tbuckley/cabot-search huggingface dataset:
Abstract 1400: Inhibition of cell migration by the synthetic triterpenoid acetylenic tricyclic bis-(cyano enone)
Authors: Eddie Chan, John Di Guglielmo
Journal: Cancer Research (2011)

Abstract Triterpenoids are a family of naturally occurring compounds that have multiple anti-tumorigenic effects, including the ability to induce cell differentiation, apoptosis and inhibit proliferation. Research in our lab has demonstrated that a synthetically derived 5 ring triterpenoid, 2-cyano-3, 12-dioxooleana-1,9-dien-28-oic acid-imidazolide (CDDO-Im), inhibits cell migration (To et al., 2008, J. Biol. Chem. 283:11700), which is essential in numerous physiological processes including tumor metastasis. Recently, a smaller 3 ring compound containing the same active functional groups as CDDO-Im has been derived; acetylenic tricyclic bis-(cyano enone) [(+/-)-(4aa,8aa,10ab)-1,2,4a,6,8a,9,10,10a-octahydro-8a-ethynyl-1,1,4a-trimethyl-2,6 dioxophenanthrene-3,7-dicarbonitrile] (TBE-31). Here we examined the effect of TBE-31 on cell migration. Using scratch assays with Rat2 fibroblasts we demonstrated that concentrations of TBE-31 above 0.75 µM were effective in inhibiting fibroblast migration. To elucidate the mechanism(s) for this inhibition we examined different components of the cytoskeleton and the polarity complex, which are both crucial for cell migration. To examine cell polarity, we used immunofluorescence microscopy to assess the localization of two proteins involved in the polarization of migrating cells, IQGAP1 and RAC1. Similar to CDDO-Im, TBE-31 was observed to reduce the elongation and polarity of cells, however unlike CDDO-Im, IQGAP1 and RAC1 in TBE-31 treated cells were localized in punctate fashion around the cell perimeter instead of at the leading edge. Using immunofluorescence imaging, the cytoskeleton of Mv1Lu mink lung cells or COS7 cells treated with TBE-31 were analyzed. The microtubule network of treated cells displayed a unique cross-hatched phenotype and were resistant to nocodazole depolymerization. In addition, the intermediate filament cytoskeleton was observed to retract towards the nucleus. Lastly, in vitro actin polymerization assays revealed that TBE-31 inhibits linear but not branched actin polymerization. We conclude that TBE-31 is an effective inhibitor of cell migration and further research will shed light on the mechanisms that TBE-31 uses to modulate the cell migration machinery. 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 1400. doi:10.1158/1538-7445.AM2011-1400
Screening of esophageal varices by esophageal capsule endoscopy: results of a French multicenter prospective study
Authors: Sylvie Sacher-Huvelin, Paul Calès, Christophe Bureau, Dominique Valla, Jean Vinel, Clotilde Duburque, Alain Attar, Isabelle Archambeaud, Robert Benamouzig, Marianne Gaudric, Dominique Luet, Patrice Couzigou, Lucie Planche, Jean Galmiche, Emmanuel Coron
Journal: Endoscopy (2015)

