tbuckley/cabot-search huggingface dataset:
Abstract LB-395: STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells contributes to the malignant progression of gastric cancer cells
Authors: Jinfei Chen, Fen Yang
Journal: Cancer Research (2018)

Abstract BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of functional regulators involved in gastric cancer (GC). Studying aberrantly expressed lncRNAs may provide us with new insights into the occurrence and development of gastric cancer by acting as oncogenes or tumor suppressors. In this study, we aim to examine the expression pattern of lncRNA HAGLROS in GC and its biological role and mechanisms in tumor progression. METHODS: Bioinformatics analysis and qRT-PCR were performed to detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or loss of function approaches were used to investigate the biological functions of HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony formation assay and nude mouse xenograft model. Wound healing and Transwell assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA-seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to measure molecular mechanisms. Results are shown as means ± S.D. and differences were tested for significance using Student's t-test (two-tailed). RESULTS: We screened out HAGLROS, whose expression was significantly increased and correlated with outcomes of GC patients by publicly available lncRNAs expression profiling and integrating analyses. Exogenous down-regulation of HAGLROS expression significantly suppressed the cell proliferation, invasion and migration. Mechanistic investigations showed that HAGLROS was a direct target of transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR expression and increased autophagy-related genes ATG9A and ATG9B expression. Further investigation showed that HAGLROS regulated mTOR signals in two manners. In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling pathway which was known to be an important negative signal of autophagy. Here activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells. CONCLUSION: The present study demonstrates that HAGLROS overexpression contributes to GC development and poor prognosis and will be a target for GC therapy and further develop as a potential prognostic biomarker. Citation Format: Jinfei Chen, Fen Yang. STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells contributes to the malignant progression of gastric 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 LB-395.
Differential Distribution of Inward Rectifier Potassium Channel Transcripts in Human Atrium Versus Ventricle
Authors: ZhiguoWang, LixiaYue, MichelWhite, GuyPelletier, StanleyNattel
Journal: Circulation (1998)

Background—The inward rectifier K+ current (IK1) plays an important role in governing cardiac electrical activity and is well known to have different properties in the atrium compared with the ventricle. Several inward rectifier K+ channel (IRK) subunits (hIRK, HH-IRK1, HIR, and TWIK-1) with different properties have been cloned from human tissues, but their relative expression in cardiac tissues has not been quantified. The present study was designed to define the relative levels of mRNA for various IRKs in human atrium and in failing and nonfailing ventricle. Methods and Results—Competitive reverse transcription–polymerase chain reaction was used to quantify in human atrium and ventricle the mRNA levels of hIRK, HH-IRK1, HIR, and TWIK-1. The absence of important noncardiac contamination was confirmed by demonstrating a lack of detectable mRNA markers for neuronal (acetylcholine receptor) and vascular (maxi-K channel) tissue. mRNA of HIR was more abundant in normal atrium (7.1±1.3 amol/μg total RNA) than...
Abstract 375: Origins of fractional control in regulated cell death
Authors: Luis C. Santos, Robert Vogel, Jerry E. Chipuk, Marc Birtwistle, Gustavo Stolovitzky, Pablo Meyer
Journal: Cancer Research (2018)

Abstract Fractional killing of a population of cancer cells is often linked to cell-to-cell variability due to stochastic gene expression and fluctuations in protein levels. We found that mitochondria abundance is a major source of cell-to-cell variability that determines the fraction of cells that live or die in response to TNF-related apoptosis-inducing ligand (TRAIL). We show that the IC50 of TRAIL of clonogenic cancer cell populations correlates with mitochondria abundance, and cell-to-cell variability in mitochondria abundance controls up to 40% of the response to TRAIL. Our coarse-grained quantitative model of apoptosis reveals that increasing the mitochondrial surface area decreases the density of proapoptotic Bax pores, which in turn decreases the sensitivity of cells to TRAIL. We demonstrate that the clinically relevant small-molecule inhibitor of antiapoptotic Bcl-2 proteins ABT-263 reduces the IC50 of TRAIL by reducing the contribution of mitochondria to variability in apoptosis. Citation Format: Luis C. Santos, Robert Vogel, Jerry E. Chipuk, Marc Birtwistle, Gustavo Stolovitzky, Pablo Meyer. Origins of fractional control in regulated cell death [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 375.
Abstract 18828: Sudden Cardiac Death Risk Score as a Tool for Population Health
Authors: Leonardo Tamariz, Ruaa Mansi, Alia Baqais, Donald LLoyd-Jones, Jeffrey Goldberger
Journal: Circulation (2017)

