tbuckley/cabot-search huggingface dataset:
Intravascular Ultrasound Observation of an Obstruction of the Left Main Coronary Artery Caused by Displaced Leaflet Calcification and Hematoma After Transcatheter Aortic Valve Implantation
Authors: TomohikoTaniguchi, NaritatsuSaito, KenjiMinakata, MasaoImai, HirotoshiWatanabe, ToshiakiToyota, ShinWatanabe, JunichiTazaki, ShigekiKoizumi, ShingoHirao, KazuhiroYamazaki, HirokiDaijo, RyuzoSakata, TakeshiKimura
Journal: Circulation (2015)
Systemic Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Delivery Shows Antiatherosclerotic Activity in Apolipoprotein E–Null Diabetic Mice
Authors: PaolaSecchiero, RiccardoCandido, FedericaCorallini, SerenaZacchigna, BarbaraToffoli, ErikaRimondi, BrunoFabris, MauroGiacca, GiorgioZauli
Journal: Circulation (2006)

Background— Although in vitro studies have suggested that tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) might be involved in vascular biology, its potential role in the pathogenesis and/or treatment of atherosclerosis has not been investigated. Methods and Results— Both recombinant human TRAIL and an adeno-associated virus vector expressing human TRAIL were used to deliver TRAIL in apolipoprotein E (apoE)–null mice in which diabetes mellitus was induced by destruction of islet cells with streptozotocin. Diabetes in apoE-null mice was associated with a significant increase in atherosclerotic plaque area and complexity in the aorta as assessed by a marked increase in interstitial collagen, cellular proliferation, and macrophage infiltration and a focal loss of endothelial coverage. Repeated intraperitoneal injections of recombinant human TRAIL and a single intravenous injection of adeno-associated virus–human TRAIL significantly attenuated the development of atherosclerotic plaques in apoE...
Abstract 3163: Wnt7a promotes bladder cancer cell invasion via canonical Wnt/β-Catenin signaling
Authors: Ruimin Huang, Xiaojing Huang, Hongwen Zhu, Junlong Zhuang, Yu Dong, Hu Zhou, Hongqian Guo, Jun Yan
Journal: Cancer Research (2018)

Abstract The mortality rate of urinary bladder cancer (UBC) increases dramatically, once low grade non-muscle invasive bladder cancer develops into muscle invasive bladder cancer. Hence, understanding the mechanisms underlying UBC invasion/metastasis and identification of biomarkers for invasion/metastasis will help clinicians to determine how to treat patients. Herein we generated two sublines from parental 5637 UBC cells with low invasive and high invasive capacities, which were designated as 5637 NMI and 5637 HMI, respectively. Mass spectrometry analysis was performed to identify the invasion-associated proteins. 5,987 proteins were quantified across all six samples with the coefficients among different channels all nearly 1.00, suggesting good biological repeatability and minor differences between 5637 HMI and NMI samples. Fold change &amp;gt; 1.2 and p value &amp;lt;0.05 were set as the cut-off standard, and 16 upregulated proteins and 26 downregulated proteins were identified in 5637 HMI cells. Among them, Wnt7a overexpression was confirmed in 5637 HMI cells compared to 5637 NMI cells, which was also associated with metastasis potential and worse clinical outcome in UBC patients. Depletion of Wnt7a in 5637 HMI and T24 cells reduced UBC cell invasion, with the reduction of active β-Catenin and its downstream target genes involved in epithelial-to-mesenchymal transition (EMT) and extracellular matrix (ECM) degradation. Consistently, introduction recombinant Wnt7a protein to 5637 NMI and J82 cells induced cell invasion, EMT, and the expression of ECM degradation-associated genes. Using luciferase reporter driven by the wildtype or mutants of matrix metalloproteinase 10 (MMP10) promoter, a canonical Wnt/β-Catenin regulation pattern was demonstrated. Four miRNAs downregulated in UBCs were predicted directly targeting Wnt7a using bioinformatics analysis. miRNA mimic could decrease Wnt7a expression, reduce the activation of MMP 10 reporter and suppress the invasion of 5637 HMI cells. Treatment of UBC cells with Wnt7a partially abrogated such miRNAs-induced invasion suppression. Taken together, our data identify a new miRNA/Wnt7a axis to mediate cell invasion and metastasis of UBC through canonical Wnt/β-Catenin pathway, which may offer prognostic and therapeutic opportunity. Citation Format: Ruimin Huang, Xiaojing Huang, Hongwen Zhu, Junlong Zhuang, Yu Dong, Hu Zhou, Hongqian Guo, Jun Yan. Wnt7a promotes bladder cancer cell invasion via canonical Wnt/β-Catenin signaling [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 3163.
Potential Effects of Bariatric Surgery and Reduced Interleukin 32 Levels on Type 2 Diabetes and Its Comorbidities—Reply
Authors: Thomas H. Inge, Philip S. Zeitler
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Therapeutic Attenuation of Cardiac Remodeling After Acute Myocardial Infarction
Authors: Marc A. Pfeffer, John D. Rutherford
Journal: Circulation (2018)

