tbuckley/cabot-search huggingface dataset:
Abstract 3488: Elucidation of Warburg effect and cell cycle regulations through analysis of cancer tissue omics data and kinetic modeling
Authors: Tao Sheng
Journal: Cancer Research (2018)

Abstract Cancer cells tend to depend more on anerobic glycolysis to generate adenosine 5'- triphosphate (ATP), which is an inefficient energy producing process termed as “The Warburg effect”. The causes or functions of Warburg effect have been extensively studied, however, the growth advantage it confers to cancer cells still remains unclear. In this study, we propose that the metabolic shift in cancer cells would facilitate the accumulation of nutrients and biomass (e.g., nucleotides, amino acids and lipids), which would promote the cell cycle initiation and progression as unicellular organisms do. Specifically, by comprehensively analyze the gene expression and mutational profile in 16 cancer types, we identified (1) the gene expression profile of cancer cells is evolutionarily more unicellular like when compared to normal; and (2) certain cell cycle associated mutations are associated with the metabolic alternations in cancer cells, such as nucleotide synthesis pathways and lipids metabolism. Moreover, we developed a system of kinetic equations to capture the metabolic relations between nutrient metabolism and cell cycle initiation and progression. The kinetic model shows that the rapid nucleotide synthesis as well as high influx of glutamate would affect the activities of cell cycle signaling and CDKs genes. Our study provides a novel mechanistic view in linking the Warburg effect and cancer cell cycle initiation and progression. Citation Format: Tao Sheng. Elucidation of Warburg effect and cell cycle regulations through analysis of cancer tissue omics data and kinetic modeling [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 3488.
Abstract 13104: Comparison of Patient Characteristics and Outcomes Between Adult Non-traumatic Out-of-hospital Cardiac Arrests With and Without Extracorporeal Cardiopulmonary Resuscitation - A Community-wide Evaluation
Authors: Patrick Chow-In Ko, Nai-Kuan Chou, Matthew Huei-Ming Ma, Yu-Wen Chen, Tzong-Luen Wang, Wen-Han Chang, Wei-Fong Kao, Young-Long Wu, Bin-Chou Lee, Ying-Ju Chen, Mei-Fen Yang, Yueh-Ping Liu, Hsien-Tang Lin, Chi-Hung Lin, Allen Wen-Hsiang Chiu, Yih-Sharng Chen
Journal: Circulation (2015)

Objectives: The outcome of patients after OHCA is poor. Return to spontaneous circulation (ROSC) dramatically decreases with the duration of CPR. Extracorporeal membrane oxygenation has been proposed to assist CPR (ECPR) in OHCA. This study was to investigate the effects and characteristics of ECPR for adult non-traumatic (ANT) OHCA versus Non-ECPR on a community-wide basis. Methods: A prospective four-year observational database collected from a community-wide OHCA web registry in an urban EMS (emergency medical services) was studied. The EMS ambulance teams were capable with advanced airway, intravenous (iv) fluid skills, basic and advanced life support and automated external defibrillator techniques. Outcomes included survival and cerebral performance category scale (CPC) at discharge. ANT OHCA with and without ECPR in emergency were compared by regression analysis including factors of patient, pre-hospital and hospital characteristics and outcomes. Results: Comparing OHCA receiving ECPR (n=79) to those without (n=959), ECPR group were younger (median age 56 vs 78 p&lt;0.001) and had higher portion for men (89 vs 64% p&lt;0;001), witnessed arrest (Wit) (60.8 vs 32.5% p&lt;0.001), bystander CPR (BCPR) (53.2 vs 36.8% p=0.005), initial shockable rhythms (SR) (74.6 vs 12.2% p&lt;0.001) and therapeutic hypothermia (TH) (22.8 vs 1.1%, p&lt;0.001). They (EPCR vs non-ECPR) had no difference for prehospital time intervals (22.5 vs 23 min.), laryngeal mask airway treatment (55.7 vs 52.8%), EMS iv epinephrine (20.3 vs 15.5%), endotracheal intubation (6.3 vs 8.0%), prehospital ROSC (11.4 vs 6% p=0.09), and ROSC upon hospital arrival (10.1 vs 8.5%). Outcomes were better in ECPR for discharged survival (41 vs 7% p&lt;0.001) and CPC 1or2 (20.8 vs 3.8% p&lt;0.001). After adjusting for Wit, BCPR, SR, TH, age and sex, both survival (adjusted odds ratio: 3.6 [95% 2.0-6.6]) and good CPC 1or2 (adjusted OR: 2.9 [95% 1.2-6.9]) were still significantly higher in ECPR. Conclusions: In current emergency practice for ANT OHCA, ECPR tended to apply to patients of younger age, men, witnessed arrest, BCPR, and initially shockable rhythms regardless of positive ROSC upon hospital arrival, that can independently lead to higher survival and good neurological outcome compared to non-ECPR.
Abstract 3981: Exosomal microRNA profiles in peritoneal fluids as a therapeutic biomarker for peritoneal metastasis of gastric cancer
Authors: Hideyuki Ohzawa, Akira Saito, Yuko Kumagai, Hironori Yamaguchi, Yoshinori Hosoya, Naohiro Sata, Joji Kitayama
Journal: Cancer Research (2019)

