamous cell carcinoma
Authors: Vincent Zimmer, Markus Casper, Frank Lammert
Journal: Endoscopy (2014)

A 90-year-old woman presented to the emergency ward with chest pain and odynophagia. Her medical history included chronic atrial fibrillation, for which she had been started a treatment with the novel oral anticoagulant dabigatran 6 months previously. The patient had not complied with the strict instructions relevant to the intake of dabigatran, namely that it needs to be taken while in an upright position with food or with an 8-ounce glass of water.
Phase II ECOG trial of atrasentan in advanced renal cell carcinoma
Authors: J. Manola, M. Carducci, S. Nair, G. Liu, S. Rousey, G. Wilding
Journal: Journal of Clinical Oncology (2007)

5102 Background: Atrasentan, an oral selective endothelin A receptor antagonist, demonstrated activity in patients with RCC included in Phase I studies. Based on these preliminary findings, a phase II study was undertaken in patients with measurable or nonmeasurable (bone only) metastatic RCC. Methods: Patients with locally recurrent or metastatic disease were stratified on disease status (measurable or bone only metastases) and prior immunotherapy. Eligible patients also had no prior chemotherapy, no more than 1 prior immunotherapy, and ECOG PS 0, 1, or 2. Prior nephrectomy was permitted. Patients received atrasentan 10 mg/day po until progression or unacceptable toxicity. Standard RECIST criteria were used to assess response. The primary endpoint was the progression-free rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A two-stage design was used for cohorts with no prior immunotherapy. Results: Between July 2003 and July 2005, 98 patients were registered. Four patients were ineligible and 1 withdrew before treatment. Median duration of treatment was 10 weeks (range, 2 to 107 weeks). Toxicities were mild, with 73% of patients reporting no Grade 3 or higher treatment- related adverse events. Grade 4 adverse events included neutropenia (n=3), dyspnea (n=2), thrombosis and supraventricular arrhythmia (n=1 each). Six-month progression-free rates (90% CI) were 14% (6 - 25%), 0% (0 - 39%), 12% (3 - 28%) and 17% (5 - 38%) respectively for patients with prior immunotherapy and measurable disease (n=44), prior immunotherapy and bone metastases only (n=6), no prior immunotherapy and measurable disease (n=25), and no prior immunotherapy and bone metastases only (n=18). Median progression-free survival was 2.3 months (95% CI, 2.0 - 3.5 months). Conclusions: While well-tolerated, atrasentan did not yield 6-month progression-free rates that would support its use as first-line monotherapy in patients with advanced RCC. No significant financial relationships to disclose.
Abstract 1469: Cyclin D1 plays a critical role in the response of mammary gland to estrogen and progesterone by regulating progesterone receptor expression
Authors: Chuanwei Yang, Li Chen, Cuiqi Li, Mary C. Lynch, Emmett V. Schmidt
Journal: Cancer Research (2010)

