tbuckley/cabot-search huggingface dataset:
Proteomic and IHC measurements of cellular sensitivity to EGF receptor kinase inhibitors
Authors: Stuart Thomson, Filippo Petti, Elizabeth Buck, Sharon Barr, Alexandra Eyzaguirre, Gina Sennello, David Young, Ken Iwata, Pablo Cagnoni, Neil Gibson, John D. Haley
Journal: Clinical Cancer Research (2006)

B66  Aim:The molecular determinants which confer cell sensitivity in wild type (wt) EGFR tumors are multifactorial and complex. Proteomic and IHC assays for key protein markers indicative of sensitive or insensitive to EGFR inhibitors were used to characterize tumor lines, xenografts and tissue samples.Methods and Results: Proteins altered in abundance in NSCLC lines sensitive or insensitive to EGFR inhibitors were identified and quantitated from cellular and phosphotyrosine affinity fractions using LC-MS/MS and stable isotope peptide tag approaches. These data indicated that wild-type EGFR containing human NSCLC lines grown both in culture and as xenografts show a range of sensitivities to EGFR inhibition dependent on the degree to which they have undergone an epithelial to mesenchymal transition (EMT). NSCLC lines which expressed the epithelial cell junction protein E-cadherin showed greater sensitivity to EGFR inhibition in vitro and in xenografts. In contrast, NSCLC lines expressing the mesenchymal markers vimentin and/or fibronectin, were insensitive to the growth inhibitory effects of EGF receptor kinase inhibition in vitro and in xenografts.New Findings: Both fluorescence and chromagenic antibody IHC assays were developed for evaluation of EMT-like transitions in human NSCLC, CRC and pancreas tumors. Qualitative and/or quantitative measurement of EMT markers in human tumor IHC specimens was correlated with tumor stage in NSCLC, CRC and pancreas cancer tissue microarrays. Additional protein markers indicative of EGFR inhibitor sensitivity from LC-MS/MS experiments included α-catenin, β-catenin, Zeb1/ΔEF1, cytokeratins and profilin, which could be verified by immunoblot, confocal and/or IHC analysis. Cross comparison with DNA microarray datasets served to further validate key genes and proteins which correlate an EMT-like transition with erlotinib sensitivity. Unexpected EGFR-independent pathways by which tumor cells with a mesenchymal phenotype activate Akt were identified.Conclusion: These data suggest new targeted drug combinations for treatment of advanced carcinomas containing mixed populations of epithelial and mesenchymal-like tumor cells.
Abstract 4585: Efficacy and Safety of Clopidogrel in Acute Coronary Syndrome Patients at High Risk of Bleeding: Data from the CURE Trial
Authors: John W Eikelboom, Shamir R Mehta, Keith A Fox, Janice Pogue, Salim Yusuf
Journal: Circulation (2008)

In the TRITON-TIMI 38 trial, prasugrel compared with clopidogrel was associated with net harm in aspirin-treated patients with a history of stroke or TIA and there was no net benefit of prasugrel i...
Abstract 17677: Mortality Risk Associated with Apparent Treatment-Resistant Hypertension Among Women
Authors: Steven M Smith, Tianyao Huo, Yan Gong, Eileen M Handberg, Martha Gulati, C. Noel Bairey Merz, Carl Pepine, Rhonda M Cooper-DeHoff
Journal: Circulation (2014)

Background: The extent to which apparent treatment-resistant hypertension (aTRH) is associated with mortality in women is not well-established. We assessed mortality risk associated with aTRH among women with varying underlying CV risk. Methods: We analyzed data from 3 cohorts of women: Women Take Heart (WTH; women without active CV disease at baseline); Women’s Ischemia Syndrome Evaluation (WISE; women with signs/symptoms of ischemia at baseline); and, the INternational VErapamil SR-trandolapril STudy (INVEST; women with CAD+HTN at baseline). Per cohort, women were categorized into 3 groups: no current/previous HTN; non-resistant HTN (non-rHTN; BP ≥140/90 mmHg on ≤2 drugs or BP <140/90 mmHg on 1-3 drugs); and, aTRH (BP ≥140/90 mmHg on ≥3 drugs or anyone on ≥4 drugs). The primary outcome was all-cause death at 10-year follow-up. Results: aTRH prevalence ranged from 0.4% in WTH to 31.4% in INVEST. Within each cohort, women with aTRH, compared to those without, were older, more often Black, and more likely ...
THE DIAGNOSIS OF SILICOSIS, WITH SPECIAL REFERENCE TO ROENTGENOLOGICAL MANIFESTATIONS
Authors: Leroy U. Gardner
Journal: Annals of Internal Medicine (1936)