<b>Background and study aim: </b>Esophageal video capsule endoscopy (ECE) is a new technique that allows examination of the esophagus using a noninvasive approach. The aim of this study was to compare ECE with esophagogastroduodenoscopy (EGD) for the diagnosis of esophageal varices in patients with cirrhosis. <b>Patients and methods:</b> A total of 330 patients with cirrhosis and with no known esophageal varices were prospectively enrolled. Patients underwent ECE first, followed by EGD (gold standard). The endoscopists who performed EGD were blind to the ECE result. Patient satisfaction was assessed using a visual analog scale (maximum score 100). <b>Results</b>: A total of 30 patients were excluded from the analysis because they did not undergo any endoscopic examinations. Patients (mean age 56 years; 216 male) had mainly alcoholic (45 %) or viral (27 %) cirrhosis. The diagnostic indices of ECE to diagnose and correctly stage esophageal varices were: sensitivity 76 % and 64 %, specificity 91 % and 93 %, positive predictive value 88 % and 88 %, and negative predictive value 81 % and 78 %, respectively. ECE patient satisfaction scored significantly higher than EGD (87 ± 22 vs. 58 ± 35; <i>P</i> < 0.0001). <b>Conclusions: </b>ECE was well tolerated and safe in patients with liver cirrhosis and suspicion of portal hypertension. The sensitivity of ECE is not currently sufficient to replace EGD as a first exploration in these patients. However, due to its excellent specificity and positive predictive value, ECE may have a role in cases of refusal or contraindication to EGD. ECE might also improve compliance to endoscopic follow-up and aid important therapeutic decision making in the prophylaxis of bleeding. Trial registration: EudraCT (ID RCB 2009-A00532-55) and ClinicalTrials.gov (NCT00941421).
AB1174-HPR Effects of Disease Activity on Hand Functions in Rheumatoid Arthritis
Authors: Z. Tuna, D. Onbulak, D. Oskay, S.M. Günay, R. Mercan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease with exacerbation and remission periods. Patients tend to limit their physical activity levels further during the exacerbations in addition to already existing physical inactivity due to the chronic disease course. Such a decrease in physical activity results in impairments in activities of daily life requiring musculoskeletal structures especially the hand. <h3>Objectives</h3> The aim of this study is to evaluate the relationship between the disease activity and hand functional level. <h3>Methods</h3> Patients (30-60 years) with RA from both inpatient and outpatient departments participated in the study. Disease activity was determined with Disease Activity Score-28 (DAS-28) and functional level of hand was assessed by grip and pinch (lateral, bipod, tripod) strength measurements and Nine-Hole Peg Test. All participants completed Michigan Hand Outcome Questionnaire in order to determine the disability level of hand. <h3>Results</h3> Fifty patients (29 inpatients and 21 age-matched outpatients) participated in the study. Comparison of the two groups showed that DAS-28 scores were significantly different (p&lt;0,05). DAS-28 scores were significantly inversely correlated to all three pinch strenghts, Nine-Hole Peg Test and Michigan scores (p&lt;0,05). Intra-group correlations showed no relationship between DAS-28 scores and hand functions in the outpatient group (p&gt;0,05); however, inpatient group showed a significant correlation between the disease activity and hand functional tests (p&lt;0,05). <h3>Conclusions</h3> Our results showed that disease activity is in an inverse relationship with the functional level of hand in patients with RA. Additionally, that relationship still exists in the inpatient group, indicating the increase in disease activity results in more impairment of hand despite the outpatient group showed no relationship between the outcomes. Therefore, hand therapy should be established as a crucial part of the treatment of RA even in the flaring period of the disease. <h3>References</h3> Arreguín Reyes R, Lόpez Lόpez CO, Alvarez Hernández E, Medrano Ramírez G, Montes Castillo Mde L, Vázquez-Mellado Evaluation of hand function in rheumatic disease. Validation and usefulness of the Spanish version AUSCAN, m-SACRAH and Cochin questionnaires.J.Reumatol Clin. 2012 Sep-Oct;8(5):250-4. Epub 2012 May 17. O9Connor D, Kortman B, Smith A, Ahern M, Smith M, Krishnan J.J Correlation between objective and subjective measures of hand function in patients with rheumatoid arthritis.Hand Ther. 1999 Oct-Dec;12(4):323-9. Öksüz Ç, Akel BS, Oskay D, Leblebicioglu G, Hayran KM. Cross-Cultural Adaptation, Validation, and Reliability Process of the Michigan Hand Outcomes Questionnaire in a Turkish Population J Hand Surg 2011;36A:486–492. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3115
CARDIAC FATIGUE, BIOMARKERS AND PERFORMANCE OF RECREATIONAL CYCLISTS ENGAGED IN LOW INTENSITY, HIGH VOLUME ENDURANCE EXERCISE
Authors: Steen Carstensen, Christopher Voigt Carstensen, Frederik Voigt Carstensen, Nasim Samandari, Jacob Marott, Lars Odum, Lars Juel Andersen
Journal: Journal of the American College of Cardiology (2016)
Persistent Immune Responses after Ebola Virus Infection
Authors: Ariel Sobarzo, David E. Ochayon, Julius J. Lutwama, Steven Balinandi, Ofer Guttman, Robert S. Marks, Ana I. Kuehne, John M. Dye, Victoria Yavelsky, Eli C. Lewis, Leslie Lobel
Journal: New England Journal of Medicine (2013)

More than a decade after infection with the Gulu strain of Sudan Ebola virus, persons in Uganda were found to have persistent immune responses.
123I-Ioflupane SPECT Findings of Pantothenate Kinase–Associated Neurodegeneration
Authors: Arnold Kang, Satoshi Minoshima
Journal: Clinical Nuclear Medicine (2014)

