tbuckley/cabot-search huggingface dataset:
Abstract 425: Alteration of ADAM9 and integrin interaction regulated cancer invasion and metastasis potential
Authors: Yun-Chi He, Jer-Ming Liu, Shian-Ying Sung
Journal: Cancer Research (2011)

Abstract Alteration of integrin composition is highly correlated with cancer malignancy and metastasis. Recent evidence demonstrated the metastasis activities involved the interaction of integrin and ADAM gene family, such as ADAM8, ADAM9, ADAM10 and ADAM17. These may either stabilized or cleavage of integrin-matrice interaction at the lamellipodia of cancer cell. Mahimakar et al., recently demonstrated the interaction of ADAM9 with integrins alpha3, alpha6 and beta1 by pull down assay, suggests ADAM9 might work together with β1 class integrins. To further analyze their roles and possible downstream regulatory proteins, we perform knockdown of ADAM9 using shRNA and determine its role in cancer metastasis both in vitro and in vivo. Western blotting confirmed the knockdown of ADAM9 in prostate cancer, and oral cell carcinoma. Cell migration assay was performed using micro-slide Chemotaxis chambers either with or without collagen coating. Time-Lapse microscope analysis of cell migration was plotted and analyzed. Interestingly, we observed the opposite cell migration behavior in which faster and longer cell migration activities was observed in cancer cell with knockdown of ADAM9 expression in the chamber coated with collagen, whereas less migration activities was observed in chamber without collagen coating. This may reflect the possible role of ADAM9 in alteration of integrin composition or function. Flow Cytometry analyses of integrin composition on the surface of prostate cancer cells revealed no integrin composition change in knockdown strain compared to parental. We also notice highly expression of integrin alpha2beta1 and alpha6beta4 in C4-2 and PC3 cells. Analyses of signaling pathways demonstrated no significant changes in p-FAK, p-Erk and p-Akt, suggesting not through beta1 downstream signal regulation. Immunoprecipitation of ADAM9 demonstrated the highly associated with integrin beta4 but not beta1. Intra-cardiac injection of prostate cancer cell line, PC3-pSM2C, PC3-siADAM9 demonstrated 100% metastasis activities in PC3-pSM2C, and no any metastasis in mice with PC3-siADAM9. In summary, we notice ADAM9 may associated with the activation/stabilization of integrin complex. Knockdown of ADAM9 demonstrated decreased of cell migration on dish and metastasis when inoculated in mice, suggests hemidesmosome-ADAM9 interaction may involved in cancer migration and metastasis potential. 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 425. doi:10.1158/1538-7445.AM2011-425
Epidemiologic Approach to the Etiology of Type I Diabetes Mellitus and Its Complications
Authors: Jeffrey S. Flier, Lisa H. Underhill, Andrzej S. Krolewski, James H. Warram, Lawrence I. Rand, C. Ronald Kahn
Journal: New England Journal of Medicine (1987)

DIABETES arises through two etiologically distinct routes.1 Type I diabetes is the result of immunologically mediated destruction of the pancreatic beta cells, and usually requires replacement therapy with insulin. Type II appears to result from a combination of alterations in insulin sensitivity and insulin secretion. It can be treated with dietary therapy or oral hypoglycemic agents, and infrequently requires exogenous insulin. In this seminar we will focus on the use of epidemiologic data to develop and test hypotheses about the cause of Type I diabetes and its complications.Incorporation of all the principal features of the distribution of Type I . . .
PTH-009 Endoscopists Who are Meticulous in their Caecal Image Documentation Detect more Polyps: Abstract PTH-009 Table 1
Authors: M H Thoufeeq, B Rembacken
Journal: Gut (2013)

