tbuckley/cabot-search huggingface dataset:
Abstract 4366: ShRNA-based cellular proliferation signaling analysis revealed DRD2 as a novel therapeutic target for glioblastoma.
Authors: Jie Li, Shan Zhu, David Kozono, Diahnn Futulan, David Gonda, Deepa Kushwaha, Kristopher Kahle, Stephen Elledge, Clark C. Chen
Journal: Cancer Research (2013)

Abstract Glioblastoma remains one of the deadliest of human cancers, with most patients succumbing to the disease within one year of diagnosis. Our best current understanding of its etiology is that glioblastoma involves genetic and epigenetic changes that subvert the inherent molecular circuitry of glial cells to drive uncontrolled cellular proliferation. Unfortunately, this molecular circuitry in glioblastoma appears sufficiently complex and redundant that disruption at any particular point tends to redirects signaling through the remaining circuit. In this context, meaningful therapeutic gains will require the identification of therapeutic agents that target critical nodes within this circuit. To identify novel therapeutic agents that target critical nodes which regulate cellular proliferation, a genome-wide retroviral shRNA library screen was conducted in two glioblastoma cell lines (U87MG and A172) and two lung carcinoma lines (A549 and NCI-H460). Pathway analysis of the pro-proliferative genes using both PANTHER and Ingenuity software revealed an over-representation of G-protein coupled neurotransmitter receptors (GPCR), including dopamine receptor subtype 2 (DRD2), which was also highly expressed in glioblastoma specimens relative to the matched normal parentchymal. Further investigation demonstrated that DRD2 signal regulates cell growth by GNAI2-induced ERK activation. Moreover, Haloperidol, one of DRD2 antagonists, enhances significantly anti-tumor efficacy of EGFR inhibitor AG1478 using U87 and mesenchymal neuroshpere xenografy mouse models. Given that both AG1478 and DRD2 antagonists have been approved for the treatment of glioblastoma and psychotics, separtately, Haloperidol combined with chemotherapy represents a novel and likely conducted strategy for the treatment of glioblastoma. Citation Format: Jie Li, Shan Zhu, David Kozono, Diahnn Futulan, David Gonda, Deepa Kushwaha, Kristopher Kahle, Stephen Elledge, Clark C. Chen. ShRNA-based cellular proliferation signaling analysis revealed DRD2 as a novel therapeutic target for glioblastoma. [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 4366. doi:10.1158/1538-7445.AM2013-4366
FRI0470 Modification of ‘the asas modification of the berlin algorithm’ in patients with chronic low back pain can be useful for primary care
Authors: L. Van Hoeven, J. Luime, M. Hazes, A. Weel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recently the ASAS modification of the Berlin algorithm (ASAS algorithm) for diagnosing axial spondyloarthritis (aSpA) was published<sup>1</sup>. The entry criterion, chronic low back pain (CLBP), started before the age of 45, implies that all young patients with CLBP can be referred to the rheumatologist for further diagnostic work-up. Since CLBP is one of the most frequent complaints in primary care, referring all these patients is unfeasible due to high cost. <h3>Objectives</h3> To assess the performance of the ASAS modification of the Berlin algorithm in an unselected CLBP population; the CAFASPA cohort. To assess whether incorporating the referral model of the CaFaSpA study in the ASAS algorithm, has added value for primary care<sup>2</sup>. <h3>Methods</h3> Patients (18-45 yrs) with CLBP were identified from GP records by the ICPC code L03. Assessments included questionnaires, history, physical examination, HLA-B27, CRP, X-ray and MRI. ASpA was defined by the ASAS criteria. A modification was assessed by incorporating the CaFaSpA referral rule in the ASAS algorithm. Descriptive statistics were used to determine the performance both the ASAS algorithm and the CaFaSpA modification of the ASAS algorithm. <h3>Results</h3> 364 patients participated in the CaFaSpA study. In total 86 (23%) were classified as aSpA. The performance of the ASAS algorithm was 73.2% (n=30) for the X-ray arm, 40.0% (n=12) for the arm having ≥4 SpA features or 