tbuckley/cabot-search huggingface dataset:
SP0032 Angiogenesis in Synovial Inflammation; Differences Between OA and RA
Authors: D. A. Walsh
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Synovitis is a feature of both OA and RA, and in both it may contribute to pain. OA and RA are often viewed as separate diseases, but OA may occur secondarily to, or coincidentally with RA. In both OA and RA, synovial inflammation is associated with the growth of new blood vessels. However, the mechanisms and consequences of synovial angiogenesis display both similarities and differences between diseases. Macrophages and macrophage-derived growth factors such as vascular endothelial growth factor (VEGF) are increased in the inflamed synovium of both OA and RA joints. However, biological agents such as anti-TNF therapies more convincingly reduce angiogenesis in RA than in OA. Angiogenesis is associated with sensory nerve growth. In RA, densities of both blood vessels and nerves near the synovial surface may be reduced, whereas vascular densities in OA synovium are more consistently increased, perhaps suggesting a greater contribution of vascular regression in RA synovitis. RA is associated with joint erosion, and growth of erosive pannus may be dependent on angiogenesis. However, in both OA and RA, redistribution of blood vessels from the synovial surface into the deeper synovial layers may compromise cartilage metabolism and exacerbate chondropathy. Differences between OA and RA may reflect either the intensity or underlying mechanisms of inflammation, and direct interventional studies are required to definitively dissect specific features of angiogenesis and inflammation between the 2 diseases. Better understanding the similarities and differences in blood vessel growth between OA and RA may lead to better treatments for both diseases in the future. <h3>Disclosure of Interest</h3> None Declared
Abstract 695: LA480, a c-Met antibody with neutralization and internalization properties, inhibits HGF-dependent and HGF-independent c-Met pathway activation and tumor growth
Authors: Mark A. Wortinger, Wei Zeng, Wei Jennifer Yang, Victoria Peek, Lei Yan, Jirong Lu, Chi-Kin Chow, Peter Vaillancourt, Julian Davies, Irene Denning, Spring Weir, James Wooldridge, Ling Liu
Journal: Cancer Research (2010)

Abstract c-Met is a receptor tyrosine kinase that binds hepatocyte growth factor (HGF) and has been implicated in human cancer. Inappropriate activation of c-Met can be induced by ligand-independent mechanisms such as gene amplification, specific genetic mutations, and transcriptional upregulation, or by ligand-dependent autocrine or paracrine mechanisms. Indeed, amplification of the c-Met gene, with consequent protein overexpression and constitutive kinase activation, has been reported in a number of human cancers, including gastric, esophageal and non-small-cell lung carcinomas. Activating mutations of the c-Met gene have been found in a subset of patients with hereditary and sporadic papillary renal cancer, lung cancer, childhood hepatocellular carcinoma and gastric carcinoma. Another common constitutive c-Met activation in human tumors is increased protein expression as a consequence of transcriptional upregulation, in the absence of gene amplification. c-Met expression level has been correlated with poor prognosis in multiple tumor types. In addition, cMet activation by an elevated level of HGF has also been described in gliobastoma, breast carcinomas, rhabdomyosarcoma and osteosarcoma. We report here that LA480, a humanized monoclonal c-Met antibody, inhibits HGF-dependent and HGF-independent c-Met pathway activation and tumor growth. Our data demonstrate that LA480 blocks binding of HGF to c-Met as shown by ELISA, blocks HGF stimulation of phospho-Met in HCT116 cells, and blocks HGF stimulation of primary human hepatocyte proliferation. Moreover, LA480 internalizes and depletes cell surface c-Met, significantly reduces phospho-c-Met and total c-Met in multiple tumor cell lines, and inhibits proliferation of tumor cell lines that have c-Met gene amplification. In addition, LA480 does not stimulate biological activities that are elicited by HGF. Furthermore, LA480 reduces total c-Met and phospho-Met in xenograft tumors and significantly inhibits tumor growth in both ligand-independent and ligand-dependent mouse xenograft models. These findings suggest that LA480 may be a promising therapy for treatment of cancers driven by ligand-dependent and ligand-independent c-Met activation. 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 695.
THU0444 Assessment of Global Disease Activity in RA by Patients and Physicians: Cultural Differences across Countries in the Meteor Database
Authors: E. Gvozdenovic, C. Allaart, R. Wolterbeek, C. Brenol, A. Chopra, M. Dougados, P. Emery, G. Ferraccioli, D. Van Der Heijde, T. Huizinga, J. Kay, E. Mola, R. Moots, J. Da Silva, J. Smolen, D. Veale, R. Landewé
Journal: Annals of the Rheumatic Diseases (2014)

