tbuckley/cabot-search huggingface dataset:
Abstract 234: Fibroblast growth factor receptor (FGFR)-3 as a suitable target in bladder cancer
Authors: Kilian M. Gust, David J. McConkey, Paul K. Hegarty, Jolanta E. Bondaruk, Bogdan A. Czerniak, Colin P. Dinney, Peter C. Black
Journal: Cancer Research (2011)

Abstract Introduction and Objective: Mutations in the FGFR3 gene, which can confer constitutive activity, are found in up to 80% of low grade papillary bladder cancers (BC). Overexpression of FGFR3 has been detected in approximately half of high grade and invasive tumors. In this study we evaluate FGFR3 in a cohort of American patients and investigate the effect of targeting FGFR3 in pre-clinical models of bladder cancer. Materials and Methods: DNA was extracted from 170 fresh frozen BC specimens using a commercial kit and PCR of exons 7 and 10 was performed. Mutation analysis was performed by ABI Big Dye Terminator Cycle Sequencing. FGFR3 expression was analyzed by immunohistochemistry in an overlapping cohort of 143 patients with BC. FGFR3 expression, phosphorylation and downstream signaling were measured in a panel of BC cell lines, and the efficacy of two small molecule inhibitors (TKI258 and BGJ398) was tested on signaling and 3H-thymidine incorporation. A specific inhibitory monoclonal antibody targeting FGFR3 was evaluated in an orthotopic xenograft model of BC. Tumor burden was measured with bioluminescent imaging. Results: FGFR3 mutations were identified in 44 (26%) BC samples, including 28/50 (56%) of low grade papillary lesions. Overexpression of FGFR3 was noted in 53% of all BC specimens regardless of stage and grade, but not in normal urothelium. FGFR3 inhibition effectively abrogated constitutive phosphorylation of FGFR3 and p42/44MAPK in a subset of bladder cancer cell lines. A growth inhibitory effect was observed in the same cell lines. The growth of UC14 xenografts in the bladder of nude mice was inhibited by 40%. Conclusion: These studies underline the potential clinical relevance of FGFR3 mutation and expression in bladder cancer. Furthermore, the preclinical investigations offer proof of principle for moving forward with clinical trials studying the administration of specific FGFR3 inhibitors in patients with bladder cancer. 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 234. doi:10.1158/1538-7445.AM2011-234
PWE-229 Assessing patient reported outcome in Crohn's disease
Authors: J Wilburn, S R Crawford, S P McKennna, J Twiss, M Ben-L'amri, K Kemp, S Campbell
Journal: Gut (2012)

<h3>Introduction</h3> Research into the impact of Crohn9s Disease (CD) and its treatment on the patient relies on outdated and inappropriate generic questionnaires. These do not address important impacts of the illness and ask questions of limited relevance. As part of a study to develop CD-specific patient-reported outcome measures (PROMS), qualitative interviews were conducted with CD patients. <h3>Methods</h3> Item generation was based on the International Classification of Functioning, Disability and Health (ICF) and the needs-based quality of life (QoL) models. Interviewees were recruited via out-patient clinics and interviewed in a private room or at the researcher9s offices. Interviews covered all aspects of the impact of CD and its treatment and were audio-recorded. Transcripts were content analysed to identify impacts on symptoms, activity limitations and QoL. <h3>Results</h3> 26 patients (69.2% female; aged 25–68; mean (SD): 46.2 (14.7) years) were interviewed. Participants had a wide range of duration of CD (2–40; mean (SD): 13.0 (12.9) years). 2641 statements relating to the impact of CD were identified. These statements fell into three major categories with a number of sub-themes identified: Symptoms (such as pain, fatigue and emotional impairment), activity limitations (such as difficulties with walking, lifting and jobs around the house) and QoL (including preoccupation with the disease, self-conscious of appearance and reduced socialisation). <h3>Conclusion</h3> The study was successful in identifying the most important impacts of CD from the patients9 perspective. In addition to generating potential items for the new measure the findings of the interviews have implications for clinical practice and clinical trial design. Audit of services and assessment of new interventions for CD should assess whether or not these impacts of CD are improved. Only then will it be possible to determine whether interventions are of true benefit to the patient. <h3>Competing interests</h3> None declared.
Abstract LB-129: CAFET algorithm reveals WNT/PCP specific signature in squamous cell carcinoma of lung cancer
Authors: Yue Hu
Journal: Cancer Research (2010)

