tbuckley/cabot-search huggingface dataset:
AB1215 Juvenile idiopathic arthritis: Interaction of attitude of parents and children to the disease
Authors: V. Malievsky, G. Gareeva
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Peculiarities of functioning of family and of social support of patents with juvenile idiopathic arthrities can have the determining knowledge in formation of social and psychological adaptation of sick children. <h3>Objectives</h3> There were questionnaired 108 patients with juvenile idiopathic arthritis (46 boys and 62 girls aged from 7 to 16 years) and their parents. <h3>Methods</h3> To study psychological reaction of parents on the child's disease, there was used "Procedure of diagnostics of parents' attitude to the child's disease" by V.E. Kagan and I.P. Zhuravleva. "The internal picture of disease" was estimated with use of "Methods for psychological diagnostics of types of attitude to disease". The test was represented by questions about the effect of disease on the state of health, mood, sleep, attitude to relatives, closes and surroundings, studying, attitude to solitude and future, as well as about questions on attitude to medical staff. <h3>Results</h3> With aid of linear correlational analysis, there was established effect of parents' attitude to the child's disease on formation of the "internal picture of disease", attitude of child to his disease. The positive correlational connections of moderate strength are revealed between parameters of scale of anxiety of test of parents' attitude to child's disease and the anxiety scales (<i>r</i> =0.32, <i>d</i> =0.031) and sensitivity (<i>r</i> =0.36, <i>d</i> =0.014) of test of attitude to disease. The negative correlational connection between the scale "Nosognosia" and scale of anosognosia TOB (<i>r</i> = -0,35, <i>p</i> =0.02) indicates that in development of the anosognosical type of child's attitude to disease, a certain role is played by the parental perception of seriousness and severity of the child's disease. <h3>Conclusions</h3> It can be suggested that the parents' anxious reaction to child's disease promotes development of such adverse psychological child's reaction to disease as anxiety and concern on the occasion of possible unfavorable outcomes of disease, inefficiency of treatment (the anxious type) or unfavorable expression on surroundings, fear of poor-disposed attitude from their side (the sensitive type). <h3>Disclosure of Interest</h3> None Declared
Abstract 3809: Tumor-released GPI-anchored proteins bind to mannose receptor and polarize tumor-infiltrating macrophages
Authors: Denarda Dangaj, Aizhi Zhao, Selene Nunez-Cruz, Raphael Sandaltzopoulos, Nathalie Scholler
Journal: Cancer Research (2010)

Abstract Tumors polarize their microenvironment to escape immune-mediated destruction and to promote their growth. Macrophages respond to microenvironmental signals and can be activated toward a classical (M1) or an alternative (M2) phenotype. Tumor-associated macrophages (TAM) resemble to M2 macrophages with a phenotype characterized by the overexpression of IL10, scavenger receptor SR-A, CD68 and MR phenotype but hampered levels of IL-12. M2, in contrast to M1 macrophages, promote TH2 immune responses as well as tissue remodelling and M2 infiltration in solid tumors has been shown to significantly correlate with poor prognosis. Recent evidences suggest that macrophage differentiation towards TAM involves a “chemical conversation” via exchange of unknown soluble extracellular mediators between tumor cells and macrophages. In addition, previous work showed that the cross-linking mannose receptor (MR) with an anti-MR mAb could cause dendritic cell differentiation into APCs promoting T-cell anergy. We hypothesized that MR expressed by macrophages could be bound by tumor-released GPI-anchored glycoproteins through the GPI-anchor mannose residues freed by cleavage. We also hypothesized that MR binding by GPI-anchor could trigger macrophage polarization toward TAMs. To test our hypotheses, we established an in vitro model system of cell co-culture in transwell allowing chemical exchanges between human monocyte-derived macrophages and human ovarian cancer cell line Ovcar3 that sheds mesothelin, a cancer biomarker and a GPI-anchored glycoprotein. Macrophage phenotype changes were monitored by flow cytometry and qRT-PCR. We also isolated three novel recombinant antibodies (scFv) against MR by magnetic and flow sortings from a novel yeast-display human scFv library. We describe here for the first time that tumor-released mesothelin bound to macrophage cell surface in presence of calcium, and that mesothelin binding to macrophages could be blocked by the anti-MR scFv. Furthermore, macrophage phenotype switch toward M2 during coculture with tumor cells could be prevented by one of the anti-MR scFv. Finally, we demonstrated that M1 phenotype could be rescued during coculture with tumor cells with one of the anti-MR scFv. To further characterize the role of MR in vivo, we have implanted mannose receptor knock-out mice intraperitoneally (IP) with luminescent-labeled ovarian cancer cells that overexpress mesothelin. We are now monitoring the tumor growth by in vivo imaging. 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 3809.
