tbuckley/cabot-search huggingface dataset:
Abstract 3536: Caulobacter crescentus as new intravesical treatment for bladder cancer
Authors: Kilian M. Gust, Dirk Lange, John F. Nomellini, John Smit, Alan I. So
Journal: Cancer Research (2011)

Abstract Introduction and Objectives: The standard of care for high risk non-muscle invasive bladder cancer is the intravesical instillation of Bacillus Calmette-Guérin (BCG), an attenuated strain of the pathogen Mycobacterium bovis, associated with significant side effects often ending treatment prematurely. Using nonpathogenic bacterial strains with anti-tumor activity would thus be beneficial. Caulobacter crescentus is a gram-negative, non-pathogenic fresh water bacterium that does not replicate in a mammalian host and therefore qualifies for having a good bio-safety profile. Caulobacter crescentus has previously been shown to have anti-tumor activity in a model of mammary carcinoma. The aim of this study was to evaluate the anti-tumor activity of intravesical administered Caulobacter cresecentus in an immuno-competent animal model for bladder cancer. Materials and Methods: In vitro, the mouse bladder tumor cell line MBT-2, derived from C3H/He mice, was treated with increasing concentrations of Caulobacter crescentus (C.cresc.). Microscopy and growth assays were performed. In vivo, the same cell line, previously lenti-viral transduced with a luciferase gene (MBT-2 luc), was instilled in the bladder of 6 week old, female C3H/He mice (3×106 cells/50ul). Bioluminescent imaging was performed to determine tumor burden on day 5 and mice were randomized to treatment groups. Intravesical treatments (109 C.cresc. in 50ul of H2O or H2O as control) were performed on days 6, 8, 11 and 15 and tumor growth was examined by bioluminescence after i.p. injection of luciferin. Mice were euthanized on day 20 and mouse bladders processed for histology and immuno-histochemistry. Results: In vivo, intravesical treatment of MBT-2 luc tumor bearing C3H/He mice showed a significant inhibition of tumor growth compared to the control group, while no side-effects due to the intravesical C.cresc. application were observed. Additionally performed in vitro experiments revealed that incubation of MBT-2 cells with C.cresc. resulted in a concentration dependent growth inhibition. Conclusions: These preliminary results support the safety and efficacy of Caulobacter crescentus as a novel intravesical treatment for bladder cancer. Further investigation is needed to reveal the exact mechanism of action and to distinguish, if a direct anti-tumor effect of C.cresc. or the host immune-response is the driving component of the anti-tumor effect. 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 3536. doi:10.1158/1538-7445.AM2011-3536
Phase I Study of LY2523355, an EG5 Inhibitor, in Japanese Patients with Advanced Solid Tumors
Authors: S. Nakamichi, H. Nokihara, H. Mizugaki, H. Wakui, Y. Fujiwara, Y. Yamada, N. Yamamoto, K. Suzuki, S. Akinaga, T. Tamura
Journal: Annals of Oncology (2013)
ASPIRIN DOSING IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION TREATED WITH TICAGRELOR: INSIGHT FROM THE NATIONAL CARDIOVASCULAR DATA REGISTRY (NCDR)
Authors: Sukhdeep S. Basra, Tracy Wang, DaJuanicia Simon, Karen Chiswell, Salim Virani, Mahboob Alam, Vijay Nambi, Ali Denktas, Anita Deswal, Biykem Bozkurt, Christie Ballantyne, Eric Peterson, Hani Jneid
Journal: Journal of the American College of Cardiology (2016)
Abstract 5194: Induction of Fyn via the Ras/PI3K pathway is necessary and sufficient for enhanced migration and invasion
Authors: Vipin Yadav, Mitchell F. Denning
Journal: Cancer Research (2010)

