tbuckley/cabot-search huggingface dataset:
Abstract 11802: Transforming the Convergent Procedure- Thinking Inside the Box
Authors: M. Clive Robinson, Lindsey Scierka
Journal: Circulation (2016)

Introduction: We report on intermediate follow up using a technique of confluent posterior left atrial wall epicardial ablation designed to eliminate both existing and future atrial fibrillation (AF) substrate. Hypothesis: The purpose of this study is to report on our experience with a technique of extended ablation using a confluent pattern of posterior left atrial epicardial lesions combined with endocardial ablation, as part of the Convergent hybrid closed chest procedure, performed in a single setting. Methods: Multiple confluent epicardial ablations with radiofrequency energy were delivered spanning the vertical and transverse dimensions of the posterior left atrium, along with facilitated pulmonary vein isolation (PVI). Endocardial mapping and ablation were performed to complete PVI and ablate the cavo-tricuspid isthmus. All patients were followed clinically and with 2 to 4 weekly continuous monitoring at 6, 12, and 24 months. Average follow-up was 488 days. Results: Of 57 patients with long-standing or persistent AF (NPAF), mean duration of AF was 5.6 years. Single procedure freedom from AF at 24 months was 64.5% and for all arrhythmias was 58.9%. Sixty-eight percent were off antiarrhythmic drugs (AADs). Four patients (7%) required a second endocardial ablation procedure. Sub-analysis of the observed arrhythmia burden through follow-up showed it to be small (0 to less than 1%) in the majority of patients. Conclusions: This extended posterior wall ablation technique, as part of the Convergent hybrid method, achieved notable single procedure success in a consecutive series of patients with NPAF.
Abstract 18119: Lesion Formation in Atrial Fibrillation Ablation: Integration of Force Sensing Catheter With LGE-MRI
Authors: Mihail G Chelu, Alan Morris, Eugene G Kholmovski, Gagandeep Kaur, Nassir F Marrouche
Journal: Circulation (2016)

Introduction: Contact force (CF) is a critical factor in lesion formation during radiofrequency (RF) atrial fibrillation (AF) ablation. Late gadolinium enhancement magnetic resonance imaging (LGE-M...
Abstract 780: Molecular chaperone is a novel biomarker for disease outcome in multiple myeloma
Authors: Yingqi Li, Ping L. Zhang, Zihai Li, Bei Liu
Journal: Cancer Research (2018)

Abstract Multiple myeloma (MM) is an incurable plasma cell neoplasm whose pathogenesis is closely linked to dysregulated unfolded protein response (UPR) in the endoplasmic reticulum (ER). MM typically evolves from an asymptomatic premalignant stage called monoclonal gammopathy of undetermined significance (MGUS), to an intermediate asymptomatic smoldering MM (SMM), to eventually symptomatic MM. However, no single pathologic or molecular biomarker can be used to distinguish MM patients from SMM, who have clonal premalignant plasma cells from those with clonal myeloma cells. Therefore, there is a compelling need for further development of novel diagnosis and prognosis biomarkers for MM. Heat shock protein grp94 is a key downstream chaperone in the ER to mediate UPR. Using genetic approaches, we have demonstrated that grp94 is an obligate chaperone for Wnt co-receptor low-density lipoprotein receptor-related protein 6 and that it is required for multiple myeloma cell survival, which is mediated in part by the Wnt target survivin. Moreover, we found that grp94 is highly expressed in malignant plasma cells in MM, and the higher level of grp94 is significantly associated with more advanced stage of this disease. Additionally, the grp94 expression is significantly associated with the levels of serum M protein in MM patients, but not in patients with MGUS and SMM. Thus, our studies demonstrated that molecular chaperone grp94 is a novel diagnostic and prognostic biomarker for MM as well as a potential target for treatment of this disease. Citation Format: Yingqi Li, Ping L. Zhang, Zihai Li, Bei Liu. Molecular chaperone is a novel biomarker for disease outcome in multiple myeloma [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 780.
Abstract 3070: Cancer stem cells in field cancerization of oral squamous cell carcinoma
Authors: Simple Mohanta, Ravindra DR, Vikram Kekatpure, Naveen Hedne, Vijay Pillai, Shubhra Chauhan, Naveen BS, Athira Ramakrishnan, Bichu Jacob, Vishak Surendra, Leeky Mohanty, Anjana Muralidharan, Amritha Suresh, Moni Abraham Kuriakose
Journal: Cancer Research (2018)

