tbuckley/cabot-search huggingface dataset:
Immunotoxin Therapy: Prospects For the Future
Authors: J. Corliss
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Immunotoxin Therapy: Prospects For the Future Get access Julie Corliss Julie Corliss Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 24, 20 December 1989, Pages 1862–1863, https://doi.org/10.1093/jnci/81.24.1862 Published: 20 December 1989
Inhibition of <i>BCL-2</i> by Stealth siRNA results in growth suppression of LNCaP cells
Authors: P. C. Mack, R. A. Burich, P. Axentiev, D. R. Gandara, R. W. Devere White
Journal: Journal of Clinical Oncology (2005)

9626 Background: RNA interference is a powerful laboratory tool for gene silencing; however, the kinetics of unmodified small interfering RNA (siRNA) currently preclude most in vivo or clinical applications. Despite these limitations, targeted inhibition of key cancer survival genes would increase therapeutic options. We therefore tested Stealth siRNA (Invitrogen Corp), a novel modified siRNA with enhanced stability, directed against the Bcl-2 gene, a key anti-apoptotic regulator, in the prostate cell line LNCaP. Methods: Proof-of-principle experiments were conducted using an LNCaP sub-line constitutively expressing enhanced green fluorescent protein (eGFP). Fluorescent intensity was measured by flow cytometry and with a 96-well fluorescent plate reader controlling for cell number. Lipofectamine 2000 was used as a delivery vehicle. Bcl-2 silencing was measured by RT-PCR and Western blotting and cell growth was assessed by MTT assay and flow cytometry of DNA content. Non-silencing Stealth siRNA with matched GC content served as controls. Results: Stealth siRNA reduced fluorescent emission of the highly stable eGFP by 72% by day 5, with an increased duration of inhibition compared to conventional siRNA of the same sequence and concentration. Based on these findings, Stealth siRNA were developed against the BCL-2 gene. A single administration of anti-BCL-2 inhibitors (40nM) reduced BCL-2 mRNA to below the threshold of detection and greatly decreased protein levels. In a 96-well format, treatment resulted in substantial inhibition of LNCaP growth (>70%), compared to non-silencing controls. DNA content was measured on day 5 after transfection. At this time-point, minimal effect on cell cycling was observed, while apoptosis was modestly increased (8%). In androgen depleted media, where LNCaP growth is minimized, silencing of Bcl-2 resulted in a further reduction in cell number. Conclusions: In controlled comparisons measuring reduction in eGFP fluorescence, Stealth siRNA showed potent inhibition and an increased duration of response, likely stemming from its enhanced stability. Treatment with anti-Bcl-2 Stealth siRNA resulted in substantial growth inhibition of LNCaP cells, warranting further testing in in vivo models. No significant financial relationships to disclose.
OUTCOMES OF SINGLE VERSUS DUAL ANTIPLATELET THERAPY WITH TARGET SPECIFIC ORAL ANTICOAGULANT AGENTS IN PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING CORONARY ARTERY INTERVENTION
Authors: Saba Lahsaei, Ashul Govil, Jonathan Wong, Jamal Brewster, Anna Beyer, Richard Shaw
Journal: Journal of the American College of Cardiology (2016)
THU0064 Endothelial Progenitor Cell Biology in Ankylosing Spondylitis
Authors: A. Syngle, I. Verma, P. Krishan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming the endothelial damage and reducing cardiovascular risk<sup>1</sup>. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. However, EPCs have not been investigated in AS. <h3>Objectives</h3> The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. <h3>Methods</h3> Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease severity was evaluated using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). <h3>Results</h3> EPCs were depleted in AS as compared to the healthy controls (CD34+/CD133+: 0.027±0.010% vs. 0.044±0.011%, p&lt;0.001) (Figure 1A). EPC depletion was significantly associated with disease duration (r= -0.52, p=0.01) (Figure 1B), BASDAI (r= -0.45, p=0.04) (Figure 1C) and CRP (r= -0.5, p=0.01). <h3>Conclusions</h3> This is the first study to demonstrate endothelial progenitor cells depletion in AS patients. EPCs depletion inversely correlates with disease duration, disease severity and inflammation, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS. <h3>References</h3> Hill JM et al. N Engl J Med. 2003; 348:593–600. <h3>Acknowledgements</h3> This study has been supported by a Research Fellowship from University Grant Commission, New Delhi (Govt. of India) [No. F.10-15/2007 (SA-I)]. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5181
