tbuckley/cabot-search huggingface dataset:
Abstract A58: Wnt signaling pathway components are associated with telomerase activity in breast cancer
Authors: Imke Listerman, Francesca S. Gazzaniga, Laura M. Heiser, Jason J. Lukas, Ted Goldstein, David Haussler, Joe W. Gray, Elizabeth H. Blackburn
Journal: Cancer Research (2011)

Abstract Telomerase is a ribonucleoprotein complex that adds TTAGGG repeats to telomeres in a highly regulated fashion. Telomerase activity is absent in normal somatic cells, thus limiting their number of cell divisions due to telomere shortening. In contrast, the large majority of tumor cells upregulate telomerase activity, consistent with their ability to maintain stable telomere lengths and to divide indefinitely. Telomerase activity is detectable in over 90% of breast tumors, and it is well established that telomerase overexpression is an important step in the progression of normal epithelium to invasive breast cancer. In addition to telomerase upregulation, deregulation of various signaling pathways promotes tumor progression and metastasis. To better understand in which cellular pathway telomerase and telomeres are involved, we comprehensively quantified telomerase activity and telomere length in a panel of 52 extensively characterized breast cancer cell lines and correlated these metrics with the expression profiles of the cell lines. Across the entire panel of breast cancer cell lines, expression of 530 genes was significantly correlated with telomerase activity (FDR-corrected p-val &amp;lt; 0.2), while expression of 585 genes was significantly correlated with telomere length. Secondary G0-term analysis revealed that telomere length was significantly associated with genes involved in Alzheimer's disease, apoptosis regulation and negative regulation of transcription. Genes significantly correlated with telomerase activity were associated with apoptosis regulation, DNA repair, nucleotide metabolism and Wnt signaling. Several Wnt target genes, including MYC, KLF5, and FGF18 were also correlated with telomerase activity. We also used the network analysis tool PARADIGM (1) to identify cellular pathways associated with telomerase activity and telomere length. Notably, Wnt signaling components were significantly correlated with telomerase activity. Given the recent evidence that the telomerase component TERT can act as a transcriptional modulator of the Wnt/beta-catenin signaling pathway (2), we are currently testing how Wnt signaling is altered due to telomerase perturbation in breast cancer cells. (1) Vaske, C. J. et al. Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM. Bioinformatics 2010; 26:i237–245 (2) Park, J. I. et al. Telomerase modulates Wnt signaling by association with target gene chromatin. Nature 2009; 460:66–72 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A58.
Artificial cognitive systems: Where does argumentation fit in?
Authors: John Fox
Journal: Behavioral and Brain Sciences (2011)

Abstract Mercier and Sperber (M&amp;S) suggest that human reasoning is reflective and has evolved to support social interaction. Cognitive agents benefit from being able to reflect on their beliefs whether they are acting alone or socially. A formal framework for argumentation that has emerged from research on artificial cognitive systems that parallels M&amp;S's proposals may shed light on mental processes that underpin social interactions.
SAT0250 Cardiovascular Risk Predictors under Non-Tnf Biological DMARD Treatment. A 12-Month Longitudinal Study
Authors: S.A. Provan, I.J. Berg, A.G. Semb, A. Mathiessen, H.B. Hammer, T.K. Kvien
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have an increased level of cardiovascular (CV) risk markers. <h3>Objectives</h3> To assess whether treatment with one of three biological DMARDs; Rituximab (Rit), Abatacept (Aba) or Tocilizumab (Toc) can reduce the level of CV risk markers in patients with RA. <h3>Methods</h3> An open, observational, longitudinal study with study visits at baseline, 3, 6, and 12 months. Patients aged 18-80 years, fulfilling the ACR 1987 classification criteria for RA and starting on either Rit, Aba or Toc based on the decision of a rheumatologist, were included. CV risk was assessed by blood pressure and arterial stiffness measurements (pulse wave velocity (PWV) and augmentation index (AIx)). Change in CVD risk markers over 3 months were compared using paired samples bivariate tests. Change over the 12 months follow-up in patients receiving Rit was assessed using mixed models repeated analyses. <h3>Results</h3> 36 patients were included in the study and 4 patients were re-entered into the study after switching to either Toc or Aba prior to the 6 month follow-up. The final number included was 40, 24 patients receiving Rit, 5 Aba and 7 Toc. In the bivariate analyses of paired samples at 3 months DAS28 was significantly improved in the Rit and Toc groups. Only patients receiving Toc had a significant reduction in CRP, ESR and PWV at 3 months (Table 1). Over the 12-month follow-up period patients in the Rit group showed a significant reduction in CRP, DAS28 and PWV (Fig. 1). <h3>Conclusions</h3> Toc and Rit reduce PWV, a marker of CVD risk, in patients with RA. The reduction in PWV was apparent at 3 months for patients taking Toc and at 12 months for patients receiving Rit. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3409
A Metabolic Imaging Severity Rating Scale for the Assessment of Cognitive Impairment
Authors: ANDREW NEWBERG, ADOLFO COTTER, MICHELLE UDESHI, ABASS ALAVI, CHRISTOPHER CLARK
Journal: Clinical Nuclear Medicine (2003)