Abstract We analyzed the global gene expression patterns of 138 lung cancer samples containing Squamous Cell Carcinoma (SCC) and Adenocarcinoma (AC). Gene set enrichment analysis revealed developmental and cell cycle functional groups were specifically overexpressed in SCC samples. To refine and focus our analysis on specific signaling pathways, we developed a complementary algorithm called Coverage Analysis with Fisher Exact Test (CAFET). In our analysis, the WNT signaling pathway had the most significant enrichment of overexpressed genes in a cluster of predominantly SCC. Most interestingly, the differential expression pattern in this cluster had a strong tendency to inhibit the WNT canonical pathway while enhancing the WNT/PCP pathway. The non-canonical WNT/PCP pathway is obligatory for cell migration during embryogenesis, and it has also been proposed to be involved in cancer metastasis. While the WNT canonical pathway has been reported to be important in metastasis of AC in lung cancer, our results suggest SCC of lung makes use of a different branch of the WNT pathway for survival and development. This WNT/PCP signature for lung SCC was also confirmed in several independent sample sets. It is also present in some cell lines derived from lung SCC. To find potential clinical biomarkers, we identified 174 genes present in blood and highly expressed in samples carrying this WNT/PCP signature. These results demonstrate that the new algorithm CAFET is a promising approach for mining large gene expression data sets to identify pathways with differential activity, and could be particularly useful in exploring cancer expression datasets. 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 LB-129.
An Economic Perspective on the Individual Mandate's Severability from the ACA
Authors: Bradley Herring
Journal: New England Journal of Medicine (2011)

Four U.S. district court judges have now ruled on the constitutionality of the individual mandate of the Affordable Care Act (ACA), which requires people to obtain health insurance coverage or pay a penalty through their federal income taxes. Two of these judges, both nominated by a Democratic president, upheld the mandate; the other two, both appointed by Republican presidents, rejected it. Given that party-line split and the similar one in Congress on both the passage of the ACA and the recent effort to repeal it, many observers have speculated that the mandate's constitutionality will ultimately have to be decided by . . .
Hepatobiliary Scintigraphy in Liver Transplant Patients
Authors: Steven A. Young, George N. Sfakianakis, Nikolaos Pyrsopoulos, Seigo Nishida
Journal: Clinical Nuclear Medicine (2003)

Purpose Hepatobiliary scintigraphy is commonly performed on liver transplant patients to exclude biliary complications such as obstruction or leak. Biliary reconstruction in these patients is performed using either a direct duct-to-duct anastomosis (choledochocholedochostomy) or a biliary–enteric anastomosis (Roux-en-Y hepaticojejunostomy). The authors have observed a finding in scans performed on the latter group of patients that often simulates a bile leak. They postulate this finding to represent retention of activity in the blind end of the Roux limb (the “blind end sign”). The purpose of this study was to determine characteristics of this blind end activity, which may help differentiate it from true bile leaks. Methods Two nuclear medicine physicians reviewed 36 Tc-99m mebrofenin hepatobiliary scans (31 patients). Biliary reconstruction was performed in 25 patients with a Roux-en-Y hepaticojejunostomy, and in 6 patients with a choledochocholedochostomy. Each scan was evaluated regarding whether there was focal, persistent retention of activity in the anastomotic region, and, if so, various features of the activity were noted. Activity was concluded to represent a true bile leak based on subsequent surgical confirmation, and if there was no such confirmation, the activity was concluded to represent blind end retention in patients with Roux-en-Y hepaticojejunostomies. Results There were 8 total examples of blind end activity and 3 examples of bile leak activity. Useful discriminators between the 2 types of activity included the following: fluctuation in size and/or intensity with time (8 of 8 blind end cases vs. 0 of 3 bile leak cases); size comparable with bowel (8 of 8 vs. 1 of 3); tubular (4 of 8 vs. 0 of 3), round (4 of 8 vs. 1 of 3), or irregular (0 of 8 vs. 2 of 3) shape; and movement into bowel (3 of 8 vs. 0 of 3). Delayed imaging was performed in 3 cases at 1.5 hours, but was only conclusive in 1 case in which diffuse extravasation was seen consistent with bile leak. Conclusion Retention of activity in the blind end of the Roux limb in patients with Roux-en-Y hepaticojejunostomies may simulate bile leak, but certain typical features, as well as delayed imaging, may aid in distinguishing the two.
AN AUDIT OF THE LAST 500 BOWEL CANCER SCREENING PROCEDURES WITHIN THE NORTHERN TRUST
Authors: J Somerville, P Lynch, C Rodgers, G Jacob, D McCrory
Journal: Gut (2013)

