tbuckley/cabot-search huggingface dataset:
Health Care Policies and Europe: The Implications for Practice, by Carol Ludvigsen, Kathleen Roberts
Authors: S. Nicholas
Journal: BMJ (1997)

Carol Ludvigsen, Kathleen Roberts Heinemann, £14.99, pp 224 ISBN 0 7506 2485 X

Until recently “Europe” was a faraway continent of which most health professionals knew little, but the European Union is now making its mark on British medicine. It has made us change our specialist training system, for example, and European law on the mutual recognition of qualifications, coupled with our shortages and high medical unemployment elsewhere, means that more and more British doctors work alongside colleagues from other European countries. Doctors in training are exempted from the controversial directive on working time, but this may soon change. “Public health” per se has moved up the European …
Abstract 4163: Oncogenic function of miR-196s promote cell invasion through suppression of NME4 to regulate JNK-TIMP1-MMP signaling pathway in head and neck cancer.
Authors: Ann-Joy Cheng, Ya-Ching Lu, Joseph T. Chang
Journal: Cancer Research (2013)

Abstract Dysregulation of microRNA (miRNA) is associated with malignant transformation, while elucidating the roles remains an ongoing process. In this study, we characterize miR-196 functions in head and neck cancer (HNC). We found that neither miR-196a or miR-196b has an effect on cell growth, only miR-196a plays a role in protection cells from radiation damage, while both miR-196a and miR-196b actively promotes cell migration (1.7- to 2.7-fold) and invasion (2.1- to 2.3-fold), which were supported by the altered expressions of fibronectin and N-cadherin. Mechanistically, miR-196 achieves these functions by targeting and inhibiting the anti-metastatic family member NME4, which is further elucidated as a tumor suppressor to repress JNK protein phosphorylation, leading to TIMP1 inhibition and MMP1/9 activation. Furthermore, both miR-196a and miR-196b was significantly over-expressed in the cancer tissues compared to the normal counterparts, with approximately 60 and 10 fold elevations respectively in average. Over-expression of miR-196 was correlated to lymph node metastasis and poor survival. In summary, our findings define miR-196 as a crucial oncomir in HNC which acts at least in part, through NME4-pJNK-TIMP-MMP signaling pathway to promote cell invasion and cellular transformation. Citation Format: Ann-Joy Cheng, Ya-Ching Lu, Joseph T. Chang. Oncogenic function of miR-196s promote cell invasion through suppression of NME4 to regulate JNK-TIMP1-MMP signaling pathway in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4163. doi:10.1158/1538-7445.AM2013-4163
First line hormonal treatment (HT) for metastatic breast cancer (MBC) with exemestane (E) or tamoxifen (T) in postmenopausal patients (pts) - A randomized phase III trial of the EORTC Breast Group
Authors: R. Paridaens, P. Therasse, L. Dirix, L. Beex, M. Piccart, D. Cameron, T. Cufer, K. Roozendaal, M. Nooij, M.-R. Mattiacci
Journal: Journal of Clinical Oncology (2004)

515 Background: E is an aromatase inactivator, with demonstrated efficacy in MBC progressing under T, which remained standard 1st line HT over decades. The randomized EORTC phase II trial of E vs T, which showed promising activity in 1st line MBC (Ann. Oncol. 2003, 14: 1391–8) was extended in a phase III reported here, aiming at a true comparison of efficacy and tolerability of both drugs. Methods: Postmenopausal MBC pts with ECOG PS ≤2 and measurable, hormone responsive disease (ER &/or PgR + or unknown with disease free interval >2y) previously untreated with HT for MBC, were randomized to receive open label E 25mg or T 20mg daily. One prior chemotherapy (CT) for MBC was permitted. Prior adjuvant T was allowed if treatment free interval exceeded 6 mo. The trial was powered to detect an increase in median progression free survival (PFS, primary endpoint) of 3 mo in favor of E. Secondary endpoints were survival and tolerability. All analyses were intent to treat. Results: 382 pts accrued by 81 centers received E (190 pts) or T (192 pts). Both groups were balanced for median age (62.5), prior adjuvant CT (E 28%, T 29%) or CT for MBC (E 8%, T 7%), hormone receptor status, PS, prior adjuvant T (21% both) and dominant metastatic site (visceral E 48%, T 47%; bone E 35%, T 36%; soft tissue E 17%, T 17%). On 15/12/2003, 286 events (progression or death under treatment) and 136 deaths were reported. The median PFS is significantly longer under E than T (10.9 vs 6.7 months, p 0.04) with an HR of 0.79 (95% CI 0.62 - 0.99) in favor of E. Best response rates (%) under E were CR 7.4, PR 36.8, SD 27.4, PD 18.4, NE (not evaluable) 10.0; under T, CR 2.6, PR 26.6, SD 37.0, PD 27.6, NE 6.2). No pt withdrew due to toxicity. Grade 2–3 toxicities observed in ≥10% were bone pain (E 12%, T 18%), other pain (E 7%, T 14%) and hot flashes (E 5%, T 12%). Conclusions: E is a safe and highly active steroidal aromatase inactivator, superior to T in MBC. In view of its efficacy and excellent tolerance, E represents a good choice as first line therapy in hormone responsive MBC. Its safety profile makes E also attractive for use in the adjuvant and preventive settings. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca; Pfizer; Schering-Plough Pfizer
Abstract 2186: Characterization of a novel ubiquitin E3 ligase that targets tumor suppressor RASSF1A for degradation during mitosis
Authors: Lingyan Jiang, Rong Rong, M. Saeed Sheikh, Ying Huang
Journal: Cancer Research (2011)

