tbuckley/cabot-search huggingface dataset:
Abstract 3964: In colorectal cancer cells, the beta-catenin/TCF complex regulates several growth suppressive microRNAs that target cancer promoting genes
Authors: Troels Schepeler, Anja Holm, Patrick Halvey, Iver Nordentoft, Philippe Lamy, Lise Lotte Christensen, Kasper Thorsen, Daniel C. Liebler, Torben F. Ørntoft, Claus L. Andersen
Journal: Cancer Research (2011)

Abstract Aberrant activation of the Wnt signaling pathway is causally involved in the formation of most colorectal cancers (CRCs). Whereas detailed knowledge exists regarding Wnt regulated protein coding genes, much less is known about the possible involvement of non-coding RNAs. Here we used TaqMan Array MicroRNA Cards, capable of detecting 664 unique human microRNAs (miRNAs), to describe changes of the miRNA transcriptome following disruption of beta-catenin/TCF4 activity in DLD1 CRC cells. Most miRNAs appeared to respond independently of host gene regulation and proximal TCF4 chromatin occupancy. A module of miRNAs suppressed by Wnt signaling in vitro was downregulated in a series of human primary CRCs (n = 46), and CRC cell lines (n = 7), relative to normal adjacent mucosa (n = 14). Several of these miRNAs (miR-145, miR-126, miR-30e-3p, and miR-139-5p) markedly inhibited CRC cell growth in vitro when ectopically expressed. By using an integrative approach of proteomics and microarrays, together interrogating thousands of proteins and genome-wide mRNA levels, we also provide detailed insight into the target gene network controlled by miR-30e-3p. Specifically HELZ and PIK3C2A were directly repressed via several functional seed matching binding motifs located within the transcripts. siRNA-mediated silencing of PIK3C2A partly phenocopied the growth suppressive phenotype of miR-30e-3p suggesting that miR-30e-3p restricts CRC cell growth in part by targeting PIK3C2A. Collectively, our study demonstrates that multiple miRNAs are upregulated as a consequence of forced attenuation of Wnt signaling in CRC cells, and some of these miRNAs inhibit cell growth, possibly through repression of several growth stimulatory cancer-related genes. 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 3964. doi:10.1158/1538-7445.AM2011-3964
Abstract 640: SIRT2 deacetylates peroxiredoxin and increases sensitivity to oxidative stress in human breast cancer cells
Authors: Veena CoothanKandaswamy, Jianguang Chen, Atul Joshi, Rekha Rao, Warren Fiskus, Kathleen M. Buckley, Srilatha Nalluri, Kapil N. Bhalla
Journal: Cancer Research (2010)

