tbuckley/cabot-search huggingface dataset:
Abstract 1125: Developmental pluripotency associated 4 oncogene interacts with Wnt/β-catenin signaling and stem cells regulatory genes to control pituitary tumor cells invasiveness
Authors: Dipak K. Sarkar, Shaima Jabbar, Omkaram Gangisetty
Journal: Cancer Research (2018)

Abstract The developmental pluripotency associated 4 (DPPA4) gene has an important role in self-renewal and pluripotency in embryonic stem cells. It is re-expressed in several malignant tumors and is identified as a new pluripotency-related oncogene. We have recently identified elevated expression of DPPA4 in aggressive pituitary tumors induced by estrogen in fetal alcohol exposed rats. In this study, we determined the role of DPPA4 in pituitary tumor growth and invasiveness by employing CRISPR/Cas9 knock-down of DPPA4 and conducting cell proliferation, in vitro soft agar anchorage-independent growth assays, and in vivo tumor formation assay using cell spheres from pituitary tumors of alcohol-fed and control-fed animals. Pituitary tumor cells of fetal alcohol-fed rats and control diet-fed rats were grown in ultra-low attachment plate to develop pituispheres. In vitro and in vivo studies showed pituispheres of alcohol-fed rats had higher cell proliferation rate, increased colony formation in soft agar, and higher tumor development in mice xenografts compared to those in pituispheres of alcohol-fed rats. Pituispheres of alcohol-fed rats also had increased mRNA levels of cell growth, cell stemness and EMT regulatory genes. CRISPR-Cas9 knockdown of DPPA4 in pituispheres reduced the tumor cell ability to proliferate, migrate and form colony in soft agar and grow in mice xenografts. Pituispheres of alcohol-fed rats also showed increased protein levels of Wnt/beta-catenin signaling molecules (Wnt 3, beta-catenin, LPR5, GSK3), stemness regulatory factors (KLF4, Sox2, Nanog) and EMT factors as compared to those in control-fed pituispheres. DPPA4 knockdown reduced the levels of Wnt signaling and stem cells regulatory proteins and EMT factors in alcohol-fed rat pituispheres. These data suggest that DPPA4 is expressed in aggressive pituitary tumors and regulates the growth and invasion of these tumors via activation of Wnt/beta-catenin signaling and stem cells regulatory genes. (This work is supported by a National Institute of Health grant R01 AA11591). Citation Format: Dipak K. Sarkar, Shaima Jabbar, Omkaram Gangisetty. Developmental pluripotency associated 4 oncogene interacts with Wnt/β-catenin signaling and stem cells regulatory genes to control pituitary tumor cells invasiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1125.
Abstract 589: A systematic review of randomized clinical trials for therapeutic outcomes of anti-EGFR agents used in combination with other targeted therapies
Authors: Sonali Kurup, Pavlina Liskova, Paiboon Jungsuwadee, Prashant Sakharkar, Soniya Tambe
Journal: Cancer Research (2018)