Introduction: Estimating SCD risk in asymptomatic patients is challenging. Recently a SCD score was developed. Hypothesis: The aim of our study is to evaluate the health care utilization of patient...
Abstract 19204: Higher Physical Activity and Lower Sedentary Time are Associated With Less Insulin Resistance and Favorable Adipokine Profile: The Framingham Study
Authors: Nicole L Spartano, Meredith D Stevenson, Vanessa Xanthakis, Martin G Larson, Charlotte Andersson, Joanne M Murabito, Ramachandran S Vasan
Journal: Circulation (2015)

Background: Physical activity (PA) and sedentary time (ST) are associated with metabolic diseases. More PA and less ST may also be associated with a more favorable adipokine profile and greater insulin sensitivity, even in the absence of weight loss. We tested this hypothesis by relating a comprehensive panel of adipokines in relation to accelerometry-determined PA measures in a community-based cohort. Methods: We assessed PA and ST using Actical accelerometers in 2109 participants from Framingham Heart Study Generation 3 and Omni 2 cohorts (mean age 40 y, 54% F) free of diabetes. Circulating adipokines, C-reactive protein (CRP), insulin-like growth factor (IGF)-1 and insulin resistance (HOMA-IR) were dependent variables, and steps/day, moderate to vigorous PA (MVPA), and ST/weartime were independent variables in multivariable regression analyses. We adjusted for cohort, age, sex, season of exam, overnight wear, residence (New England or other), body mass index (BMI), cardiovascular disease, hypertension, and smoking. Models for PA were also adjusted for ST, and models for ST also adjusted for MVPA. Results: Overall, 49% of participants met the PA Guidelines (&gt;150 min/wk MVPA). Higher MVPA and more steps per day were associated with lower insulin resistance and CRP levels. More steps were also associated with lower leptin and higher IGF-1 levels. ST was positively associated with insulin resistance (p&lt;0.001), but this relation was not significant after adjusting for MVPA. ST was associated with higher leptin, adipocyte fatty acid-binding protein (FABP)4 and retinol binding protein (RBP)4 levels. Conclusions: Our cross-sectional study of a community-based sample demonstrated associations of PA and ST with metabolic factors and several adipokines, after adjusting for BMI. These findings may provide clues linking PA to cardiometabolic risk by influencing insulin resistance and inflammation, compared to ST potentially modulating fatty acid binding proteins.
Methods for Determining the Refractory Period and Excitable Gap During Persistent Atrial Fibrillation in the Goat
Authors: MattiasDuytschaever, FransMast, MatthijsKillian, YuriBlaauw, MauritsWijffels, MauritsAllessie
Journal: Circulation (2001)

Background— Recently, the temporal excitable gap during atrial fibrillation (AF) has been identified as a vulnerable parameter for cardioversion of AF. In this study, we evaluated 5 methods to measure the refractory period (RPAF) and the excitable period (EPAF) during persistent AF. Methods and Results— In 11 goats instrumented with 83 epicardial atrial electrodes, persistent AF (43±34 days) was induced with a median AF cycle length (CL) of 98±14 ms. To measure RPAF, premature stimuli were applied to the center of the electrode array on the right or left atrium. The RPAF measured by mapping of premature stimuli was 70±12 ms (“gold standard”). The RPAF determined during entrainment of AF was 77±17 ms (R2=0.88, P<0.01). Statistical analysis of the effects of synchronized stimuli (each coupling interval ×100) on the AFCL histogram yielded an RPAF of 70±13 ms (R2=0.94, P<0.01). A further simplification was to apply slow fixed-rate pacing (1 Hz) during AF. For each stimulus (n=250 to 500), the paced AFCL was p...
Subpopulation of Proepicardial Cells Is Derived From the Somatic Mesoderm in the Chick Embryo
Authors: JanSchlueter, ThomasBrand
Journal: Circulation Research (2013)

