tbuckley/cabot-search huggingface dataset:
Restoration of transforming growth factor (TGF) beta signaling pathway in the human prostate carcinoma LNCaP cell line by the histone deacetylase inhibitor MS-275
Authors: Yukihiko Kato, David Qian, Byungwoo Ryu, Yongfeng Wei, Xiaofei Wang, Lu Zhang, Rhoda Alani, Astrid Schott, Roberto Pili
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4172 

Transcriptional repression of the TGF-beta type II receptor (RII) is a major mechanism underlying TGF-beta resistance in many solid tumors including prostate cancer. Histone deacetylase inhibitors have been shown to inhibit tumor growth by increasing histone acetylation, chromatin remodeling, and modulation of gene expression. In this study, we treated TGF-beta RII negative human prostate carcinoma LNCaP cell line with the histone deacetylase inhibitor MS-275. LNCaP treated cells showed a reduced growth rate both in vitro and in vivo . The antiproliferative effect of MS-275 on LNCaP cells was associated with a dose dependent induction of both TGF-beta and TGF-beta RII. We also observed cell cycle arrest at G1 phase, increased apoptosis, and expression of the plasminogen activation inhibitor-1, a down-stream target of TGF-beta signaling pathway. Surprisingly, we also observed the gene and protein expression up-regulation of Id1, a transcription factor involved in inhibition of differentiation and induction of proliferation. However, recent evidence also showed that Id1 knockout mice were more susceptible to chemical carcinogen induced skin cancer. In order to elucidate the mechanism and consequence of MS-275 up-regulation of TGF-beta RII and Id1, we developed RNA interference (RNAi) strategy targeting Id1. Preliminary results indicated that RNAi induced a >75% inhibition of Id1 protein expression and G1 cell cycle arrest in a melanoma cell line. We are currently testing combination treatments of LNCaP cells with MS-275 and Id1 RNAi to determine the role of Id1 induction in the antitumor activity of MS-275, and the results will be presented at the meeting. In conclusion, these preliminary results suggest that the antitumor activity of MS-275 may be mediated in part through the induction of TGF-beta and TGF-beta RII expression and consequent restoration of an impaired TGF-beta autocrine inhibitory circuit.
Clinical Trial Evaluating DC/AML Fusion Cell Vaccination In AML Patients
Authors: Jacalyn Rosenblatt, Richard M. Stone, Lynne Uhl, Donna S. Neuberg, Baldev Vasir, Poorvi Somaiya, Robin Joyce, James D. Levine, Vassiliki A. Boussiotis, Jeffrey I. Zwicker, Jon Arnason, Katarina Luptakova, David P. Steensma, Daniel J. DeAngelo, Ilene Galinsky, Heidi Mills, Emma Breault, Carol Delaney, Dina Stroopinsky, Donald Kufe, David Avigan
Journal: Blood (2013)
Treatment Approaches in Acute Leukemia Patients Relapsing Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Pervin Topcuoglu, Mehmet Gunduz, Mehmet Ozen, Sinem Civriz Bozdag, Selami Kocak Toprak, Onder Arslan, Muhit Ozcan, Taner Demirer, Osman Ilhan, Hamdi Akan, Meral Beksac, Nahide Konuk, Gunhan Gurman
Journal: Blood (2014)
Abstract 8635: Novel Role of the Osteoclast-Associated Receptor (oscar) In Oxidative Stress-Mediated Atherogenesis
Authors: Claudia Goettsch, Stefanie Lauckner, Kathrin Sinningen, Michael Schoppet, Martin von Bergen, Stefan Kalkhof, Elena Aikawa, Lorenz C Hofbauer
Journal: Circulation (2011)