Abstract Estrogen and progesterone are important hormones in normal female development, yet both have critical roles in breast carcinogenesis. Cyclin D1 is a breast cancer oncogene whose amplification is linked to poor prognosis in estrogen and progesterone receptor positive breast cancers. Here we show that cyclin D1 regulates progesterone receptor expression, consequently enhancing responses to estrogen and progesterone in breast development and carcinogenesis. Estrogen treatment of cyclin D1 transgenic mice caused mammary hyperplasias expressing increased progesterone receptors, which were stimulated by progesterone and blocked by a progesterone antagonist. Cyclin D1 regulated progesterone receptor expresion through a novel estrogen- and cyclin D1-responsive enhancer in DNA encoding part of the 3’ untranslated region of the progesterone receptor gene. Small inhibitory RNAs for cyclin D1 decreased progesterone receptor expression in human breast cancer cells, which sensitized them to progesterone-antagonists. Since estrogen and progesterone regulate cyclin D1, our results suggest that cyclin D1's participation in a feed-forward loop could contribute to increased breast cancer risks associated with estrogen and progesterone combinations. Additionally, its regulation of the progesterone receptor identifies a novel role for cyclin D1 in ovarian hormone control of breast development and breast carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1469.
AB0854 Infectious Sacroiliitis: Clinical and Therapeutic Features (About 17 Cases)
Authors: Z. Alaya, N. El Amri, F. Bellazreg, K. Baccouche, S. Belghali, H. Zeglaoui, N. Amara, W. Hachfi, A. Letaief, E. Bouajina
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Bone and joint infections are polymorphic and can take various forms. Infectious sacroiliitis are a special rare form and a misleading diagnosis. <h3>Methods</h3> This is a retrospective study of 17 cases of infectious sacroiliitis collected in department of Rheumatology and Infectious Diseases in Hospital Farhat Hached in Tunisia over a period of 21 years [1993-2013]. <h3>Results</h3> Our population consists of 10 women and 7 men with a mean age of 42.7 years [21-78 years]. Clinical signs of appeal were inflammatory buttock pain (n=17), low back pain (n=1), pseudo- radicular pain (n=2) and a major functional impairment (n=4). General symptoms observed were fever (n=15), night sweats (n=7) and deterioration of the general status (n=12). These symptoms were acute in 7 cases, subacute and chronic in 5 cases each. Comorbidities were diabetes (n=1) and hemodialysis (n=1). The inflammatory syndrome was missing in one case, and leukopenia was noted in 3 cases. Standard radiographs were normal in 6 cases. Soft tissue abscess were objectified by CT (n=5) and MRI (n=1). Contributing factors of sacroiliitis were urinary tract infection (n=7), genital infection (n=1), recent blood transfusion (n=1), intramuscular injection (n=1), skin infection (n=3) and pregnancy (n=4) (1 case of ongoing pregnancy, 1 case of peri -abortion and 2 cases of post- partum). In 6 cases, sacroiliitis was secondary to sepsis. The causative organisms were isolated in 13 cases by blood cultures (n=4), urinalysis (n=4), biopsy of the sacroiliac joint (n=1), biopsy of soft tissue abscess (n=3) and Wright serology (n=5). Identified germs were brucellosis (n=5), Staphylococcus aureus (n=4), Escherichia coli (n=4), Mycobacterium tuberculosis (n=2), Klebsiella pneumonia (n=1), Klebsiella oxytoca (n=1) and Pseudomonas aeruginosa (n=1). Associated osteoarticular infectious locations occurred in 5 cases. These were an infectious spondylitis (n=2), a symphysis pubis arthritis (n=2), a shoulder arthritis (n=1) and a hip bilateral arthritis (n=1). The treatment consisted of appropriate antibiotics in all cases and surgical drainage of soft tissue abscess resistant to medical treatment in one case. The outcome was unfavorable in 2 patients who presented with septic shock. <h3>Conclusions</h3> The diagnosis of infectious sacroiliitis should be considered in any febrile buttock pain, especially in case of some contexts (septicemia, urogenital infections, peri-partum ...). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5463
The practice of physical activity of the Portuguese adults and fulfilment of physical activity recommendations
Authors: João Pedro Carvalho, Joana André, Luís Raia, João Martins, Adilson Marques, Francisco Carreiro da Costa
Journal: British Journal of Sports Medicine (2011)

The aim of the study was to analyse (by sex and age) the practice of physical activity (PA) in Portuguese adults according to the recommendation for PA. The sample consisted of 2657 adults (1130 male, 1527 female) age 20 to 60 y (43±7 y). PA was assessed by a questionnaire about leisure time activities and PA participation. The number of PA sessions per week and their intensity were taken into account to determine the meeting of the recommendations (moderate-intensity aerobic PA for a minimum of 30 min. 5 days/week, or vigorous PA for a minimum of 20 min 3 days/week). The data were analysed separating age, by brackets of 10 years, and sex. Statistical analyses were performed using qui-square and t-test. For the entire sample, only 32% (men 32%, women 31%) met the guidelines of PA. While the percentage of male that met the recommendation was higher among youngsters (43%), among women the oldest were the most active (33%). In general, there was no significant differences between sexes and the meeting of the recommendations ( p =0.636). Within adults, both male and female, age-groups were not different ( p =0.860, p =0.932). Analysing each age-group, the percentage of males that meet the recommendation was higher than female at age of 20–30 (43% vs 30%) and 41–50 (33 vs 315). On the other hand, the opposite was observed at age of 31–40 (30% vs 32%) and 51–60 (32% vs 33%). Although the percentage of men and women that meet the recommendation were different in all age-groups, it was observed that the meeting of the PA guidelines were independent of the sex – 20–30 ( p =0.181), 31–40 ( p =0.513), 41–50 ( p =0.398) and 51–60 ( p =0.912). Most of the participants did not practise enough PA to meet the recommendations. Both sexes have similar results in each age-group, demonstrating that both sex and age have no relationship with the meeting of PA guidelines.
Abstract 1531: HtrA1 sensitizes ovarian cancer cells to cisplatin-induced cytotoxicity by targeting XIAP for degradation
Authors: Xiaoping He, Ashwani Khurana, Jacie L Maguire, Jeremy Chien, Viji Shridhar
Journal: Cancer Research (2011)

