tbuckley/cabot-search huggingface dataset:
Abstract 3106: Intestinal mesenchymal fibroblasts promote early epithelial tumorigenesis through activation of integrin beta4 and receptor tyrosine kinases, bypassing common mutational mechanisms
Authors: Janghee Woo, Teppei Morikawa, Shuji Ogino, D. Gary Gilliland, Ramesh A. Shivdasani
Journal: Cancer Research (2011)

Abstract Cancer cells communicate extensively with their stroma, exchanging signals that influence growth and metastasis. Intestinal sub-epithelial myofibroblasts (ISEMFs) direct organogenesis and constitute the colorectal cancer (CRC) microenvironment. ISEMFs from the mouse small intestine and colon express regional characteristics and different cytokines. In line with these regional patterns, ApcMin mice develop adenomas principally in the small intestine but not in the colon; conversely, humans develop tumors mainly in the colon and rarely in the small bowel. We hypothesize that intestinal ISEMFs influence tumor regionality through cell-cell communication. Murine ileal ISEMFs supported growth of human CRC cells markedly better than those originating in the colon in NOD/SCID xenografts and in vitro. We traced this effect to a single secreted factor, matrix metalloproteinase 9 (MMP9), which is exclusively mesenchymal in expression and substantially enriched in native ileal over colonic ISEMFs. Actively cycling intestinal epithelial progenitors and Lgr5+ stem cells showed selectively reduced bromodeoxyuridine uptake in Mmp9-/- mouse ileum, revealing that Mmp9 deficiency impairs epithelial self-renewal. Moreover, ApcMin mice developed fewer ileal adenomas upon treatment with an Mmp9 inhibitor or on the Mmp9-/- genetic background. MMP9 immunohistochemistry revealed expression in 106 of 642 (16.5%) human CRC samples; expression was confined to stromal fibroblasts and considerably enriched among CRCs that lack characteristic KRAS mutations and harbor the CpG island methylator phenotype. Gene expression in epithelial cells interacting with ileal fibroblasts pointed to activation of cytoskeletal remodeling and integrin ß4 signaling pathways, signatures absent in cells cultured with colonic ISEMFs. Biochemical assays verified that stromal MMP9 activates epithelial integrin ß4 and, in turn, ErbB and c-Met receptor tyrosine kinases (RTKs) in adjoining epithelial, including human CRC, cells. This activation is mediated by MMP9 cleavage of the integrin ligand laminin alpha4. Activation of epithelial integrin ß4 and RTKs and the paucity of KRAS mutations in CRCs with stromal MMP9 expression together suggest that potent MMP9-mediated microenvironment signals can help bypass common mutational mechanisms of constitutive growth factor pathway activation in CRC. These results define a novel and therapeutically tractable pathway of tumor-stromal interaction in early CRC pathogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3106. doi:10.1158/1538-7445.AM2011-3106
MYOCARDIAL FIBROSIS IS A POWERFUL PREDICTOR OF MORTALITY IN PATIENTS WITH ISCHEMIC MITRAL REGURGITATION WHO HAVE UNDERGONE SURGICAL MITRAL VALVE INTERVENTION
Authors: Kenya Kusunose, Nancy Obuchowski, Zoran Popovic, Milind Desai, Scott Flamm, Brian Griffin, Deborah Kwon
Journal: Journal of the American College of Cardiology (2016)