Abstract 871: Dual inhibition of PI3K and Erk1/2 shows synergy and efficacy in human tumor cells, either by using drug combinations or novel dual PI3K/Erk inhibitors
Authors: Irene Seipelt, Matthias Gerlach, Lars Blumenstein, Gilbert Mueller, Eckhard Guenther, Jürgen Engel, Michael Teifel
Journal: Cancer Research (2012)

Abstract The Ras/Raf/Mek/Erk and the PI3K/Akt signaling pathways are frequently deregulated in cancer due to activation of upstream receptors, decreased expression of tumor suppressors like PTEN or activating mutations of Ras, B-Raf or PI3K. Several clinical studies with kinase inhibitors targeting single members of the Ras/Raf/Mek/Erk or the PI3K/Akt pathway are ongoing. However, preclinical and clinical trials indicated limited success by single pathway inhibition and different resistance mechanisms were defined. Further clinical trials with drug combinations of Ras/Raf/Mek/Erk and PI3K/Akt suppressors have been initiated, suggesting a more favorable outcome than targeting only one single pathway, Ras/Raf/Mek/Erk or PI3K/Akt. We performed in-vitro combination experiments with Raf, Mek or Erk inhibitors and PI3K or Akt inhibitors in several human tumor cell lines. Strong synergy was achieved with various combinations including the Mek inhibitor CI-1040 and the PI3K inhibitor GDC-0941 (CI = 0.17) or the Erk inhibitor AEZS-131 and the PI3K inhibitor D-117073 (CI = 0.23) in A549 cells. Also Raf inhibitors like Sorafenib and Zelboraf were combined with different PI3K inhibitors, resulting in synergistic anti-proliferative activity. Due to the attractiveness of parallel inhibition of the Ras/Raf/Mek/Erk and PI3K/Akt pathways, we developed AEZS-136 that concurrently inhibits Erk1/2 (IC50 ∼ 50nM) and PI3K (IC50 ∼ 100nM) by an ATP competitive mode of action. Derivatives of the dual PI3K/Erk inhibitor were co-crystallized with Erk2 and PI3Kα enabling an optimization process by SAR driven medicinal chemistry. The anti-proliferative efficacy of AEZS-136 was evaluated in more than 40 human tumor cell lines and physico-chemical as well as in-vitro ADMET properties were widely assessed. Furthermore, the in-vivo pharmacokinetics and anti-tumor efficacy was explored. AEZS-136 was well tolerated and showed dose dependent inhibition of human colon tumor growth of up to 74% in a Hct116 mouse model. Here we present the concept of dual targeting of the Ras/Raf/Mek/Erk and the PI3K/Akt pathways, either by using drug combinations or our novel dual PI3K/Erk inhibitor. AEZS-136 is a small molecule in preclinical development showing a uniquely advantageous kinase inhibition profile. Broad clinical anti-tumor activity is expected for AEZS-136 in tumors with deregulated Ras/Raf/Mek/Erk and PI3K-Akt signaling. 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 871. doi:1538-7445.AM2012-871
Abstract 1432: The heterogeneous genomic landscape of posterior fossa ependymoma
Authors: Hendrik Witt, Stephen C. Mack, Sebastian Bender, Marina Ryzhova, Sill Martin, Ruth Isserlin, David T. W. Jones, Paul A. Northcott, Milde Till, Marc Remke, Axel Benner, Thomas Hielscher, Nalin Gupta, Livia Garcia, William A. Weiss, Kelsey Betrand, Timothy van Meter, Andreas von Deimling, Stefan Rutkowski, Torsten Pietsch, Andreas E. Kulozik, Yoon-Jae Cho, Uri Tabori, Cynthia E. Hawkins, Olaf Witt, Gary D. Bader, James T. Rutka, Peter Lichter, Andrey Korshunov, Michael D. Taylor, Stefan M. Pfister
Journal: Cancer Research (2012)

Abstract Brain tumors are the most common cause of cancer-related death in childhood. Ependymomas, are the third most common pediatric brain tumor. The disease remains incurable for about 45% of patients even after gross total resection and radiotherapy. Despite showing a very homogeneous histological picture, ependymomas display distinct molecular behavior, which supports the existence of several independent entities of the disease. We examined two non-overlapping cohorts of 102 and 75 ependymomas by mRNA expression profiling, on two different array platforms (Affymetrix, Agilent). When performing multiple statistical clustering methods (unsupervised consensus NMF and consensus HCL), we could consistently identify three major clusters, including two subgroups of posterior fossa (PF) ependymoma, a variant common in children and associated with heterogeneous clinical outcome. Subgroup-specific chromosome aberrations of