tbuckley/cabot-search huggingface dataset:
Abstract 2048: USF2 is HIF2α specific co-transcriptional activator
Authors: Matthew Pawlus, Liyi Wang, Johnny Sena, Cheng-Jun Hu
Journal: Cancer Research (2011)

Abstract Hypoxia inducible factor HIF1α, and in particular HIF2α have been shown to drive malignant progression by activation of angiogenesis, proliferation, anaerobic metabolism, and other processes that enable tumor cells to survive or to escape their O2-deficient microenvironments. The dominant role of HIF2α in tumor biology is likely due to its selective activation of genes such as cyclin D1, TGFa, PDGFb, and OCT4 that are not regulated by HIF1α. The mechanism through which the highly conserved HIF1 and HIF2 regulate distinct target genes has not been established. We have previously shown that the transcriptional domain, but not the DNA binding domain of HIF determines its target gene specificity, suggesting that HIFs achieve their target gene specificity by interacting with other transcriptional factors or cofactors via their transactivation domains. Here we reported that HIF2α achieves its target gene specificity and enhanced transcriptional activity by interacting with the b/HLH/LZ transcription factor USF2 (upstream stimulatory factor 2) on promoters of HIF2α specific genes. We observed that siRNA-mediated USF2 knockdown significantly inhibited hypoxic induction of HIF2α (but not HIF1α) target genes in Hep3B and RCC4T cells. Additionally, overexpression of a USF2 dominant negative construct in Hep3B cells significantly reduced the levels of HIF2α (but not HIF1α) target genes under hypoxia. These data determined that USF2 is required for HIF2α to activate its target gene under hypoxia. By HIF2 target gene promoter functional analysis, gel-shift, and Chromatin-IP, we found that USF2 enhances HIF2α transcriptional activity by binding to HIF2α specific gene promoters and recruiting co-activator CBP/P300. In summary, we have uncovered a novel function of USF2 in HIF2α target gene regulation and demonstrated that USF2 is required for HIF2, but not HIF1 to activate its target genes. This finding has laid a foundation for the development of specific HIF2α inhibitors for use in solid tumor treatment. NIH T32-GM08730; RO1 CA134687 NIH/NCI (Hu); Cancer League of Colorado (Hu) 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 2048. doi:10.1158/1538-7445.AM2011-2048
609 A SIMPLE DIAGNOSTIC STRATEGY BASED ON ROUTINE CLINICAL DATA AND TRANSIENT ELASTOGRAPHY ACCURATELY DETECTS EARLY PORTAL HYPERTENSION IN PATIENTS WITH ASYMPTOMATIC LIVER DISEASE
Authors: S. Augustin, L. Badia, L. Millan, A. González, A. Gelabert, A. Romero, A. Segarra, R. Esteban, J. Guardia, J. Genesca
Journal: Journal of Hepatology (2012)
The Role of Axl in Ewing Sarcoma
Authors: E.D.G. Fleuren, W.T.A. van der Graaf, M.H.S. Roeffen, U.E. Flucke, B. Schreuder, O. Boerman, Y.M.H. Versleijen-Jonkers
Journal: Annals of Oncology (2014)
Release of Endogenous Pyrogen by Human Monocytes
Authors: Phyllis Bodel, Elisha Atkins
Journal: New England Journal of Medicine (1967)

ALTHOUGH fever is often a prominent sign in diseases associated with agranulocytosis1 its pathogenesis has remained obscure. Most experimental studies of the mechanism of fever have been carried out in rabbits that have been either injected intravenously or infected with various microbes or their products.2 From this work it now seems clear that such agents produce fever indirectly by liberating a circulating endogenous pyrogen from the tissues of the host. This material, in turn, appears to act directly on the hypothalamic thermoregulatory center to produce fever. Since granulocytes derived from sterile acute exudates liberate large quantities of pyrogen,3 it has . . .
Electroencephalographic Studies in Diabetes Mellitus
Authors: Milton Greenblatt, Jean Murray, Howard F. Root
Journal: New England Journal of Medicine (1946)

