tbuckley/cabot-search huggingface dataset:
Abstract 2713: Small-molecule FASN inhibitors promote growth inhibition growth and apoptosis of breast cancer
Authors: Ruth Lupu, Anatilde Gonzalez Guerrico, Ashwani Khurana, Timothy Heuer, George Kemble, Chandra Mohan KVP
Journal: Cancer Research (2014)

Abstract Increased de novo lipogenesis due to enhanced expression of several lipogenic enzymes has been found in many types of human cancers. Fatty acid synthase (FASN), the key enzyme in the de novo lipogenesis pathway, is one of the most commonly over-expressed lipogenic enzymes. Studies in the past decade have recognized FASN overexpression as a molecular marker for poor prognosis and malignant phenotype of many cancers. Tumor-associated FASN, by conferring growth and survival advantages rather than functioning as an anabolic energy-storage pathway, has also been suggested to play an active part in the development, maintenance, and metastatic progression of human cancers. More recently, FASN has been implicated in contributing to cellular resistance to several anticancer treatments. A variety of agents have been developed to target lipogenic enzymes and the key regulators involved in lipid metabolism in cancer cell for therapeutic purposes. The development of several FASN inhibitors has been reported from both academic labs and industries. When used in in vitro, xenograft and genetically induced mouse model studies, these inhibitors have supported FASN as an excellent target. A new generation of FASN inhibitors was developed at 3-V Biosciences that are highly specific, reversible inhibitors of FASN. One compound in this series, TVB-2640, is orally bioavailable and has progressed into Phase 1 clinical studies. The effect of two anti-FASN drugs in this series, TVB-3150 and TVB-3199 were tested for their effect on breast cancer cells. We demonstrated that the EC50 is between 9-50 nM, depending on the drug and the tested cell line. We then demonstrated that the drugs inhibited the anchorage-dependent and -independent growth of FASN expressing cells in a dose dependent manner. The apparent mechanism by which the FASN inhibitors promote inhibition of growth is by inducing apoptotic cell death in a time- and dose-dependent manner that involves regulation of apoptotic and pro-apoptotic proteins. Furthermore, the combination of the anti-FASN drugs with small molecule inhibitors of the antiapoptotic proteins Bcl-2 and Bcl-xL significantly increased the apoptotic effect in a synergistic manner compared to either of the synthetic inhibitors alone. In vivo studies demonstrate tumor growth inhibition without toxicity. Clinical development of a first-in-class, orally active, potent, and reversible FASN inhibitor as a novel cancer therapeutic is ongoing. Citation Format: Ruth Lupu, Anatilde Gonzalez Guerrico, Ashwani Khurana, Timothy Heuer, George Kemble, Chandra Mohan KVP. Small-molecule FASN inhibitors promote growth inhibition growth and apoptosis of breast cancer. [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 2713. doi:10.1158/1538-7445.AM2014-2713
French cattle to be screened for BSE
Authors: Alexander Dorozynski
Journal: BMJ (2000)

The French government has launched a programme to screen the country's cows for bovine spongiform encephalopathy (BSE).

Some 48 000 tests will be carried out with the Swiss test kit “Prionics” on animals more than 2 years old either found dead for no known reason or after accidental death. If an animal …
Role of radiation therapy in primary mediastinal large <scp>B</scp>‐cell lymphoma in rituximab era: A <scp>US</scp> population‐based analysis
Authors: Smith Giri, Vijaya Raj Bhatt, Ranjan Pathak, R. Gregory Bociek, Julie M. Vose, James O. Armitage
Journal: American Journal of Hematology (2015)

The use of radiation (RT) in primary mediastinal large B-cell lymphoma (PMBCL) may predispose young patients to the risk of cardiopulmonary toxicities and secondary malignancies. We used Surveillance, Epidemiology and End Results (SEER) 18 database to compare the overall survival (OS) differences among adult patients treated with and without RT after rituximab approval in the US. Multivariate analyses were performed using Cox proportional hazards regression to compare OS based on the use of RT while adjusting for age, year of diagnosis, race, stage and gender. PMBCL patients (n = 258), who received RT (48%), were similar in terms of age, gender, race, and stage at diagnosis to patients who did not receive RT. The five year OS was similar between patients treated with versus without RT (82.5% vs. 78.6%, P = 0.47). In a multivariate analysis, the use of RT did not influence OS in the rituximab era (HR 0.83; 95% CI 0.43-1.59; P = 0.56). Rituximab may reduce the benefit of RT in select patients such as those who achieve a metabolic complete remission at the end of chemotherapy.
microRNA-mediated keratinocyte hyperproliferation in psoriasis vulgaris
Authors: A. Ichihara, M. Jinnin, K. Yamane, A. Fujisawa, K. Sakai, S. Masuguchi, S. Fukushima, K. Maruo, H. Ihn
Journal: British Journal of Dermatology (2011)