Purpose: This study was designed to validate a simple scoring system for evaluating fluorodeoxyglucose (FDG) positron emission tomographic (PET) scans that can be used routinely in patients undergoing the clinical assessment of cognitive impairment. Methods: The FDG-PET scans of 106 patients with cognitive impairment (65 with Alzheimer disease, 16 with frontal lobe dementia, and 25 atypical cases) were acquired using the PENN-PET scanner 40 minutes after the intravenous administration of 8 mCi FDG. Metabolic activity in various anatomic structures of the brain was scored using the following qualitative scale: 4 = normal; 3 = mildly decreased; 2 = moderately decreased; 1 = severely decreased; and 0 = no activity. Regions of interest were also placed over these regions to obtain a quantitative value. Two distinct scores were obtained. Values for visual and sensorimotor cortices, thalami, basal ganglia, and cerebellum comprised score I. Score II consisted of the values for the frontal, temporal, and parietal cortices. The qualitative metabolic imaging severity rating scale (MISRS) was compared with a quantitative MISRS (obtained from the region-of-interest analysis of the same structures). The MISRS was then compared with the results from the Mini-Mental Status Examination (MMSE) and the Dementia Severity Rating Score (DSRS). Results: In all patients, the qualitative MISRS scores correlated significantly with the quantitative MISRS (r = 0.73,P< 0.0001). In all patients with cognitive impairment, the qualitative and quantitative MISRS scores correlated significantly with the DSRS and the MMSE (P< 0.001). In patients with Alzheimer disease, the qualitative and quantitative MISRS significantly correlated with the DSRS and MMSE. Conclusion: A simple and practical rating scale can be used to assess the severity of cognitive impairment in patients with different types of dementing illnesses.
Incidental Finding of a Urinoma on Bone Scintigraphy
Authors: SHIH-CHUAN TSAI, CHIA-HUNG KAO, WAN-YU LIN, SHYH-JEN WANG
Journal: Clinical Nuclear Medicine (1997)

Tc-99m MDP whole-body bone imaging in a patient with carcinoma of the lung showed an area suspicious for urine leakage from the left kidney or ureter into the scrotum Tc-99m DTPA renal imaging and a CT scan supported the diagnosis of urinoma.
Increased Prognostic Value of Combined Myocardial Perfusion SPECT Imaging and the Quantification of Lung Tl-201 Uptake
Authors: Milan Kamínek, Miroslav Myslivecek, Marcela Skvarilová, Václav Husák, Pavel Koranda, Iva Metelková, Otto Lang
Journal: Clinical Nuclear Medicine (2002)

The authors wanted to identify those patients assessed by exercise SPECT in whom the quantification of lung Tl-201 uptake helps to evaluate disease prognosis.One hundred forty-nine patients (114 men, 35 women; 74 after myocardial infarction [MI]; mean age, 54 +/- 9 years) underwent exercise Tl-201 SPECT. The SPECT patterns were divided into normal (n = 45), fixed defects (n = 29), and inducible ischemia (n = 75). Anterior planar imaging was performed before SPECT acquisition to calculate the lung-to-heart ratio (L:H).During an average follow-up of 20 +/- 9 months, eight patients had died of cardiac causes and 13 patients experienced nonfatal MIs. Among the 45 patients with normal perfusion, no cardiac event was observed and the L:H ratio was not helpful for risk stratification. In 29 patients with fixed defects, four cardiac deaths occurred (all in patients with L:H ratios >0.5; annual event rate, 21.1% for L:H ratios >0.5 compared with 0% for L:H ratios <0.5; chi-square = 4.07, P < 0.05). Among the 75 patients with ischemia, 4 died and 13 had nonfatal MIs (annual event rate, 15.4% for L:H ratios >0.5 compared with 13% for L:H ratios <0.5; P = NS).These findings suggest a benign prognosis in patients with normal SPECT (regardless of the L:H ratio). Conversely, all patients with ischemia are at high risk for future cardiac events. Quantification of the Tl-201 lung uptake seems to be valuable in evaluations of disease prognosis, especially in patients with fixed defects.
Randomized Trial of Diet and Gastroplasty Compared with Diet Alone in Morbid Obesity
Authors: Teis Andersen, Ole G. Backer, Knud H. Stokholm, Flemming Quaade
Journal: New England Journal of Medicine (1984)

