tbuckley/cabot-search huggingface dataset:
Epigallocatechin-3-gallate (EGCG) down-regulates the androgen receptor and the IGF pathway in the prostate of TRAMP mice
Authors: Curt E. Harper, Brijesh B. Patel, Jun Wang, Coral A. Lamartiniere
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4888 

Prostate cancer (PCa), a major health concern for men, starts to develop early in life. By their sixties, over 40% of men have high-grade PIN, the precursor to PCa. Many have implemented chemopreventive agents into their daily diet in an attempt to delay the onset of a variety of cancers. Green tea, one such agent, has been shown to be chemopreventive in breast, skin, and prostate cancers. We hypothesized that EGCG, the major polyphenol found in green tea, will exert its chemopreventive effect in the prostate via regulation of sex steroid and growth factor signaling pathways. In the current study, TRAMP (Transgenic Adenocarcinoma Mouse Prostate) heterozygous male offspring were routinely produced as [TRAMP C57BL/6 females X C57BL/6 male breeders]. Five week old male TRAMP offspring were fed phytoestrogen-free powdered AIN-76A diet and 0.06% EGCG in tap water. The latter is based on a green tea extract dose that previously showed chemoprevention in this model. Animals were sacrificed at 12 weeks of age and ventral and dorsolateral prostates were removed for immunoblot analyses or ELISA to evaluate sex steroid and growth factor signaling. In the ventral prostate lobe, EGCG significantly decreased androgen receptor (AR), insulin-like growth factor-1 (IGF-1), insulin-like growth factor receptor 1 (IGF-R1), and phospho-extracellular regulating kinase 1 and 2 (P-ERK 1/2). In contrast, in the dorsolateral lobe, EGCG significantly decreased IGF-1, but did not alter AR, IGF-R1, or P-ERK 1/2. Elevated IGF-1 is associated with a higher risk for prostate, breast, lung, and colorectal cancer and P-ERK 1/2 activation leads to the transcription of genes responsible for cell growth and proliferation. EGCG mediates most of its action via the VP, although IGF-1 was decreased in both lobes. In summary, the attenuation of the androgen receptor, decrease in the potent growth factor IGF-1 and its receptor, IGF-R1, and the downregulation of downstream effectors, P-ERK1/2 in the VP, may provide a biochemical basis for EGCG suppressing PCa without significant toxicity.
The Resurrection of Stanley Kunitz, 3/3/03
Authors: D. A. Feinfeld
Journal: JAMA (2005)

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
E7389 and ER-076349, synthetic halichondrin B analogs, suppress centromere dynamics in concert with mitotic block
Authors: Tatiana Okouneva, Leslie Wilson, Bruce A. Littlefield, Mary Ann Jordan
Journal: Cancer Research (2004)

5436  E7389 and ER-076349 are synthetic macrocyclic ketone analogs of halichondrin B with potent antiproliferative activities; E7389 is in Phase I clinical trials. The compounds bind to tubulin, inhibit polymerization of tubulin into microtubules at high (micromolar) concentrations, induce G2/M cell cycle arrest, inhibit tumor cell proliferation at picomolar concentrations, and inhibit tumor growth (Towle et al., Cancer Res 61: 1013-1021, 2001). Recent work indicates that E7389 appears to work in cells by a novel mechanism, by aggregating tubulin and thus reducing the rates and lengths of microtubule growth events in cells (M.A. Jordan, K. Kamath, H. Miller, C. Davis, B.A. Littlefield, and L. Wilson, unpublished data). We asked whether this suppression of microtubule dynamics leads to mitotic block in living human osteosarcoma cells (U2Os). We used a fluorescently-labeled centromere-binding protein (GFP-CENP-B) to quantitate the effects of E7389 and ER-076349 on the dynamic behavior of spindle microtubules by high-resolution time-lapse confocal microscopy in the cells. Chromosomes oscillate during prometaphase as they congress to the metaphase plate, and sister chromatids are rhythmically stretched apart and relaxed together by the attached dynamic microtubules. Spindle microtubule (+)-ends attached to chromosomes are marked by fluorescent centromeres. Half-maximal mitotic block was induced by 30 nM E7389 and by 2 nM ER-076349, and complete block was induced by 1 mM and by 100 nM, respectively. We found that E7389 and ER-076349 altered the centromere stretching /relaxation movements in a concentration-dependent manner, in concert with mitotic block. For example, in the absence of drug, the centromeres spent 68% of the time in movements of stretching and relaxation whereas this percentage was significantly reduced to 53% at 30 nM E7389 and to 59% at 2 nM ER-076349. The time centromeres were paused increased from 31% in untreated cells to 46% and 40% in cells with 30 nM E7389 and 2 nM ER-076349, respectively. Interestingly, the rates of stretching were increased by 27% with 30 nM E7389 and by 13% with 2 nM ER-076349. These results suggest that there are significant differences between the mechanisms of E7389 and ER-076349 as compared with those of paclitaxel, vincristine, and vinblastine. The results also support the hypothesis that alterations of microtubule dynamics play a role in the antimitotic and antitumor activity of E7389 and ER-076349. Supported by a grant from Eisai Research Institute and NIH CA 57291.
Expediting clinical trials in a pandemic
Authors: A. J Pollard, A. Reiner, T. John, E. Sheasby, M. Snape, S. Faust, A. Collinson, A. Finn, P. T Heath, E. Miller
Journal: BMJ (2009)