Abstract SIRT2, the mammalian ortholog of yeast Hst2, is a predominantly cytosolic and nuclear member of sirtuins, which is the class III, NAD+ dependent, histone deacetylase (HDAC) family. Sirtuins play a key role in modulating cellular stress resistance, longevity and cancer transformation. SIRT2 is known to deacetylate FOXO1 and FOXO3, thereby regulating FOXO-regulated stress resistance. In the cytosol, SIRT2 co-localizes with microtubules and deacetylates α-tubulin at the lysine-40, indicating a role in proper cytokinensis. Here, we determined other biologically important SIRT2 targets and their functions. Knockdown and overexpression of SIRT2 in HEK293 cells significantly altered the acetylation status of many proteins, including a group of proteins ranging in molecular weight from 23-50 kDa. In cells with knockdown of SIRT2, differential in-gel electrophoresis of cytosolic extract of cells followed by mass spectrometric analysis identified several significantly hyper-acetylated proteins, notably peroxiredoxin 1. Peroxiredoxins are ubiquitous family of evolutionarily conserved, thiol-dependent peroxidases, which catalyze the reduction of hydrogen peroxide. SIRT2 co-immunoprecipitated with peroxiredoxin 1, and ectopic overexpression of SIRT2 attenuated acetylation of peroxiredoxin 1 in HEK 293 cells. While acetylation activates, reduced acetylation is known to inhibit the activity of peroxiredoxins. Ectopic overexpression of SIRT2, but not the catalytically dead SIRT2 mutant, markedly increased reactive oxygen species (ROS) levels as well as increased the sensitivity of the human breast cancer MCF7 and MDA MB231 cells to oxidant stress induced by hydrogen peroxide. SIRT2 overexpression in breast cancer cells also increased their sensitivity to ROS generating agents such as arsenic trioxide and menadione. These findings demonstrate that SIRT2 plays an important role in regulating oxidative stress in cells by modulating the activity of peroxiredoxin 1. The findings also highlight the possibility that increased SIRT2 levels and activity can be therapeutically exploited for augmenting the antitumor effects of therapeutic agents that induce cancer cell death by increasing intracellular ROS levels. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 640.
THU0068 Prevalence of dyslipidaemia in an early arthritis rheumatoid cohort (ESPOIR cohort). Lack of improvement after 4 years of follow-up:
Authors: M. Margerit, P. Nguyen, B. Pereira, Y. Allanore, X. Le Loët, A.C. Rat, M. Soubrier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiovascular disease accounts for about half of all deaths in RA. This excess risk is driven in part by inflammation but may be reduced by management of traditional risk factors. The recommendation of the EULAR for CV management is to assess CV risk annually with a risk equation (SCORE or Framingham equation (FRS)). A multiplier of 1.5, applied to a conventional CV risk assessment, is recommended for patients with RA with two of the following three criteria: disease duration &gt;10 years, RF or ACPA positivity and presence of extra-articular manifestations. Crowson suggests multiplying by 1,5 when only one criterion is fulfilled. New targets for LDL-cholesterol have been defined with SCORE equation (&lt;70 mg/dl if SCORE &gt;10%, &lt;100 mg/dl if 5% ≤ SCORE&lt;10%, &lt;115 mg/dl if 1% &lt; SCORE &lt;5%). With the NCEP guidelines, LDL-C goal is &lt;100mg/l when the FRS is &gt;20%, &lt;130 mg/l with &gt;2 and &lt;160 mg/dl with 0-1 major risk factors. A new FRS (FRS global) has been developed for a composite of all cerebrovascular events. <h3>Objectives</h3> The aim of our study was to determine in an early arthritis rheumatoid cohort during 4-year follow-up the proportion of patients in whom the LDL-Cholesterol level was not reached. <h3>Methods</h3> ESPOIR cohort is a nationwide, longitudinal, prospective study of 813 patients with early RA (&lt;6 months) organized by the French Society for Rheumatology in which the patients were assessed once a year for at least 10 years. Only patients with RA according to ACR 1987 criteria aged between 40 and 65 years (age range that allows calculation of SCORE) were included in the study. <h3>Results</h3> See Table 1 <h3>Conclusions</h3> The percentage of patients identified as being at risk ranged significantly depending on the method. The application of a 1.5 multiplier identified more patients especially when only one factor was taken into account (ie RF or ACPA). Although rheumatologists are increasingly aware of the increase in cardiovascular risk, there was no improvement in management of lipid disorders over time. <h3>References</h3> Crowson. Ann Rheum Dis 2011;70:719-21. <h3>Disclosure of Interest</h3> None Declared
P147 CD4+ T CELL EGRESS THROUGH HEPATIC EPITHELIA HAS PROFOUND IMPLICATIONS FOR PHENOTYPE AND FUNCTION
Authors: D. Niesen, E. Liaskou, L. Jeffery, S. Purswani, T. Bruns, D.H. Adams, J.A. McKeating, R. Thimme, Z. Starnataki
Journal: Journal of Hepatology (2014)
TM-08 * DIFFERENTIAL VASCULAR PATTERN OF GLIOMA STEM CELLS
Authors: S. Jalali, G. Zadeh
Journal: Neuro-Oncology (2014)

Treatment of the glioblastoma (GBM) tumors with anti-angiogenic therapies has not significantly improved patients’ survival. The lack of clear response is partly due to the heterogeneous nature of GBMs. Such heterogeneity is evident in different molecular subtypes, in tumor microenvironment including hypoxia and tumor metabolic profiles and also at the level of tumor vascularity, such as microvascular density (MVD) and permeability. While heterogeneity in vasculature results in heterogeneous metabolic profile of the tumor cells, no data is available explaining the effect of metabolic status on tumor vasculature. Deciphering the underlying mechanism of tumor vascular heterogeneity is needed, as it can improve design of targeted therapies. We aimed to establish the differential pattern of tumor vascularity in GBM xenografts of different glioma stem cells (GSCs). Furthermore, we investigated whether GSC tumor vasculature is regulated by changes in glucose metabolism. GSCs were isolated from operative GBM samples and their in-vitro angiogenic profile established using angiogenic arrays and western blot analysis. Glucose metabolism was altered by generating HK2 knockdown of each GSC line and used to generate intracranial xenografts. Tumor growth parameters, overall survival and the in-vivo vascular properties were determined using MRI characteristics and histological analysis. Our results showed that survival rate of the mice and tumor growth pattern varied between different GSCs. MVD and expression of angiogenic factors were different amongst different GSCs and in their matched xenografts. Furthermore, reduced glucose metabolism resulted in reduced MVD and increased animal survival, in GSCs with high MVD. GSC cell lines demonstrate significant variability in their vascular profile. Our data suggests that inhibition of glycolysis may be effective in GBMs with high MVD or perhaps regions of the tumor with highest vascular profile. Effective therapeutic strategies would require individual tumor vascular and metabolic status to be taken into account, prior to any therapeutic intervention.
Discordance Between Appropriate Use Criteria for Nuclear Myocardial Perfusion Imaging From Different Specialty Societies
Authors: David E. Winchester, David Wolinsky, Rebecca J. Beyth, Leslee J. Shaw
Journal: JAMA Cardiology (2016)

