tbuckley/cabot-search huggingface dataset:
Abstract 3938: The alkylphosphocholine erufosine induces ER and mitochondrial stress in OSCC cells
Authors: Shariq S. Ansari, Ashwini Sharma, Doaa M. Ali, Rainer Köng, Martin R. Berger
Journal: Cancer Research (2018)

Abstract Endoplasmic reticulum (ER) plays an essential role in cell function and survival. Accumulation of unfolded or misfolded proteins in the lumen of the ER activates the unfolded protein response (UPR), resulting in ER-stress and subsequent apoptosis. The alkylphosphocholine erufosine is a known Akt-mTOR inhibitor in oral squamous cell carcinoma (OSCC). In the present study we decipher a new facet of erufosine's mechanism of action and evaluate its role to induce ER and mitochondrial stress leading to autophagy, apoptosis and ROS induction. The cellular toxicity of erufosine was determined by MTT assay after 24h, 48h and 72h exposure in two OSCC cell lines, HN-5 and SCC-61. Based on these results, HN-5 cells were exposed to erufosine at concentrations corresponding to IC25, IC50 and IC75 concentrations, and then their mRNA was isolated and analyzed by Illumina Chip array. Gene expression and gene set enrichment analyses were performed to identify core KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways and GO (Gene Ontology) terms. A positive enrichment of ER stress upon erufosine exposure was observed, which was verified at protein level for the ER stress sensors and their downstream mediators. Upon erufosine exposure, calcium influx into the cytoplasm of the two OSCC cell lines was also observed. A differential regulation of genes and positive enrichment of processes pertaining to autophagy and apoptosis was also observed upon erufosine exposure. Autophagy was confirmed by increased acidic vacuoles and LC3-B levels. Apoptosis was confirmed by nuclear staining, annexin-V and immuno-blotting of caspases. The induction of mitochondrial stress upon erufosine exposure was predicted by gene enrichment analysis and shown by erufosine's effect on mitochondrial membrane potential, ATP and ROS production in OSCC cells. These data show that ER and mitochondrial targeting by erufosine represents a new facet of its mechanism of action as well as a promising new framework in the treatment of head and neck cancers. They furthermore support the future evaluation of erufosine as a therapeutic approach in cancer treatment alone, or in combination. Citation Format: Shariq S. Ansari, Ashwini Sharma, Doaa M. Ali, Rainer Köng, Martin R. Berger. The alkylphosphocholine erufosine induces ER and mitochondrial stress in OSCC 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 3938.
Abstract 15429: Predictors of Resuscitation Success Prior to EMS Arrival in Out of Hospital Cardiac Arrest Patients Treated With a Public Access AED
Authors: Hidetada Fukushima, Annemarie Silver, Jeffery Gould, Kristopher Edgell, David Appleby, Taku Iwami, Margarett Mullins, Robyn McDannold, Bentley J Bobrow
Journal: Circulation (2016)

Introduction: In some instances, out of hospital cardiac arrest (OHCA) patients receiving bystander CPR and/or defibrillation by a public access AED (PAD) are successfully resuscitated prior to EMS...
Abstract 10806: The Role of Neuronal Nitric Oxide Synthase on the Vascular Hyporeactivity and Multiple Organ Failure Associated With Hemorrhagic Shock
Authors: Regina Sordi, Fausto Chiazza, Massimo Collino, Jamil Assreuy, Christoph Thiemermann
Journal: Circulation (2015)