Cross talk between the vascular and the immune system plays a crucial role in cardiovascular diseases including atherosclerosis and ectopic calcification. The osteoclast-associated receptor (OSCAR) is a regulator of osteoclast differentiation and dendritic cell maturation, and recently was implicated as a modulator of osteoimmunology. But the role of OSCAR in vascular biology and its impact on atherogenic processes provoked by pro-inflammatory stimuli is unknown. We recently identified OSCAR on the surface of human primary endothelial cells. Endothelial cell survival was significantly enhanced by activation of OSCAR (+22 %, p&lt;0.001). In contrast, apoptosis was inhibited, as measured by DNA fragmentation (−19 %, p&lt;0.01) and by determination of caspase 3/7 activity (−22 %, p&lt;0.05). Furthermore, OSCAR overexpression increased adhesion of monocytic cells to the endothelium up to 2-fold (p&lt;0.05). In an in-depth proteomic study using stable isotope labelling with amino acids in cell culture (SILAC) more than 2,500 proteins (FDR &lt; 1%) were reproducibly quantified by nano-HPLC/nano-ESI-MS in OSCAR expressing endothelial cells. 116 proteins were determined to be significantly regulated due to OSCAR overexpression, which are mainly involved in cell proliferation, anti-apoptosis, and stress response. Stimulation of endothelial cells with oxidized low-density lipoprotein (oxLDL) caused a time-dependent and dose-dependent induction of OSCAR that was LOX-1-dependent and Ca 2+ -dependent. Specific inhibition of the nuclear factor of activated T cells (NFAT) pathway prevented the oxLDL-mediated increase of endothelial OSCAR expression, and oxLDL induced binding of NFATc1 to the OSCAR promoter as assessed by EMSA and OSCAR promoter analysis. Interestingly, in vivo modified LDL from patients with diabetes mellitus stimulated OSCAR mRNA expression in human endothelial cells 2.5-fold (p&lt;0.01). Furthermore, ApoE knockout mice fed a high-fat diet showed enhanced aortic OSCAR expression (+220%, p&lt;0.01), accompanied by increased NFATc1 expression. Our data suggest that OSCAR, originally described as immunological mediator and regulator of osteoclast differentiation, may also participate in cell activation and inflammation in atherosclerosis.
Abstract 5442: Oxidative Stress Regulates Cardiac Stem Cell Differentiation in a MicroRNA-Mediated Mechanism
Authors: Kathryn Maiellaro-Rafferty, Michael E Davis
Journal: Circulation (2009)

Oxidative stress, specifically hydrogen peroxide (H 2 O 2 ) is significantly increased following myocardial infarction and its effect on adult cardiac stem cell (CSC) differentiation is largely unknown. To promote endogenous and implanted CSC differentiation into functional cardiac cells in ischemic tissue, mechanisms of deleterious redox signaling on cardiomyogenesis must be determined. Our data demonstrate that H 2 O 2 time- and dose-dependently inhibits Nkx2.5 expression in CSCs exposed to differentiating medium. Since overexpression of microRNA (miR)-1 increases embryonic stem cell cardiac differentiation, we hypothesized that H 2 O 2 regulates CSC differentiation in a miRNA-mediated mechanism. CSCs exposed to H 2 O 2 (1–100 μ M) in differentiating media demonstrated time-dependent, decreased expression of miR1 compared to cells exposed to differentiating media alone (1 μ M: 37±7.6% decrease from Day 5 control; 100 μ M: 47±11% decrease from Day 8 control). MiR133a, essential for normal cardiac development, was not time-dependently regulated by H 2 O 2 , suggesting it is not redox sensitive. Since cardiac differentiation in Drosophila is regulated by miR-1 binding to the Notch ligand Delta and Notch activation attenuates embryonic stem cell cardiogenesis, we next examined the effect of miR1 on the Notch pathway in CSCs. Delta1 expression increased 24±5% above the time-matched control exposed to differentiating media alone after 8 days exposure to H 2 O 2 (0.1 μ M). Since miR1 exhibited the inverse response to H 2 O 2 , the data support Delta1 as a target for miR1-mediated silencing in CSCs. In summary, our data suggest a mechanism for redox-mediated attenuation of CSC differentiation. H 2 O 2 decreases miR1 expression, which prevents normal Delta1 silencing by miR-1 that occurs during differentiation. This failure of Delta1 degradation increases Notch activation, which subsequently suppresses cardiogenic differentiation. This study underscores the importance of H 2 O 2 scavenging following cardiac injury to promote CSC differentiation, and suggests that targeting anti-cardiogenic miRNA regulation may be a promising strategy for successful CSC-based therapy.
Retraction：Effects of Valsartan on Cardiovascular Morbidity and Mortality in High-Risk Hypertensive Patients With New-Onset Diabetes Mellitus:– Sub-Analysis of the KYOTO HEART Study –
Authors: Shinzo Kimura, Takahisa Sawada, Jun Shiraishi, Hiroyuki Yamada, Hiroaki Matsubara
Journal: Circulation (2012)
Breast Arterial Calcifications and Their Association With Incident Cardiovascular Disease and Diabetes
Authors: Eva J.E. Hendriks, Joline W.J. Beulens, Willem P.Th.M. Mali, David Beijerinck, Yolanda van der Graaf, Pim A. de Jong, Yvonne T. van der Schouw
Journal: Journal of the American College of Cardiology (2015)
Abstract 4870: Cardiovascular Effects Of Apelin In Healthy Volunteers And Patients With Heart Failure
Authors: Alan G Japp, Nicholas L Cruden, Martin A Denvir, Andrew D Flapan, David E Newby
Journal: Circulation (2008)