Appropriate use criteria (AUC) assist health care professionals in making decisions about procedures and diagnostic testing. In some cases, multiple AUC exist for a single procedure or test. To date, the extent of agreement between multiple AUC has not been evaluated.To measure discordance between the American College of Cardiology Foundation (ACCF) AUC and the American College of Radiology (ACR) Appropriateness Criteria for gauging the appropriateness of nuclear myocardial perfusion imaging.Retrospective cohort study at an academically affiliated Veterans Affairs medical center. Participants were Veteran patients who underwent nuclear myocardial perfusion imaging between December 2010 and July 2011 with rating of appropriateness by the ACCF and ACR criteria. Analysis was performed in March 2015.The primary outcome was the agreement of appropriateness category as measured by κ statistic. The secondary outcome was a comparison of nuclear myocardial perfusion imaging results and frequency of ischemia across appropriateness categories for the 2 rating methods.Of 67 indications in the ACCF AUC, 35 (52.2%) could not be matched to an ACR rating, 18 (26.9%) had the same appropriateness category, and 14 (20.9%) disagreed on appropriateness. The study cohort comprised 592 individuals. Their mean (SD) age was 62.6 (9.4) years, and 570 of 592 (96.2%) were male. When applied to the patient cohort, 111 patients (18.8%) could not be matched to an ACR rating, 349 patients (59.0%) had the same appropriateness category for the ACR and ACCF methods, and 132 patients (22.3%) were discordant. Overall, the agreement of appropriateness between the 2 methods was poor (κ = 0.34, P < .001). Ischemia was rare among patients rated as "inappropriate" by the ACCF AUC (1 of 39 patients [2.6%]), while ischemia was more common among patients rated as "usually not appropriate" by the ACR Appropriateness Criteria (14 of 80 patients [17.5%]).Substantial discordance may exist between methods for assessing the appropriateness of advanced imaging tests. Discordance in methods may translate into differences in clinically relevant outcomes, such as the detection of myocardial ischemia.
Polar Beat: train to your heart's content
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2015)

Both Android and Apple compatible.

Free for the mobile app, although the Polar H6 and H7 sensors cost US$89. Additionally, there are four upgrades users can purchase for between $2.99 and $3.99.

Polar Beat is an exercise-tracking application that provides users with detailed tracking of the duration, distance and intensity of their training sessions. Competing in the same market as Strava and Nike+, Polar Beat provides users with another app-based means of tracking and analysing their workouts. Utilising the built in global positioning system and accelerometry of the mobile devices, the app tracks the users’ speed, distance and route travelled. Although users are not obligated to purchase and wear a heart rate (HR) sensor, the app is designed to track real-time heart rate using the Polar H6 or H7 sensors. The integration of HR will come as no …
Abstract LB-367: New evidence supports the potential use of methotrexate in children with <i>MYCN</i>-amplified neuroblastoma.
Authors: Diana T. Lau, Murray D. Norris, Glenn M. Marshall, Michelle Haber, Lesley J. Ashton
Journal: Cancer Research (2011)