Abstract Introduction: Field cancerization, the occurrence of transformed cells in the area adjacent to the tumor, has been attributed to the probable reasons of local recurrence of oral squamous cell carcinoma. Cancer stem cells (CSCs) have properties of tumor initiation, migration, and metastasis. The objective of the study was to evaluate their role in field cancerization. Experimental Procedure: A panel of CSCs and its related markers was established from literature and validated in i) samples from surgical margins, ii) samples from 1 cm and 2 cm distance from margin around the tumor and in additional sides. First-phase validation was done in retrospective surgical margins of tumor (N=23) by qPCR and immunohistochemistry. The best marker subset from qPCR to predict recurrence was identified by ROC curve and logistic regression analysis and validated by immunohistochemistry. The final validation is being carried out in prospective samples from tumor-adjacent normal area as mentioned above. The marker profiles were correlated with the histology of the samples and the clinical outcome of the patients on follow-up. Summary of Data: Out of 18 markers selected from literature CD44, CD147, SOX2, Snail, ATR, CyclinD1, MMP9 were selected from gene expression of first-phase validation. Among these SOX2, ATR, Cyclin D1, CD44 and CD147 were selected from IHC of first phase for second-phase validation in prospective samples (n=10) collected from 27 patients, which were clinically normal with varied grades of dysplasia; these samples were evaluated by the selected markers from the first set of validation. The correlation of markers expression with disease outcome of patients and with other clinical parameters is currently ongoing. Conclusion: Our results suggest that CSCs have role in field cancerization and might be predictive of tumor recurrence/reinitiation and/or development of second primary tumor. Citation Format: Simple Mohanta, Ravindra DR, Vikram Kekatpure, Naveen Hedne, Vijay Pillai, Shubhra Chauhan, Naveen BS, Athira Ramakrishnan, Bichu Jacob, Vishak Surendra, Leeky Mohanty, Anjana Muralidharan, Amritha Suresh, Moni Abraham Kuriakose. Cancer stem cells in field cancerization of oral squamous 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 3070.
Establishment of a Simple and Practical Procedure Applicable to Therapeutic Angiogenesis
Authors: ShinichiKanno, NobuyukiOda, MayumiAbe, SachikoSaito, KatsuyoshiHori, YasunobuHanda, KoichiTabayashi, YasufumiSato
Journal: Circulation (1999)

Background—Therapeutic angiogenesis is thought to be beneficial for serious ischemic diseases. This investigation was designed to establish a simple and practical procedure applicable to therapeutic angiogenesis. Methods and Results—When cultured skeletal muscle cells were electrically stimulated at a voltage that did not cause their contraction, vascular endothelial growth factor (VEGF) mRNA was augmented at an optimal-frequency stimulation. This increase of VEGF mRNA was derived primarily from transcriptional activation. Electrical stimulation increased the secretion of VEGF protein into the medium. This conditioned medium then augmented the growth of endothelial cells. The effect of electrical stimulation was further confirmed in a rat model of hindlimb ischemia. The tibialis anterior muscle in the ischemic limb was electrically stimulated. The frequency of stimulation was 50 Hz and strength was 0.1 V, which was far below the threshold for muscle contraction. After a 5-day stimulation, there was a sign...
Abstract 5339: Epigenetic silencing of ANGPTL4 in tumor tissues and its overexpression in the urothelial carcinoma microenvironment
Authors: Michael WY Chan, Hsiao-Yen Hsieh, Yeong-Chin Jou, Chun-Liang Tung, Yuh-Shyan Tsai, Yuan-Hung Wang, Chen-Lin Chi, Ru-Inn Lin, Shih-Kai Hung, Yu-Ming Chuang, Shu-Fen Wu, Chin Li, Cheng-Huang Shen, Cheng-Da Hsu
Journal: Cancer Research (2018)

