tbuckley/cabot-search huggingface dataset:
Abstract 5145: Y-27632 inhibits Myc-induced apoptosis and cooperates with Myc to immortalize human keratinocytes
Authors: Aleksandra Dakic, Kyle Divito, Shuang Fang, Nancy Palechor-Ceron, Vera Simic, Sujata Choudhury, Songtao Yu, Cynthia M. Simbulan-Rosenthal, Dean Rosenthal, Richard Schlegel, Xuefeng Liu
Journal: Cancer Research (2015)

Abstract The high-risk HPV E6 and E7 genes are sufficient to immortalize human foreskin keratinocytes (HFKs) through activation of telomerase and inactivation of the RB/p16 pathway, respectively. Our previous work has shown that Myc (via induction of hTERT) may substitute for E6 and immortalize HFKs when combined with HPV E7. When expressed alone, however, Myc induced p53 expression and apoptosis. In the current study we found that Myc, in combination with the ROCK inhibitor (Y-27632), led immortalization of human foreskin keratinocytes. Our data confirmed that Myc induced apoptosis and blebbing of human keratinocytes when cultured in serum free synthetic medium (KGM) and that Y-27632 rapidly inhibits this process. Thus, our data demonstrate that Myc is capable of independently immortalizing HFKs when apoptosis pathways are blocked. Citation Format: Aleksandra Dakic, Kyle Divito, Shuang Fang, Nancy Palechor-Ceron, Vera Simic, Sujata Choudhury, Songtao Yu, Cynthia M. Simbulan-Rosenthal, Dean Rosenthal, Richard Schlegel, Xuefeng Liu. Y-27632 inhibits Myc-induced apoptosis and cooperates with Myc to immortalize human keratinocytes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5145. doi:10.1158/1538-7445.AM2015-5145
Efficacy and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire Disorder in Women
Authors: Loes Jaspers, Frederik Feys, Wichor M. Bramer, Oscar H. Franco, Peter Leusink, Ellen T. M. Laan
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> In August 2015, the US Food and Drug Administration (FDA) approved flibanserin as a treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, despite concern about suboptimal risk-benefit trade-offs. <h3>Objective</h3> To conduct a systematic review and meta-analysis of randomized clinical trials assessing efficacy and safety of flibanserin for the treatment of HSDD in women. <h3>Data Sources</h3> Medical databases (among others, Embase, Medline, Psycinfo) and trial registries were searched from inception to June 17, 2015. Reference lists of retrieved studies were searched for additional publications. <h3>Study Selection</h3> Randomized clinical trials assessing treatment effects of flibanserin in premenopausal and postmenopausal women were eligible. No age, language, or date restrictions were applied. Abstract and full-text selection was done by 2 independent reviewers. <h3>Data Extraction and Synthesis</h3> Data were extracted by one reviewer and checked by a second reviewer. Results were pooled using 2 approaches depending on the blinding risk of bias. <h3>Main Outcomes and Measures</h3> Primary efficacy outcomes included number of satisfying sexual events (SSEs), eDiary sexual desire, and Female Sexual Function Index (FSFI) desire. Safety outcomes included, among others, 4 common adverse events (AEs): dizziness, somnolence, nausea, and fatigue. <h3>Results</h3> Five published and 3 unpublished studies including 5914 women were included. Pooled mean differences for SSE change from baseline were 0.49 (95% CI, 0.32-0.67) between 100-mg flibanserin and placebo, 1.63 (95% CI, 0.45-2.82) for eDiary desire, and 0.27 (95% CI, 0.17-0.38) for FSFI desire. The risk ratio for study discontinuation due to AEs was 2.19 (95% CI, 1.50-3.20). The risk ratio for dizziness was 4.00 (95% CI, 2.56-6.27) in flibanserin vs placebo, 3.97 (95% CI, 3.01-5.24) for somnolence, 2.35 (95% CI, 1.85-2.98) for nausea, and 1.64 (95% CI, 1.27-2.13) for fatigue. Women’s mean global impression of improvement scores indicated minimal improvement to no change. <h3>Conclusions and Relevance</h3> Treatment with flibanserin, on average, resulted in one-half additional SSE per month while statistically and clinically significantly increasing the risk of dizziness, somnolence, nausea, and fatigue. Overall, the quality of the evidence was graded as very low. Before flibanserin can be recommended in guidelines and clinical practice, future studies should include women from diverse populations, particularly women with comorbidities, medication use, and surgical menopause.
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Authors: Laurence F. McMahon, Renuka Tipirneni, Vineet Chopra
Journal: JAMA (2016)

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
Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives
Authors: César Magro-Checa, Elisabeth J. Zirkzee, Tom W. Huizinga, Gerda M. Steup-Beekman
Journal: Drugs (2016)

