tbuckley/cabot-search huggingface dataset:
Identification of potentially predictive biomarkers for tumor sensitivity to proapoptotic receptor agonists
Authors: A. Ashkenazi, K. Wagner, E. Punnnoose, D. Lawrence, R. Pitti, L. Amler
Journal: Journal of Clinical Oncology (2008)

14505 Background: Apo2L/TRAIL selectively stimulates cancer-cell death through the proapoptotic receptors DR4 and DR5. Endogenous Apo2L/TRAIL is expressed on natural killer cells and has been implicated in immune surveillance against metastatic tumor cells. We have generated two proapoptotic receptor agonists (PARAs) as experimental cancer- therapeutic agents: soluble recombinant human (rh)Apo2L/TRAIL, which induces apoptosis through DR4 and/or DR5; and Apomab-a fully human, affinity-matured agonistic antibody that triggers apoptosis through DR5. Both PARAs display antitumor efficacy and cooperate with various chemotherapy and other agents in diverse cancer xenograft models. Systemic infusion of either PARA is well tolerated in non-human primates, and both molecules are currently in clinical trials. Methods: To identify potential determinants of tumor susceptibility to rhApo2L/TRAIL, we characterized a panel of cancer cell lines for sensitivity to the ligand in relation to gene expression profiles. Results: mRNA expression of the peptidyl O-glycosyl transferase GALNT14 correlated with rhApo2L/TRAIL sensitivity in pancreatic carcinoma, non-small cell lung carcinoma and melanoma cell lines (P < 9X10−6; n=83), and up to 30% of primary tumor samples from various human malignancies displayed GALNT14 overexpression. Loss- and gain-of function experiments revealed that GALNT14 promotes O-glycosylation of DR4 and DR5; this modification facilitated ligand- stimulated receptor clustering, to mediate recruitment and activation of the apoptosis-initiating protease caspase-8. Conclusion: These results uncover a novel link between O-glycosylation of cell-surface receptors and apoptosis signaling, providing potentially predictive biomarkers for PARA-based cancer therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology
Abstract 13965: Utility on Right Heart Catheterization and NTproBNP-Levels for Riskstratification in Patients Treated by Transcatheter Aortic Valve Implantation (TAVI)
Authors: Jury Schewel, Dimitry Schewel, Christian Frerker, Felix Meincke, Thomas Thielsen, Felix Kreidel, Karl-Heinz Kuck, Ulrich Schaefer
Journal: Circulation (2011)

Introduction: TAVI is a new treatment option for high-risk patients with severe aortic valve stenosis (AVS). Risk-stratification is still an important and insufficiently explored issue. The objecti...
Abstract 15645: Exosomes from Human CD34+ Cells Are a Crucial Paracrine Component for Ischemic Tissue Repair and Angiogenesis
Authors: Susmita Sahoo, Sol Misener, Tina Thorne, Meredith Millay, Kathryn M Schultz, Ting Liu, Aiko Ito, Christine Kamide, Ekaterina Klyachko, Douglas W Losordo
Journal: Circulation (2011)

In early clinical trials, human CD34+ stem cells (CD34) have been shown to improve exercise tolerance in patients with myocardial ischemia and reduce amputation rates in limb ischemia. CD34 have be...
Abstract 16561: Mechanical Unloading via Left Ventricular Assist Device Implantation Ameliorates Systemic and Adipose Tissue Inflammation and Increases Adipocyte Size in Patients With Advanced Heart Failure
Authors: Raffay Khan, Aalap Chokshi, Collette R Harris, Shuiqing Yu, Christina Wu, Hiroo Takayama, Tomoko S Kato, Gissette Reyes-Soffer, Daniel E Forman, Yoshifumi Naka, Donna Mancini, P. Christian Schulze
Journal: Circulation (2011)

Introduction: Heart failure (HF) is a complex multi-organ syndrome characterized by systemic inflammation, insulin resistance (IR) and peripheral hypoperfusion. Recent studies have implicated local...
Analysis of BCR-ABL1 Tyrosine Kinase Domain Mutations In Primitive Chronic Myeloid Leukemia Cells Identifies a Unique Mutator Phenotype.
Authors: Xiaoyan Jiang, Hannah Grant, Justin Stebbing, Letizia Foroni, Charles Craddock, Mike Griffiths, Richard E. Clark, Stephen O'Brien, Jamshid S. Khorashad, Gareth Gerrard, Lihui Wang, Julie Irving, Meng Wang, Loraine Karran, Martin JS Dyer, Donna L. Forrest, Karen Page, Connie J. Eaves, Adrian Woolfson
Journal: Blood (2010)
Abstract 16709: Heritability of Early Repolarization - a Population-Based Study
Authors: Wibke Reinhard, Bernhard Kaess, Christopher P Nelson, Radoslaw Debiec, Paraskevi Christofidou, Klaus Stark, Martin D Tobin, Maciej Tomaszewski, Nilesh J Samani, Christian Hengstenberg
Journal: Circulation (2010)

