tbuckley/cabot-search huggingface dataset:
Abstract 3039: The MELK/FOXM1 axis is a master regulator of proneural to mesenchymal transition (PMT) in glioma stem cells by controlling EZH2 transcriptional activity
Authors: Kaushal Joshi, Sunghak Kim, Jeongwu Lee, Ronald Waclaw, Lisa Salcini, Ichiro Nakano
Journal: Cancer Research (2014)

Abstract In the Central Nervous System, stem cells are present in the normal brain and primary brain tumor, glioblasotoma multiforme (GBM). Both normal and oncogenic stem cells play central roles in organogenesis and tumorigenesis, respectively. Previously we identified that the mitotic kinase MELK binds and phosphorylates the oncogenic transcription factor FOXM1 to regulate the growth of both brain-derived and GBM-derived stem cells (GSCs). Here we demonstrate that the Enhancer of Zeste Homolog 2 (EZH2), the lysine methyltransferase of Polycomb repressive complex 2, is the major transcriptional target of the MELK-FOXM1 complex in GSCs. PCR-based analysis of FOXM1 immunoprecipitated chromatin determined the binding of FOXM1 to the EZH2 promoter region to drive its transcriptional activity. This signaling is mediated through the protein complex formation of FOXM1 and MELK in a MELK kinase-dependent manner. The MELK-FOXM1 driven EZH2 signals are required to retain the immature stem cell trait and mesenchymal identity in GBM, as well as GSCs' radiation resistant phenotype in a MELK kinase-dependent manner. Clinically, GBM tumors co-express MELK and EZH2 with significant elevation in post-irradiation recurrent tumors. This post-irradiation elevation of MELK and EZH2 was observed specifically in GSCs. Irradiation induces transformation of proneural (PN) GSCs into a Mesenchymal (Mes)-like GSC phenotype (PMT) that is highly resistant to radiation treatment, and inhibition of EZH2 by shRNA reverses the radiation-resistant phenotype of Mes GSCs. Elimination of MELK or FOXM1 by shRNA reduced EZH2 expression resulting in attenuated stemness and radiation resistance in vitro and in vivo. These phenotypes were completely restored by exogenous expression of EZH2. To our knowledge, this study provides the first evidence of the role of MELK-FOXM1-EZH2 signaling axis for maintenance of stem cell trait and PMT regulation in GSCs. Identification of the role of transcriptional regulator EZH2 in PMT by the mitotic kinase MELK and transcription factor FOXM1 complex sheds lights on a novel therapeutic target for aggressive cancers including GBM. Citation Format: Kaushal Joshi, Sunghak Kim, Jeongwu Lee, Ronald Waclaw, Lisa Salcini, Ichiro Nakano. The MELK/FOXM1 axis is a master regulator of proneural to mesenchymal transition (PMT) in glioma stem cells by controlling EZH2 transcriptional activity. [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 3039. doi:10.1158/1538-7445.AM2014-3039
Mitochondrial DNA heteroplasmy in cloned cattle produced by fetal and adult cell cloning
Authors: Ralf Steinborn, Pamela Schinogl, Valeri Zakhartchenko, Roland Achmann, Wolfgang Schernthaner, Miodrag Stojkovic, Eckhard Wolf, Mathias Müller, Gottfried Brem
Journal: Nature Genetics (2000)
Impact of right ventricular involvement on mortality and morbidity in patients with inferior myocardial infarction11Drs. Mehta and Eikelboom were recipients of Heart and Stroke Foundation of Canada Research Fellowship Awards. Professor Yusuf is the recipient of a Medical Research Council of Canada Senior Scientist Award and holds a Heart and Stroke Foundation of Ontario Research Chair.
Authors: Shamir R Mehta, John W Eikelboom, Madhu K Natarajan, Rafael Diaz, Cheelong Yi, Raymond J Gibbons, Salim Yusuf
Journal: Journal of the American College of Cardiology (2001)
Abstract 96: A novel <i>in vivo</i> preclinical model for the study of human tumor angiogenesis with human vessels
Authors: Kirsty A. Holden, Michael A. Batey, Martyn Bottomley, Catherine Booth
Journal: Cancer Research (2014)

