tbuckley/cabot-search huggingface dataset:
Abstract 20023: Impact of Targeted Temperature During Therapeutic Hypothermia: A Pooling Analysis of Published Literature
Authors: Aldo L Schenone, Aaron Cohen, Gabriel Patarroyo, Mehdi H Shishehbor, Venugopal Menon, Abhijit Duggal
Journal: Circulation (2015)

Introduction: Two small RCTs demonstrated benefit of therapeutic hypothermia (TH) after out-hospital cardiac arrest (OHCA). We explored the benefit of targeted temperature during TH and also performed an updated meta-analysis to determine the intervention effect in the community. Methods: We identified studies by searching electronic databases (MEDLINE, EMBASE and Cochrane Library). We selected RCTs and cohort studies restricted to those reporting achieved temperature during TH after OHCA, and describing mortality and neurological outcomes at discharge. Studies were assessed for risk of bias. Data from all individual hypothermia arms were pooled by achieved temperature. Pooled outcomes were compared across achieved temperatures. Meanwhile, we meta-analyzed controlled studies comparing hypothermia against normothermia. Results: The search identified 32,275 studies of which 24 studies (34 hypothermia arms) were used in the pooling analysis and 14 controlled studies were meta-analyzed. Pooling analysis reported an overall in-hospital mortality of 47.2% with a rate of good neurological outcome at discharge of 38%. There was no difference in hospital mortality (p=0.86) or neurological outcomes at discharge (p=0.32) across temperatures (Figure 1). Sub-group analysis by rhythm showed a non-significant trend towards benefit when the lower temperature were applied to non-shockable rhythms. Meta-analysis demonstrated a MTH mortality (OR 0.51, 95%CI:0.41-0.64, I2=4.1%) and neuro-protective benefit (OR 2.48, 95%CI:1.91-3.22, I2=0%). Conclusions: No discernible clinical benefit was noted based on target temperature achieved. The signal toward potential benefit when applying lower temperature to non-shockable rhythms warrants exploration. Consistent with prior meta-analysis, TH provides mortality and neuro-protective benefit after OHCA even when including cohort studies thought to be more representative of performance in the community.
Sex Differences in the Prognosis of Congestive Heart Failure
Authors: TabassomeSimon, MurielleMary-Krause, ChristianFunck-Brentano, PatriceJaillon
Journal: Circulation (2001)

Background—Whether female sex is associated with a better prognosis in patients with congestive heart failure (CHF) remains uncertain. The Cardiac Insufficiency Bisoprolol Study (CIBIS) II showed that bisoprolol reduced all-cause mortality and morbidity rates in CHF patients treated with diuretics and ACE inhibitors. We examined whether survival was different in men (n=2132) and women (n=515) enrolled in CIBIS II. Methods and Results—Women differed from men with regard to age, NYHA functional classification, primary cause of CHF, and risk factors such as left bundle-branch block. After adjustment for baseline differences, the probability of all-cause mortality was significantly reduced by 36% in women compared with that in men (hazard ratio 0.64, 95% CI 0.47 to 0.86, P=0.003). Women also had a 39% reduction in cardiovascular deaths (hazard ratio 0.64, 95% CI 0.45 to 0.91, P=0.01) and a 70% reduction in deaths from pump failure (hazard ratio 0.30, 95% CI 0.13 to 0.70, P=0.005) compared with men. Kaplan-Mei...
Left Ventricular Versus Simultaneous Biventricular Pacing in Patients With Heart Failure and a QRS Complex ≥120 Milliseconds
Authors: BernardThibault, AniqueDucharme, FrançoisHarel, MichelWhite, EileenO'Meara, Marie-ClaudeGuertin, JoelLavoie, NancyFrasure-Smith, MarcDubuc, PeterGuerra, LaurentMacle, LénaRivard, DenisRoy, MarioTalajic, PaulKhairy
Journal: Circulation (2011)

Background—Left ventricular (LV) pacing alone may theoretically avoid deleterious effects of right ventricular pacing. Methods and Results—In a multicenter, double-blind, crossover trial, we compared the effects of LV and biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LV ejection fraction ≤35%, QRS ≥120 milliseconds, and symptoms of heart failure. A total of 211 patients were recruited from 11 centers. After a run-in period of 2 to 8 weeks, 121 qualifying patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. The greatest improvement in New York Heart Association class and 6-minute walk test occurred during the run-in phase before randomization. Exercise duration at 75% of peak Vo2 (primary outcome) increased from 9.3±6.4 to 14.0±11.9 and 14.3±12.5 minutes with LV and BiV pacing, respectively, with no difference between groups (P=0.4327). LV ejection fraction improved from 24.4±6.3% to 31.9±10.8% and 30.9±9.8% with LV an...
Fibrinogen After Coronary Angioplasty as a Risk Factor for Restenosis
Authors: GillesMontalescot, AnnickAnkri, EricVicaut, GérardDrobinski, YvesGrosgogeat, DanielThomas
Journal: Circulation (1995)