The electrocardiographic pattern of Early Repolarization (ER) has been known for decades and was generally considered a benign normal variant of the surface ECG. ER is characterized by a slurring o...
Abstract 2849: Family Variables in Early Recovery Predict Stroke Survivor Quality of Life in 12 months
Authors: N. J Klinedinst, M. C Gebhardt, Dawn M Aycock, Sandra B Dunbar, Steve L Wolf, Gitendra Uswatte, Patricia C Clark
Journal: Circulation (2007)

Purpose : Quality of life (QOL) after stroke may be influenced by the family context in addition to the stroke survivor’s physical ability. The purpose of this study was to determine whether baseline caregiver (CG) and family characteristics (age, physical function, depressive symptoms, and family communication) predict stroke survivor (SS) QOL: physical function, memory/thinking, social activities, communication, and mood at 1 year follow-up. Methods : Data were collected on 132 SS-CG dyads. SSs were 3–9 months post stroke, 30 to 83 years old ( M = 62.2 ± 12.6), male (64%), Caucasian (74 %), and had an ischemic stroke (88%). CGs were age 25 to 85 years ( M = 56.7 ± 13.7), female (74 %), well-educated (73 %), and spouses (80 %) enrolled in a multi-site caregiving study complementary to a clinical trial testing constraint-induced movement therapy in SSs. Measures included CG physical function (SF-36), CG depressive symptoms (CES-D), family communication (McMaster Family Assessment Device), and SS QOL (Stroke Impact Scale). Pearson’s correlations and hierarchal multiple regression analyses (n = 107) controlling for SS gender, the EXCITE intervention group, and SS functional level were used for analysis. Results : Baseline CG depressive symptoms were negatively related to both SS mood ( r = -.24, p &lt; .01) and social activities ( r = -.26, p = .01) at 1 year. Better family communication was related to higher SS memory/thinking ( r = -.24, p = .01). CG age and physical function were not associated with any SS QOL domains. In the regression models, CGs with more depressive symptoms (β = -.28, p = .007) at baseline predicted poorer SS mood ( F = 2.56, p = .02; R 2 = .13) and worse social participation (β = -.27, p = .01; F = 1.61, p = .15; R 2 = .09). Although the overall model was not significant ( F = 1.20, p = .31; R 2 = .07), worse family communication (β = -.22; p = .04) predicted poorer SS memory and thinking at 1 year. No CG or family characteristics were associated with SS physical or communication QOL domains. Conclusions : Early recognition and intervention of CG depressive symptoms may have profound effects on both CG and aspects of SS QOL in the early and chronic stroke recovery periods. Family interventions focusing on improving communication early may also improve long term stroke recovery.
Abstract 14708: Pradaxa Can Be Safely Used As Monotherapy Or As A Bridge To Therapeutic Warfarin After Atrial Fibrillation Ablation
Authors: Thomas J Bunch, Brian G Crandall, J. P Weiss, Jeffrey S Osborn, Heidi T May, John D Day
Journal: Circulation (2011)

Background: After catheter ablation for atrial fibrillation (AF), it is recommended that all patients be treated with warfarin for 2 months and in those with a CHADS2 ≥2 indefinitely. Dabigatran re...
Abstract 5659: Regular Atrial Tachycardias After Ablation Of Complex Fractionated Atrial Electrograms (CFAE) For Atrial Fibrillation: Acute Incidence And Recurrence In Clinical Follow-up
Authors: Tilko Reents, Gabriele Hessling, Stephanie Fichtner, Jinjin Wu, Heidi L Estner, Christian von Bary, Martin R Karch, Isabel Deisenhofer
Journal: Circulation (2008)