Abstract Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor suppressor genes (TSGs). By qRT-PCR array, we found that one potential TSG, ANGPTL4, was expressed at very low levels in all UC cell lines we examined. Previous studies had demonstrated that ANGPTL4 is highly expressed in some cancers, but downregulated, by DNA methylation, in others. Consequently, due to these seemingly conflicting functions in distinct cancers, the precise role of ANGPTL4 in the etiology of UC remains unclear. In this study, using methylation-specific PCR and bisulfite pyrosequencing, we show that ANGPTL4 is transcriptionally repressed by promoter hypermethylation in UC cell lines and primary tumor samples, as compared to adjacent noncancerous bladder urothelium. Functional studies further demonstrated that ectopic expression of ANGPTL4 potently suppressed UC cell proliferation, monolayer colony formation in vitro, and invasion, migration, and xenograft formation in vivo. As ANGPTL4 is a secreted factor, we therefore examined the circulating ANGPTL4 (cir-ANGPTL4) level in UC patients. Surprisingly, cir-ANGPTL4 was significantly higher in plasma samples from UC patients than normal control, suggesting it might be secreted from other cell types. More importantly, exogenous c-terminal fragment of ANGPTL4 (cANGPTL4) could promote cell proliferation and cell migration via activation of signaling through the Erk/FAK axis. We further confirmed that mouse xenograft tumor growth could be promoted by administration of exogenous cANGPTL4. Finally, immunohistochemistry demonstrated that ANGPTL4 was downregulated in tumor cells but overexpressed in tumor-adjacent stromal tissues including muscle and macrophages of muscle-invasive UC tissue samples. In conclusion, our data supports dual roles for ANGPTL4 in urothelial carcinoma progression, either as a tumor suppressor or oncogene, in response to microenvironmental context. Citation Format: Michael WY Chan, Hsiao-Yen Hsieh, Yeong-Chin Jou, Chun-Liang Tung, Yuh-Shyan Tsai, Yuan-Hung Wang, Chen-Lin Chi, Ru-Inn Lin, Shih-Kai Hung, Yu-Ming Chuang, Shu-Fen Wu, Chin Li, Cheng-Huang Shen, Cheng-Da Hsu. Epigenetic silencing of ANGPTL4 in tumor tissues and its overexpression in the urothelial carcinoma microenvironment [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 5339.
Abstract 839: Treatment and signaling contexts for the application of the imipridone ONC201 to prostate cancer cells
Authors: Francesca Amoroso, Adam Pickard, Kimberly Glass, Rohinton Tarapore, J. E. Allen, Ian G. Mills
Journal: Cancer Research (2018)