<h3>Introduction</h3> The Bowel Cancer Screening Programme (BCS) in Northern Ireland offers screening every two years to all men and women aged 60 to 71. An FOB (faecal occult blood) kit is sent to the patient9s home, with FIT (faecal immunochemical testing) testing if inconclusive or unsuitable test. All patients with positive tests are then offered screening with CT colography or colonoscopy. <h3>Aims/Background</h3> To assess the detection rate of pathology during the last 500 procedures performed on patients entering the Northern Trust BCS programme and the percentage requiring follow-up procedures or surveillance. <h3>Method</h3> Data was collected and analysed from patient records kept by the BCS Special Screening Practitioners in Whiteabbey Hospital. <h3>Results</h3> Data was collected from the 11th January 2012 to 20th February 2013 inclusive. Of the last 500 screening procedures, 396 were colonoscopies (caecal intubation rate 93.4%), 68 CT colographies and 36 flexible sigmoidoscopies. 8% (40 patients) had a cancer detected and 48.6% (243 patients) had polyps excised. Bleeding was recorded as a complication following polypectomy in 2% (10 patients). Poor preparation complicated 5.8% (29 procedures). 22 prcoedures were abandoned–19 a decision by the colonoscopist, 3 at patient request. 91 (18.2%) patients required further investigation for screening completion - 41 required colonoscopy, 31 flexible sigmoidoscopy, 17 CT colography and 2 patients surgery for complex polyps. 131 will require a follow-up surveillance colonoscopy–38 at 1 year and 93 at 3 years. <h3>Conclusion</h3> The BCS programme has a high pathology detection rate and many patients require further procedures to complete screening and follow-up procedures for surveillance.
Abstract 4834: Microarray gene expression analysis on formalin-fixed, paraffin embedded material is feasible and the resulting profiles are comparable to profiles from fresh frozen matched material
Authors: Lorenza Mittempergher, Jorma J. de Ronde, Marja Nieuwland, Ron M. Kerkhoven, Iris Simon, Lodewyk FA Wessels, Laura J. Van ‘t Veer
Journal: Cancer Research (2011)

Abstract Formalin Fixed Paraffin Embedded (FFPE) samples represent a valuable resource for cancer research and clinical setting. However, the discovery and development of new cancer biomarkers often requires fresh frozen (FF) samples. In this study, we profiled, in duplicate, 20 FFPE breast cancer tissues and 20 matched FF tissues and evaluated the concordance of the gene expression results from FFPE and matched FF material using the whole Genome (WG) DASL assay. We show that clinically relevant biomarkers developed on FF samples can be applied to FFPE samples. We show that after proper normalization, all FFPE and FF pairs exhibited a high level of similarity (Pearson correlation &amp;gt; 0.7), significantly larger than the similarity between non-paired samples. Interestingly, the probes showing the highest correlation had a higher G/C content percentage and were enriched for cell cycle genes. Predictions of gene expression signatures developed on frozen material (Intrinsic subtype, Genomic Grade Index, 70 gene prognosis signature) show a high level of concordance between FFPE and FF matched pairs. Predictions based on a 60 gene DASL list (best match with the 70 gene signature) show very high concordance with MammaPrint® results. We demonstrate that data generated from FFPE material with the DASL assay, if properly processed, are comparable to data extracted from the FF counterpart. This opens up the possibility of using both FFPE and FF material in gene expressions analyses, leading to a vast increase in the potential resources available for cancer research. 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 4834. doi:10.1158/1538-7445.AM2011-4834
Abstract P4-06-06: RNAi screen of the breast cancer genome identifies KIF14 and TLN1 as genes that modulate chemosensitivity in breast cancer
Authors: SM Singel, C Cornelius, K Batten, G Fasciani, WE Wright, L Lum, JW Shay
Journal: Cancer Research (2012)