AB0626 Dynamic study of B-cells using highly sensitive flow cytometry (HSFC) in systemic lupus erythematosus patients’ receiving anti-B-cell therapy
Authors: M.E. Tsanyan, A. Aleksankin, E.N. Aleksandrova, S.K. Soloviev, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Dynamic study of B-cell using HSFC in systemic lupus erythematosus (SLE) patients’(pts) receiving anti-B-cell therapy with Rituximab (RTM) and definition of correlation with clinical and laboratory disease activity on the background of the therapy. <h3>Methods</h3> 41 pts with definite SLE (7 male, 35 female; mean age Me 28 [23-40]) were included. 19 of them received a second course of RTM. 41pts were examined before treatment and after 1 month, 13 and 11 of them after 3 and 6 months respectively. SLE activity was assessed with SLEDAI2K scale. B lymphocytes number was evaluated using HSFC <i>on</i> BECKMAN COULTER CYTOMICS FC 500 (USA). Minimum detectable concentration of CD3-CD19+ was 1O10<sup>3</sup> cells/μl. 3pts received RTM in a total dose of 2000mg, 34pts 1000mg, 4pts 500 mg. Anti-double-stranded DNA (anti-ds-DNA) was assessed using immunoenzyme methods. <h3>Results</h3> Before treatment B-cells was reduced in 25pts (El0,967 [0.17-2.45]%), compared to the other 16pts (El14.61 [9.43-19.37]%). At 1 month after therapy 25pts with reduced B-cell numbers exhibited complete depletion (El0[0-0.1]%, p=0.0002) and SLEDAI2K had lower values (Me 8 [4-14]) than in 16pts with incomplete depletion (El0.2665 [0.05-0.66]%, d=0.0004) with higher SLEDAI2K score (Me 10 [6-20]). In the group of pts (n=3) receiving RTM in a total dose of 2000mg, 2pts had reduced number of B-cells but in 1pt number of B-cells was normal. At 1 month after RTM treatment all has developed a complete depletion. In the group of pts (n=4) receiving RTM in a total dose of 500mg, number of B-cells was also reduced. At 1month after treatment 3 of this pts exhibited complete depletion but in 1pt number of B-cells did not change and at 1 week after the infusion had developed rashes on the hands (delayed allergic reaction). In the group of pts (n=34) receiving RTM in a total dose of 1000mg, number of B-cells were also reduced El3,67[0,6-12,89]%. In this group, at 1 month after therapy pts exhibited incomplete depletion El0,07 [0-0,333]%, d=0. Correlation analysis of B cells and SLE activity showed a significant association between the number of B-cells, the level of anti-ds-DNA and the SLEDAI2K index before treatment and after 1,3,6 months. Number of B cells also correlated with the level of C3,C4 components of complement before therapy and with the C3 component at 1 month after therapy. Found no correlation between levels of C3,C4 and B-cells at 3,6 months after therapy RTM. <h3>Conclusions</h3> The number CD3-CD19+ lymphocytes was associated with clinical and laboratory activity of SLE: SLEDAI2K, anti-ds-DNA. After treatment reduction in the number of B-lymphocytes correlates with decreased levels of anti-ds-DNA and the index SLEDAI2K through 1,3,6 months after therapy RTM. Found no correlation of B cells and C3,C4 complement components. <h3>Disclosure of Interest</h3> None Declared
AB0401 Carotid intimae-media thickness in mexican patients with systemic erythematosus lupus.
