tbuckley/cabot-search huggingface dataset:
BMP4 Induces M2 Macrophage Polarization and Favors Tumor Progression in Bladder Cancer
Authors: Víctor G. Martínez, Carolina Rubio, Mónica Martínez-Fernández, Cristina Segovia, Fernando López-Calderón, Marina I. Garín, Alicia Teijeira, Ester Munera-Maravilla, Alberto Varas, Rosa Sacedón, Félix Guerrero, Felipe Villacampa, Federico de la Rosa, Daniel Castellano, Eduardo López-Collazo, Jesús M. Paramio, Ángeles Vicente, Marta Dueñas
Journal: Clinical Cancer Research (2017)

Purpose: Bladder cancer is a current clinical and social problem. At diagnosis, most patients present with nonmuscle-invasive tumors, characterized by a high recurrence rate, which could progress to muscle-invasive disease and metastasis. Bone morphogenetic protein (BMP)-dependent signaling arising from stromal bladder tissue mediates urothelial homeostasis by promoting urothelial cell differentiation. However, the possible role of BMP ligands in bladder cancer is still unclear.Experimental Design: Tumor and normal tissue from 68 patients with urothelial cancer were prospectively collected and analyzed for expression of BMP and macrophage markers. The mechanism of action was assessed in vitro by experiments with bladder cancer cell lines and peripheral blood monocyte-derived macrophages.Results: We observed BMP4 expression is associated and favored type II macrophage differentiation. In vitro experiments showed that both recombinant BMP4 and BMP4-containing conditioned media from bladder cancer cell lines favored monocyte/macrophage polarization toward M2 phenotype macrophages, as shown by the expression and secretion of IL10. Using a series of human bladder cancer patient samples, we also observed increased expression of BMP4 in advanced and undifferentiated tumors in close correlation with epithelial-mesenchymal transition (EMT). However, the p-Smad 1,5,8 staining in tumors showing EMT signs was reduced, due to the increased miR-21 expression leading to reduced BMPR2 expression.Conclusions: These findings suggest that BMP4 secretion by bladder cancer cells provides the M2 signal necessary for a protumoral immune environment. In addition, the repression of BMPR2 by miR-21 makes the tumor cells refractory to the prodifferentiating actions mediated by BMP ligands, favoring tumor growth. Clin Cancer Res; 23(23); 7388-99. ©2017 AACR.
THU0125 Progression of subclinical atherosclerosis over eleven years is increased in patients with early rheumatoid arthritis
Authors: A Södergren, K Karp, E Lundström, T Smedby, B Möller, S Rantapää-Dahlqvist, S Wållberg-Jonsson
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have an increased mortality and morbidity due to cardiovascular disease (CVD). <h3>Objectives</h3> In this prospective follow up over eleven years, we investigated the progression of atherosclerosis measured by intima media thickness (IMT), in relation to traditional CVD risk factors and inflammation, in patients with early RA compared to controls. <h3>Methods</h3> Patients from northern Sweden diagnosed with early RA are consecutively recruited into an ongoing prospective study. A subgroup aged ≤60 years (n=54) was consecutively included for ultrasound measurements of IMT of a. Carotis communis at inclusion (T0), and after 11 years (T11). 31 age-sex-matched controls were included. The patients were clinically assessed, SCORE, Reynolds Risk Score and Larsen score were calculated and blood samples drawn from all individuals at T0 and T11. Data and results presented in this abstract are preliminary. <h3>Results</h3> Patients with RA as well as controls had a significant aggravation in IMT over 11 years (0.52 at T0 and 0.68 at T11 in RA: p&lt;0.001; 0.54 at T0 and 0.63 at T11 in controls: p&lt;0.05; IMT in RA vs controls at T0 and at T11: p&gt;0.05). The patients with RA had a significantly higher progression in IMT from T0 until T11 (0.16 vs 0.08, p&lt;0.001). In simple linear regression analyses among RA-patients, the IMT at T11 was significantly associated with several variables at T0: age, systolic blood pressure, SCORE, Reynolds Risk Score, tPA, L-selectin (inversely), MCP-1 and Larsen score. The progression in IMT over 11 years was associated with age and Larsen score at T0. <h3>Conclusions</h3> In this prospective study, the progression of sub-clinical atherosclerosis over 11 years was significantly higher in patients with RA than in controls. The IMT at T11 was associated with several traditional cardiovascular risk factors, as well as disease severity, at time of diagnosis. <h3>Disclosure of Interest</h3> None declared