Psoriasis is a chronic inflammatory skin disease characterized by intense proliferation and abnormal differentiation of keratinocytes, although the pathogenesis is still not completely clarified.We investigated the mechanism of keratinocyte proliferation seen in psoriasis, focusing on microRNA (miRNA).miRNAs were extracted from tissues and sera of psoriasis, atopic dermatitis and healthy control. To determine pathogenic miRNAs, we performed miRNA polymerase chain reaction (PCR) array analysis. The results were confirmed with quantitative real-time PCR, in situ hybridization, immunohistochemistry, transient transfection of siRNA and inhibitor in cultured keratinocytes and Western blotting.PCR array analysis using tissue miRNA demonstrated miR-424 level was markedly decreased in psoriasis skin in vivo. Protein expression of mitogen-activated protein kinase kinase 1 (MEK1) or cyclin E1, predicted target genes of miR-424, was increased in psoriatic skin, although their mRNA levels were not. The transfection of specific inhibitor of miR-424 in normal human keratinocytes led to upregulation of MEK1 or cyclin E1 protein, and resulted in increased cell proliferation. On the other hand, cell number was significantly decreased when cells were transfected with siRNA for MEK1 or cyclin E1. Furthermore, we first investigated serum miRNA levels in psoriasis. Although not significant, serum miR-424 concentration tended to be decreased in patients with psoriasis compared with healthy controls.Decreased miR-424 expression and subsequently increased MEK1 or cyclin E1 may play a key role in the pathogenesis of psoriasis. Investigation of the regulatory mechanisms of keratinocyte proliferation by miRNA may lead to new treatments and a disease activity marker.
Cerebral Mechanisms in Behavior: The Hixon Symposium
Authors: Lloyd A. Jeffress
Journal: JAMA (1952)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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 18976: A Role of an HDL-associated Anti-inflammatory Protein, Progranulin, in Acute Coronary Syndrome
Authors: Ryota Kawase, Tohru Ohama, Masaya Morita, Yuma Kurozumi, Noritoshi Ito, Takeshi Okada, Daisaku Masuda, Masahiro Koseki, Makoto Nishida, Hirotaka Sawano, Yasuharu Doi, Yasushi Sakata, Shizuya Yamashita
Journal: Circulation (2014)

We previously reported that Progranulin (PGRN) is secreted from human monocyte-derived macrophages and bound to HDL/ApoA-I. Recently, we also demonstrated that PGRN deficiency leads to accelerated evelopment of atherosclerosis by generating ApoE -/- PGRN -/-  (double knockout, DKO) mice compared with ApoE -/-  mice. DKO mice exhibited enhanced systemic inflammation and impairment of endothelial function as well as excessive cholesterol accumulation in peritoneal macrophages. In addition, PGRN was mainly expressed in macrophages of atherosclerotic plaque. We hypothesized that PGRN may play some role in the coronary plaque stability in acute coronary syndrome. We enrolled consecutive patients (40 males and 11 females; mean age, 65.6±10.3 years) with ACS who underwent emergency coronary angiography. We also enrolled patients without coronary artery disease (79 male, 79 female; mean age, 61.8±13.5 years). There are not significant differences in peripheral blood PGRN concentration between two groups. We obtained peripheral vein blood samples, arterial blood samples as well as the aspirated samples obtained from the culprit lesion at the time of emergency PCI. Serial blood samples were obtained from on arrival to at discharge from the hospital and at the later outpatient visit. Immunostaining of aspirated samples showed that PGRN was mainly expressed in macrophages. Compared to peripheral vein and arterial samples, PGRN concentration in the coronary artery was significantly lower (47.9 ng/ml, 47.5 ng/ml vs 41.7 ng/ml,respectively). However, PGRN concentration gradually increased after PCI and became highest after 48 hours (47.9 ng/ml vs 59.7 ng/ml). We suggest that higher plasma PGRN concentration might stabilize the vulnerable plaque. We will show the  in vitro  studies using THP-1 cells and HAoSMC to demonstrate the effect of PGRN on the plaque stability such as MMP9 expression and fibrous cap formation. Taken together, HDL-associated anti-inflammatory protein PGRN may be involved in the stabilization of vulnerable coronary arterial plaques.
Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma
Authors: Hector Ortega, Lynn Katz, Benjamin Hartley, Steve Yancey
Journal: European Respiratory Journal (2013)