AB0234 Low hdl is the most prominent feature in lipid profile of patients with early active rheumatoid arthritis
Authors: J. Nedovic, S. Stojanovic, B. Stamenkovic, N. Dimic, J. Jocić, A. Dimic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the past decade, it is well recognized that patients with rheumatoid arthritis (RA) have increased morbidity and mortality from premature atherosclerosis. There is 1.5 fold increase in mortality due to cardiovascular events compared to general population. Both, traditional and nontraditional factors, such as systemic inflammation and immune dysregulation contribute to this. There are considerable variations between different studies regarding lipid profile and its role in patients with RA. <h3>Objectives</h3> Objective of our study was to investigate relationship between systemic inflammation and lipid profile in RA patients. <h3>Methods</h3> 90 RA patients (84,33% female, mean age 53,92±12,83 years) who fulfilled 1987. ACR criteria for RA and 40 age-matched controls with osteoarthritis were enrolled in the study. Group of RA patients consisted from 50 patients treated with Methotrexate (MTX group), mean disease duration 9,27±4,78 years and from 40 patients with early RA (less than 1 year duration) not treated with DMARDs (ERA group). Patients with known cardiovascular, cerebrovascular and peripheral vascular diseases were excluded as well as patients with diabetes, familiar dyslipidemia and those on hypolipemic therapy. Erythrocyte sedimentation rate (ESR), CRP, total cholesterol, LDL, HDL and triglyceride were determined to all subjects. <h3>Results</h3> Patients in ERA and MTX groups had, as expected, increased markers of inflammation : ESR (64,36±28,91 mm and 41,44±18,68 mm respectively) and CRP (48,48±63,16 mg/L and 11,44±21,77 mg/L respectively) which was significantly higher than in control group (ESR 12,79±6,7 mm and CRP 1,81±0,35 mg/L, p&lt;0,05). There were no significant differences in mean values of lipid components between ERA, MTX and control group. There were neither positive nor negative correlation between ESR and CRP with any of the lipid components in MTX or in control group. In spite of this, ERA group total cholesterol negatively correlated with ESR (r=-0,32, p&lt;0,05) as well as with CRP (r=-0,43, p&lt;0,01), LDL negatively correlated only with CRP (r=-0,31, p&lt;0,05), HDL strongly negatively correlated with both ESR (r=-0,59, p&lt;0,01) and with CRP (r=-0,44, p&lt;0,01) while triglyceride showed no correlation with ESR and CRP. <h3>Conclusions</h3> Patients with active untreated RA have tendency to have reduced total cholesterol, LDL and HDL. Low levels of HDL are most prominent aterogenic factor in these patients mostly influenced by systemic inflammation. <h3>Disclosure of Interest</h3> None Declared
EUS-guided Choledocho-duodenostomy (ECD) for immediate and long-term treatment of biliary obstruction using prototype PathCreator™ compression coil and twin-headed needle
Authors: K Chang
Journal: Endoscopy (2011)

Background: We previously reported our initial feasibility canine study for ECD using a novel EUS-guided coil technique (PathCreator™). While placement of the coil through the duodenum into the dilated common bile duct (CBD) with subsequent biliary drainage using a short stent for immediate drainage, and formation of a choledocho-duodenostomy fistula was shown to be possible (successful in 1/6), substantial design modifications were necessary to maximize safety and efficacy. Parameters to be addressed included: 1) consistent fistula formation, 2) avoid bile leak, 3) prevent coil extrusion into CBD, 4) immediate biliary drainage without need for stenting. To this end, several reiterations resulted in the current “fin-coil” configuration and specifications. In addition, a prototype “twin-headed” needle was developed for immediate biliary drainage. The aim of this animal study was to determine the efficacy and safety of the modified PathCreator™ coil and the twin-headed needle for ECD.