Abstract We conducted a RNA-interference screen for genes whose loss-of-function enhanced doxorubicin and docetaxel chemosensitivity in a “triple-negative,” estrogen receptor negative, progesterone receptor negative, and Her2 negative (ER− PR− Her2−) breast cancer cell line, MDA-MB-231. From ranking chemosensitivity of 334 short-hairpin RNA (shRNA) MDA-MB-231 cell lines (targeting 134 genes with known somatic mutations in breast cancer), we focused on two genes, kinesin family member 14 (KIF14) and talin (TLN1) that not only enhanced chemosensitivity but also have oncogenic annotations. KIF14 has robust expression in breast cancer cells compared to normal mammary cells. TLN1 expression is important for migration of breast cancer cells. In TLN1-deficient cells, CK19 and ZO-1 are upregulated while CK14 and snail are downregulated, suggesting that TLN1 is important for the maintenance of epithelial-mesenchymal transition in MDA-MB-231 cells. KIF14 and TLN1 loss-of-function also enhanced chemosensitivity in 3 other triple negative breast cancer cell lines (HCC1937, HCC38, and Hs578T) but not in normal human mammary epithelial cells (HMECs). Examining protein-protein-interaction networks, we identified RIP2 as a target whose inhibition via SB203580 or PP2 can further enhance chemosensitization in KIF14-deficient cells. Knock-down of a number of other known protein-protein interaction partners of KIF14 and TLN1, including FAK, CIT, ARRB2, PSTPiP1, PRC1, SVIL, ITGA2B, ITGB3, VCL and PXN, do not significantly alter doxorubicin or docetaxel chemosensitivity in MDA-MB-231 cells. Mammary fat pad xenografts of KIF14- and TLN1- deficient MDA-MB-231 cells into NOD/SCID mice demonstrated significantly less tumor mass compared to control MDA-MB-231 cells after chemotherapy. Expressions of KIF14 and TLN1 from breast cancer expression arrays improve prognostic predictions compared to clinicopathological features alone. In summary, screenings for therapeutic targets using chemotherapy and genes with known somatic mutations in breast cancer not only provide a rational targeted screen, but also present possible up-front novel treatment combinations for patients with triple negative breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-06.
SP0119 Biomechanical and Immunological Aspects of Fracture Healing: Update 2013
Authors: G. N. Duda
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The initial events after fracture seem to be essential for fast and uneventful bone healing. Tissue organization (e.g. invasion of vessels) starts early, leading to a restructuring of the hematoma. Interestingly, almost all accounts of the fracture healing process begin with the discussion of the invasion of inflammatory cells to the wound site as the first event. However, this starting point ignores the important fact that the initial fracture hematoma already contains inflammatory cells. The initial cell composition and its particular microenvironment could be among the factors, which crucially determine whether fracture healing proceeds effectively. This talk aims to give a detailed overview, beginning with the first events in fracture healing and bone regeneration, followed by a description of the close interplay between bone and the immune system, which already implicates an important role for immune cells in fracture healing. Bone healing in knockout mice devoid of mature T and B cells is compared with the healing in mice depleted of cytotoxic (CD8) T cells at the time of injury. The data is considered in the context of in vitro results and compared to a large animal model as well as clinical studies. Results focus on aspects of the early fracture hematoma with special regard to the initial immunologic features. We will demonstrate the importance of immune cells for the cellular composition in the injured region dictating the healing course and progression. This research seems to be of vital importance, especially in immunologically suppressed patients, suffering from delayed healing or non-union situations. The understanding of the initial phase of healing could play a pivotal role in future fracture treatment strategies and allow us to differentiate between aspects of inflammation that are essential for bone healing and those that delay bone healing. <h3>Disclosure of Interest</h3> None Declared
HOSPITALIZATION OF LOW RISK CHEST PAIN PATIENTS WITH NORMAL TROPONIN AND COPEPTIN
Authors: Neil Beri, Nicholas Marston, Paul Clopton, Lori Daniels, Donald Schreiber, Christian Mueller, Allan Jaffe, Christopher DeFilippi, W. Frank Peacock, Inderjit Anand, James McCord, Alexander Limkakeng, Judd Hollander, Alan Wu, Fred Apple, Deborah Diercks, John Nagurney, Chad Cannon, Sean-Xavier Neath, Robert Christenson, Richard Nowak, Christopher Hogan, Gary Vilke, Alan Maisel
Journal: Journal of the American College of Cardiology (2016)
GW25-e3388 Three-Dimensional Rotation, Twist and Torsion Analyses by Real-time 3-D Speckle Tracking Imaging: Feasibility, Reproducibility, and Normal Ranges in Pediatric Population
Authors: Zhang Li, Xie Mingxing, Wu Wenqian, Gao Jun, Ge Shuping
Journal: Journal of the American College of Cardiology (2014)
892 ANEMIA PREDICTS SUSTAINED VIROLOGIC RESPONSE IN CIRRHOTIC AND NON-CIRRHOTIC CHRONIC HEPATITIS C (CHC) PATIENTS TREATED WITH PEGINTERFERON alfa-2a AND RIBAVIRIN IN FOUR CLINICAL TRIALS
Authors: N. Reau, E.J. Korner, J. Han, D.M. Jensen
Journal: Journal of Hepatology (2013)
Abstract 15762: Gapdh Interaction With Ape1 Endonuclease Protects Vascular Smooth Muscle Cells Against Apoptosis: Potential Role of These Enzymes in Prevention of Atherosclerotic Plaque Destabilization
Authors: XW. Hou, T. Yoshida, Y. Higashi, SY Shai, C. Kim, P. Delafontaine, S. Sukhanov
Journal: Circulation (2015)