Abstract Objectives: Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer and has poor prognosis even with systemic chemotherapy. Intraperitoneal chemotherapy (IPC) using paclitaxel (PTX) combined with systemic chemotherapy has demonstrated a remarkable clinical efficacy for gastric cancer with PM. However, there is no reliable biomarker to reflect the response of peritoneal lesions as well as to predict the outcome of the patients receiving IPC. Although peritoneal fluids are considered to contain many factors derived from disseminated tumor cells in peritoneal cavity, little information is available so far. In this study, we examined exosomal miRNA profiles derived from peritoneal fluids in patients with gastric cancer and explored possible biomarkers useful for IPC of the patients with PM. Methods: Peritoneal fluids were collected from 2 groups; with or without PM. Peritoneal fluids were obtained either laparoscopically, during open surgery or from subcutaneous infusion port connected to an intraperitoneal catheter. Exosomal fractions were isolated using ultracentrifuge method (150,000 xg, 70 min, 4°C) and the presence of exosome was confirmed with nanotracking analysis. Total RNA including small RNA was extracted from exosomal fractions and expression analyses of miRNAs were performed using RT-PCR. Results: At first, we comprehensively analyzed the expression of miRNAs between 11 samples with PM and 14 samples without PM and identified 11 miRNAs which showed particularly different expression pattern between the 2 groups. Among them, 4 miRNAs (miR-21-5p,miR-223-3p, miR-342-3p and miR-92a-3p) were selected and further analysed using 51 samples derived from the peritoneal fluids of gastric cancer. Expression of these 4 miRNAs were significantly up-regulated in samples with PM which was consistent with formeranalysis. Moreover, expression of miR-21-5p was significantly upregulated in in samples fromT4 tumor (invaded serosa or adjacent structure) as compared with those from T1 to T3 tumor. Conclusion: We identified several dysregulated exsosomal miRNAs derived from peritoneal fluids of the patients with PM from gastric cancer, which were supposed to reflect the tumor burden on peritoneum. Exosomal miRNA profiles might be useful biomarkers to determine the presence of PM as well as the response to IPC. Citation Format: Hideyuki Ohzawa, Akira Saito, Yuko Kumagai, Hironori Yamaguchi, Yoshinori Hosoya, Naohiro Sata, Joji Kitayama. Exosomal microRNA profiles in peritoneal fluids as a therapeutic biomarker for peritoneal metastasis of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3981.
Abstract 12298: Inducible Nitric Oxide Synthase Expression in Mesenchymal Stromal Cells Induces Immunomodulation but Enhances Tumorigenic Conversion in Allogenic Cell Sheet Transplantation for Rat Myocardial Infarction
Authors: YukikoImanishi, EskoKankuri, AnttiSiltanen, ShigeruMiyagawa, SatsukiFukushima, YoshikiSawa, AriHarjula
Journal: Circulation (2014)