Background: Measurement of peripheral blood eosinophils (eos) may be informative in the identification of severe eosinophilic asthma.

Objective: We investigated whether a single measurement of blood eos is predictive of future blood eos levels or whether multiple measurements over time are significantly more predictive.

Methods: DREAM ([NCT01000506][1]) included patients (pts) with frequent serious exacerbations and measured eos at screening, start of treatment (week 0) and every four weeks up to week 56. Based on data from placebo pts (N=155) we determined whether pts with a eos count of ≥150/μL at screening remained on average above this level during the following year. A repeated measures model examined the relationship between screening blood eosinophil level and subsequent measurements.

Results: Of 115 pts with eos ≥150/µL at screening, 17 (15%) fall below this level in their post-screening average. Using the average of 2, 3 or 4 measures ≥150/µL, selects 120, 116 and 118 pts respectively; of these, 18 (15%), 12 (10%) and 10 (8%) have post-screening averages below 150/µL. The data shows that extreme values at screening tend not to be replicated. The model suggests that pts with 150/µL at screening would have a mean post-screening average in the following year of 168/µL 95%CI (149, 189).

Conclusion: A single measurement ≥150/µL appears highly sensitive (85%) to predict the average of subsequent measurements being ≥150/µL in this population. A higher cut-off may be less predictive. Using an average of multiple measurements only marginally increases the sensitivity. Therefore, a single eos measurement in severe asthma pts may be a reliable biomarker for the eosinophilic asthma phenotype.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01000506&atom=%2Ferj%2F42%2FSuppl_57%2FP855.atom
The correlation of clinical efficacy, serum trough levels and antidrug antibodies in ustekinumab-treated patients with psoriasis in a clinical-practice setting
Authors: S.P. Menting, J.M.P.A. van den Reek, E.M. Baerveldt, E.M.G.J. de Jong, E.P. Prens, L.L.A. Lecluse, G.J. Wolbink, D. Van der Kleij, Ph.I. Spuls, T. Rispens
Journal: British Journal of Dermatology (2015)

Several therapeutic antibodies are available for the treatment of chronic plaque type psoriasis. Ustekinumab (a monoclonal IL12/23 antagonist) is one of these antibodies (1) and it is currently being investigated for other indications. For adalimumab (a monoclonal tumour necrosis factor α antagonist) a positive correlation has been observed between adalimumab trough levels and clinical efficacy, both showing a negative correlation with anti-drug antibodies (ADA) to adalimumab (present in 49% of patients) (2). In rheumatoid arthritis, a therapeutic range for adalimumab trough level has been established, which can eventually lead to a more personalised way of administering adalimumab (3). This article is protected by copyright. All rights reserved
291. Comparison of Anti-Tumor Effects between Transmembrane and Secretory Tumor Necrosis Factor-alpha In Vitro and In Vivo
Authors: Wenfang Shi, Qingfen Li, Zhuoya Li
Journal: Molecular Therapy (2005)