Dr Rutherford asks: In the early 1970s, you, and your late wife Janice, studied adrenergic mechanisms and cardiac hypertrophy and ventricular function, as well, in spontaneously hypertensive rats.What led to your initial animal studies on acute myocardial infarction and your interest in the renin-angiotensin-aldosterone system?
Abstract 2926: The glycogen synthase kinase-3 inhibitor, 9-ING-41, synergizes with chemotherapy to inhibit pancreatic tumor growth in vivo
Authors: Li Ding, Jin-san Zhang, John R. Dube, Vijay S. Madamsetty, Daniel M. Schmitt, Debabrata Mukhopadhyay, Daniel D. Billadeau
Journal: Cancer Research (2018)

Abstract Glycogen synthase kinase-3 (GSK3) is a ubiquitously expressed serine-threonine protein kinase involved in multiple cellular functions ranging from the control of glycogen metabolism to transcriptional regulation. We have previously demonstrated that GSK-3β is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) and aberrant nuclear accumulation of GSK-3β serves as a hallmark of poorly differentiated PDAC. Moreover, genetic ablation of GSK-3β or GSK-3 inhibition led to PDAC tumor cell killing, identifying GSK-3β as a therapeutic target in PDAC. Herein, we describe a novel GSK-3 inhibitor, 9-ING-41. The effect of 9-ING-41 on tumor cell growth was tested using several PDAC and patient-derived xenograft (PDX) cell lines in vitro and in vivo using an orthotopic pancreatic cancer animal model. Interestingly, 9-ING-41 treatment resulted in the stabilization of cyclin B levels as well as enhanced serine-10 phosphorylated histone H3 (pS10HH3) and consequently M phase arrest and blocked mitotic exit. The prolonged M phase arrest induced mitotic catastrophe in pancreatic cancer cell lines and inhibited in vitro colony formation. An in vivo orthotopic pancreatic cancer animal model study using PDX-derived cell lines demonstrated that 9-ING-41 hindered tumor growth in combination with several standard chemotherapeutic agents. Significantly, we found that 9-ING-41 treatment impaired the DNA damage response pathway activated by Gemcitabine in pancreatic cancer cell lines. In conclusion, our study indicates that GSK-3 plays an important role in pancreatic cancer progression and 9-ING-41 in combination with existing gemcitabine or irinotecan could be a new strategy for treating patients with PDAC. Citation Format: Li Ding, Jin-san Zhang, John R. Dube, Vijay S. Madamsetty, Daniel M. Schmitt, Debabrata Mukhopadhyay, Daniel D. Billadeau. The glycogen synthase kinase-3 inhibitor, 9-ING-41, synergizes with chemotherapy to inhibit pancreatic tumor growth in vivo [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 2926.
Remnant Lipoprotein Levels in Fasting Serum Predict Coronary Events in Patients With Coronary Artery Disease
Authors: KiyotakaKugiyama, HidekiDoi, KeijiTakazoe, HiroakiKawano, HirofumiSoejima, YujiMizuno, RyusukeTsunoda, TomohiroSakamoto, TakamitsuNakano, KatsuyukiNakajima, HisaoOgawa, SeigoSugiyama, MichihiroYoshimura, HirofumiYasue
Journal: Circulation (1999)

Background—Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD). Methods and Results—Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti–apoB-100 monoclonal antibodies. Patients were followed up for ≤36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coron...
Transcriptomics and Transposon Mutagenesis Identify Multiple Mechanisms of Resistance to the FGFR Inhibitor AZD4547
Authors: Sjors M. Kas, Julian R. de Ruiter, Koen Schipper, Eva Schut, Lorenzo Bombardelli, Ellen Wientjens, Anne Paulien Drenth, Renske de Korte-Grimmerink, Sunny Mahakena, Christopher Phillips, Paul D. Smith, Sjoerd Klarenbeek, Koen van de Wetering, Anton Berns, Lodewyk F.A. Wessels, Jos Jonkers
Journal: Cancer Research (2018)