AB0956 Influence of biological therapy on bone mineral density in children with juvenile idiopathic arthritis
Authors: I Chyzheuskaya, L Byelyaeva, N Vasiljeva, R Filonovich, L Zajtseva
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is one of the most common and most disabling rheumatic diseases in children. JIA is a systemic chronic inflammatory immunopathological disease, which leads to dysfunction of the joints, their deformation and limitations of life of the child, violates the child9s growth and development. One of the complications of systemic JIA in children is osteoporosis. In the pathogenesis of osteoporosis important place is given to the use of glucocorticoids. In world Rheumatology successfully used drugs aimed at the major pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), and others. <h3>Objectives</h3> The purpose of research - to determine the influence of biological therapy on bone mineral density in children with JIA. <h3>Methods</h3> 15 children with systemic JIA (mean age 11,9±3,4 years) were examined in the rheumatological department of 4th city clinical hospital of Minsk. Bone mineral density was assessed by 2-energy X-ray absorptiometry (DEXA) at two points of the skeleton. The level of mineralization of skeletal mineral content was estimated in the bone tissue (BMC), bone mineral density (BMD) and the parameter Z-score. Z-score was used to determine the incidence of osteopenia and osteoporosis in children surveyed. In accordance with the WHO criteria for normal bone mineral density was diagnosed with the Z-score&gt; -1 SD, osteopenia - at Z-score &lt;-1 SD, but&gt; - 2,5 SD, osteoporosis - with Z-score &lt;-2,5 SD. Statistical data processing carried out using an integrated application package "Statistics 6 for Windows". <h3>Results</h3> In a study of children osteopenia was diagnosed in 9 patients with systemic JIA (mean Z-score -2,3 SD) Osteoporosis was diagnosed in 6 patients with systemic JIA (mean Z-score -2,7 SD). All children received a mean dose of methotrexate 12.7 mg/m<sup>2</sup> of body surface area, an average dose of methylprednisolone 0.34 mg/kg body weight per day and treatment of IL-6 inhibitor - tocilizumab 8 mg/kg body weight every 2–4 weeks. Bone mineral density was measured prior to initiating therapy tocilizumab and after 2 years of therapy. During tocilizumab therapy achieved remission of the disease, all children was canceled methylprednisolone. After re densitometry of 2 years after the beginning of therapy improvement noted tocilizumab Z-score in children with osteopenia with Z-score -2.3 SD to Z-score -1.4 SD, in children with osteoporosis a Z-score -2 7 SD to Z-score - 2,1 SD. <h3>Conclusions</h3> The results indicate a positive influence tocilizumab therapy to bone mineral density in children with JIA. <h3>Acknowledgements</h3> This study would not have been possible without the collaboration of numerous Belarusian pediatric rheumatologists, patients and their parents. <h3>Disclosure of Interest</h3> None declared
Summary of Research Needs&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Summary of Research Needs Get access Barbara A. Underwood Barbara A. Underwood 3 2Special Assistant for Nutrition Research and International Programs, Office of the Director, National Eye Institute, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, Bethesda, Md. 20205. 3Address reprint requests to Dr. Underwood, Building 31, Room 6A08, National Institutes of Health, Bethesda, Md. 20205. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 73, Issue 6, December 1984, Page 1489, https://doi.org/10.1093/jnci/73.6.1489 Published: 01 December 1984
Effect of Definition on Incidence and Prognosis of Type 2 Myocardial Infarction
Authors: Thomas Nestelberger, Jasper Boeddinghaus, Patrick Badertscher, Raphael Twerenbold, Karin Wildi, Dominik Breitenbücher, Zaid Sabti, Christian Puelacher, Maria Rubini Giménez, Nikola Kozhuharov, Ivo Strebel, Lorraine Sazgary, Deborah Schneider, Janina Jann, Jeanne du Fay de Lavallaz, Òscar Miró, F. Javier Martin-Sanchez, Beata Morawiec, Damian Kawecki, Piotr Muzyk, Dagmar I. Keller, Nicolas Geigy, Stefan Osswald, Tobias Reichlin, Christian Mueller, Lukas Schumacher, Samyut Shrestha, Dayana Flores, Katharina Rentsch, Beatriz López, M. Cecilia Yañez-Palma, Jiri Parenica, Jens Lohrmann, Andreas Buser