Article1 August 1936THE DIAGNOSIS OF SILICOSIS, WITH SPECIAL REFERENCE TO ROENTGENOLOGICAL MANIFESTATIONSLEROY U. GARDNER, M.D.LEROY U. GARDNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-10-2-166 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBecause conditions caused by the inhalation of dust are so frequently involved in litigation it is necessary that they be defined with the greatest clarity. Our terminology developed forty to fifty years ago, before the pathology of such conditions had been worked out. Pneumoconiosis was the term coined to designate disease of the lungs due to inhaled dust, regardless of its nature. Anthracosis, siderosis, chalicosis, silicosis were specific forms of pneumoconiosis due to inhaled coal, iron, stone dust and silica respectively. All were considered of equal significance as it was believed that any dust was merely a foreign body which,...References1. MEREWETHER ER: Memorandum on asbestosis, Tubercle, 1934, xv, 69-81, 109. Google Scholar2. GLOYNE SR: Effect of inhalation of asbestos dust on lungs of asbestos workers, Tubercle, 1932-33, xiv, 445, 493, 450. Google Scholar3. LANZAMCCONNELLFEHNEL AJWJJW: Morbid anatomy and histology of asbestosis, U. S. Pub. Health Rep., 1935, l, 1-12. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Saranac Lake, N. Y.*Read at the Detroit meeting of the American College of Physicians, March 5, 1936. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1936Volume 10, Issue 2Page: 166-173KeywordsDustInhalationLungsPneumoconiosesSilicosis ePublished: 1 December 2008 Issue Published: 1 August 1936 PDF downloadLoading ...
Pharmacokinetic and thrombolytic properties of cysteine-linked polyethylene glycol derivatives of staphylokinase
Authors: Sophie Vanwetswinkel, Stephane Plaisance, Zhang Zhi-yong, Ingrid Vanlinthout, Kathleen Brepoels, Ignace Lasters, Désiré Collen, Laurent Jespers
Journal: Blood (2000)
The Novel Protease-Activated Receptor Type-1 Antagonist, F16618, Reduces Thrombus Formation in a Clinical Model of Thrombosis
Authors: Raj K. Chelliah, Laura Tattersall, Shruti Daga, Andrew Lucking, Karolina Skorupskaite, Bruno Le Grand, Michel Perez, David E. Newby
Journal: Journal of the American College of Cardiology (2009)
Abstract 764: A role for GLI1 in the development of multidrug resistance in rhabdomyosarcoma (RMS) cells
Authors: Joon Won Yoon, Marilyn Lamm, King-Fu Leong, Stephen Iannaccone, Philip Iannaccone, David Walterhouse
Journal: Cancer Research (2014)

Abstract RMS is the most common sarcoma of childhood. About 30% of patients with localized tumors will recur following treatment. The outcome for patients with recurrent RMS remains poor. Therefore, development of chemotherapy resistance during RMS therapy represents an important problem and novel approaches to prevent or reverse drug resistance are essential. Activation of multidrug transporter genes, including MDR1, MRP1, LRP and TAP1 represents an important mechanism for drug resistance in RMS. However, the mechanism of expression of multidrug resistance genes in RMS is incompletely understood. Recent reports have suggested a role for the Hedgehog (HH) signaling pathway and its downstream mediator GLI1 in acquisition of a multidrug resistance phenotype in esophageal adenocarcinoma, glioblastoma, and myeloid leukemia. Since approximately 60% of embryonal RMS (ERMS) and more rarely alveolar RMS (ARMS) express HH pathway components, we hypothesized that HH pathway activation may up-regulate the expression of multidrug resistance genes in RMS. We demonstrated expression of HH pathway components, including GLI1, in ERMS (RD, Rh18 and Ruch-2) and ARMS (Rh30 and Rh41) cell lines by qRT PCR and/or Western blot. We found variable expression of MDR1, MRP1, LRP and TAP1 by qRT PCR in these cell lines. Treatment of RMS cells with GLI1 siRNA (RD, Rh18 and Rh41) or the GLI1 antagonist GANT61 (Rh18 and Rh30) caused down-regulation LRP and TAP1 expression. In addition, GLI1, MDR1, LRP and TAP1 expression was increased in vincristine resistant UKF Rhb-1 RMS cells compared with parental cells (obtained from Dr. Cinatl) by qRT PCR. Treatment of vincristine resistant UKF Rhb-1 cells with vincristine together with either GANT61 or Cpd#33 (GLI1 inhibitors), each at a dose, which did not reduce cell viability individually, significantly decreased cell viability by MTT assay. Our results suggest that GLI1 up-regulates a subset of multidrug resistance genes in RMS cells and that GLI1-inhibitors may reduce multidrug resistance. Citation Format: Joon Won Yoon, Marilyn Lamm, King-Fu Leong, Stephen Iannaccone, Philip Iannaccone, David Walterhouse. A role for GLI1 in the development of multidrug resistance in rhabdomyosarcoma (RMS) cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 764. doi:10.1158/1538-7445.AM2014-764
Pathological Classification of Goiter and Its Clinical Significance
Authors: Wm. Carpenter Maccarty
Journal: Annals of Internal Medicine (1931)