<h3>ABSTRACT</h3> Single-cell analysis is a powerful tool for dissecting the cellular composition within a tissue or organ. However, it remains difficult to detect rare and common cell types at the same time. Here we present a new computational method, called GiniClust2, to overcome this challenge. GiniClust2 combines the strengths of two complementary approaches, using the Gini index and Fano factor, respectively, through a cluster-aware, weighted ensemble clustering technique. GiniClust2 successfully identifies both common and rare cell types in diverse datasets, outperforming existing methods. GiniClust2 is scalable to very large datasets.
AB1382 Reasons for hospitalization of patients with rheumatologic disorders
Authors: R. Mueller, M. Gengenbacher, M. Weber, C. Gabay, J. von Kempis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Even though hospitalization is a major cost driver in patients with rheumatic disorders there is limited information and analysis of reasons for their hospitalization <h3>Objectives</h3> To analyze the reasons for hospitalization of rheumatologic patients in divisions of rheumatology in emergency hospitals in Switzerland based on questionnaires sent to the heads of all 30 departments of rheumatology in the country <h3>Methods</h3> The questionnaires contained 51 open questions on 8 different topics: Which criteria are important for hospitalization? What defines a severe course of the disease? Which threatening organic damage or pain level require hospitalization? How does the complexity of diagnostics or interventions influence the decision for hospitalization? Are costs or primary patient care relevant factors for hospitalization? The questions were asked in separate for inflammatory arthritis/spondyloarthritides (Art), connective tissue diseases/vasculitis (Vasc), and degenerative or other musculoskeletal disease. (Degen). <h3>Results</h3> 25 of the 30 heads of divisions (83.3%) have answered the questionnaires. Two additional ones have sent letters stating that such questionnaires are too limiting for adequately reflecting the clinical reality. The overall majority of responders stated that acute organic problems 79.6% (Art), 81.2% (Vasc), and 73.5% (Degen) are an important factor for hospitalization. These manifestations were closely associated with other primary diseases (Art, 81.8%), with organic manifestations of the primary disease (Vasc, 64.2%), and with complex interventions (Degen, 66.9%). The most important other diagnoses in association with a rheumatologic diagnosis were pneumologic (16.8%), neurologic (13.0%), and cardiological (13%) for Art patients, pneumologic (16.8%), neurologic (13.0%), and renal (13%) for Vasc patients, and neurologic (74.2%) for Degen patients. Primary care problems were understood to be more important for Art (52.6%) and Vasc patients (54.1%), but less important for Degen patients (28.6%). <h3>Conclusions</h3> Acute medical rather than chronic problems are the major factor for the hospitalization of rheumatic patients. These acute problems are mainly associated with primary manifestations of other diseases for patients with inflammatory arthritis/spondyloarthritides, with organ manifestations of the primary disease for patients with connective tissue diseases/vasculitis, and with interventions for patients with degenerative or other musculoskeletal disease. <h3>Discussion</h3> Since many rheumatologic diseases are closely associated with other diseases, especially of internal organs, it is possible that many of these patients are not seen by a rheumatologist during their hospitalization. <h3>Disclosure of Interest</h3> None Declared
P1129 EFFECT OF HCV GENOTYPE-1 SUBTYPE ON RESPONSE TO FALDAPREVIR PLUS PEGYLATED INTERFERON a-2a AND RIBAVIRIN IN TREATMENT-NAIVE PATIENTS: POOLED DATA FROM PHASE III TRIALS
Authors: I.M. Jacobson, D.M. Jensen, D. Dieterich, C. Sarrazin, G.R. Foster, E.M. Yoshida, M. Nelson, P. Ingiliz, V. Soriano, C. Cooper, J.O. Stern, A.-M. Quinson, G. Kukolj, J. Scherer, M. Drulak, J.-P. Gallivan, M. Schobelock, P. Ferenci
Journal: Journal of Hepatology (2014)
Resistance training reduces systolic blood pressure in metabolic syndrome: a systematic review and meta-analysis of randomised controlled trials
Authors: Ítalo Ribeiro Lemes, Paulo Henrique Ferreira, Stephanie Nogueira Linares, Aryane Flauzino Machado, Carlos Marcelo Pastre, Jayme Netto
Journal: British Journal of Sports Medicine (2016)