We present a case of a 72-year-old man with a 9-year history of memory decline and 7-year history of parkinsonian symptoms. An MRI demonstrated an "eye-of-the-tiger" sign in the basal ganglia, suggestive of pantothenate kinase-associated neurodegeneration (formerly known as Hallervorden-Spatz syndrome). An 123I-ioflupane SPECT scan demonstrated absence of radiotracer uptake in the caudate nuclei and putamina. Genetic testing confirmed a single-point mutation in the PANK2 gene, consistent with pantothenate kinase-associated neurodegeneration.
Supreme Court to decide whether payments by patent holders to delay production of generics are anticompetitive
Authors: B. Roehr
Journal: BMJ (2012)

The US Supreme Court has agreed to review the legality of so called pay for delay agreements where the owner of a branded drug pays another drug company not to bring a generic version of that drug to market for an agreed time period.

Such agreements are one tool used by patent holders to effectively extend the period of exclusivity of their drug on the market. They allow the patent holders to charge higher prices than if a generic equivalent were also available. Legal challenges to the practice have been going through the courts for a number of years, with varying outcomes.

Some generic drug manufacturers have challenged a patent, and often the company holding …
OC-034 Salvage of central venous catheters in HPN catheter-related blood stream infections is safe and effective: 18 years experience from a national centre
Authors: M Dibb, G Carlson, A Abraham, J Shaffer, A Teubner, S Lal
Journal: Gut (2012)

<h3>Introduction</h3> Catheter-related blood stream infections (CRBSI) are a serious and life-threatening complication in the provision of HPN. European guidelines recommend antibiotic salvage of central venous catheters (CVCs) with CRBSI, wherever possible, to minimise repeated catheter replacement and preserve venous access, but this is based on limited reported evidence.<sup>1</sup> <h3>Methods</h3> Data were analysed from a prospectively-maintained register of all confirmed CRBSIs occurring in patients on HPN since January 1993 to December 2011, managed in a National Intestinal Failure Unit (IFU). Diagnosis of a CRBSI was based on quantitative and qualitative assessment of central and peripheral blood cultures and pour plates. Treatment was commenced according a standardised protocol involving antibiotic and urokinase CVC locks and systemic antibiotic administration. <h3>Results</h3> A total of 299 CRBSIs occurred in 138 patients (66 single CRBSI, 72 multiple CRBSI) with 377 patients having no catheter infections. The mean number of catheter days prior to developing an infection was 712 (range 5–6128). This represents an overall rate of infection in all patients of 0.39 per 1000 catheter days. A single microorganism caused 87.9% of infections, most commonly coagulase negative staphylococcus (CNS; 49.5% cases). Overall catheter salvage was achieved in 62.2% (intention to treat) of all patients presenting with CRBSIs (Coagulase negative staphylococcus 70.5% (105/149), MRSA 36.4% (4/11), polymicrobial infections 58.3% (21/36), other <i>Staphylococcus aureus</i> 48.3% (14/29) and miscellaneous 56.8% (42/74)). Line salvage was not attempted in 46 patients because of life-threatening sepsis (n=18), fungal line infection (n=7), mechanical catheter problems (eg, co-existing line fracture; n=18) and tunnel line infection (n=3). The catheter was removed in 37.7% (95/299) of cases. There were five deaths in patients admitted to the IFU for management of the CRBSI. <h3>Conclusion</h3> This is the largest reported series of catheter salvage in CRBSIs and demonstrates that catheter salvage according to a standardised protocol is a safe and effective strategy to preserve essential venous access in patients dependent on HPN. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Pittiruti M</b>, Hamilton H, Biffi R, <i>et al.</i> ESPEN guidelines on parenteral nutrition: central venous catheters (access, care, diagnosis, and therapy of complications). <i>Clin Nutr</i> 2009;<b>28</b>:365–77.
Abstract 243: Functional dissection of hoxD genes in regulation of neuroblastoma cell proliferation and differentiation
Authors: Yunhong Zha, Emily Ding, Ling Mao, Han-fei Ding
Journal: Cancer Research (2011)