In response to the urgent need for paediatric data comparing the two new variant A/H1N1 vaccines in the UK before the onset of a second wave of flu,1 and a call for proposals related to new variant A/H1N1 by the National Institute for Health Research (NIHR),2 we designed a clinical trial of immunogenicity and tolerability in children aged 6 months-12 years. We submitted a collaborative funding application to NIHR on 24 July 2009, receiving an award letter …
Abstract 13643: MicroRNA-Mediated Reduction of Mutant Kv7.1 Expression by Functional Variants in the 3’Untranslated Region of KCNQ1 Contributes to the Auditory Phenotype and Parental Non-Penetrance Associated with Jervell and Lange-Nielsen Syndrome Compound Heterozygosity
Authors: John R Giudicessi, Katy M Harris, Yigal M Pinto, Arthur A Wilde, Michael J Ackerman
Journal: Circulation (2011)

Introduction: Jervell and Lange-Nielsen syndrome (JLNS) is a rare autosomal recessive form of long QT syndrome (LQTS) that most commonly stems from either homozygous or compound heterozygous mutati...
Abstract 16984: Role of Inositol 1,4,5-Triphosphate Receptor 2 in Post-Ischemic Heart Failure
Authors: Gaetano Santulli, BiXing Chen, Frances Forrester, Henry Wu, Steve Reiken, Andrew R Marks
Journal: Circulation (2014)

Introduction: The type 2 inositol 1,4,5-triphosphate receptor (IP3R2) is the predominant isoform expressed in ventricular cardiomyocytes. IP3R2-mediated Ca 2+ release has been proposed to participate in atrial arrhythmogenesis. However, its involvement in post-ischemic heart failure (HF) has not been elucidated. Methods: To investigate whether myocardial IP3R2 plays a functional role in HF, we generated myocardial specific IP3R2 knock-out (KO) mice by crossing IP3R2 flox/flox mice (obtained by opportunely placing loxP sequences flanking exon 3 of IP3R2 gene) with α-MHC Cre mice. Results: We confirmed cardiomyocyte-specific IP3R2 deletion in IP3R2 flox/flox /α-MHC Cre mice (hereafter referred to as KO) at mRNA and protein levels. The loss of IP3R2 in the heart does not result in embryonic lethality: KO mice survived to adulthood and we did not detect any morphological or functional defects in baseline conditions. Serial cardiac ultrasound analyses performed following coronary artery ligation revealed a significant amelioration in cardiac function post myocardial infarction (MI) in KO mice compared with flox littermates (p&lt;.05, ANOVA rep. measures, n=5-8/group). No significant differences were detected by radiotelemetry in blood pressure. Hemodynamic studies performed post-MI confirmed the improved cardiac contractility (dP/dt max ,KO:6424±424; flox:5794±410 mmHg/s; p&lt;.05, n=6/group). These data are further supported by increased IP3R2 levels detected in HF patients. A markedly reduced percentage of apoptotic cells after MI was revealed by TUNEL assay in cardiac sections from KO mice compared with flox controls, mirrored by an augmented caspase activity and a decreased calcineurin phosphatase activity (p&lt;.05, n=7/group). Furthermore, we observed decreased interstitial cardiac fibrosis in failing hearts from KO mice compared with their flox littermates (p&lt;.05, n=6/group). No obvious difference was noticed examining ultrastructural mitochondria morphology. Conclusions: Taken together our results indicate that myocardial IP3R2 plays a crucial role in the pathophysiology of HF, participating via a mechanism involving the calcineurin pathway in the regulation of fibrosis and apoptosis during post-ischemic cardiac remodeling.
Interleukin-13 interferes with activation-induced t-cell apoptosis by repressing p53 expression
Authors: Li Yang, Ling-Zhi Xu, Zhi-Qiang Liu, Gui Yang, Xiao-Rui Geng, Li-Hua Mo, Zhi-Gang Liu, Peng-Yuan Zheng, Ping-Chang Yang
Journal: Cellular and Molecular Immunology (2015)
Abstract 12368: Clinical Features, Prognosis and Risk Stratification of Acute Myocardial Infarction Due to Coronary Embolism
Authors: Tatsuhiro Shibata, Teruo Noguchi, Shoji Kawakami, Masaharu Ishihara, Yoichi Goto, Hisao Ogawa, Satoshi Yasuda
Journal: Circulation (2014)