Abstract Introduction: The epidermal growth factor receptor (EGFR) plays a prominent role in cancer cell proliferation and metastasis in non-small-cell lung cancer (NSCLC). Targeted cancer therapies include agents that block tumor-specific molecular targets and thereby interfere with tumor growth, progression and metastasis. This study focuses on a systematic review of outcomes from phase II and III clinical trials for standard anti-EGFR therapy plus a targeted therapy to EGFR monotherapy. Methods: Studies were identified through a thorough literature search using, EMBASE, Pubmed, Scifinder Scholar, clinicaltrials.gov and the Cochrane library using the following terms: “epidermal growth factor receptor kinase”, “combination therapy”, “non small cell lung cancer”. Eligible studies included patients of any stage and mutation status. Data abstraction included patient demographic characteristics; sample size, patient inclusion and exclusion criteria, overall response rate (ORR), median progression free survival (PFS), median overall survival (OS), and adverse effects (AE). Results: Literature search resulted in the identification of 1543 studies of which 153 were found to be relevant for this review and 31 fit the inclusion criteria. Of the 31 studies, 28 included erlotinib and 3 studies included gefitinib as the control. Twenty-five of the studies focused on kinase inhibitors targeting VEGFR, EGFR, MET, IGF-1R, AKT, mTOR and HER3 as the combination agent. The remaining six studies focused on alternate pathways of targeted inhibition including hormonal agents and histone deacetylase inhibitors. The identified studies included patients (N=7552) of mean age (63 ± 2), female (22-80%), smokers in combination therapy (12-96%) versus monotherapy (8-95%). Median OS (months) for patients on the EGFR-based combination regimen (range 5.7-24.7) vs monotherapy (range 4.5-21.8). Median PFS (months) for patients on the EGFR-based combination regimen (range 1.3-16.0) vs monotherapy (1.5-9.7). A greater incidence of AE was observed for EGFR-based combination therapy compared to EGFR monotherapy. Conclusions: Several different targeted therapies have been evaluated as part of clinical trials for NSCLC in combination with EGFR-based therapies, and compared to EGFR-based monotherapy. For patients with NSCLC, a higher range for median OS and median PFS was observed for EGFR-based combination regimens compared to EGFR monotherapy. Citation Format: Sonali Kurup, Pavlina Liskova, Paiboon Jungsuwadee, Prashant Sakharkar, Soniya Tambe. A systematic review of randomized clinical trials for therapeutic outcomes of anti-EGFR agents used in combination with other targeted therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 589.
Public Health Consequences of a 2013 Measles Outbreak in New York City
Authors: Jennifer B. Rosen, Robert J. Arciuolo, Amina M. Khawja, Jie Fu, Francesca R. Giancotti, Jane R. Zucker
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Internationally imported cases of measles into the United States can lead to outbreaks requiring extensive and rapid control measures. Importation of measles from an unvaccinated adolescent in 2013 led to what has been the largest outbreak of measles in New York City, New York, since 1992. <h3>Objective</h3> To describe the epidemiology and public health burden in terms of resources and cost of the 2013 measles outbreak in New York City. <h3>Design, Setting, and Participants</h3> This epidemiologic assessment and cost analysis conducted between August 15, 2013, and August 5, 2014, examined all outbreak-associated cases of measles among persons residing in New York City in 2013. <h3>Exposures</h3> Measles virus. <h3>Main Outcomes and Measures</h3> Numbers of measles cases and contacts. Total personnel time and total direct cost to the New York City Department of Health and Mental Hygiene (DOHMH), calculated as the sum of inputs (supplies and materials, equipment, and logistics) and personnel time (salary and fringe benefits). <h3>Results</h3> Between March 13, 2013, and June 9, 2013, 58 persons in New York City with a median age of 3 years (range, 0-32 years) were identified as having measles. Among these individuals, 45 (78%) were at least 12 months old and were unvaccinated owing to parental refusal or intentional delay. Only 28 individuals (48%) visited a medical health care professional who suspected measles and reported the case to the DOHMH at the initial clinical suspicion. Many case patients were not immediately placed into airborne isolation, resulting in exposures in 11 health care facilities. In total, 3351 exposed contacts were identified. Total direct costs to the New York City DOHMH were $394 448, and a total of 10 054 hours were consumed responding to and controlling the outbreak. <h3>Conclusions and Relevance</h3> Vaccine refusals and delays appeared to have propagated a large outbreak following importation of measles into the United States. Prompt recognition of measles along with rapid implementation of airborne isolation of individuals suspected of measles infection in health care facilities and timely reporting to public health agencies may avoid large numbers of exposures. The response and containment of measles outbreaks are resource intensive.
Association of High-Altitude Pulmonary Edema With the Major Histocompatibility Complex
Authors: MasayukiHanaoka, KeishiKubo, YoshitakaYamazaki, TakashigeMiyahara, YukinoriMatsuzawa, ToshioKobayashi, MorieSekiguchi, MasaoOta, HidetoWatanabe
Journal: Circulation (1998)