Abstract Over-expression and activation of Src family kinases, particularly Fyn, is relatively frequent in human cancers. Fyn promotes cancer progression, tumor survival and carcinoma invasion, making it a potential molecular target for cancer therapeutics; however the mechanism of Fyn over-expression in cancers is not clear. Since activation of Ras oncogenes in human cancers is a very common oncogenic event, we explored if an active Ras oncogene could induce Fyn expression. Interestingly, retroviral transduction of the immortalized human keratinocyte cell line HaCaT with oncogenic H-Ras dramatically upregulated Fyn mRNA, protein, and activity (&amp;gt;100 fold mRNA induction, p&amp;lt;0.001). Src levels and kinase activity were not affected by H-Ras transduction. Furthermore, activation of Akt, but not MAPK or EGFR, was necessary and sufficient for induction of Fyn by H-Ras. The enhanced migration and invasion induced by H-Ras could be significantly blocked (70% reduction, p&amp;lt;0.0001) by Fyn specific siRNA knockdown or inhibition by PP2 (10 µM). In addition, expression of active Fyn in HaCaT cells was sufficient for increased migration or invasion of cells. These results implicate induction of Fyn in Ras-induced enhanced migration and invasion of cancer cells. Focal adhesion kinase (FAK) activation has been strongly linked with the Ras-mediated increased migratory phenotype of tumor cells. We found that Fyn was necessary and sufficient for Ras induced activation of FAK. In summary, we show that Fyn induction by oncogenic Ras/PI3K/Akt pathway can account for the elevated Src family kinase activity in cancers, and is a critical mediator of the Ras-stimulated invasive cell phenotype. These results have strong implications for the development of therapeutic strategies targeting Akt/Fyn pathway to block migration and invasion of tumor cells. 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 5194.
Streptomycin in the Treatment of Subacute Bacterial Endocarditis
Authors: Robert Wallach, Norman Pomerantz
Journal: New England Journal of Medicine (1949)

UP TO the present there have been scattered reports on the use of streptomycin in the treatment of subacute bacterial endocarditis. No individual series of cases has been large enough from which to draw conclusions. It is the purpose of this paper to present another unusual case of subacute bacterial endocarditis successfully treated with streptomycin, and to summarize the literature on the subject to May, 1949.After several unencouraging reports, Loewe et al.,1 1944, showed that subacute bacterial endocarditis could be cured by penicillin given in sufficiently high doses for adequate lengths of time. Prior to this the prognosis in . . .
Abstract 953: Knockdown of kinases that regulate microtubule stability and centrosome function enhance paclitaxel sensitivity in multiple ovarian cancer cell lines.
Authors: Hailing Yang, Xiaoyan Wang, Ahmed A. Ahmed, Zhen Lu, Robert C. Bast
Journal: Cancer Research (2013)

Abstract Virtually all patients with newly diagnosed ovarian cancer are treated with a combination of paclitaxel and carboplatin. While 70% of ovarian cancers respond to carboplatin, more than half do not respond to the paclitaxel. Inhibition of kinases that modulate primary resistance to paclitaxel, could enhance response to therapy. To identify kinases that regulate sensitivity to paclitaxel, high throughput screening with a kinome wide siRNA library was performed in SKOv3 ovarian cancer cells. Among 45 hits, 14 target proteins (AATK, ACRBP, BMP2K, CHUK, EDN2, IKBKB, ILK, RAPGEF3, RAPGEF4, RFP, SIK2, STK24, STK39 and TBK1) regulated sensitivity to paclitaxel and were expressed or overexpressed in a fraction of ovarian cancers. siRNAs against each of these kinases were tested for the ability to enhance sensitivity to paclitaxel in each of 12 ovarian cancer cell lines that reflected the heterogeneity observed in ovarian cancers including mutations of TP53, BRCA1/2, KRAS, BRAF, PI3K and PTEN. Knockdown of 7 individual genes reduced the IC50 of paclitaxel in more than half of the cell lines by 25 to 80 percent. Knockdown of STK39 and NFKB pathway kinases IKBKB and TBK1 enhanced microtubule stability judged by microtubule fractionation assay. Other kinases are known to affect centrosome function (SIK2, ACRBP). Our studies have identified several proteins that regulate primary sensitivity to paclitaxel in ovarian cancer cells and that could serve as targets to enhance response to primary therapy. Citation Format: Hailing Yang, Xiaoyan Wang, Ahmed A. Ahmed, Zhen Lu, Robert C. Bast. Knockdown of kinases that regulate microtubule stability and centrosome function enhance paclitaxel sensitivity in multiple ovarian cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 953. doi:10.1158/1538-7445.AM2013-953
757 ADDING PEGINTERFERON alfa-2a ON NUCLEOS(T)IDE ANALOGUES THERAPY IMPROVES HBeAg SEROCONVERSION AND qHBsAg DECLINE IN HBeAg-POSITIVE CHRONIC HEPATITIS B PATIENTS WHO HAVE ACHIEVED VIROLOGICAL RESPONSES
Authors: Q. Li, G. Dong, J. Yu, C. Sun, S. Xie
Journal: Journal of Hepatology (2013)
Detection of Rhabdomyolysis Associated with Compartment Syndrome by Bone Scintigraphy
Authors: Nir Hod, Sigal Fishman, Tifha Horne
Journal: Clinical Nuclear Medicine (2002)