Rationale:The proepicardium (PE) is a transient structure forming at the venous pole of the heart and gives rise to the epicardium, fibroblasts, and smooth muscle cells. The embryological origin of the PE is presently unclear. Asymmetrical formation of the PE on the right inflow tract is a conserved feature of many vertebrate embryos, and in the chicken is under the control of fibroblast growth factor 8 and snail homolog 1. Objective:To gain further insight into the process of asymmetrical PE formation, we studied the role of TWIST1 during PE formation in the chick embryo. Methods and Results:TWIST1 is asymmetrically expressed on the right side in the somatic mesoderm under the control of snail homolog 1. Fate mapping experiments revealed a contribution of the somatic mesoderm to the PE. After colonization of the heart, this cell lineage gives rise to the epicardium, smooth muscle cells, and potentially fibroblast. Suppression of TWIST1 function in the right coelomic cavity caused a severe disruption of t...
Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo
Authors: Ming-Shu Mo, Gui-Hua Li, Cong-Cong Sun, Shu-Xuan Huang, Lei Wei, Li-Min Zhang, Miao-Miao Zhou, Zhuo-Hua Wu, Wen-Yuan Guo, Xin-Ling Yang, Chao-Jun Chen, Shao-Gang Qu, Jian-Xing He, Ping-Yi Xu
Journal: Translational Neurodegeneration (2018)

Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (β5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. In this study, we investigated the role of β5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo. We showed that 6-OHDA upregulated β5i expression in DA neurons in a concentration- and time-dependent manner. Inhibition and downregulation of β5i induced the expression of glucose-regulated protein (Bip) and exacerbated 6-OHDA neurotoxicity in DA neurons. The inhibition of β5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA. β5i also activated transporter associated with antigen processing 1 (TAP1) and promoted MHC-I expression on DA neurons. Taken together, our data suggest that β5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.
Abstract 15887: MURC/cavin-4 Functions as a Negative Regulator of Caveolin-3 in Tte Development of Heart Failure
Authors: Daisuke Naito, Tomomi Ueyama, Miyuki Kobara, Katsuya Amano, Takehiro Ogata, Takuya Taniguchi, Naohiko Nakanishi, Kotaro Miyagawa, Hiroaki Matsubara
Journal: Circulation (2012)

Background: Muscle-restricted coiled-coil protein (MURC)/cavin-4 is a novel member of the cavin family that regulates caveolae function. Caveolae formation and function are also regulated by caveol...
Abstract 20831: Cognitive Ability, Lifestyle Risk Factors, and Two-Year Mortality in First Myocardial Infarction Men: A Swedish National Registry Study
Authors: John Wallert, Guy Madison, Claes Held, Erik Olsson
Journal: Circulation (2016)

Introduction: General cognitive ability (CA) estimated early in life is positively associated with later physical and mental health, health literacy, and longevity. Methods: We investigated young a...
Recent research trends and updates on nonalcoholic fatty liver disease
Authors: Jeong-Ju Yoo, Won Kim, Moon Young Kim, Dae Won Jun, Sang Gyune Kim, Jong-Eun Yeon, Jin Woo Lee, Yong Kyun Cho, Sang Hoon Park, Joo Hyun Sohn
Journal: Clinical and Molecular Hepatology (2018)