Introduction: Trauma can cause severe hemorrhage leading to a state of global ischemia and hemorrhagic shock (HS), resulting in multiple organ failure (MOF) and death. Several studies have shown the participation of nNOS-derived NO in the pathogenesis of the systemic inflammatory response and sepsis. However, the role of nNOS in HS is poorly understood. Hypothesis: The aim of this study is to investigate the role of nNOS-derived NO in the MOF associated with HS. Methods: Rats were subjected to HS under sodium thiopental anesthesia (120 mg/kg; i.p.). The blood pressure was reduced to 30 ± 2 mmHg for 90 min, followed by resuscitation with the shed blood. Rats were treated with 3 different nNOS inhbitors (S-methyl-L-thiocitrulline, ARL 17477 or 7 nitroindazol) or vehicle upon resuscitation. Four hours later, organ injury and dysfunction and the signaling events involved in the observed protective effects of nNOS inhibitors were investigated. Results: When compared to sham rats, HS resulted in a significant decrease in creatinine clearance and rises in serum creatinine, creatine kinase, lactate, aspartate and alanine aminotransferases, indicating the development of MOF. HS also resulted in vascular hyporeactivity to norepinephrine. Treatment of HS-rats with nNOS inhibitors protected animals against the MOF and vascular dysfunction induced by HS. When compared to HS control, analysis of kidney and liver tissue from HS rats treated with nNOS inhibitors revealed decreases in phosphorylation of IκB and p65 nuclear translocation of NF-κB, reduction in iNOS expression, NOx production and protein nitrosylation. nNOS inhibitors treatment also attenuated systemic pro-inflammatory cytokines formation. Conclusions: Our findings show that nNOS inhibition at the onset of resuscitation protects rats against the MOF and vascular dysfunction associated with HS thorough the attenuation of NF-κB activation and consequent reduction of NF-κB-dependent proteins (such as iNOS and pro-inflammatory cytokines), and thorough the attenuation of proteins nitrosylation by NO-derived species.
High Prevalence of Sleep Apnea Syndrome in Patients With Long-Term Pacing
Authors: StéphaneGarrigue, Jean-LouisPépin, PascalDefaye, FrancisMurgatroyd, YannPoezevara, JacquesClémenty, PatrickLévy
Journal: Circulation (2007)

Background— Cardiovascular diseases leading to pacemaker implantations are suspected of being associated with a high rate of undiagnosed sleep apnea syndrome (SAS). We sought to determine the prevalence and consequences of SAS in pacemaker patients according to pacing indications: heart failure, symptomatic diurnal bradycardia, and atrioventricular block. Methods and Results— Ninety-eight consecutive patients (mean age, 64±8 years) not known to have sleep apnea were included; 29 patients were paced for dilated cardiomyopathy (29%), 33 for high-degree atrioventricular block (34%), and 36 for sinus node disease (37%). All underwent Epworth Sleepiness Scale assessment and polysomnography with the pacemaker programmed to right ventricular DDI pacing mode (lower pacing rate, 50 pulses per minute). SAS was defined as an apnea-hypopnea index ≥10/h. Mean Epworth Sleepiness Scale was in the normal range (7±4), although 13 patients (25%) had an abnormal score >11/h. Fifty-seven patients (59%) had SAS; of these, 21 ...
Abstract 2127: RSK2 phosphorylates T-bet to attenuate colon cancer metastasis and growth
Authors: Ke Yao, Cong Peng, Yuwen Zhang, Tatyana A. Zykova, Mee-Hyun Lee, Hanyong Chen, Joohyun Ryu, Enyu Rao, Wei-Ya Ma, kangdong liu, Ann M. Bode, Bing Li, zigang dong
Journal: Cancer Research (2018)