Abstract We have previously identified serine protease HtrA1 as a down-regulated gene in ovarian cancer and loss of HtrA1 may contribute to cell resistance to cisplatin treatment. However, the exact mechanism by which HtrA1 regulates chemosensitivity in ovarian cancer is currently unknown. Here, we used mixture-based oriented peptide library approach and identified XIAP, an important member of the inhibitor of apoptosis (IAP) protein family, as one possible substrate of HtrA1. Recombinant wild type (WT) HtrA1 but not protease-inactive SA mutant HtrA1 can cleave XIAP protein in vitro. Over-expression of HtrA1 led to decreased level of XIAP in OV167 and OV202 ovarian cancer cells, while down-regulation of HtrA1 resulted in increased level of XIAP in SKOV3 ovarian cancer cells. CDDP treatment enhanced the cleavage of XIAP by HtrA1. Immuno-precipitation assay revealed that HtrA1 binds to XIAP directly both in vitro and in vivo. Increased cell resistance to cisplatin treatment was observed in SKOV3 and TOV-21G cells after stable knockdown of HtrA1 with shRNA. In contrast, over-expression of HtrA1 in OV202 cells promotes cell sensitivity to cisplatin treatment which can be reversed by increased expression of XIAP. In conclusion, our experiments reveal XIAP as a novel substrate of HtrA1 and the mechanism by which HtrA1 confers cell sensitivity to cisplatin treatment may be partially through its degradation of XIAP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1531. doi:10.1158/1538-7445.AM2011-1531
SAT0004 Genomic signatures characterize leukocyte infiltration in myositis muscles
Authors: W. Zhu, K. Streicher, N. Shen, B.W. Higgs, C. Morehouse, L. Greenlees, K. Ranade, L. Richman, D. Fiorentino, B. Jallal, S.A. Greenberg, Y. Yao
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. <h3>Objectives</h3> We employed a genomics approach to assess the inflammatory cell infiltration in myositis. <h3>Methods</h3> Muscle biopsies from 31 myositis patients and 5 normal healthy donors were profiled by microarray in parallel with microRNA (miRNA) expression analyses. <h3>Results</h3> Several gene signatures, such as the leukocyte index, type 1 interferon (IFN), MHC-1 and immunoglobulin signatures, were developed to characterize myositis patients at the molecular level. The leukocyte index was comprised of genes predominantly associated with the immune function and displayed a strong concordance with the pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to evaluate expression changes of transcripts due to leukocyte infiltration in myositis muscle biopsies. The ability to distinguish different sources of altered gene expression in heterogeneous tissues increased our understanding of the complex interactions crucial to the pathogenesis of myositis. Such approach can be applied to various other studies and allowed more accurate interpretation of the underlying biology with gene expression data from heterogenous tissue samples. One application of the leukocyte index comparing miRNA and mRNA expression profiles revealed a complex interaction between miR-146a expression and the regulation of the type 1 IFN pathway in dermatomyositis. <h3>Conclusions</h3> Collectively, the distinct miRNA and mRNA signatures identified in this study may contribute to the development of new therapeutic targets and provide utility as molecular biomarkers for characterizing inflammatory myopathies. <h3>Disclosure of Interest</h3> W. Zhu Shareholder of: Astra Zeneca, Employee of: MedImmune, K. Streicher Shareholder of: Astra Zeneca, Employee of: MedImmune, N. Shen Consultant for: MedImmune, B. Higgs Shareholder of: Astra Zeneca, Employee of: MedImmune, C. Morehouse Shareholder of: Astra Zeneca, Employee of: MedImmune, L. Greenlees Shareholder of: Astra Zeneca, Employee of: MedImmune, K. Ranade Shareholder of: Astra Zeneca, Employee of: MedImmune, L. Richman Shareholder of: Astra Zeneca, Employee of: MedImmune, D. Fiorentino: None Declared, B. Jallal Shareholder of: Astra Zeneca, Employee of: MedImmune, S. Greenberg Consultant for: MedImmune, Y. Yao Shareholder of: Astra Zeneca, Employee of: MedImmune
House dust mite: a new player in intestinal inflammation?
Authors: Manon E Wildenberg, Gijs R van den Brink
Journal: Gut (2016)

Over the past decades, incidence rates of immune-mediated inflammatory diseases including asthma and IBDs have been rising steadily in both Western and low/middle-income countries.1 The cause of this increase has been a topic of intense investigation, and a variety of factors such as diet, hygiene and pollution have been implicated. One of the most clear correlations between disease and environment is that between exposure to house dust mite (HDM) and asthma exacerbations.2 HDM contains several antigens, including Der p1 , a cysteine protease that damages the airway epithelium thus allowing antigens to pass into the pulmonary tissue.3 In atopic individuals, this results in a potent IgE-mediated specific anti- Der …