Nonalcoholic fatty liver disease (NAFLD), together with metabolic syndrome and obesity, has shown a rapid increase in prevalence worldwide and is emerging as a major cause of chronic liver disease and liver transplantation. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to development of end-stage liver disease and cardiometabolic disease, resulting in liver-related and non-liver-related mortality. Nonetheless, there is no standardized pharmacotherapy against NASH and many drugs are under development in ongoing clinical trials. To develop a successful anti-NASH drug, it is necessary to select an appropriate target population and treatment outcomes depending on whether the mode of action is anti-metabolic, anti-inflammatory or anti-fibrotic. Recently, innovative surrogate markers have been investigated to replace hard outcomes such as liver histology and mortality and reduce the clinical trial duration. Currently, several drugs with fast track designation are being tested in phase III clinical trials, and many other drugs have moved into phase II clinical trials. Both lean NAFLD and typical obese NAFLD have been extensively studied and genetic variants such as PNPLA3 and TM6SF2 have been identified as significant risk factors for lean NAFLD. In the near future, noninvasive biomarkers and effective targeted therapies for NASH and associated fibrosis are required to develop precision medicine and tailored therapy according to various phenotypes of NAFLD.
Fluvastatin Enhances the Inhibitory Effects of a Selective Angiotensin II Type 1 Receptor Blocker, Valsartan, on Vascular Neointimal Formation
Authors: MasatsuguHoriuchi, Tai-XingCui, ZhenLi, Jian-MeiLi, HironoriNakagami, MasaruIwai
Journal: Circulation (2003)

Background— The present studies were undertaken to investigate the potential effect of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) to enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT1) receptor blocker (ARB) on vascular neointimal formation and to explore the cellular mechanism of cross-talk of the AT1 receptor and statin in vascular smooth muscle cells (VSMCs). Methods and Results— Neointimal formation and the proliferation of VSMCs induced by cuff placement around the femoral artery were significantly inhibited by treatment with an ARB, valsartan, at a dose of 0.1 mg · kg−1 · d−1 and with fluvastatin at a dose of 1 mg · kg−1 · d−1, which did not influence mean arterial blood pressure or plasma cholesterol level, whereas valsartan or fluvastatin alone at these doses did not affect neointimal formation or the proliferation of VSMCs. Pretreatment with fluvastatin (≈5 μmol/L) for 24 hours significantly inhibited Ang II (1 μmol/L)–mediated DNA synthesis and c-fos promot...
Five vitamin D receptor polymorphisms (FokI, BsmI, Apa1, Taq1, and Cdx2) and lung cancer risk.
Authors: Rong Li, Ming Tian, Meili Ma, Jun Pei, Yiyi Song, Baohui Han
Journal: Journal of Clinical Oncology (2012)

e12013 Background: Vitamin D and its receptor (VDR) have been implicated in lung cancer incidence and mortality. Here we assess the relationships between VDR single nucleotide polymorphisms (SNPs) (FokI, BsmI, ApaI, Taq, Cdx2) and lung cancer incidence in Chinese patients. Methods: Genomic DNA was extracted from peripheral blood samples. Five VDR SNPs (FokI, BsmI, ApaI, Taq, Cdx2) were detected by polymerase chain reaction. Genotype analysis was conducted using mass spectrograph. Results: A total of 67 lung cancer patients and 72 healthy controls participated in the study. There were more males and current smokers among the lung cancer patients than among healthy controls. Lung cancer patients were much older than controls. Age and smoking status were included in the equation for predicting disease status. The CC-AA (Apa1-Cdx2) and the CC-AA-CC (ApaI-Cdx2- FokI) haplotypes were associated with higher lung cancer incidence. The rs1544410 (BsmI) and rs731236 (TaqI) were not associated with higher lung cancer incidence, but they were associated with rs797523 (ApaI). Conclusions: There is a significant correlation between certain VDR SNPs (FokI, ApaI, Cdx2) and lung cancer incidence in Chinese people.
Cardiac Myosin Binding Protein C
Authors: EmilyFlashman, CharlesRedwood, JohannaMoolman-Smook, HughWatkins
Journal: Circulation Research (2004)

Myosin binding protein-C (MyBP-C) is a thick filament–associated protein localized to the crossbridge-containing C zones of striated muscle sarcomeres. The cardiac isoform is composed of eight immunoglobulin I–like domains and three fibronectin 3–like domains and is known to be a physiological substrate of cAMP-dependent protein kinase. MyBP-C contributes to thick filament structure via interactions at its C-terminus with the light meromyosin section of the myosin rod and with titin. The protein also has a role in the regulation of contraction, due to the binding of its N-terminus to the subfragment-2 portion of myosin, which reduces actomyosin ATPase activity; phosphorylation abolishes this interaction, resulting in release of the “brake” on crossbridge cycling. Several structural models of the interaction of MyBP-C with myosin have been proposed, although its precise arrangement on the thick filament remains to be elucidated. Mutations in the gene encoding cardiac MyBP-C are a common cause of hypertroph...
“Apoptotic” Myocytes in Infarct Area in Rabbit Hearts May Be Oncotic Myocytes With DNA Fragmentation
Authors: MichiyaOhno, GenzouTakemura, AtsukoOhno, JunMisao, YukihiroHayakawa, ShinyaMinatoguchi, TakakoFujiwara, HisayoshiFujiwara
Journal: Circulation (1998)