Abstract Metastasis is the major cause of death for patients with solid malignancies. Approximately 80 and 20% of colorectal cancer (CRC) patients develop liver metastasis and lung metastasis, respectively. We found that at different stages of colon cancer, the patients' interferon (IFN) γ secretion from peripheral blood mononuclear cells (PBMCs), was decreased compared with healthy people. The ribosomal S6 kinase (RSK) family of kinases has multiple cellular functions, and we examined their role in this observed IFNγ decrease. Flow cytometry analysis of wild-type (WT) and RSK2 knockout (KO) mice, revealed that the level of IFNγ was significantly lower in RSK2 KO mice as compared to WT mice. Since IFNγ is a component of immunity, which contributes to protection against metastatic carcinomas, a colon cancer liver metastasis experiment was conducted. We found that metastasis was significantly increased in RSK2 KO mice, compared to WT mice. Transcription factor T-bet can directly activate Ifnγ gene transcription. In vitro kinase assay results showed that RSK2 phosphorylated T-bet at serines 498 and 502. We show that phosphorylation of T-bet by RSK2 is required for IFNγ expression, because knocking down RSK2 expression or over-expressing T-bet S498A/S502A mutants reduces IFNγ mRNA expression. To verify the function of the phosphorylation sites, a constitutively active mutant T-bet (S498E/S502E) was over-expressed in bone marrow. Mutant T-bet restored the IFNγ mRNA levels and dramatically reduced the metastasis rate in these mice. Overall, these results indicate that phosphorylation of T-bet is required for inhibiting colon cancer metastasis and growth through a positive regulation of RSK2/T-bet/IFNγ signaling. Citation Format: Ke Yao, Cong Peng, Yuwen Zhang, Tatyana A. Zykova, Mee-Hyun Lee, Hanyong Chen, Joohyun Ryu, Enyu Rao, Wei-Ya Ma, kangdong liu, Ann M. Bode, Bing Li, zigang dong. RSK2 phosphorylates T-bet to attenuate colon cancer metastasis and growth [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 2127.
Meta-analysis to Evaluate High-Dose Therapy Followed by Stem Cell Transplant in Patients With Multiple Myeloma—Reply
Authors: Binod Dhakal, Aniko Szabo, Parameswaran Hari
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Abstract 13205: Validation of a Risk Score for Hospitalization for Heart Failure in Atrial Fibrillation Patients: From the Fushimi Af Registry
Authors: MoritakeIguchi, HisashiOgawa, NobutoyoMasunaga, MitsuruIshii, MasahiroEsato, Yeong-HwaChun, HiromichiWada, KojiHasegawa, MitsuruAbe, MasaharuAkao
Journal: Circulation (2014)

Purpose: Heart failure (HF) is the important comorbidity associated with atrial fibrillation (AF) and related to poor prognosis. Previous study showed H2ARDD score (H2: Heart disease (valvular heart disease, coronary heart disease, myocardial infarction, and cardiomyopathy), A: Anemia (hemoglobin<11 g/dl), R: Renal dysfunction (estimated glomerular filtration rate<60 ml/min/m2), D: Diabetes mellitus, D: Diuretics) efficiently identify the population of patients with AF at high risk of HF events. We investigated the effectiveness of H2ARDD score in one-year outcomes of the Fushimi AF registry. Methods: The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Kyoto, Japan. Fushimi-ku is densely populated with a total population of 283,000, and is assumed to represent a typical urban community in Japan. At present, we have enrolled 3,821 patients (1.3% of total population) from March 2011 to April 2014. One-year follow-up was completed in 3,1...
Insulin Resistance, Hyperlipidemia, and Hypertension in Mice Lacking Endothelial Nitric Oxide Synthase
Authors: HervéDuplain, RémyBurcelin, ClaudioSartori, StéphaneCook, MarcEgli, MattiaLepori, PeterVollenweider, ThierryPedrazzini, PascalNicod, BernardThorens, UrsScherrer
Journal: Circulation (2001)

Background Insulin resistance and arterial hypertension are related, but the underlying mechanism is unknown. Endothelial nitric oxide synthase (eNOS) is expressed in skeletal muscle, where it may govern metabolic processes, and in the vascular endothelium, where it regulates arterial pressure. Methods and Results To study the role of eNOS in the control of the metabolic action of insulin, we assessed insulin sensitivity in conscious mice with disruption of the gene encoding for eNOS. eNOS−/− mice were hypertensive and had fasting hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose uptake than control mice. Insulin resistance in eNOS−/− mice was related specifically to impaired NO synthesis, because in equally hypertensive 1-kidney/1-clip mice (a model of renovascular hypertension), insulin-stimulated glucose uptake was normal. Conclusions These results indicate that eNOS is important for the control not only of arterial pressure but also of glucose and lipid homeostasis. A single...
Attenuation of Nitrate Tolerance and Oxidative Stress by an Angiotensin II Receptor Blocker in Patients With Coronary Spastic Angina
Authors: NobutakaHirai, HiroakiKawano, HirofumiYasue, HidekiShimomura, ShinzoMiyamoto, HirofumiSoejima, IchiroKajiwara, TomohiroSakamoto, MichihiroYoshimura, HajimeNakamura, JunjiYodoi, HisaoOgawa
Journal: Circulation (2003)

