tbuckley/cabot-search huggingface dataset:
AB0236 What Level of Disease Activity at 6 Months Predicts Achieving or Sustaining Remission at 12 Months?
Authors: E. Keystone, P. Baer, B. Haraoui, J.A. Avina-Zubieta, A. Chow, D. Sholter, D. Choquette, E. Rampakakis, J.S. Sampalis, F. Nantel, A.J. Lehman, M. Shawi, S. Otawa
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Achievement of clinical remission in rheumatoid arthritis (RA) is a process that may take several months. Identification of clinical signs predicting future remission may assist physicians in clinical decision making. <h3>Objectives</h3> The aim of this analysis was to describe the association between DAS28-ESR scores at 6 months and remission at 12 months in RA patients treated with infliximab (IFX) in a real-world, clinical practice setting. <h3>Methods</h3> BioTRAC is an ongoing, prospective Canadian registry of patients initiating treatment for RA, ankylosing spondylitis (AS), or psoriatic arthritis (PsA) with IFX or golimumab as first biologics or after having been treated with a biologic for &lt;6 months. Eligible patients for this analysis included RA patients treated with IFX who were enrolled between 2002 and 2012 and had available DAS28 data at 6 and 12 months of follow-up. The association between DAS28-ESR score at 6 months and remission achievement at 12 months was assessed with logistic regression. Receiver operator curve (ROC) analysis was used to determine the optimal cut-off points for achieving and maintaining remission. <h3>Results</h3> A total of 293 patients were included with a mean (SD) age of 56 (13.5) years and disease duration of 10.0 (9.7) years. Mean (SD) DAS28 was 3.8 (1.5) and 3.5 (1.5) at 6 and 12 months, respectively, and the percent with DAS28-ESR remission was 24.6% and 27.0%. Of the patients in remission at 6 months, 65.3% sustained the remission at 12 months, while of those not in remission at 6 months, 14.5% achieved remission at 12 months (P&lt;0.001). Logistic regression analysis showed a significant inverse association between DAS28-ESR score at 6 months and the likelihood of achieving remission at 12 months [for each increase in DAS28-ESR score by one unit there was a 64.6% lower probability of achieving remission; P&lt;0.001]. ROC curve analysis identified a DAS28 score at 6 months ≤3.54 as most accurately predicting remission at 12 months with a sensitivity of 82% and a specificity of 70% (Fig. 1A). Stratified analysis showed that, among patients in remission at 6 months, a DAS28 score of ≤2.13 was the optimal cut-off for predicting sustained remission at 12 months (68% sensitivity, 64% specificity) (Fig. 1B). <h3>Conclusions</h3> The results of this analysis demonstrate that a DAS28-ESR target of ≤3.54 at 6 months maximizes the likelihood of remission at 12 months while a value of ≤2.13 should be targeted for optimal sustainment of remission. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4755
Abstract 5068: Identification of RASSF1A as a novel RhoA antagonist: direct interaction with and Smurf1-mediated ubiquitination of RhoA
Authors: Byung-Kyu Ryu, Min-Goo Lee, Min-Ju Kang, Tae-Kyu Ha, Jikhyon Han, Nam-Gu Her, Seong-In Chung, Sung-Gil Chi
Journal: Cancer Research (2010)