Introduction: Coronary embolism (CE) is recognized as an important non-atherosclerotic cause of acute myocardial infarction (AMI). Atrial fibrillation (AF) is associated with systemic thromboembolism, and the CHADS2 and CHA2DS2-VASc scores are known to be useful for risk stratification. Therefore, we investigated the clinical features and prognosis of CE, and assessed the potential usefulness of these scores for predicting CE. Methods: We studied a total of 2,115 consecutive patients with AMI (M/F 1,528/587, age 68±12 [SD] years) hospitalized between 2001 and 2013. CE was diagnosed according to the criteria shown in Figure 1 Results: The overall prevalence of CE in AMI was 2.4% (n=51, M/F 31/20, age 65±14 years). Compared with non-CE AMI patients, CE patients were characterized as lower prevalence of risk factors. Most common cause of CE was AF (73%). However, only 15 (41%) out of 37 AF patients were treated with vitamin K antagonists (VKAs) and their PT-INR was low, 1.42 (range, 0.95-1.80) at the onset of AMI. Importantly, among 28 CE patients with nonvalvular AF, 17 patients (59%) had a CHADS2 score of 0 or 1. When those particular patients were re-evaluated by CHA2DS2-VASc score, 10 out of 17 (59%) were categorized into a higher risk category (≥ 2) that would benefit from VKAs therapy. During a median follow-up of 4.1 years (interquartile range, 1.5-7.0 years), 8 patients (16%) had major adverse cardiovascular events and 5 patients (10%) recurred CE or systemic embolization (Figure 2). Conclusions: AF is the major underlying cause of CE, recurrence of which seems to be not rare. The CHA2DS2-VASc score may provide reliable risk stratification with a superior ability to predict CE.
ACUTE COR PULMONALE
Authors: I L RUBIN, G FLAUM
Journal: Annals of Internal Medicine (1950)