Background— Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by the rapid development of tolerance. Recently, the renin-angiotensin system has been suggested to play an important role in the development of nitrate tolerance. Methods and Results— Sixty-four patients with coronary spastic angina were investigated to clarify the effect of angiotensin II type 1 receptor blocker (ARB) therapy on nitrate tolerance. Transdermal nitroglycerin (10 mg/d) and an ARB (candesartan, 8 mg/d) were administered to 21 patients (GTN+ARB group) for 3 days, whereas transdermal nitroglycerin and placebo were administered to 19 patients (GTN group). Another 18 patients were treated with placebo skin patches and placebo tablets for 3 days (control group). The brachial artery response to incremental doses of intravenous nitroglycerin (0.01, 0.1, and 1.0 μg/kg) was measured by ultrasound before and after transdermal nitroglycerin therapy. Before treatment, the arterial diameter ...
Response to Letters Regarding Article, “Cardiac Arrhythmogenic Remodeling in a Rat Model of Long-Term Intensive Exercise Training”
Authors: BegoñaBenito, GemmaGay-Jordi, AnnaSerrano-Mollar, EduardGuasch, YanfenShi, Jean-ClaudeTardif, JosepBrugada, StanleyNattel, LluisMont
Journal: Circulation (2011)
Abstract 19966: Hemodynamic and Metabolic Correlates of Taurine Sodas or Colas in Healthy Young to Middle-age Adults: The IPC Cohort
Authors: Nicolas Danchin, Sebastien Czernichow, Frederique Thomas, Yedid Elbez, Cedric Lemogne, Jean-Marc Simon, Olivier Hanon, Tabassome Simon, Bruno Pannier
Journal: Circulation (2015)

Background: The hemodynamic and metabolic correlates of specific sodas have not been extensively studied. We used data from the IPC cohort, a large cohort of presumably healthy individuals having a general medical work-up reimbursed by the French National Health Insurance, to determine blood pressure, heart rate, BMI, waist circumference, glycemia, and LDL-cholesterol according to soda drinking habits. A self-administered questionnaire recorded daily habits for drinking colas or taurine sodas, with a 3-grade scale (no daily consumption, average daily consumption of 1-4 drinks, average daily consumption &gt;= 4 drinks. Because consumption of taurine sodas and colas strongly declined after 50 years, only individuals aged 50 years or less (n=26,127) were included in the present analysis. Results: Daily consumption of colas and taurine drinks was reported in 8614 (33%) and 657 (2.5%) individuals, respectively. Compared with non-drinkers, cola and taurine soda consumers were younger (37 vs 34 vs 29 years, respectively, P&lt;0.001), more often male (54 vs 58 vs 73%), more often socially deprived (8% vs 10% vs 10%), and more often current smokers (23% vs 33%, vs52%). After adjustment for age, sex, education, social status, and smoking status cola consumption was associated with slightly but significantly elevated BMI, waist circumference, blood pressure and heart rate, with no difference for fasting glucose or LDL-c. Taurine soda consumers had significantly higher BMI, and a trend to higher systolic blood pressure. Conclusion: Daily consumption of colas was associated with a modest increase in hemodynamic risk factors and body mass index, and the association with taurine sodas was essentially similar. Overall, very high consumers (5+ drinks per day) had hemodynamic nd metabolic effects similar to those of milder daily consumers.
Abstract 1986: IRAK1 augments cancer stemness and drug resistance via the AP-1/AKR1B10 signaling cascade in hepatocellular carcinoma
Authors: Bowie Yik Ling Cheng, Doris Hoi Wing Leung, Eunice Yuen Ting Lau, Irene Oi Lin Ng, Kin Wah Lee
Journal: Cancer Research (2018)

