tbuckley/cabot-search huggingface dataset:
FRI0141 Rapid3 in 90 Korean Patients with Ankylosing Spondylitis Yields Similar Information to BASDAI and Asdas, with Greater Feasibility for Busy Clinical Settings:
Authors: S.-H. Park, J.-Y. Choe, S.-K. Kim, H. Lee, T. Pincus
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) is a self-report index to assess disease activity in patients with ankylosing spondylitis (AS). The ASDAS (AS disease activity score) is recorded by the rheumatologist, based on the ASAS (Assessment of SpondyloArthritis International Society) core data set of 11 measures in 7 domains: patient global estimate of status, spinal pain, spinal stiffness, fatigue, physical function, spinal mobility, acute phase reactant. These quantitative measures are invaluable in clinical trials and clinical research, but difficult to administer in busy clinical care settings, in which the most feasible procedure generally is for the receptionist to provide the same questionnaire to all patients. A multidimensional health assessment questionnaire/routine assessment of patient index data (MDHAQ/RAPID3) is completed easily by all patients in 5-10 minutes, in a waiting area prior to seeing a rheumatologist, and has been found an informative in patients with all rheumatic diseases. <h3>Objectives</h3> To compare scores on 3 indices, BASDAI, ASDAS and RAPID3 in 90 Korean patients with AS seen in a usual care setting. <h3>Methods</h3> All patients complete an MDHAQ/RAPID3 in this setting. Patients with AS complete a BASDAI, and have ASDAS assessed by a rheumatologist. Indices and individual measures were computed and compared using Spearman correlation coefficients, cross-tabulations, and kappa statistics. <h3>Results</h3> Ninety AS patients in usual clinical care were studied; median age was 39.1 years, median duration of disease 7.0 years, and 76.7% were male. RAPID3 scores were correlated significantly with BASDAI (rho=0.751) and ASDAS (rho=0.690), as well as with individual BASDAI and ASDAS scores for spinal pain, spinal stiffness, fatigue, Bath AS Functional Index (BASFI) physical function (rho &gt;0.66) (all p&lt;0.001) (data not shown). Overall, 39, 14, 17 and 20 patients had RAPID3 scores indicating high, moderate, low severity, and remission, respectively. All 21 patients with BASDAI scores ≥4, indicating active AS, had RAPID3 scores greater than 12, indicating high severity (Table). Among 56 patients with ASDAS ≥1.3 indicating active disease, 36 (64%) had high and an additional 8 (total=79%) moderate RAPID3 severity (Table). <h3>Conclusions</h3> RAPID3 provides similar information to BASDAI and ASDAS. BASDAI and ASDAS are more specific for clinical trials and clinical research, but the feasibility of MDHAQ/RAPID3 in busy clinical settings suggests possible value in usual clinical care of patients with AS. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3931
Abstract 5415: Targeting lipogenic signaling to repress cancer cell growth.
Authors: Chenguang Wang, Weihua Li, Jie Zhou, Yanhong Tai, Weiting Gu, Bhaskar C. Das, Junyuan Ji
Journal: Cancer Research (2013)

Abstract The significantly enhanced lipogenesis is a metabolic hallmark of rapidly proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than 90% of required lipids de novo. The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression. Although it is known that SREBP1 and its target genes are overexpressed in a variety of cancers, the role of SREBP1 in endometrial cancer is largely unknown. Herein, we screened a panel of endometrial cancer specimen for their lipogenic gene expression by quantitative PCR and showed a significant increase in mRNA abundance of SREBF1, SREBF2, and FASN genes in cancer compared to normal endometrium. Immunohistochemical staining confirmed SREBP1 protein overexpression and further demonstrated increased nuclear distribution of SREBP1 in EC. SREBP1 promotes cellular proliferation in cell culture and enhances tumor growth in a xenograft model. Knockdown of endogenous SREPF1 gene impaired the viability of cells cultured in medium supplemented with lipid-depleted serum. BF175, a small molecule inhibitor designed to target SREBP1, repressed SREBP1-dependent gene expression and cell growth and induced EC cell death. We extended our observation to over 100 cancer cell lines from 12 different cancer types and showed promising results of BF175 in repressing tumor growth and inducing cell death. Together, this study established a role of SREBP1 in tumor growth and validated BF175 for its therapeutic effectiveness in targeting SREBP1 and lipogenesis to block cancer cell growth. Citation Format: Chenguang Wang, Weihua Li, Jie Zhou, Yanhong Tai, Weiting Gu, Bhaskar C. Das, Junyuan Ji. Targeting lipogenic signaling to repress cancer cell growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5415. doi:10.1158/1538-7445.AM2013-5415
SP0146 Using Psychological and Motivational Approaches in Routine Consultations: Barriers and Facilitators