Aim To evaluate the effects of resistance training on metabolic syndrome risk factors through comparison with a control group. Design Meta-analysis comparing resistance training interventions with control groups. Two independent reviewers selected the studies and assessed their quality and data. The pooled mean differences between resistance training and the control group were calculated using a fixed-effects model. Data sources The MEDLINE, PEDro, EMBASE, SPORTDiscus and The Cochrane Library databases were searched from their earliest records to 10 January 2015. Eligibility criteria for selecting studies Randomised controlled trials that compared the effect of resistance training on metabolic syndrome risk factors with a control group were included. All types of resistance training, irrespective of intensity, frequency or duration, were eligible. Results Only systolic blood pressure was significantly reduced, by 4.08 mm Hg (95% CI 1.33 to 6.82; p&lt;0.01), following resistance training. The pooled effect showed a reduction of 0.04 mmol/L (95% CI −0.12, 0.21; p&gt;0.05) for fasting plasma glucose, 0.00 (95% CI −0.05, 0.04; p&gt;0.05) for high-density lipoprotein (HDL) cholesterol, 0.03 (95% CI −0.14, 0.20; p&gt;0.05) for triglycerides, 1.39 mm Hg (95% CI −0.19, 2.98; p=0.08) for diastolic blood pressure and 1.09 cm (95% CI −0.12, 2.30; p=0.08) for waist circumference. Inconsistency (I 2 ) for all meta-analysis was 0%. Conclusions Resistance training may help reduce systolic blood pressure levels, stroke mortality and mortality from heart disease in people with metabolic syndrome. Trial registration number CRD42015016538.
Abstract 69: Genomic deletions clustered on chromosomes 8 and 9 are associated with pancreatic cancer progression
Authors: Arkadeep Sinha, Elizabeth Lenkiewicz, Michael Barrett, Brian B. Haab
Journal: Cancer Research (2012)

Abstract Pancreatic cancer cells that have mesenchymal traits can be particularly migratory and resistant to chemotherapeutics. These cells are presumed to represent a more advanced and deadly population of cells relative to cancer cells with more differentiated, epithelial traits. The factors leading to the acquisition of a mesenchymal phenotype in pancreatic cancer are not well characterized. In this study, we tested the hypothesis that the development of a mesenchymal phenotype occurs selectively in tumor cells that harbor specific enabling genomic alterations. As a model system, we used pancreatic cancer cell lines that had either an epithelial-like or a mesenchymal-like phenotype when cultured in vitro, as defined by morphology and key molecular indicators. We used whole-genome comparative genomic hybridization to compare the genomic amplifications and deletions between 17 epithelial-like cell lines and 9 mesenchymal-like cell lines. An unbiased search revealed that 18 genes (each comprising at least three contiguous probes in a coding region) had alterations in a significantly greater percentage of the mesenchymal-like cells than the epithelial-like cells, whereas no genes had more frequent alterations in the epithelial-like cells. Sixteen of the 18 alterations were deletions, and 14 of the deletions were clustered in specific regions on chromosomes 8 and 9, suggesting the importance of those regions for suppressing de-differentiation. Some of the 18 genes were previously identified in studies of pancreatic cancer, such as SGCZ, KIAA1797 and SMAD4, while others were not. Certain genes showed a good correlation between DNA copy number and mRNA expression, providing evidence for the functional importance of those alterations. The known functions of the 18 genes include cell cycle control, cell membrane homeostasis, immune system regulation, and TGF-β pathway transduction, the deletion of which might provide improved survival advantage and cell structure modification required for metastasis. These findings support the concept that mesenchymal-like cancer cells are genetically more progressed than their epithelial-like counterparts and provide leads on the genomic hits that enable such progression. 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 69. doi:1538-7445.AM2012-69
Abstract 5332: Evaluation of GD2 expression in patients with osteosarcoma
Authors: John Tarim, Rebecca S. Sowers, Sajida Piperdi, Chand Khanna, Richard G. Gorlick
Journal: Cancer Research (2011)

