tbuckley/cabot-search huggingface dataset:
MicroRNAs Play an Essential Role in the Development of Cardiac Hypertrophy
Authors: DanishSayed, ChullHong, Ieng-YiChen, JacquelineLypowy, MahaAbdellatif
Journal: Circulation Research (2007)

MicroRNAs are naturally existing, small, noncoding RNA molecules that downregulate posttranscriptional gene expression. Their expression pattern and function in the heart remain unknown. Here we report an array of microRNAs that are differentially and temporally regulated during cardiac hypertrophy. Significantly, the muscle-specific microRNA-1 (miR-1) was singularly downregulated as early as day 1 (0.56±0.036), persisting through day 7 (0.29±0.14), after aortic constriction–induced hypertrophy in a mouse model. Overexpression experiments showed that miR-1 inhibited its in silico–predicted, growth-related targets, including Ras GTPase–activating protein (RasGAP), cyclin-dependent kinase 9 (Cdk9), fibronectin, and Ras homolog enriched in brain (Rheb), in addition to protein synthesis and cell size. Thus, we propose that microRNAs play an essential regulatory role in the development of cardiac hypertrophy, wherein downregulation of miR-1 is necessary for the relief of growth-related target genes from its re...
Vascular Inflammation Is Negatively Autoregulated by Interaction Between CCAAT/Enhancer-Binding Protein-δ and Peroxisome Proliferator-Activated Receptor-γ
Authors: YasunoriTakata, YutakaKitami, Zhao-HuiYang, MichitsuguNakamura, TakafumiOkura, KunioHiwada
Journal: Circulation Research (2002)

CCAAT/enhancer-binding proteins (C/EBPs) upregulate transcription of various inflammatory cytokines and acute phase proteins, such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and cyclooxygenase-2. Recent studies have demonstrated that peroxisome proliferator-activated receptor (PPAR)-γ is present in atherosclerotic lesions, and negatively regulates expression of these genes. Interestingly, PPAR-γ gene promoter has tandem repeats of C/EBP-binding motif, and C/EBP-δ plays a pivotal role in transactivation of PPAR-γ gene. It has been well known that the interaction between C/EBPs and PPAR-γ plays a central role in maintaining adipocyte differentiation and glucometabolism; however, the relationship between PPAR-γ and C/EBPs in the vessel wall remains unclear. In the present study, we showed that a high level of C/EBP-δ expression induced by inflammation positively regulated transcription and protein expression of PPAR-γ in vascular smooth muscle cells (VSMCs). On the other hand, PPAR-γ ligands trog...
Automated Cardiac MR Scar Quantification in Hypertrophic Cardiomyopathy Using Deep Convolutional Neural Networks
Authors: Ahmed S. Fahmy, Johannes Rausch, Ulf Neisius, Raymond H. Chan, Martin S. Maron, Evan Appelbaum, Bjoern Menze, Reza Nezafat
Journal: JACC. Cardiovascular imaging (2018)

Scar volume quantified by cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) is a novel imaging biomarker for risk stratification in patients with hypertrophic cardiomyopathy (HCM) [(1)][1]. In current practice, scar quantification often relies on manual delineation of
Abstract 19516: Trends in Non-Statins Utilization and Expenditures Among U.S. Adults With Established Atherosclerotic Cardiovascular Disease: Medical Expenditure Panel Survey 2002-2013
Authors: Joseph A Salami, Haider J Warraich, Javier Valero-Elizondo, Oluseye Ogunmoroti, Salim S Virani, Ron Blankstein, Erica S Spatz, Nihar Desai, Michael J Blaha, Amit Khera, Roger S Blumental, Donald Lloyd-Jones, Khurram Nasir
Journal: Circulation (2016)

Objectives: The recent AHA/ACC cholesterol guideline updates do not advocate non-statins as first-line agents of choice among patients with established atherosclerotic cardiovascular disease (ASCVD...
Abstract 2875: Calycosin is a double-edged sword in the treatment of pancreatic cancer
Authors: Zhu Zhang, Joshua KS Ko
Journal: Cancer Research (2018)