Authors: E. Dures
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Self-management requires informed, activated patients to manage the physical and psychosocial consequences of arthritis, and to make lifestyle changes. The process of self-management focuses on developing skills such as problem solving, decision making, and appropriate use of healthcare resources. Taking an active role in their own care is rarely a choice that patients can enact alone, and is highly influenced by the dynamic created in the way care is provided. Rheumatology clinicians are well placed to utilise a range of basic psychological skills and techniques to facilitate a collaborative interaction and support self-management. These include: key questions at the start of the consultation to prompt patients to identify their priorities; formulation to unpick the relationship between thoughts, feelings, symptoms and behaviours, and how they are driving symptoms; and double-sided reflection and listing pros and cons of a behaviour. Qualitative research conducted with rheumatology clinicians who have undertaken brief skills training, identified barriers and facilitators of using psychological approaches in routine clinical care to facilitate self-management. Barriers included: a lack of time in clinic; the difficulties of changing the existing pattern and focus of interaction; and concerns about exploring social and emotional aspects of living with arthritis. Facilitators included: training that balanced theory with time to practice skills and receive feedback; access to clinical supervision to gain confidence and develop more advanced techniques; and the perception that patients gained a greater sense of control and were better able to take responsibility for their treatment, as a consequence of a more collaborative consultation. <h3>Disclosure of Interest</h3> None Declared
PMO-233 A prospective audit of the use of calcineurin inhibitors in patients with refractory ulcerative procto-colitis in a district general hospital
Authors: B D Warner, L Blackmore, C Mungalsingh, A W Harris
Journal: Gut (2012)

<h3>Introduction</h3> Calcineurin inhibitors (CI), most commonly ciclosporin, may be used as salvage therapy in patients with refractory moderate-severe ulcerative procto-colitis (UC), who would otherwise require surgery.<sup>1</sup> However, use of CI may be limited by drug toxicity. For patients who have a good clinical response to ciclosporin but experience side effects, tacrolimus may be used as an alternative.<sup>2</sup> We report our experience with CI in patients with moderate-severe UC whom either failed, or were intolerant of, thiopurines and as an alternative to surgery. <h3>Methods</h3> NICE (January 2008) did not support the use of infliximab in patients with moderate-severe UC.<sup>3</sup> Our patients were offered the choice of surgery or treatment with CI. Clinical response was assessed by AWH in clinic. If ciclosporin (4–6 mg/kg/day in two divided doses) led to a clinical response but caused intolerable side effects, tacrolimus (0.1 mg/kg/day in two divided doses) was offered as an alternative. Failure of therapy prompted referral for surgery. <h3>Results</h3> 14 patients (8 female; mean age 38 [range 22–56] years) were treated with CI (13 ciclosporin, 1 tacrolimus). Ten of 14 (71%) patients had an initial clinical response to CI. Adverse effects were common (57%): nausea, paraesthesia, menstrual disturbance, maculopapular rash, hypertension (two patients) and renal dysfunction (one patient). Of the four patients who failed to respond to CI, three were referred for surgery and one patient is managed on mesalazine suppositories. A further four patients stopped treatment with CI due to adverse effects: two were referred for surgery and two were offered treatment with methotrexate. 6 (43%) of 14 patients responded successfully to CI and without side effects. 4 (30%) of these remain on CI: 3 on ciclosporin (mean duration of treatment 39 [range 19–71] months) and one patient on tacrolimus (duration of treatment 24 months); two patients stopped treatment with CI for reasons unrelated to efficacy or adverse effects (one to start a family and the other out of choice). <h3>Conclusion</h3> CI should be considered as an alternative therapy for patients with refractory moderate-severely active UC who would otherwise require surgery. CI can be used safely and effectively in the presence of an established evidence-based protocol to ensure safe prescribing and monitoring for adverse side effects. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Lichtiger S</b>, Present DH, Kornbluth A, <i>et al.</i> Cyclosporine in severe ulcerative colitis refractory to steroid therapy. <i>N Eng J Med</i> 1994;<b>330</b>:1841–5. 2. <b>Ogata H</b>, Matsui T, Nakamura M, <i>et al.</i> A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. <i>Gut</i> 2006;<b>55</b>:1255–62. 3. Ulcerative colitis (subacute manifestations)–Infliximab (TA140) NICE.