ELECTROENCEPHALOGRAPHIC studies have become an almost routine procedure at the New England Deaconess Hospital in examining diabetic patients who have frequent insulin reactions or seizures in which hypoglycemia is considered a possible precipitating factor. Although the incidence of epilepsy among diabetic patients has not proved to be greater than that in unselected persons of corresponding age groups, the occurrence of repeated insulin reactions in a specific case always raises the question whether they are due to an abnormally rapid change in the blood sugar or to instability of the nervous mechanism — that is, to an epileptoid tendency. The electroencephalogram . . .
Données de l'échoendoscopie au cours de l'achalasie: étude cas-témoin
Authors: A Tebaibia, M Balamane, N Oumnia, M Lahcene, M Boudjella, N Matougui, B Touchene
Journal: Endoscopy (2008)

Rationnel: Au cours de l'achalasie, un épaississement circonférentiel de la couche musculaire muqueuse est inconstamment retrouvé à l'échoendoscopie et l'intérêt de cet examen pour le diagnostic de l'affection est très limité. Cependant, il a un intérêt majeur dans le diagnostic de l'achalasie secondaire à une formation cardiale sous muqueuse. Buts: comparer l'épaisseur de la couche musculaire chez les patients achalasiques versus les patients non achalasiques et rechercher une relation entre les données échoendoscopiques et le profil des patients des deux groupes.
Abstract 3981: Evaluation of mutation detection sensitivity in exome sequencing and other genotyping platforms
Authors: Isabella H. Wulur, Swee Seong Wong, Kun Yu, Thomas D. Barber, Yong Gang Yue
Journal: Cancer Research (2012)

Abstract An evaluation was performed to compare mutation calls from exome capture sequencing data to publicly available data sets derived from Sequenom MassARRAY and Sanger sequencing methods. We compared hot-spots KRAS and BRAF mutations using Sanger sequencing method in patient-derived tumor grafts. Mutation data of the tumor grafts were also generated with Sequenom MassARRAY using the OncoCarta panel. We also evaluated the sensitivity of mutation detection for a panel of cancer genes in &amp;gt;100 cancer cell lines against the data from the Cancer Cell Line Encyclopedia Project (OncoMap mutation panel) as well as the Sanger's Cancer Genome Project. Overall, we observed high sensitivity and concordance of the mutation calls from the exome sequencing with the other platforms and technologies. The above comparisons support the use of exome sequencing as a sensitive mutation detection method for patient-derived tumor grafts and cancer cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3981. doi:1538-7445.AM2012-3981
P17.48 * SURVIVAL BENEFIT OF LEVETIRACETAM IN GLIOBLASTOMA: A PROSPECTIVE SINGLE-CENTER STUDY
Authors: C. Kim, Y. Kim, J. Han, Y. Kim, I. Kim, C. Yun, T. Kim, J. Joo
Journal: Neuro-Oncology (2014)

OBJECTIVE: A chemo-sensitizing effect of levetiracetam (LEV) has been suggested because LEV inhibits O-6-methylguanine-DNA methyltransferase (MGMT). However, the survival benefit of LEV has not been clinically documented. This study was performed to assess the survival benefit of LEV as a chemo-sensitizer of temozolomide for glioblastoma patients compared to other anti-epileptic drugs (AEDs). METHODS: A total of 46 consecutive patients with primary supratentorial glioblastoma who were treated with concomitant chemoradiotherapy and adjuvant temozolomide therapy with LEV were prospectively enrolled. Forty-four consecutive patients with the same condition who had not taken LEV during identical chemoradiotherapy were selected as the control group. Gender, age, extent of lesion, the Karnofsky performance scale (KPS) score, extent of removal, and methylation status of the MGMT promoter were not significantly different between the LEV group and the control group. RESULTS: The median progression-free and overall survival (PFS and OS, respectively) of the LEV group (10.8 months [95% CI, 8.3-13.3] and 25.7 months [95% CI, 21.0-30.4], respectively) were significantly longer than those of the control group (6.6 months [95% CI, 5.2-8.0] and 16.8 [95% CI, 12.2-21.4], respectively) (p = 0.017 and 0.035, respectively). Significant prognostic factors for OS of all 90 patients were the preoperative KPS score (p = 0.027; HR = 0.360), methylation status of the MGMT promoter (p = 0.002; HR = 0.203), and LEV (p = 0.004; HR = 0.244) in multivariate analysis. CONCLUSIONS: LEV may provide a survival benefit in glioblastoma patients who receive temozolomide-based chemotherapy compared with other AEDs. A prospective randomized study may be indicated.
Abstract LB-421: Dual shRNA technique to screen gene-to-gene interaction
Authors: Marianne K. H Kim, Christina Annunziata
Journal: Cancer Research (2012)