Article1 August 1931Pathological Classification of Goiter and Its Clinical SignificanceWM. CARPENTER MACCARTY, M.D., F.A.C.P.WM. CARPENTER MACCARTY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-2-178 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn 1912,2a report of more than two thousand goiters revealed that they divided themselves into two great groups: those which were thyroid shaped and those which were nodular. Both groups were then studied from the standpoint of their structural and functional units and these were correlated with the clinical pictures. Since then, 32,479 goiters have been examined grossly and microscopically. In this large amount of material universal facts and principles have been sought in the hope of giving to practicing physicians and surgeons some simple clinical classification based on gross and microscopic characteristics which have become known to be...Bibliography1 BOOTHBY WM: The thyroid problem. Collected Papers of Mayo Clinic, 1928, xx, 495-515. Google Scholar2 MACCARTY WC: Goiter and its relation to its structural and physiological units, Surg., Gynec., and Obst., 1913, xvi, 406-411. Google Scholar3 PLUMMER HS: Personal communication. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota*Read before the American College of Physicians, Baltimore, Maryland, March 26, 1931.†From the Section on Surgical Pathology, The Mayo Clinic, Rochester, Minnesota. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1931Volume 5, Issue 2Page: 178-183KeywordsSurgeonsSurgical pathologyThyroid ePublished: 1 December 2008 Issue Published: 1 August 1931 PDF downloadLoading ...
Abstract 4158: Identification of somatic mutations in <i>EGFR/KRAS/ALK</i>-negative lung adenocarcinoma from never smokers
Authors: Han Sang Kim, Jin Woo Ahn, Jung-Ki Yoon, Soo Min Han, Hoon Jang, Sungho Eun, Hyo Sup Shim, Hyun Jung Kim, Dae Joon Kim, Jin G. Lee, Chang Young Lee, Mi Kyung Bae, Kyung Young Chung, Eun Young Kim, Ji Y. Jung, Se Kyu Kim, Joon Chang, Hye Ryun Kim, Joo Hang Kim, Ji Hyun Lee, Duhee Bang, Byoung Chul Cho
Journal: Cancer Research (2014)