We compared the weight-reducing effect of diet and gastroplasty with that of diet alone in a randomized trial in 60 morbidly obese patients followed for two years. Initial median body weight was 120 kg in patients randomly assigned to gastroplasty plus diet and 115 kg in those assigned to diet alone. Maximum weight losses did not differ significantly between the groups (26.1 kg in the gastroplasty group and 22.0 kg in the group treated with diet alone, P>0.05). The risk of a Type II error with a true difference larger than 9.5 kg was less than 5 per cent. However, the group treated with diet alone regained significantly more weight after maximum weight loss had been achieved, so that the gastroplasty group had a more favorable net outcome at two years (P<0.05). (N Engl J Med 1984; 310:352–6.)
DEGREE OF ISCHEMIA REDUCTION DURING PERCUTANEOUS CORONARY INTERVENTION IS A STRONG PREDICTOR OF LONG TERM ADVERSE EVENTS: MAKING THE CASE FOR ROUTINE POST PERCUTANEOUS CORONARY INTERVENTION FRACTIONAL FLOW RESERVE ASSESSMENT
Authors: Shiv Kumar Agarwal, Yalcin Hacioglu, Srikanth Kasula, Ernesto Ruiz-Rodriguez, Naga Venkata Pothineni, Barry Uretsky, Abdul Hakeem
Journal: Journal of the American College of Cardiology (2015)
HALLAZGOS PATOLÓGICOS EN MODELO ANIMAL PORCINO DE OBSTRUCCIÓN BILIAR MEDIANTE CLIP OTSC®
Authors: Á Terán Lantarón, B Castro Senosiain, PL Fernández Gil, P Iruzubieta Coz, D Hernández Amunarriz, JC González Cueli, JC Manuel-Palazuelos, J De La Peña García
Journal: Endoscopy (2013)

Introducción: Los clips OTSC® tienen indicación para hemostasia y cierre de perforaciones, ofreciendo buenos resultados para su control inmediato. En modelos animales se han utilizado sobre la papila duodenal para provocar obstrucción biliar. A diferencia de otros clips endoscópicos, y debido a su diseño, pueden permanecer largo tiempo anclados a la pared gastrointestinal. Objetivo: Describir los hallazgos patológicos secundarios a la colocación de clip OTSC® en papila duodenal de modelo animal porcino. Material y Método: Estudio descriptivo de los hallazgos patológicos en cerdos preparados con clip OTSC® sobre papila duodenal para un curso de entrenamiento práctico en terapéutica guiada por ecoendoscopia. Tras la sesión de trabajo los animales fueron sacrificados, con posterior estudio necrópsico. Resultados: Se utilizaron 12 cerdos hembras de raza Large White de 3 meses de edad y 35 – 40 kg de peso. Los clips OTSC® fueron colocados 8 – 10 días antes de la fecha intervención. Dos animales no sobrevivieron, falleciendo al 5 ° y 7 ° día. Uno de los supervivientes no presentaba el clip en el momento de la exploración (8 ° día). Los 9 restantes tenían una clara dilatación de vía biliar extrahepática, aunque sólo 4 presentaban ictericia. Un animal presentaba datos de colecistitis aguda, otro animal un ulcus extenso en curvadura menor gástrica y un ulcus profundo en duodeno, y otro animal una combinación de ambos casos anteriores. Conclusiones: Estos resultados deben tenerse en cuenta a la hora de planificar la utilización de animales como modelo de obstrucción biliar, siendo 7 días un tiempo probablemente suficiente para dilatar la vía biliar, incluso sin ictericia, y con menores efectos adversos. Aunque la mayoría de hallazgos se relacionan con la patología biliar provocada, deben tenerse en cuenta los hallazgos ulcerosos y la inflamación periduodenal objetivada en 2 casos y atribuible al clip OTSC® por posible compresión vascular, decúbito, isquemia y/o perforación.
The IL23R R381Q gene variant protects against psoriasis by impairing IL-23-induced STAT-3 phosphorylation and IL-17A production in human Th17 cells
Authors: Paola Di Meglio, A. Di Cesare, Ute Laggner, Chung-Ching Chu, Luca Napolitano, Federica Villanova, I. Tosi, Francesca Capon, Richard Trembath, K. Peris, Frank Nestle
Journal: British Journal of Dermatology (2011)
Abstract C57: Role of aneuploidy in cellular adaptation, drug resistance, and cancer
Authors: Giulia Rancati, Norman Pavelka, Jin Zhu, Rong Li
Journal: Cancer Research (2011)