Authors: I. J. Colunga-Pedraza, D. A. Galarza-Delgado, F. Góngora-Rivera, D. Vega-Morales, M. A. Garza-Elizondo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The carotid intima-media thickness (CIMT) nowadays is an early marker of atherosclerosis. A CIMT above 75th percentile of a reference population is considered abnormal, and indicates sub clinical atherosclerosis. In patients with SLE, there has been accelerated atherosclerosis, being the leading cause of morbi-mortality in this population. <h3>Objectives</h3> To assess the clinical and epidemiological profile of SLE patients with thickening of the CIM. <h3>Methods</h3> Descriptive, observational study. Carotid Doppler ultrasound, was performed, obtaining the value of the CIM, with a line equivalent to 200 points. Descriptive analysis was performed for demographic and clinical variables, including measures of central tendency and dispersion. To contrast binomial variables, chi square or Fisher's exact test, with 2x2 contingency tables; for nonparametric variables, Mann Whitney test was performed; taking as significant, P ≤ 0.05. <h3>Results</h3> 69 patients with SLE. Demographics: 95.7% (n = 66) women. Mean age: 30 years, hypertension in 2 subjects and Diabetes Mellitus type 2, in one subject. Post-menopause: 5 patients. Framingham Scale: mean 1.63 ± 1.48. Mean of BMI 25.96 ± 5.93 kg/m<sup>2</sup>. We obtained the mean carotid intima-media thickness of both lines of 200 points, equivalent to the average of 400 measurements. Then we compared it versus an historical cohort of the same age and gender, and then, we obtained the 75th percentile of the CIMT; the values above the 75th percentile were reported as thickening. We obtained such as 75th percentile: 0571, in people without SLE. 14 patients with SLE exceeded this value, so it is classified with carotid thickening. Later, we compared the main characteristics of the SLE patients with and without carotid thickening, finding statistical significance for: total cholesterol, LDL, menopause and time of use of corticosteroids. We did not found difference between the time of evolutions, age, gender, SLEDAI, autoantibodies. <h3>Conclusions</h3> We did not found difference in the traditional cardiovascular risk factors, neither with activity of SLE. <h3>Disclosure of Interest</h3> None Declared
GENO-13NETWORK-BASED APPROACH AIDS IN THE DISCOVERY OF CONTEXT-SPECIFIC DRUGGABLE TARGETS FOR TREATMENT OF GLIOBLASTOMA
Authors: Harshil Dhruv, Seungchan Kim, Jeff Kiefer, Sungwon Jung, Dorothea Emig-Agius, Alexander Ivliev, Darren Finlay, Pedro Aza-Blanc, Kristiina Vouri, Michael Berens
Journal: Neuro-Oncology (2015)

Systematic discovery of actionable cancer targets could fill an unmet need for improved approaches to manage Glioblastoma Multiforme (GBM). Critical barriers to the discovery of druggable targets in cancer include: 1)  heterogeneity of the disease across patients, 2) uncertainty in the implementation of a systematic approach to utilize existing knowledge and  data for target discovery, and 3) the lack of a clinically-relevant, rapid and systematic pipeline for empiric testing of hypotheses. We describe a network-based method to stratify GBM clinical samples into molecularly homogeneous subsets based on gene expression, gene copy number, and miRNAs, which we term molecular contexts, or mCs. Within these mCs, a knowledge-based topological analysis of pathway elements was used to uncover discrete mC-specific targets. For initial target discovery and validation experiment, two molecularly orthogonal context mC4 and mC14 were selected. mC4 and mC14 context-specific targets identified by network based topological analysis were further manually curated by querrying a druggable genome database, and final mC4 and mC14 specific target gene lists were produced. Using this target list, a pooled siRNA library for each specific gene target in mC4 and mC14 was prepared. The siRNA screen was carried out using short-term in vitro cultures derived from patient-derived GBM xenografts, which mapped to mC4 (GBM102) and mC14 (GBM59) based on gene expression. Results from siRNA screens demonstrate that siRNA mediated knockdown of 5 genes specifically targets mC14 glioma cells and not mC4 glioma cells. Two of those 5 genes targeting mC14 (APC and HTR1A) were mC14 predicted targets by the network based topological analysis. In summary, our results suggest that context analysis coupled with knowledge-based enrichment and topological analysis identifies specific GBM contexts with distinct druggable targets. Supported by NIH U01 {type:entrez-nucleotide,attrs:{text:CA168397,term_id:35089778,term_text:CA168397}}CA168397.