Abstract Neuroblastoma is a common malignant tumor in children, arising in the sympathetic nervous system. The tumor cell differentiation state influences clinical outcome, and induction of differentiation has been considered as a promising therapeutic strategy for neuroblastoma. Retinoid acid (RA) is an effective inducer of neuroblastoma cell differentiation and has been used in clinic for treatment of high-risk neuroblastomas. However, resistance to RA presents a major obstacle to successful RA-based therapy. Therefore, identification of target genes that mediate the anti-neoplastic activity of RA is of paramout importance, as targeting these genes offers opportunities to bypass resistance to RA. A variety of experimental evidence has linked RA action to the activation of HOX genes, which function as master regulators of development and cell fate specification. Particularly, it has been shown that RA induces several HOXD genes in neuroblastoma cells including HOXD1, D8 and D9. Our microarray analysis confirmed the predominant upregulation of HOXD genes in the human neuroblastoma cell line BE(2)-C cells following RA treatment. To investigate the functional significance of the RA-induced upregulation of HOXD genes, we conducted a comprehensive functional analysis of HOXD genes in regulation of neuroblastoma cell proliferation and differentiation. The HOXD cluster contains 9 genes (HOXD1, D3, D4, and D9-13) that are positioned from 3’ to 5’ within the cluster, with HOXD1 at the 3’ end and HOXD13 the 5’ end. We established BE(2)-C-derived cell lines with inducible expression of individual HOXD genes. Induction of HOXD1, D12 or D13 had no significant effect on BE(2)-C cell growth and differentiation. By contrast, individual induction of other HOXD genes caused G1 arrest, which was associated with downregulation of cyclins and CDKs required for cell cycle progression through the S, G2 and M phases. Ectopic expression of HOXD3, D4, D8, D9, D10 or D11 also induced morphologic changes characteristic of neuronal differentiation. Interestingly, HOXD8 and D9 appeared to be most potent in the induction of G1 arrest and differentiation. These findings suggest that HOXD genes positioned in the middle of the cluster have higher differentiation-inducing activity compared to those positioned more 5’ and 3’ in the cluster. Thus, pharmacological activation of HOXD8 and HOXD9 may represent a therapeutic strategy for RA-resistant neuroblastomas. 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 243. doi:10.1158/1538-7445.AM2011-243
ALDH1 is a useful marker of basalness in human breast cancer and its stem/progenitor cells.
Authors: F Jolicoeur, I Garcia de la Fuente, L Gaboury, D Balicki
Journal: Cancer Research (2009)

Abstract Abstract #104 Background: The basal cell subtype is a particularly aggressive form of breast cancer. The molecular mechanisms which underlie the aggressive course of basal cell breast cancer, as well as its corresponding tumor markers are currently under intense study. In addition, there is increasing evidence that cancer stem/progenitor cells are integral to the formation and perpetuation of breast cancer. Together with their progenitors, cancer stem cells may determine the therapeutic outcome and the clinical course of cancer. The first isoform of aldehyde dehydrogenase (ALDH1) has recently been reported to be a marker of breast stem/progenitor cells. Thus, we undertook this study to determine whether the immunohistochemical detection of ALDH1 in fixed breast cancer tissues correlates with selected basal and luminal cell surface markers.&amp;#x2028; Methods: Formalin-fixed, paraffin-embedded specimens were studied in triplicate using tissue microarrays from 57 breast cancer patients. In addition to ALDH1 staining, each of the following markers were studied using immunohistochemistry (IHC) in each sample: ER, PR, HER-2, the basal cell markers EGFR/HER1, CK5, CK14, CK17, SMA, and the luminal cell markers CK19, and EMA.&amp;#x2028; Results: ALDH1 staining was performed using IHC and subsequently evaluated using the Quick score. The Quick score takes into account both the percentage of positive cells, as well as the corresponding staining intensity. Our results suggest that breast cancer samples expressing the triple negative phenotype (ER-, PR-, HER-2 negative) together with one or more basal cell markers (EGFR/HER1,CK5, CK14, CK17, SMA) are associated with an elevated Quick score for ALDH1 staining, when compared with samples lacking the expression of these markers.&amp;#x2028; Conclusions: As it has been demonstrated that IHC detection of ALDH1 detects stem/progenitor cells in fixed breast samples, our results suggest that an elevated Quick score is associated with the enrichment of IHC basal cell markers in these samples. We are currently focusing on a larger number of breast cancer samples so that correlations can be studied as a function of therapeutic outcome and overall survival of breast cancer patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 104.
EFFECTS OF EXTENDED-RELEASE NIACIN ON LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 LEVELS AND CLINICAL OUTCOMES IN PATIENTS WITH ESTABLISHED CARDIOVASCULAR DISEASE AND LOW BASELINE LEVELS OF HDL-CHOLESTEROL: POST HOC ANALYSIS OF THE AIM HIGH TRIAL
Authors: Radmila Lyubarova, Santica Marcovina, Jerome Fleg, Patrice Desvigne Nickens, Alexandru Topliceanu, Yao Yao, Ruth McBride, William Boden
Journal: Journal of the American College of Cardiology (2016)
1095 ROLE OF FXR IN THE ACTIVATION OF HEPATOCYTE CHEMOPROTECTION AND IN THE REFRACTORINESS OF LIVER TUMORS TO CHEMOTHERAPY
Authors: J. Vaquero, O. Briz, E. Herraez, J. Muntane, M.R. Romero, M.A. Serrano, M.J. Monte, J.J.G. Marin
Journal: Journal of Hepatology (2013)
NO TWO SYSTOLES THE SAME: PERSONALIZING TRANSCATHETER HEART VALVE SELECTION FOR TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Lynn Carlyle, Dee Dee Wang, Andrew Taylor, Benjamin Swanson, Janet Wyman, Milan Pantelic, Thomas Song, Marvin Eng, Gaetano Paone, Adam Greenbaum, William O’Neill
Journal: Journal of the American College of Cardiology (2016)
P1-05-03: Relationship between Polycomb Repressive Complex EZH2/CBX7, Large Non-Coding RNA ANRIL and Stem Cells Biomarkers in Triple Negative Breast Carcinomas: Important Role in Carcinogenesis through an Epigenetic Silencing Process and New Clues for Targeted Therapies.
Authors: D Meseure, S Vacher, M Trassard, K Drak-Alsibai, R Le Scodan, C Le Ray, C Regnier, R Lidereau, I Bieche
Journal: Cancer Research (2011)