Abstract Background: Lung adenocarcinoma is a highly heterogeneous disease with various etiologies, prognoses, and responses to therapy. Although genome-scale characterization of lung adenocarcinoma has been performed, somatic mutation analysis of never-smoker EGFR/KRAS/ALK-negative lung adenocarcinoma has not been comprehensively conducted. Methods: Patients with lung adenocarcinoma were eligible if they were never smoker without EGFR/KRAS mutation and ALK rearrangement. Whole exome sequencing was performed using the Illumina HiSeq 2,000 platform. Candidate loci identified in whole exome sequencing were validated using hybridization capture method and Sanger sequencing. Results: We present an analysis of whole exome sequencing data from 16 EGFR/KRAS/ALK-negative lung adenocarcinomas with additional 54 tumors in two independent cohort sets. We identified 27 genes potentially implicated in the pathogenesis of lung adenocarcinoma. In addition to targetable PI3K/mTOR signaling (TSC1, PIK3CA, AKT2) and receptor tyrosine kinase (RTK) signaling (ERBB4) genes, some of the genes including SETD2 and PBRM1 (chromatin remodeling), CHEK2 and CDC27 (cell cycle), CUL3 and SOD2 (oxidative stress), and CSMD3 and TFG (immune response) have not been previously highlighted in lung adenocarcinomas. In total (N=70), TP53 is the most frequently altered gene (11%), followed by SETD2 (6%), CSMD3 (6%), ERBB2 (6%), and CDH10 (4%). In pathway analysis, majority of altered genes were involved in cell cycle/DNA repair (P&amp;lt;0.001), and cAMP-mediated protein kinase A signaling (P&amp;lt;0.001). Conclusions: Genomic makeup of EGFR/KRAS/ALK-negative adenocarcinomas in never-smokers was remarkably diverse. Impairment in cell cycle/DNA repair may be involved in tumorigenesis and therapeutic targets in lung adenocarcinoma. Note: This abstract was not presented at the meeting. Citation Format: Han Sang Kim, Jin Woo Ahn, Jung-Ki Yoon, Soo Min Han, Hoon Jang, Sungho Eun, Hyo Sup Shim, Hyun Jung Kim, Dae Joon Kim, Jin Gu Lee, Chang Young Lee, Mi Kyung Bae, Kyung Young Chung, Eun Young Kim, Ji Ye Jung, Se Kyu Kim, Joon Chang, Hye Ryun Kim, Joo Hang Kim, Ji Hyun Lee, Duhee Bang, Byoung Chul Cho. Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma from never smokers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4158. doi:10.1158/1538-7445.AM2014-4158
Abstract 46: A Randomized Trial of Moderate and Intensive Exercise on Fatty Liver and Cardiometabolic Risk Factors in Obese Adults
Authors: Huijie Zhang, Xuejun Li, ZhiMin Ma, LingLing Pan, Zheng Chen, zhufeng Huang, ChengKun Han, Shi Chen, XiongJie Zhuang, Mingzhu Lin, ZhiBin Li, Jiang He, ShuYu Yang, Xiaoying Li
Journal: Circulation (2015)

Corresponding authors: Shu-yu Yang, Xiamen Diabetes Institute, Department of Endocrinology and Metabolism, The First Hospital of Xiamen, Xiamen University, 55 Zhenhai Road, Xiamen 361003, China ( xmyangshuyu@126.com). Jiang He, MD, PhD, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1440 Canal St, Ste 2000, New Orleans, LA 70112 ( jhe@tulane.edu ). Xiao-Ying Li, MD, PhD, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025 (lixy@sibs.ac.cn). Introduction: Nonalcoholic fatty liver disease (NAFLD) and its cardiovascular complications are common public health problems. Hypothesis: Although the benefit of exercise on NAFLD and cardiometabolic risk factors is documented, the effects of intensive and moderate exercise on these outcomes have not been thoroughly investigated.. Methods: We conducted a randomized controlled trial among 220 individuals aged 40-65 years with a waist circumference of ≥90 cm in men and ≥85 cm in women. NAFLD was defined by proton magnetic resonance spectroscopy (1H-MRS). Participants were randomly assigned to the intensive exercise group (vigorous exercise at 65-80% maximum oxygen consumption by running on a treadmill 30 min/day and 5 days/week for 6 months, followed by moderate exercise by brisk walking 150 min/week for another 6 months), the moderate exercise group (brisk walking 150 min/week for the entire 12 months), or the usual care control (lifestyle counseling for 12 months). The primary outcome was the change of intra-hepatic triglyceride content as determined by 1 H-MRS. Secondary outcomes were metabolic risk factors. Results: At 12 months, the mean change of intra-hepatic triglyceride content from baseline was -6.10% in the intensive exercise, -5.91% in the moderate exercise, and -2.73% in the control groups (P&lt;0.0001). Compared to the control group,the intensive and moderate exercise groups had significant net reductions of intra-hepatic triglyceride content at 6 months (-4.56%, 95% CL-6.71 to -2.42, p&lt;0.001 for intensive and -3.86%, 95% CL-6.01 to -1.71, p&lt;0.001 for moderate) and 12 months (-3.37%, 95% CL-5.52 to -1.22, p&lt;0.001 for intensive, and -3.19%, 95% CL-5.34 to -1.04, p&lt;0.001 for moderate). The net changes of intra-hepatic triglyceride content were not significantly different between the two exercise groups. Both intensive and moderate exercise reduced waist circumference, body weight, and blood pressure; additionally, intensive exercise reduced body fat mass, visceral fat, and body fat percent. Conclusions: Moderate intensity and vigorous intensity exercise were equally effective in improving NAFLD and blood pressure while vigorous exercise produced greater reductions of body fat.
Abstract 19686: Perturbations in Redox Homeostasis in Visceral Fat Due to Decreases in HO-1, Adiponectin and pAMPK Adversely Effects Vascular Function in Obese Mice.
Authors: Luca Vanella, Ming Li, Rita Rezzani, Luigi Rodella, Pavel Martasek, Stephen J Peterson, Nader G Abraham
Journal: Circulation (2010)