Background: The catheter ablation of atrial fibrillation (AF) can be performed by ablation of complex fractionated atrial electrograms (CFAE). Endpoint of CFAE ablation is the regularisation or termination of AF. However, the impact of regular atrial tachycardia (AT) occurring during CFAE ablation on long term outcome has not been investigated. Thus, it is not clear whether these tachycardias should be acutely targeted for ablation. Methods: In 43 patients (31 male, age 62±9 years with paroxysmal (15 patients), persistent (25 patietns) or permanent AF (3 patients) organisation of AF to regular AT was achieved by ablation of CFAE. Mapping of AT with subsequent successful ablation was performed in 14/43 patients (33%), in the remaining 29/43 patients (67%) AT was terminated with external cardioversion or pace overdrive. After ablation procedure, patients were seen in our out-patient clinic with repetitive Holter ECG after 1, 3, and subsequently every 3 months and were intensively screened for the occurrence of regular AT. Results: In follow-up 22/43 patients (51%) developed sustained AT necessitating in 20 patients repeat catheter ablation (12 patients) or external cardioversion (8 patients). AF had been paroxysmal in 7/22 and persisten in 15/22 patients with AT in follow-up. In 14/22 patients (63%), no attempt for ablation of AT had been made during the initial procedure, in 8/22 AT (36%) had been mapped and initially successful ablated. Of 21 patients without AT occurrence during follow-up, AF had been paroxysmal in 8/21 and persistent or permanent in 13/21 patients. AT had been mapped and ablated in 6 (29%) whereas in 15/21 patients (71%), AT had not been targeted. Ablation of AT during initial procedure, number of ablation applications, procedure and fluoroscopy duration were not predictive for freedom of AT in follow-up. Conclusion: In our study, mapping and successful ablation of new onset regular atrial tachycardias (AT) occurring during ablation of CFAE for atrial fibrillation was not predictive for the occurrence of AT in follow-up. Thus, results after termination of AT by cardioversion was in long-term comparable to sometimes time-consuming mapping/ablation for AT.
Abstract 17457: Radiation Exposure is Incresead Through the Last Ten Years
Authors: Doralisa Morrone, Paul G Kolm, Xin Xu, Claudine Jurkovitz, Deborah Ehrenthal, Rahman Ehsanur, William S Weintraub
Journal: Circulation (2011)

BACKGROUND: Since the first percutaneous coronary intervention (PCI) numerous efforts have been made to reduce the exposure time to radiation and protect the operator against the radiation damage. Our purpose is to compare two periods of time and determine if the exposure time has changed over the years. METHODS: We collected all myocardial infarction (MI) procedures entered into the Cath/PCI Registry from 2006 to 2011. Our population was divided in two groups according to years of PCI (2006-2008) and (2009-2011). We used interrupted time series analysis to compare mean time of exposure between the groups. The results were adjusted according to the complications in cath lab using linear regression. Complications included tamponade, vessel dissection and bleeding at the entry site during the procedure. RESULTS: 1403 consecutive percutaneous coronary intervention (PCI) were recorded. Among the complication we had 0.1% vessel dissection; 0.6% bleeding in the entry site, and 0.1% tamponade. The mean time of fluoro exposure was 11 minutes ± 7.1 (SD) in the first group and 14 minutes ± 8.5 in the second group. The results of the linear regression showed that the p value for the comparison between the means was highly significant (=0.000) Figure CONCLUSION: In the era of new technologies and emphasis on prevention, fluoro exposure for the operators has increased through the years. This finding suggests that efforts should be made to identify the reasons and establish the best approaches to avoid unnecessary exposure.
Abstract 8534: Combination of Cyclosporine and Erythropoietin Improves Brain Infarct Size and Neurological Function in Rats after Ischemic Stroke
Authors: Steve Leu,, Sarah Chua, Chun-Man Yuen, Yung-Long Chen, Hon-Kan Yip
Journal: Circulation (2011)

Objectives: This study tested the superiority of combined cyclosporine (CsA)-erythropoietin (EPO) therapy compared with either one in limiting brain infarction area (BIA) and preserving neurological function in rat after ischemic stroke (IS). Methods: Fifty adult-male SD rats were equally divided into sham control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48h after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group 3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA and EPO treatment (group 5) after occlusion of distal left internal carotid artery. Results: BIA on day 21 after acute IS was highest in group 2 and lowest in group 5 (all p&lt;0.01). The sensorimotor functional test showed highest frequency of left turning in group 2 and lowest in group 5 (all p&lt;0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were highest in group 2 and lowest in group 1 and 5, whereas the anti-apoptotic markers exhibited an opposite trend (all p&lt;0.05). The expressions of inflammatory and oxidized protein were highest in group 2 and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and 5 (all p&lt;0.05). The number of aquaporin - 4+ and glial fibrillary acid protein+ stained cells were highest in group 2 and lowest in groups 1 and 5 (all p&lt;0.01). Conclusion: Combined treatment with CsA and EPO was superior to either one alone in protecting rat brain from ischemic damage after IS (the proposed mechanisms of potential therapeutic impact of combined therapy with CsA and EPO on acute IS have been summarized in the figure)
Abstract 18122: Cerebral Embolization during Transcatheter Aortic Valve Implantation (TAVI): A Transcranial Doppler Study.
Authors: Philipp Kahlert, Philipp Doettger, Kathrine Mori, Fadi Al-Rashid, Matthias Thielmann, Daniel Wendt, Heinz Jakob, Raimund Erbel, Holger Eggebrecht
Journal: Circulation (2010)