Background Fibrinogen is a risk factor for cardiovascular disease and is related to the severity of coronary atherosclerosis. Its role in restenosis after coronary angioplasty remains unknown. Although platelets and thrombosis contribute to the pathogenesis of restenosis, few clinical data are available concerning the relations between restenosis and proteins of the coagulation and fibrinolytic systems. Methods and Results In 107 consecutive patients undergoing coronary angioplasty, we measured plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor–1 (PAI-1), von Willebrand factor, and fibrinogen before and immediately after angioplasty and at a 6-month follow-up. The individual changes of intraluminal diameter were measured by quantitative coronary angiography, and patients were classified according to four definitions of restenosis: (1) a final stenosis >50%, (2) a loss of minimal luminal diameter during the follow-up period greater than the measurement variability in...
Abstract 5140: Lipoxins and their role in Kaposi's sarcoma-associated herpesvirus (KSHV) infection and pathogenesis
Authors: Neelam Sharma-Walia, Jayashree A. Chandrasekharan
Journal: Cancer Research (2018)

Abstract Lipoxins are host anti-inflammatory molecules, which play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and related diseases have been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation-related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins. Our study demonstrates how KSHV manipulates and downregulates the secretion of the anti-inflammatory lipoxin A4 in host cells and the viral factors involved in this process using in vitro KS and PEL cells as models. Presence of lipoxin receptor [ALX/Formyl peptidyl receptor (FPR)] in human KS patient tissue sections and in vitro KS and PEL cell models offers a novel possibility for treating KS and PEL with lipoxins. Treating de novo KSHV-infected endothelial cells with lipoxin and epilipoxin creates an anti-inflammatory environment by decreasing levels of NFκB, AKT, ERK1/2, COX-2, and 5-lipoxygenase. Lipoxin treatment on CRISPR/CAS9 technology-mediated ALX/FPR gene-deleted U2OS cells revealed the importance of the lipoxin receptor ALX for effective lipoxin signaling. A viral miRNA cluster was identified as the primary factor contributing to the downregulation of lipoxin A4 secretion in host cells. The KSHV miRNA cluster probably targets enzyme 15-lipoxygenase, which is involved in lipoxin A4 synthesis. Lipoxin treatment in KSHV-infected cells has been shown to reduce cell proliferation and cell survival. Latency factor LANA-1 levels were found to decrease on lipoxin and epilipoxin treatment. Several pro-apoptotic gene levels were upregulated on lipoxin treatment. Several host transcription factors were found to play an important role in regulating KSHV life cycle. This study provides a new insight into the treatment of KS and PEL using nature's own anti-inflammatory molecule, lipoxin. Citation Format: Neelam Sharma-Walia, Jayashree A. Chandrasekharan. Lipoxins and their role in Kaposi's sarcoma-associated herpesvirus (KSHV) infection and pathogenesis [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 5140.
Pinch1 Is Required for Normal Development of Cranial and Cardiac Neural Crest-Derived Structures
Authors: XingqunLiang, YunfuSun, JurgenSchneider, Jian-HuaDing, HongqiangCheng, MaoqingYe, ShoumoBhattacharya, AnnRearden, SylviaEvans, JuChen
Journal: Circulation Research (2007)

Pinch1, an adaptor protein composed of 5 LIM domains, has been suggested to play an important role in multiple cellular processes. We found that Pinch1 is highly expressed in neural crest cells and their derivatives. To examine the requirement for Pinch1 in neural crest development, we generated neural crest conditional Pinch1 knockout mice using the Wnt1-Cre/loxP system. Neural crest conditional Pinch1 mutant embryos die perinatally from severe cardiovascular defects with an unusual aneurysmal common arterial trunk. Pinch1 mutants also exhibit multiple deficiencies in cranial neural crest-derived structures. Fate mapping demonstrated that initial migration of neural crest cells to the pharyngeal arch region occurs normally in the mutant embryos. However, in the cardiac outflow tract of mutants, neural crest cells exhibited hyperplasia and failed to differentiate into smooth muscle. Markedly increased apoptosis is observed in outflow tract cushions of mutants between embryonic days 11.5 and 13.5, likely c...
Abstract 9257: Atrial Fibrillation is Associated With Worse Outcomes in Patients With Diastolic Heart Failure than Patients With Systolic Heart Failure
Authors: Sakima A Smith, Arnold J Hite, Abiodun Ishola, Ayesha K Hasan
Journal: Circulation (2013)