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most common pharmacological treatments used in NPSLE, based on both a literature search and our expert opinion. The extent to which new drugs in the advanced development of SLE, or the blockade of new targets, may impact future treatment of NPSLE will also be discussed.
Effect of Bursectomy and Thymectomy on the Development of Visceral Lymphomatosis in the Chicken2
Authors: Raymond D. A. Peterson, Ben R. Burmester, T. N. Fredrickson, H. Graham Purchase, Robert A. Good
Journal: JNCI Journal of the National Cancer Institute (1964)

The surgical removal of the bursa of Fabricius from White Leghorn line 151 chickens prevents the development of visceral lymphomatosis ordinarily induced by virus RPL12. Such an effect was noted whether the bursectomy was performed at 1 day or 29 days of age, or whether the infectious virus was administered at 1 day or 28 days of age. Thymectomy alone did not affect the incidence of the lymphocytic malignancy. The incidence of erythroblastosis, the red blood cell type of avian leukosis, was unaffected by any of the surgical procedures. The influence of the bursa of Fabricius on the occurrence of virus-induced avian lymphomatosis can now be added to the functions of the organ in the development of the immunologic system of the chicken.
Inspiratory muscle training improves breathing pattern during exercise in COPD patients
Authors: Noppawan Charususin, Rik Gosselink, Alison McConnell, Heleen Demeyer, Marko Topalovic, Marc Decramer, Daniel Langer
Journal: European Respiratory Journal (2016)

Dyspnoea is typically the main symptom limiting exercise capacity in patients with chronic obstructive pulmonary disease (COPD) [1–3]. Exertional dyspnoea has been linked to dynamic hyperinflation (DH), when lung expansion critically encroaches upon the inspiratory reserve volume (IRV) [4]. Consequently, patients develop a rapid and shallow breathing pattern, which is energetically opposite to the pattern required to minimise the work of breathing [5]. Furthermore, the restriction of tidal volume ( V T) expansion has recently been linked to daily physical activity limitation [6]. The addition of IMT to a PR programme for selected COPD patients changes breathing pattern during exercise <http://ow.ly/WWrFT> The authors would like to acknowledge the physiotherapists V. Barbier, I. Muylaert, and I. Coosemans (Pulmonary Rehabilitation Dept, Respiratory Division, University Hospital Leuven, Belgium) for performing the pulmonary rehabilitation programme and all measurements of included patients as blinded outcome assessors. We would also like to thank Hans Scheers (Lung Toxicology and Epidemiology Research Unit, KU Leuven, Leuven, Belgium) for providing statistical advice. Regarding the access to the University Hospital Leuven rehabilitation database, we would like to thank Geert Celis (Lung function Dept, University Hospitals Gasthuisberg, Leuven, Belgium).
Perfluorooctane Sulfonate Concentrations in Amniotic Fluid, Biomarkers of Fetal Leydig Cell Function, and Cryptorchidism and Hypospadias in Danish Boys (1980–1996)
Authors: Gunnar Toft, Bo A.G. Jönsson, Jens Peter Bonde, Bent Nørgaard-Pedersen, David M. Hougaard, Arieh Cohen, Christian H. Lindh, Richard Ivell, Ravinder Anand-Ivell, Morten S. Lindhard
Journal: Environmental Health Perspectives (2015)