Abstract Background: Epigenetic deregulation and carcinogenesis are intimately connected and gene silencing is a major consequence of epigenetic modifications. Polycomb group proteins (PcG) play important roles by inhibiting chromatin remodeling and transcription, silencing tumor suppressor genes, regulating stem cells and interconnecting with Wnt/beta-catenin, TGF-beta and Sonic-Hedgehog pathways. EZH2 is a transcriptional repressor and acts mainly as an oncogenic silencer gene involved in cell cycle regulation. Large non coding RNA are major regulators of oncogenic and oncosuppressive pathways at epigenetic, transcriptional and post-transcriptional levels. Recent studies have showed that (i) EZH2 overexpression is associated with cancer progression and aquisition of stem cell properties and (ii) disruption of ANRIL/CBX7 interactions repress the INK4b/ARF/INK4a locus. The aim of the study was to analyze PRC complexes, large non-coding RNA ANRIL and downstream signaling targets in triple negative breast carcinomas (TNC). Design: By using real time quantitative RT-PCR in a series of 432 invasive breast ductal carcinomas (IDC), we quantified gene expression levels of the large non coding RNA ANRIL, PcG (EZH2, CBX7, SUZ12), stem cells markers (ALDH1, CD133, ASCL1) and oncosuppressor genes (p15, p16 and p19). Immunohistochemistry (IHC) was performed using EZH2, CBX7, ALDH1 and b-catenin Abs. We compared mRNA expression levels and IHC intensity score in TNC with non TNC and normal breast parenchyma. Results: EZH2 overexpression was respectively found by RT-PCR and IHC in the TNC subgroup of IDC. We observed variable mRNA expression levels of SUZ12, CBX7, ANRIL, ALDH1, CD133, ASCL1, p15, p16, and p19. IHC showed EZH2 and CBX7 nuclear staining. Mutual positive correlations were found between EZH2, CBX7, ALDH1, ASCL1 and CCND1 (p&amp;lt;10-5). Conclusion: Polycomb EZH2/CBX7 and the large non coding RNA ANRIL are epigenetic transcriptional repressors overexpressed in the TNC subgroup of IDC. Their implication in the process of gene silencing (p16, p15, p19), activation of oncogenic pathways (Wnt, TGFb) and tumor stem cells self-renewal may explain several hallmarks of TNC and open new avenues to target this aggressive subgroup. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-05-03.