2-3 features plus HLA-B27 and 100.0% (n=3) for having 0-1 features plus HLA-B27 and a positive MRI. The data of the CaFaSpA modification were respectively, 100.0%, 60.0% and 100.0% (Fig. 1). <h3>Image/graph</h3> <h3>Conclusions</h3> The ASAS algorithm, assessed in secondary care, can not be applied in an unselected CLBP population. Adding the CaFaSpA referral model improves the performance of the ASAS algorithm substantial, leading to useful and more cost-effective model, for daily practice in both primary and secondary care. <h3>References</h3> vd Berg et al. Annals of the Rheumatic diseases, 2012. v Hoeven et al. Arthritis and Rheumatism 2010 <h3>Disclosure of Interest</h3> L. Van Hoeven: None Declared, J. Luime: None Declared, M. Hazes: None Declared, A. Weel Grant/research support from: Unrestricted grand from Abbott
PWE-175 Simple Intervention Improves Outcome in Delivery of Parenteral Nutrtion
Authors: P Davies, J Bowness, C Whittingham, A Bassi
Journal: Gut (2013)

<h3>Introduction</h3> Recent report by NCEPOD into hospital care of patients receiving parenteral nutrition (PN) suggested that only 19% adult patients had PN care that was considered to represent good practise. An initial audit (retrospective audit over six months) in our hospital suggested lack of quality control at the point of initiation of PN. Simple remedial actionwas introduced and the audit cycle was completed to assess the impact of mandatory minimal set documentation prior to initiation of PN. <h3>Methods</h3> A mandatory request sticker was introduced which prompted the clinical team to document why enteral nutrition is inappropriate and duration of inadequate enteral intake, the clinical purpose and goal of PN and expected duration of PN. A prospective re-audit was performed to assess any change over the same six month period. <h3>Results</h3> The initial audit included 43 patients and 34 patients received PN during the reaudit period. Administration of PN was predominantly in surgical (47%) or critical care (20%) areas. The indication was documented in the case notes in 88% of cases (initially 43%), and considered appropriate by the nutrition team in 94% of cases (initially 67%). There were unreasonable delays in 21% of cases (initially 29%), mostly related to delays in placing appropriate central venous access. The treatment goal was documented in 82% of cases (initially 36%). Alternatives were considered in 100% of cases (initially 64%) and an appropriate assessment was made in 97% of cases (initially 69%). TPN was reviewed and monitored appropriately in the initial audit and there was no change in the re-audit. Metabolic complications occurred in 38% of cases (initially 52%), all cases were managed appropriately. Nine percent of patients received PN for fewer than 5 days (initially 12%) but the vast majority received an appropriate course length. Seventy four percent of patients were weaned onto oral diet (initially 67%) and 6% of patients died during their stay (initially 17%). <h3>Conclusion</h3> A relatively simple intervention, involving no additional cost, vastly improved the delivery of PN in our hospital. Mandatory information prior to starting helped to focus the thoughts of the requesting clinicians to decide on the appropriateness of using PN. This simple win-win strategy can be easily adopted in other hospitals to improve delivery of PN. <h3>Disclosure of Interest</h3> None Declared.
Complete Resolution of Neuroendocrine Tumor Soft Tissue Metastases After 177Lu DOTATATE PRRT Induction and Maintenance Therapy
Authors: William Makis, Karey McCann, Francois A. Buteau, Alexander J.B. McEwan
Journal: Clinical Nuclear Medicine (2014)

A 60-year-old woman diagnosed with a well-differentiated neuroendocrine tumor metastatic to the liver and lymph nodes was treated with 4 induction cycles and 2 maintenance cycles of 177Lu [DOTA0,Tyr3]octreotate (DOTATATE) peptide receptor radionuclide therapy. Her posttreatment imaging showed partial response after 4 induction cycles and complete response after 2 additional maintenance cycles. This case highlights the need for further research into maintenance 177Lu DOTATATE therapy to improve outcomes in neuroendocrine tumor patients.