Abstract RASSF1A is a tumor suppressor which plays a critical role in the regulation of various aspects of cellular functions, including cell proliferation, apoptosis, and motility. RASSF1A is frequently inactivated in various types of human cancers by transcriptional silencing of the gene due to aberrant promoter hypermethylation. However, molecular mechanisms underlying its tumor suppressive functions were largely undefined. We characterized RASSF1A regulation of a small GTPase RhoA and its implication in tumor cell migration and invasion. Effect of RASSF1A expression on RhoA activity was examined by immunoblot, immunopricipitation, and ubiquitinylation assays, and RASSF1A modulation of RhoA-mediated cell migration and invasion was determined using wound healing and in vitro invasion assay. We identified that RASSF1A inhibits serum- or LPA-induced RhoA activation in both cancer cells and noncancerous cells. SiRNA-mediated knockdown of RASSF1A increases RhoA activity and RhoA-mediated tumor cell migration. RASSF1A promotes the protesomal degradation of GTP-bound RhoA via Smurf1-mediated ubiquitinylation, but does not affect the activity and stability of Rac1 and CDC42. Immunofluoroscence and immunopricipitation assays revealed that RASSF1A colocalizes and interacts with RhoA and Smurf1. The N-terminal region of RASSF1A interacts with Smurf1, and its C-terminal residues (amino acids 266-272) are critical for the interaction with RhoA. The mutant RASSF1A (delNC-RASSF1A) having a sequence alteration in the Smurf1 and RhoA binding region fails to inhibit the RhoA-mediated tumor cell migration and invasion. Consistent with theses results, loss or abnormal reduction of RASSF1A expression exhibits a tight correlation with RhoA activation in both cancer cell lines and primary tumors of various tissues origins. Our study demonstrates first that RASSF1A regulates cell motility through the proteosomal degradation of activated RhoA through Smurf1-mediated ubiquitinylation, indicating that genetic and epigenetic inactivation of RASSF1A during tumorigenic process increases the invasive and metastatic potential of tumor cells by deregulation of RhoA. 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 5068.
THU0211 Gastrointestinal manifestations of behçet’s disease in japan: A study of 43 patients:
Authors: H. Ideguchi, A. Suda, M. Takeno, S. Ohno, Y. Ishigatsubo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> We analyzed the clinical gastrointestinal (GI) characteristics of Behçet's disease (BD) patients in Japan. <h3>Methods</h3> We retrospectively reviewed the clinical charts of 412 patients who fulfilled the 1987 Japanese criteria for BD and were treated in two University hospitals from July 1991 to December 2007. <h3>Results</h3> Forty-three patients (10.4%) had BD related GI lesions which were shown by imaging examinations. Mean age at BD diagnosis and onset of GI episodes were 34.2 and 36.2 years, respectively. The patients suffered from abdominal pain (70%) and GI bleeding (42%), while they had lower frequency of eye involvement and higher incidence of arthritis and vascular involvement than BD patients without GI lesions. The lesions were prevalent in the ileum (74%) followed by cecum (49%) and esophagus (21%). The patients were treated with mesalazine and sulfasalazine (96%), corticosteroids (74%), immunosuppressants (30%), and infliximab for 7 patients having refractory lesions (16%), while 10 patients had surgical operation (23%). Two patients died due to non-GI events during the observation. <h3>Conclusions</h3> The diagnosis of BD was often difficult because of lack of eye involvement. Surgery is required for some patients in spite of intensive immunosuppressive therapies. Appropriate use of anti-TNF agents may be promising for the GI involvement. <h3>Disclosure of Interest</h3> None Declared
Abstract 1725: HDAC inhibition induces Bim expression and apoptosis in breast cancer cells undergoing paclitaxel or antiestrogen treatment.
Authors: Aric Berning, Alexander Eason, Nathan Gilley, Suchreet Takhar, Sally ElShafey, Muthusamy Thangaraju, Patricia V. Schoenlein
Journal: Cancer Research (2013)

Abstract Paclitaxel functions by preventing microtubule degradation, leading to mitotic arrest and apoptotic death. Of particular interest, paclitaxel-induced death in breast cancer cells is dependent, in part, on the levels of BimEL, a pro-apoptotic member of the Bcl-2 family of proteins. In addition, our recent studies demonstrated that BimEL is required for 4-hydroxytamoxifen-induced apoptosis of estrogen receptor positive (ER+) MCF-7 breast cancer cells [Breast Cancer Res. 2012 Mar 19;14(2):R52]. In contrast, we demonstrated low-level BimEL expression in ER+ T47D breast cancer cells that do not undergo antiestrogen-induced apoptosis. Thus, low-level BimEL expression in ER+ breast cancer may predict a poor apoptotic threshold which ultimately would facilitate the development of acqured resistance to paclitaxel, as well as antiestrogen therapy. Based on the ability of HDAC inhibitors to increase the transcription of pro-apoptotic genes, we hypothesized that the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) would increase BimEL expression in T47D breast cancer cells and induce a robust apoptotic response to paclitaxel chemotherapy and antiestrogen treatment. In this study, we now demonstrate that SAHA does significantly up-regulate BimEL expression in T47D cells, as well as in MCF-7 cells. Concomitant with BimEL upregulation, SAHA sensitizes T47D and MCF-7 cells to paclitaxel-induced apoptosis. Similarly, SAHA sensitizes T-47D cells to antiestrogen-induced apoptosis, while augmenting the level of antiestrogen-induced apoptosis in MCF-7 cells. These studies indicate that the pro-apoptotic protein BimEL is required for SAHA-induced sensitization of breast cancer cells to paclitaxel and/or antiestrogen-induced apoptosis. Currently, siRNA studies are being conducted to determine if BimEL is a key death effector in response to SAHA treatment and if the increased death from SAHA and paclitaxel or SAHA and antiestrogens is synergistic or additive. Our results provide strong support for the use of HDAC inhibitors when designing novel combination therapies to reduce the emergence of acquired resistance in breast cancer cells undergoing chemo- or antihormonal therapy. Acknowledgement: this work was supported by teh MCG foundation and NIHRO1 CA121438 to P.V.S. Citation Format: Aric Berning, Alexander Eason, Nathan Gilley, Suchreet Takhar, Sally ElShafey, Muthusamy Thangaraju, Patricia V. Schoenlein. HDAC inhibition induces Bim expression and apoptosis in breast cancer cells undergoing paclitaxel or antiestrogen treatment. [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 1725. doi:10.1158/1538-7445.AM2013-1725
Evaluation of Costs and Impact in Quality of Life in Patients with Surgical Site Complications after Breast Cancer Surgery.
Authors: P. Arrieta-Joffe, O. Cerezo, E. Bargallo, E. Cruz, A. Lozano, D. Vilar-Compte
Journal: Cancer Research (2009)