Abstract The preclinical assessment of anti-angiogenic drug efficacy is hampered by the lack of availability of suitable model systems to study anti-human therapies. Good in vitro assays exist for testing anti-human-specific therapies but these are let down by the lack of robust translatable in vivo models. Currently available preclinical models such as the matrigel plug assay and the window chamber assay focus on the angiogenesis of mouse vessels which may not be truly reflective of the influence of test items on human vasculature, and in vivo models to study the angiogenesis of human tumors by human vessels are unfortunately lacking. We have developed a sophisticated model to address this using adult human skin engrafted onto immunocompromised CB17-SCID mice. Angiogenesis of the skin follows, with human and host vessels anastomosing, resulting in a viable skin graft containing functioning human CD31-labelled vessels. This skin graft can be intradermally injected with a cell line of interest, such as the human melanoma cell line A375, and the ensuing tumors contain human vessels as evidenced by immunohistochemistry with a human-specific anti-CD31 antibody. Using the Aperio® Scanscope and FDA-approved microvessel analysis algorithm, 5-10 human vessels per mm2 of human tumor are observed. Furthermore, the model has the potential to be used in combination with non-invasive in vivo imaging techniques to assess tumor growth inhibition in response to therapies in a longitudinal fashion. This novel technique could potentially enable the rapid preclinical testing of anti-angiogenic anti-human therapies to help provide a go/no-go decision prior to costly clinical trials. Citation Format: Kirsty A. Holden, Michael A. Batey, Martyn Bottomley, Catherine Booth. A novel in vivo preclinical model for the study of human tumor angiogenesis with human vessels. [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 96. doi:10.1158/1538-7445.AM2014-96
Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis
Authors: Ken-ichiro Sasaki, Toyoaki Murohara, Hisao Ikeda, Takeshi Sugaya, Toshifumi Shimada, Satoshi Shintani, Tsutomu Imaizumi
Journal: Journal of Clinical Investigation (2002)

The role of the renin-angiotensin system (RAS) in angiogenesis is little known. Here, we show that the angiotensin II (ATII) type 1 (AT1) receptor plays an important role in ischemia-induced angiogenesis. Well-developed collateral vessels and angiogenesis were observed in wild-type (WT) mice in response to hindlimb ischemia, whereas these responses were reduced in ATII type 1a receptor knockout (AT1a–/–) mice. Ischemia-induced angiogenesis was also impaired in WT mice treated with the AT1 receptor blocker TCV-116. These effects were not due to reduced systemic blood pressure (SBP), because hydralazine treatment preserved angiogenesis in WT mice although it reduced SBP to a level similar to that of AT1a–/– mice. Infiltration of inflammatory mononuclear cells (MNCs), including macrophages and T lymphocytes, was suppressed in the ischemic tissues of AT1a–/– mice compared with WT mice. Double immunofluorescence staining revealed that infiltrated macrophages and T lymphocytes expressed VEGF, and the expression of VEGF and monocyte chemoattractant protein-1 was also decreased in AT1a–/–. Finally, the impaired angiogenesis in AT1a–/– mice was rescued by intramuscular transplantation of MNCs obtained from WT mice, further indicating the importance of MNC infiltration in ischemia-induced angiogenesis. Thus, the ATII–AT1 receptor pathway promotes early angiogenesis by supporting inflammatory cell infiltration and angiogenic cytokine expression.
NIH Budget Battle Looms
Authors: Mike Mitka
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 4237: Antitumor activity of 2-hydroxycinnamaldehyde against human colorectal cancer cells is mediated by the Wnt/β-catenin signaling pathway
Authors: Won Kyung Kim, Jedo Oh, Song Yi Bae, Jayoung Song, Yoonho Shin, Tae Joon Choi, Eun Ju Jeong, So Hyun Park, Eun Jeong Jang, Ji In Kang, Hyen Joo Park, Ji-Young Hong, Min Ai Lee, Hwa-Jin Chung, Sang Kook Lee
Journal: Cancer Research (2014)

