tbuckley/cabot-search huggingface dataset:
Abstract LB-137: YAP promotes breast cell proliferation and survival partially through stabilizing the KLF5 transcription factor
Authors: Xu Zhi, Dong Zhao, Zhongmei Zhou, Rong Liu, Ceshi Chen
Journal: Cancer Research (2011)

Abstract The Yes-associated protein (YAP) is an oncoprotein in the Hippo tumor suppressor pathway that regulates tumorigenesis. Although YAP functions through its WW domains, the YAP WW domain binding partners have not been completely determined. In this study, we demonstrate that YAP functions partially through binding to KLF5, a transcription factor promoting breast cell proliferation and survival. YAP interacts with the KLF5 PY motif through its WW domains, prevents WWP1, a KLF5 E3 ubiquitin ligase, from binding to KLF5, and stabilizes KLF5 by decreasing the WWP1-mediated KLF5 ubiquitination and degradation. Over-expression of the wild type but not WW domain deficient YAP up-regulates the KLF5 protein levels and the mRNA expression levels of the KLF5 downstream target genes, including FGF-BP and ITGB2. In addition, knockdown of YAP decreases the expression levels of KLF5, FGF-BP, and ITGB2. Depletion of either YAP or KLF5 decreases breast cell proliferation and survival in MCF10A and SW527 breast cells. Importantly, stable knockdown of YAP or KLF5 significantly suppresses SW527 xenograft growth in mice. The YAP upstream kinase LATS1 suppresses the KLF5-FGF-BP signaling axis and cell growth through YAP. Finally, both YAP and KLF5 are co-expressed in estrogen receptor (ERα)-negative breast cell lines. These findings suggest that KLF5 is an important transcription factor partner for YAP and contributes to the Hippo tumor suppressor pathway. This study is supported by a grant from the American Cancer Society (RSG-08–199–01) and a grant from the Department of Defense (W81XWH-07–1–0191). 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 LB-137. doi:10.1158/1538-7445.AM2011-LB-137
SAT0382 Arthrosonographic Findings in Crystal Arthropathies
Authors: R. Bergner, L. Peters, V. Schmitt, H. Sattler, C. Löffler
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> At the time, crystal arthropathies (CA) (e.g. calcium pyrophosphate crystal deposition disease (CPPD) and gout (GA)) can be diagnosed definitely only by microscopic investigation of joint effusion with polarisation filter, especially if the clinical aspect is atypical. <h3>Objectives</h3> It is known that gout arthritis (GA) can show a typical double contour (DC) sign in joint ultrasound. Previous studies investigated only GA compared with non crystal arthropathies (NCA). But there are no data about the sensitivity and specificity of different sonographic findings in NCA, compared with GA and CPPD. We investigated the sensitivity and specificity of sonographic findings in GA and CA (GA + CPPD) in patients with GA, CPPD and NCA. <h3>Methods</h3> In this observational study we analyzed arthrosonographic findings like synovitis (SYN), hypervascularisation (HV) and a DC sign in patients who underwent diagnostic joint puncture. Relevant were only the findings in the punctured joint. SYN and HV were measured semiquantitatively on a scale from 0 – 3. The joint effusion was investigated with native microscopy and with polarisation filter. Sensitivity and specificity were calculated for the different findings for GA alone and crystal arthritis (GA and CPPD) in general. <h3>Results</h3> Analyzed were 103 patients with 113 punctered joints. In 39 joints we found GA, in 17 CPPD and in 57 NCA, respectively. Investigated were knee joints (n=74), small finger or toe joints (n=10), elbows (n=5), ankle (n=12), shoulders (n=6) and wrists (n=6). SYN was 2.2±0.8 (GA), 2.4±0.8 (CPPD) and 2.3±0.8 (NCA) (n.s.), respectively. HV was 2.2±1.0 (GA), 1.9±1.0 (CPPD) and 1.2±1.1 (NCA); (p&lt;0.001 GA vs. NCA and p=0.03 CPPD vs. NCA), respectively. DC was found in 36 of 39 patients with GA, in 14 of 17 patients with CPPD and 7 from 57 with NCA, respectively. The sensitivity and specificity of DC was 92% and 72% for GA, and 89% and 88% for CA in general. For HV ≥ 2 sensitivity and specificity was 69% und 51% for GA and 71% and 60% fpr CA in general. If HV ≥ 2 and positive DC were combined specificity increased to 80% for GA and 93% for CA, but sensitivity decreased to 67% and 66%, respectively. There was no significant difference in serum uric acid between GA and CPPD (9.8±3.4 and 7.6±4.2 mg/dl) at the time of joint puncture. <h3>Conclusions</h3> Ultrasonography has good sensitivity and specificity to diagnose CA in general. If a DC was detected and the HV was ≥ 2, more than 90% of CA were detected, but arthrosonography was weak in differentiation of GA and CPPD. A joint puncture is still necessary to differentiate GA and CPPD. <h3>Disclosure of Interest</h3> None Declared