From the Departments of Nuclear Medicine* and Internal Medicine A,† Assaf Harofeh Medical Center, Zerifin and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Received for publication March 6, 2002. Revision accepted June 6, 2002. Reprint requests: Dr. Tifha Horne, Department of Nuclear Medicine, Assaf Harofeh Medical Center, Zerifin 70300, Israel.
PTU-028 Transient elastography in the risk stratification of patients with abnormal liver function tests
Authors: E J Britton, R Saravanan, T Woodhouse, K Koss
Journal: Gut (2012)

<h3>Introduction</h3> Transient elastography (TE) (Fibroscan) is a well validated method for assessing liver fibrosis in a trial setting. Gastroenterology Department at Macclesfield DGH is one of the first centres in the UK to adopt Fibroscan examination into the diagnostic pathway of patients with abnormal LFT. This is the first publication of our data of unselected patients undergoing liver stiffness measurement (LSM) demonstrating practicalities and limitations of Fibroscan. <h3>Methods</h3> Data were collected from 366 patients with abnormal LFT attending Gastroenterology Clinic from July 2010 to December 2011. Fibroscan examination was performed by two gastroentrology consultants and one specialist nurse. The cohorts of Fatty liver disease (FLD) and Alcoholic liver disease (ALD) were further analysed comparing fibrosis score from TE with clinical findings, laboratory blood tests, ultrasound imaging and liver biopsy. <h3>Results</h3> Patients diagnosis were as follows: FLD 35.8% (n=131), ALD 14.8% (n=54), Chronic hepatitis C 15.6% (n=57), PSC/PBC 7.7% (n=28), chronic hepatitis B 4.6% (n=17), haemochromatosis 2.2% (n=8), AIH 1.4% (n=5), chronic usage of Methotrexate 1.9% (n=7). Additionally 42 healthy volunteers participated. The mean time duration for each successful scan was 173 (30–1363) seconds with 18% of patients requiring the XL probe due to central obesity. The fibrosis scores recorded for all patients scanned were F0-1 41% (n=150), F2 6.3% (n=23), F3 7.1% (n=26) and F4 26% (n=95). 15% of scans were considered to be failed as LSM/IQR was &gt;33, most prevalent in the FLD group 16.8% (n=22) and wasn9t operator or probe dependent. Significant proportion of patients with liver fibrosis (F3-4) had no clinical signs of chronic liver disease. 80% of patients F3-F4 fibrosis demonstrated portal hypertension on imaging and 32% of patients in that group had low platelets (3. The sensitivity and specificity of low platelets for significant fibrosis was 32% and 91% and for portal hypertension on imaging was 64% and 89% respectively. There was significant correlation between liver fibrosis scoring on TE and Metvir fibrosis scoring on biopsy in patients without high degree of inflammation. However, coexisting acute inflammation in some cases contributed to false positive results on Fibroscan. <h3>Conclusion</h3> The Fibroscan technology has allowed rapid stratification of patients with chronic liver diseases. Significant proportion of patients (40%) were appropriately reassured without need of undergoing liver biopsy. 20% of patients without stigmata of chronic disease and without conventional laboratory markers of liver fibrosis were diagnosed with liver cirrhosis. Early experience has shown difficulties of performing TE in patients with central obesity and FLD. Fibroscan finds its valuable role in the care pathway of patients with abnormal LFT. <h3>Competing interests</h3> None declared.
IB-04 * EXPRESSION OF RAGE BY TUMOR MACROPHAGES PROMOTES ANGIOGENESIS IN GLIOMAS
Authors: X. Chen, L. Zhang, I. Zhang, J. Liang, L. Weng, Y. Yamamoto, H. Yamamoto, R. Natarajan, B. Badie
Journal: Neuro-Oncology (2014)

Interaction of RAGE with its ligands can promote tumor progression, invasion and angiogenesis. Although blockage of RAGE signaling has been proposed as a potential anti-cancer therapy, the contribution of RAGE expression in tumor microenvironement (TME) to tumorigenesis has not been investigated in detail. Here, we evaluated the effect of genetic depletion of RAGE in TME on the growth of gliomas. In both invasive and non-invasive glioma models, animal survival was prolonged in Rage−/- mice. This improvement in animal survival, however, was not due to changes in tumor growth rate, but a reduction in tumor-associated inflammation in Rage−/- mice. Furthermore, RAGE ablation in TME abrogated angiogenesis by downregulating the expression of pro-angiogenic factors which prevented vessel pruning, and resulted in the generation of leaky vasculature. These alterations, however, were most prominent in non-invasive gliomas where the expression of VEGF and pro-inflammatory cytokines were also lower in Rage−/- tumor-associated macrophages. Interestingly, reconstituting Rage−/- tumor macrophages with either wild-type microglia or macrophages normalized tumor vascularity. This is the first report to demonstrate the pro-angiogenic function of RAGE signaling in tumor macrophages and underscores the complex role of RAGE and its ligands in gliomagenesis.
PWE-252 Trends in imaging and impact of diagnostic medical radiation in inflammatory bowel disease
Authors: S Chatu, A Poullis, R Holmes, R Greenhalgh, R Pollok
Journal: Gut (2012)