Journal: Journal of the American College of Cardiology (2017)
FRI0327 Gastroscopic features and clinical characteristics in 172 cases of children with henoch-schonleinpurpura
Authors: H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To investigate gastroscopic features and explore the relationship between clinical characteristics in children with Henoch-Schonleinpuepura (HSP). <h3>Methods</h3> To take gastroscope in 172 cases of children with HSP in our hospital and summarize the gastroscopic performance.All the case were divided into two groups by gastroduodenal mucosal bleeding or not.It was compared among the total time of abdominal pain, pain relief, hospitalization, fasting and kidney injury case in the groups. <h3>Results</h3> Gastroscope with varying degrees of injury of 172 cases has accounted for 169 cases (98.3%).Gastroscopic mainly revealedgastroduodenal mucosal congestion, edema, rough, erosion, bleeding and ulcer, which involved 148 cases of gastric (86.0%), 158 cases of duodenal involvement (91.9%). Mucosal erosion and bleeding occurs mainly in duodenum,mostly in the descending duodenum. Duodenal bleeding accounted for 36 cases (21.8%) in the bulb and 92 cases (55.8%) in the descendant. Only five cases (2.9%) of ulcer occurred in the duodenum, where four cases of bulbar ulcer, one case of descending ulcer. Esophageal and gastric cardia mucosal just occurred in one case. There were not significant difference (P&gt;0.05) among the time of abdominal pain, pain relief, hospitalization and fasting in the group. There was no significant difference (P&gt;0.05) in the incidence of kidney injury between two groups of children during hospitalization. <h3>Conclusions</h3> Gastroscopic features of HSP in children is characterized by bleeding, erosion of duodenal mucosa and occasional duodenal ulcer formation, which mostly involve the antral mucosa, rarely involving the esophagus, cardia. There was no significant difference (P&gt;0.05) among the severity of gastroscopic performance and the time of abdominal pain, fasting,hospitalization and kidney injury of the cases during hospitalization. <h3>Disclosure of Interest</h3> None declared
Mast cell exosomes can suppress allergic reactions by binding to IgE
Authors: Guogang Xie, Haiwei Yang, Xia Peng, Lihui Lin, Juan Wang, Kun Lin, Zelin Cui, Jia Li, Hui Xiao, Yuting Liang, Li Li
Journal: Journal of Allergy and Clinical Immunology (2017)

Allergic diseases are characterized by the increased serum levels of total IgE and specific IgE against common allergens.1 After sensitization of susceptible individuals, the synthesis and binding of allergen-specific IgE to mast cells (MCs) via high-affinity IgE receptors (FcεRI), atopic individuals respond to allergens by releasing mast cell–derived mediators.2 Secreted by multiple cell types including MCs, exosomes are nano-sized, cell membrane–surrounded structures harboring a broad range of biomolecules linked to cell type–associated functions.
FRI0688 Prera (predicting rheumatoid arthritis): preliminary findings from an on-going prospective study of seropositive and seronegative individuals and their risk for developing ra
Authors: M Mayr, M Hucke, V Nell-Duxneuer, T Stamm, G Steiner, T Perkmann, E Hitzelhammer, J Smolen, K Machold, H Radner
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> A characteristic feature of RA is the presence of autoantibodies (AAB), such as rheumatoid factor (RF) and antibodies against citrullinated peptides (ACPA). RF and ACPA are not only diagnostically helpful but are also prognostic indicators for progression of joint destruction. <h3>Objectives</h3> This is an on-going prospective study to investigate the prevalence of AAB in healthy individuals presenting to community health centres and to subsequently determine the incidence of RA in AAB-positive individuals compared to AAB-negative persons over five years considering the presence of certain risk factors. <h3>Methods</h3> Blood drawn at the time of the screening examination was anonymously analyzed for the presence of AAB. AAB positive and age and sex matched AAB negative individuals (2 for each AAB positive subject) were enrolled for further assessment at the central outpatient clinic and examined every 6 months over 5 years. Assessment included laboratory testing (AAB, acute phase parameters), questionnaires on nutrition, lifestyle and general health, 28 joint counts (SJC28, TJC28), the health assessment questionnaire (HAQ), and visual analogue scales for pain and global health. Risk factors were analysed by clusters according to EULAR recommendations for terminology of individuals at risk of RA: hereditary, environmental, systemic autoimmunity and unclassified arthritis and the number of clusters per individual was reported at baseline (1). The primary outcome was the development of RA; individuals lost to follow up were telephone-interviewed for signs and symptoms of RA. <h3>Results</h3> 4858 sera were obtained from which 148 (3%) were seropositive (14 ACPA, 124 RF, 10 both). 