Abstract Background Folate is essential for cell growth and differentiation. Cancer cells frequently up-regulate folate receptors to increase folate uptake to meet their elevated need for nucleotides to support DNA synthesis and growth. SLC19A1 encodes for a major folate or anti-folate transporter and has been reported to be regulated by oncogenic transcription factors. In childhood neuroblastoma, amplification of the MYCN oncogene is a strong prognostic marker for predicting unfavourable outcome. In light of previous findings showing that overexpression of SLC19A1 increases folate influx and methotrexate (MTX) sensitivity, we aimed to investigate the relationship between SLC19A1 expression, MYCN amplification and expression, to determine if this relationship modified MTX sensitivity in neuroblastoma. Methods Expression levels of SLC19A1 and MYCN were examined in 42 neuroblastoma patient samples and in two independent in vitro MYCN functional systems. The impact of MYCN amplification/expression and SLC19A1 expression on MTX sensitivity were evaluated on 13 neuroblastoma cell lines. SLC19A1 G80A polymorphism was also examined to determine its impact on SLC19A1 gene expression and MTX sensitivity. Results Expression levels of SLC19A1 and MYCN were positively correlated in neuroblastoma tumour samples (p=0.0001). Induction of MYCN in vitro increased the mRNA expression levels of SLC19A1 by 12-fold (p=0.0003) while silencing of MYCN reduced the expression levels of SLC19A1 by 7-fold (p=0.0017). Neuroblastoma cell lines with MYCN overexpression or amplification were at least 2000-fold more sensitive to MTX than those without (expression: p=0.0002; amplification: p&amp;lt;0.0001). However, SLC19A1 G80A polymorphism did not appear to impact on SLC19A1 gene expression or MTX sensitivity. Conclusions Our data indicate a potential functional link between MYCN and the regulation of anti-folate uptake. Our findings suggest that MYCN amplification confers MTX sensitivity through the regulation of the folate receptor; SLC19A1. Targeting SLC19A1 mediated anti-folate uptake in patients with MYCN amplification may provide a new therapeutic approach in children with neuroblastoma. 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 LB-367. doi:10.1158/1538-7445.AM2011-LB-367
Esophageal Crohn’s disease
Authors: G.-C. Lou, J.-M. Yang, W. Huang, J. Zhang, B. Zhou
Journal: Endoscopy (2009)

Esophageal involvement in Crohn's disease is uncommon event, especially solitary esophageal Crohn's disease, with an incidence ranging from 0.3 % to 2 % [1] [2] [3]. We report a case of solitary esophageal Crohn's disease.
OP0262-PARE What is the Knowledge Level that Ankylosing Spondylitis Patients Have About their Own Disease?
Authors: J. L. Garrido-Castro, E. Collantes-Estevez, C. Gonzalez-Navas, L. Carmona
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patient's knowledge about his or her own disease is critical for an acceptable management and improved quality of life. Aspects such as symptoms, treatment, diagnosis, etc. should be known to all patients. In ankylosing spondylitis (AS), ASAS/Eular recommendations for the management of the disease recognize the need to educate the patient on their disease; but how knowledgeable are patients and their families about AS?. <h3>Objectives</h3> To assess patients' and families' current level of knowledge about AS and to analyse basic predictors of educational level. <h3>Methods</h3> A multiple-choice test with 10 questions about different topics related with AS, plus about other diseases and general health, was developed by rheumatology teachers and patients. It was agreed that the answer to these questions should be known to all the patients. The survey was placed at the web-site of a patients' AS association in Cordoba, Spain (ACEADE), with links to other related websites. Questions about educational level, family history of AS, etc. were added to analyse the association of knowledge level and specific variables. <h3>Results</h3> 146 subjects participated in the survey (133 AS patients and 13 family members). Mean score of participants on AS knowledge was 6.82 over 10 and 4.45 over 10 in other diseases. 37.0% of participants demonstrated to have a high level of knowledge about AS (score &gt; 8), compared to 2.1% with this level about other diseases. A disturbing very low knowledge level (&lt; 5) was present in 13.5% of participants. The graphic shows the general scores according to the studied variables. Significant differences in knowledge (p&lt;0.05) were found only between those who belonged to patients' associations and those who did not. <h3>Image/graph</h3> <h3>Conclusions</h3> Patients' and families' knowledge about AS is fundamental. According to our results, knowledge level is in general acceptable; although in a significant proportion of cases it is too low. Our study underscores the important role of patients' associations in education on disease. <h3>Acknowledgements</h3> The authors would like to thank LIRE and CEDADE, patients' associations, their colaboration. <h3>Disclosure of Interest</h3> None Declared
TCT-752 Asian Comparative Outcomes of Balloon-Expandable versus Self-expandable valves for Transcatheter Aortic Valve Implantation
Authors: Sung-Han Yoon, Jung-Min Ahn, Michael Kang-Yin Lee, Edgar L. Tay, Young-Hak Kim, Cheol Whan Lee, Jong-Young Lee, Dong Hyun Yang, Joon-Won Kang, Hyo In Choi, Jae Hyung Roh, Pil Hyung Lee, Mineok Chang, Hyun Woo Park, Soo-Jin Kang, Duk-Woo Park, Seung-Whan Lee, Jong-Min Song, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2014)
SC-01 * HnRNPA1 PROTEIN DEREGULATES Baf45d mRNA SPLICING IN GLIOMA: FUNCTION AND MECHANISM
Authors: G. Aldave-Orzaiz, M. Gonzalez-Huarriz, E. Xipell, F. Pastor, R. Verhaak, A. Ayuso, R. Diez-Valle, S. Tejada-Solis, M. M. Alonso
Journal: Neuro-Oncology (2014)