PF tumors were detected by aCGH, and biological signaling pathways distinguishing PF subgroups were identified by gene set enrichment analysis and visualized in Cytoscape. We validated the most significantly classifying markers of each subgroup by immunohistochemistry on a tissue microarray containing an independent set of 265 PF ependymomas. Our findings delineate two subgroups of PF ependymoma (groups A and B) which are demographically, transcriptionally, genetically, and clinically distinct. Group A patients are younger, have laterally located tumors with a balanced genome, more frequently develop secondary metastases and are much more likely to have an extremely poor outcome as compared with group B patients. Based on a multi-variate Cox proportional-hazards model, our identified markers have the strongest independent prognostic value among demographic and molecular variables with Hazard ratios of 8.45 (PFS) and 10.55 (OS). Prognostic significance and predictive impact is being validated in the GPOH HIT2000 Ependymoma study. The identification of two distinct subgroups of PF ependymoma, and markers applicable for their clinical distinction, will allow for better prognostication of individual cases, independent of age, level of resection and WHO grade, and also for stratification in future ependymoma clinical trials. 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 1432. doi:1538-7445.AM2012-1432
FRI0308 Is Tuberculosis Screening Sufficient for Preventing TB Reactivation in Biologic Treated Patients?
Authors: D. Opris, D. Mazilu, I. Saulescu, R. Ionescu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The risk of latent tuberculosis (TB) reactivation in patients treated with biologics for rheumatic inflammatory diseases is well-established. This is a great concern especially in countries with high TB burden. Most national guidelines recomend screening for latent TB before the initiation of biologic treatament. In our country the mandatory screening consists of combination of patient9s personal history evaluation asscociated with tuberculin skin test (TST positive &gt;5 mm), QuantiFERON TB gold test and chest x-ray. <h3>Objectives</h3> To evaluate the efficacy of correct secreening for latent tuberculos in patients treated with biologics. <h3>Methods</h3> 91 rheumatoid arthritis and ankylosing spondylitis patients (72.6% females, 27.4% males, mean age 50.8 years, mean disease duration 68.9 months) treated with biologics betwee Jan 2009- Dec2013 were prospectively analysed. When indicated (TST≥5mm and/or QuantiFERON positive) isoniazid treatment for latent TB was initiated for 9 months and the chosen biologic started 1 month later. Our cohort excluded patients treated for less than 3 months with biologics. <h3>Results</h3> 24.5% were treated with Infliximab (mean treatment duration 29.7±14.1), 10,6% with Etanercept (mean treatment 33±11.9), 25,5% with Adalimumab (mean treatment 22.6±13.1), 4,3% with Golimumab (mean duration 22±8), 4.3% with Certolizumab (mean duration 14±5.88), 17% with Tocilizumab (mean duration 25.8±8.3) and 16% with Rituximab (mean treatment 25.8±8.32 months). Three (3.3%) patients developed active TB. All of them had negative screening (TB history and contact, QuantiFERON and TST) and all were BCG vaccinated since childhood. One of these patients was on Golimumab for 18 months; the second patient was on certolizumab pegol for 11 months; and the third one on Iinfliximab for 16 months. One patient developed a solitary lung tuberculom and two extralung involvement (one ganglionar and one multiorgan TB). None of the patients with latent TB (consecutively treated with isoniazid) developed TB during biological treatment. Treatment duration was negatively correlated to TB development (r=-0.219, P=0.037). <h3>Conclusions</h3> Negative screening tests for latent TB are not sufficient for preventing TB development in patients treated with biological agents. Statistical analysis suggested that constant monitoring of patients treated with biological agents should be done, especially in the first months. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5664
S30 Red Cell Distribution Width As A Predictor Of Hospital Mortality In Acute Exacerbations Of Copd (aecopd)
Authors: C. Echevarria, J. Steer, G. Gibson, S. Bourke
Journal: Thorax (2014)