AB0014 Circulating cytokine pattern and factors describing rheumatoid arthritis: il-15 as one of the prognostic factor of the disease progression
Authors: P. Nemec, J. Lipkova, N. Pavek, J. Gatterova, M. Soucek, A. Vasku, M. Pavkova Goldbergova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The progression of rheumatoid arthritis (RA) is strongly associated with the immune mechanisms and substances affecting the immune system including chemokines and cytokines. <h3>Objectives</h3> The aim of the study was to examine the relation among polymorphisms and serum levels of selected cytokines (IL-6, IL-13, IL-15), production of autoantibodies, and factors describing activity and progression of RA, such as DAS28 and Total Sharp score. <h3>Methods</h3> A total of 144 RA patients according to the ACR classification criteria 1987, and 50 control subjects were recruited into the study. The measurements of serum levels of CRP, ACPA, and RFs, radiographs of both hands with calculation of Total Sharp score (TSS), DAS28, and serum levels of cytokines (IL-6, IL-13, IL-15) were obtained from all RA patients. <h3>Results</h3> Significant difference in allele frequencies between RA patients and controls was observed for IL-15 -267C/T polymorphism. No significant association of IL-15 gene polymorphisms (367 G/A, 14035 A/T), IL-13 (-1112 C/T), and IL-6 with RA was found. Significant difference between RA patients and controls was observed for IL-15 -267C/T polymorphism in allele frequencies (p = 0.05). Higher prevalence of heterozygote variants of IL-15 14035 A/T and -267C/T polymorphisms in the RFs negative subgroup (IgG, IgA, IgM; p &lt; 0.05) were observed. The frequency of the T allele of the IL-13 polymorphism C1112T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1, p = 0.03). <h3>Conclusions</h3> In conclusion, we present a correlation of IL-15 gen promoter polymorphisms with the rheumatoid factor subtypes (RF IgG, IgA, IgM) underlined by association with increased levels in circulation. <h3>Disclosure of Interest</h3> None Declared
OP0233-HPR The Feasibility of the Use of Patient-Derived Joint Counts in Treat-to-Target Strategies in Rheumatoid Arthritis
Authors: A. J. L. Meier, M. van Onna, K. L. Tsoi, J. W. J. Bijlsma, A. A. A. Westgeest
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Treat-to-target strategies require instruments for valid detection of joint inflammation. In clinical practice, Disease Activity Score 28 (DAS28) is often used for this purpose. Patient-derived joint counts are a potential alternative for determining DAS28. <h3>Objectives</h3> The aim of this study is to evaluate the reliability of patient derived joint counts and to test how often DAS28 based treatment decisions are different when patient-derived DAS28 (patDAS28) in stead of physician derived DAS28 (physDAS28) are used. <h3>Methods</h3> This study was part of a study on assessment of synovitis in the hand and wrist in RA in which 59 patients with rheumatoid arthritis (RA) were included. Of these, 20 patients with DAS28 &lt; 2.6, 26 with 2.6 &lt; DAS28 &gt;5.1 and 13 with DAS28&gt; 5.1. Patients completed a self-assessment of joint tenderness and swelling of 44 joints. At the same day, counts of swollen (SJC) and tender joints (TJC) of 44 joints have been performed by two experienced examiners. Disease activity was classified as remission (DAS28 &lt; 2.6), low-disease activity (2.6 &lt; DAS28 &gt;5.1) and high disease activity (DAS28&gt; 5.1). Spearman's rho correlation coefficients were used to test the relationship between the joint counts. The agreement in the classification of disease activity is given in percentages. Factors related to differences between physDAS28 and patDAS28 (sex, age and disease duration) were explored using logistic regression analyses. <h3>Results</h3> Of the 59 included patients (61% women), the mean age was 55 (SD ± 13) years and on average they had been diagnosed with RA 7.5 years ago. There were high correlation coefficients for the relationship between patDAS28 and physDAS28 (examiner 1 r= 0.90, examiner 2 r=0.87 ). Age, sex and disease duration were not related to differences between physDAS28 and patDAS28. The correlations between TJC were higher (r= 0.72 and r= 0.65) than between SJC (r=0.47 and r= 0.45). The correlation between the two examiners was high for both tender (r=0,82) and swollen (r=0,85) joints. Using the DAS28 cut-off points, in 82% of the patients agreement with regard to the disease activity classification as compared to mean physDAS28. According to patDAS28 22% remission, 40% low-disease activity, and 20% high disease activityy and according to the average of examiners 32%, 40% and 20% respectively. Agreement of the disease activity classification between examiners was 92%. <h3>Conclusions</h3> Patient-derived joint counts might be useful to evaluate disease activity in patients with RA. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-89: A combined epigenetic and genetic biomarker panel for detection of lung cancer.