Background—A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects. Methods and Results—The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects (P=.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects (P=.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subje...
Functional Upregulation of the Vascular Endothelial Growth Factor Receptor KDR by Hypoxia
Authors: JohannesWaltenberger, UlrikeMayr, SiegwaldPentz, VinzenzHombach
Journal: Circulation (1996)

Background Vascular endothelial growth factor (VEGF) is a specific endothelial mitogen and chemoattractant that has been shown to be useful for inducing therapeutic angiogenesis in ischemic myocardium and found to stimulate mitogenicity and chemotaxis of endothelial cells through the receptor tyrosine kinase KDR. Although VEGF expression is upregulated by hypoxic stimuli, regulation of KDR remained unknown under these conditions. Methods and Results With the use of human umbilical vein endothelial cells and transfected porcine aortic endothelial cells, KDR protein was found to be upregulated under hypoxic conditions (2% O2) in both cell types. This process of KDR upregulation was found to be reversible, was maximal after 24 hours of hypoxia, and was regulated on a posttranscriptional level. Furthermore, the susceptibility for VEGF-induced mitogenicity was enhanced under hypoxic conditions as shown by [3H]-thymidine incorporation assay. The activated state of increased VEGF function in hypoxic endothelial ...
Activation of β2-Adrenergic Receptors Hastens Relaxation and Mediates Phosphorylation of Phospholamban, Troponin I, and C-Protein in Ventricular Myocardium From Patients With Terminal Heart Failure
Authors: AlbertoKaumann, SabineBartel, PeterMolenaar, LouiseSanders, KylieBurrell, DonatheVetter, PetraHempel, PeterKarczewski, Ernst-GeorgKrause
Journal: Circulation (1999)

Background—Catecholamines hasten cardiac relaxation through β-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of β1- and β2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results—Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 μmol/L) or zinterol (10 μmol/L), mediated through β2-adrenergic receptors, and of norepinephrine (10 μmol/L), mediated through β1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinep...
Abstract 5450: Anticancer effects of picrasidine Q from <i>Angelica keiski</i> on esophageal squamous cell carcinoma by downregulation of FGFR2 signaling pathways
Authors: Xuejiao Liu, Yuanyuan Shi, Mengqiu Song, Ran Zhao, Hanyong Chen, Jung Hyun Shim, Zigang Dong, Mee-Hyun Lee
Journal: Cancer Research (2018)

Abstract Fibroblast growth factor receptor (FGFR) 2 and its downstream signaling cascades, PI3 K/AKT/mTOR is playing an important role in cell survival and proliferations. In this study, we firstly found that picrasidine Q (PQ), an alkaloid component extracted from Angelica keiskei species, has the capacity of anti-cell transformation and anticancer. After ligand shape similarity approach of PQ, we found that PQ targeted FGFR 2 and verified by FGFR2 kinase assay as well as computational docking model. FGFR2 highly expressed in esophageal cancer tissues and PQ inhibited fibroblast growth factor (FGF)-induced cell transformation. Furthermore, PQ inhibited cell proliferation and induced G1 phase arrest of cell cycle and apoptosis in KYSE30, KYSE410, and KYSE450 esophageal squamous cell carcinoma (ESCC) cells. It was confirmed by detecting of biological markers such as cyclinD1, cyclinD3 and cyclinB1 for cell cycle or cleaved caspase-7, caspase-3, and PARP for apoptosis. PQ targeting of FGFR2 kinase activities suppressed downstream target proteins including phosphorylation of AKT and mTOR but not MEK/ERK signaling pathways. Taken together, our results are the first to identify that PQ might be a chemopreventive and chemotherapeutic agent by direct targeting FGFR2 and inhibiting cell proliferation of ESCC cells. Citation Format: Xuejiao Liu, Yuanyuan Shi, Mengqiu Song, Ran Zhao, Hanyong Chen, Jung Hyun Shim, Zigang Dong, Mee-Hyun Lee. Anticancer effects of picrasidine Q from Angelica keiski on esophageal squamous cell carcinoma by downregulation of FGFR2 signaling pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5450.
Involvement of Tumor Necrosis Factor-α in the Development of T Cell–Dependent Aortitis in Interleukin-1 Receptor Antagonist–Deficient Mice
Authors: TaizoMatsuki, KikuoIsoda, ReikoHorai, AkikoNakajima, YoshifusaAizawa, KazuoSuzuki, FumitakaOhsuzu, YoichiroIwakura
Journal: Circulation (2005)