We have shown that oxidized lipids (OxLDL) co-localized with apoptotic vascular smooth muscle cells (VSMC) in atherosclerotic plaque and that OxLDL downregulated the major glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cultured VSMC via H2O2-dependent mechanism. We hypothesized that maintenance of sufficient GAPDH levels is critical for cell survival under oxidative stress. H2O2 (220 uM, 12h) decreased GAPDH protein (55±5% decrease) and induced apoptosis (TUNEL assay) in human VSMC. Human VSMC transfection with pCMV-GAPDH increased GAPDH protein (3.5-fold) and prevented H2O2-induced apoptosis (74±4% decrease) vs. pCMV-GFP. We generated rat VSMC with constitutive 2-fold overexpression GAPDH (R3-VSMC). R3-VSMC had increased glycolysis (2.5 folds increase, pyruvate levels), ATP levels (38±2% increase) and reduced oxidative DNA damage (40±2% reduction in number of apurinic/apyrimidinic (AP) sites) and these effects correlated with suppressed H2O2-induced cell apoptosis (&gt;90% reduction, TUNEL assay; 45.7±3.6% reduction, Cell Death ELISA). GAPDH-targeted siRNA reduced GAPDH protein (for 55%) and potentiated H2O2-induced apoptosis (9.4±0.3 folds increase, TUNEL; 8.6±0.4 folds increase, ELISA) in WT-VSMC and blocked anti-apoptotic effect seen in R3-VSMC. GAPDH known to bind apurinic/apyrimidinic (AP) endonuclease 1 (APE1), a major DNA repair enzyme. We found that GAPDH was co-immunoprecipitated and co-localized with APE1 in cytosolic/nuclear fraction and H2O2 induced further GAPDH-Ape1 co-localization and migration toward nuclei. APE1 specific activity was increased in H2O2-treated R3-VSMC vs. H2O2-treated WT VSMC, suggesting that GAPDH preserved APE1 activity under oxidative stress. APE1-targeted siRNA abrogated the protection of GAPDH overexpression against H2O2-induced apoptosis in VMSC. In summary, GAPDH downregulation mediates oxidant-induced VSMC apoptosis and forced expression of GAPDH protects VSMC from H2O2-induced cell death potentially via activation of APE1-dependent DNA repair. Our data suggest that preservation of GAPDH and APE1 activity in plaque VSMC could be a potential strategy to stabilize plaque and prevent acute coronary events.
Some Observations of the Behavior of Amylase in Relation to Acute Renal Insufficiency
Authors: William H. Meroney, Natalie L. Lawson, Milton E. Rubini, John V. Carbone
Journal: New England Journal of Medicine (1956)

THE increased concentration of plasma amylase during chronic renal insufficiency has long been recognized and is considered to be a result of renal excretory failure. Plasma amylase is reported to rise in parallel with urea concentration1 but not to heights encountered in acute pancreatitis.2 Similar rises in amylase might be expected to accompany urea retention in acute renal insufficiency, but this phenomenon has received little attention.The clinical interest in plasma amylase elevation during acute renal insufficiency is heightened by the occurrence in this condition of acute abdominal crises that may resemble acute pancreatitis. The decision to perform or defer . . .
Impact Of Rad50 On Telomere Recombination Mechanisms In Primary Bone Marrow and B-Cell Lymphomas Lacking Telomerase
Authors: Tammy Morrish, Vivek Behera, Joshua Budman, Stephen Dria, Michelle Morgan, David Velliquette, Dulat Bekbolysnov, Alyza Skaist, Sarah Wheelan
Journal: Blood (2013)
A Gut Instinct
Authors: Cybéle L. Abad, Richard H. Moseley, Christopher J. Crnich, Sanjay Saint, Nasia Safdar
Journal: New England Journal of Medicine (2014)

A 30-year-old female physician presented to the emergency department in mid-August, with a 4-day history of anorexia, nausea, vomiting, and diarrhea. She had no fever or respiratory symptoms but had mild abdominal discomfort.