BACKGROUND Apelin is the most potent inotrope yet described. In preclinical models, it increases cardiac output in normal and failing hearts and lowers blood pressure through peripheral vasodilatation. We have recently demonstrated that apelin causes nitric oxide-dependent vasodilatation in man. Here, we aimed to establish the effects of apelin on cardiac and systemic hemodynamics variables. METHODS All studies were performed in a randomized, double-blinded manner. Forearm blood flow responses to intrabrachial infusions of (Pyr1)apelin-13 (0.3–3 nmol/min), acetylcholine (5–20 μg/min) and sodium nitroprusside (SNP; 1– 4 μg/min) were measured by venous occlusion forearm plethysmography in 12 patients with stable chronic heart failure (CHF; NYHA class II–III) and 12 matched controls. Cardiac index (CI; assessed non-invasively by thoracic electrical bioimpedance) blood pressure and heart rate (HR) were measured during intravenous infusions of (Pyr1)apelin-13 (30 –300 nmol/min) and saline placebo in 6 patients with stable CHF and 7 matched controls. The maximum rate of pressure rise within the left ventricle (dP/dt max) was measured in 4 patients following intracoronary boluses of apelin-36 (20 and 200 nmol) and saline placebo. RESULTS Apelin infusions were well tolerated with no reported symptoms or ECG abnormalties. Apelin, acetylcholine and SNP caused vasodilatation in forearm resistance vessels of both CHF patients and controls (all p&lt;0.0001). Responses to acetylcholine (P=0.01) but not apelin (p=0.3) or SNP (p=0.9) were diminished in patients with CHF compared with controls. In CHF patients, apelin increased cardiac index by 16% (p&lt;0.05) and lowered mean arterial pressure (MAP) by 7% (p&lt;0.05) but had no effect on HR (p=0.17). In controls, apelin increased CI by 8% (p&lt;0.05) and HR by 13% (p&lt;0.01) and lowered MAP by 8% (P&lt;0.01). Intracoronary injection of apelin appeared to increase cardiac contractility (dP/dt max rise of 8%, p=0.056). CONCLUSIONS Apelin increases cardiac output and lowers blood pressure in man, through both peripheral arteriolar vasodilatation and increased cardiac contractility. These effects of apelin are preserved in patients with CHF suggesting a potential therapeutic role for apelin agonism in heart failure.
AF10 Fusion Transcripts Are Identified By HOXA9/10 and MEIS1 Overexpression In T-ALL: A Report From Children’s Oncology Group AALL0434
Authors: Richard C. Harvey, Nyla A. Heerema, Andrew J. Carroll, Meenakshi Devidas, Mignon L. Loh, Stephen P. Hunger, Elizabeth A. Raetz, Charles G. Mullighan, Frcpa, Naomi J. Winick, William L. Carroll, Richard S. Larson, Kimberly Dunsmore, Peter D. Aplan, Stuart S. Winter
Journal: Blood (2013)
Extent of Thoracic Aortic Atheroma Burden and Long-Term Mortality After Cardiothoracic Surgery
Authors: Vikram Kurra, Michael L. Lieber, Srikanth Sola, Vidyasagar Kalahasti, Donald Hammer, Stephen Gimple, Scott D. Flamm, Michael A. Bolen, Sandra S. Halliburton, Tomislav Mihaljevic, Milind Y. Desai, Paul Schoenhagen
Journal: JACC. Cardiovascular imaging (2010)
Abstract 1456: Proteomic Analysis Of Proteins Bound By D-4F In Plasma From C57bl/6 And ApoA-I KO Mice
Authors: Hao Xu, Kirkwood A Pritchard, Basam Wakim, Michael Olivier, Yang Shi
Journal: Circulation (2007)