Abstract Background: Synthetic lethality screening in human cells is one of the most powerful tools to identify potential therapeutic targets in a genotype specific manner and this screening has been performed in isogenic models of matched cell-line pairs. The procedure of establishing and isolating isogenic cell lines can be arduous. And despite this laborious work, specific target(s) identified in this specific isogenic cell line may not be valid in other similar cells and experimental conditions. Therefore, we have optimized a fast and robust dual shRNA technique to screen gene-to-gene interaction. Methods and Results: To create a matched cell line pair, we utilized a bicistronic vector containing the transmembrane and extracellular domains of the mouse T-cell surface glycoprotein CD8 alpha, co-expressed with a specific shRNA, to model a specific gene deficiency. This retroviral vector was transduced into target cells, and the positively transduced cells were isolated at two days post-infection using MACS separation columns with mouse CD8a-specific microbeads. This yielded greater than 95% purity. At this time point, the decreased expression of specific gene by shRNA was minimal. After recovery from beads purification, the second bicistronic shRNA vector was introduced. This second vector contained a puromycin selectable marker with GFP and an shRNA targeting the proposed synthetic lethal gene. After second transduction, cells were selected under puromycin allowing two doubling times. The purity was 96-98% based on GFP signal measured by FACS at the end of puromycin selection. The dual-gene knockdown by sequentially introduced shRNAs achieved 70-90% depletion of each gene product. This level of knockdown was maintained for up to three weeks without significant loss of purity. After maintaining the cells in culture for several weeks CD8a purity did decrease to 70-80%, but was restored to 98-99% purity after re-applying the separation columns. The second level of purity was maintained even longer than single purification. Conclusion: In summary, we have developed a fast and efficient dual shRNA technique to apply to shRNA experimentation, obviating the need for establishing conventional isogenic cell line models. Due to its fast and simple procedure, this can be simultaneously performed in multiple cell lines. This technique can easily be adapted to screen shRNA libraries for the discovery of unknown synthetic lethal interactions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-421. doi:1538-7445.AM2012-LB-421
PTU-216 A survey of patients attitudes to colonoscopy demonstrates high value for endoscopist interaction but not the single sex environment
Authors: J McEntire, J Sahota, T Hyde, T Trebble
Journal: Gut (2012)

<h3>Introduction</h3> Understanding patient attitudes to their medical experience is essential for optimising care and use of resources. This includes their interaction with their health practitioner and their healthcare environment. This study was undertaken to determine patient9s preferences and expectations for outpatient colonoscopy, a common gastrointestinal procedure for which there is limited such data from the UK. <h3>Methods</h3> Unselected patients attending for elective colonoscopy at a large District General Hospital on randomly selected days in October and November 2011 were invited to participate. Patients independently completed a composite, validated dedicated endoscopy questionnaire, with Likert scale anxiety-related and single sex environment questions and a 15-point preference (ranking) scale of aspects of endoscopy care that were considered most important (1) to least important (15) as contributing to a satisfactory experience. Qualitative and pilot studies were performed initially to confirm validity and reliability in the local population. <h3>Results</h3> 217 out of 225 patients agreed to participate (96.4%); male (49%) and female (51%), with mean age of 58 years (range 16–87 years). Mild to moderate anxiety was recorded in over 70% of patients, commonly with respect to anticipation of pain or the results of the procedure. The ranked preference scores suggested that interaction with the endoscopist, including technical skill of the endoscopist, discomfort during the procedure, manner of the endoscopist and the pre-and post procedure discussions were considered as most important to patients. A majority of patients (55%) preferred the endoscopist to explain the findings, but only 26% specified that they needed to explain the procedure itself. Environmental factors were considered of relatively low importance, including the single sex environment (least important), noise levels, explanation of delay, privacy and intra department waiting time. A majority (82.1%) thought that having a single sex environment was minimally/not important, and only 14.3% of patients were prepared to have a delayed appointment for a single sex environment. <h3>Conclusion</h3> Patients undergoing colonoscopy appear to highly prioritise aspects of care relating to the interaction with the endoscopist and the procedure itself. Environment factors are considered to have much less value and specifically having a single sex environment. These findings may assist in service redesign around patient-centred care and patients priorities, and the development of patient satisfaction surveys in endoscopy. <h3>Competing interests</h3> None declared.
Abstract 2741: Applying a biological pathway-based approach to interrogate the genome-wide association data on prostate cancer
Authors: Junjie Feng, Jielin Sun, Zheng Zhang, Yi Zhu, Jianfeng Xu
Journal: Cancer Research (2011)