Introduction: Atrial fibrillation (AF) is prevalent and is associated with heart failure (HF). HF causes changes in atrial structure and physiology that predispose to AF. Our goal was assess the impact of AF on HF patients with either preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Hypothesis: We hypothesized that patients with HFrEF would likely have more adverse events and worse outcomes. Methods: This was a retrospective review of 763 patients with HF at baseline who developed AF. We analyzed the CHADS and CHADS-Vasc scores and time to death, time to AF development, time to death from AF development, time to adverse events (figure 1), and length of stay (LOS). Results: Patients with HFpEF had significantly longer LOS for AF or HF hospitalizations. While patients with HFrEF on average developed AF four months sooner than patients with HFpEF, those with HFpEF died six months earlier (table 1). Using multiple linear regression only age was a significant predictor for time to AF development. There were no significant differences between HFrEF vs HFpEF patients with respect to time to an adverse event. When patients were stratified into younger vs older cohorts (&lt; or ≥ 50 years of age) there was a significant difference for the waiting time to an adverse event between the younger and older patients (figure 1). Conclusion: Patients with HFpEF and AF represent a cohort of patients that have a significant burden of disease and poor outcomes. Their increased LOS is likely a product of their multiple co-morbid conditions complicating their underlying HF. Our data also suggests that the most important factor for time to an adverse event for HF patients with AF is age, not the LVEF.
Complex Electrophysiological Characteristics in Atrioventricular Nodal Reentrant Tachycardia With Continuous Atrioventricular Node Function Curves
Authors: Ching-TaiTai, Shih-AnnChen, Chern-EnChiang, Shih-HuangLee, Zu-ChiWen, Chuen-WangChiou, Kwo-ChangUeng, Yi-JenChen, Wen-ChungYu, Jin-LongHuang, Mau-SongChang
Journal: Circulation (1997)

Background Although typical atrioventricular nodal reentrant tachycardia (AVNRT) with discontinuous AV node function curves has been well studied, there has been a lack of any significant information about AVNRT without evidence of dual AV nodal pathway physiology during atrial extrastimulus testing or atrial pacing. Methods and Results Group 1 included 9 patients with continuous curves during atrial extrastimulus testing but without a jump (≥50 ms) of the atrial–His bundle (AH) interval during incremental atrial pacing. The maximal AH interval during atrial pacing (266±61 versus 168±27 ms, P=.007) or extrastimulus testing (290±60 versus 176±18 ms, P=.005) shortened significantly after ablation. Antegrade and retrograde AV node properties were similar before and after ablation. Group 2 included 14 patients with continuous curves and a jump of the AH interval during incremental atrial pacing. The atrial pacing cycle length with 1:1 AV conduction and effective refractory period (ERP) of the antegrade AV nod...
Abstract LB-107: Repurposing endogenous immune pathways to improve chimeric antigen receptor T-cells potency
Authors: Mohit Sachdeva, Brian Busser, Sonal Temburni, Alexandre Juillerat, Laurent Poirot, Philippe Duchateau, Julien Valton
Journal: Cancer Research (2018)