Abstract Ras association domain family 1 isoform A (RASSF1A) is an important tumor suppressor. Loss or altered expression of RASSF1A has been associated with pathogenesis of a variety of cancers. RASSF1A is known to play an important role in regulation of mitosis, however, little is known about how RASSF1A is regulated during mitotic-phase of the cell cycle. In the present study, we have identified Cul4A as a RASSF1A E3 ligase and DDB1 serves as an adaptor protein to bring RASSF1A into the Cul4A-DDB1 complex. We have found that depletion of Cul4A E3 ligase results in increased levels of RASSF1A protein due to increased half-life; whereas overexpression of the Cul4A ligase markedly enhances RASSF1A protein ubiquitination resulting in reduced RASSF1A levels. We have further shown that Cul4A-mediated RASSF1A degradation occurs during mitosis and depletion of the E3 ligase markedly reverses mitotic-phase-stimulated RASSF1A degradation. Thus, our present study demonstrates that Cul4A is important for regulation of RASSF1A during mitosis and it may contribute to inactivation of RASSF1A thereby promoting cell cycle progression. 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 2186. doi:10.1158/1538-7445.AM2011-2186
AB0315 Is the efficacy of biologic therapeutic in rheumatoid arthritis is affected by body mass index?
Authors: J. F. Ferreira, M. G. Santiago, C. Duarte, J. A. P. Da Silva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Weight could be expected to affect the response to biological therapies by simply reducing the mg/Kg dose in fixed dose regimens. Furthermore, adipose tissue produces a variety of pro-inflammatory cytokines (as TNFa, IL-6, IL- 1) whose role in Rheumatoid Arthritis (RA) activity, remains unclear. <h3>Objectives</h3> The purpose of this study was to determine whether body mass index (BMI) is related with response to the biologic therapy adjusted to the weight (tocilizumab, infliximab) in RA patients. <h3>Methods</h3> Patients with RA followed in our day-hospital and registered in BioReportAR who had complete information of baseline and 12<sup>th</sup> week visit were included. Only patients with intravenously weight-adjusted therapy were considered. The body mass index (BMI) at baseline was calculated. Sociodemoraphic and clinical data were collected using data from the BioReportAR. Spearman correlation coefficient was used to analyse correlation between BMI and disease activity at baseline and its change after 12 weeks. Comparison between BMI categories was performed using Kruskal-Wallis test. p-values &lt;0,05 were considered as statistically significant. <h3>Results</h3> 45 patients were included (86,7% women, mean disease duration 12,93±10,69 years, mean age 57,11±11,0 years), 20 receiving tocilizumab and 25 infliximab. The BMI mean was 25,55±3,92 kg/m<sup>2</sup>, and at baseline the mean DAS28 was 3,06±1,33. No correlation between BMI and baseline DAS28 (r= -0,158; p=0,519), change DAS28 (r= -0,207; p= 0,177) and individual parameters of DAS calculation were observed. When we compared change in DAS 28 between BMI categories (BMI£25 kg/m<sup>2</sup> and &gt;25 kg/m<sup>2</sup>) it didn't show difference (p=0.607). <h3>Conclusions</h3> This study is the first that correlates tocilizumab and BMI. In this study, BMI was not associated with disease activity or response to tocilizumab or infliximab therapy. These negative results might be at least partially explained by the low number of patients with BMI <sup>3</sup>30 kg/m<sup>2</sup> (only 6) or by using BMI as unique marker of adipose tissue. <h3>Disclosure of Interest</h3> None Declared
THU0131 Long Term Results of Inhibition of Radiographic Joint Damage Progression in Small and Medium and Large Joints in Patients with Rheumatoid Arthritis Treated with Tofacitinib Monotherapy
Authors: K. Katayama, T. Okubo, T. Sato, R. Fukai, S. Abe, H. Ito
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tofacitinib is a novel oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). There was a study concerned with the efficacy for inhibiting the progression of radiographic joint damage (RJD) by tafacitinive (1). However, there has been no study to investigate inhibitory effects of small (hand and feet), medium and large (M-L) sized joints by tofacitinive. Here we report the tofacitinib efficacy of response up to 48 months with mono-therapy in long-term extension studies. <h3>Objectives</h3> To analyze inhibitory effects of RJD progression in small joints (12 and 48 months) and M-L sized joints (48 months) treated with tofacinitib mono-therapy. <h3>Methods</h3> The modified total sharp score (mTSS) was assessed to find small joint destruction. Twelve M-L sized joints (bilateral elbow, shoulder, hip, knee, ankle, and subtalar joints) were radiographically assessed by the Larsen method (Grade 0–5). Wilcoxon test was used for the statistical analysis. <h3>Results</h3> Data were shown in Table. ΔmTSS/year after tafacitinive treatment was significantly decreased from 22.1 (baseline) to 3.93 (median:1) (after 1 year) (p&lt;0.01), and 3.03 (median:1.8) (after 4 year) (p&lt;0.01). Only one patient with severe MRI osteitis in hand progressed joint destruction resistant to the therapy. Mean Larsen score of M-L joints from baseline (1.29) to the last observation (1.31) did not have significant changed. Atlant-axial subluxation occurred in 4 patients did not progress during tofacitinive therapy. <h3>Conclusions</h3> Progression of small and M-L sized joints were effectively inhibited by tofacitinive mono-therapy. <h3>References</h3> Désirée van der Heijde et al. Arthritis Rheum 2003;65:559-570 <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5385
Liver immunology and its role in inflammation and homeostasis
Authors: Mark W Robinson, Cathal Harmon, Cliona O’Farrelly
Journal: Cellular and Molecular Immunology (2016)