Abstract 1181: Expression of epithelial splicing regulatory protein 1 and 2 in ovarian cancer
Authors: Yutaka Shoji, Siri Chirumamilla, GVR Chandramouli, John I. Risinger
Journal: Cancer Research (2010)

Abstract Epithelial Splicing Regulatory Proteins (ESRP1 and ESRP2) have recently been reported as RNA binding proteins that regulate epithelial specific splicing. We identified over-expression of ESRP1 and ESRP2 in ovarian cancer. The aim of this study was to determine the extent of expression of ESRP1 and ESRP2 in ovarian cancers and to examine whether its expression affects the abundance of the epithelial isoform of the Fibroblast Growth Factor receptor 2 (FGFR2) in ovarian cancer. Furthermore, we studied the regulation of FGFR2 splicing following knock-down of ESRPs in ovarian cancer cells. Affymetrix U133 Plus2.0 Array and quantitative real-time polymerase chain reactions (qRT-PCR) were used to measure gene expression levels in ovarian cancers and normal ovaries. ESRP1, ESRP2, epithelial specific FGFR2 IIIb and mesenchymal isoform FGFR2 IIIc mRNA levels were determined via qRT-PCR. RNA interference (RNAi) was used to knock-down ESRP1 and/or ESRP2 to examine its function on determining FGFR2 isoform expression in ovarian cancer cell line OVCAR3. Affymetrix GeneChip expression array analysis of 20 Stage IIIC serous ovarian cancers and 8 normal ovary surface epithelium brushings identified over-expression of ESRP1 (235 fold) and ESRP2 (33 fold). qRT-PCR confirmed that ESRP1 (7586 fold, p &amp;lt; 0.00001) and ESRP2 (21 fold, p &amp;lt;0.00001) were over-expressed in an independent set of 27 ovarian cancers compared to 11 normals. Since ESRP1 and ESRP2 function to drive the epithelial specific splicing of FGFR2, we examined the relative expression of FGFR2 IIIb and FGFR2 IIIc via qRT-PCR. The epithelial specific FGFR2 IIIb was over-expressed (313 fold; p &amp;lt; 0.00001), whereas the mesenchymal isoform FGFR2 IIIc was down-regulated (75 fold). RNAi knock-down of ESRP1 in OVCAR3 cells resulted in increased levels of mesenchymal specific FGFR2 IIIc (6 fold), but had a minimal effect on FGFR2 IIIb expression (−1 fold). ESRP2 knock-down had no detectable effect on FGFR2 IIIc and IIIb expression. However, ESRP1 and ESRP2 double knock-down results in the predominant expression of FGFR2 IIIc (25 fold) and down-regulation of FGFR2 IIIb (−3 fold) when standardized to a scramble control. Our results confirmed that ESRP1, ESRP2 and FGFR2 IIIb are over-expressed and FGFR2 IIIc is down-regulated in ovarian cancers. Also, results of RNAi double knock-down of ESRP1 and ESRP2 indicate that ESRPs drive the expression of the epithelial isoform FGFR2 IIIb in ovarian cancer cells. These data have implications on the ligand specificity of the FGFR2 receptor and for potential individualized therapies targeting FGF signaling in ovarian cancer. 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 1181.