<h3>Introduction</h3> Adenoma detection is now accepted as an important quality indicator of colonoscopy. There is a significant variation in polyp detection rates among colonoscopists. Although the ESGE has recommendations regarding quality of images taken during endoscopy, there are no studies looking at the quality of caecal images versus outcomes of the procedures. Here we tested our hypothesis of endoscopists who have better quality image documentation of the caecum have higher polyp detection. <h3>Methods</h3> This retropective study was between June 2011 and May 2012. Planned colonoscopies performed by 16 experienced colonoscopists were included. We excluded procedures with planned therapeutic procedures, inadequate bowel preparation, rectal hyperplastic polyps, bowel cancer screen colonoscopies, previous hemicolectomy and incomplete procedures. The pre-procedure data collected were age and gender of patients, indication of procedures. The intra-procedure data collected were duration of the procedure, number of images stored in the endoscopy database, quality of caecal image, number of polyps (excluding rectal hyperplastic polyps). We cross-checked our pathology database to confirm histology of the polyps. We formulated a new scoring system, caecal image documentation score (CIDS). The CIDS was as follows; no image = 0, unclear image = 1, clear image = 2 and clear image with a label = 3. <h3>Results</h3> A total of 651 procedures performed by 16 colonoscopists were analysed. The mean number of procedures performed by each colonoscopist was 41. Mean age of the patients was 60.3 years. 46% of the patients were males. The mean CIDS for the 16 endoscopists was 2.13. The mean polyp detection rate (PDR) was 24% and mean polyp per procedure (PPP) was 0.42. Colonoscopists with mean CIDS &gt; 2.0 (n = 429 procedures, 10 colonoscopists) had PDR of 28% and PPP of 0.52. On the other hand, 6 colonoscopists (222 procedures) with mean CIDS of &lt; 2.0 had PDR of 16% and PPP of 0.24. Mean CIDS &gt; 2.0 was associated with greater PDR (OR 2.1, CI 1.4 – 3.2 p = 0.001). When adjusting for age, gender, and indication for colonoscopy, the mean CIDS &gt; 2.0 remained an independent predictor of greater PDR, OR 2.4, 95% CI 1.5 – 3.8 p &lt; 0.001. Mean CIDS &gt; 2.0 was associated with greater right-sided polyp detection rate, OR 3.4, CI 1.9 – 6.6 p &lt; 0.001. When adjusting for age, gender, and indication for colonoscopy, the mean CIDS &gt; 2.0 remained an independent predictor of greater right-sided PDR, OR 4.0, 95% CI 2.2 – 8.1 p &lt; 0.001. <h3>Conclusion</h3> Colonoscopists who are more meticulous in caecal image documentation detect more polyps per procedure and have higher polyp detection rates. Better caecal image documentation also improves right colonic polyp detection. <h3>Disclosure of Interest</h3> None Declared.
Splenic-Vein Thrombosis Following Transthoracic Gastrectomy and Incidental Splenectomy
Authors: Stuart Quan, Benjamin Castleman
Journal: New England Journal of Medicine (1949)

ALTHOUGH thrombosis of the splenic vein is infrequently reported in the literature,1 , 2 it is common knowledge among surgeons that this condition may follow splenectomy. In fact, local thrombosis at the site of ligation of the splenic artery and vein with extension back to the first branching vessel is to be expected. This degree of involvement of the splenic vein, however, should be symptomless, but it is potentially important because of possible extension into the portal venous system and as a source of emboli to the liver. Since splenectomy is usually performed for definite diseases of the spleen such as trauma, . . .
189 EFFICACY OF TIPS FOR THE PREVENTION OF TOTAL PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS WAITING FOR LIVER TRANSPLANTATION
Authors: D. D'Avola, J.I. Bilbao, G. Zozaya, F. Pardo, F. Rotellar, M. Inarrairaegui, J. Quiroga, B. Sangro, J.I. Herrero
Journal: Journal of Hepatology (2012)
SAT0324 Comparison of ACR 1980'S and Acr/Eular 2013'S Systemic Sclerosis Classification Criteria in the RESCLE Cohort
Authors: L. Sáez-Comet, M. Pérez-Conesa, C. Vallejo-Rodríguez, V. Fonollosa-Pla, D. Colunga-Argüelles, M.V. Egurbide-Arberas, B. Marí-Alfonso, J.A. Vargas-Hitos, M.C. Freire-Dapena, C.P. Simeόn-Aznar
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The 19809s ACR classification criteria for systemic sclerosis (SSc) show low sensitivity for diagnosing the disease. A new set of classification criteria by the ACR/EULAR has been developed along 2013. <h3>Objectives</h3> To compare the performance of both set of classification criteria. To assess the proportion of SSc and its cutaneous subsets classified with both criteria and to analyse the degree of agreement between them. <h3>Methods</h3> Cross-sectional multicentric study with patients from the RESCLE database from the Spanish Group of Systemic Autoimmune Diseases (GEAS) in April 2013. All patients fulfilled LeRoy-Medsger SSc criteria. Epidemiological, clinical, immunological and capillaroscopic variables were collected. 23 pre-selected criteria were first analysed. The ACR/EULAR criteria were compared with the ACR criteria by the proportion of patients fulfilling each criteria and by Cohen9s Kappa coefficient. A p&lt;0.05 was considered significative. <h3>Results</h3> 1222 SSc patients were included and 1157 were selected for comparing both set of criteria (65 excluded for incomplete data). The most prevalent preselected items were Raynaud9s phenomenon (95%), skin thickening (91%), ANA+ antibodies (91%), abnormal nailfold capillaroscopy (89%) and reduced carbon oxide diffusion (78%). Table 1 shows number of patients classified as SSc with both criteria Table 2 shows patients classified as SSc and its Kappa index in their different cutaneous subsets. <h3>Conclusions</h3> New ACR/EULAR classification criteria show better accuracy than the old ACR ones. A greater number of patients are classified as SSc, specially in their limited cutaneous, sine and pre-scleroderma subsets. <h3>References</h3> Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23:581–90. van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis 2013;72: 1747-1755. Fransen J, Johnson SR, van den Hoogen F, et al. Items for developing revised classification criteria in systemic sclerosis: results of a consensus exercise. Arthritis Care Res (Hoboken) 2012;64:351–7. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3769
P253 Meta - Analysis On Statins In Chronic Obstructive Pulmonary Disease
Authors: G. Ambrocio, I. Roque, M. Jorge
Journal: Thorax (2014)

