tbuckley/cabot-search huggingface dataset:
AB0362 B-Cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) in Postmenopausal Rheumatoid Arthritis Patients with Low Bone Mass: A Possible Protective Role of Hydroxychloroquine
Authors: T.A. Gheita, S.A. Kenawy, H.A. Gheita
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The increasing role of B-cells in the pathogenesis and management of RA, the common occurrence of postmenopausal osteoporosis with RA and the suggested responsibility of BAFF in autoantibodies production with affection of bone density were main motives to research in this area <h3>Objectives</h3> The aim of the present work was to study the serum concentration of BAFF in relation to postmenopausal low bone mass (LBM) associated with RA compared to those without RA and to study its relation to the bone turnover markers and bone mineral density. Comparing the results with an RA group with normal BMD was considered with the healthy control subjects. Relation of the findings to intake of hydroxychloroquine (HCQ) was considered. <h3>Methods</h3> The study included 68 postmenopausal LBM patients 34 with RA and another 34 without. Thirty age-matched postmenopausal healthy subjects were included as control. The laboratory investigations performed for the patients and control, included markers of bone formation; Osteocalcin (OC) and bone-specific alkaline phosphatase (b-ALP) and a marker of bone resorption; N- terminal cross linked telopeptides of type I collagen. Serum BAFF level was assessed in patients and control. Bone mineral density was quantified by dual energy x-ray absorptiometry (DXA). <h3>Results</h3> The bone turnover markers and DXA t scores were significantly different in the patients compared to control. The level of BAFF was significantly higher in RA patient with LBM (1.58±1.17 ng/ml) compared to patients with LBM only (1.03±1.04 ng/ml) (p=0.045) but was insignificantly different from the level in RA patients with normal BMD (1.29±0.87 ng/ml). BAFF significantly correlated with the DXA t score over distal radius and negatively correlated with the b-ALP. In the present study, the t score of the hip was significantly improved and the BAFF level significantly lower in those RA patients receiving hydroxychloroquine (HCQ). <h3>Conclusions</h3> the responsibility of B-cells and BAFF in the pathogenesis of postmenopausal LBM (osteopenia/osteoporosis) is shown in addition to their established role in RA. Hydroxychloroquine has a potential effect in reducing bone loss and should be considered among the first line armamentarium regimens in the management of RA cases. Introduction of new therapeutic options that selectively inhibit B-cells and target BAFF in osteoporosis should be considered especially when associated with RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1444
FRI0313 Prediction of total knee replacement in a 6-month multicentre clinical trial with chondroitin sulfate in knee osteoarthritis: Results from a 4-year observation
Authors: J.-P. Raynauld, J. Martel-Pelletier, M. Dorais, F. Abram, B. Haraoui, D. Choquette, F. Morin, L. Bessette, A. Beaulieu, J.-P. Pelletier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The guidelines from the regulatory agencies require that joint structure modification also translate into a significant clinical benefit for the patient before allowing the claim of DMOAD (1). To this end, the prevention of patient disability and of the need for joint replacement has been suggested as possible clinically relevant outcomes (2). <h3>Objectives</h3> To predict from clinical trial and MRI data the incidence of total knee replacement (TKR) during the long-term follow-up of knee osteoarthritis (OA) patients who formerly received chondroitin sulfate (CS) or placebo. <h3>Methods</h3> Symptomatic knee OA patients participating in a previous 6-month randomized, double-blind controlled trial evaluating the impact of CS (Condrosan®, Bioibérica S.A., Barcelona, Spain) (800 mg/day) vs. placebo, with subsequent 6-month extension with all patients on CS, were contacted to evaluate retrospectively the incidence of TKR of the study knee. A sub-group of patients (n=51) belonging to the according-to-protocol cohort were selected for this post-hoc retrospective analysis. The TKR incidence was assessed with a standardized phone interview. <h3>Results</h3> The patients' mean age was 62.9 years, 61% were female and the average body mass index was 30.6 kg$/$m<sup>2</sup>. A total of 13.7% TKRs were performed upon this sub-population in the time frame of 4 years after patient enrolment. More TKRs were performed within the placebo (71%) than the CS group (29%) (p=0.150, logistic regression). The baseline values of WOMAC pain (p=0.019, logistic regression), stiffness (p=0.013) and function (p=0.044), bone marrow lesions of the medial compartment (p=0.030), and C-reactive protein (CRP) levels (p=0.040) were strong predictors of TKR. Changes at 1 year in the medial cartilage volume (p=0.046) also predicted the occurrence of TKR. <h3>Conclusions</h3> In a knee OA clinical trial, it is possible to predict a "hard" outcome such as TKR using information from clinical and MRI data. The results also support the use of MRI as a surrogate for joint tissue damage upon which a DMOAD such as CS may act. <h3>References</h3> Guidance for the Industry. Clinical Development Programs for Drugs, Devices and Biological Products Intended for the Treatment Osteoarthritis. US Department of Health and Human Services. Food and Drug Administration, Center for Drug Evaluation and Research, July 1999. Altman RD et al. Osteoarthritis Cartilage 2005;13:13-9. <h3>Disclosure of Interest</h3> None Declared
Abstract 431: Cigarette-smoke-induced expression of MUC4 in human pancreatic cancer cells: Potential pathological roles
Authors: Navneet Momi, Moorthy Palanimuthu Ponnusamy, Surinder K. Batra
Journal: Cancer Research (2010)

Abstract Pancreatic cancer is a major problem worldwide and the fourth leading cause of cancer-related deaths in the United States. In the pancreatic malignancy, long term smoking is the most established risk factor. Cigarette smoke contains a variety of constituents of which nicotine is the major component present. Previously, we have shown that MUC4, a member of transmembrane mucin family, is aberrantly expressed in the pancreatic tumors compared to the normal pancreas and is functionally involved in the tumorigenecity and metastasis of pancreatic cancer. The aim of the study was to investigate the role of nicotine on the pathogenesis of pancreatic cancer and to check if MUC4 is the major regulator involved in the process. The western blot and confocal analysis showed a gradual increase in the expression of MUC4 with nicotine treatment of the cells in a dose-dependent manner. Further, it was seen that retinoic acid (RA), a known MUC4 regulator, plays a synergistic role along with the nicotine, in up-regulating MUC4 expression in CD18/HPAF-SF. Further, studies were performed in order to elucidate the possible regulatory mechanism behind the nicotine mediated MUC4 induction and it's downstream signaling. RT PCR and western blot analysis showed an over expression of the nicotine receptor subunit α7 in nicotine-treated CD-18/HPAF as compared to the untreated cells. In addition, the study revealed that the α7 nicotine receptor subunit mediated JAK2-STAT3 pathway and the FAK activation, are the main regulatory mechanisms involved. Furthermore, the role of the α7 nicotine receptor subunit was confirmed by treating the cells with an α7 receptor antagonist, DhβE, which reduced the MUC4 expression and the JAK2 mediated activation of STAT3. In addition, in vitro functional assays were performed to assess the effect of nicotine induced MUC4 on CD-18/HPAF cells. Interestingly, the wound healing assay showed an increase in the migration potential of nicotine treated CD-18/HPAF cells as compared to the untreated cells. The western blot analysis provides clear evidence that nicotine also facilitate the phenomenon of EMT in CD-18/HPAF cells as shown by the down-regulation of the epithleial marker, E-cadherin, and an up-regulation of the mesenchymal marker, N-cadherin. Overall, our study shows a malignant potential of nicotine in the pancreatic cancer pathogenesis through α7 receptor subunit mediated MUC4 induction, thereby, increasing the migration potential of pancreatic cancer cells. 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 431.
Endoscopic resection of an anal gland cyst
Authors: K. Uchimoto, N. Nishigori, H. Fujii, F. Koyama, T. Nakagawa, S. Nakamura, T. Ueda, Y. Nakajima
Journal: Endoscopy (2011)

A 61-year-old woman presented with the chief complaint of anal bleeding. On digital examination, a 5-mm elastic soft tumor was palpated in the posterior wall of the anal canal. Colonoscopy was performed which demonstrated a transparent 5-mm submucosal tumor in the posterior wall below the dentate line ([Fig. 1 a, b]).
545 HEAVY ALCOHOL USE IN THE ELDERLY IS ASSOCIATED WITH HEPATIC STEATOSIS BUT ONLY RESULTS IN SIGNIFICANT FIBROSIS IN A MINORITY OF SUBJECTS
Authors: J.G. Reijnders, J.N. Schouten, E.M. Koehler, B.E. Hansen, A. Hofman, H. Tiemeier, B. Stricker, H.L. Janssen
Journal: Journal of Hepatology (2013)
EMID: résultats finaux d'une étude prospective bicentrique évaluant l'endomicroscopie dans les voies biliaires. Impact dans la prise en charge des sténoses biliaires
Authors: F Caillol, E Bories, A Autret, F Poizat, R Dumas, C Pesenti, JF Demarquay, G Monges, M Giovannini
Journal: Endoscopy (2013)

L'endomicroscopie confocale (ECM) permet une biopsie optique, une histologie in vivo. Nous présentons ici les résultats définitifs de l'étude EMID comparant les biopsies optiques à l'histologie définitive.