SAT0033 The Clinical Application of Detection of Antinuclear Antibodies Spectrum Eighteen Items in Systemic Lupus Erythematosus
Authors: Z. Ye, Z. Yin, W. He, X. Luo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To explore the clinical application value of detection of antinuclear antibodies (ANA) spectrum eighteen items in the diagnosis and treatment of systemic lupus erythematosus (SLE). <h3>Methods</h3> ANA spectrum eighteen item were detected with indirect immunoflurescence and immunoblotting methods. The results of ANA spectrum in 370 inpatients cases of our hospital were retrospectively analyzed, including SLE patients (158 cases), other autoimmune diseases patients (142 cases) and other diseases patients (70 cases). <h3>Results</h3> The positive rate of ten antibodies of ANA spectrum eighteen items showed significant defference between SLE group with other autoimmune diseases group and other diseases group, including ANA (96.84%, 55.47%, 27.10%; P&lt;0.01), Anti-SSA/Ro60 (55.06%, 14.34%, 3.39%; P&lt;0.01), Anti- SSA/Ro52 (46.20%, 12.83%, 1.69%; P&lt;0.01), Anti-SmD1 (31.65%, 2.64%, 1.69%; P&lt;0.01), Anti- U1-snRNP (25.95%, 2.26%, 0%; P&lt;0.01), AnuA (25.32%, 0.75%, 0%; P&lt;0.01), Anti- SSB/La (25.32%, 5.66%, 0.85%; P&lt;0.01), Anti-dsDNA (24.05%, 0.38%, 0%; P&lt;0.01), AHA (20.89%, 0.38%, 0%; P&lt;0.01), Anti-P0 (18.35%, 0.38%, 0%; P&lt;0.01) <h3>Conclusions</h3> The detection of ANA spectrum eighteen items is valuable on the screening and diagosis of SLE. <h3>References</h3> Cortes-Hernandez J, Ordi-Ros J, LabradorM,et al. Anti-histone and anti-double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus. Am J Med 2004;116:F165. Hung WT, Chen YM, Lan JL et al. Anti-nucleosome antibodies as a potential biomarker for the evaluation of renal pathological activity in patients with proliferative lupus nephritis. Lupus 2011;20(13):1404-1410. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1719
THE CENTRAL MECHANISM OF THE EMOTIONS
Authors: E. A. SPIEGEL, H. T. WYCIS, H. FREED, C. ORCHINIK
Journal: American Journal of Psychiatry (1951)

Thus we arrive at the conclusion that it is not possible to refer emotional reactions to a single circumscribed nucleus within the diencephalon or to its connections with the frontal lobes, but that there exists a multiple representation of this function. Following the elimination of one or two of these circuits others are able to compensate for the loss. As far as our present experience permits us to localize this function the following systems seem to play a part: (a) the connections of the dorsomedial nuclei with the frontal association areas, (b) connections of the anterior nuclei with the cingulate gyrus, (c) connections of the hypothalamus with the frontal lobe, (d) intradiencephalic connections chiefly between the dorsomedial nuclei and the hypothalamus, perhaps also between the anterior nuclei and the mammillary bodies. (Fig. 3.) For the systems a, b, and d fibers in either direction have been demonstrated anatomically; centrifugal connections between frontal lobe and hypothalamus probably synapse in the septum pellucidum (Wallenberg) and in the zona incerta (Clark). Centripetal connections between the hypothalamus and frontal lobe are possible by way of the dorsomedial nucleus. It should be emphasized that in enumerating these circuits we do not wish to submit a definite "new theory" of emotions but only a preliminary working hypothesis that may help to explain our findings, a hypothesis that may be subject to modifications in the light of further observations.
AB0201 Assessment of protein-energy nutritional status and physical activity of ankylosing spondylitis and rheumatic arthritis patients - preliminary report.