Authors: Michael X. Wang, Dan Guo, Mary Andersen, Vamsi Guntur
Journal: Cancer Research (2013)

Abstract Introduction: Lung cancer is the leading cause of cancer-related deaths in human. However, there is no valid screening procedure or test available at the present time. Although National Lung Screening Trial (NLST) demonstrated, for the first time, that low-dose helical CT screening in high-risk population reduced lung cancer mortality by 20%, the procedure is associated with over 95% false positive results (Aberle DR et al. N Engl J Med. 2011, 365:395). A confirmatory test is urgently needed. We have been developing a combined epigenetic and genetic molecular biomarker panel to verify the presence of lung cancer on the blood samples. Methods: Lung cancer cell lines NCI-H69 (small cell carcinoma), NCI-H1299 and NCI-H460 (large cell lung cancer), NCI-H1781 and A549 (adenocarcinoma), NCI- H358 (bronchioalveolar carcinoma) and NCI-H520 (squamous cell carcinoma) were obtained from ATCC (Manassas, VA). Blood samples of patients with lung cancer (n=105) and non-cancer patients were collected at MU Health Care System with an IRB approval. Genomic DNA was extracted from cell lines, mononuclear cell fraction and plasma using QIAamp DNA mini kit and circulating nucleic acid kit (QIAGEN, Valencia, CA), respectively. Isolated DNAs were digested with 4 methylation sensitive restriction enzymes followed by PCR for DNA methylation assay. Genomic DNAs were also subject to allele-specific PCR for PT53, EGFR and BRAF gene mutation assay. All PCR reactions were carried out in an iQ5 Real-time PCR system (Bio-Rad, Hercules, CA). Results: Specific CGI DNA methylation of HOXA7, HOXA6 and PCDHGA12A was detected in all lung cancer cell lines except NCI-H1299 in HOXA7. Only NCI-H460 was positive for EGFR L858R mutation. Among patient blood samples, HOXA7 methylation was detectable in 9 out of 105 patient mononuclear cell DNAs, but neither in patient plasma nor in non-cancer patients or normal blood control DNAs. EGFR L858R mutation was detected in only 4 lung cancer patient DNA samples. The sensitivity of HOXA7 DNA methylation assay, determined by serial dilutions of cancer cell DNA into normal DNA, was 0.1%. Conclusion: A combined epigenetic DNA methylation and genetic mutation panel could be utilized for lung cancer detection or verification in patient blood sample. Citation Format: Michael X. Wang, Dan Guo, Mary Andersen, Vamsi Guntur. A combined epigenetic and genetic biomarker panel for detection of lung cancer. [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 LB-89. doi:10.1158/1538-7445.AM2013-LB-89
THU0489 Enho Gene Expression and Serum Adropin Level in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Table 1.
Authors: S. Yolbas, M. Kara, A. Yildirim, B. Gundogdu, M. Kalayci, S. Aydin, S.S. Koca
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic inflammatory diseases. Adipokines, including leptin, adiponectin, resistin, and visfatin have been studied widely in chronic inflammatory diseases due to the metabolic, cardiovascular and inflammatory actions of adipokines. Adropin, a secreted protein, is encoded by the Energy Homeostasis Associated (<i>ENHO</i>) gene. It is expressed by a variety of tissues and cells. It has been implicated in the several physiological and pathological processes such as angiogenesis and apoptosis. <h3>Objectives</h3> The aim of the present study was to investigate the ENHO gene expressions and serum adropin levels and in patients with RA and SLE. <h3>Methods</h3> The study included 36 patients with RA, 22 patients with SLE, and 20 healthy controls (HC). The patients were fulfilling the established classification criteria. Disease activity statuses were determined by the disease activity score (DAS)28-erythrocyte sedimentation rate in the RA group (patients with &gt;2.6 score were accepted as active) and SLE disease activity index (SLEDAI) in the SLE group (patients with &gt;6 score were accepted as active). Serum adropin levels were analyzed by ELISA method using an appropriate commercial kit. ENHO and GAPDH gene expressions by peripheral blood mononuclear cells were analyzed by