Abstract Calycosin is known for its suppression of breast cancer cell growth. We are the first group to report the effects of calycosin in pancreatic cancer development. Growth inhibition of the human pancreatic cell line MIA PaCa-2 was evaluated by MTT assay. Cell cycle distribution was determined by flow cytometry. Cell migratory activity was investigated by a wound healing assay. Subcutaneous xenografting of MIA PaCa-2 cells was conducted in Balb/C nude mice, while orthotopic inoculation of the mouse Pan01 pancreatic cancer cells was performed in C57BL/6 mice. Our results have shown that calycosin exhibited modest growth inhibition of MIA PaCa-2 cells, together with induction of S phase arrest and restoration of p53. Besides, promotion of both caspase-dependent apoptosis and autophagy implicate that the anticancer mechanism of calycosin strongly rely on programmed cell death. Alternatively, calycosin also inhibited the migration of MIA PaCa-2 cells in line with downregulation of epithelial–mesenchymal transition (EMT) and pro-metastatic biomarkers. The above in vitro benefits of calycosin was confirmed by a significant reduction of tumor mass in the MIA PaCa-2 xenograft. Nevertheless, when we look closely on the in vivo anticancer effect of calycosin in the Pan01 orthotopic mice model, although both attenuation of tumor growth and proapoptotic action were confirmed by histological findings, the tumor tissue expression of Snail, vimentin and CD31 was all elevated, indicating possible promotion of EMT and pro-angiogenic potential of the drug. These controversial findings suggest that calycosin could be an effective anticancer agent by promoting programmed cell death and inhibition of cell proliferation of pancreatic cancer cells, while it may also facilitate metastatic development of tumor, particular at the advanced stages. It would be essential to further dissect the conditions and factors that differentiate the dual actions of calycosin in pancreatic cancer therapy. Citation Format: Zhu Zhang, Joshua KS Ko. Calycosin is a double-edged sword in the treatment of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2875.
Insulin Signaling and Its Regulation of System A Amino Acid Uptake in Cultured Rat Vascular Smooth Muscle Cells
Authors: ToshiyukiObata, AtsunoriKashiwagi, HiroshiMaegawa, YoshihikoNishio, SatoshiUgi, HidekiHidaka, RyuichiKikkawa
Journal: Circulation Research (1996)

Hyperinsulinemia has been recognized as an independent risk factor for atherosclerosis. However, its exact mechanisms are still unclear. In our previous work, we showed that 10 nmol/L insulin stimulated neither mitogen-activated protein kinase (MAP kinase) activity nor [3H]thymidine incorporation but did stimulate S6 kinase through the specific insulin receptors in cultured rat vascular smooth muscle cells (VSMCs). In this study, we observed that ≥1 nmol/L insulin stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and activated IRS-1–dependent phosphatidylinositol 3′-kinase (PI 3′-kinase) and p70 S6 kinase (p70S6K) but not MAP kinase (extracellular signal-regulated kinase 2) and p90 S6 kinase (p90RSK). However, 10 nmol/L insulin-like growth factor I stimulated all these pathways. Finally, 10 nmol/L insulin stimulated α-aminoisobutyric acid (AIB) uptake, and wortmannin (100 nmol/L) completely inhibited insulin-stimulated AIB uptake, whereas rapamycin (20 nmol/L) had no such effect....
Erratum. Reduction in the Incidence of Type 2 Diabetes With the Mediterranean Diet: Results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care 2011;34:14–19
Authors: Jordi Salas-Salvadó, Monica Bulló, Nancy Babio, Miguel Ángel Martínez-González, Núria Ibarrola-Jurado, Josep Basora, Ramon Estruch, Maria Isabel Covas, Dolores Corella, Fernando Arós, Valentina Ruiz-Gutiérrez, Emilio Ros
Journal: Diabetes Care (2018)

Some slight departures from the protocol of individual randomization affecting only a small subset of participants in the Prevencion con Dieta Mediterranea (PREDIMED) trial (at most 14%) occurred and prompted a thorough reanalysis of data and republication of the main PREDIMED paper (see Estruch et al., Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34). The authors report the …
TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence
Authors: Thomas G. Bird, Miryam Müller, Luke Boulter, David F. Vincent, Rachel A. Ridgway, Elena Lopez-Guadamillas, Wei-Yu Lu, Thomas Jamieson, Olivier Govaere, Andrew D. Campbell, Sofía Ferreira-Gonzalez, Alicia M. Cole, Trevor Hay, Kenneth J. Simpson, William Clark, Ann Hedley, Mairi Clarke, Pauline Gentaz, Colin Nixon, Steven Bryce, Christos Kiourtis, Joep Sprangers, Robert J. B. Nibbs, Nico Van Rooijen, Laurent Bartholin, Steven R. McGreal, Udayan Apte, Simon T. Barry, John P. Iredale, Alan R. Clarke, Manuel Serrano, Tania A. Roskams, Owen J. Sansom, Stuart J. Forbes
Journal: Science Translational Medicine (2018)