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterised by progressive airflow limitation. Statins have anti-inflammatory and immunomodulating properties that could alter inflammation of the airways. The objective of this study is to systematically evaluate the effectiveness of adjunct statin therapy in improving exercise tolerance and pulmonary function indices in patients with chronic obstructive pulmonary disease. <h3>Search strategy and inclusion criteria</h3> A thorough search was done using Medline and PubMed, with limits set on studies involving humans in a randomised control trial in English that examined the effect of statins in COPD. <h3>Study manoeuvres</h3> All the articles retrieved were appraised separately and independently by two reviewers for its applicability, validity and the methodological quality of the randomised control trials by assessing allocation, blinding, and if follow up rate was adequate. Disagreements between the reviewers were resolved by consensus. <h3>Statistical analysis</h3> Data collected were analysed using Review Manager Version 5.2. <h3>Results</h3> A total of two articles met the end criteria. Outcome shows improvement in exercise time (treadmill test) at 95% CI, with statistically significant benefit with mean difference of 335.18 [253.93, 416.43] favouring Pravastatin group. The studies show inconclusive results for Pravastatin in improving FEV1(%) with 95% CI with mean difference of 0.05 [-4.61, 4.7]. The outcome in total lung capacity shows inconclusive results but shows a trend toward benefit with 95% CI with mean difference of -0.08 [-0.46, 0.30]. Inspiratory capacity results at 95% CI with mean difference of 0.13 [-0.06, 0.32] showed an inconclusive outcome but has a trend toward benefit. Improvement in the Borg dyspnea score at 95% CI, showing statistically significant benefit with mean difference of -2.91 [-3.19, -2.63] favouring the Pravastatin group. <h3>Conclusions</h3> Statins already have an established role in treating cardiovascular patients because of their cholesterol-lowering ability, but also have anti-inflammatory and immunomodulatory effects that are beneficial in airway inflammation in COPD. Statin administration to COPD patients showed amelioration in exercise tolerance, improvement in dyspnea scores and augmentation in pulmonary function indices. Thus, statins may be useful as adjunct to currently available therapies as well as improvement in lipid status.
Abstract 3435: Proteomic analysis of changes to the cellular kinome in the epithelial to mesenchymal transition
Authors: Michael Tanowitz, James Bean, John D. Haley, Andrew Garton
Journal: Cancer Research (2011)