Abstract GD2 is a disialoganglioside that is expressed on the cell surface in specific normal and malignant human tissues. Tumor specific cell surface antigens serve as important targets in cancer therapy. Anti-GD2 therapy using antibodies targeted to the cell surface antigen GD2 to induce antibody-dependent cellular cytotoxicity has been proven effective in treating GD2 expressing tumors like neuroblastoma and melanoma. Prior studies of osteosarcoma have shown GD2 to be expressed in malignant cells of osteosarcoma patients. In this study, the expression of GD2 in osteosarcoma will be evaluated further. A previously created and described tissue microarray was stained with 14.G2a, a murine monoclonal anti-GD2 antibody that was obtained from the National Cancer Institute. The intensity and location of tissue staining were assessed by a comparison between the positive and negative control slides. To evaluate GD2 expression quantitatively a cell-based ELISA was performed on different osteosarcoma patient derived cell cultures. The results of the tissue microarray showed that 34.8% of patient samples stained positive for GD2 while 60.9% of samples showed intermediate staining and only 4.3% of samples showed negative staining for GD2 (n=88). Nearly all of the osteosarcoma cell lines (n=24) showed levels of GD2 expression comparable to the neuroblastoma and fibrosarcoma cell lines and in some cases GD2 expression was significantly greater. Anti-GD2 therapy has been proven effective in treating patients with neuroblastoma and melanoma. The findings in this paper indicate that osteosarcomas express GD2 to a similar extent as neuroblastomas. These results would suggest clinical trials are worthwhile to further evaluate the benefit of anti-GD2 therapy in patients with osteosarcoma. 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 5332. doi:10.1158/1538-7445.AM2011-5332
Propranolol-Withdrawal Rebound Phenomenon
Authors: Richard R. Miller, Harold G. Olson, Ezra A. Amsterdam, Dean T. Mason
Journal: New England Journal of Medicine (1975)

Effects on anginal symptoms of sudden withdrawal of large doses of propranolol or placebo were evaluated in 20 patients in a double-blind crossover efficacy trial requiring sudden cessation of the agent. With propranolol, 160 to 320 mg per day for six and 12 weeks, no patients had increased angina or nitroglycerin use, and there were no hospitalizations or deaths. However, within two weeks of discontinuance of propranolol, untoward ischemic events developed in 10 patients. Six had serious withdrawal complications: intermediate coronary syndrome in three, and ventricular tachycardia, fatal myocardial infarction, and sudden death in one each. In four patients discontinuance of placebo increased anginal symptoms; in the remaining 10, ischemic symptoms were not provoked. The rebound phenomenon was related to degree of pre-propranolol angina and relief of pain by the agent. Thus, chronically administered propranolol should be gradually reduced, and activity restricted during its withdrawal. (N Engl J Med 293:416–418, 1975)
Detection of Recurrent Non-Hodgkin Lymphoma on In-111 Capromab Pendetide Imaging
Authors: Benjamin L. Franc, Hank Lin
Journal: Clinical Nuclear Medicine (2015)

A 73-year-old man presented with a rising prostate-specific antigen (PSA) level 5 years following brachytherapy for prostate cancer. In-111 capromab pendetide (ProstaScint) whole-body planar imaging revealed abnormal uptake in the right knee, localizing to a mass in the popliteal fossa on SPECT/CT. MRI showed a mass encasing the popliteal artery and vein, subsequently found to be non-Hodgkin lymphoma on biopsy. Response of the mass to chemotherapy was documented on 18F-FDG PET/CT. Elevated In-111 capromab pendetide uptake in soft tissue can be important but unrelated to prostate cancer, as demonstrated in this case.
Endoscopic management of malignant biliary obstruction by means of covered metallic stents: primary stent placement vs. re-intervention
Authors: M. Kida, S. Miyazawa, T. Iwai, H. Ikeda, M. Takezawa, H. Kikuchi, M. Watanabe, H. Imaizumi, W. Koizumi
Journal: Endoscopy (2011)