Background: Mesenchymal stromal cell (MSC) reportedly induce immune tolerance against allogenic antigens via inflammation-related expression of inducible nitric oxide synthase (iNOS). Combination of MSC may be promising therapeutic option in treating allogenic cell for cell therapy. However, tumorigenic conversion of MSCs is a major concern. Here, we hypothesized that immunomodulation property induced by iNOS in MSC impacts their tumorigenic conversion. We evaluated tumor formation following combined transplantation of iNOS-expressing MSCs with allogenic skeletal myoblasts in a rat model of myocardial infarction. Methods and Results: Fischer rat-derived MSCs were prepared as a cell sheet for transplantation on the surface of the infarcted or normal myocardium of Wistar rats. Seven days after transplantation, iNOS expression of the cell sheet which was transplanted on the infarcted myocardium was greater than that transplanted on the normal myocardium. Next, iNOS expression in the MSC was enhanced by inter...
Circadian Rhythms of Cardiovascular Functions Are Modulated by the Baroreflex and the Autonomic Nervous System in the Rat
Authors: MitsutakaMakino, HiroshiHayashi, HirotoTakezawa, MakotoHirai, HidehikoSaito, ShizufumiEbihara
Journal: Circulation (1997)

Background We assessed the hypothesis that the baroreflex and the autonomic nervous system are important in the control of the circadian rhythms of cardiovascular functions. Methods and Results We continuously measured blood pressure (BP), heart rate (HR), and locomotor activity in sinoaortic denervated (SAD), sympathectomized, and atropine-injected rats by use of a radiotelemetry system. The circadian rhythm of mean blood pressure (MBP) was selectively disrupted in SAD rats under 12-hour light-dark (LD12:12) cycles as a result of an increase in MBP during the light period and disappeared under constant darkness (DD). The locomotor activity and HR were not remarkably affected by SAD. The circadian rhythm of MBP was suppressed in sympathectomized rats by a decrease in the MBP during the dark period, and the abrupt changes in MBP when the lighting was altered were not seen under LD. Under DD, an MBP rhythm similar to that observed under LD was obtained. Sympathectomized rats also showed lower HR levels duri...
Sodium chloride is an ionic checkpoint for human T <sub>H</sub> 2 cells and shapes the atopic skin microenvironment
Authors: Julia Matthias, Julia Maul, Rebecca Noster, Hanna Meinl, Ying-Yin Chao, Heiko Gerstenberg, Florian Jeschke, Gilles Gasparoni, Anna Welle, Jörn Walter, Karl Nordström, Klaus Eberhardt, Dennis Renisch, Sainitin Donakonda, Percy Knolle, Dominik Soll, Stephan Grabbe, Natalie Garzorz-Stark, Kilian Eyerich, Tilo Biedermann, Dirk Baumjohann, Christina E. Zielinski
Journal: Science Translational Medicine (2019)

Sodium chloride induces and amplifies human T H 2 cell responses, potentially shaping the atopic skin microenvironment.
Targeted Proteolysis Sustains Calcineurin Activation
Authors: NatalieBurkard, JanBecher, CorneliaHeindl, LudwigNeyses, KaiSchuh, OliverRitter
Journal: Circulation (2005)