P1033 CARBONYLATED PROTEINS AND GLUTATHIONE LEVELS AS IMPORTANT OXIDATIVE BIOMARKERS IN ALCOHOLIC LIVER DISEASE
Authors: M. Galicia, D. Rosique Oramas, T. Álvarez Torres, L. Very Pineda, K. Medina Avila, L. Raya Soto, J.L. Pérez Hernández, D. Kershenobich, G. Gutiérrez Reyes
Journal: Journal of Hepatology (2014)
MAYO REGISTRY FOR TELEMETRY EFFICACY IN ARREST (MR TEA) STUDY: AN ASSESSMENT OF THE UTILITY OF TELEMETRY IN PREDICTING CLINICAL DECOMPENSATION
Authors: David Snipelisky, Jordan Ray, Gautam Matcha, Archana Roy, Dana Harris, Veronica Bosworth, Adrian Dumitrascu, Brooke Clark, Tyler Vadeboncoeur, Fred Kusumoto, Colleen Thomas, Michael Heckman, M.C. Burton
Journal: Journal of the American College of Cardiology (2015)
FRI0279 Anemic hypoxia is associated with pulmonary arterial hypertension in patients with systemic lupus erythematosus
Authors: K.-J. Kim, I.-W. Baek, C.-H. Yoon, J.-J. Choi, W.-U. Kim, C.-S. Cho
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pulmonary arterial hypertension (PAH) is a serious and often fatal complication of systemic lupus erythematosus (SLE), but its pathogenesis is still unclear. Hypoxia-induced pulmonary vascular remodelling has been suggested to be a crucial mechanism for PAH. <h3>Objectives</h3> To investigate the association between anemic hypoxia and PAH in patients with SLE. <h3>Methods</h3> A post hoc analysis was performed of the prospective cross-sectional study to determine the PAH in 116 patients with SLE. PAH was defined as resting pulmonary artery systolic pressure (PASP) ≥ 40 mmHg by echocardiography. Duration of anemia was calculated as cumulative months of anemia (defined by hemoglobin [Hb]&lt;10 g/dL) during the preceding years. Oxygen delivery (DO<sub>2</sub>) was estimated by the product of cardiac output (CO) and arterial oxygen content (CO x %Saturation x 1.39 x Hb). Serum IL-6 level and plasma N terminal-pro B-type natriuretic peptide (NT-proBNP) were also quantified. <h3>Results</h3> Among 116 SLE patients, PAH was detected in 11 patients (9.5%). The range of PAH was 40.4-90 mmHg. Twenty-one patients (18.1%) showed PASP of 30-40 mmHg. Compared to patients without PAH, patients with PAH had lower Hb levels (9.8±0.5 versus 11.9±0.2 g/dL, <i>P</i>=0.001), but longer duration of anemia during the preceding 1, 2, and 3 years, respectively (all <i>P&lt;</i>0.05). Importantly, DO<sub>2</sub> value of patients with PAH were significantly lower than those of patients without PAH (7.9±0.8 versus 10.0±0.2 ml/min/kg, <i>P</i>=0.006). Moreover, DO<sub>2</sub> value inversely correlated with PASP and serum NT-proBNP levels (Y=-0.241, <i>P</i>=0.013 and Y=-0.292, <i>P</i>=0.001, respectively). In multivariate regression analysis, duration of anemia was independently associated with the presence of PAH in SLE patients (<i>P</i>=0.006). When patients were divided into three groups according to tertiles of Hb well as PASP, serum IL-6 significantly increased across the tertiles of PASP (<i>P</i> for trend=0.038), but decreased across the tertiles of Hb (<i>P</i> for trend=0.001). <h3>Conclusions</h3> Our study suggests that prolonged exposure to anemic hypoxia, which is associated with increased serum IL-6, might be a component of pathogenesis of PAH in SLE patients. <h3>Acknowledgements</h3> Nothing specified. <b>Disclosure of Interest</b>: None Declared
Endoscopic ultrasound, endoscopic sonoelastography, and strain ratio evaluation of lymph nodes with histology as gold standard
Authors: M. Larsen, C. Fristrup, T. Hansen, C. Hovendal, M. Mortensen
Journal: Endoscopy (2012)

<b>Background and study aims: </b>Accurate lymph node staging is essential for the selection of an optimal treatment in patients with upper gastrointestinal cancer. Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) are considered to be the most accurate method for locoregional staging. Endoscopic sonoelastography (ESE) assesses the elasticity of lymph nodes and has been used to differentiate lymph nodes with promising results. The aim of this study was to evaluate the use of EUS, EUS – FNA, ESE, and ESE-strain ratio using histology as the gold standard. <b>Patients and methods: </b>Patients with upper gastrointestinal cancer who were referred for EUS examination were enrolled if surgical treatment was planned and the patient had a lymph node that was accessible for EUS – FNA and EUS-guided fine-needle marking (FNM). The lymph node was classified using EUS, ESE, and ESE-strain ratio. Finally, EUS – FNA and EUS – FNM were performed. The marked lymph node was isolated during surgery for histological examination. <b>Results: </b>The marked lymph node was isolated for separate histological examination in 56 patients, of whom 22 (39 %) had malignant lymph nodes and 34 (61 %) had benign lymph nodes. There were no complications of EUS – FNM. The sensitivity of EUS for differentiation between malignant and benign lymph nodes was 86 % compared with 55 % – 59 % for the different ESE modalities. The specificity of EUS was 71 % compared with 82 % – 85 % using ESE modalities. <b>Conclusion: </b>The use of the EUS – FNM technique enabled the identification of a specific lymph node and thereby the use of histology as gold standard. ESE and ESE-strain ratio were no better than standard EUS in differentiating between malignant and benign lymph nodes in patients with resectable upper gastrointestinal cancer.