Abstract Genome-wide association studies (GWAS) have been successful in identifying common susceptibility loci for several complex diseases, yet the massive amounts of data generated from GWAS have not been maximally leveraged. We have applied a previously reported pathway-based approach to analyze the prostate cancer (PCa) GWAS data from the Cancer Genetic Markers of Susceptibility (CGEMS) project. This approach examines whether the cumulative contribution of a set of SNPs that occur on genes within a predefined biological pathway is greater than expected by chance, and thus may provide important novel biological insights that have been missed by most current GWAS. Out of the 555 pathways analyzed from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology, and BioCarta databases, a total of 32 pathways reached a nominal P &amp;lt; 0.05 in their associations with PCa. Among these notably include six KEGG-defined cancer pathways (thyroid, prostate, renal, and pancreatic cancer, non-small cell lung cancer, and acute myeloid leukemia), three well-established cancer-related molecular pathways (ATR-BRCA, ionizing radiation response, and apoptosis), and three pathways that have cancer implications (glycolysis, calcium-dependent cell-cell adhesion, and regulation of actin cytoskeleton), which together constitute more than one third of the top-ranked pathways. Of closest relevance is the prostate cancer pathway (hsa05215), which was ranked the third highest (nominal P = 0.01) in our analysis. However, no associations of these top pathways remained significant after correction for multiple testing, indicating that the common variants involved in PCa risk are likely to occur in genes from multiple pathways. This genome-wide pathway analysis supports a model that alterations from multiple pathways may combinatorially contribute to the etiology of PCa. 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 2741. doi:10.1158/1538-7445.AM2011-2741
PTU-050 Effect of vitamin E and alfa lipoic acid (ALA) in non-alcoholic fatty liver disease: a randomise placebo control open label prospective clinical trial: V A I N trial
Authors: P Basu, N James Shah, S Farhat
Journal: Gut (2012)