Background—Modes of cell death have been defined morphologically as apoptosis and oncosis. Infarcted myocytes have been reported to show apoptosis, as revealed by DNA fragmentation by DNA ladder and by in situ terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL) at the light microscopic level. We investigated whether TUNEL-positive infarcted myocytes have apoptotic or oncotic ultrastructures by using electron microscopic TUNEL, which can simultaneously observe the ultrastructure and DNA fragmentation of the same myocytes. Methods and Results—Thirty rabbits were divided into 5 groups (n=6 each) that were subjected to a sham operation or to 30-minute ischemia followed by 0-minute, 30-minute, 2-hour, or 4-hour reperfusion of a coronary artery. In the 2- and 4-hour reperfusion groups only, DNA electrophoresis showed a ladder pattern, and the light microscopic TUNEL finding was positive in the nuclei of myocytes localized in the infarcted area (6±2% and 11±3%, respectively). Electron m...
Introductory commentary: a strategic review of options for building on lessons learnt from IMCI and iCCM
Authors: Marian Jacobs, Michael Merson
Journal: BMJ (2018)

Despite advances in child health over the past 20 years, children are still failing to reach their full health and development. <b>Marian Jacobs</b> and <b>Michael Merson</b> examine what the 2016 strategic review tells about how IMCI and iCCM have contributed to gains in child health, as well as the changes in child health epidemiology, health systems, technology and innovations, and health science
Abstract 114: Basal-like breast cancer engages tumor-supportive macrophages via cytokines triggered by extracellular S100A4
Authors: Lina Prasmickaite, Ellen M. Tenstad, Eivind Valen Egeland, Solveig Pettersen, Shakila Jabeen, Silje Nord, Mads Haugland Haugen, Siri Juell, Tove Øyjord, Olav Engebråten, Gunhild Mari Mælandsmo
Journal: Cancer Research (2018)

Abstract Recently the biological and therapeutic perspective on cancer has evolved from focusing on tumor cells only, to include the complex impact of the tumor microenvironment (TME). The TME appears to have a strong influence on both tumor progression and response to treatment. In breast cancer, and in particular the triple-negative subgroup, patient outcome together with the therapeutic response are strongly linked to the tumor's inflammatory profile: presence of tumor-infiltrating leukocytes and their regulatory cytokine. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the TME, and expression of such cells has been strongly correlated with both poor outcome and development of resistance. In this study we explored the effect of the pro-metastatic, inflammation-associated, TME factor S100A4 on breast cancer cells (BCCs) of different subtypes, and their further interactions with inflammatory cells. We show that S100A4 activates BCCs, stimulating secretion of pro-inflammatory cytokines, which, in turn, promotes monocyte conversion into TAM-like cells. This was in particular prominent for cytokines secreted from basal-like BCCs. The TAM-like cells possess pro-tumorigenic activities, including increased resistance and ability to migrate. In conclusion, we demonstrate that S100A4 instigate an inflammatory microenvironment, involving a network of cytokines and TAMs, which is particularly pronounced in basal-like BC and could facilitate aggressive phenotypes of this subtype. Citation Format: Lina Prasmickaite, Ellen M. Tenstad, Eivind Valen Egeland, Solveig Pettersen, Shakila Jabeen, Silje Nord, Mads Haugland Haugen, Siri Juell, Tove Øyjord, Olav Engebråten, Gunhild Mari Mælandsmo. Basal-like breast cancer engages tumor-supportive macrophages via cytokines triggered by extracellular S100A4 [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 114.