Changes in splicing have been implicated in numerous pathologies including cancer. Previously, our group identified Baf45d as aberrantly spliced in GBM using paired normal looking/GBM samples. Baf45d is part of the SWI/SNF complex and plays a key role in the development of the CNS. The objective of this work was to elucidate the function of Baf45d tumoral-spliced form (Baf45d-T) and to understand the mechanism underlying its aberrant regulation. Overall Baf45d mRNA levels (all isoforms) are unchanged when we compare normal brain with low grade astrocytomas and GBM. However, Baf45d-T is overexpressed meanwhile Baf45d normal isoform (Baf45d-N) is significantly downregulated in GBM. Baf45d-T loses exon 7, leading to the formation of a zinc finger domain which increases the DNA binding. TCGA data support our results demonstrating the loss of exon 7 in 166 GBM. The inhibition of Baf45d-T in GBM cells resulted in a reduction in proliferation and in morphology and expression changes towards a more differentiated phenotype. Interestingly, Baf45d-T was the predominant transcript in early postnatal murine neural precursors and its expression disappeared as these cells were instructed towards neurons. In vivo studies, using nude mice bearing intracranial U87-MG cells overexpressing Baf45d-N resulted in a significant increase in overall survival. Analyses of Baf45d sequence revealed several binding sites for HnRNPA1 (an RNA protein that participates in splicing and is overexpress in GBM) flanking exons 6, 6a, 7 and 8. Inhibition of HnRNPA1 in U87 MG cells lead to an increase of Baf45d-N and a reduction of Baf45d-T. Moreover, RIP assays demonstrated the binding of HnRNPA1 to Baf45d mRNA. Our results suggest that the aberrant splicing of Baf45d in GBM could participate in the malignant phenotype of these tumors and define a pathway that regulates an alternative splicing event required for the maintenance of an undifferentiated state in tumor cells.
NON-INVASIVE IMAGING TO IDENTIFY SUSCEPTIBILITY FOR VENTRICULAR ARRHYTHMIAS IN ISCHEMIC CARDIOMYOPATHY
Authors: Mischa T. Rijnierse, Cornelis P. Allaart, Stefan de Haan, Hendrik Harms, Marc Huisman, Aernout Beek, Adriaan Lammertsma, Albert van Rossum, Paul Knaapen
Journal: Journal of the American College of Cardiology (2016)
Abstract 2595: KML001 displays vascular-disrupting properties and irinotecan-combined antitumor activities against a murine tumor model
Authors: Young Joo Min, Ho Yong Lee, Chang Hoon Moon, Seung Joo Cha, Hee-Soon Lee, Hee Jeong Cha
Journal: Cancer Research (2011)

Abstract Purpose: KML001 (sodium metaarsenite) is an orally available arsenic compound that has entered phase II clinical trials in solid tumors. The aim of this study is to assess vascular-disrupting properties of KML001 and to investigate whether KML001 as VDA (vascular-disrupting agent) augments anti-tumor effects of irinotecan in a murine model of colon cancer. Experimental Design: Female BALBc mice bearing subcutaneos CT26 colon carcinoma cells were injected intraperitoneally with KML001(10 mg/kg) or irinotecan alone, or coadministered weekly for 4 weeks. Moreover, we assessed cytoskeletal changes of HUVEC cells when treated with KML001. Results: We observed massive necrosis in the central part of the tumor by 24 h after treated with KML001 alone and the regrowth was seen from the periphery of the tumor after 2 days. Otherwise, we observed the significant tumor growth delay when KML001 was administered either 24 hr or 72hr after irinotecan. In addition, we found that KML001 degraded tubulin in HUVEC cells, which might be related with vascular disrupting properties of KML001. Evidence of proteosome-mediated degradation was obtained by demonstrating that adding a proteosome inhibitor. Conclusions: These results suggest that KML001 is a novel VDA, which can increase anti-tumor activities of irinotecan. 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 2595. doi:10.1158/1538-7445.AM2011-2595