<h3>Introduction</h3> An increased red cell distribution width (RDW), a routinely available index of the variability of erythrocyte size, has been associated with an adverse prognosis in cardiac and respiratory disease, including COPD.<sup>1</sup> We have assessed its value in AECOPD and whether adding RDW improves the predictive power of the DECAF score.<sup>2</sup> <h3>Methods</h3> We studied 2 groups of patients with AECOPD, the “derivation cohort” (n = 920) in whom DECAF was derived<sup>2</sup> and the “internal validation cohort” (n = 880) in whom its prognostic value was confirmed.<sup>3</sup> In the validation cohort RDW was collected prospectively and relationships to mortality assessed by univariate and multivariate logistic regression. RDW values were dichotomised by visual inspection of the receiver operator characteristic (ROC) curve which showed the optimal prognostic threshold for hospital mortality to be 15.5%, consistent with other studies.<sup>1</sup> “RDW score” (15.5% or less=0, greater than 15.5%=1) was added to the DECAF score and the areas under the ROC (AUROC) curves for the DECAF and DECAF-RDW scores were compared by the method of DeLong. In the derivation cohort RDW was collected from laboratory records and the prognostic utility assessed separately by logistic regression. <h3>Results</h3> In the validation cohort RDW &gt;15.5% was a strong predictor of inpatient mortality in both univariate (OR 2.70, 95% CI 1.68–4.32, p &lt; 0.001) and multivariate analysis (OR 2.16, 95% CI 1.28–3.6 4, p = 0.004). However, there was no difference between the AUROC curves for the DECAF and DECAF-RDW scores (Figure 1; p = 0.63). In the derivation cohort RDW &gt;15.5% showed a non-significant trend towards higher inpatient mortality on univariate analysis (OR 1.55, 95% CI 0.96–2.50, p = 0.07), but there was no association on multivariate analysis (OR 1.05, 95% CI 0.60–1.84, p = 0.86). <h3>Discussion</h3> The significant association of RDW with inpatient mortality in AECOPD in one cohort but not the other suggests limited value in this population. When forced into the DECAF model, RDW did not improve its predictive power and is a weaker prognostic index than the component parts of DECAF. <h3>References</h3> Seyhan <i>COPD</i> 2013 Steer <i>Thorax</i> 2012 Echevarria <i>Thorax</i> 2013(68:A138)
AB1295 Ultrasound assessment at patients with late onset of rheumatoid arthritis: Higher scores of inflammation activity of joint compared to early onset of rheumatoid arthritis
Authors: R. Osipyants, E. Panasyuk, D. Karateev, S. Gluchova, E. Aleksandrova, A. Volkov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Growing evidence supports the hypothesis that in elderly onset of rheumatoid arthritis (RA) patients (pts) showed higher sonographic scores of inflammation despite similar clinical disease activity compared to in young onset of RA. <h3>Objectives</h3> To evaluate inflammatory changes of joints by grey scale (GS) ultrasonography (US) at pts with late and early onset of RA. To compare US findings with clinical and laboratory data. <h3>Methods</h3> Twenty-one pts (76% women) with RA were enrolled. All pts were divided into two groups: 1st (n=11) – pts with early onset of RA (before the age of 55 years), 2nd (n=10) – with late onset of disease (after the age of 55 years). US examination (``Voluson-i" (GE, USA), 4-13MHz probe) was included the GSUS scores of the wrists and hands: the US scores in 24 joints (bilateral wrist and hand) - US24; in dominated hand - 8 (wrist (2), II-IV MCP and II-IV PIP) - US8 and 5 joints (wrist, II-III MCP and II-III PIP) - US5. Different semiquantitative synovitis sum scores were generated by GS results. On the same day, laboratory data (CRP, ESR), clinical disease activity (28 tender/swollen joints, disease activity score-28 (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI)) were evaluated. <h3>Results</h3> Ten pts with late onset of RA [median age 65 (range 63-67) years; disease duration 36 (12-48) months; DAS28 6.6 (5.6-7.2); 70% "+" for rheumatoid factor (RF) and 80% "+" for anti-citrullinated peptide antibodies (ACCP))] and eleven pts with early onset of disease [48 (39-53) years; 60 (24-96) months; DAS28 6.8 (5.9-7.1); 91% "+" for RF, 80% "+" for ACCP)]. Pts with late onset of RA had higher the US scores from the 24, 8, 5 joints vs. pts with early onset of RA [26.5 (19-32) vs. 16 (13-18) for US24, p=0.026; 12 (8-13) vs. 7 (5-10) for US8, p=0.048; 8.5 (6-10) vs. 5 (3-6) for US5, p=0.022]. Interestingly, a level of RF (titer) in pts with early onset of disease was higher compared to the other group [279 (205-665) vs. 113 (9.5-215), p=0.029]. The laboratory markers of inflammation as well as parameters of clinical disease activity were comparable between both groups of pts. <h3>Conclusions</h3> RA pts with onset of disease after the age of 55 years showed high US scores of inflammation despite laboratory data and clinical disease activity. Consequently, it is possible more rapid subclinical disease progression compared to pts with early onset of RA. <h3>Disclosure of Interest</h3> None Declared
Modified fishing-line traction system in endoscopic submucosal dissection of large esophageal tumors
Authors: S. Tsao, T. Toyonaga, Y. Morita, T. Fujita, T. Hayakumo, T. Azuma
Journal: Endoscopy (2011)

Endoscopic submucosal dissection (ESD) is a proven and safe technique in the en bloc removal of early gastrointestinal tract cancers [1]. With the array of available ESD devices and improvement in ESD techniques, it is now safe to resect lesions even in difficult locations, such as the esophagus [2]. However, technical challenges remain when attempting to resect large lesions in locations within a confined space. When the tumor occupies greater than three-quarters of the esophageal circumference, the endoscopic view is diminished when the resection reaches the central portion of the tumor, making further resection difficult and unsafe. To counteract this problem, we have devised a modified version of a traction system previously described in the resection of intragastric lesions [3].
Abstract 4794: Kras mutation is associated with elevated myeloblastin activity in human lung adenocarcinoma
Authors: Sven Hillinger, Thomas Wiedl, Stephane Collaud, Stephan Arni, Peter Schraml, Alex Soltermann, Holger Moch, Walter Weder
Journal: Cancer Research (2012)

Abstract Background Lung cancer is the leading cause of all cancer deaths worldwide with suboptimal prognosis and treatment options. Therefore we aimed to identify molecular characteristics with a predictive clinical utility that at the same time might represent novel therapeutic targets for human lung adenocarcinoma. Within this study we investigated KRAS mutations, a gene frequently mutated in lung adenocarcinoma and their association with enzymatic activities of members of the serine hydrolase superfamily, a large class of enzymes that have previously been linked to cancer. Methods Participating individuals underwent surgery for lung adenocarcinoma at the University Hospital Zurich between 2003 and 2006. Formalin fixed, paraffin embedded as well as snap-frozen lung adenocarcinoma samples were histologically reviewed by a pathologist. Mutation detection was performed via a custom service by Sequenom. Cell extracts derived from human snap-frozen biopsies were processed prior to mass spectrometric analysis as previously described to analyze serine hydrolase activities. Results Mutation analysis of 40 human lung adenocarcinoma specimens identified 4 patients (10%) harbouring a cysteine for glycine substitution at position 12 (G12C) in the KRAS gene. By employing two-sided unpaired t-test we found a statistical significant (p = 0.01) activity difference of the enzyme myeloblastin between patients harbouring a G12C mutation in the KRAS gene and patients harbouring no KRAS mutation. Conclusions The results of this study revealed that the activity of myeloblastin is significantly altered in lung adenocarcinoma biopsies harboring a KRAS gene mutation. Based on the results of this study we conclude that the combination of activity-based proteomics with mutational analysis is a valid approach for the discovery of novel biomarkers for human lung adenocarcinoma. 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 4794. doi:1538-7445.AM2012-4794
Availability of junk food should be reduced
Authors: J. Tammam, L. Gillam, B. Gesch, J. Stein
Journal: BMJ (2012)

Prison inmates rely on two sources of food—main meals (provided by the prison) and items purchased from the canteen,1 2 the penal equivalent of a convenience store.

Prison meals meet nutritional guidelines, but purchased items—much of it “junk” food—may not.3We analysed macronutrient and energy content of food available in a canteen from …