Abstract Background: Surgical site complications (infection, dehiscence, necrosis) continue to be an important cause of morbidity in patients undergoing breast cancer surgery. It seems to have a negative impact in quality of life and an increase in health-care costs in comparison with patients with a satisfying outcome.Meterial and Methods:Using two questionnaires to evaluate quality of life from the European Organization for the Research and Treatment of Cancer (EORTC), QLQ-C30 and BR-23, we analyzed 90 breast cancer patients after surgery. We obtained information about direct costs (gloves, gauze, antibiotics, wound dressing, hospital admission) and indirect costs (travel time, transport, day off at work) related to post-surgery consults. We analyzed dissimilarities concerning self-perception of quality of life between patients with and without surgical complications and differences in health-care treatment costs.Results: Twelve (11.76%) patients developed surgical site infection (SSI), 6 (5.88%) necrosis and 9 (8.8%) dehiscence.Self-perception of quality of life was decreased in patients with surgical site complications.The crude median costs of complicated patients was $1,368 US dollars compared to $992 US dollars in non-complicated patients. After adjusting costs according to type of complications only statistical significance was found in patients with SSI and dehiscence (95% confidence interval, $203-$301 and $94-$170 respectively) and the direct costs showed the most important difference.Discussion: The direct and indirect costs was superior in complicated than in non-complicated patients and there was a decrease in self-percieved quality of life, which is consistant with other findings. This should awaken interest in applying new methods to reduce risk of surgical site complications. There is an important lack of evidence regarding quality of life and costs related to post-surgery complications in any health care facilities in our country, which wil make this the first study to do it, specially in breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3110.
Abstract 908: Identification of novel dynamic biomarkers of FGFR inhibition by the FGFR1,2 and 3 selective inhibitor AZD4547.
Authors: Oona Delpuech, Claire Rooney, Lorraine Mooney, Robert McEwen, Sarah Fenton, Dawn Baker, Robert Shaw, Jonathan Dry, Elaine Kilgour, Paul Smith
Journal: Cancer Research (2013)