Case Reports1 October 1950ACUTE COR PULMONALEIRA L. RUBIN, M.D., GERALD FLAUM, M.D, F.A.C.P.IRA L. RUBIN, M.D., GERALD FLAUM, M.D, F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-33-4-1013 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPulmonary infarction is a relatively common condition, but acute cor pulmonale is seldom diagnosed. This may be due to the transient nature of the process, or to confusion with other disease states. The purpose of this report is to present an interesting case of acute cor pulmonale and to draw attention to the confusion in the diagnosis of this condition.1CASE REPORTA 22 year old white bricklayer was admitted with chief complaint of severe sharp pain in the left lumbar region of one day's duration. His past history included a duodenal ulcer while in military service in April, 1945....Bibliography1. Myers WK: Penicillin therapy of gonococcic endocarditis of the pulmonary valve, J. A. M. A. 133: 1205, 1947. CrossrefMedlineGoogle Scholar2. White PD: The acute cor pulmonale, Ann. Int. Med. 9: 115, 1935. LinkGoogle Scholar3. McGinnWhite SPD: Acute cor pulmonale resulting from pulmonary embolism, J. A. M. A. 104: 1473, 1935. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication April 3, 1948.From the Medical Division, Veterans Hospital, Kingsbridge Road, Bronx, N. Y.Published with permission of the Chief Medical Director, Department of Medicine and Surgery, Veterans Administration, who assumes no responsibility for the opinions expressed or conclusions drawn by the authors. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCor pulmonale caused by recurrent pulmonary emboliSubacute cor pulmonale 1 October 1950Volume 33, Issue 4Page: 1013-1016KeywordsArmed forcesDuodenal ulcersHospital medicineInfarctionSurgery Issue Published: 1 October 1950 PDF downloadLoading ...
806. HSV Based Genetic Selection System for Identification of Pain Signaling Regulators
Authors: Rahul Srinivasan, Darren Wolfe, Shaohua Huang, David Krisky, Joseph Glorioso
Journal: Molecular Therapy (2004)

Top of pageAbstract
The vanilloid receptor type 1 (VR1, also known as TRPV1) is a calcium channel that plays a central role in pain signaling (nociception). The receptor is directly gated by heat, chemicals (e.g. capsaicin), and protons. In addition, VR1 is indirectly activated by NGF and bradykinin through the stimulation of protein kinase C (PKC) isoforms via G-protein coupled receptor mechanisms. PKC directly potentiates VR1 activity by phosphorylation of specific target residues. However, regulatory molecules and mechanisms involved upstream and downstream of the channel remain to be discovered. In the presence of capsaicin (a component of chili peppers), non-neuronal cells overexpressing the VR1 receptor undergo apoptosis as a result of calcium influx mediated excitotoxicity. Using the rationale of calcium influx induced excitotoxic cell death through the VR1 receptor, we developed an HSV-1 based selection system to dissect VR1 receptor biology with respect to its ligand interactions and regulation. Our aim is to identify novel genes or peptides that will specifically modulate VR1 activity that may be useful in the gene therapy based treatment of chronic pain states. First, we placed the VR1 cDNA under transcriptional control of the HSV-1 TK early promoter in the ICP4 locus of a replication defective HSV-1 genome. The genomic structure of the vector was confirmed by Southern blotting. Immunofluorescence for VR1 on infected complementing cell lines localized to the plasma membrane and perinuclear regions. We have developed a genetic selection system to identify regulators of VR1 activity from cDNA or peptide libraries using TkpVR1 replication as the gauge. Second, we tested the effect of a known agonist, capsaicin, on viral titers. In the presence of 40 μm capsaicin, TKpVR1 viral titers are reduced by greater than 100-fold at 48 hpi as compared to control virus. Low pH (6.8) similarly causes a 40-fold reduction in TKpVR1 viral titers when compared with control virus, due to proton mediated VR1 potentiation. Having established a drug induced genetic selection system for regulators of VR1 receptor activity, we have now initiated the process of screening libraries in order to identify novel regulatory proteins of VR1 channel activity within the framework of the selection system described above.
Abstract 3278: Hibiscus sabdariffa L. Tea (Tisane) Lowers Blood Pressure in Prehypertensive and Mildly Hypertensive Adults
Authors: Diane L McKay, Edward Saltzman, Chung-Yen Chen, Jeffrey B Blumberg
Journal: Circulation (2008)

In vitro studies have shown Hibiscus sabdariffa L., an ingredient of many herbal tea blends and other beverages, has antioxidant properties. In animal models, extracts of hibiscus calyces possess h...
Abstract 2412: Rapid Induction Of Head Cooling By The Intranasal Route During Cardiopulmonary Resuscitation Improves Survival and Neurological Outcomes
Authors: Jun Guan, Wanchun Tang, Hao Wang, Min-Shan Tsai, Yongqin Li, Shijie Sun, Denise Barbut, Max H Weil
Journal: Circulation (2007)