Abstract The antiproliferative and antitumor activities of 2-hydroxycinnamaldehyde (1), a phenylpropanoid isolated from the bark of Cinnamomum cassia , were investigated using human colorectal cancer cells. Compound 1 exhibited antiproliferative effects in HCT116 colon cancer cells, accompanied by modulation of the Wnt/β-catenin cell signaling pathway. This substance was found also to inhibit β-catenin/T-cell factor (TCF) transcriptional activity in HEK293 cells and HCT116 colon cancer cells. Further mechanistic investigations in human colon cancer cells with aberrantly activated Wnt/β-catenin signaling showed that 1 suppressed significantly the binding of β-catenin/TCF complexes to their specific genomic targets in the nucleus and led to the down-regulation of Wnt target genes such as c-myc and cyclin D1. In an in vivo xenograft model, the intraperitoneal administration of 1 (10 or 20 mg/kg body weight, three times/week) for four weeks suppressed tumor growth in athymic nude mice implanted with HCT116 colon cancer cells significantly, without any apparent toxicity. In an ex vivo biochemical analysis of the tumors, compound 1 was also found to suppress Wnt target genes associated with tumor growth including β-catenin, c-myc, cyclin D1, and survivin. The suppression of the Wnt/β-catenin signaling pathway is a plausible mechanism of action underlying the antiproliferative and antitumor activity of 1 in human colorectal cancer cells (Acknowledgements: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MEST) No. 20120004939) Citation Format: Won Kyung Kim, Jedo Oh, Song Yi Bae, Jayoung Song, Yoonho Shin, Tae Joon Choi, Eun Ju Jeong, So Hyun Park, Eun Jeong Jang, Ji In Kang, Hyen Joo Park, Ji-Young Hong, Min Ai Lee, Hwa-Jin Chung, Sang Kook Lee. Antitumor activity of 2-hydroxycinnamaldehyde against human colorectal cancer cells is mediated by the Wnt/β-catenin signaling pathway. [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 4237. doi:10.1158/1538-7445.AM2014-4237
<i>BMJ USA:</i> A British contribution to American medicine
Authors: Ronald M Davis, Richard Smith
Journal: BMJ (2002)

This article originally appeared in BMJ USA 

Throughout its history the United States has benefited from British contributions.1 In the early days of the republic, Americans used James Watt's steam engine in locomotives and steamboats. The works of British authors from Shakespeare to Kipling have featured in the curriculum of American schools. Recently British journalism—led by Nature and The Economist —has become popular and influential, while the success of the film American Beauty has shown how much can be achieved by a combination of British and American talent.

We hope to emulate some of these successes in BMJ USA . The BMJ ( British Medical Journal ) Publishing Group, in partnership with the Clinicians Group, will be sending BMJ USA each month to about 100,000 primary care physicians in the US.

BMJ USA will feature articles from the weekly BMJ that are particularly relevant to primary care medicine in the US. Although the BMJ began in Britain, it publishes material from all over the world, and it is the international first choice for many primary care researchers. On occasion BMJ USA will also contain material from other journals published by the BMJ Publishing Group—such as Heart, …
Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus
Authors: Elisabeth Verpy, Saber Masmoudi, Ingrid Zwaenepoel, Michel Leibovici, Tim P. Hutchin, Ignacio Del Castillo, Sylvie Nouaille, Stéphane Blanchard, Sophie Lainé, Jean-Luc Popot, Felipe Moreno, Robert F. Mueller, Christine Petit
Journal: Nature Genetics (2001)
Abstract 15999: The Divergent Effects of Exercise Training After Myocardial Infarction or Pressure Overload Depend Critically on Endothelial Nitric Oxide Synthase
Authors: Yanti Octavia, Elza v Deel, Monique d Waard, Martine d Boer, An Moens, Dirk J Duncker
Journal: Circulation (2014)

AIMS: Beneficial effects of aerobic exercise training are widely recognized. However, previously we discovered that the positive effects of exercise depend on the underlying cause of cardiac failure. Here we tested the hypothesis that endothelial nitric oxide synthase (eNOS) dependent regulation of the balance between nitric oxide and superoxide (O2•-) is critically involved in determining the effects of exercise. METHODS: Mice were exposed to 8 weeks of voluntary wheel running exercise training (EX) or sedentary housing (SED) immediately following myocardial infarction (MI), pressure overload from a transverse aortic constriction (TAC), or sham (SH) surgery. Subsequently, left ventricular (LV) ejection fraction (EF) was measured by echocardiography and Picrosirius Red staining was performed to measure collagen content. Additionally, total and NOS-dependent LV O2•- were measured using lucigenin-enhanced chemiluminescence without or with NOS inhibitor, L-NAME. eNOS uncoupling was evaluated by determining eNOS monomer dimer protein ratio and peroxynitrite (ONOO-) levels were measured through luminol-enhanced chemiluminescence. RESULTS: Cardiac dysfunction and fibrosis were ameliorated by exercise in MI but not in TAC mice (Table 1). MI and TAC both increased LV O2•- levels. Strikingly, EX diminished O2•- generation in MI, but exacerbated O2•- generation in TAC (Table 1). Furthermore, the EX-induced increase in O2•- levels in TAC were largely NOS-dependent. Accordingly, MI and TAC-induced eNOS uncoupling was normalized by EX in MI but aggravated in TAC mice (Table 1). Similarly, increased ONOO- levels following MI and TAC were diminished by EX in MI, but exacerbated by EX in TAC (Table 1). CONCLUSIONS: EX reduces eNOS-mediated cardiac oxidative stress in MI. In contrast, beneficial effects of EX are lacking in cardiac pressure-overload following TAC, due to EX-induced aggravation of ONOO- formation, eNOS uncoupling and concomitant oxidative stress.
Abstract 13777: Relationship of Office and Ambulatory Blood Pressure with Left Ventricular Global Longitudinal Strain
Authors: Fusako Sera, Zhezhen Jin, Cesare Russo, Edward S Lee, Joseph E Schwartz, Tatjana Rundek, Mitchell S Elkind, Shunichi Homma, Ralph L Sacco, Marco R Di Tullio
Journal: Circulation (2014)