In human cancers, FGFR signaling is frequently hyperactivated by deregulation of FGF ligands or by activating mutations in the FGFR receptors such as gene amplifications, point mutations, and gene fusions. As such, FGFR inhibitors are considered an attractive therapeutic strategy for patients with mutations in FGFR family members. We previously identified Fgfr2 as a key driver of invasive lobular carcinoma (ILC) in an in vivo insertional mutagenesis screen using the Sleeping Beauty transposon system. Here we explore whether these FGFR-driven ILCs are sensitive to the FGFR inhibitor AZD4547 and use transposon mutagenesis in these tumors to identify potential mechanisms of resistance to therapy. Combined with RNA sequencing-based analyses of AZD4547-resistant tumors, our in vivo approach identified several known and novel potential resistance mechanisms to FGFR inhibition, most of which converged on reactivation of the canonical MAPK-ERK signaling cascade. Observed resistance mechanisms included mutations in the tyrosine kinase domain of FGFR2, overexpression of MET, inactivation of RASA1, and activation of the drug-efflux transporter ABCG2. ABCG2 and RASA1 were identified only from de novo transposon insertions acquired during AZD4547 treatment, demonstrating that insertional mutagenesis in mice is an effective tool for identifying potential mechanisms of resistance to targeted cancer therapies.Significance: These findings demonstrate that a combined approach of transcriptomics and insertional mutagenesis in vivo is an effective method for identifying potential targets to overcome resistance to therapy in the clinic. Cancer Res; 78(19); 5668-79. ©2018 AACR.
Progress in the Reprogramming of Somatic Cells
Authors: TianhuaMa, MinXie, TimothyLaurent, ShengDing
Journal: Circulation Research (2013)

Pluripotent stem cells can differentiate into nearly all types of cells in the body. This unique potential provides significant promise for cell-based therapies to restore tissues or organs destroyed by injuries, degenerative diseases, aging, or cancer. The discovery of induced pluripotent stem cell (iPSC) technology offers a possible strategy to generate patient-specific pluripotent stem cells. However, because of concerns about the specificity, efficiency, kinetics, and safety of iPSC reprogramming, improvements or fundamental changes in this process are required before their effective clinical use. A chemical approach is regarded as a promising strategy to improve and change the iPSC process. Dozens of small molecules have been identified that can functionally replace reprogramming factors and significantly improve iPSC reprogramming. In addition to the prospect of deriving patient-specific tissues and organs from iPSCs, another attractive strategy for regenerative medicine is transdifferentiation—the ...
Abstract 967: Targeting notch one notch above
Authors: Deniz A. Ucar-Bilyeu, Margarite D. MATOSSIAN, VAN Hoang Barnes, Fokhrul M. Hossain, Mohit Gupta, HOPE E. BURKS, THOMAS D. WRIGHT, Jane Cavanaugh, Patrick Flaherty, Matthew E. Burow, Lucio Miele
Journal: Cancer Research (2018)

Abstract Triple negative breast cancer (TNBC) is a molecularly heterogeneous, clinically aggressive disease group that is highly prevalent among African-Americans and younger patients. Standard chemo/radio therapy often produces clinical responses, but recurrence and metastasis are unfortunately common. Metastatic disease is generally incurable. Chemo/radiotherapy has been shown to induce EMT and enrich a chemo-resistant cancer stem cell-like (CSC) population in TNBC. CSCs are thought to drive disease recurrence. Notch signaling, particularly Notch1, is critical for maintenance of TNBC CSC. Expression of Notch1 and its ligand Jagged1 are correlated with poor prognosis. Efforts to pharmacologically target Notch directly have been impaired by the systemic toxicity of the Gamma Secretase Inhibitors (GSI) used, and by the fact that Notch1 also plays a key role in anti-tumor adaptive immunity. Therapeutic agents that target Notch signaling in breast cancer cells indirectly and selectively are a potentially attractive strategy. However, no such target has been identified to date. We have found that the MAPK5-ERK5 kinase pathway, which contains at least two druggable targets, functions as a master regulator of Notch signaling in TNBC cells. ERK5 knockout TNBC cells have dramatically decreased expression of Notch receptors, ligands and targets. In vivo, these cells form barely detectable tumors that do not metastasize and express lower levels of Notch1 and its ligand Jagged1. Using in silico screening method, we have identified a small molecule compound that targets MAP2K5 (MEK5) and decreases phosphorylation of MAPK7 (ERK5). Expression of ERK5 is associated with poor prognosis in TNBC. Consistent with ERK5KO cells, suppression of ERK5 phosphorylation decreased the amount of Notch1 and Jagged1 protein and mRNAs. More importantly, a selective MEK5 inhibitor, SC-181, reversed EMT and reduced the CD44hi/CD24lo CSC population in TNBC cells without suppressing T-cell proliferation. Treatment with nanomolar concentration of this compound decreased the number and size of mammospheres in a dose- dependent manner. Our preliminary results suggest that targeting the MEK5-ERK5 pathway is a promising strategy to selectively target Notch signaling in TNBC CSC without systemic Notch inhibition. Citation Format: Deniz A. Ucar-Bilyeu, Margarite D. MATOSSIAN, VAN Hoang Barnes, Fokhrul M. Hossain, Mohit Gupta, HOPE E. BURKS, THOMAS D. WRIGHT, Jane Cavanaugh, Patrick Flaherty, Matthew E. Burow, Lucio Miele. Targeting notch one notch above [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 967.
Abstract 4324: Systematic characterization of A-to-I RNA editing in cancer development
Authors: Han Liang
Journal: Cancer Research (2018)