Redox homeostasis and the expression of antioxidant genes in visceral fat influence adiponectin release and inflammatory cytokines, TNFα and IL-6 levels. The redox state of visceral fat may also be...
Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1
Authors: Peter Timpl, Rainer Spanagel, Inge Sillaber, Adelheid Kresse, Johannes M. H. M. Reul, Günter K. Stalla, Veronique Blanquet, Thomas Steckler, Florian Holsboer, Wolfgang Wurst
Journal: Nature Genetics (1998)
IL4‐R1 (5q31–q33) and FcεRI‐βca (11q13) markers and atopy: a case/control study in a Spanish population
Authors: M. Torres‐Galván, J. Quiralte, J. J. Pestano, N. Ortega, C. Blanco, R. Castillo, T. Carrillo, P. Pérez‐Aciego, F. Sánchez‐García
Journal: Allergy (2001)

Background: Rhinoconjunctivitis and bronchial asthma are atopic diseases with a high prevalence in the Canary Islands (Spain). Given that the most prevalent allergen is the house‐dust mite Dermatophagoides pteronyssinus , early detection of genetically susceptible subjects would allow the application of preventive measures. The objective was to investigate the possible association of IL4‐R1 (chromosome 5q31–q33) and FcεRI‐βca (chromosome 11q13) markers with the atopic disease in our population. Methods: We performed a case/control study in which patients were recruited on the basis of diagnosis of rhinoconjunctivitis and/or bronchial asthma, and positive skin prick test to D. pteronyssinus . Analysis of IL4‐R1 and FcεRI‐βca microsatellites was carried out by PCR and electrophoresis in acrylamide gels. Results: We have not found evidence of association between IL4‐R1 and FcεRI‐βca markers and atopic disease in our population. In addition, these markers have shown a high percentage of homozygosis. Conclusions: IL4‐R1 and FcεRI‐βca markers have not proved to be useful genetic markers for linkage or association studies in our population.
Darapladib for Preventing Ischemic Events in Stable Coronary Heart Disease
Authors: Harvey D. White, Claes Held, Ralph Stewart, Elizabeth Tarka, Rebekkah Brown, Richard Y. Davies, Andrzej Budaj, Robert A. Harrington, P. Gabriel Steg, Diego Ardissino, Paul W. Armstrong, Alvaro Avezum, Philip E. Aylward, Alfonso Bryce, Hong Chen, Ming Fong Chen, Ramon Corbalan, Anthony J. Dalby, Nicolas Danchin, Robbert J. De Winter, Stefan Denchev, Rafael Diaz, Moses Elisaf, Marcus D. Flather, Assen R. Goudev, Christopher B. Granger, Liliana Grinfeld, Judith S. Hochman, Steen Husted, Hyo Soo Kim, Wolfgang Koenig, Ales Linhart, Eva Lonn, José López-Sendón, Athanasios J. Manolis, Emile R. Mohler, José C. Nicolau, Prem Pais, Alexander Parkhomenko, Terje R. Pedersen, Daniel Pella, Marco A. Ramos-Corrales, Mikhail Ruda, Mátyás Sereg, Saulat Siddique, Peter Sinnaeve, Peter Smith, Piyamitr Sritara, Henk P. Swart, Rody G. Sy, Tamio Teramoto, Hung Fat Tse, David Watson, W. Douglas Weaver, Robert Weiss, Margus Viigimaa, Dragos Vinereanu, Junren Zhu, Christopher P. Cannon, Lars Wallentin
Journal: New England Journal of Medicine (2014)

Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2.In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization).During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02).In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).