Exposure to perfluorooctane sulfonate (PFOS) may potentially disturb fetal Leydig cell hormone production and male genital development.We aimed to study the associations between levels of amniotic fluid PFOS, fetal steroid hormone, and insulin-like factor 3 (INSL3) and the prevalence of cryptorchidism and hypospadias.Using the Danish National Patient Registry, we selected 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls with stored maternal amniotic fluid samples available in a Danish pregnancy-screening biobank (1980-1996). We used mass spectrometry to measure PFOS in amniotic fluid from 645 persons and steroid hormones in samples from 545 persons. INSL3 was measured by immunoassay from 475 persons. Associations between PFOS concentration in amniotic fluid, hormone levels, and genital malformations were assessed by confounder-adjusted linear and logistic regression.The highest tertile of PFOS exposure (> 1.4 ng/mL) in amniotic fluid was associated with a 40% (95% CI: -69, -11%) lower INSL3 level and an 18% (95% CI: 7, 29%) higher testosterone level compared with the lowest tertile (< 0.8 ng/mL). Amniotic fluid PFOS concentration was not associated with cryptorchidism or hypospadias.Environmental PFOS exposure was associated with steroid hormone and INSL3 concentrations in amniotic fluid, but was not associated with cryptorchidism or hypospadias in our study population. Additional studies are needed to determine whether associations with fetal hormone levels may have long-term implications for reproductive health.Toft G, Jönsson BA, Bonde JP, Nørgaard-Pedersen B, Hougaard DM, Cohen A, Lindh CH, Ivell R, Anand-Ivell R, Lindhard MS. 2016. Perfluorooctane sulfonate concentrations in amniotic fluid, biomarkers of fetal Leydig cell function, and cryptorchidism and hypospadias in Danish boys (1980-1996). Environ Health Perspect 124:151-156; http://dx.doi.org/10.1289/ehp.1409288.
Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial
Authors: Evelien de Jong, Jos A van Oers, Albertus Beishuizen, Piet Vos, Wytze J Vermeijden, Lenneke E Haas, Bert G Loef, Tom Dormans, Gertrude C van Melsen, Yvette C Kluiters, Hans Kemperman, Maarten J van den Elsen, Jeroen A Schouten, Jörn O Streefkerk, Hans G Krabbe, Hans Kieft, Georg H Kluge, Veerle C van Dam, Joost van Pelt, Laura Bormans, Martine Bokelman Otten, Auke C Reidinga, Henrik Endeman, Jos W Twisk, Ewoudt M W van de Garde, Anne Marie G A de Smet, Jozef Kesecioglu, Armand R Girbes, Maarten W Nijsten, Dylan W de Lange
Journal: The Lancet Infectious Diseases (2016)
Abstract 16252: MiRNA-24 Over-Expression Potentiates Mesenchymal Stem Cells Survival in the Infarcted Myocardium Through Autophagy Activation via Targeting Rubicon
Authors: Jianfeng Xu, Juying Qian, Li Lin, Mingqiang Fu, Yanhua Gao, Yangang Su, Yunzeng Zou, Junbo Ge
Journal: Circulation (2013)

Objective:  The efficacy of mesenchymal stem cells (MSCs)-based therapy for myocardial infarction (MI) is limited by the poor cells survival in the infarcted myocardium. We aimed to investigate the hypothesis that microRNA-24 (miR-24) protected MSCs against apoptosis in a hypoxic niche.   Methods and Results:  Using miRNA microarrays and quantified-PCR, miR-24 was previously discovered to be highly expressed in human MSCs after 6-hour hypoxia exposure. Following the establishment of gain- and loss-of-function through lentivirus trans-infection, it was revealed that MSCs miR-24 , compared with MSCs null , robustly decreased the cells apoptosis in a hypoxic condition, indicated as TUNEL [(35.5±3.63) % vs. (46.7±6.72) %,  P  P  Rubicon , an inhibitor of autophagy, was evidenced to be suppressed by miR-24 via a luciferase reporter examination. Meanwhile, miR-24 over-expression was verified to reduce  Rubicon , thus evoking subsequent  hVps34  up-regulation, whereas miR-24 down-regulation reversed this process. Most importantly, the protective effect of miR-24 on MSCs apoptosis was observed to be abolished by  Rubicon  over-expression or  hVps34  knockdown (both  P  miR-24 , transplanted into the infarcted myocardium, significantly enhanced by 1.83 folds than that of MSCs null  on day four after transplantation; and that MSCs miR-24  group exhibited a statistical improvement of cardiac function [LVEF: (50.2±3.9) % vs. (42.9±2.7) %,  P  null  one in a four-week follow-up.   Conclusions:  MiR-24 promotes autophagy, suppressing  Rubincon , therefore increases the viability of MSCs under hypoxia, suggesting that miR-24 might be developed as a novel target of cell-base therapy for MI.
TMPRSS2-ERG in Blood and Docetaxel Resistance in Metastatic Castration-resistant Prostate Cancer
Authors: Òscar Reig, Mercedes Marín-Aguilera, Gemma Carrera, Natalia Jiménez, Laia Paré, Susana García-Recio, Lydia Gaba, Maria Verónica Pereira, Pedro Fernández, Aleix Prat, Begoña Mellado
Journal: European Urology (2016)
Abnormal Response of Tumor Vasculature to Vasoactive Drugs23
Authors: Rosanna C. Chan, Charles F. Babbs, Richard J. Vetter, Carlton H. Lamar
Journal: JNCI Journal of the National Cancer Institute (1984)

The effects of the vasoconstrictor phenylephrine and the vasodilator hydralazine on blood flow to tumor were studied and compared to those on blood flow to normal tissues in vivo. Regional blood flow and cardiac output were measured with the use of radioactive microspheres in 150- to 250-g inbred Harlan F344 rats bearing subcutaneous nodules of two types of transplantable carcinoma (“hard” and “soft”) with microscopically different vascular patterns. Three groups of rats were treated with hydralazine, saline, or phenylephrine, and regional blood flow was determined at the time of maximum blood pressure response. Results were correlated with quantitative morphometric analysis of arteriolar and capillary wall thickness in tumor and normal tissue. Phenylephrine decreased and hydralazine increased normal tissue perfusion as indicated by cardiac output. Tumor blood flow remained low and was not significantly influenced by drug treatment, except for the phenylephrine effect on hard tumors. Histologic study of tumor vessel walls revealed an absence of smooth muscle capable of responding to the vasoactive drugs by constriction or dilation. Evidently, by their selective action on normal vessels, vasoactive drugs can change the ratio of tumornormal tissue perfusion. In particular, the increase of normal tissue:tumor blood flow by vasodilator drugs may enhance the selectivity of local heat therapy.
An Assessment of Long-term Anticoagulant Administration after Cardiac Inarction
Authors: E RICE-WRAY
Journal: BMJ (1964)