Background— Calcineurin (CnA) is important in the regulation of myocardial hypertrophy. We demonstrated that targeted proteolysis of the CnA autoinhibitory domain under pathological myocardial workload leads to increased CnA activity in human myocardium. Here, we investigated the proteolytic mechanism leading to activation of CnA. Methods and Results— In patients with diseased myocardium, we found strong nuclear translocation of CnA. In contrast, in normal human myocardium, there was a cytosolic distribution of CnA. Stimulation of rat cardiomyocytes with angiotensin (Ang) II increased calpain activity significantly (433±11%; P<0.01; n=6) and caused proteolysis of the autoinhibitory domain of CnA. Inhibition of calpain by a membrane-permeable calpain inhibitor prevented proteolysis. We identified the cleavage site of calpain in the human CnA sequence at amino acid 424. CnA activity was increased after Ang II stimulation (310±29%; P<0.01; n=6) and remained high after removal of Ang II (214±17%; P<0.01; n=6)...
Immunomodulatory function of surfactant protein D in eosinophilic asthma
Authors: Youngwoo Choi, Dong‐Hyun Lee, Ji‐Ho Lee, Yoo Seob Shin, Seung‐Hyun Kim, Hae‐Sim Park
Journal: Allergy (2018)

The authors declare no competing financial interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Inhibition of MEF2A Using 3rd Generation Antisense Enhances Neovascularization via Posttranscriptional Regulation of 14q32 MicroRNAs miR-329 and miR-494
Authors: S. Welten, M. de Vries, E. Peters, S. Agrawal, P. Quax, A.Y. Nossent
Journal: Circulation (2016)

Introduction and Hypothesis: The 14q32 locus encodes 54 individual microRNAs. Inhibition of 14q32 microRNAs leads to improved blood flow recovery after ischemia. Snyder et al (Development 2013) sho...
Abstract 4713: BET bromodomain inhibition synergizes with PD-1 blockade to facilitate anti-tumor response in <i>Kras</i>-mutant non-small cell lung cancer
Authors: Dennis O. Adeegbe, Shengwu Liu, Michaela Bowden, Peter S. Hammerman, James E. Bradner, Anil K. Rustgi, Adam J. Bass, Gordon J. Freeman, Huawei Chen, kwok-Kin Wong
Journal: Cancer Research (2018)

Abstract KRAS mutation is present in about 30% of human lung adenocarcinomas. While recent advances in targeted therapy have shown great promise, KRAS remains undruggable and concurrent alterations in tumor suppressors render KRAS mutant tumors even more resistant to existing therapies. Contributing to the refractoriness of KRAS mutant tumors harboring these co-mutations are immunosuppressive mechanisms such as increased presence of suppressive Tregs in tumors and elevated expression of the inhibitory receptor PD-1 on tumor-infiltrating T cells. BET bromodomain inhibitors demonstrate clinical benefit in hematologic malignancies, and prior reports demonstrate their Treg-disruptive effects in a NSCLC model. Targeting PD-1 inhibitory signals through anti-PD-1 antibody blockade has also shown substantial therapeutic impact in lung cancer although these outcomes are still limited to a minor pool of patients. We therefore hypothesized that the BET bromodomain inhibitor JQ1 would synergize with PD-1 blockade to promote robust anti-tumor response in lung cancer. In the present study, using Kras+/LSL-G12D; Trp53L/L (KP) mouse models of non-small cell lung cancer, we identified cooperative effects among JQ1 and anti-PD-1 that included reduced numbers of tumor-infiltrated Tregs and enhanced activation of tumor-infiltrating T cells, which exhibited a Th1 cytokine profile that favored their demonstrated improved effector function. Furthermore, lung-tumor-bearing mice under this combinatorial treatment regimen showed robust and long-lasting anti-tumor responses compared to either agent alone, culminating in substantial improvement in the survival of treated mice. Thus, combining BET bromodomain inhibition with immune checkpoint blockade offers a promising therapeutic approach for solid malignancies such as lung adenocarcinoma. Citation Format: Dennis O. Adeegbe, Shengwu Liu, Michaela Bowden, Peter S. Hammerman, James E. Bradner, Anil K. Rustgi, Adam J. Bass, Gordon J. Freeman, Huawei Chen, kwok-Kin Wong. BET bromodomain inhibition synergizes with PD-1 blockade to facilitate anti-tumor response in Kras-mutant non-small cell lung 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 4713.
Abstract 3562: Merkel cell polyomavirus t-antigen regulates aggresome formation and autophagy in merkel cell carcinoma
Authors: Hao Shi
Journal: Cancer Research (2018)