Introduction:  High blood pressure (BP) is a strong risk factor for heart failure. Ambulatory BP (ABP) is a better predictor of cardiovascular events, including heart failure, than office BP. Left ventricular (LV) global longitudinal strain (GLS) can detect early subclinical cardiac dysfunction even when LV ejection fraction (EF) is normal. We investigated the relationship of ABP with GLS in a community-based cohort with normal LVEF.   Methods:  Two-dimensional speckle tracking echocardiography and 24-hour ABP monitoring were performed in 577 participants (mean age 70 ± 9 years; 60% women) with normal LVEF (≥50%) from the Cardiovascular Abnormalities and Brain Lesions (CABL) study.   Results:  Higher BP values, both ABP and office BP, were consistently associated with lower (i.e., less negative) GLS. After adjustment for pertinent covariates (age, sex, race/ethnicity, body mass index, diabetes mellitus, coronary artery disease, LV mass index, and antihypertensive medication), office diastolic BP [B (SE)=0.04 (0.01), p=0.003] and 24-hour systolic and diastolic ABP [B (SE)=0.04 (0.01), p   Conclusions:  Higher ABP values are strongly associated with lower GLS in subjects with normal LVEF, independent of cardiovascular risk factors and office BP. ABP monitoring may be of value for the early identification of subjects at increased risk of developing heart failure.
Carbohydrate tolerance in patients with granuloma annulare*.
Authors: S. HAIM, R. FRIEDMAN-BIRNBAUM, N. HAIM, A. SHAFRIR, A. RAVINA
Journal: British Journal of Dermatology (1973)

Journal Article Carbohydrate tolerance in patients with granuloma annulare: STUDY OF FIFTY‐TWO CASES Get access S. HAIM, S. HAIM Department of Dermatology, Rambam Government Hospital and Aba Khoushy School of Medicine, Diabetes Clinic, Workers Sick Fund of the General Federation of Labour, Haifa, Israel Search for other works by this author on: Oxford Academic Google Scholar R. FRIEDMAN‐BIRNBAUM, R. FRIEDMAN‐BIRNBAUM Department of Dermatology, Rambam Government Hospital and Aba Khoushy School of Medicine, Diabetes Clinic, Workers Sick Fund of the General Federation of Labour, Haifa, Israel Search for other works by this author on: Oxford Academic Google Scholar N. HAIM, N. HAIM Department of Dermatology, Rambam Government Hospital and Aba Khoushy School of Medicine, Diabetes Clinic, Workers Sick Fund of the General Federation of Labour, Haifa, Israel Search for other works by this author on: Oxford Academic Google Scholar A. SHAFRIR, A. SHAFRIR Department of Dermatology, Rambam Government Hospital and Aba Khoushy School of Medicine, Diabetes Clinic, Workers Sick Fund of the General Federation of Labour, Haifa, Israel Search for other works by this author on: Oxford Academic Google Scholar A. RAVINA A. RAVINA Department of Dermatology, Rambam Government Hospital and Aba Khoushy School of Medicine, Diabetes Clinic, Workers Sick Fund of the General Federation of Labour, Haifa, Israel Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 88, Issue 5, 1 May 1973, Pages 447–451, https://doi.org/10.1111/j.1365-2133.1973.tb15448.x Published: 01 May 1973 Article history Accepted: 03 November 1972 Published: 01 May 1973
Differences in national influenza vaccination policies across the European Union, Norway and Iceland 2008-2009
Authors: J Mereckiene, S Cotter, F D'Ancona, C Giambi, A Nicoll, D Lévy-Bruhl, P L Lopalco, J T Weber, K Johansen, L Dematte, S Salmaso, P Stefanoff, D Greco, F Dorleans, A Polkowska, D O’Flanagan, None on behalf of the VENICE project gatekeepers group
Journal: Eurosurveillance (2010)