Abstract The epithelial to mesenchymal transition (EMT) is a developmental program characterized by loss of cell-cell contacts, loss of cell polarity, and acquisition of a migratory phenotype. Many of the hallmarks of EMT correspond to aspects of carcinogenesis, particularly with regard to metastasis and invasion, and EMT is associated with the development of tumor cell resistance to EGFR inhibitors. We have applied proteomic approaches to examine changes to the cellular kinome in response to various EMT-inducing ligand treatments. For our studies we chose the H358 NSCLC line after week-long single or combination treatments with Hepatocyte Growth Factor (HGF), Transforming Growth Factor Beta (TGFβ) and Oncostatin M (OSM). We used several approaches to probe for changes following EMT using mass spectroscopy: whole cell lysate fractionation to provide an unbiased overview of cellular proteins, affinity isolation of cellular phospho-proteins, and targeted analysis of ATP binding proteins (KinativTM). Using these methods we have identified a host of protein changes that are clustered across several signaling pathways and cellular functions. Among these are changes in receptor tyrosine kinases centered around phylogenetically related groupings such as Tyro3/Mer/Axl and Ron/Met, concerted changes in actin-dependent motor proteins consistent with changes in migratory behavior, and changes indicative of reorganization of calcium signaling networks. Functional consequences of these changes and their potential to inform therapeutic interventions will be discussed. 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 3435. doi:10.1158/1538-7445.AM2011-3435
Evaluation of Reperfusion and Recovery of Brain Function Before and After Intracarotid Arterial Urokinase Therapy in Acute Cerebral Infarction With Brain SPECT
Authors: Y H Ryu, T S Chung, P H Yoon, D I Kim, J D Lee, B I Lee, J H Suh
Journal: Clinical Nuclear Medicine (1999)

Perfusion defects can be demonstrated reliably at an early stage with regional cerebral blood flow studies using SPECT. The administration of thrombolytic therapy in ischemic stroke is targeted at restoring cerebral perfusion immediately, leading to salvage of ischemic penumbra, smaller infarct size, and improved clinical outcome. This study considered the role of brain perfusion SPECT in the evaluation of reperfusion and brain function recovery of the infarcted area after early recanalization (less than 6 hours) of the occluded artery using intracarotid arterial urokinase therapy (ICAU).Intracranial artery occlusion was confirmed in seven patients using emergency carotid angiography performed within the initial 6-hour period. Intracarotid arterial urokinase (500,000 to 800,000 units) was administered into the occluded arterial system (the left middle cerebral artery in four and the right middle cerebral artery in three patients). CT scanning was performed when the patients arrived in the emergency department and was repeated 24 to 48 hours after ICAU and at 7 days or earlier if clinically indicated. All patients had two SPECT studies, the first before urokinase administration and the second 24 or 48 hours later.Complete recanalization of the occluded vessels was seen in one patient after ICAU, effective partial recanalization was achieved in four patients, and minimal recanalization occurred in the other two. Before ICAU, Tc-99m HMPAO brain SPECT showed decreased uptake of the infarcted area in all patients, whereas the follow-up brain SPECT performed 24 or 48 hours after ICAU revealed improvement in the uptake of the recanalized area on qualitative and semiquantitative assessments using an asymmetry index, suggestive of brain function recovery and clinical improvement. Hemorrhagic transformation adjacent to the reperfused regions occurred in two patients with partial recanalization of the left middle cerebral artery.Reperfusion of the recanalized area and brain function recovery could be achieved if the occluded artery is recanalized within the initial 6-hour period using ICAU, and this was documented using brain perfusion SPECT without a delay in the therapeutic time window. Because the number of patients we studied was limited, further study is necessary to evaluate the effect of ICAU and to determine its prognostic significance.
A Clinical Trial of the Angiotensin-Converting–Enzyme Inhibitor Trandolapril in Patients with Left Ventricular Dysfunction after Myocardial Infarction
Authors: Lars Køber, Christian Torp-Pedersen, Jan E. Carlsen, Henning Bagger, Per Eliasen, Kjeld Lyngborg, Jørgen Videbæk, David S. Cole, Laurent Auclert, Nancy C. Pauly, Etienne Aliot, Stig Persson, A. John Camm
Journal: New England Journal of Medicine (1995)