Abstract Adenosine (A) to inosine (I) RNA editing, mediated by ADAR enzymes, is a well-established RNA modification mechanism. Recent studies show that A-to-I RNA editing introduces a large number of nucleotide changes in both coding and noncoding regions in cancer transcriptomes. First, to elucidate the contribution of RNA editing to proteomic diversity in human cancer, we performed an integrated analysis of The Cancer Genome Atlas (TCGA) genomic data and proteomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). We detected a considerable contribution of RNA editing in terms of amino acids changes induced per tumor sample in breast cancer. We validated some of these editing events at both RNA and protein levels, and further experimentally demonstrated the functional effects of some edited protein (e.g., increased proliferation, migration, and invasion of cancer cells in vitro). Second, we systematically characterized the miRNA editing hotspots across 20 cancer types from TCGA miRNA sequencing data and independently validated the vast majority of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to that pattern for the wild-type miR-200b expression. We further experimentally showed that in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets including LIFR, a well-characterized metastasis suppressor. Our results highlight the contribution of A-to-I RNA editing in cancer development and suggest its translational potential as both biomarkers and therapeutic targets. Citation Format: Han Liang. Systematic characterization of A-to-I RNA editing in cancer development [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 4324.
Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice
Authors: Rodolfo G. Gatto, Manish Y. Amin, Daniel Deyoung, Matthew Hey, Thomas H. Mareci, Richard L. Magin
Journal: Translational Neurodegeneration (2018)

Amyotrophic lateral sclerosis (ALS) is a disease characterized by a progressive degeneration of motor neurons leading to paralysis. Our previous MRI diffusion tensor imaging studies detected early white matter changes in the spinal cords of mice carrying the G93A-SOD1 mutation. Here, we extend those studies using ultra-high field MRI (17.6 T) and fluorescent microscopy to investigate the appearance of early structural and connectivity changes in the spinal cords of ALS mice. The spinal cords from presymptomatic and symptomatic mice (80 to 120 days of age) were scanned (ex-vivo) using diffusion-weighted MRI. The fractional anisotropy (FA), axial (AD) and radial (RD) diffusivities were calculated for axial slices from the thoracic, cervical and lumbar regions of the spinal cords. The diffusion parameters were compared with fluorescence microscopy and membrane cellular markers from the same tissue regions. At early stages of the disease (day 80) in the lumbar region, we found, a 19% decrease in FA, a 9% decrease in AD and a 35% increase in RD. Similar changes were observed in cervical and thoracic spinal cord regions. Differences between control and ALS mice groups at the symptomatic stages (day 120) were larger. Quantitative fluorescence microscopy at 80 days, demonstrated a 22% reduction in axonal area and a 22% increase in axonal density. Tractography and quantitative connectome analyses measured by edge weights showed a 52% decrease in the lumbar regions of the spinal cords of this ALS mice group. A significant increase in ADC (23.3%) in the ALS mice group was related to an increase in aquaporin markers. These findings suggest that the combination of ultra-high field diffusion MRI with fluorescent ALS mice reporters is a useful approach to detect and characterize presymptomatic white matter micro-ultrastructural changes and axonal connectivity anomalies in ALS.
Association of Serum Retinoic Acid With Risk of Mortality in Patients With Coronary Artery Disease
Authors: YanLiu, HongenChen, DiMu, DiLi, YuanZhong, NanJiang, YuanZhang, MinXia
Journal: Circulation Research (2016)

Rationale:Retinoic acid (RA) and its mediated nuclear receptor signaling have broad protective effects on vascular systems. Whether circulating levels of RA are associated with mortality in patients with coronary artery disease is still unknown. Objective:To evaluate the association of circulating RA with the risk of mortality. Methods and Results:We measured serum RA concentrations in 1499 patients with angiographically confirmed coronary artery disease (mean age, 61 years; male, 67%) recruited from October 2008 and December 2011 in the Expanded Guangdong Coronary Artery Disease Cohort. During a median (interquartile range) period of 4.4 (3.6 to 6.1) years of follow-up, there were 295 all-cause mortality, among which 208 had cardiovascular mortality. Serum RA level was significantly lower in participants with mortality (median 21 [11–47] nmol/L) than in those without mortality (median 39 [19–86] nmol/L). In multivariate analyses, the hazard ratios for total mortality among those in the lowest (referent) ...