real-time PCR. <h3>Results</h3> ENHO gene mRNA expression was significantly higher in the RA group than in HC group (p=0.024, Table), although it was similar in the SLE and HC groups (p=0.920). On the other hand, there was no significant differences among the study groups in terms of serum adropin levels (p&gt;0.05, for all). Moreover, there was no significant difference in terms of ENHO expression and serum adropin level between active (n=17) and inactive (n=19) RA patients, and between active (n=13) and inactive (n=9) SLE patients. <h3>Conclusions</h3> Although ENHO gene expression is increase, serum adropin level is not altered in RA. Similarly, adropin seems not to be associated with SLE. However, the potential link between adropin and inflammatory diseases may be tested by a further study. <h3>References</h3> Krysiak R, et al. Eur J Nutr 2012;51:513-28. Lovren F, et al. Circulation. 2010;122:185-92. Aydin S, et al. Mol Cell Biochem. 2013;380:73-81. Ganesh Kumar K, et al. Obesity (Silver Spring). 2012;20(7):1394-402. Topuz M, et al. J Investig Med. 2013;61(8):1161-4. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5252
649 TOLL-LIKE RECEPTOR 4 D299G AND T399I POLYMORPHISMS AND BACTERIAL INFECTIONS IN PATIENTS WITH CIRRHOSIS AND ASCITES
Authors: G. Soriano, J.C. Nieto, E. Román, E. Sánchez, C. Guarner-Argente, S. Vidal, O. Pavel, C. Romero, C. Juárez, C. Guarner
Journal: Journal of Hepatology (2012)
857 TRIPLE THERAPY FOR HEPATITIS C VIRUS (HCV) INFECTION IN PATIENTS WITH COMPENSATED LIVER CIRRHOSIS: LESSONS LEARNED FROM THE FIRST REAL-WORLD EXPERIENCE
Authors: B. Maasoumy, K. Port, A.A. Markova, B. Calle Serrano, L. Sollik, J. Kirschner, C. Mix, M.P. Manns, H. Wedemeyer, M. Cornberg
Journal: Journal of Hepatology (2013)
Abstract 2085: The antileukemic drug nilotinib inhibits the invasive activity and the metastatic potential of colorectal cancer cells by targeting the receptor tyrosine kinase DDR1.
Authors: Priscillia Tosti, Cédric Leroy, Valérie Simon, Bruno Robert, Josiane Pierre, Audrey Sirvent, Serge Roche
Journal: Cancer Research (2013)

Abstract Tyrosine kinases (TK) are frequently deregulated in human cancer and they play important roles in tumor progression. Since then, they have become valuable therapeutic targets and several inhibitors are currently used in the clinic. For example, the BCR-ABL inhibitor nilotinib is currently used for the treatment of patients with chronic myeloid leukemia (CML). Here we show that this antileukemic drug also inhibits invasive properties of colorectal cancer (CRC) cells. Inhibition was observed at the same dose-range for growth inhibition of CML cells. Nilotinib also strongly reduced liver metastasis induced by injection of CRC cells in the spleen of nude mice. Since we could not detect Abl deregulation in CRC cells, we speculated the involvement of an alternative target to be identified. Interestingly, a previous chemical-proteomic approach identified DDR1 as a novel target of nilotinib (Rix et al, Blood, 2007). DDR1 is a poorly-characterized TK and a receptor for collagen, a major component of the extracellular matrix. Accordingly, we found that DDR1 catalytic activity regulates cell invasion and metastasis of CRC cells. In addition, we demonstrate that nilotinib pharmacological activity is mediated by the inhibition of DDR1 in CRC cells: expression of the nilotinib resistant DDR1/T701I mutant renders CRC cells resistant to nilotinib treatment. Finally, we found that DDR1 catalytic activity is significantly increased in metastatic nodules compared to the primary tumor and the healthy tissue of the same patient. Altogether, these data suggest that the targeting of DDR1 by nilotinib may be of therapeutic value in metastatic CRC. Citation Format: Priscillia Tosti, Cédric Leroy, Valérie Simon, Bruno Robert, Josiane Pierre, Audrey Sirvent, Serge Roche. The antileukemic drug nilotinib inhibits the invasive activity and the metastatic potential of colorectal cancer cells by targeting the receptor tyrosine kinase DDR1. [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 2085. doi:10.1158/1538-7445.AM2013-2085 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.