The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the non-diseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear 'dangerous' stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.
538 IMPROVED PREDICTIVE VALUE FOR SUSTAINED IMMUNE CONTROL IN PEGINTERFERON ALFA-2A (40KD) (PEGASYS)-TREATED HBEAG-POSITIVE PATIENTS USING COMBINED HBSAG AND HBV DNA LEVELS AT WEEK 24
Authors: T. Piratvisuth, H.L.Y. Chan, P. Marcellin, C. Wat, L. Regep, D. Messinger, H.-P. Kapprell, Z.M. Lu, K.X. Luo
Journal: Journal of Hepatology (2012)
Abstract 1753: High expression of the microtubule destabilizing protein stathmin is prognostic for worse outcome in breast cancer
Authors: Maria Baquero, Jason Hanna, Seema Agarwal, Elizabeth Killiam, Robert L. Camp, David L. Rimm
Journal: Cancer Research (2010)

Abstract INTRODUCTION: Taxanes are microtubule targeting agents (MTAs) and potent cytotoxic molecules recognized as highly effective chemotherapeutic agents. In large randomized clinical trials, taxane-based chemotherapies provided benefits in overall and disease-free survival, but they are accompanied by significant adverse effects. Thus the clinical utility of taxane therapy would be enhanced if there were companion diagnostic tests so that only the taxane-sensitive patients (about half of breast cancers) could be treated with this drug. Accumulating evidence indicates that microtubule associated proteins (MAPs) may be responsible for tumor cell resistance to taxanes. Here we use a large retrospective cohort to measure expression levels of stathmin, a microtubule destabilizing protein, and to determine prognostic value, as a first step toward development of a companion diagnostic. METHODS: Stathmin expression was measured in a large retrospective breast cancer cohort (n= 645) with 20 year follow-up using tissue microarray technology (TMA) in two-fold redundancy and quantitative immunofluorescence (AQUA). Patient stathmin expression levels were correlated with clinical, pathological, and disease free survival variables. RESULTS: Stathmin expression exhibited nonparametric distribution with high correlation (R= 0.70) between redundant TMA cores. Prognostic evaluation of the cohort using univariate analysis indicated an inverse correlation between high stathmin expression and overall survival (HR = 1.30, 95% confidence interval [CI] = 1.02-1.65; p&amp;lt; 0.028). Kaplan Meier survival analysis showed 10-year survival of 54% for patients with high stathmin expression versus a 65% survival rate for low expressers (log rank, P&amp;lt;.0058). Multivariate analysis indicated that high stathmin expression, nodal status, HER2 expression, and tumor size are independent predictors of survival. CONCLUSIONS: Stathmin expression in breast tumor tissue functions as a prognostic factor where high expression is associated with worse outcome. Since stathmin expression is useful in predicting survival, it may serve as marker to accurately select patients for current taxane-based or other anti-microtubule therapies. 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 1753.
Successful Repair of Subvalvular Annular Aneurysm of the Left Ventricle
Authors: John A. Waldhausen, Eugene L. Petry, Gerald J. Kurlander
Journal: New England Journal of Medicine (1966)