Between November 1955 and May 1960 a controlled trial was carried out to compare the clinical progress of patients who had recovered from the acute stage of cardiac infarction when given high dosages of phenindione with the experience of a similar series of patients given low dosages.The patients on the high-dosage regime were given sufficient phenindione approxi- mately to double the one-stage prothrombin time, while those on the low-dosage regime were given tablets containing only 1 mg. of phenindione.New patients were admitted to this trial between November 1955 and March 1958.The design of the trial and the progress of these patients up to the end of 1958 have already been given (Report to M.R.C., 1959).The present report describes the subsequent progress of the patients up to May 1960, when the trial in its original design was dis- continued.A later phase of this trial extending up to December 1962 is also described. Summary of Results at May 1960On reviewing the full hospital case-notes of the patients in this trial, a few errors in transcription-for example, of age or date of birth (and in one instance of sex)-were discovered in the summary sheets used in the preparation of the preliminary report.These have been rectified in this report.A problem in the conduct of long-term clinical trials is the maintenance of contact with patients and follow-up of those who have either defaulted or been withdrawn, for one reason or another, from the trial.Thanks to the patients' family physicians and to the Ministry of Pensions and National Insurance, it has proved possible to obtain some information on 67 out of 78 (86%) of those lost from the original series. Follow-up on WithdrawalsTable I shows the reasons for withdrawal and the subse- quent fate of those withdrawn from the trial.Of the 188 patients in the low-dosage group 45 were withdrawn.Thirteen of them suffered recurrent myocardial infarction of such severity that their attendant physicians removed them from the trial in order that they might be treated without the resrictions imposed by it.Among the remainder, the medical reasons for withdrawal were: pulmonary embolism (1 patient), cardiac failure (8 patients), cerebrovascular accident (1 patient), signs and symptoms of peptic ulcer (3 patients), pulmonary tuber- culosis (1 patient), phenindione-sensitivity skin rashes (2 patients), carcinoma of bronchus (1 patient), brain abscess (1 patient), atrial fibrillation and cerebral incident (1 patient).One patient was removed from the trial after publication of the initial report.Of the 195 patients in the high-dosage group 33 were with- drawn from the trial.Among these patients the causes for withdrawal were: cerebrovascular accidents (3 patients), cardiac failure (3 patients), signs and symptoms of peptic ulcer (9 patients), traumatic episodes with bleeding (3 patients), other disorders associated with bleeding (3 patients), congestive TABLE I.-Cause and Fate of Withdrawals No. of No.
Blood Monocytes and Turnor-lnfiltratinq Macrophagesin Human Breast Cancer: Differences in Activation Level as Assessed by Lysozyme Content
Authors: R J Steele, O Eremin, M Brown
Journal: JNCI Journal of the National Cancer Institute (1983)

The lysozyme content of tumor-infiltrating macrophages (TIM) from human breast carcinomas has been compared with that of blood monocytes both from breast cancer patients and tumor-free controls. Cells were identified as macrophages or monocytes with the use of rosetting reactions to detect receptors for the Fc portion of IgG and differentiation antigens, and lysozyme was detected by an immunoperoxidase technique on cytocentrifuge preparations of rosetted cells. Significantly more monocytes from patients with breast cancer contained lysozyme than monocytes from comparable controls, suggesting the presence of activated circulating blood monocytes. Conversely, TIM were virtually devoid of lysozyme. This lack of enzyme was not due to methodologic factors and may represent defective antitumor activity.
P-0262 Prospective Evaluation of Candidate Snps of Vegf/Vegfr Pathway in Metastatic Colorectal Cancer Patients Treated with First-Line Folfiri Plus Bevacizumab (BV)
Authors: Chiara Cremolini, Fotios Loupakis, Dongyun Yang, Lisa Salvatore, Wu Zhang, Takeru Wakatsuky, Marta Schirripa, Sara Lonardi, Carlotta Antoniotti, Giuseppe Aprile, Gianluca Masi, Francesco Graziano, Annamaria Ruzzo, Sara Lucchesi, Martin Maus, Guido Bocci, Alfredo Falcone, Heinz Joseph Lenz
Journal: Annals of Oncology (2012)