Tumor necrosis factor-alpha (TNF-a) exists naturally in two forms, transmembrane and secretory form. In the present study, three recombinant retroviral vectors containing human wild type TNF-a (Wt-TNF), secretory TNF-a (S-TNF, a mutant replaced its signal peptide by that of IL-2), and transmembrane TNF-a (TM-TNF, a mutant deleted a site for cleavage of TNF into the secretory form) were constructed respectively and transfected stably into murine hepatic carcinoma cell line (H22). TNF-a either secreted in supernatants by S-TNF and Wt-TNF producing tumor cells or expressed on cell surface of TM-TNF and Wt-TNF synthesizing tumor cells was demonstrated to be cytotoxic against TNF sensitive L929 cells. Also, the H22 cells transfected with three types of TNF-a can kill parental H22 in effect/target (E/T) dependent manner in vitro and their maximal killing rates were about 38|[sim]|43% at E/T ratio of 5:1. Injection of total 2.5|[prime]|105 cells mixed with transfected and parental H22 tumor cells at different ratios into syngeneic mice resulted in the inhibition of tumor growth and their maximal inhibition rates were about 57|[sim]|72% at E/T 5:1. A transient weight loss was found in mice bearing S-TNF producing tumors, whereas no obvious side effects were seen in mice bearing TM-TNF or Wt-TNF expressing tumors. It has been shown that S-TNF secreting tumor promoted significantly lymphocytes infiltration and attracted more CD4+ T cells than CD8+ T cells to the tumor site, while TM-TNF expressing tumor stimulated Fas expression and inhibited a tumor metastasis associated molecule CD44v3 expression on tumor cells. These results suggest that S-TNF and TM-TNF kill cancer cells in vivo through different mechanisms and that transmembrane form of TNF-a might be a safer candidate for tumor gene therapy due to its less side effects and retainable antitumor activity.
Serum and Tissue Magnesium Concentrations in Patients with Heart Failure and Serious Ventricular Arrhythmias
Authors: M A Ralston, M R Murnane, D V Unverferth, C V Leier
Journal: Annals of Internal Medicine (1990)

Objective: To compare magnesium concentrations in serum and tissue from patients with heart failure. Two groups of patients were compared, those with or without serious ventricular arrhythmias. Design: Consecutive enrollment. Blinded laboratory analyses. Setting: Referral inpatient service of the cardiology division of a university hospital. Patients: Twenty-three patients with idiopathic dilated cardiomyopathy and mild to moderately severe congestive heart failure (New York Heart Association functional class II to IV) were divided into two groups: 9 patients with sustained ventricular tachycardias and 14 patients without serious ventricular arrhythmias (control). Interventions: Medications for heart failure were withdrawn 12 hours or more before study. Antiarrhythmic therapy was continued throughout the study. Measurements and Main Results: The patients had skeletal muscle biopsies, myocardial biopsies, and blood sampling for the analysis of magnesium concentrations. No statistically significant differences in the mean magnesium concentrations in serum, circulating mononuclear cells, skeletal muscle, and myocardium were found when the 9 patients with ventricular arrhythmias were compared with the 14 control patients without serious ventricular arrhythmias. Conclusions: In a general, ambulatory sample of patients with heart failure, magnesium depletion in serum and tissue does not appear to occur more commonly in patients with serious ventricular arrhythmias than in patients without serious ventricular arrhythmias.
Abstract 3580: Hotspot mutation and fusion transcript detection from the same non-small lung adenocarcinoma sample
Authors: Angie Cheng, Varun Bagai, Joey Cienfuegos, Natalie Hernandez, Mu Li, Jeff Schageman, Richard Fekete, Rosella Petraroli, Alexander Vlassov, Susan Magdaleno
Journal: Cancer Research (2014)

Abstract The presence of certain chromosomal rearrangements and the subsequent fusion gene derived from translocations has been implicated in a number of cancers. Hundreds of translocations have been described in the literature recently but the need to efficiently detect and further characterize these chromosomal translocations is growing exponentially. The two main methods to identify and monitor translocations, fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH) are challenging, labor intensive, the information obtained is limited, and sensitivity is rather low. Common sample types for these analyses are biopsies or small tumors, which are very limited in material making the downstream measurement of more than one analyte rather difficult; obtaining another biopsy, using a different section or splitting the sample can raise issues of tumor heterogeneity. The ability to study mutation status as well as measuring fusion transcript expression from the same sample is powerful because you're maximizing the information obtained from a single precious sample and eliminating any sample to sample variation. Here we describe the efficient isolation of two valuable analytes, RNA and DNA, from the same starting sample without splitting, followed by versatile and informative downstream analysis. This methodology was applied to FFPE and degraded samples as well as fresh tissues and cells. DNA and RNA were recovered from the same non-small lung adenocarcinoma sample and both mutation analysis, as well as fusion transcript detection was performed using the Ion Torrent PGM™ platform on the same Ion 318™ chip. Using 10ng of DNA and 10ng of RNA input, we applied the Ion AmpliSeq™ Colon and Lung Cancer panel to analyze over 500 COSMIC mutations in 22 genes and the Ion AmpliSeq™ RNA Lung Fusion panel to detect 40 different fusion transcripts. Citation Format: Angie Cheng, Varun Bagai, Joey Cienfuegos, Natalie Hernandez, Mu Li, Jeff Schageman, Richard Fekete, Rosella Petraroli, Alexander Vlassov, Susan Magdaleno. Hotspot mutation and fusion transcript detection from the same non-small lung adenocarcinoma sample. [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 3580. doi:10.1158/1538-7445.AM2014-3580
Abstract 21: Laryngeal Mask Airway Use by Prehospital Personnel in Simulated Pediatric Arrest
Authors: Francis X Guyette, Kimberly Roth, David C Lacovey, Jon C Rittenberger
Journal: Circulation (2006)