TEMPORAL TRENDS IN UTILIZATION OF FRACTIONAL FLOW RESERVE FOR PATIENTS WITH STABLE CORONARY ARTERY DISEASE IN THE UNITED STATES
Authors: Sahil Khera, Dhaval Kolte, Tanush Gupta, Wilbert Aronow, Kathir Subramanian, Neel Khanna, Howard Cooper, Robert Timmermans, Diwakar Jain, Gregg Fonarow, Deepak Bhatt, Julio Panza
Journal: Journal of the American College of Cardiology (2016)
PTH-042 Iron Deficiency Anaemia in Young Males: Do Gi Symptoms and Haemoglobin Level Affect Diagnostic Yield?
Authors: R Kalla, S Campbell, R Willert
Journal: Gut (2013)

<h3>Introduction</h3> Young males with iron deficiency (IDA) routinely undergo endoscopy. There is paucity of data on the diagnostic yield of bi-directional endoscopy, level of HB that requires investigation and the yield in symptomatic vs. asymptomatic young men. We aim to study the diagnostic yield of bi-directional endoscopy in young males and the influence of gastrointestinal symptoms and HB level on yield. <h3>Methods</h3> Data was collected from UNISOFT endoscopy software for all male patients referred for iron deficiency anaemia. Strict inclusion criteria were set and defined as: 1. Age 20–50 years 2. No prior gastrointestinal (GI) diagnosis 3. Blood indices - hypoferritinemia confirming IDA at the time of referral A total of 36 patients were identified from January 2010 to July 2012. A retrospective review of blood parameters, symptoms, non-steroidal anti-inflammatory drug (NSAID) use, endoscopic findings and histologies were recorded. Data was recorded on an excel sheet and analysed using SPSS version 15. <h3>Results</h3> A total of 36 patients were included in the study. The median age was 42 years. Eleven percent (n = 4) were referred from general medicine, 22% (n = 8) from general surgery and 67% (n = 24) from Gastroenterology for endoscopic investigations. Median HB level was 10g/dL. There were 4 patients on NSAIDs prior to referral. Gastroscopy was performed in all patients and was normal in 94% (n = 34). The remaining 6% (n = 2) were diagnosed with h pylori gastritis (n = 1), and benign pyloric stenosis (n = 1). Duodenal (D2) biopsies were performed in 32 patients (89%), of which 1 patient was diagnosed with coeliac disease on histology. Three of the 4 patients with no D2 biopsies had a normal coeliac blood screen. Lower GI endoscopy (colonoscopy n = 30, flexible sigmoidoscopy n = 3) was performed in 33 (92%), of which 85% (n = 28/33) were macroscopically normal. Five patients had pathology encountered at endoscopy, these included adenomas (n = 3), ulcerative colitis (n = 1) and caecal carcinoma (n = 1). Patients with IDA and no GI symptoms (n = 21); endoscopic diagnostic yield was 5% (n = 1) for gastroscopy and 11% (n = 2/19) for colonoscopy. The diagnostic yield in symptomatic patients was 7% (n = 1) for gastroscopy and 21% (n = 3/14) for colonoscopy. There were 11 patients with IDA and an HB level over 11g/dL. All patients underwent gastroscopy with D2 biopsies and 10 patients underwent colonoscopy. All endoscopic investigations including D2 biopsies were normal. <h3>Conclusion</h3> IDA in young males should always be investigated with bi-directional endoscopy, irrespective of symptoms. Although a small cohort, our study shows that the diagnostic yield is higher amongst patients with IDA and GI symptoms as well as IDA with an HB level below 11g/dL. <h3>Disclosure of Interest</h3> None Declared.