In 2009 the second cross-sectional web-based survey was undertaken by the Vaccine European New Integrated Collaboration Effort (VENICE) project across 27 European Union (EU) member states (MS), Norway and Iceland (n=29) to determine changes in official national seasonal influenza vaccination policies since a survey undertaken in 2008 and to compare the estimates of vaccination coverage between countries using data obtained from both surveys. Of 27 responding countries, all recommended vaccination against seasonal influenza to the older adult population. Six countries recommended vaccination of children aged between six months and &lt;18 years old. Most countries recommended influenza vaccination for those individuals with chronic medical conditions. Recommendations for vaccination of healthcare workers (HCW) in various settings existed in most, but not all countries. Staff in hospitals and long-term care facilities were recommended vaccination in 23 countries, and staff in out-patient clinics in 22 countries. In the 2009 survey, the reported national estimates on vaccine coverage varied by country and risk group, ranging from 1.1% - 82.6% for the older adult population; to between 32.9% -71.7% for clinical risk groups; and from 13.4% -89.4% for HCW. Many countries that recommend the influenza vaccination do not monitor the coverage in risk groups. In 2008 and 2009 most countries recommended influenza vaccination for the main risk groups. Hovewer, despite general consensus and recommendations for vaccination of high risk groups many countries do not achieve high coverage in these groups. The reported vaccination coverage still needs to be improved in order to achieve EU and World Health Organization goals.
Evaluation of rapid influenza diagnostic tests for detection of novel influenza A (H1N1) virus - United States, 2009.
Authors: A. Balish, C. M. Warnes, K. Wu, N. Barnes, S. Emery, L. Berman, B. Shu, S. Lindstrom, X. Xu, T. Uyeki, M. Shaw, A. Klimov, J. Villanueva
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Abstract P152: Clinical Utility Of Visceral Adipose Tissue Volume In Identification Of Middle Age Adults With Type 2 Diabetes
Authors: Prasenjeet N Motghare, Christina Shay, Mercedes R Carnethon, David R R Jacobs, Cora E. E Lewis, J. Greg Terry, Jeffrey Carr
Journal: Circulation (2014)

Background: Higher visceral adipose tissue (VAT) volume is associated with greater risk for the development of type 2 diabetes (T2D). Although VAT volume and prevalence of T2D vary by sex and race, differences in VAT volumes that are associated with the identification of individuals with prevalent T2D across these groups has not been fully examined. Objective: Our goal was to determine VAT volume cut points that maximize true positive, true negative, and optimal identification of individuals with T2D according to sex and race. Methods: Data were examined from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a multi-center longitudinal study of the development of cardiovascular risk in black and white men and women ages 18-30 years at baseline. In 2010-2011, the Year 25 exam was performed (43-55 years). VAT (cm 3 ) was quantified by computed tomography based on two 5 mm contiguous slices at the level of the 4 th -5 th lumbar vertebra (n=3,161). T2D was defined based on the presence of fasting plasma glucose ≥126 mg/dL, 2-hour post load blood glucose ≥200 mg/dL, HbA1c ≥6.5% and/or diabetes medication use. Receiver operating characteristic (ROC) curve analysis was used to identify VAT cut points associated with identification of T2D. Results: Prevalence of T2D at the year 25 exam ranged from 8.8% in white women to 17.7% in black men; mean (SD) VAT volume ranged from 113.5 (79.9) cm 3 in white women to 170.2 (80.2) in white men. White men exhibited the highest cut points of VAT volume needed to identify cases of T2D (26-35% higher) and black women exhibited the lowest cut points (4-36% lower) for true positive, true negative, and optimal identification of T2D compared to other race and sex groups (Table 1). Conclusions: Although the utility of VAT volume to identify individuals with T2D is modest [[Unable to Display Character: &amp;#8211;]] likely a result of other unaccounted metabolic risk factors [[Unable to Display Character: &amp;#8211;]] these cross-sectional findings display race and sex differences in the VAT volume cut points associated with prevalent T2D.