Abstract CAR T-cell therapies hold great promise for treating a range of liquid malignancies but are however challenged to access and eradicate solid tumors. To overcome this hurdle, CAR T-cell were engineered to secrete different cytokines known to improve T-cell antitumor activity, prevent T-cell anergy and reduce activation induced cell death. While cytokine-expressing CAR T-cell were shown to be be highly active against solid tumor in in vivo models, they have also led to toxicity associated with the systemic release of cytokine. Therefore, new engineering strategies enabling the fine tuning of cytokine secretion by CAR T-cell are warranted. We sought to explore one of these engineering strategies by integrating an IL-12 chimeric heterodimer expression cassette under the control of the endogenous promoters regulating PD1 or CD25. Because both genes are known to be activated upon tumor engagement by CAR T-cells, they could be repurposed to secrete cytokine only in the vicinity of a given tumor. This approach would reduce the potential side effects induced by their systemic secretion while maintaining their capacity to improve antitumor activity. By combining TALEN® technology with AAV6 repair vectors delivering the CAR to the TRAC locus and the IL-12 to the CD25 or PD1 loci, we have engineered CAR and IL-12 expressions under the respective control of TCR and CD25 or PD1 regulatory elements. This double targeted insertion led to the disruption of PD1 and TRAC genes, to the expression of a tool CAR and to the conditional secretion of IL-12 in the media. Such secretion was found to be transient, dependent on tumor engagement and to follow the regulation patterns of CD25 or PD1 genes, commonly observed upon T-cell activation. In addition, it was also found to enhance the antitumor activity and the proliferative capacities of CAR T-cells. Similar results were obtained when IL-15 was substituted for IL-12. This proof of concept paves the way for seamless multi-repurposing of immune pathways to generate smarter CAR T-cells able to sense and react to their environment in a highly regulated and specific manner. Citation Format: Mohit Sachdeva, Brian Busser, Sonal Temburni, Alexandre Juillerat, Laurent Poirot, Philippe Duchateau, Julien Valton. Repurposing endogenous immune pathways to improve chimeric antigen receptor T-cells potency [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-107.
Abstract 813: Development of anti-Globo H ADC against cancer
Authors: Wei-Ting Sun, Shih-Hsien Chuang, Chao-Pin Lee, Yi-Jen Chen, Win-Yin Wei, Ying-Shuan Lee, Chuan-Lung Hsu, Yu-Chin Nieh, Chia-Cheng Wu
Journal: Cancer Research (2018)

Abstract Globo H antigen is a hexasaccharide originally isolated as a ceramide-linked glycolipid from the human breast cancer cell line MCF-7. Globo H is also highly expressed in many other cancers such as colon cancer, ovarian cancer, gastric cancer, pancreatic cancer, lung cancer, and prostate cancer. DCBD16001 is an ADC from humanized anti-Globo H antibody DCBPR1101. DCBPR1101 and DCBD16001 both show good binding affinities against Globo H antigen. DCBD16001 also shows high cytotoxicity in Globo H overexpressing cell line MCF-7 and HCC-1428 and shows no cytotoxicity in Globo H negative cell line BT-474. DCBD16001 can internalize to target cell more than 50% within 4.0 hours. In vivo evaluation data indicates that DCBD16001 shows acceptable PK profiles and good efficacy. It shows nearly 80% tumor growth inhibition in HCC-1428 xenograft model. DCBD16001 is a candidate under pre-clinical development and expected to apply IND submission within two years. Citation Format: Wei-Ting Sun, Shih-Hsien Chuang, Chao-Pin Lee, Yi-Jen Chen, Win-Yin Wei, Ying-Shuan Lee, Chuan-Lung Hsu, Yu-Chin Nieh, Chia-Cheng Wu. Development of anti-Globo H ADC against 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 813.
Abstract 15751: Inorganic Nitrate Improves Exercise Tolerance and Symptoms in Heart Failure With Preserved Ejection Fraction - A Dose Finding Study
Authors: Payman Zamani, Victor Tran, Haideliza Soto-Calderon, Melissa Beraun, Jeffrey A Brandimarto, Lien Trieu, Swapna Varakantam, Paschalis-Thomas Doulias, Raymond R Townsend, Jesse Chittams, Kenneth B Margulies, Thomas P Cappola, David C Poole, Harry Ischiropoulos, Julio A Chirinos
Journal: Circulation (2016)

Background: Heart Failure with Preserved Ejection Fraction (HFpEF) leads to significant impairments in exercise and quality of life (QOL). Inorganic nitrate has been shown to improve exercise in HF...
Abstract 1259: Loss of TFF1 promotes growth and chemotherapeutic resistance in gastric cancer
Authors: Zheng Chen, Zheng Li, Mohammed Soutto, Weizhi Wang, Shoumin Zhu, Alejandro Corvalan, Zekuan Xu, Wael El-Rifai
Journal: Cancer Research (2018)