<h3>Introduction</h3> Non-Alcoholic Fatty Liver Disease (NAFLD) is a global epidemic. NAFLD progress to Non-Alcoholic Steatohepatitis (NASH), cirrhosis and cancer. Obesity and insulin insensitivity is the hallmark. Liver participates in glucose and fatty acid homeostasis. Nonexpelled free fatty acid and its toxic metabolites impact oxidative stress; free radicals influx which initiate inflammatory cascade to Steatohepatitis (NASH) and activate fibrotic path causing cirrhosis. This clinical trial highlights the effects of anti-oxidants in NAFLD. <h3>Methods</h3> One hundred and fifty-five (n=155) with BMI over 28% with NAFLD and NASH were recruited and randomised into Group A (n=35)- Control, Group B (n=40) ALA 300 mg, Group C (n=40) Vitamin E 700 IU and Group D (n=40) ALA plus Vitamin E orally for 6 months. Pre and Post BMI, HOMA, Triglyceride, Haemoglobin A1c, Alanine aminotransferase (ALT), Retinol Binding Protein 4, Tumour Necrosis factor α (TNFα), Leptin and adiponectin levels were compared. Everyone was allowed 1600 cal/day with modest exercise. Exclusion criteria: Diabetics, BMI &gt;33%, Alcohol intake &gt;30 g/day, Hepatitis B, C, Hypothyroidism, medications including herbs and supplements. <h3>Results</h3> <h3>Conclusion</h3> Pre and post analysis between ALA plus Vitamin E over placebo in 6 month; TG 43%, HbA1c 14%, HOMA 62.8%, ALT 14.4%, RBR4 50%, Leptin23%, Adiponectin19% TNF α 70%, and Steatotic score 70.7%. This clinical trial demonstrates the additive effects of ALA and vitamin E in NAFLD and NASH with significant improvements of inflammatory and steatotic score but no difference in the fibrotic score. Therapeutic application of ALA and Vitamin E should be considered for NAFLD. <h3>Competing interests</h3> None declared.
Congress Weighs NIH Bid for Patent Rights to Human Genes
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Congress Weighs NIH Bid for Patent Rights to Human Genes Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 2, 15 January 1992, Pages 76–77, https://doi.org/10.1093/jnci/84.2.76 Published: 15 January 1992
SAT0027 Baseline Factors That PREDICT High Blys Levels (≥2 NG/ML) in Patients with Systemic Lupus Erythematosus: Data from the BLISS Trials
Authors: D. Roth, A. Thompson, T. Tang, A. Hammer, C. Molta
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Post-hoc analyses from the BLISS trials demonstrated that patients with high baseline B-lymphocyte stimulator (BLyS) levels (≥2 ng/ml) had an increased risk of a clinically meaningful flare over 1 year.<sup>1</sup> <h3>Objectives</h3> Given that BLyS levels are not routinely collected in clinical practice, further analyses were conducted to identify clinical variables that may be predictive of high BLyS levels. <h3>Methods</h3> Data from BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) were pooled (GSK200619). All randomised subjects with baseline BLyS levels were included. A logistic regression analysis was performed. A univariate logistic regression was first employed to identify a subset of baseline factors (e.g. demographic, disease activity, laboratory, biomarker and systemic lupus erythematosus [SLE] medication usage) predictive of high baseline BLyS levels. Only baseline factors that were significant at the 0.05 level entered the final logistic regression as covariates. <h3>Results</h3> A total of 380 out of 1664 (22.8%) subjects had high baseline BLyS levels (≥2 ng/ml). Most subjects were female (n=344, 90.5%); mean age was 36 (11.0 SD) years, and mean SELENA-SLEDAI score was 10.8 (4.29 SD). Significant baseline predictors of high baseline BLyS levels included positive anti-Smith (≥15 U/ml; χ<sup>2</sup> =17.04, p&lt;0.01), low C3 (χ<sup>2</sup> =4.81, p&lt;0.05), anti-dsDNA (&gt;200 IU/ml; χ<sup>2</sup> =20.41, p&lt;0.01) and anti-dsDNA (80–200 IU/ml; χ<sup>2</sup> =5.85, p&lt;0.05), use of immunosuppressant medication (χ<sup>2</sup> =27.39, p&lt;0.01), proteinuria (≥0.5 g/24 h; χ<sup>2</sup> =18.91, p&lt;0.01) and elevated C-reactive protein (&gt;3 mg/L; χ<sup>2</sup> =51.61, p&lt;0.01). <h3>Conclusions</h3> Positive anti-Smith, low C3, positive anti-dsDNA, immunosuppressant usage, proteinuria and elevated C-reactive protein were predictors of high BLyS levels. Identifying routinely collected clinical variables predictive of high BLyS levels, which are associated with moderate-to-severe flare and high disease activity, is useful in the ongoing management of SLE. <h3>Disclosure of Interest</h3> D. Roth Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, A. Thompson Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, T. Tang Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, A. Hammer Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, C. Molta Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4975
Case 83-1962
Authors: Francis M. Ingersoll, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of CaseA twenty-five-year-old mother of 3 children was admitted to the hospital because of pain in the right side of the chest.During the two weeks before entry the patient had a cough and coryza associated with increasing weakness and discomfort in the chest. There was no sputum or hemoptysis. Three days before admission a shaking chill occurred, followed by pleuritic pain and elevation of the temperature to 102°F.The patient's mother had recently been confined to a hospital because of pulmonary tuberculosis and had previously cared for the patient's son, who had subsequently been admitted to a . . .