Abstract Merkel cell carcinoma (MCC) is an aggressive and deadly skin cancer. About 80% of MCCs harbor integrated Merkel cell polyomavirus (MCV) genome with a mutation in the large T (LT) gene, leading to expression of truncated LT and intact small T (sT). The molecular mechanism how the virus contributes to MCC development is still not fully understood. Paranuclear dot-like staining of cytokeratin 20 is a typical characteristic of MCC. However, it is unexplored whether these dot-like structures are functionally important in MCC. In this study, we aimed to characterize the identity of these dot-like structures and to determine whether MCV T-antigens play a role in the formation of these structures. Using immunostaining, we showed that these structures were co-localized with aggresome markers (including intermediate filaments, BAG3 and HSP70) and were localized at the microtubule organization center, as demonstrated by the presence of γ-tubulin. These structures became dispersed to the periphery upon microtubule depolymerization using colcemid. Similarly, silencing of BAG3 in MCV-positive MCC cells resulted in aggresome clearance. Interestingly, we observed that these structures were associated with MCV-positive MCCs and silencing of MCV T-antigens led to dispersion of the aggresome. Additionally, ectopically expressed truncated, but not wild-type, LT could facilitate aggresome formation in MCV-negative cells. We also showed that silencing of MCV T-antigens induced autophagy in MCV-positive MCC cells, while ectopically expressed MCV T-antigens suppressed autophagy in MCV-negative MCC cells. In conclusion, we uncover a novel role of MCV T-antigen in hijacking cellular degradation pathways, suggesting that the autophagy-aggresome pathway plays important roles in MCV infection and MCC tumorigenesis. Citation Format: Hao Shi. Merkel cell polyomavirus t-antigen regulates aggresome formation and autophagy in merkel cell 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 3562.
Gallop Rhythm of the Heart
Authors: Josephgrayzel
Journal: Circulation (1959)

The 2 fundamental types of gallop are ventricular gallop and atrial gallop. Adequate cardiac acceleration modifies these gallops and may produce a summation gallop, an augmented ventricular gallop, or an augmented atrial gallop. The summation and augmented gallops were examined and their relation to the 2 fundamental gallops was quantitated. The cardiac rate at which summation and augmentation occur is unique. A graph and 2 corresponding equations were derived which relate the summation cardiac rate and corresponding cycle length to familiar electrocardiographic and phonocardiographic intervals.
Atrioventricular Node Modification in Patients With Chronic Atrial Fibrillation
Authors: SteliosRokas, StylianiGaitanidou, SofiaChatzidou, CostasPamboucas, DennisAchtipis, StamatiosStamatelopoulos
Journal: Circulation (2001)

Background—This study evaluates the role of RR interval distribution pattern as an outcome predictor of radiofrequency (RF) modification of atrioventricular (AV) node in chronic atrial fibrillation (AF) and attempts to elucidate the likely mechanism of rate control. Methods and Results—Sixty-five patients with chronic AF underwent AV node modification. The RR interval distribution pattern was derived from 24-hour ECG recordings obtained before and after the procedure. The preablation pattern was bimodal (B) in 36 patients (55%) and unimodal (U) in 29 patients (45%). After the modification procedure, the B pattern shifted to U (78%) or became modified B (22%). The mean number of RF pulses delivered and the fluoroscopy time were n=8±5 and 24±11 minutes, respectively, in patients with B pattern versus n=18±7 and 45±17 minutes in patients with U pattern (P<0.001 for both). The location of successful ablation was posteroseptal and lower midseptal in 26 patients (81%) with B pattern versus 2 (13%) with U patter...
Abstract 18096: Blood Pressure is Increased in Female Mice Lacking Orphan G Protein-Coupled Receptor Gpr37L1
Authors: James L Coleman, Margaret A Mouat, Jianxin Wu, Nikola Jancovski, David T Humphreys, Maurizio Stefani, Cristobal G Dos Remedios, Michael P Feneley, Andrew M Allen, Robert M Graham, Nicola J Smith
Journal: Circulation (2016)