Coronary Angioplasty with or without Stent Implantation for Acute Myocardial Infarction
Authors: Cindy L. Grines, David A. Cox, Gregg W. Stone, Eulogio Garcia, Luiz A. Mattos, Alessandro Giambartolomei, Bruce R. Brodie, Olivier Madonna, Marcel Eijgelshoven, Alexandra J. Lansky, William W. O'Neill, Marie-Claude Morice
Journal: New England Journal of Medicine (1999)

Coronary-stent implantation is frequently performed for treatment of acute myocardial infarction. However, few studies have compared stent implantation with primary angioplasty alone.We designed a multicenter study to compare primary angioplasty with angioplasty accompanied by implantation of a heparin-coated Palmaz-Schatz stent. Patients with acute myocardial infarction underwent emergency catheterization and angioplasty. Those with vessels suitable for stenting were randomly assigned to undergo angioplasty with stenting (452 patients) or angioplasty alone (448 patients).The mean (+/-SD) minimal luminal diameter was larger after stenting than after angioplasty alone (2.56+/-0.44 mm vs. 2.12+/-0.45 mm, P<0.001), although fewer patients assigned to stenting had grade 3 blood flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) (89.4 percent, vs. 92.7 percent in the angioplasty group; P=0.10). After six months, fewer patients in the stent group than in the angioplasty group had angina (11.3 percent vs. 16.9 percent, P=0.02) or needed target-vessel revascularization because of ischemia (7.7 percent vs. 17.0 percent, P<0.001). In addition, the combined primary end point of death, reinfarction, disabling stroke, or target-vessel revascularization because of ischemia occurred in fewer patients in the stent group than in the angioplasty group (12.6 percent vs. 20.1 percent, P<0.01). The decrease in the combined end point was due entirely to the decreased need for target-vessel revascularization. The six-month mortality rates were 4.2 percent in the stent group and 2.7 percent in the angioplasty group (P=0.27). Angiographic follow-up at 6.5 months demonstrated a lower incidence of restenosis in the stent group than in the angioplasty group (20.3 percent vs. 33.5 percent, P<0.001).In patients with acute myocardial infarction, routine implantation of a stent has clinical benefits beyond those of primary coronary angioplasty alone.
Abstract 1468: MTA2 enhances breast cancer metastasis via regulation of the cytoskeleton and rho signaling pathways
Authors: Kyle R. Covington, Lauren Brusco, Amanda Beyer, Weiyan Cai, Arnoldo Corona-Rodriguez, Suzanne A.W. Fuqua
Journal: Cancer Research (2011)

Abstract Metastasis tumor associated (MTA) 2 is a component of the nucleosome remodeling and histone deacetylation complex and is implicated in regulating gene expression through its associated histone deacetylase activity. We have previously found that MTA2 enhanced the anchorage independent growth phenotype of estrogen receptor alpha (ER)-positive cells, implicating a potential role in metastasis. As MTA2-overexpression in these cells also resulted in an estrogen independent phenotype, we hypothesized that MTA2-overexpression may similarly enhance the aggressiveness of ER-negative cells. We found that MTA2-overexpressing MDA-MB-231 cells were more invasive through Matrigel, had enhanced soft-agar colony formation activity compared with vector controls, and demonstrated increased migration in wound healing assays. Furthermore, we found that MTA2 overexpression resulted in rapid systemic metastases when grown as orthotopic xenografts, while vector control cells failed to form metastases, in the same time period. Microarray analysis revealed enrichment for genes regulating the cytoskeleton and cell-environment interactions, which was validated using a previously published microarray dataset. We found that the negative regulator of the Rho pathway, Rho GDP dissociation inhibitor alpha (RhoGDI-alpha), was also decreased in expression at the protein level in the MTA2-overexpressing MDA-MB-231 cells. We found that blocking signaling through the Rho pathway by either using a Rho Kinase inhibitor or by overexpressing RhoGDI-alpha significantly reduced the soft-agar colony forming ability of MTA2-overexpressing cells. We examined the effect of MTA2 and RhoGDI-alpha expression in a retrospective breast cancer microarray dataset and found that patients classified as MTA2-high and RhoGDI-alpha-low had significantly earlier recurrence compared with all other patients. These data indicate that MTA2-overexpression results in an increase in the metastatic potential of breast cancer cells. These results have potential clinical implications as patients who have the MTA2-high/RhoGDI-alpha-low phenotype are at increased risk for early recurrence. In conclusion, our data show that MTA2 and RhoGDI-alpha enhances breast cancer metastasis possibly by promoting invasiveness and anchorage independent growth and survival. 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 1468. doi:10.1158/1538-7445.AM2011-1468