P102 CLEVER-1 mediates the transmigration of B cells across human hepatic sinusoidal endothelium
Authors: S. Shetty, C. Weston, Y. Oo, Z. Stamataki, M. Salmi, S. Jalkanen, P. Lalor, D. Adams
Journal: Gut (2011)

<h3>Introduction</h3> Lymphocytes are recruited via the unique hepatic sinusoidal channels during chronic inflammatory liver diseases. This low shear vascular bed is lined by hepatic sinusoidal endothelium (HSEC) which lacks certain conventional adhesion molecules leading us to look for novel receptors involved in lymphocyte recruitment. HSEC express several scavenger receptors including CLEVER-1 which we have recently shown mediates regulatory T cell recruitment to HSEC. B cells have been implicated in the pathogenesis of liver disease and driving liver fibrosis. <h3>Aim</h3> B cells must be recruited from the peripheral circulation into liver tissue but the molecular mechanisms that mediate this process are not known. Our aim was to study if CLEVER-1 plays a role in this process. <h3>Method</h3> We used isolated HSEC in flow adhesion assays to study the functional role of CLEVER-1 in lymphocyte subset recruitment. Immunofluorescent staining and confocal microscopy were used to characterise the transmigration of lymphocytes across HSEC under conditions of flow. Time lapse video recordings and Image J software was used to compare T cell and B cell recruitment via HSEC monolayers under conditions of flow. <h3>Results</h3> Flow-based adhesion assays using human HSEC demonstrated that B cells were captured from flow and adhered to human HSEC but they had limited motility in comparison to T cells. B cells also underwent transmigration and CLEVER-1 blockade led to a reduction of B cells undergoing transmigration. Blockade of CLEVER-1, VAP-1 and ICAM-1 in combination had a cumulative effect on transmigration, suggesting that all three receptors contributed to B cell transmigration. <h3>Conclusion</h3> Up to now most interest has focused on the role of T cells but hepatic infiltrates contains B cells and B cells have been directly implicated in models of liver disease and as drivers of liver fibrosis. This work demonstrates that CLEVER-1 is an adhesion molecule within the hepatic sinusoids and contributes to B cell transmigration. CLEVER-1 is a potential target for modulating B cell recruitment to the human liver.
A Surprising Cause of Chronic Cough
Authors: Deepti Damaraju, Ted Steiner, John Wade, Kenneth Gin, J. Mark FitzGerald
Journal: New England Journal of Medicine (2015)

A 63-year-old nonsmoking man presented to clinic with a 2-year history of cough. The cough was dry, was worse at night, and began after an upper respiratory tract infection and a trip to South America.
Gated SPECT Offers Improved Interobserver Agreement Compared With Echocardiography
Authors: Anders Hovland, Uwe H. Staub, Hanne Bjørnstad, Jan Prytz, Joe Sexton, Asbjørn Støylen, Harald Vik-Mo
Journal: Clinical Nuclear Medicine (2010)

Left ventricular ejection fraction (EF) is a powerful predictor of prognosis in coronary artery disease. The purpose of the present study was to measure interobserver differences for gated SPECT (GSPECT) software and echocardiography, and to compare these modalities regarding left ventricular volumes and EF.Eighty-four patients scheduled for nuclear imaging underwent a 1-day GSPECT with Tc-99m-tetrofosmin. Images were processed by 2 raters who calculated volumes and EF using Cedar-Sinai quantitative gated-SPECT (QGS), Emory Cardiac Toolbox (ECT), and 4D-MSPECT of the University of Michigan. Echocardiographic volumes were measured by 2 raters. Interobserver reliability was assessed by intraclass correlation coefficient (ICC). Differences in volumes and EF between echocardiography and GSPECT were compared with t-tests.ICC was 0.61 for echocardiography, 0.94 for QGS, 0.88 for ECT, and 0.91 for 4D-MSPECT (P < 0.0001 compared with echocardiography). For small ventricles (ESV ≤30 mL), ICC was 0.58 for echocardiography and 0.90 for QGS (P = 0.008 compared with echocardiography); 0.77 and 0.73 for ECT and 4D-MSPECT, respectively (P = ns). End-diastolic and end-systolic volumes were significantly larger with GSPECT than with echocardiography, also echocardiographic ejection fraction was significantly different from GSPECT.There is better interobserver reliability in GSPECT as compared with echocardiography, and QGS seems more robust in this study especially when it comes to small ventricles.