Inhibiting acute injury–induced senescence mediated by TGFβ signaling in regenerative epithelium improves liver regeneration.
Joint Effects of C-Reactive Protein and Glycated Hemoglobin in Predicting Future Cardiovascular Events of Patients With Advanced Atherosclerosis
Authors: MartinSchillinger, MarkusExner, JasminAmighi, WolfgangMlekusch, SchilaSabeti, HelmutRumpold, OswaldWagner, ErichMinar
Journal: Circulation (2003)

Background— C-reactive protein (CRP) and glycohemoglobin (HbA1c) are established risk factors for the development of cardiovascular disease. We investigated the joint effects of these parameters on cardiovascular outcome of patients with advanced atherosclerosis. Methods and Results— We studied 454 patients with advanced atherosclerosis (median age, 69 years; 264 male). Cardiovascular risk profile, high-sensitivity CRP (hs-CRP), and HbA1c were obtained at baseline, and patients were followed for a median of 21 months (interquartile range, 13 to 26) for the occurrence of major adverse cardiovascular events (MACE) (myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death). We observed 166 MACE in 128 patients (28%). Cumulative event-free survival rates at 6, 12, and 24 months were 91%, 85%, and 73%, respectively. Adjusted hazard ratios for the occurrence of MACE according to increasing quartiles of hs-CRP and HbA1c were 1.35 (P=0....
Abstract 5709: Effect of IL-18 on the expansion and phenotype of human natural killer cells
Authors: Hiroaki Senju, Asuka Kumagai, Yoichi Nakamura, Shinnosuke Takemoto, Masaaki Fukuda, Hiroshi Gyotoku, Katsumi Nakatomi, Minoru Fukuda, Hiroshi Mukae, Yoshimasa Tanaka
Journal: Cancer Research (2018)

Abstract When pathogenic stresses are recognized by innate immune cells, inflammasomes are assembled and caspase-1 is activated, resulting in the conversion of pro-IL-18 into mature IL-18. Because natural killer (NK) cells express IL-18 receptors, IL-18 may play roles in the immune functions of NK cells. In the present study, we examined the effect of IL-18 on NK cells derived from lung cancer patients and healthy adult volunteers. When peripheral blood NK cells were stimulated with IL-2, the cells formed clusters beginning on day 5-6 and proliferated thereafter, in which the number of NK cells increased by 10-fold in 10 days. When IL-18 was added, cell clusters were observed as early as on day 4 and NK cells proliferated vigorously. On day 10, the expansion rate was 56-fold on average, showing that IL-18 promoted the expansion of NK cells. It was also notable that IL-18 enhanced the expression of CD80, CD86, HLA-DR and HLA-DQ on NK cells, suggesting that IL-18 conferred NK cells an APC-like phenotype. When cellular cytotoxicity was determined, APC-like NK cells efficiently killed tumor cells and the anti-tumor activity was augmented by the addition of tumor antigen-specific mAbs. In addition, IFN-γ was produced by APC-like NK cells in response to tumor cells, and the cytokine production was further enhanced by mAbs. Taken together, IL-18 not only promoted the expansion of NK cells, but also changed the phenotype of NK cells, and the IL-2/IL-18-induced NK cells might serve as a bridge between innate immunity and adaptive immunity and be useful for cancer immunotherapy. Citation Format: Hiroaki Senju, Asuka Kumagai, Yoichi Nakamura, Shinnosuke Takemoto, Masaaki Fukuda, Hiroshi Gyotoku, Katsumi Nakatomi, Minoru Fukuda, Hiroshi Mukae, Yoshimasa Tanaka. Effect of IL-18 on the expansion and phenotype of human natural killer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5709.
Abstract 2479: LncRNA <i>GAS8-AS1</i> directs epigenetic modulation of the tumor suppressor <i>GAS8</i> via MLL1/WDR5 to suppress hepatocarcinogenesis
Authors: Ming Yang
Journal: Cancer Research (2018)