Background— Interleukin-1 receptor antagonist–deficient (IL-1Ra−/−) mice on the BALB/c background spontaneously develop inflammatory arthropathy that resembles rheumatoid arthritis in humans. These mice also frequently develop aortitis at the root of the aorta, but the mechanism underlying the development of this disease has not been completely elucidated. Methods and Results— Using IL-1Ra−/− mice (backcrossed 8 generations to the BALB/c background) and wild-type mice, we studied the histopathology and examined the immunologic mechanisms involved in the development of aortic inflammation by cell transplantation experiments. Half of the IL-1Ra−/− mice developed aortitis at the root of the aorta, with massive infiltration of macrophages and monocytes and loss of elastic lamellae in the aortic media. Left ventricular hypertrophy and mild aortic stenosis were also shown by transthoracic echocardiography. Transplantation of T cells from IL-1Ra−/− mice induced aortitis in recipient nu/nu mice. Bone marrow cell ...
Functional Significance of Adenosine 5′-Diphosphate Receptor (P2Y12) in Platelet Activation Initiated by Binding of von Willebrand Factor to Platelet GP Ibα Induced by Conditions of High Shear Rate
Authors: ShinyaGoto, NorikoTamura, KojiEto, YasuoIkeda, ShunnosukeHanda
Journal: Circulation (2002)

Background— The role of the adenosine 5′-diphosphate receptor P2Y12 in platelet activation initiated by the von Willebrand factor (VWF)–GP Ibα interaction under high shear rate was investigated. Methods and Results— Blood samples were obtained from 11 donors. Shear-induced platelet aggregation was detected by optically modified cone-plate viscometer. Shear-induced VWF binding, P-selectin expression, and microparticle release were detected by flow cytometry. Platelet interaction with immobilized VWF was also investigated by parallel-plate flow chamber equipped with epifluorescent videomicroscopy. Effects of a selective P2Y12 antagonist AR-C69931 MX were tested. AR-C69931 MX inhibited shear-induced platelet aggregation in a dose-dependent manner, achieving the maximum inhibition at 100 nmol/L. The extent of aggregation after exposure to a shear rate of 10 800 s−1 for 6 minutes in the presence of 100 nmol/L AR-C69931 MX was 32.4±8.2% (mean±SD), which was significantly lower than the value in the controls of ...
Requisite Role for Interleukin-4 in the Acceleration of Fatty Streaks Induced by Heat Shock Protein 65 or Mycobacterium tuberculosis
Authors: JacobGeorge, YehudaShoenfeld, BorisGilburd, ArnonAfek, AvivShaish, DrorHarats
Journal: Circulation Research (2000)