Over 100 mammalian G protein-coupled receptors (GPCRs) are yet to be matched with endogenous ligands; these so-called ‘orphans’ offer hope as novel drug targets in the treatment of disease. One such orphan is GPR37L1; abundant in the brain and shown by our laboratory to be the first protease-inactivated GPCR. A previous study reports genetic deletion of GPR37L1 to cause hypertension and left ventricular hypertrophy (LVH) in mice. Hypothesising that GPR37L1 is a cardiovascular regulator, we investigated the cardiovascular role of GPR37L1 using knockout and reporter mice. GPR37L1wt/wt (WT) and GPR37L1ko/ko (KO) mice were subject to blood pressure (BP) measurement by micromanometry, and LVH was assessed by morphometry and qPCR assays for induction of the fetal gene programme. Intriguingly, we report that the previously described hypertensive phenotype of KO mice is limited to females, which had significantly (p≤0.05) elevated systolic (+11.6 mmHg), diastolic and mean arterial pressures, relative to WT, with ...
Role of Lipoxygenase Metabolites in Ischemic Preconditioning
Authors: ElizabethMurphy, WayneGlasgow, TeresaFralix, CharlesSteenbergen
Journal: Circulation Research (1995)

Abstract Preconditioning with brief intermittent periods of ischemia before a sustained period of ischemia has been shown to reduce infarct size and improve recovery of function in rat hearts. The mediators of this protective response are unknown in rats. We tested the hypothesis that a lipoxygenase metabolite might be involved in preconditioning, since lipoxygenase metabolites such as 12-hydroperoxyeicosatetraenoic acid have been shown to increase K+ channel activity and to decrease Ca2+ channel activity, which could have a protective effect on ischemic injury. In support of this hypothesis, we report that the lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA, 5 μmol/L) and eicosatetraynoic acid (7 μmol/L) added just before and during preconditioning blocked the protective effects of preconditioning on recovery of function during reflow after 30 minutes of global ischemia. In addition, these lipoxygenase inhibitors partially blocked the ability of preconditioning to attenuate the rise in cytosolic ...
Abstract 163: Interleukin-13 Expression Attenuates Left Ventricular Dilation and Mortality After Myocardial Infarction
Authors: UlrichHofmann, SusanneKnorr, JohannesWeirather, AnnaFrey, StefanFrantz
Journal: Circulation Research (2012)

Background: Monocyte infiltration and extracellular matrix breakdown/ de novo formation critically influence wound healing and remodeling after myocardial infarction (MI). Interleukin-13 (IL-13) has potent pro-fibrotic properties and is a differentiation factor for monocytes/ macrophages. Therefore, we studied whether IL-13 affects myocardial wound healing and remodelling after MI. Methods and results: MI was induced by permanent ligation of the left coronary artery in WT and IL-13-/- mice. Expression of IL-13 was upregulated in the myocardium after MI. IL-13 expression was in part dependent on angiotensin II signalling as in vivo treatment with the Angiotensin-receptor blocker losartan attenuated myocardial IL-13 expression in response to MI. Intracellular FACS analysis of myocardial leukocytes further demonstrated IL-13 expression in a subset of myeloid CD11b+ cells within the myocardium. IL-13-/- mice showed higher mortality than WT mice after MI without difference in infarct size. Echocardiography fur...