Abstract AZD4547 is an orally bio-available, highly selective and potent small molecule inhibitor, ATP competitive inhibitor of FGF receptors 1, 2 and 3. To identify novel dynamic transcript biomarkers of FGFR signalling inhibition by AZD4547, a gene expression profiling study was performed. Cell lines defined as sensitive or resistant to AZD4547 (n=10 for each class) were treated with AZD4547 or DMSO control for 2, 6 or 24 hours and processed for microarray analysis. Amongst those genes modulated by AZD4547, the MEK signature genes DUSP6 and ETV5, together with the MAPK pathway regulator SPRED1 were repressed on AZD4547 treatment across all sensitive cell lines over time, consistent with FGFR signalling through this pathway. Further in vivo validation using three FGFR sensitive/responsive xenograft models (SNU16, KMS11, KG1a) was performed. We observed time dependent repression (16h to 24h) of DUSP6, ETV5 and SPRED1 across all three xenograft models which was consistent with plasma exposure of AZD4547 in vivo. In addition, modulation of these transcript biomarkers corresponded with inhibition of phosphorylation of FGFR, FRS2 and ERK, supporting engagement of the FGFR signalling pathway. Taken together, these data identify novel dynamic biomarkers of FGFR inhibition in vivo. Citation Format: Oona Delpuech, Claire Rooney, Lorraine Mooney, Robert McEwen, Sarah Fenton, Dawn Baker, Robert Shaw, Jonathan Dry, Elaine Kilgour, Paul Smith. Identification of novel dynamic biomarkers of FGFR inhibition by the FGFR1,2 and 3 selective inhibitor AZD4547. [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 908. doi:10.1158/1538-7445.AM2013-908
Immunologic defects in severe mucocutaneous HSV-2 infections: Response to IFN-γ therapy
Authors: Peer Arts, Frank L. van de Veerdonk, Robin van der Lee, Martijn A. Langereis, Christian Gilissen, Wendy A.G. van Zelst-Stams, Martijn A. Huynen, Jos W.M. van der Meer, Frank J. van Kuppeveld, Joris A. Veltman, Bart Jan Kullberg, Alexander Hoischen, Mihai G. Netea
Journal: Journal of Allergy and Clinical Immunology (2016)
Panel sketches out plan for US neuroscience initiative
Authors: M. McCarthy
Journal: BMJ (2013)

The initial focus of a new major US neuroscience initiative should be to accelerate the development of technology needed to gain insights into how the nervous system functions, concentrating on the analysis of neuronal circuits, says a working group charged to draw up a plan for the project.1

The project, the BRAIN (short for brain research through advancing innovative neurotechnologies) Initiative, was launched last April by President Barack Obama, who said that the goal of the multi-year project was to give “scientists the tools …
p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia
Authors: Audrey M. Hendley, Yue J. Wang, Kishore Polireddy, Janivette Alsina, Ishrat Ahmed, Kelly J. Lafaro, Hao Zhang, Nilotpal Roy, Samuel G. Savidge, Yanna Cao, Matthias Hebrok, Anirban Maitra, Albert B. Reynolds, Michael Goggins, Mamoun Younes, Christine A. Iacobuzio-Donahue, Steven D. Leach, Jennifer M. Bailey
Journal: Cancer Research (2016)

Abstract Aberrant regulation of cellular extrusion can promote invasion and metastasis. Here, we identify molecular requirements for early cellular invasion using a premalignant mouse model of pancreatic cancer with conditional knockout of p120 catenin (Ctnnd1). Mice with biallelic loss of p120 catenin progressively develop high-grade pancreatic intraepithelial neoplasia (PanIN) lesions and neoplasia accompanied by prominent acute and chronic inflammatory processes, which is mediated, in part, through NF-κB signaling. Loss of p120 catenin in the context of oncogenic Kras also promotes remarkable apical and basal epithelial cell extrusion. Abundant single epithelial cells exit PanIN epithelium basally, retain epithelial morphology, survive, and display features of malignancy. Similar extrusion defects are observed following p120 catenin knockdown in vitro, and these effects are completely abrogated by the activation of S1P/S1pr2 signaling. In the context of oncogenic Kras, p120 catenin loss significantly reduces expression of genes mediating S1P/S1pr2 signaling in vivo and in vitro, and this effect is mediated at least, in part, through activation of NF-κB. These results provide insight into mechanisms controlling early events in the metastatic process and suggest that p120 catenin and S1P/S1pr2 signaling enhance cancer progression by regulating epithelial cell invasion. Cancer Res; 76(11); 3351–63. ©2016 AACR.
Chemotherapy for Tuberculous Meningitis
Authors: Peter R. Donald
Journal: New England Journal of Medicine (2016)

Tuberculous meningitis, the most destructive form of tuberculosis, continues to be associated with considerable mortality and morbidity; among children, it is the major cause of death resulting from tuberculosis. The consequences of tuberculous meningitis are yet again clearly shown in the article by Heemskerk et al. in this issue of the Journal.1 This randomized, controlled study of tuberculous meningitis in Vietnamese adults, probably the largest ever undertaken, was carefully planned and executed and evaluated an intensified regimen that included both a higher dose of oral rifampin than the standard dose (15 mg per kilogram of body weight vs. 10 . . .
We can learn much from the air force
Authors: Annelies E Mitchell, Thomas A Eastwood, Ian M Mitchell
Journal: BMJ (2011)

The NHS has begun to learn lessons from other professions and industries. An example derived from aviation is the introduction of safety checklists. A 2008 World Health Organization directive now requires surgical teams to complete a theatre checklist to ensure correct identification of the patient and the operation to be performed and that equipment is available (www.who.int/patientsafety/safesurgery/ss_checklist/en/index.html). However, checklists alone do not improve patient safety. Anecdotal evidence suggests that in many cases such imposed checklists are resented; are too non-specific; and are often completed in haste, with a routine “yes” being given when really the answer was “no.”