VENTRICULAR aneurysms most commonly occur as a result of myocardial infarction after coronary-artery occlusion.1 Less common causes include congenital defects, trauma and infection. Recently, Abrahams and his associates2 reviewed 12 cases of subvalvular annular aneurysms of the left ventricle of unknown etiology in which single or multiple sacs arose directly adjacent to the fibrous ring of the mitral or aortic valve. Additional cases have been reported by others,3 , 4 suggesting that the lesion is not extremely rare. With 1 exception3 previously reported cases have been in Negroes.In the present case a subvalvular annular aneurysm of the left ventricle was discovered . . .
Abstract 5014: Analysis of recruitment of patients into clinical trials for colorectal cancer
Authors: Richard Joubert, Moehler Thomas, Ulrich Raeth
Journal: Cancer Research (2011)

Abstract Background: Correct estimation of patient enrollment is an important success factor for planning clinical studies including studies for metastatic colorectal cancer (CRC). Methods: We performed a systematical review of all published articles on clinical studies in the indication colorectal cancer published in the Journal of Clinical Oncology and Annals of Oncology between 01/2007 and 10/2008 focusing on aspects relevant for patient recruitment. Results: Of the 43 studies we identified, 37 studies could be integrated in the final analysis. Most clinical studies were performed in the metastatic indication. Overall, a mean enrollment of 0.77 Patient/Site/Month (range 0.10 to 6.50) was observed with highest recruitment efficacy of 3.30 Patients/Site/Month (range 1.81 to 6.50) found in 4 single institution phase II trials. The recruitment rates in Patients/Site/Month were 0.67 for phase I trials, 1.35 for phase II trials and 0.32 phase III trials. The mean recruitment rate for all phase II/III multicenter trials was 0.46 Patients/Site/Month. Highest recruitment rates were recorded for third line studies investigating novel agents either as single agents or in an combination regimen in phase II settings. Conclusions: Phase II clinical trials on novel agents with high potential to change future treatment standard demonstrate almost a threefold higher-than-mean recruitment rate for multi-center trials (0.46 Patient/Site/Month). Despite some limitations in the interpretation of results, our analysis provides important information to support estimation of patient recruitment in future clinical trials for colorectal cancer. 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 5014. doi:10.1158/1538-7445.AM2011-5014
Soundings: The flagon... with the dragon
Authors: Liam Farrell
Journal: BMJ (2005)

It was more than just a heartsink consultation; it was tedious, nagging, grating, the kind of consultation that whispers the o'erwrought heart and bids it break. “You are in perfect health, Mrs Maguire,” I repeated.

“Are you sure I'm all right?”

“I'm sure.”

“Are you definitely sure?”

“Definitely.”

“Are you absolutely definitely sure?”

“Absolutely.”

“Are you absolutely definitely positively sure?”

“When was the last time someone actually hit you?” Of course I didn't say that; I was too busy gouging a scalpel into my left inner thigh and lapsing into my old defence mechanism of mumbling classic comedy sketches. “The pellet with the poison's in the vessel with the pestle, the chalice from the palace has...”

“I beg your pardon,” she said sharply.

“I'm sorry,” I said, “Did I say that out loud?”

“In any case,” she said, “there's been a change; the chalice is broken, they've had to replace it with a flagon.”

“With a flagon?” I said, surprised.

“With the figure of a dragon.”

“The flagon with the dragon,” I mused.

“Yes,” she said, “The vessel with the pestle has the pellet with the poison, the flagon with the dragon...”

“... has the brew that is true,” we shouted in unison, laughing and jumping up and down with excitement.

It was like being on the Road to Damascus while riding a bike for the first time and losing your virginity, all in one glorious blast; patients aren't one dimensional, I realised, they are real people with families, friends, lovers, jobs, passions. And Mrs Maguire's passion, I found out, was Hollywood comedies, pre-1960.

“Your proposition may be good...” I ventured.

“...but let's have one thing understood.” She was right with me.

Then, altogether, “Whatever it is, I'm against it.” We spent an agreeable last few minutes sparring over the relative merits of Bringing Up Baby and The Man Who Came To Dinner.

“By the way,” she said, “I've an awful sore throat; can I have an antibiotic?”

I looked at her, a trifle disappointed; had our time together meant nothing?

“Only kidding,” she said, deadpan.