Abstract Cancer is a multistep Darwinian process whereby mutant cells able to escape internal, environmental, or drug-mediated proliferative roadblocks expand and outcompete less-fit cells. Mutations characterizing this somatic evolution range from single-point mutations to whole-chromosome aneuploidy. Although sequence mutations clearly play a role in cancer evolution, the role of aneuploidy in cancer is far less clear. Previously, we investigated how yeast cells can adapt in response to a proliferative roadblock and the role of aneuploidy during this process. We showed that aneuploidy could provide a source of heritable variation driving the emergence of large phenotypic changes that can be adaptive under strong selective conditions. Recently, we provided evidence that aneuploidy is sufficient to generate global changes at the proteome level and to provide phenotypic variation. Taken together, our data suggest that aneuploidy might thus be beneficial to cancer cells that are trying to escape growth inhibitory signals and chemotherapy treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C57.
Metastatic Pulmonary Calcification
Authors: Sophie Timmins, Michael Hibbert
Journal: New England Journal of Medicine (2010)

A chest radiograph of a 47-year-old woman with a dry cough and mild exertional dyspnea showed poorly defined bilateral nodular opacities in the superior lung fields (Panel A). The patient had undergone renal transplantation at 23 years of age for an unspecified glomerulonephritis. She had no history of exposure to tobacco or occupational aerosols. An axial computed tomographic scan of the chest showed centrilobular ground-glass nodules and heterogeneous attenuation, features that were suggestive of calcium deposition (Panel B). Results of serum tests revealed increased serum creatinine (285 μmol per liter [3.2 mg per deciliter]), a normal calcium level (2.3 mmol . . .
The Cardiovascular Perils of Cancer Survivorship
Authors: Javid Moslehi
Journal: New England Journal of Medicine (2013)

Since 1990, breast cancer mortality has decreased yearly in developed nations. In 2012, there were an estimated 3 million survivors of breast cancer in the United States alone.1 This decrease in mortality can be partly attributed to effective treatment strategies developed through collaborations among breast surgeons and medical and radiation oncologists. Radiation therapy has evolved as a critical component of treatment for women who have undergone breast-conservation surgery and for those with a high risk of recurrence who have undergone mastectomy.2 Older radiation techniques for breast cancer are associated with subsequent cardiac disease. Less clear is the cardiac risk associated . . .
Abstract 5425: Characterization of synergistic antiproliferative effects of combined γ-tocotrienol and celecoxib treatment on neoplastic mouse mammary epithelial cells in vitro
Authors: Amit B. Shirode, Paul W. Sylvester
Journal: Cancer Research (2010)

Abstract In the present study, synergistic antiproliferative effects of combined treatment of γ-tocotrienol and celecoxib on +SA mouse mammary epithelial cells were evaluated and characterized for their mechanism(s) of action. Earlier studies have shown that these effects are mediated partly by inhibition of PGE2, which is a direct indicator of COX-2 activity in cells. Since 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes NAD+-dependent oxidation of 15(S)-hydroxyl group of prostaglandins and has been considered a key enzyme in biological inactivation of prostaglandins, the effects of these drugs on intracellular levels of 15-PGDH were assessed. Consistent with earlier findings, western blot analysis showed increased levels of 15-PGDH by individual treatment of effective doses of both γ-tocotrienol (3.5 μM) and celecoxib (20 μM). Combined treatment with subeffective doses of γ-tocotrienol (0.25 μM) and celecoxib (2.5 μM) showed increased levels of 15-PGDH as compared to the same individual doses when treated alone. These studies indicate that the antiproliferative effects are mediated by inducing the expression of 15-PGDH, which leads to enhanced inactivation of PGE2. Similar to earlier studies which showed that these effects were associated with a suppression of Akt and NFκB activity, the present studies showed that treatment with 3.5 μM γ-tocotrienol alone induced a relatively large decrease in phospho-PDK-1 and phospho-Akt levels, but had no effect on PI3K p85, PTEN and phospho-PTEN levels. In contrast, treatment with 20 μM celecoxib alone was associated with a relatively large decrease in PI3K p85 levels. Combined treatment with subeffective doses of γ-tocotrienol and celecoxib caused a large decrease in PI3K, phospho-PDK-1, phospho-Akt and phospho-GSK-3β levels as compared to vehicle treated controls. In addition, a large decrease in phospho-IKK-α/β, phospho-IκB-α, and phospho-NFκB levels was observed in the combination treatment group relative to the same subeffective doses when given alone. In conclusion, these studies show that synergistic antiproliferative effects of combination treatment of γ-tocotrienol and celecoxib are associated with two different mechanisms; 1) a COX-2-dependent mechanism of induction of 15-PGDH leading to enhanced inactivation of PGE2; and 2) a COX-2-independent mechanism of attenuation of EGF-dependent PI3K/PDK-1/Akt and NFκB mitogenic signaling pathways. Further studies are required to evaluate the role of prostaglandin and EGF receptors in mediating these two independent mechanisms. This study was supported by grants from NIH (CA86833) and First Tech International Ltd. 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 5425.
Abnormalities of 53BP1 in Basal-Like Breast Cancer.
Authors: A. Aly, Q. Yang, E. Bilal, M. Yao, G. Bhanot, D. Toppmeyer, B. Haffty, S. Ganesan
Journal: Cancer Research (2009)