The Royal Air Force (RAF) is a large, financially stretched, public sector employer that has many similarities to the NHS, and we may have much to learn from it. Correct completion of safety checklists is a training priority for aircrews, and gaining competency in the completion of such checklists is a prerequisite before a new pilot starts flying. The checklists are highly …
Pertussis immunisation and control in England and Wales, 1957 to 2012: a historical review
Authors: G Amirthalingam, S Gupta, H Campbell
Journal: Eurosurveillance (2013)

This review summarises the epidemiology and control of pertussis in England and Wales since the introduction of routine immunisation and considers the implications for future control. Routine infant immunisation with a whole-cell pertussis (wP) vaccine was introduced in 1957 and had a marked impact on the overall disease burden. Following a fall in vaccine coverage during the 1970s and 80s linked to a safety scare with wP vaccine, there was an extended period of high coverage and pertussis incidence fell dramatically. Incidence continued to decrease with the introduction of an acellular pertussis vaccine in the pre-school booster in November 2001 and in the primary United Kingdom (UK) schedule in September 2004 but has increased since July 2011. In response to a high rate of pertussis in infants, a temporary vaccination programme for pregnant women was introduced in October 2012. The key aim of the programme is to protect vulnerable infants from birth in the first months of life, before they can be fully protected by routine infant immunisation. A review of the UK adolescent immunisation programme is currently ongoing and the inclusion of a pertussis booster is being considered.
LONG-TERM USE OF DUAL ANTIPLATELETS FOR THE SECONDARY PREVENTION OF ATHEROTHROMBOTIC EVENTS IN PATIENTS WITH AND WITHOUT MI: META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Zaher Fanari, Amratash Malodiya, Sandra Weiss, Sumaya Hammami, Paul Kolm, William Weintraub
Journal: Journal of the American College of Cardiology (2016)
Abstract 4209: Organotypic multicellular glioma spheroids prepared from tissue fragments obtained by ultrasonic aspiration
Authors: Stine S. Jensen, Charlotte Aaberg-Jessen, Javad Jabbari, Claus Andersen, Henrik D. Schrøder, Bjarne W. Kristensen
Journal: Cancer Research (2010)

Abstract Ultrasonic aspirators are commonly used to resect brain tumors because they allow safe, rapid and accurate removal of dissected tissue. However, the tissue fragments removed by ultrasonic aspirators are used surprisingly little in daily diagnostics and in clinical research. Due to the increasing need for vital human tumor tissue for these purposes, which today require multidisciplinary approaches, the aim of this study was to investigate whether tissue fragments obtained by ultrasonic aspiration could be cultured as organotypic multicellular spheroids. These spheroids have earlier been shown to represent an important alternative to commercially available cell lines having multiple mutations and phenotypic changes. Fragments obtained by ultrasonic aspiration (sonocut) from one anaplastic astrocytoma and seven glioblastomas and tumor biopsy tissue from four of these glioblastomas were included in the present study. Sonocut and tumor biopsy tissue were mechanically dissociated into small tissue fragments and cultured in a serum containing medium on agar-coated plates. If excess tissue was available the fragments were also cultured in a serum-free medium. After 12-18 days of culturing the tissue fragments had formed spheroids which were fixated and paraffin embedded. Hematoxylin eosin staining was performed in order to investigate the viability and morphology of the spheroids. Part of the material was stained immunohistochemically for the astrocytic marker GFAP and the blood vessel markers VWF, CD31 and CD34. In the present study all sonocut cultures contained viable spheroids, whereas one of the cultures obtained from tumor biopsy tissue did not. The spheroids were able to survive and proliferate under both serum and serum-free conditions. The spheroids from both sonocut and tumor biopsy tissue contained malignant traits including high cellularity, cellular pleomorphism, mitoses and necrosis. Some spheroids consisted solely of GFAP positive tumor cells, while others contained preserved blood vessels confirmed by VWF, CD31 and CD34 immunohistochemistry. In conclusion, we found that it was possible to obtain viable spheroids from sonocut-material under both serum and serum-free conditions. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4209.