Abstract Prostate cancer is the most common non-cutaneous cancer in men and a significant cause of cancer mortality. In the majority of the cases localised disease is treated with surgery or radiotherapy and whilst androgen deprivation therapy can extend survival in the subset of cases that progress, metastatic disease is incurable. We have previously reported that oncogenic drivers of prostate cancer (e.g. PTEN loss or mutation), as well as therapy, lead to changes in the activation of prostate cancer cell stress signalling pathways and in particular the unfolded protein response (UPR)1. Here we assess whether the activation of the UPR in response to radiation mirrors the immunogenic/inflammatory response, which is known to characterize the initially acute apoptotic phase before resolving to a chronic level. Further we have evaluated the impact of combining radiation with ONC201, a novel anti-cancer small molecule in clinical trials that is known to activate the pro-apoptotic stress response signalling2. We find that ONC201 has a delayed cytotoxic effect as a single agent in prostate cancer cells, with significant dose-dependent reductions in cell viability occurring 72 hours post-treatment. However activation of multiple arms of the UPR occurs earlier and is detectable at 24 hours for ATF4, ATF6 and IRE1-XBP1 at the protein/mRNA levels in the absence of impacts on cell viability. This delayed impact on viability offers a time window within which to evaluate short-term administration of ONC201 as a ‘primer' to enhance the cytotoxic response to radiation. We show that ‘priming' does indeed enhance radiotherapy response as assessed by cell viability and clonogenic assays. Since PTEN-loss is a high-incidence event in the development and progression of prostate cancer and has been linked to prognosis, we have also evaluated the impact of altering PTEN expression in our models as well as the effect of knocking down core regulators of the UPR. Cumulatively this work represents a further progression to positioning ONC201 in an appropriate molecular context to have durable effects when combined with other therapies to treat prostate cancer. 1.Sheng, X. et al., EMBO Molecular Medicine 7, 788-801 (2015). 2.Allen, J. et al. Discovery and clinical introduction of first-in-class imipridone ONC201. Oncotarget (2016). doi:10.18632/oncotarget.11814 Citation Format: Francesca Amoroso, Adam Pickard, Kimberly Glass, Rohinton Tarapore, J. E. Allen, Ian G. Mills. Treatment and signaling contexts for the application of the imipridone ONC201 to prostate 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 839.
Human Resistin Stimulates Hepatic Overproduction of Atherogenic ApoB-Containing Lipoprotein Particles by Enhancing ApoB Stability and Impairing Intracellular Insulin Signaling
Authors: JustinaCostandi, MichelleMelone, AlexZhao, ShiryaRashid
Journal: Circulation Research (2011)

Rationale:Obese individuals are at high risk for developing atherosclerosis primarily attributable to elevated plasma concentrations of apolipoprotein (apo)B-containing particles, including very-low-density lipoprotein (VLDL). Plasma levels of the adipose tissue adipokine resistin are increased in human obesity, and resistin expression is positively correlated with coronary atherosclerosis and VLDL levels. Objective:We sought to determine for the first time whether resistin directly stimulates human hepatocyte production of apoB-containing particles and to elucidate the mechanisms responsible. Methods and Results:Treatment of human hepatocytes with resistin at levels observed in human obesity stimulated apoB secretion up to 10-fold, because of increased microsomal triglyceride transfer protein (MTP) activity and decreased expression/phosphorylation of proteins in the insulin signaling pathways (insulin receptor substrate-2, Akt, and extracellular signal-regulated kinase). Resistin also increased hepatocyt...
Abstract 13432: Clinical Significance of Early Gadolinium Enhancement for Detecting Myocardial Damage in Patients With Takotsubo Cardiomyopathy
Authors: Yukio Aikawa, Teruo Noguchi, Yoshiaki Morita, Naoaki Yamada, Yoichi Goto, Masaharu Ishihara, Hisao Ogawa, Satoshi Yasuda
Journal: Circulation (2013)

Background: T2-weighted imaging (T2WI) on cardiovascular magnetic resonance (CMR) allows for identification of acute inflammation and myocardial edema. We have previously shown that early gadoliniu...
Abstract MP91: Self-Reported Sitting Time Using a Two-Question Method Is a Good Measure of Sedentary Behavior: Findings in the New York City Adult Population
Authors: StellaYi, KatherineBartley, MelanieFirestone, DonnaEisenhower
Journal: Circulation (2014)