Abstract Background: Abnormalities in the DNA repair mechanism have been proposed to play a central role in the development of breast cancers. However the specific mechanism underlying DNA repair defects in sporadic breast cancer are mostly unknown. As 53BP1 plays a critical role in DNA repair response and has been identified as a potential tumor suppressor, its expression in basal-like breast cancer cell lines and clinical samples was investigated.Experimental Design: mRNA expression of 53BP1 was investigated in publicly available gene expression data sets. Protein expression of 53BP1 was evaluated in a large set of clinically annotated breast cancer specimens by immunohistochemistry. Analysis of 53BP1 and related proteins was performed in a set of human and mouse breast cancer cell lines.Results: Gene expression analysis demonstrated that a subset of basal-like breast cancer had decreased expression of 53BP1. Analysis of over 400 breast cancers in a tissue microarray showed that loss of 53BP1 staining was almost exclusively found in tumors that lacked ER, PR and HER2 expression; this "triple-negative" phenotype is characteristic of BLC. Approximately 42% of "triple-negative" breast cancers have abnormally low levels of 53BP1, while &amp;lt;2% of tumor that express either ER or HER2 lack 53BP1 expression. Tumors that have low 53BP1 expression are associated with worse distant metastasis free survival when compared to tumors with normal 53BP1 expression. A set of breast cancer cell lines with abnormal 53BP1 expression was also identified. 53BP1 abnormalities were present in some tumors and cell lines with known BRCA1 mutations.Discussion: These data suggest that a subset of basal-like breast cancers lack normal 53BP1 expression and imply that these tumors may have profound defects in DNA repair/check point function that could be exploited therapeutically. As 53BP1 abnormalities were found in some tumors with known BRCA1 mutations, this suggests that loss of 53BP1 may cooperate with abnormalities in the BRCA1-related DNA repair pathways in the pathogenesis of basal-like breast cancers. Data regarding the molecular mechanisms underlying 53BP1 abnormalities in breast cancer cell lines and samples will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1122.
Closure with an over-the-scope clip allows therapeutic ERCP to be safely performed after acute duodenal perforation during diagnostic endoscopic ultrasound
Authors: Gianfranco Donatelli, Bertrand Vergeau, Stavros Dritsas, Jean-Loup Dumont, Thierry Tuszynski, Bruno Meduri
Journal: Endoscopy (2013)

The use of endoscopic ultrasound (EUS) before endoscopic retrograde cholangiography (ERC), if performed, can prevent two-thirds of unnecessary ERC procedures [1]. Duodenal perforation during diagnostic EUS occurs with an incidence of less than 1 % [2]. When perforation does occur, surgical or conservative management is possible. Surgery permits simultaneous treatment of the perforation and any biliary pathology if present [3]. Conservative management has been described using closure by endoscopic clipping [4]. Endoscopic retrograde cholangiopancreatography (ERCP) is then postponed, so avoiding duodenal maneuver and insufflation that could damage endoscopically placed sutures or aggravate the clinical picture. The over-the-scope clip (OTSC; Ovesco Endoscopy GmbH, Tübingen, Germany) is a new full-thickness clipping device that has been used successfully to treat gastrointestinal perforation [5].