Abstract—Atherosclerotic lesions can be induced in rabbits and mice immunized with heat shock protein 65 (HSP65). In the current study, we investigated the role of interleukin (IL)-4 in the HSP65- and Mycobacterium tuberculosis (MT)–induced models that exhibit an inflammatory phenotype. Fatty streak formation in IL-4–knockout (IL-4 KO) mice immunized with HSP65 or MT was significantly reduced when compared with lesions in wild-type C57BL/6 mice. However, when injected with control (HSP-free) adjuvant, no differences were evident in the lesion size between wild-type and the IL-4 KO mice. Next, we studied comparatively the extent of humoral and cellular immune responses to HSP65 in the IL-4 KO and wild-type mice, as those are thought to be influential in murine atherosclerosis. Anti-HSP65 antibody levels were reduced in the HSP65-immunized IL-4 KO mice as compared with their wild-type littermates, whereas no differences were evident between the groups with respect to the primary cellular immune response to ...
Rates of and Factors Associated With Infection in 200 909 Medicare Implantable Cardioverter-Defibrillator Implants
Authors: Jordan M. Prutkin, Matthew R. Reynolds, Haikun Bao, Jeptha P. Curtis, Sana M. Al-Khatib, Saurabh Aggarwal, Daniel Z. Uslan
Journal: Circulation (2014)

Background— The rate of implantable cardioverter-defibrillator (ICD) infections has been increasing faster than that of implantation. We sought to determine the rate and predictors of ICD infection in a large cohort of Medicare patients. Methods and Results— Cases submitted to the ICD Registry from 2006 to 2009 were matched to Medicare fee-for-service claims data using indirect patient identifiers. ICD infections occurring within 6 months of hospital discharge after implantation were identified by ICD-9 codes. Logistic regression was used to examine factors associated with risk of ICD infection. Of 200 909 implants, 3390 patients (1.7%) developed an ICD infection. The infection rate was 1.4%, 1.5%, and 2.0% for single, dual, and biventricular ICDs, respectively ( P &lt;0.001). Generator replacement had a higher rate compared with initial implant (1.9% versus 1.6%, P &lt;0.001). The factors associated with infection were adverse event during implant requiring reintervention (odds ratio [OR], 2.692; 95% confidence interval [CI], 2.304–3.145), previous valvular surgery (OR, 1.525; 95% CI, 1.375–1.692), reimplantation for device upgrade, malfunction, or manufacturer advisory (OR, 1.354; 95% CI, 1.196–1.533), renal failure on dialysis (OR, 1.342; 95% CI, 1.123–1.604), chronic lung disease (OR, 1.215; 95% CI, 1.125–1.312), cerebrovascular disease (OR, 1.172; 95% CI, 1.076–1.276), and warfarin (OR, 1.155; 95% CI, 1.060–1.257). Conclusions— Patients who developed an ICD infection were more likely to have had peri-ICD implant complications requiring early reintervention, previous valve surgery, device replacement for reasons other than battery depletion, and increased comorbidity burden. Efforts should be made to carefully consider when to reenter the pocket at any time other than battery replacement.
Abstract 11279: Heart Type Fatty Acid-Binding Protein is a Factor for Predicting Concomitant Presence of Coronary Artery Disease in Patients With Abdominal Aortic Aneurysms
Authors: AkiraFunayama, TetsuWatanabe, YoichiroOtaki, SatoshiNishiyama, HirokiTakahashi, TakanoriArimoto, TetsuroShishido, TakuyaMiyamoto, IsaoKubota
Journal: Circulation (2014)

Introduction: Abdominal aortic aneurysm (AAA) is not unusual to find such aneurysms accompanied by coronary artery disease (CAD). However, no risk factors that allow the prediction of accompanying CAD among AAA patients have yet been identified. Heart type fatty acid-binding protein (H-FABP) is available as indicators of myocardial damage. Recent reports suggest that H-FABP can be a factor for predicting the severity and prognosis in patients with CAD. This study dissected AAA cases and considered whether H-FABP may be a predictive factor in the concomitant presence of CAD. Methods: The study focused on 90 patients awaiting surgery for AAA, who underwent coronary angiography examinations for the purpose of undergoing the detailed examination of the coronary artery. H-FABP and a range of other blood sampling markers were measured, and the patients were divided into groups according to the concomitant presence of CAD. Results: Forty cases tested positive for CAD. The H-FABP of the CAD group was compared wit...