Abstract 2719: MM-141, a novel bispecific antibody co-targeting IGF-1R and ErbB3, blocks ligand-induced signaling and demonstrates antitumor activity
Authors: Jason Baum, Bryan Johnson, Sharlene Adams, Jian Tang, Neeraj Kohli, Rachel Rennard, Pragalath Sundararajan, Lihui Xu, Yang Jiao, Birgit Schoeberl, Ulrik Nielsen, Jonathan Fitzgerald, Alexey Lugovskoy
Journal: Cancer Research (2012)

Abstract Monoclonal antibodies have significantly advanced our ability to treat cancer, but most patients do not show durable responses to therapy. This, in part, can be explained by the tumor cells responding to two or more growth factors in a redundant fashion. We show that cancer cell lines frequently rely on Insulin-like growth factor 1 (IGF-1) and Heregulin (HRG) signaling to support their survival and proliferation. Using a Network Biology approach, we have designed, constructed and optimized a novel bispecific antibody, MM-141, for co-targeting of ErbB3 and IGF-1R. MM-141 blocks IGF-1, IGF-2, and HRG binding to IGF1R and ErbB3, and causes downregulation of these receptors. MM-141 inhibits phosphorylation of IGF1R and ErbB3 as well as downstream activation of the PI3K/Akt pathway. In our in vitro and in vivo testing, MM-141 displays potency in the presence of single or multiple ligands, over a broad range of receptor profiles. Inhibition of growth by MM-141 has been observed in vitro as well as in vivo in multiple xenograft models including human pancreatic cancer (BxPC-3) and human prostate cancer (DU145). MM-141 does not bind the insulin receptor, thus reducing the risk of metabolic side effects. Our in vivo and in vitro studies reveal that MM-141 has favorable pharmaceutical properties and pharmacokinetic profiles. We are advancing MM-141 into preclinical development. Taken together, these results suggest that MM-141 has the potential to be an effective therapeutic for treatment of patients with solid tumors. 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 2719. doi:1538-7445.AM2012-2719
Abstract LB-140: Targeting brain tumour initiating cells using a dual-pronged approach of oncolytic virotherapy and chemotherapeutics
Authors: Brienne McKenzie, Franz J. Zemp, Xueqing Lun, Aru Narendran, Grant McFadden, Ebba Kurz, Peter Forsyth
Journal: Cancer Research (2012)

Abstract BACKGROUND: Brain tumour initiating cells (BTICs) are stem-like cells hypothesized to mediate tumorigenesis and recurrence in glioblastoma multiforme (GBM). Patient-derived BTICs represent highly relevant preclinical GBM models, forming aggressive, infiltrative tumours in nude mice that closely recapitulate the phenotypic heterogeneity of patient GBMs. BTICs have also been shown to possess mechanisms mediating both chemo- and radio-resistance. Recently, success has been demonstrated in treating BTICs with oncolytic virotherapy (OV), which uses replication-competent viruses to specifically target and kill malignant cells. Myxoma virus (MyxV) is a promising oncolytic candidate, which our lab has shown to be highly efficacious in preclinical GBM models, effectively curing GBM xenografts with a single intra-cranial injection. By contrast, long-term survival is not obtained in MyxV-treated, BTIC-tumour-bearing mice, though survival is prolonged. HYPOTHESIS: We hypothesize that MyxV treatment of BTICs can be improved by utilizing clinically relevant chemotherapeutics identified via high-throughput pharmacoviral screens. RESULTS: We utilized a diverse, comprehensive panel of 80 small molecule inhibitors with preclinical and clinical anti-cancer efficacy to screen for synergy with MyxV treatment in vitro. Multiple candidates have been identified and are currently being validated for synergy (Chou-Talalay method) using a panel of genetically distinct, patient-derived BTICs. Our results implicate multiple potential targets for OV combination therapy, including topoisomerase I and the PI-3K/Akt/mTOR pathway. Target validation is currently underway using shRNA knockdowns and additional targeted inhibitors of these pathways. Further, the mechanism of synergistic cell death during these combination treatments is being explored. In vivo experiments utilizing the dual-pronged pharmacoviral approach are also underway. SIGNIFICANCE: We describe the nature and identity of compounds that carry the potential to sensitize BTICs to MyxV infection. Our findings offer an effective avenue to elucidate resistance mechanisms and develop efficacious combination therapies for targeting disease reservoirs within highly refractory GBMs. 