Authors: A. Juszkiewicz, K. Klos, M. Tlustochowicz, B. Kisiel, A. Raczkiewicz, W. Tlustochowicz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Active rheumatic diseases can lead to malnutrition. However, the influence of the remission on the nutritional status is not clear. <h3>Objectives</h3> To assess nutritional status and physical activity in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients during remission. <h3>Methods</h3> 48 AS and RA patients (20 AS patients and 28 RA patients, 20 women and 28 men, mean age was 46.2) and 30 healthy controls were included in the study. AS and RA patients were in clinical remission. All AS patients and 17 out of 28 RA patients were treated with biologic agents. BMI, body fat percentage (BFP) and lean body mass (LBM) were calculated in all subjects (BFP and LBM were calculated on the basis of subscapular, suprailiac, biceps and triceps skinfolds measurements). Physical activity including type of job and regular physical exercises was also assessed. <h3>Results</h3> 20 RA/AS patients (41.7%) and 13 controls (43.3%) had normal nutritional status (p&gt;0.05), 19 RA/AS patients (39.6%) and 9 controls (30.0%) were overweight (p&gt;0.05), 7 RA/AS patients (14.6%) and 8 controls (26.7%) were obese (p&gt;0.05). The skinfold thickness as well as BFP (18.7% vs 19.8%) were also similar study and control groups. 2 RA patients had low BMI, both had long-term and advanced disease. 23 RA/AS patients (74.9%) and 13 controls (43.3%) declared regular physical activity (4.6 hours/week and 9.4 hours/week, respectively; p&gt;0.05). <h3>Conclusions</h3> We did not find significant differences in nutritional status and physical activity between rheumatic patients in remission and healthy controls. Our results suggest that an adequate disease control may prevent malnutrition in rheumatic disease. <h3>Disclosure of Interest</h3> None Declared
Risk of Recurrence after First Episodes of Genital Herpes
Authors: William C. Reeves, Lawrence Corey, Harry G. Adams, Louis A. Vontver, King K. Holmes
Journal: New England Journal of Medicine (1981)

To define risk factors associated with recurrent genital herpes-simplex-virus infection caused by either Type 1 or 2 herpesvirus (HSV-1 or HSV-2), we prospectively studied 137 patients with a first symptomatic episode of the disease and 87 with a recurrent episode. First episodes were divided into 78 primary infections (no antibodies to HSV in acute-phase serum) and 59 nonprimary infections (antibodies present). HSV-1 infections were less frequent and less likely to recur than HSV-2 infections. Fifteen per cent of primary first episodes were caused by HSV-1, as compared with 3 per cent of nonprimary first episodes and 2 per cent of recurrent episodes. Moreover, during follow-up of first-episode patients, only 14 per cent of HSV-1 infections recurred, as compared with 60 per cent of HSV-2 infections. Recurrences were more likely to follow an index recurrent episode than an index first episode, whether primary or nonprimary, and were more likely to occur in men than in women. Among patients with primary HSV-2 infections, the probability of recurrence was directly related to the presence and titer of neutralizing antibody to HSV-2 in convalescent-phase serum.
PTH-019 Colonic Stenting in a Dgh Without a Radiologist Support
Authors: R K Mehmood, P Kirkbride, E Jehangir
Journal: Gut (2013)

<h3>Introduction</h3> The aim of this study is to assess our outcomes of colonic stenting for colorectal malignancies in a DGH where we provide stenting without the support of interventional radiologist. NICE guidelines recommend facilities and services should be established to provide stenting for patients with intestinal obstruction, particularly those with serious co-morbidity to avoid emergency surgery<sup>1</sup>. We run a colorectal laparoscopic unit adequately according to NICE recommendations although we do not have support of interventional radiologist <h3>Methods</h3> It is retrospective study of all stents which were inserted in a DGH by a surgeon between 2004 and 2012. All patients had presented with acute bowel obstruction caused by malignant colorectal diseases and structuring. Data was collected prospectively by the colorectal specialist nurse on a pre-designed database format. In the stent insertion no support of interventional radiologist was available. However all stents were inserted by a surgeon with the help of