D-4F, an 18 amino acid apolipoprotein A-I (ApoA-I) mimetic, has been shown to be highly effective at improving vascular function in murine models of atherosclerosis. It has been hypothesized that D-4F inhibits atherosclerosis and increases vasodilation by interacting with ApoA-I to improve HDL function. However, the mechanisms by which D-4F protects vascular function remain unclear. We hypothesize that D-4F binds proteins involved in atherosclerosis. To test this hypothesis, we incubated HA-tagged D-4F with plasma from C57bl/6 and ApoA-I knockout mice (ApoA-I KO) on a C57bl/6 background and identified the proteins that were bound. Plasma from C57bl/6 mice or ApoA-I KO mice (n=6/group) was incubated with HA-GG-D-4F (Ac-YPYDVPDYA-GG-DWFKAFYDKVAEKFKEAF-NH2) or HA-GG-scramble-D-4F (Ac-YPYDVPDYA-GG-DWFAKDYFKKAFVEEFAK-NH2) at 10μg/ml. Next an anti-HA antibody was used to immunoprecipitate the HA-tagged peptides and associated proteins. The proteins were then analyzed by ESI-nano-LC/MS/MS. Analysis revealed that D-4F bound several proteins involved in lipid metabolism (ApoA-I, -II, -IV, ApoE, ApoC-I, -II and -III, -IV); complement regulatory protein (Complement C3); several kinases (PKC and Serine/threonine-protein kinase); and Serpins (Serine protease inhibitor 1 and A3K) which inhibit serine endopeptidases in C57bl/6 mice plasma. Although ApoA-I KO mice do not express ApoA-I, D-4F bound several lipoproteins associated with lipid metabolism (ApoE, ApoA-II, -IV, and ApoC-II, -III, -IV) in plasma from ApoA-I KO mice. D-4F also associated with the complement regulatory protein, Complement C3 in plasma of ApoA-I KO mice. Interestingly, D-4F bound serum paraoxonase and bradykinin only in the plasma of ApoA-I KO mice. These data show that D-4F associates, either directly or indirectly through lipoproteins, with a unique array of proteins involved in lipid metabolism; and second; that D-4F’s ability to associate with Complement C3, serum paraoxonase, bradykinin and Serpins suggest that D-4F may be able to modify the atherogenic properties of proteins involved in inflammation.
Abstract 15808: Whole Exome Sequencing and Hypertrophic Cardiomyopathy
Authors: Frederick E Dewey, Sergio Cordero, Matthew T Wheeler, Aleksandra Pavlovic, Krishna K Bommakanti, Stephen Pan, Colleen Caleshu, Rui S Chen, Michael Snyder, Euan A Ashley
Journal: Circulation (2011)

Background: Hypertrophic cardiomyopathy (HCM) is a common cause of sudden death in young people and a source of morbidity and mortality in patients of all ages. Targeted sequencing identifies the g...
Abstract P172: What Facilities Reserve Public Access Defibrillation Programs? A Suvey from a Japanese Metropolis
Authors: Hiroshi Kaneko, Tetsuo Hatanaka, Aki Nagase, Hiroko Noguchi, Tetsuya Sakamoto, Seishiro Marukawa
Journal: Circulation (2008)