Abstract Background: Downregulation or loss of TFF1 expression occurs in more than half of human gastric adenocarcinomas through gene deletions, mutation, and a loss of heterozygosity or hypermethylation. Our previous studies have shown that Tff1 knockout (KO) in mice induces gastric lesions from low- grade dysplasia (LGD), high- grade dysplasia (HGD) to adenocarcinoma. BRD2, a family member of BET proteins, promotes aberrant gene expression in a variety of malignant tumors. In this study, with the analysis of Tff1 KO mice and human gastric cancer tissue samples, we discovered that loss of Tff1 promotes gastric cancer proliferation and drug resistance through upregulating BRD2 expression level. Methods and Results: Integration Next Generation Sequencing data analysis in both Tff1 KO mice and human gastric cancer tissue samples demonstrated that miR-143-3p was significantly down-regulated in both mice and human gastric cancer samples (P&amp;lt;0.05). Our findings were further validated by RT-PCR in Tff1 KO mouse gastric legions (LGD and adenocarcinoma) and 3 different cohorts of human gastric cancer tissue samples from USA, Chile, and China. Using different gastric cancer cell models we further confirmed the decrease of miR-143-3p regulated by loss of TFF1. Next, we wanted to find out the downstream effector of miR-143-3p down-regulation. Western blot data showed that BRD2 protein level was regulated by miR-143-3p in 4 gastric cancer cell lines. BRD2 3'UTR luciferase reporter assay further confirmed that miR-143-3p decreased BRD2 protein expression through directly binding to its 3'UTR sites. These data suggested that, for the first time, BRD2 is a direct downstream target of miR-143-3p. At the meantime, the reconstitution of TFF1 in gastric cancer cells up-regulated miR-143-3p expression level, which in turn, decreased the protein expression levels of BRD2, MYC and BCL-2. Using western blot, we showed the synergistic effect of BRD2 inhibitor and CDDP chemotherapy in human gastric cancer cells. Data from 320 human gastric cancer patients demonstrated that high BRD2 expression level in gastric cancer tissues significantly decreased the overall patient survival rate (P&amp;lt;0.0001). Conclusion: This study unveils, for the first time, loss of TFF1 promotes BRD2 activation in gastric cancer through decreasing miR-143-3p. This axis presents novel therapeutic opportunities by using approaches that reconstitute miR-143-3p or utilizing the recently developed clinical trials in human gastric cancer. Citation Format: Zheng Chen, Zheng Li, Mohammed Soutto, Weizhi Wang, Shoumin Zhu, Alejandro Corvalan, Zekuan Xu, Wael El-Rifai. Loss of TFF1 promotes growth and chemotherapeutic resistance in gastric 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 1259.
Abstract 5515: Ras-like estrogen-regulated growth-inhibitory gene (RERG): A novel biomarker and potential therapeutic target for women with lung cancer
Authors: Michelle Van Scoyk, Sreedevi Avasarala, Pei-Ying Wu, Yanlin Su, Lane Lerner, Alicia Hulbert, Kamesh Bikkavilli, Robert A. Winn
Journal: Cancer Research (2018)

Abstract Background: Lung cancer is the second most common cancer diagnosed in women. In fact, twice as many women will die from lung cancer compared to breast cancer, the key risk factor being tobacco use. Hence, there is a need to identify new molecular biomarkers to aid in early detection and develop new therapeutic strategies in tobacco-related lung cancer. Ras-like Estrogen-Regulated Growth-Inhibitory Gene (RERG) is a member of the Ras superfamily of GTPases that play an important role in cellular processes such as proliferation, differentiation, and apoptosis. Unlike other members of the Ras superfamily members of proto-oncogenes, RERG functions as a tumor suppressor. Objective: To investigate the utility of RERG expression as a novel biomarker and a potential therapeutic target in lung cancer. Results: In silico analysis of The Cancer Genome Atlas (TCGA) lung cancer datasets revealed a significant downregulation of RERG expression in lung tumors. Furthermore, reduced expression of RERG in lung tumors was also observed to be correlated with poor prognosis as determined by Kaplan-Meier survival analysis. Evaluation of formalin-fixed, paraffin-embedded (FFPE) human lung cancer tissues and fresh frozen lung tumor tissues corroborated our in silico observations. Most notably, tobacco smoke was identified to be associated with decreased RERG expression in lung tumors. The most intriguing observation from this study is the significant decrease of RERG expression in female smokers as a result of promoter hypermethylation. Conclusion: Taken together, these findings suggest that RERG may represent a potential biomarker in lung cancer, particularly among smokers. Further investigation would focus on the mechanism of RERG loss and its influence on lung tumor development, particularly in female smokers. Citation Format: Michelle Van Scoyk, Sreedevi Avasarala, Pei-Ying Wu, Yanlin Su, Lane Lerner, Alicia Hulbert, Kamesh Bikkavilli, Robert A. Winn. Ras-like estrogen-regulated growth-inhibitory gene (RERG): A novel biomarker and potential therapeutic target for women with 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 5515.