A Quantitative Analysis of Subclonal and Clonal Gene Mutations before and after Therapy in Chronic Lymphocytic Leukemia
Authors: Nisar A. Amin, Erlene Seymour, Kamlai Saiya-Cork, Brian Parkin, Kerby Shedden, Sami N. Malek
Journal: Clinical Cancer Research (2016)

Chronic lymphocytic leukemia (CLL)-associated gene mutations that influence CLL cell fitness and chemotherapy resistance should increase in clonal representation when measured before therapy and at relapse.To uncover mutations associated with CLL relapse, we have performed whole-exome sequencing in a discovery cohort of 61 relapsed CLL patients identifying 86 recurrently mutated genes. The variant allele fractions (VAF) of 19 genes with mutations in ≥3 of 61 cases were measured in 53 paired pre- and posttreatment CLL samples sorted to purity using panel-based deep resequencing or by droplet digital PCR.We identify mutations in TP53 as the dominant subclonal gene driver of relapsed CLL often demonstrating substantial increases in VAFs. Subclonal mutations in SAMHD1 also recurrently demonstrated increased VAFs at relapse. Mutations in ATP10A, FAT3, FAM50A, and MGA, although infrequent, demonstrated enrichment in ≥2 cases each. In contrast, mutations in NOTCH1, SF3B1, POT1, FBXW7, MYD88, NXF1, XPO1, ZMYM3, or CHD2 were predominantly already clonal prior to therapy indicative of a pretreatment pathogenetic driver role in CLL. Quantitative analyses of clonal dynamics uncover rising, stable, and falling clones and subclones without clear evidence that gene mutations other than in TP53 and possibly SAMHD1 are frequently selected for at CLL relapse.Data in aggregate support a provisional categorization of CLL-associated recurrently mutated genes into three classes (i) often subclonal before therapy and strongly enriched after therapy, or, (ii) mostly clonal before therapy or without further enrichments at relapse, or, (iii) subclonal before and after therapy and enriching only in sporadic cases. Clin Cancer Res; 22(17); 4525-35. ©2016 AACR.
Oregon Health System Overhaul May Become National Model
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Oregon Health System Overhaul May Become National Model Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 14, 15 July 1992, Pages 1064–1065, https://doi.org/10.1093/jnci/84.14.1064 Published: 15 July 1992
SAT0439 Treatment of lateral epicondylitis with injection of platelet-rich plasma or corticosteroid versus saline: A randomized, double-blind, placebo-controlled trial
Authors: T. Krogh, U. Fredberg, K. Stengaard-Pedersen, R. Christensen, T. Ellingsen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lateral epicondylitis (LE) is a common musculoskeletal disorder for which an effective treatment strategy still remains absent. <h3>Objectives</h3> To examine whether one injection with Platelet-rich plasma (PRP) is more effective than saline and corticosteroid (CS) in reducing pain in adults with LE. <h3>Methods</h3> A block randomized, double-blind, placebo-controlled trial with primary outcome assessed at 3 months, and with a 12 months follow-up, conducted between January 2009, and June 2011. Patients who did not achieve a satisfying treatment response (assessment made by patient and doctor) at 3 month had the option to discontinue the study and receive other treatment. In total, 60 patients with chronic LE were randomized (1:1:1) to receive either a blinded injection of PRP, saline or CS. The primary outcome was change in pain compared to baseline using the Patient Rated Tennis Elbow Evaluation (PRTEE) questionnaire at 3 months. Secondary endpoints were all assessed at 1 month, plus ultrasonographic changes in tendon thickness and color doppler activity at 3 months. <h3>Results</h3> The 60 enrolled patients in the intention to treat population had an average PRTEE pain score at baseline of 26.8 (SD 7.6). All randomized patients completed the study. At endpoint 3 months from baseline pain reduction was observed in all three groups, with no statistical significant difference between the groups. CS vs. saline -3.76 (95% CI -9.94 to 2.42), PRP vs. saline -2.64 (95% CI -8.80 to 3.52) and CS vs. PRP -1.12 (95% CI -7.23 to 4.99). However, at one month CS reduced pain more efficiently than both saline and PRP. The mean difference at one month between CS and saline was -8.11 (95% CI -14.29 to -1.93), between CS and PRP -9.27 (95% CI -15.38 to -3.16). CS was more efficient than PRP and saline in reducing both color doppler activity and tendon thickness at three months. Only 16 of 60 patients completed the entire 12 months follow-up. The huge attrition rate was due to lack of treatment efficacy. <h3>Conclusions</h3> This RCT showed no superiority of either PRP or CS compared to saline in pain reduction in LE at primary endpoint. However, anticipating immediate relief, CS had a short term pain reducing effect at one month in contrast to the other therapies. At 6 and 12 months the attrition rates in all treatment arms were too high for any meaningful conclusions to be made. <h3>Disclosure of Interest</h3> None Declared
ECHOCARDIOGRAPHIC PREDICTORS OF COMBINED PRE AND POST CAPILLARY PULMONARY HYPERTENSION (PH) IN A POPULATION OF SYSTOLIC HEART FAILURE WITH WHO GROUP II PULMONARY HYPERTENSION
Authors: Guha Ashrith, Nadia Fida, Andrea Cordero-Reyes, Javier Amione-Guerra, Zahoor Khan, Arvind Bhimaraj, Barry Trachtenberg, Guillermo Torre-Amione, Sherif Nagueh, Jerry Estep
Journal: Journal of the American College of Cardiology (2015)
Abstract LB-296: Involvement of T-cell immunity in changes in the plasma amino acid profiles of patients with colorectal cancer
Authors: Eiji Ohara, Yasuhiko Kitadai, Kei Shinagawa, Tomonori Sumida, Miwako Tanaka, Mayu Ohnishi, Kenta Nagai, Yoshitaka Ueno, Shinji Tanaka, Kiyomu Fujii, Kazuki Nakamura, Junya Yoneda, Kazuaki Chayama
Journal: Cancer Research (2011)

Abstract Metabolic changes in patients with various disorders, including liver disease and cancer, lead to alterations in amino acid balance, and plasma amino acid profiles can be used to discriminate between non-malnourished patients with cancer and healthy individuals. Not with standing, the mechanisms of amino acid imbalance are not well understood. In patients with cancer, various factors including metabolic changes in the tumor itself and immune responses may affect plasma amino acid levels. To investigate involvement of the immune system, we measured plasma amino acid levels in an orthotopic transplant model of colon cancer established in both conventional BALB/c mice and athymic BALB/c nude mice (T-lymphocyte-deficient mice). CT26 colon cancer cells (murine colon cancer cell line) were implanted into the cecal wall of the BALB/c mice (n=10) and nude mice (n=10). Plasma samples were collected from the tumor-bearing mice at 7 and 14 days after transplantation, and changes in plasma amino acid profiles were compared. Plasma was also collected from mice that underwent sham operation (control mice, n=10). Plasma amino acid concentrations were measured by LC/MS/MS. The plasma concentrations of several amino acids changed significantly in tumor-bearing mice compared to concentrations in control mice. Although cells from the same line were injected into the cecal wall of BALB/c mice and nude mice, a difference was noted in the change in plasma amino acid levels. Plasma Val, Ile, Leu, and Met levels decreased in BALB/c mice but increased in nude mice. There was no difference in the amino acid profile of CT26 tumor tissues between BALB/c mice and nude mice. We then injected antiCD3-antibody into the peritoneal cavity of tumor-bearing BALB/c mice (n=5) to eliminate T-cell function. We also injected IgG into tumor-bearing BALB/c mice (n=5) for control. The pattern of change in amino-acid profiles differed between the two groups of mice. Our findings suggest that T-lymphocyte-mediated immunoreactions are involved in changes in the plasma amino acid profile in patients with colorectal 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 LB-296. doi:10.1158/1538-7445.AM2011-LB-296
P215 The effect of Oxygen prescription at hospital discharge on re-admission rates in Chronic Obstructive Pulmonary Disease (COPD)
Authors: R. Mukherjee, M. Kotska, J. A. Brebner, R. Rashid, B. Chakraborty, Y. Khan, P. Sweeney, P. S. Burge
Journal: Thorax (2011)