113 individuals (2,3%) were followed over 5 years. 37 (32,7%) were seropositive of whom 32 (28,3%) were RF-positive, 2 (5,4%) were ACPA-positive and 3 (8,1%) positive for both. We found no significant differences in demographics and risk factors between seropositive and seronegative individuals at baseline (Table 1). The number of risk clusters per individuals is reported in figure 1. Until now, 43 people were followed for 5 years; additional 52 telephone interviews were conducted. No evidence of RA (clinically or by history) was found. <h3>Conclusions</h3> By now none of the followed individuals had any evidence of inflammatory joint disease based on patient-telephone interviews conducted and completed 5-year follow-up examinations. We were unable to find evidence for practical value of routine AAB screening in healthy individuals without clinical signs of inflammatory joint diseases. <h3>References</h3> Gerlag et al. (2012) Ann Rheum Dis 2012;71:638–641. <h3>Disclosure of Interest</h3> None declared
THU0607 Risk factors for early retirement in systemic sclerosis
Authors: AM Gheorghiu, C Vrancianu, C Draganescu, R Oneata, L Macovei, M Sasu, M Milicescu, O Olteanu, M Speriatu, M Bojincă, V Stoica, C Mihai
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is a connective tissue disease characterized by skin and internal organs fibrosis, microvascular impairment and frequently by disability and early retirement. <h3>Objectives</h3> To assess employment status, risk factors for early retirement (ER) and the associations of ER with disease characteristics and with patients9 health-related questionnaires (Scleroderma Health Assessment Questionnaire (SHAQ)) and hand function (Duruoz hand index (DHI)). <h3>Methods</h3> This study included patients with SSc according to the 2013 ACR/EULAR classification criteria, examined in our EUSTAR center from 11.2011 to 11.2016, who were under the legal age of retirement of in our country (62 years). Patients completed a work assessment questionnaire, the DHI and the SHAQ, as well as a full assessment as per the recommendations of EUSTAR. Logistic regression was used to investigate the associations between employment status (outcome) and potential predictors (including socio-economic status, education, disease characteristics and health-related questionnaires). <h3>Results</h3> There were 66 patients (8 males, mean±SD age 49.1±9.3 years, 19 with diffuse cutaneous SSc (dcSSc), 46 with history of digital ulcers (DUs) and 23 with joint contractures) included. Forty-two patients lived in urban environments and 42 had higher education (high school or above). Twenty patients were active professionally, whereas 46 were retired, of which 32 retired because of SSc. Of those active professionally, 8 had to do manual labor, 7 had to spend many hours at work standing and 3 had a cold or moist work environment. Using logistic regression adjusted for age and gender, higher education was found to be highly associated with employment (OR (95% CI) 9.0 (1.5, 52.4)), whereas labor conditions (manual labor, stress) had no significant influence on employment status in our cohort. No association was found between employment status and disease characteristics or SHAQ and DHI questionnaires. <h3>Conclusions</h3> SSc is associated with substantial work disability and unemployment. Completing less education than high school was associated with early retirement. <h3>Acknowledgements</h3> <sup>*</sup><i>This abstract was realized as part of the “Development of a computer-based nailfold videocapillaroscopy (NVC) system for longitudinal evaluation of patients with systemic sclerosis” (QUANTICAP) project, financed by the UEFIS-CDI PN-II-PT-PCCA-2013–4-1589 grant.</i> <h3>Disclosure of Interest</h3> None declared
Phase II trial of daily pulse interleukin-2 (IL-2) therapy during marrow recovery in patients with acute myeloid leukemia (AML) NCT#01289678.