endoscopes and fluoroscopy in X-ray department. <h3>Results</h3> Out of 54 patients 51 had successful stenting initially. However on three occasions stenting was not successful. Out of 51 who had successful stenting in three of them stents were not found adequately relieving obstruction so they ended up having stoma. The complete success rate in 48 patients was 88%. The indications of stenting were for relief of acute bowel obstruction, palliation and as a bridge to surgery. Complications were noted in Seven cases (14.58) including one perforations and one migration, one obstructive symptoms persisted and four had growth of the tumour at the lower end of the stents where restenting was not successful.. There were no incidents of acute or delayed haemorrhage in any patients. <h3>Conclusion</h3> This study demonstrated that stenting for obstructing colorectal cancers is a safe and effective method of relieving acute and impending bowel obstruction. It is also a preferred method of converting an acute surgery into an elective surgery by “bridging to surgery” in order to optimise patient’s condition before surgery. Our study also showed that stenting can be provided safely and effectively in a district general hospital by a trained surgeon without the help of interventional radiologist. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> http://www.nice.org.uk/nicemedia/pdf/CSGCCfullguidance.pdf
COEXISTENT HYPERTROPHIC CARDIOMYOPATHY AND OBSTRUCTIVE SLEEP APNEA INCREASE THE RISK OF ARRHYTHMIA RECURRENCE FOLLOWING CATHETER ABLATION OF ATRIAL FIBRILLATION
Authors: Sanghamitra Mohanty, Prasant Mohanty, Chintan Trivedi, Carola Gianni, Amin Al-Ahmad, John Burkhardt, G. Joseph Gallinghouse, Rodney Horton, Javier Sanchez, Patrick Hranitzky, Luigi Di Biase, Andrea Natale
Journal: Journal of the American College of Cardiology (2016)
Abstract 1482: Abnormal abundance of senescent fibroblasts in the tumor stroma of non-small cell lung cancer patients
Authors: Marta Puig, Roberto Lugo, Alícia Giménez, Roland Galgoczy, Sandra Genís, Josep Ramírez, Abel Gómez-Caro, Pere Gascón, Jordi Alcaraz, Noemi Reguart
Journal: Cancer Research (2012)

Abstract Although permanent cell cycle arrest through senescence has been previously regarded as a protective mechanism against tumor growth, there is growing evidence that the abnormal abundance of senescent cells observed in the stroma of some types of cancer may support cancer progression. However, the presence of senescent cells in the tumor stroma of non-small cell lung cancer (NSCLC), which is a major cause of cancer death in western countries, remains poorly defined. To fill this gap of knowledge, we set up a bank of primary human lung fibroblasts isolated from both tumor-free regions and tumors of NSCLC patients diagnosed with adenocarcinoma (ADC, n=5), squamous cell carcinoma (SCC, n=5) or large cell carcinoma (LCC, n=2) histological subtypes. Tumor-associated fibroblasts (TAFs) or patient-matched control fibroblasts (NTAFs) were seeded in collagen-coated culture dishes in culture media supplemented with 10% serum for 3 days. The presence of senescent cells was assessed by examining senescent associated signatures including increased spreading, decreased proliferation, and the positive response to the beta-galactosidase (beta-gal) assay. The beta-gal assay was negative in &amp;gt;90% of NTAFs (11/12). Likewise, TAFs from either ADC or SCC were negative for beta-gal assay in 80% of the patients examined (4/5), whereas &amp;lt;10% of cells were positive for the beta-gal assay in the remaining 20% of patients. In contrast, beta-gal positive TAFs were observed in 100% of LCC patients (2/2), with an average of ∼50% positive TAFs per patient. In agreement with these findings, LCC TAFs were poorly or non-responsive to serum stimulation in terms of cell cycle progression as assessed by flow cytometry, unlike patient-matched LCC NTAFs. Moreover, LCC TAFs exhibited a high percentage of largely spread fibroblasts, which is commonly associated with the senescent phenotype. These preliminary results strongly suggest that the senescent phenotype is absent in normal fibroblasts, and abnormally and specifically present in lung fibroblasts from the tumor stroma of LCC patients, therefore revealing the presence of NSCLC-subtype specific alterations in the tumor microenvironment. 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 1482. doi:1538-7445.AM2012-1482