Introduction: Current guidelines recommend mild hypothermia for all unconscious patients of cardiac arrest after return of spontaneous circulation (ROSC). However, the effects of intra-resuscitatio...
The Genetics of Renal Tract Disorders
Authors: M. d'A. Crawfurd
Journal: Annals of Internal Medicine (1988)

Mechanisms of human inheritance Structure and function of the renal tract Urinary tract anomalies in chromosomal disorders Inherited metabolic diseases involving the kidney Urolithiasis and crystalluria Renal tubular (transport) defects Primary hereditary nephropathies Nephropathy secondary to systemic disorders Cystic kidneys: definition and classificaion Renal tract malformations Urinary tract infections Renal tract neoplasias.
Abstract 3689: Minocycline regulates hypoxia-inducible factor-1α expression through the induction of its degradation in ovarian cancer: <i>in vitro</i> and <i>in vivo</i> studies
Authors: Parvin Ataie-Kachoie, David L. Morris, Mohammad H. Pourgholami
Journal: Cancer Research (2014)

Abstract Experimental data suggest therapeutic advantage from selective disruption of the hypoxia response in cancer. We recently found that minocycline decreases tumor VEGF expression in ovarian tumor xenografts in mice and herein report a companion laboratory study to test if this effect was the result of hypoxia-inducible factor (HIF) inhibition. Human ovarian carcinoma cell lines (OVCAR-3, SKOV-3 and A2780) were treated with minocycline in normoxic and hypoxic conditions and also in the presence of hypoxia-mimetic agent deferoxamine in vitro. Two different in vivo experiments investigated miocycline effects after single dose (30 mg/kg, 4 or 24 h) or longer exposure in nude mice bearing OVCAR-3 xenografts. Treatment with minocycline inhibited the accumulation of HIF-1alpha in a concentration-dependent fashion in vitro. A similar effect of minocycline was seen in vivo. Furthermore, the inhibtory effect of minocycline on HIF-1alpha was found to be associated with a significant decrease in HIF-1alpha half-life showing that minocycline enhances degradtion of HIF-1alpha. These data warrents further evaluation of minocycline in the treatment of ovarian cancer. Citation Format: Parvin Ataie-Kachoie, David L. Morris, Mohammad H. Pourgholami. Minocycline regulates hypoxia-inducible factor-1α expression through the induction of its degradation in ovarian cancer: in vitro and in vivo studies. [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 3689. doi:10.1158/1538-7445.AM2014-3689
Abstract 3571: mRNA spike-in control materials for cancer fusion gene detection assays
Authors: Winnie Liang, Stephanie J. Pond, Waibhav D. Tembe, Han-Yu Chuang, Christophe Legendre, Nancy Kim, Valerie Montel, Shukmei Wong, Timothy K. McDaniel, David Craig, John Carpten
Journal: Cancer Research (2014)

Abstract Oncogenic fusion genes underlie the mechanism of several common cancers and also constitute or encode important diagnostic and therapeutic targets. Studies using next-generation sequencing technologies, particularly RNA sequencing (RNA-seq), have revealed a growing number of recurrent fusions in a variety of cancers. As such, establishing analytic parameters, including the limit of detection, sensitivity, and specificity of detecting fusions in tumor RNA specimens is important. We have developed reference materials useful in assessing the ability to detect fusion events in RNA or DNA samples. These consist of a set of nine synthetic poly-adenylated RNA transcripts that correspond to common cancer fusion gene sequences. These synthetic fusion RNAs can be spiked at known concentrations into total RNA in the first stage of the mRNA sample prep and used as in-line controls to evaluate the sensitivity and specificity of the detection of these mutations. As a demonstration of the utility of these controls, we performed a series of spike-in experiments to investigate performance characteristics of three commonly used fusion-detection software algorithms. Our results show all three algorithms to be capable of detecting fusions in a dose-dependent manner. The results also show differences in performance among the algorithms for detecting specific fusions. Citation Format: Winnie Liang, Stephanie JK Pond, Waibhav D. Tembe, Han-Yu Chuang, Christophe Legendre, Nancy Kim, Valerie Montel, Shukmei Wong, Timothy K. McDaniel, David Craig, John Carpten. mRNA spike-in control materials for cancer fusion gene detection assays. [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 3571. doi:10.1158/1538-7445.AM2014-3571