<h3>Introduction</h3> A previous survey highlighted a very high degree of physiologically unnecessary home oxygen use in COPD patients (Bhattacharya M, Potter A, Mukherjee R. Assessing for Long Term Oxygen Therapy (LTOT) in an English town. <i>Am J Resp Crit Care Med</i> 2008;<b>177</b>:A665), a common reason for which was noted to be many physicians9 belief that issuing oxygen on discharge of breathless COPD patients prevents re-admissions. <h3>Methods</h3> A retrospective review of 1942 COPD admissions (including re-admissions) of Birmingham East and North Primary Care Trust patients from April 2007 to November 2010 based on International Classification of Diseases (ICD) coding (J44) of which 295 received home oxygen on discharge; Welch9s 2-sample t-test was applied to assess the significance of the difference in the admission rates of the two groups of COPD patients who receive and did not receive LTOT on discharge. A further analysis was performed in a cohort of 186 patients (93 discharged with and 93 without oxygen) with known values of Forced Expiratory Volume in 1 second (FEV<sub>1</sub>) to examine if oxygen prescription had an effect on the re-admission rate, taking the best FEV<sub>1</sub> in the 5 years preceding the first admission. In the known FEV<sub>1</sub> group, the logarithm of the number of admissions was taken to account for non-linearity and to count the readmissions only (as log 1=0). <h3>Results</h3> In the whole group (COPD diagnosis based on ICD coding: n=1942), the mean annual admission rate in the home oxygen group was 3.18 and 1.67 in the other (p&lt;0.00000000001). In the group with known FEV<sub>1</sub> (n=186), the number of re-admissions depended significantly on the FEV<sub>1</sub> (p=0.000362); home oxygen prescription on discharge did not have any significant effect on re-admissions (p=0.897). <h3>Conclusion</h3> LTOT prescription on discharge is actually associated with a crude increase in hospital admissions of COPD patients. FEV<sub>1</sub> remains the strongest predictor of re-admissions. Further prospective studies including detailed pre-discharge physiological assessment prior to issuing home oxygen are necessary.
Occult Phosphaturic Mesenchymal Tumor Detected by Tc-99m Sestamibi Scan
Authors: HERRICK J. SIEGEL, MICHAEL G. ROCK
Journal: Clinical Nuclear Medicine (2002)

From the Department of Orthopaedic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota Received for publication October 31, 2001. Accepted January 8, 2002. Correspondence: Herrick J. Siegel, 200 First Street, SW, Mayo E14, Rochester, Minnesota 55905. E-mail: [email protected]
Abstract 3054: MicroRNA expression profile in cutaneous melanoma: miR-17-92 cluster is a progression and prognostic marker
Authors: Donghwa Kim, Jianjun Zhao, William Kong, Keiran S. Smalley, Jane L. Messina, Jeffrey S. Weber, Jin Q. Cheng
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRNA) represent a novel class of RNAs that play important roles in cell survival, proliferation, differentiation and angiogenesis through negative regulation of protein-coding genes. Deregulation of miRNAs has been detected in various types of human malignancies. Some miRNAs are implicated in diagnosis, prognosis, treatment response and pathogenesis. However, aberrant miRNA expression and its pathologic significance in human melanoma have not been well documented. Here, we report on the miRNA expression profile of human cutaneous melanoma as well as melanoma cell lines. Of 650 miRNAs examined, at least 28 miRNAs were significantly deregulated in melanoma compared to normal skin and primary melanocytes, with the most common aberrantly expressed miRNAs being miR-17-92 cluster, miR-21, miR-146a/b. miR-148a/b, miR-126, miR-606, and miR-655. Notably, miRNA expression signatures could stratify patients into 2 groups (e.g., good and poor prognosis). Further analysis revealed that elevated levels of the miR17-92 cluster are associated with tumor progression and shorter overall survival. Our results suggest that miRNAs may be a useful new biomarker for and be a therapeutic target in cutaneous melanoma. 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 3054.