Treatment with angiotensin-converting–enzyme (ACE) inhibitors reduces mortality among survivors of acute myocardial infarction, but whether to use ACE inhibitors in all patients or only in selected patients is uncertain.
SAT0114 Prevalence of Cardiovascular Comorbidities Already Increased at Onset of Arthritis and Axial Spondyloarthritis - Results from the ESPOIR and DESIR Cohorts
Authors: A.M. Gherghe, M. Dougados, B. Combe, R. Landewé, C. Mihai, F. Berenbaum, X. Mariette, R. Wolterbeek, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are associated with increased cardiovascular (CV) morbidity and mortality, largely attributable to chronic inflammation. However, it has not yet been clarified if the increased CV risk is already present early in the disease process or only after prolonged periods of inflammation. <h3>Objectives</h3> To investigate the association between CV comorbidities and early RA (ERA) and early axial SpA (ESpA) in 2 French cohorts, ESPOIR (1) and DESIR (2). <h3>Methods</h3> Baseline data of 689 ESPOIR patients (age 48.2±12.1 years, symptom duration 14.2±14.5 weeks) and 645 DESIR patients (age 32.8±8.4 years, axial symptom duration 79.0±45.7 weeks) were analyzed. The most common CV comorbidities were determined in each cohort. The 10-year risk of developing CV disease (CVD) was calculated for every patient using the Framingham and the SCORE equations. The heart age was calculated using the 2008 Framingham points system. The prevalence (95% confidence intervals (95% CI)) of several CV comorbidities was compared to that in the French general population matched for age and gender (arterial hypertension (AHT) data was gathered from the ENNS survey; the rest from statistic reports of the French National Health Insurance Fund for the Employees, including almost 90% of the total French population). <h3>Results</h3> 19.0% of ERA patients and 7.1% of ESpA had at least one CVD; the most common was AHT. In ESPOIR, men aged over 55 years had high 10-year CVD risk and women over 60 years had intermediate risk. The heart age exceeded the real age by 4.1±9.6 years in ERA and 2.1±7.0 years in ESpA. AHT prevalence (95% CI) in ESPOIR was increased compared to the general population (18.2% (15.5%&gt;21.3%) vs. 7.6% (6.5%&gt;8.8%)), especially in younger women. No differences were observed for coronary heart disease. <h3>Conclusions</h3> Both in ERA and ESpA, we found an increased frequency of CV comorbidities and an increased heart age even after a short duration of symptoms. Moreover, in ERA we found an intermediate to high CVD risk and increased prevalence of AHT compared to the general population. These results should prompt rheumatologists to check these comorbidities already early in disease. <h3>References</h3> Combe B et al. Joint Bone Spine. 2007 Oct;74(5):440-5. Dougados M et al. Joint Bone Spine. 2011 Dec;78(6):598-603. <h3>Acknowledgements</h3> AMG was supported by a EULAR scientific training bursary for 6 months. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1965
Abstract 1720: Tyrosine phosphorylation of HSC70 located in the cell membrane may regulate methotrexate transportation in murine L1210 leukemia cells
Authors: Tuoen Liu, Zech Rios, Peter P. Sheridan, Alok Bhushan, James C.K. Lai, Christopher Daniels
Journal: Cancer Research (2011)

Abstract Bhushan and co-workers previously described an alteration in an unidentified 66-68 kDa membrane-associated, tyrosine-phosphorylated, methotrexate (MTX)-binding protein in the L1210 murine leukemia cell line. This protein was absent, at least in the tyrosine phosphorylated form, in cisplatin-resistant, methotrexate cross-resistant L1210/DDP cells. The 66-68 kDa protein was isolated by affinity chromatography, first on MTX-agarose followed by purification using an anti-phosphotyrosine immunoaffinity column. Amino acid sequence analysis identified the protein as heat shock cognate protein 70 encoded by the HSPa8 gene. The HSPa8 gene was found to be transcribed in both sensitive and resistant cell lines by RT-PCR and the sequence of the HSPa8 gene was identical in both cell lines. Western blot analysis showed that HSC70 was also expressed in both cell lines. A binding pull-down assay with MTX-agarose beads, followed by western blotting for HSC70, showed HSC70 to be present in cell lysates and in the MTX-binding fraction. Fractionation of cell homogenates into membrane and cytosolic fractions showed that HSC70 was found in both fractions but was not detected in the MTX-binding assay with the membrane fraction from the L1210/DDP cells, suggesting HSC70 located in the membrane fraction may be controlling MTX transport in the sensitive cells. Comparing the tyrosine phosphorylation status between L1210/0 and L1210/DDP cells, a band around 70 kDa was observed in the membrane fraction of L1210/0 cell but was not present in the L1210/DDP cells. Additionally, immunoprecipitation with anti-phosphtyrosine (PY20) agarose beads and detection of HSC70 by western blot showed little to no PY-HSC70 in the membrane fraction from the L1210/0 cells. Thse results suggest that HSC70 is a putative MTX binding protein, and HSC70 associated with the cell membrane may regulate methotrexate uptake. Tyrosine phosphorylation may contribute to the function of HSC70 in the cross-resistance mechanism in the murine L1210 cells. 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 1720. doi:10.1158/1538-7445.AM2011-1720