Introduction: Sedentary behavior is defined as activities that require low energy expenditure (1.0 - 1.5 [METs]). Sitting time is a specific domain of sedentary behavior that is associated with metabolic disturbances, decreased life expectancy, and mortality - outcomes that occur independent of meeting physical activity guidelines. Population-level prevalence estimates of the ‘active couch potato’, or active adults who engage in at least 7+ hours of sitting time a day, are needed. Hypothesis: We tested that the two-question method of self-reported sitting time would have adequate construct validity for population surveillance. Methods: The New York City Health Department conducted the 2011 Physical Activity and Transit (PAT) Survey using random-digit dial (cell and landline telephones) methods (n=3811); an additional subset of participants wore accelerometers for a seven-day period (n=679). Sedentary time was defined as accelerometer minutes with <100 counts on valid days (those with 10 hours of wear time...
S-Nitroso Human Serum Albumin Treatment Reduces Ischemia/Reperfusion Injury in Skeletal Muscle via Nitric Oxide Release
Authors: SethHallström, HaraldGasser, ChristophNeumayer, AlexanderFügl, JosephNanobashvili, AndrzejJakubowski, IhorHuk, GüntherSchlag, TadeuszMalinski
Journal: Circulation (2002)

Background— Peroxynitrite generated from nitric oxide (NO) and superoxide (O2−) contributes to ischemia/reperfusion (I/R) injury. Feedback inhibition of endothelial NO synthase by NO may inhibit O2− production generated also by endothelial NO synthase at diminished local l-arginine concentrations accompanying I/R. Methods and Results— During hindlimb I/R (2.5 hours/2 hours), in vivo NO was monitored continuously (porphyrinic sensor), and high-energy phosphates, reduced and oxidized glutathione (chromatography), and I/R injury were measured intermittently. Rabbits receiving human serum albumin (HSA) (controls) were compared with those receiving S-nitroso human serum albumin (S-NO-HSA) beginning 30 minutes before reperfusion for 1 hour or 30 minutes before ischemia for 3.5 hours (0.1 μmol · kg−1 · h− 1). The onset of ischemia led to a rapid increase of NO from its basal level (50±12 nmol/L) to 120±20 and 220±15 nmol/L in the control and S-NO-HSA–treated groups, respectively. In control animals, NO dropped b...
Abstract 21026: Macrophages Preferentially Endocytose Systemically-Delivered Exosomes at Steady State or During Acute Inflammation
Authors: Geoffrey de Couto, Ervin Jaghatspanyan, Nupur Makkar, Eduardo Marbán
Journal: Circulation (2017)

Introduction: Cardiosphere-derived cells (CDCs), which are in advanced clinical testing for heart failure, Duchenne muscular dystrophy and pulmonary hypertension, secrete exosomes (CDC exo ) which are highly anti-inflammatory. CDC exo , but not fibroblast (FB) exosomes, lead to cardioprotection through polarization of macrophages (Mφ) following ischemia/reperfusion injury (de Couto et al., Circulation, 2017). Here we demonstrate that intravenous delivery of CDC exo in mice (healthy or acutely inflamed) leads to preferential uptake by resident Mφ via phagocytosis. Methods &amp; Results: To assess biodistribution, we labeled CDC exo with the fluorescent liposomal dye DiD (Invitrogen). Healthy mice (C57Bl6; 8-12 weeks) were treated with an intraperitoneal injection of either LPS (5mg/kg) or saline prior to intravenous infusion of DiD-labeled CDC exo (in 100μL saline). Four hours later, organs were collected for ex vivo analysis. Biofluorescence imaging (Xenogen) revealed strong DiD signal in Mφ-rich organs including the liver, spleen, and lung, while immunohistochemistry and flow cytometry resolved preferential uptake of CDC exo by tissue Mφ within the liver (60-80% DiD + CD11b + ), spleen (70-80% DiD + F4/80 + ), lung (60-90% DiD + F4/80 + ), and peritoneal cavity (40-60% DiD + CD11b + ). The heart also exhibited measurable fluorescence signals. To determine how avidly distinct cardiovascular cell types preferentially take up CDC exo in vitro , Mφ, FB, endothelial cells (EC), and cardiomyocytes (CM) were exposed to DiD-labeled CDC exo and examined over time. Within one hour, Mφ demonstrated the greatest uptake of CDC exo (Mφ: 81%; FB: 60%; EC: 65%; CM: 51%; p&lt;0.05). The addition of both phagocytosis (Cytochalasin D) and clathrin (Pitstop 2) inhibitors completely blocked CDC exo uptake by Mφ. Conclusions: Intravenous delivery of CDC exo in mice (healthy or acutely inflamed) leads to preferential uptake by Mφ within organs that are rich in such cells (i.e., liver, spleen, lung, and peritoneal cavity). In vitro , Mφ take up CDC exo via phagocytosis and endocytosis more readily than other cardiac cell types. These data suggest the potential utility of CDC exo treatment in cardiovascular diseases where Mφ infiltration is prominent (e.g., atherosclerosis).
Serotonin receptor 2c-expressing cells in the ventral CA1 control attention via innervation of the Edinger–Westphal nucleus
Authors: Xinyan Li, Wenting Chen, Kai Pan, Hao Li, Pei Pang, Yu Guo, Shu Shu, You Cai, Lei Pei, Dan Liu, Henok Kessete Afewerky, Qing Tian, Ling-Qiang Zhu, Youming Lu
Journal: Nature Neuroscience (2018)
Cell Type–Specific Angiotensin II–Evoked Signal Transduction Pathways
Authors: YunzengZou, IsseiKomuro, TsutomuYamazaki, SumiyoKudoh, RyuichiAikawa, WeidongZhu, IchiroShiojima, YukioHiroi, KazuyukiTobe, TakashiKadowaki, YoshioYazaki
Journal: Circulation Research (1998)