Abstract Long noncoding RNAs (lncRNAs) are vital players in hepatocellular carcinoma (HCC). We previously identified a significantly mutated lncRNA GAS8-AS1 locating in intron 2 of GAS8. However, its involvement in HCC is still largely unknown. In this study, we thoroughly functional evaluated its critical role in regulating chromatin dynamics, gene expression, cancer development and sorafenib multi-kinase target therapy in HCC. We for the first time declare that GAS8-AS1 and its host gene GAS8 act as novel HCC tumor suppressors employing a series of in vitro and in vivo assays. Consistent with this notion, a significantly decreased GAS8-AS1 or GAS8 expression exists in HCC tissues and is associated with poor prognosis of HCC patients. Interestingly, lncRNA GAS8-AS1 could evidently promote GAS8 transcription. Although GAS8-AS1 does not impact promoter DNA methylation of GAS8, we successfully annotated two lncRNA interacting proteins, Mixed Lineage Leukemia 1 (MLL1), a histone 3 Lys4 (H3K4) methyltransferase, and its partner WD-40 Repeat Protein 5 (WDR5) based on bioinformatics methodology. Chromatin immunoprecipitation and RNA immunoprecipitation assays elucidate that lncRNA GAS8-AS1 is required to maintain the GAS8 promoter in an open chromatin state. In accord with this, knockdown of GAS8-AS1 results in reduced MLL1/WDR5 binding, decreased H3K4me3 levels, diminished RNA Pol II functions and gene silencing of GAS8. GAS8-AS1 may function as part of a surveillance mechanism that keep activation of GAS8 promoter and transcription, which thus prevents hepatocarcinogenesis. Our results highlight the prevalent involvement of regulatory lncRNAs in cancers and provide pathogenic insights into HCC development and treatment. Citation Format: Ming Yang. LncRNA GAS8-AS1 directs epigenetic modulation of the tumor suppressor GAS8 via MLL1/WDR5 to suppress hepatocarcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2479.
Abstract LB-051: An <i>Astragalus</i>-based Chinese herbal medicine extraction inhibits cancer stem cell growth and sensitizes of drug-resistant human non-small cell lung cancer cells for targeted therapy
Authors: Tse-Hung Huang, Hsuan-Min Hsu, Chi-Ying F. Huang
Journal: Cancer Research (2018)

Abstract Chinese herbal medicine has been used extensively as a complementary intervention for many diseases including cancer, based on its relatively lower cytotoxicity and side-effects. The major criticism of its clinical use remains the scientific based evidence. Here, we described a precision-based translational approach to identify and validate an Astragalus-based herbal medicine (YQ1) as an antagonist of non-small cell lung cancer. Using various big data analysis approaches, we found that the L1000 profiles of YQ1was associated with anti-cancer stem cell signatures. It suggested that treatment of YQ1 might reduce cancer stem cell population. Experimentally, YQ1 treatment resulted in the significant reduction in lung cancer stem cell properties, including side population, sphere formation, stemness marker expression, and drug resistance. YQ1 may have anti-cancer stem cell ability via suppressing Wnt/β-catenin signaling to inhibit the self-renewal or/and proliferation of lung cancer stem cells. Notably, the combination of YQ1 and gefitinib significantly suppresses tumorigenesis in vivo, reflected by the down-regulation of EGFR signaling and β-catenin. Collectively, we provided preclinical evidence for using YQ1 as a cancer stem cell inhibitor to potentiate anti-tumor effects when combined with tyrosine-kinase inhibitors to significantly improve therapeutic efficacy in NSCLC patients. Citation Format: Tse-Hung Huang, Hsuan-Min Hsu, Chi-Ying F. Huang. An Astragalus-based Chinese herbal medicine extraction inhibits cancer stem cell growth and sensitizes of drug-resistant human non-small cell lung cancer cells for targeted therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-051.
Protective Role of Angiopoietin-1 in Endotoxic Shock
Authors: BernhardWitzenbichler, DirkWestermann, SabineKnueppel, Heinz-PeterSchultheiss, CarstenTschope
Journal: Circulation (2005)