<b>Background and study aims:</b> Recent progress in chemotherapy has prolonged the survival of patients with malignant biliary strictures, leading to increased rates of stent occlusion. Occlusion of covered metallic stents now occurs in about half of all patients with malignant biliary strictures. The removal of metallic stents followed by placement of a second stent has been attempted, but outcomes remain controversial. The aim of the current study was to evaluate the effectiveness and safety of the primary placement and secondary placement (re-intervention) of covered metallic stents and to assess the feasibility and safety of stent removal. <b>Patients and methods:</b> The study included 186 patients with unresectable malignant biliary strictures who underwent primary stent placement between October 2001 and March 2010. Covered biliary self-expandable metal stents (SEMSs) were removed in 39 of these patients, and 36 underwent re-intervention. The patency times, occlusion rates of the first stent and re-intervention, success rates of stent removal, and complications were investigated. <b>Results:</b> Covered SEMSs were placed in 186 patients. The median patency time of the first stent was 352 days. Stent occlusion occurred in 48.9 % of the patients and was mainly caused by debris or food residue (37 %), dislocation (19 %), and migration with hyperplasia (19 %). Stent removal was attempted in 50 patients and was successful without complication in 39 (78 %). Most of the patients in whom stent removal was unsuccessful had migration with hyperplasia. The median patency time of the second stent was 263 days. The stent patency time did not significantly differ between the first and the second stent. <b>Conclusions:</b> Covered SEMSs could be safely removed at the time of stent occlusion. Patency rates were similar for initial stent placement and re-intervention.
Abstract 2386: High-throughput assessment of the VEGFR2 kinase activity profile in pediatric brain tumor tissue
Authors: Arend H. Sikkema, Eveline S. de Bont, Grietje Molema, Anna Dimberg, Peter J. Zwiers, Sander H. Diks, Eelco W. Hoving, Willem A. Kamps, Maikel P. Peppelenbosch, Wilfred F. den Dunnen
Journal: Cancer Research (2010)

Abstract For enhanced tumor cell survival and progression, tumors depend on angiogenesis. Vascular endothelial growth factor receptor (VEGFR) signaling plays a major part in this process. Previously we generated a comprehensive description of the biological tyrosine kinase activity present in pediatric brain tumor tissue lysates by the application of a peptide microarray containing 144 different tyrosine kinase peptide substrates (Sikkema et al., Cancer Res 2009). The results suggested the presence of activated VEGF receptors in pediatric pilocytic astrocytoma tissue. We hypothesized that this detected VEGFR activity reflects the angiogenic status of the tumor endothelium. In this study we demonstrated that VEGFR2 expression is not present in a pilocytic astrocytoma cell line. Moreover, proximity ligation assays on tumor cryosections showed VEGFR2 phosphorylation, primarily localized on endothelial cells. qRT-PCR analysis of endothelial markers and VEGFRs showed a 10 to 30-fold enrichment of VEGFR2 expression on laser microdissected endothelium compared to whole tumor. Hence, we conclude that the endothelial cells are the high producers of VEGFR2 kinase activity in these tumors and therefore responsible for the VEGFR2 kinase activity that we observed in our kinase activity screens. In conclusion, potential VEGFR kinase substrates present on the peptide microarray are adequately sensitive to pick up enzymatic activity which is present in only a subset of the total cell population within solid tumors such as pilocytic astrocytoma. In the near future, high throughput measurement of enzymatic activity of key players in angiogenesis could make a rapid assessment of the angiogenic profile of a tumor possible. This could serve as an indicator of anti-angiogenic treatment response and result in more personalized anti-angiogenic cancer treatment strategies. 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 2386.