Abstract—Angiotensin II (Ang II) induces hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. To determine the molecular mechanism by which Ang II displayed different effects on cardiac myocytes and fibroblasts, we examined signal transduction pathways leading to activation of extracellular signal–regulated kinases (ERKs). Ang II–induced ERK activation was abolished by pretreatment with pertussis toxin and by overexpression of the Gβγ subunit–binding domain of the β-adrenergic receptor kinase 1 in cardiac fibroblasts but not in cardiac myocytes. Inhibition of protein kinase C strongly inhibited activation of ERKs by Ang II in cardiac myocytes, whereas inhibitors of tyrosine kinases but not of protein kinase C abolished Ang II–induced ERK activation in cardiac fibroblasts. Overexpression of C-terminal Src kinase (Csk), which inactivates Src family tyrosine kinases, suppressed the activation of transfected ERK in cardiac fibroblasts. Ang II rapidly induced phosphorylation of Shc and assoc...
Ulinastatin, a Urinary Trypsin Inhibitor, for the Initial Treatment of Patients With Kawasaki Disease
Authors: TakashiKanai, TakahiroIshiwata, TohruKobayashi, HirokiSato, MariTakizawa, YoichiKawamura, HiroshiTsujimoto, KeigoNakatani, NaokoIshibashi, MitsunoriNishiyama, YoshihoHatai, YuhAsano, TomioKobayashi, SeiichiroTakeshita, ShigeakiNonoyama
Journal: Circulation (2011)

Background—Markedly activated neutrophils or higher plasma levels of neutrophil elastase are involved in the poor response to intravenous immunoglobulin (IVIG) and the formation of coronary artery lesions (CAL) in patients with acute Kawasaki disease. We hypothesized that ulinastatin (UTI), by both direct and indirect suppression of neutrophils, would reduce the occurrence of CAL. Methods and Results—We retrospectively analyzed the clinical records of patients with Kawasaki disease between 1998 and 2009. Three hundred sixty-nine patients were treated with a combination of UTI, aspirin, and IVIG as an initial treatment (UTI group), and 1178 were treated with a conventional initial treatment, and IVIG with aspirin (control group). The baseline characteristics did not demonstrate notable differences between the two groups. The occurrence of CAL was significantly lower in the UTI group than in the control group (3% versus 7%; crude odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25–0.86; P=0.01). The O...