Introduction Increasing use of diagnostic imaging in inflammatory bowel disease has led to concerns about the malignant potential of ionising radiation in a cohort that is already predisposed to malignancy. The aim was to quantify radiation exposure in inflammatory bowel disease patients referred from primary care, determine predictors of high exposure and evaluate temporal changes in imaging at a single centre. Methods Patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were prospectively recruited from clinic between January 2011 and June 2011. Demographic and clinical data were obtained by scrutinising medical records. The number and type of imaging procedures was obtained from the radiology database which was first set up in 1990, we only included those diagnosed after the database was initiated. The effective dose of radiation from each test was estimated from published standardised tables. Cumulative effective dose (CED) was calculated for each subject by summing the effective doses of radiation from diagnosis until end of study period which was June 2011. Cox regression analysis was performed to assess for factors associated with potentially harmful levels of ionising radiation defined as total CED >50 mSv. Results The cohort included 415 patients. Median disease duration for Crohn's disease and ulcerative colitis was 8.3 and 7.7 years. Median total CED was 7.2 mSv (IQR 3.0–22.7) in Crohn's disease and 2.8 mSv (IQR 0.8–8.9) in ulcerative colitis patients. A total of 32 patients (8%) received a CED >50 mSv. Multivariate analysis revealed a history of IBD related surgery had a HR of 7.7. During the study period usage of abdominal CT increased by 350%. Conclusion About 1 in 10 patients were exposed to potentially harmful levels of ionising radiation therefore strategies to reduce radiation exposure are needed. While there was an increased uptake of both MRI and small bowel ultrasound over the past 20 years use of CT also increased substantially. Competing interests None declared.
Abstract 4846: Genetic variants in the Wnt/beta-catenin signaling pathway as indicators of ovarian cancer risk and survival.
Authors: Jeanne A. Pierzynski, Michelle AT Hildebrandt, Xifeng Wu, Karen H. Lu, Dong Liang
Journal: Cancer Research (2013)

Abstract Ovarian cancer is the ninth most common cancer in women and the fifth leading cause of cancer death in 2012. Much is known about the correlation between BRCA mutations and ovarian cancer, but less is known about the impact of common, germline genetic variants on ovarian cancer risk and clinical outcomes. The Wnt/beta-catenin pathway has major roles in regulation of stem cells and other cellular pathways and has been shown to be involved in the development of several different cancers. Therefore, we examined 434 Single Nucleotide Polymorphisms (SNPs) in the Wnt/beta-catenin pathway in 339 ovarian cancer cases and 349 controls. These variants were then assessed for association with risk and clinical outcomes of ovarian cancer. Sixteen polymorphisms had a statistically significant association with ovarian cancer risk with the most significant association being for rs11668593 in APC2 under the dominant model [odds ratio (OR)=0.61; 95% confidence interval (CI), 0.44-0.83]. Unfavorable analysis showed a highly significant cumulative effect of these 16 SNPs on risk (P for trend = 4.22x10−15). In the clinical outcomes analysis, there were eight SNPs that showed an association with ovarian cancer survival. The most significant association with survival was seen for rs11054760 in LRP6 [OR=2.16; 95% CI, 1.33-3.50] which resulted in a poorer survival in patients carrying the heterozygous or homozygous variant genotypes compared to those with the homozygous common genotype. Individuals with the common genotype for rs11054760 had a longer median survival time of 52.7 months compared to only 25.9 months for those with variant containing genotypes (Plog-rank = 3.54x10−4). A gene-dosage effect with a decrease in survival as the number of unfavorable genotypes increased was evident (P for trend = 4.57x10−9). These results implicate genetic variation in the Wnt/beta-catenin signaling pathway as having an impact on risk and clinical outcomes of ovarian cancer. Citation Format: Jeanne A. Pierzynski, Michelle AT Hildebrandt, Xifeng Wu, Karen H. Lu, Dong Liang. Genetic variants in the Wnt/beta-catenin signaling pathway as indicators of ovarian cancer risk and survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4846. doi:10.1158/1538-7445.AM2013-4846
Cone-beam computed tomography – adding a new dimension to ERCP
Authors: Jochen Weigt, Maciej Pech, Arne Kandulski, Peter Malfertheiner
Journal: Endoscopy (2015)