Previous reports have described several facility categories as important locations for public access defibrillation (PAD) program. However, in decision-making process as to what specific facilities may deserve PAD programs, each facility needs to estimate the number of shockable cardiac arrest (CA). Such estimation depends not only on the expected number of visitors/workers but also on the profile of the visitors/workers, which may vary among types of facilities. [Methods] Nagoya City has a population of 2.2 million with ~2,000 CA annually. Locations of CA were abstracted from data collected by Nagoya FD from 2003 through 2007. Types of public facilities were tallied and grouped into 36 categories consistent with Ordinance for Enforcement of Fire Service Act, and the number of CA within each category was determined. Data on the number of visitors/workers in each category were collected from governmental databases on metropolitan statistics. The incidence rate was calculated as numbers of all CA and CA with VF per 1 billion person.year. [Results] In 8 location categories, the databases for CA and the database for numbers of visitors/workers coincided in the categorization rules of the locations. The incidence rates are shows in the table . [Discussion] The incidence rate of shockable CA varies substantially among the location categories, presumably reflecting the variations of age distribution, average length of stay and intensity of physical activities of people who gather there. Schools (teachers) and factories have the highest incidence of shockable CA. However, our data may indicate that a school with small numbers of workers (teachers) may have a low priority of a PAD program. On the contrary, a station with low incidence rate of 0.05 may be a preferred target of a PAD program if a large number of travelers are expected to pass through. Thus our study provides fundamental data to detect important and cost-effective target locations of a PAD program. Number of CA per 1 billion preson.year
Receptor Specific Clearance by the Reticuloendothelial System in Chronic Liver Diseases
Authors: Charles J. Jaffe, John M. Vierling, E. Anthony Jones, Thomas J. Lawley, Michael M. Frank
Journal: Journal of Clinical Investigation (1978)

An approach to the assessment of reticuloendothelial function that quantitates clearance specifically mediated by membrane receptors for C3b and immunoglobulin (Ig)G has been applied in man. Clearance of isologous erythrocytes coated with IgM or C3b or coated with IgG were examined in patients with primary biliary cirrhosis (PBC), chronic hepatitis, or alcoholic cirrhosis and normal control subjects and compared with the clearance of aggregated human serum albumin. Clearance of these three types of particles varied independently. None of the patients studied had a defect in the clearance of aggregated albumin. No patient with PBC (0:6) had delayed clearance of IgG-coated erythrocytes; one of six patients with chronic hepatitis had delayed clearance of these cells. Indeed, four of six with PBC had increased rates of IgG-mediated clearance. In contrast, six out of six patients with PBC had an unequivocal defect in clearance mediated by C3b receptors. The patients with PBC varied widely in terms of duration of symptoms, degree of cholestasis, and histologic stage of disease. No defect of C3b-mediated erythrocyte clearance was found in the patients with chronic hepatitis or alcoholic cirrhosis. Furthermore, a patient with severe cholestasis secondary to large duct biliary obstruction exhibited normal C3b-mediated clearance. The defect in C3b-mediated clearance in PBC did not correlate with serum levels of individual complement components or inhibitors or with the presence of circulating immune complexes as measured by the Clq precipitation assay. Thus, measurements of receptor specific clearance, but not clearance of aggregated proteins, have revealed a highly specific defect in reticuloendothelial function in PBC.
P0778 : The effect of HCV antiviral therapy on fibrosis progression
Authors: M. Lu, J. Li, L.B. Rupp, S.D. Holmberg, A.C. Moorman, P.R. Spradling, E. Tehale, F. Xu, J.A. Boscarino, V. Vijayadeva, M.A. Schmidt, L.E. Lamerato, S. Gordon
Journal: Journal of Hepatology (2015)
Abstract 11306: Heart Failure Associated with Neural Injury in a Critical Area for Planning
Authors: Mary A Woo, Haidang D Nguyen, Rajesh Kumar, Paul M Macey, Gregg C Fonarow, Michele A Hamilton, Ronald M Harper
Journal: Circulation (2010)