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 LB-140. doi:1538-7445.AM2012-LB-140
Eosinophilic cholangitis diagnosed endoscopically
Authors: Elez Vainer, Gilad Vainer, Harold Jacob, Mohammad Faroja
Journal: Endoscopy (2014)

A 15 year old girl was referred with cholestatic jaundice, but no other complaints. Biliary obstruction was identified on ultrasound scanning, and abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) demonstrated bilateral dilatation of the intrahepatic bile ducts and an enlarged gallbladder. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a short segment stricture just below the bifurcation ([Fig. 1]). Directed biopsies were taken using the Spyglass cholangioscope and a stent was placed. Histopathological examination of the biopsies showed an inflammatory infiltrate rich in eosinophils compatible with the diagnosis of eosinophilic cholangitis ([Fig. 2]).
THU0067 Endothelial-to-Mesenchymal Transition in Cultured Human Dermal Microvascular Endothelial Cells: Effects of Endothelin-1
Authors: S. Soldano, P. Montagna, R. Brizzolara, B. Seriolo, A. Sulli, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Endothelial/microvascular damage and myofibroblast activation are considered early events in the development of connective tissue diseases, such as systemic sclerosis (SSc) (1). Recent studies showed that vascular endothelial cells may aquire matrix-producing myofibroblast features through the endothelial-to-mesenchymal transition (EndoMT) process (2,3). <h3>Objectives</h3> To investigate the possible direct effect of ET-1 in inducing the EndoMT in cultured human dermal microvascular endothelial cells (HMVECs). <h3>Methods</h3> HMVECs (Lonza Clonetic, Switzerland) were cultured in endothelial cell growth medium (EGM2-MV, Lonza Clonetic) and treated with or without ET-1 (100nM, EnzoLife Science, UK) for 6 days, according to recent studies (4, 5). For the experiments, the cells were used between the second and fourth passages. Gene expression levels of α-smooth muscle actin (α-SMA) and fibroblast specific protein-1 (S100 calcium binding protein A4, S100A4), two markers of the myofibroblast phenotype, as well as plateled endothelial cell adhesion molecule (PECAM-1 or CD31), a marker of the endothelial phenotype, were evaluated by quantitative real time-polimerase chain reaction (qRT-PCR). Moreover, α-SMA and CD31 protein expressions were evaluated by immunofluorescence (IF) using primary antibodies to human α-SMA (dilution 1:50, Dako Cytomation, Denmark) and to human CD31 (dilution 1:200, CellSignaling Technology, Denver, USA). <h3>Results</h3> ET-1 induced the gene expression of α-SMA and S100A4 without modulating the expression of CD31 in cultured HMVECs after 6 days of treatment, as detected by qRT-PCR. The IF analysis supported these results by showing that ET-1 induced the expression of α-SMA but no changes in the expression of CD31 after 6 days of treatment. Results were obtained from three different experiments. <h3>Conclusions</h3> These preliminary observations show that ET-1 seems to induce in short term the expression of myofibroblast markers (α-SMA and S100A4) in cultured dermal microvascular endothelial cells, supporting a possible direct involvement in the development of the EndoMT process (6). Longer term observations seem necessary to detect further changes in phenotype markers in treated endothelial cells (i.e. CD31, von Willebrand factor). <h3>References</h3> Wynn TA et al. Nat Med 2012;18:1028-40 Chaudhury V et al. J Cutan Pathol 2007;34:146-53 Zeisberg EM et al. Nat Med 2007;13:952-61 Kitao A et al. Am J Phatol 2009;175:616-26 Widyantoro B et al. Circulation 2010;121:2407-18 Soldano S et al Arthrit &amp; Rheum 2012;64(Supplement):S640. <h3>Disclosure of Interest</h3> None Declared