Six patients with biliary duct pathologies were investigated with three-dimensional endoscopic retrograde cholangiopancreatography (3D-ERCP). The technique of 3D-ERCP consists of c-arm rotation using a flat detector c-arm to acquire a complete set of images for 3 D visualization of the biliary system. Our case series demonstrates a high level of accuracy with regard to the diagnosis of stenosis and biliary leakage. In two patients the diagnosis obtained from conventional ERCP changed significantly after 3D-ERCP. From these early observations we conclude that 3D-ERCP enhances the diagnostic performance of ERCP in a subset of patients with biliary tract disease.
AB0007 Incidence and Functional Relevance of IL-23 Receptor Gene Polymorphisms in Ankylosing Spondylitis
Authors: J. Fessler, M. Stradner, D. Peischler, W. Graninger, J. Hermann
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Interleukin-23 (IL-23) signaling is involved in Th17 immune response and thus in the pathogenesis of ankylosing spondylitis (AS). <h3>Objectives</h3> The purpose of this study was to investigate the functional relevance of single nucleotide polymorphisms (SNP) in the IL-23 receptor (IL-23R). <h3>Methods</h3> 105 patients with AS according to the modified New York criteria were prospectively enrolled into the study. Blood was drawn from all individuals and DNA was extracted to determine the SNPs rs 10889677 (SNP1), rs 11209026 (SNP2), rs 11465804 (SNP3) and rs 1343151 (SNP4) by polymerase chain reaction. To test functional relevance of the SNPs we performed intracellular flow cytometry and stained PBMCs with anti-CD3, CD4, CD8, IL-23R, pSTAT-3 and IL-17A. Phosphorylation of STAT-3 (pSTAT-3) following IL-23 stimulation (100ng/ml) and the prevalence of Th17 cells were assessed. <h3>Results</h3> We detected homozygote carriers of SNP1 in ten (9.5%) and SNP4 in four (3.8%) patients of our cohort. These patients were wildtype (WT) for the other SNPs tested. We found no homozygote carriers of the SNPs 2 and 3. Fifteen SpA patients were WT for all four SNP tested and served as control group. The frequency of IL-23R<sup>+</sup> CD4 T cells was significantly increased in the SNP1 group (median 37.3 [27.9-52.7] vs. 25.6 [16.1-38.1], p=0.05) but not in the SNP4 group (32.4 [29.3-34.9], p=0.248). IL-23 (100ng/ml) stimulation of PBMCs induced phosphorylation of STAT3 in the SNP1 group (2.2 [1.7-4.5] vs. 1.3 [0.4-2.7], p=0.087) but not in the SNP4 group compared to WT (1.7 [0.7-2.6], p=0.715). In addition, patients with SNP1 (1.2 [0.8-1.4], p=0.015) but not with SNP4 (1.1 [0.6-1.2], p=0.162) exhibit significantly elevated levels of Th17 cells after stimulation with OKT-3 compared to WT (0.6 [0.5-0.9]). <h3>Conclusions</h3> The SNP rs 10889677 increases Il-23R abundance in CD4<sup>+</sup> T cells and fosters Th17 response in patients with ankylosing spondylitis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2087
Antimicrobial Therapy for Wound Infections after Catastrophic Earthquakes
Authors: Ian N. Miskin, Ran Nir-Paz, Colin Block, Ofer Merin, Sa'ar Burshtein, Sergey Pirogovsky, Tamar Halperin, David Schwartz, Mitchell J. Schwaber
Journal: New England Journal of Medicine (2010)

To the Editor: During the past 12 years, five catastrophic earthquakes have occurred. Most overwhelmed local medical capacity and caused widespread destruction, injury, and loss of life. Medical teams were dispatched both from within the country and from abroad to treat the surfeit of patients and to bridge the gap in resources until local health services recovered. Because of the delay between injury and treatment, most of the injured presented with infected wounds, necessitating empirical antimicrobial treatment. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have proposed guidelines for managing this scenario, primarily by . . .
Thyroid Hemiagenesis Accompanying a Thyroglossal Duct Cyst: A Case Report
Authors: SAMUEL K. TSANG, JOHN MAHER
Journal: Clinical Nuclear Medicine (1998)

A case of thyroid hemiagenesis discovered incidentally in a patient presenting with a thyroglossal duct cyst is reported. Thyroid embryology is briefly reviewed. Various characteristics of thyroid hemiagenesis and thyroglossal duct cysts are explored.