Abstract 3988: Identification of miR-132 and miR-290-3p as putative tumor and metastasis suppressor microRNAs in breast cancer
Authors: Natalie E. Goldberger, Chang Hee Kim, Renard Walker, Kent Hunter
Journal: Cancer Research (2011)

Abstract Several microRNAs (miRNAs) have been classified as regulators of breast cancer metastasis [1], yet additional unidentified miRNAs may also exist that regulate metastasis. Most interesting, we propose that germline genetic changes may exist which create a predisposition towards developing breast cancer metastasis through the dysregulation of miRNAs. Thus, to identify novel miRNAs associated with a germline predisposition towards breast cancer metastasis, highly metastatic FVB/N-TgN (MMTV-PyMT) mice were crossed with 25 AKXD RI (AKR/J × DBA/2J) strains to produce F1 progeny displaying primary mammary tumors with varying degrees of pulmonary metastasis. The miRNA expression levels within all mammary tumors were evaluated using a miRNA microarray and correlated with the metastatic index for each strain. The analysis produced 27 candidate miRNAs possessing a significant p-value (p &amp;lt; 0.05). To further validate the microarray findings, the expression levels for the most promising miRNAs were measured in mammary tumors from highly metastatic AKR/J and poorly metastatic DBA/2J strains. Downregulation of miR-132 and miR-290-3p was observed in the AKR/J strain versus the DBA/2J strain, consistent with the negative correlation coefficients produced during microarray analysis. In addition, miR-132 miRNA was downregulated in normal breast tissue from the AKR/J compared to the DBA/2J strain (p &amp;lt; 0.00029), thus supporting a predisposition towards tumorigenesis. Most importantly, ectopic expression of miR-290-3p and miR-132 in highly metastatic murine breast cancer cell lines (Mvt-1 and 6DT1) reduced the mammary tumor burden and the number of pulmonary metastasis in FVB/NJ mice after orthotopic injection in the mammary fat pad. Overall, these findings suggest somatic or germline genetic changes that downregulate either miR-132 or miR-290-3p may create a predisposition towards breast cancer development and metastasis. 1. Hurst, D.R., M.D. Edmonds, and D.R. Welch, Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res, 2009. 69(19): p. 7495-8. 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 3988. doi:10.1158/1538-7445.AM2011-3988
Leflunomide for Polyomavirus Type BK Nephropathy
Authors: James W. Williams, Basit Javaid, Predeep V. Kadambi, Daniel Gillen, Robert Harland, J. Richard Thistlewaite, Marc Garfinkel, Preston Foster, Walter Atwood, J. Michael Millis, Shane M. Meehan, Michelle A. Josephson
Journal: New England Journal of Medicine (2005)

To the Editor: Polyomavirus type BK nephropathy is an aggressively destructive disease occurring in up to 8 percent of patients with renal allografts,1,2 with rates of graft loss within one year of 30 to 65 percent.3,4 There is no therapy with proven efficacy. Leflunomide (Arava), approved for the treatment of rheumatoid arthritis, is an immunosuppressive drug, yet its active metabolite, A77 1726, has substantial antiviral activity in vitro and in animals.5 From July 2001 to April 2004, we used leflunomide as the initial antiviral therapy in 17 patients with biopsy-proven BK nephropathy. All but one of these patients . . .
COLCHICINE FOR PREVENTION AND TREATMENT OF CARDIAC DISEASES: AN UPDATED META-ANALYSIS
Authors: Nikolaos Papageorgiou, Alexandros Briasoulis, George Lazaros, Emmanuel Androulakis, Gerasimos Siasos, Marietta Charakida, Konstantinos Toutouzas, Luis Afonso, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2016)