Abstract Frequent relapse and drug resistance can be attributed to the existence of tumor-initiating cells (T-ICs) within the tumor bulk. From transcriptome sequencing of 16 pairs of clinical HCC samples, we found that Interleukin-1 receptor-associated kinase 1 (IRAK1) in the TLR/IRAK pathway was significantly upregulated in hepatocellular carcinoma (HCC). IRAK1 overexpression in HCC was further confirmed at the mRNA and protein levels and correlated with advanced tumor stages and poor patents survival. Interestingly, IRAK4, an upstream regulator of IRAK1, was also found to be consistently upregulated. We demonstrated that IRAK1 regulates liver T-IC properties, including self-renewal, tumorigenicity and liver T-IC marker expression. IRAK1 inhibition sensitized the HCC cells to doxorubicin and sorafenib treatment in vitro through the suppression of the apoptotic cascade. Pharmacological inhibition of IRAK1 with a specific IRAK1/4 kinase inhibitor consistently suppressed liver T-IC populations. Through RNA sequencing analysis by comparing gene expression profiles between IRAK1-knockdown and control cells, we identified Aldo-Keto Reductase Family 1 Member 10 (AKR1B10) as a novel downstream target of IRAK1. Clinically, AKR1B10 was found to be overexpressed in HCC, which was significantly correlated with IRAK1 expression. Functional analysis demonstrated that knockdown of AKR1B10 negated the IRAK1-induced T-IC functions via modulation of the AP-1 complex. Using an HCC xenograft model, we found that an IRAK1/4 inhibitor in combination with sorafenib synergistically suppressed the tumor growth. In conclusion, targeting the IRAK4/IRAK1/AP-1/AKR1B10 signaling pathway may be a potential therapeutic strategy against HCC. Citation Format: Bowie Yik Ling Cheng, Doris Hoi Wing Leung, Eunice Yuen Ting Lau, Irene Oi Lin Ng, Kin Wah Lee. IRAK1 augments cancer stemness and drug resistance via the AP-1/AKR1B10 signaling cascade in hepatocellular carcinoma [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 1986.
Abstract 18801: Light-intensity Physical Activity After Discharge Predicts 6-month Postdischarge Adverse Events in Older Japanese Patients With Heart Failure
Authors: Naoki Fujimoto, Kaoru Dohi, So Miyahara, Keishi Moriwaki, Taku Omori, Testushiro Takeuchi, Naoto Kumagai, Emiyo Sugiura, Shiro Nakamori, Norikazu Yamada, Masaaki Ito
Journal: Circulation (2015)

Introduction: Moderate physical activity (PA) is recommended in patients with heart failure (HF). However, patient’ characteristics in those with low PA and the impact of light-intensity PA on postdischarge major adverse cardiovascular events (MACE) remain unclear in older Japanese HF patients. Methods: Thirty seven patients (Stage C/D: 76±5 yrs, 21m) who had been admitted due to HF and 23 Stage A/B patients (73±5 yrs) with risk factors were enrolled. PA was measured using the Omuron HJ350IT accelerometer from the day of discharge for 7 days. Light-intensity PA at an intensity of 1.5-3.0 metabolic equivalents (METs), moderate-intensity PA (≥3METs), and total PA were determined. At discharge, knee-extensor muscle strength, 6-min walking distance (6MWD),SF-36 score, and left ventricular (LV) structure by echocardiography were evaluated. Stage C/D patients were stratified into High-PA and Low-PA according to the median total PA value of 8.4 METs·hour/day. Stage A/B patients underwent these measurements, and values were compared. Factors related to the 6-month postdischarge MACE were assessed. Results: Stage C/D patients were anemic, took fewer steps per day, and had higher brain natriuretic peptide (BNP) than Stage A/B patients. Patients in Low-PA were less likely to engage in household work, and had shorter active time, fewer steps per day, and lower light- and moderate-intensity PA than those in High-PA. No differences were observed in 6MWD (263±110 vs. 303±77 m), knee-extensor muscle strength, BNP (405±346 vs. 267±179 pg/ml), SF-36 physical composite score, or LV ejection fraction between Low-PA and High-PA. Light-intensity and total PA, but not moderate-intensity PA, were associated with the 6-month postdischarge MACE through univariate analyses. Multivariate regression analysis showed that total PA was the independent predictor of the 6-month postdischarge MACE (odds ratio: 0.66) among functional capacity variables including 6MWD and knee-extensor muscle strength. Conclusions: Physical activity, especially at light-intensity, is inversely associated with the 6-month postdischarge MACE in older HF patients. Our results may indicate that postdischarge PA assessed by accelerometer is useful to distinguish those at high risks for MACE.