A significant issue in heart failure (HF) is diminished cognitive function, including memory, learning, and planning deficits. A basal ganglia structure, the putamen, serves many of these memory an...
Hazards of (beta) blockade
Authors: T. J M Cleophas, R. B Kalmansohn
Journal: BMJ (1995)

EDITOR,--If doctors follow Morris J Brown's recommendation that “until current trials tell us otherwise … doctors can be encouraged to use either type of β blocker”1 then probably many more patients will be killed than the one described in the case report to which the final sentence of Brown's editorial (“One drop of timolol down the lacrimal duct can kill”) refers.

For more than 10 years non-selective …
遗传药理学：“量体裁衣”用药
Authors: Susan, Mayor, 郭栋（译）, 周宏灏（校）
Journal: BMJ (2007)

全科医生David Wbite轻轻点击计算机上的遗传特征按钮，得到了适用于面前这位病人的抗高血压药物列表及剂量，White医生按照计算机提供的处方给这位病人用药。这就是国际人类基因组计划负责人、美国国家人类基因组研究所所长Francis Collins所预测的医生诊疗过程，他相信在不久的将来这将成为现实。
Updated results of local control and first analysis of survival from the randomised trial of risk-adapted TARGeted Intraoperative radioTherapy (TARGIT-A) for early breast cancer
Authors: J S Vaidya, F Wenz, Max Bulsara, J S Tobias, D Joseph, M Keshtgar, H Flyger, S Massarut, M Alvarado, C Saunders, W Eiermann, M Metaxas, E Sperk, M Sutterlin, D Brown, L Esserman, M Roncadin, A Thompson, J A Dewar, H Holtveg, S Pigorsch, M Falzon, E Harris, A Matthews, C Brew-Graves, I Potyka, T Corica, N R Williams, M Baum
Journal: The Lancet (2013)
Abstract 1150: Activation Of AMPK During Angiotensin II Induced Hypertension Improves Endothelial Function By Inhibition Of NADPH Oxidase And Xanthine Oxidase Activity.
Authors: Swenja Schuhmacher, Eberhard Schulz, Markus Hortmann, Philip Wenzel, Matthias Oelze, Andreas Daiber, Thomas Munzel
Journal: Circulation (2007)

Background: AMP-activated protein kinase (AMPK) mediates cellular adaptation to metabolic stress, but its role in vascular disease is less clear. Here we tested if AMPK modulation in vivo may affect vascular function and oxidative stress in a murine model of angiotensin II (AT-II) induced hypertension.  Methods: C57Bl6 mice were devided into 4 groups (Ctr, Aicar, AT-II, AT-II/Aicar). Hypertension was induced by continuous AT-II infusion (0,8mg/kg/d) via osmotic minipump, the AMPK activator Aicar was administrated by a daily subcutaneous injection (200mg/kg/d). After 7 days, we determined vascular function by isometric tension studies, activity of AMPK by phosphorylation of AMPK and its downstream target ACC, reactive oxygen species (ROS) formation by dihydroethidium fluorescence, NADPH oxidase activity in heart membrane fractions (lucigenin 5μM) and serum xanthine oxidase activity by cytochrome C reduction.  Results: In mice treated with AT II for 7 days we observed a 30% decrease of AMPK activity. Parallel administration of the AMPK activator Aicar restored AMPK activity and improved endothelial function in AT-II treated animals. At the same time, vascular oxidative stress in AT-II infused mice was significantly reduced by concomitant Aicar treatment assessed by dihydroethdium fluorescence in aortic sections. We identified NADPH oxidase (Ctr 124455±12255, AT-II 217552±20868, AT-IIA p  Conclusion: Restoration of AMPK activity during AT II hypertension improves vascular function by inhibition of NADPH-oxidase and xanthine oxidase activity, suggesting AMPK as a possible pharmacological target in vascular disease.