Background— Angiopoietin-1 (Ang1) plays an essential role in embryonic vasculature development, protects the adult peripheral vasculature from leakage, and has antiinflammatory properties. Because endotoxin-induced shock is a condition with microvascular leakage resulting from inflammation, we examined the potential therapeutic benefit of Ang1 in a murine model of lipopolysaccharide (LPS)-induced endotoxic shock. Methods and Results— To induce endotoxic shock, LPS was injected intraperitoneally into C57BL/6 mice. Half of the mice received an intravenous application of 1.0×109 plaque-forming units of an adenoviral construct expressing human Ang1 (AdhAng1); in the other half an identical vector expressing green fluorescent protein (AdGFP) was injected as a control. In the AdhAng1-treated mice, hepatic transfection and high expression of circulating Ang1 protein were observed. Whereas in LPS-treated control mice, hemodynamic function was severely depressed 12 hours after LPS injection (decrease of blood pres...
Pursuing an Effective Ovarian Cancer Vaccine
Authors: Rebecca Voelker
Journal: JAMA (2018)

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 1385: Galangin is an epigenetic modulator or BRCA1 and induces estrogen receptor alpha in triple negative breast cancer cells
Authors: Micah G. Donovan, Ornella I. Selmin, Donato F. Romagnolo
Journal: Cancer Research (2018)

Abstract The aryl hydrocarbon receptor (AhR) is a driver of breast cancer progression and its overexpression is often observed in triple negative breast cancer (TNBC). Activation of AhR results in epigenetic silencing of the breast cancer 1 gene (BRCA1), a necessary factor in the transcriptional activation of estrogen receptor-alpha (ERα). The purpose of this study was to examine the capacity for galangin (GAL; 3,5,7-trihydroxy-2-phenylchromen-4-one), a natural AhR antagonist, to mimic the effects of synthetic AhR antagonists alpha-naphthoflavone (αNF, 2-phenylbenzo[h]chromen-4-one) and 3'-methoxy-4'-nitroflavone (MNF; 2-(3-methoxy-4-nitrophenyl)chromen-4-one) in regards to counteracting epigenetic silencing of BRCA1 and restoring ERα protein expression. We utilized TNBC cells with hypermethylated BRCA1 and constitutively active AhR (HCC38 cells) for these experiments. After 72h in phenol-red free media, cells were treated for up to 72h against a range of GAL, αNF, and MNF concentrations in the presence or absence of estradiol (E2). Transcript levels of AhR and its downstream target genes CYP1A1 and CYP1B1 were determined by real-time polymerase chain reaction (RT-PCR). Protein levels of BRCA1, ERα, and AhR were determined by Western blot. Treatment with GAL results in stabilization of BRCA1 and ERα protein levels, similarly to αNF and MNF. To determine potential mechanisms of these observations, we are currently conducting experiments to analyze changes in BRCA1 promoter methylation using methylation-specific RT-PCR (MSP) and DNA methyltransferase 1 (DNMT1) protein levels by Western blot. These data suggest the naturally occurring flavanoid GAL may be an effective compound for modulating epigenetic repression of BRCA1 and restoring ERα levels, which may provide options for anti-hormonal therapy in ERα-negative breast cancers. Citation Format: Micah G. Donovan, Ornella I. Selmin, Donato F. Romagnolo. Galangin is an epigenetic modulator or BRCA1 and induces estrogen receptor alpha in triple negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1385.
Renal Denervation for the Treatment of Cardiovascular High Risk-Hypertension or Beyond?
Authors: MichaelBöhm, DominikLinz, ChristianUkena, MurrayEsler, FelixMahfoud
Journal: Circulation Research (2014)

Hypertension imposes a major burden of morbidity and mortality and is associated with sympathetic nervous system overactivity. Renal sympathetic denervation has been shown to reduce office blood pressure, ambulatory blood pressure, and sympathetic activity in patients with resistant hypertension. Therefore, the procedure has attracted a lot of attention. Beyond blood pressure, renal denervation has been shown to improve glucose tolerance, microalbuminuria, and arrhythmias in several experimental models and, in admittedly, often uncontrolled clinical studies. It has been demonstrated to reduce myocardial hypertrophy in a blood pressure–independent and blood pressure–dependent way. The first studies on heart failure with preserved and reduced ejection fraction are ongoing. Renal sympathetic denervation holds promise for future indications in hypertension and related comorbidities and consequences, such as metabolic disease, renal failure, and heart failure. Published data in a placebo-control blinded study,...