Authors: Manali K. Kamdar, Adam Steven Asch, Jackie Unger, Paul R. Walker
Journal: Journal of Clinical Oncology (2012)

e17008 Background: Therapeutic advances in treating AML have been limited in the past two decades. Allogeneic stem cell transplant (Allo-SCT) can cure patients with relapsed and high-risk AML with a graft versus leukemia immune effect. IL- 2 promotes the proliferation and activity of cytotoxic T cells, natural killer cells and lymphokine activated cells. IL-2 has been shown to abrogate the clonogenic leukemic blasts in murine leukemias and has achieved complete remissions in relapsed AML. Early absolute lymphocyte recovery after induction chemotherapy predicts a superior survival in AML suggesting a critical role of early immune recovery. (Behl et al Leukemia 2006) Stimulated LAK cells by IL-2 during this critical early lymphocyte recovery period may enhance a graft versus leukemia immune effect and potentially improve the outcome of first-line AML treatment. Methods: 12 adult patients with de novo or secondary AML were consented to receive IL-2 during induction and/or post-remission treatment marrow nadir recovery. The eligibility criteria included a rising WBC count &gt;500mm3, supported platelet count &gt;20,000 and hemodynamic stability. IL-2 18 million IU/m2 was administered over 15-30 minutes daily for 5 days within 7 days of a WBC rising above 500mm3. Primary end point overall survival (OS). Median age 52 yrs. (range 33-72). Results: 3 pts. received IL-2 during induction recovery; 3 during re-induction recovery, 3 during consolidation recovery. 1 pt. subsequently underwent an Allo-SCT in remission. Median OS 25 months. With a median followup of 36 months (range 12-60 months), 5 of 9 (55%) treated pts. and 4 of 8 (50%) pts. without an Allo-SCT, are alive and leukemia free. Of the 5 alive, 3 are over the age of 60 and 2 had complex cytogenetics. Expected toxicities with IL-2 included grade 3 fever/chills (77%) but there were no respiratory or hemodynamic complications requiring ventilator support. Conclusions: IL-2 therapy administered during marrow/lymphocyte recovery after standard induction/consolidation chemotherapy in first-line AML treatment achieved a 50% 3-year overall and leukemia free survival without an Allo-SCT.
SAT0311 Prolonged exposure to antiphospholipid antibodies is associated with endothelial dysfunction in patients with systemic lupus erythematosus
Authors: Y-J Park, I-W Baek, K-J Kim, W-U Kim, C-S Cho
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Antiphospholipid syndrome has been shown to be associated with increased cardiovascular mortality, but the role of antiphospholipid antibodies (aPL) on endothelial dysfunction remains elusive. <h3>Objectives</h3> We investigated the association between endothelial dysfunction and aPL in systemic lupus erythematosus (SLE) patients. <h3>Methods</h3> 188 SLE patients and 62 controls were enrolled. Endothelial function was measured by flow-mediated dilatation (FMD). Cardiovascular risk factors were assessed and quarterly measurement of anti-cardiolipin (aCL) and anti-β<sub>2</sub> glycoprotein I Ab were used to calculate time-integrated values throughout disease duration. Circulating endothelial progenitor cell (EPC), defined by CD34+/KDR+ mononuclear cells, was quantified by flow cytometry. <h3>Results</h3> Median FMD was significantly lower in SLE patient than in controls (6.9 versus 9.3%, <i>P</i>&lt;0.001). In univariate analysis, older age, hypertension, thrombocytopenia, and persistent positive lupus anticoagulant (LAC) were associated with decreased FMD in SLE patients (<i>P</i>=0.021, <i>P</i>=0.011, <i>P</i>=0.004, and <i>P</i>=0.028). Time-integrated aCL value (TI-aCL), but not a single value, was correlated with decreased FMD (<i>P</i>=0.001). Multivariate analysis showed that hypertension and TI-aCL were independent factors for decreased FMD (<i>P</i>=0.027, <i>P</i>=0.008); addition of positive LAC increased the adjusted probability of decreased FMD (<i>P</i>=0.023). FMD was correlated with EPC number (γ=0.342, <i>P</i>=0.005) and TI-aCL was also an independent factor of reduced EPC after multiple adjustment (<i>P</i>=0.019). The predicted probability of endothelial dysfunction at median EPC level was higher in group with high TI-aCL than in group with low TI-aCL (<i>P</i>=0.004). <h3>Conclusions</h3> Cumulative burden of aPL was closely associated with endothelial dysfunction in SLE patients, which was mediated in part by reduction of EPC. <h3>Disclosure of Interest</h3> None declared