Abstract 1680: Age-associated gene expression in normal breast tissue provide insights regarding associations between aging and aggressive tumor characteristics
Authors: Monica D'Arcy, Jason R. Pirone, Delisha A. Stewart, Patricia Casbas-Hernandez, Michael N. Gould, Joseph Jerry Jerry, Paul Yaswen, Sallie Smith Schneider, Melissa A. Troester
Journal: Cancer Research (2012)

Abstract Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. Though several genomic studies have characterized differences in the biology of tumors arising in younger vs. older women, understanding of age-related gene expression in the non-malignant tissue is lacking. Because non-malignant tissue represents the microenvironment and/or field from which the tumor arises, an improved characterization of the age-related change in normal breast may provide suggestions of important pathways in the etiology of distinct breast cancer subtypes. To identify age-related changes in the breast microenvironment, 96 normal tissue specimens from reduction mammoplasty patients ranging in age from 14 to 70 were assayed by gene expression microarray. Significant associations between gene expression levels and age were identified for 802 genes (481 increased and 321 decreased with increasing age). Enriched functions included ‘aging of cells’, ‘shape change’, and ‘chemotaxis’, and enriched pathways included Wnt/beta-catenin signaling, Ephrin Receptor Signaling, Oncostatin M signaling, and JAK/Stat Signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival. The poor prognosis tumor group shared features of ‘younger’ breast tissue gene expression, providing a biological link to qualitative patterns in age at incidence. Aggressive tumors common in younger women (such as ER negative and basal-like breast cancers) harbor gene expression patterns that reflect the normal tissue from which they arise. For the young, these signatures portend more aggressive disease. These data show that studies of normal tissue gene expression can yield important insights about the pathways and biological selection factors that are relevant during tumor 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 1680. doi:1538-7445.AM2012-1680
Abstract A45: An in vivo examination of the effects of ARID3B on ovarian cancer metastasis in nude mice
Authors: Lynn Roy, Serene Samyesudhas, Martin Carrasco, Karen Cowden Dahl
Journal: Cancer Research (2013)

Abstract In 2011, 21,880 women were diagnosed with ovarian cancer and more than 13,850 died from the disease. Unfortunately, the prognosis for most women diagnosed with ovarian cancer is poor due to most patients being diagnosed with local and distant metastases. ARID3B, a DNA binding protein from the AT-rich interactive domain (ARID) family, is overexpressed in late stage neuroblastoma and ovarian cancer. In early development, ARID3B is essential as evidenced by the deaths of Arid3B null embryos by midgestation. The importance of ARID3B in early development and its overexpression in cancer suggest a potential role in cancer progression and metastasis. In addition, our laboratory identified two isoforms of ARID3B a full length (FL) and a short form (SH) that is missing the c-terminal exons 5-9. To determine the effects of the two ARID3B isoforms on metastasis in vivo, human ovarian cancer SKOV3IP cells (selected for their ability to metastasize) overexpressing red fluorescent protein (RFP), ARID3B-FL, or ARID3B-Sh were injected intraperitoneally into nude mice. The mice underwent live optical fluorescence imaging using the Multispectral FX (Kodak) imaging system at frequent intervals to assess tumor burden. The mice were sacrificed when they began to show signs of significant illness. Live imaging of the mice demonstrated that ARID3B-FL expressing SKOV3IP cells formed more and larger tumors more quickly than either SKOV3IP-RFP cells or SKOV3-ARID3B-Sh cells. After sacrificing the mice, tumors and organs were recovered from the abdomen and were imaged ex vivo for tumor burden. Tumors were separated from the organs, weighed, and imaged. The average weights of the tumors were 1.91g for SKOV3IP-RFP derived tumors, 3.22g for SKOV3IP ARID3B-Sh tumors, and 5.46g for SKOV3IP-FL derived tumors. The average tumor burden was greatest for the mice bearing SKOV3IP ARID3B-FL tumors. Gross examination of the tumors post-mortem and post fixation suggested that the tumors from the RFP and ARID3B-Sh expressing cell lines were less vascular or had less vascular leakage than those from the ARID3B-FL mice. Survival analysis showed that the median survival for SKOV3IP ARID3B-FL tumor bearing mice was significantly lower than mice bearing RFP or the ARID3B-Sh expressing tumors (RFP=51 days, ARID3B-Sh=52 days, ARID3B-FL=36 days; P=0.0074). Currently, our lab is addressing potential mechanisms for how ARID3B functions in metastasis. The data presented here suggest that ARID3B plays a significant role in peritoneal metastasis in ovarian cancer. Citation Format: Lynn Roy, Serene Samyesudhas, Martin Carrasco III, Karen Cowden Dahl. An in vivo examination of the effects of ARID3B on ovarian cancer metastasis in nude mice. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A45.