Introduction: Pediatric respiratory arrest is a technically challenging scenario infrequently faced by prehospital providers. Previous studies indicate that prehospital endotracheal intubation resu...
Polymer-based paclitaxel-eluting stents reduce in-stent neointimal tissue proliferation
Authors: Neil J. Weissman, Joerg Koglin, David A. Cox, James Hermiller, Charles O’Shaughnessy, James Tift Mann, Mark Turco, Ronald Caputo, Patrick Bergin, Joel Greenberg, Michael Kutcher, S. Chiu Wong, Warren Strickland, Michael Mooney, Mary E. Russell, Stephen G. Ellis, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2005)
Improving the Utility of Population Impact Measures
Authors: K Oliver
Journal: BMJ (2010)

We are delighted to see use and development of a population impactmeasure (PIM), the Number of Events Prevented in your Population (NEPP),in the recent paper by Chamnan et al (2010). This metric, originallydeveloped by Heller et al1, offers policy-makers useful estimations ofimpact at a population level, by producing absolute measures of effect.Previous use of the NEPP includes estimation of the impact of anintervention in populations with a specific condition, of the incrementalbenefit of moving from current to best practice and disease prevention2-5,and of cost-effectiveness2;6.
From crystal structure to clinic: Highlights of the tenth international parvovirus workshop
Authors: Aravind Asokan, Richard J. Samulski
Journal: Molecular Therapy (2005)

The Tenth Parvovirus Meeting and Workshop included several additional excellent talks and posters on various related topics. We apologize for not being able to include many of these talks here due to space constraints. We do hope we have conveyed the excitement and anticipation resulting from the structural and functional characterization of new parvovirus serotypes, advances in parvoviral vector development, and the rapidly mushrooming applications of AAV vectors in gene therapy.
Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production
Authors: Denis Arsenijevic, Hiroki Onuma, Claire Pecqueur, Serge Raimbault, Brian S. Manning, Bruno Miroux, Elodie Couplan, Marie-Clotilde Alves-Guerra, Marc Goubern, Richard Surwit, Frédéric Bouillaud, Denis Richard, Sheila Collins, Daniel Ricquier
Journal: Nature Genetics (2000)
Doxycycline in the treatment of bullous pemphigoid: as good as systemic corticosteroids?
Authors: S.C. Hofmann
Journal: British Journal of Dermatology (2015)

ORIGINAL ARTICLE, p 227 Due to demographic changes, bullous pemphigoid (BP) is not only the most common bullous autoimmune disorder, but also the one with the most dramatic increase in frequency in past decades.1 BP often has a chronic course with frequent relapses impairing patients’ quality of life. In addition, BP is associated with a 1‐year mortality rate ranging from 12% to 40% in different studies. Reasons for mortality are the poor general condition of elderly patients, associated disorders, and toxicity of immunosuppressive treatments. Systemic corticosteroids represent the systemic treatment with the best level of evidence despite a high risk for development of diabetes, infections, osteoporosis and hypertension.2 The need for well‐tolerated therapies led to a large randomized controlled trial (RCT) by Joly et al.3 demonstrating that potent topical corticosteroids are effective in moderate to severe BP and superior to oral prednisone (1 mg kg−1 daily) in patients with extensive BP with regard to side‐effects and overall survival. Several national guidelines now recommend topical steroid therapy as first‐line treatment in BP.4 However, in bedridden patients, for example, this therapy is often not feasible.