AB0096 NF-KB involvement for CTLA4-IG intracellular signaling in human macrophages
Authors: M. Cutolo, P. Montagna, S. Soldano, A. Sulli, B. Seriolo, B. Villaggio, P.F. Triolo, L. Felli, R. Brizzolara
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Transcription factor NF-kB (nuclear factor kB) play an important role in the regulation of immune and inflammatory responses [1]. Previous studies showed that a significant downregulation of pro-inflammatory cytokine expression (TNFα, IL-1β and IL-6) was evident for cultured human macrophages treated with CTLA4-Ig fusion protein [2]. <h3>Objectives</h3> The aim of the study was to investigate the NF-kB pathway as possible intracellular signaling target involved in the CTLA4-Ig modulation of cytokine production (TNFα, IL-1β and IL-6) in cultured human macrophages. <h3>Methods</h3> THP1 cell line, differentiated by PMA (0.5 μg/ml for 3 hours) into adherent macrophages, were seeded in tissue culture dishes in culture medium with CTLA4-Ig [100 and 500 μg/ml for 3 and 12 hours] or without CTLA4-Ig, for mRNA extraction and qRT-PCR analysis. At the end of incubation adherent cells were harvested and mRNA was extracted and processed by qRT-PCR analysis for NF-kB1 (p50 subunit) and for TNFα, IL-1β, IL-6. Experiments were done in triplicate. <h3>Results</h3> The qRT-PCR analysis of NFKB1 mRNA, after 3 and 12 hours from CTLA4-Ig treatment, showed a significant downregulation (p&lt;0.001) of the gene expression vs. cnt at both concentrations [100 and 500 μg/ml]. At the same time, the qRT-PCR analysis of inflammatory cytokine mRNA, already after 3 hours from treatment, showed that CTLA4-Ig [100 μg/ml] induced a significant decrease for TNFα and IL-6 gene expression (p&lt;0.05), compared to untreated macrophages (cnt). CTLA4-Ig [500 μg/ml] was able to reduce TNFα gene expression vs. cnt in a larger extent (p&lt;0.001). After 12 hours from treatment with CTLA4-Ig [100, 500 μg/ml], it was still evident a significant downregulation in cytokine gene expression for IL-1β and IL-6 vs. cnt (p&lt;0.001). Interestingly, TNFα downregulation was not still significant after 12 hours from treatment. <h3>Conclusions</h3> The action of CTLA4-Ig may be exerted at level of the intracellular signaling (trascription factors) by downregulating NF-kB1 gene expression, together with a significant reduction in gene expression for tested inflammatory cytokines. <h3>References</h3> Beinke S et al. Biochem J. 2004;382:393-409; 2. Cutolo M et al. Arthritis Res Ther. 2009;11(6):R176. <h3>Disclosure of Interest</h3> None Declared
SAT0018 Identification of new epistatic interactions with the HLA region in the genetic etiology of psoriasis and psoriatic arthritis
Authors: S. Marsal, J.M. Hernanz, J.D. Cañete, E. Fonseca, C. Ferrandiz, P. Unamuno, L. Puig, J.L. Fernández-Sueiro, R. Sanmartí, J. Rodriguez, J. Gratacόs, E. Dauden, J.L. Sánchez-Carazo, J.L. Lόpez-Estebaranz, D. Moreno-Ramirez, R. Queirό, C. Montilla, J.C. Torre-Alonso, J.J. Pérez-Venegas, F. Vanaclocha, E. Herrera, S. Muñoz-Fernández, C. González, D. Roig, A. Erra, I. Acosta, A. Fernández-Nebro, P. Zarco, A. Alonso, M. Lόpez-Lasanta, A. Julià, R. Tortosa
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Psoriatic Arthritis (PsA) is a complex disease and is present in ∼11% in patients with Psoriasis (Ps). Recently, Genomewide Association Studies (GWAS) have expanded the number of risk loci for Ps in &gt;20 new loci. Two of these genes, <i>ERAP-1</i> and <i>HLA-C</i>, have been shown to interact epistatically in the risk to develop Ps. <h3>Objectives</h3> We have studied the presence of new genetic interactions between Ps risk lci with the <i>HLA</i> region in Purely cutaneous Psoriasis (PsC) and PsA. <h3>Methods</h3> Within each Ps risk locus (n=31), the SNP having the highest statistical evidence was selected. The 31 SNPs were genotyped using Taqman technology in a cohort of n=955 PsA, 1,050 PsC and 1,497 hypernormal controls of the Spanish population. The presence of statistically significant gene-gene interactions was performed using a logistic regression model with three parameters to determine the presence of interaction at the allelic level. <h3>Results</h3> We replicated the previously described interaction of <i>HLA-C</i> and <i>ERAP1</i> in the PsC cohort but not in the PsA cohort. We identified, for the first time, a significative epistatic association between <i>HLA-C</i> and <i>SERPINB8</i>. Microarray gene expression studies on cutaneous biopsies corroborate the presence of this interaction at a functional level. In PsA, no statistically significant interactions where identified with variation at <i>HLA-C</i>. However, 6 of the studied genes showed a significant (<i>P</i>&lt;0.05) association with <i>HLA-B27</i> positivity. <h3>Conclusions</h3> The present study has identified new genetic interactions associated with the risk to develop PsC and PsA. The functional study of these interactions will improve our knowledge of the biological basis of these complex diseases. <h3>Disclosure of Interest</h3> None Declared