Background: Recent MRI studies showed that TAVI is associated with a high incidence of cerebral embolization, our group having detected 115 new embolic lesions in 27/32 patients. The origin of the ...
The expression of brain-derived neurotrophic factor in hippcocampal and serum of chronic obstructive pulmonary disease model rats
Authors: Qun Wang, Yong Lin, Xuefeng Ling, Siqing Sun, Qiang Zhang
Journal: European Respiratory Journal (2011)

Objective:  In clinic,we have found that cognitive impairment frequently occurs in chronic obstructive pulmonary disease (COPD) patients, but little is known about its pathogeny. And, researchers confirmed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of cognitive impairment and is affected by many factors, for example, smoking, infection, hypoperfusion, hypoxia, et al. In this study, we aimed to explore the effects of passive smoking and intratracheal instillation of lipopolysaccharide (LPS), alone or in combination,on BDNF expression in hippcocampal and serum.   Methods:  In consideration of smoking and infection are two main inducement of COPD, we established the rat COPD model by passive smoking and intratracheal instillation of LPS. Four rat groups were studied,with equal age and gender ratios in each: control (n=6), smoking (n=6), LPS (n=6) and smoking+LPS (n=6, COPD model). Level of BDNF in serum was measured by ELISA. And the expression of BDNF in hippcocampal was assessed using immunohistochemistry and image analysis method.   Results:  We found that compared to controls, BDNF in hippcocampal and serum significantly increased after smoking, LPS and smoking + LPS exposure. However, BDNF increased less evident in COPD model than in smoking or LPS model both in hippcocampal and serum.   Conclusion:  Smoking and intratracheal instillation of LPS (alone or in combination) exposure can increase BDNF level in hippcocampal and serum. Upregulation of BDNF may be paly a protective role in the early stage of smoking, LPS and COPD.
Gold nanoparticles in ionizing radiation therapy of brain cancer
Authors: Reem Yunis, Yongquan Qu, Christabel Moy, Andrew Vaughan, Ting Guo
Journal: Cancer Research (2008)

5750   Each year about 19,000 people in the United States are diagnosed with primary brain tumors. Overall, only about 30% of these cases are alive a year later. Although it is the most effective therapy for brain malignancy, ionizing radiation (IR) remains palliative because of radioresistance. The effect of ionizing radiation is achieved primarily through DNA damage in the irradiated cells. Sensitizing tumor cells to IR would result in a more effective radiation therapy. Gold nanoparticles (AuNP) are widely used in biological and biomedical applications. In a previous study a 200% enhancement of damage to a 5.6 Kbp DNA molecule conjugated to only ten 3nm AuNP was achieved after X-ray exposure. The combination of localized X-ray absorption, effective release of low-energy electrons, and efficient deposition of energy is the mechanism by which AuNP causes DNA damage. Therefore, we aimed to test the use of AuNP in a cellular system and assess its effect on DNA damage and cell killing after exposure to ionizing radiation. Cells from a medulloblastoma-derived cell line (Daoy) were incubated with positively-charged AuNP (TMA) or negatively-charged AuNP (MUA) for 24 hours, washed and then subjected to 0, 2, 4, 6, and 8 Gy of IR. Three days after irradiation, cellular growth was measured by MTT assay. At all IR doses about 50% cellular growth inhibition was observed in cultures treated with AuNP prior to irradiation compared to the growth of their irradiated-only counterparts. In another set of experiments, survival rate was evaluated 10 days after irradiation using the clonogenic assay. The survival rate of the AuNP-pretreated cultures was also about 50% lower than that of their irradiated-only counterparts. In addition, the AuNP effect was a dose and cell density dependent. A concentration of 1ug AuNP was sufficient to sensitize cells to IR when thinly seeded (500 cells per well) whereas in a 1000-cells per well density, a concentration of 10ug was required to sensitize the cells. To overcome cytotoxicity and improve cellular uptake, other types of AuNP coating-ligands are being explored ( e.g. , neutral and sugar ligands). In summary, these preliminary findings show the potential use of gold nanoparticles in radiation therapy of brain tumors.
Abstract 13249: Oxygen Preconditioning Prevents Contrast-Induced Nephropathy after Coronary Angiography in Patient of Ischemic Heart Disease
Authors: Haruki Sekiguchi, Issei Ishida, Yoshie Uchida, Hisao Otsuki, Hidetoshi Hattori, Hiroyuki Arashi, Yasunori Kobayashi, Youichi Ajiro, Kentaro Jujo, Jyunichi Yamaguchi, Kazunori Iwade, Naohide Tanaka, Masatoshi Kawana, Nobuhisa Hagiwara
Journal: Circulation (2011)

BACKGROUND: Contrast-induced nephropathy (CIN) is reported as one of the independent predictors of long-term mortality in patients with ischemic heart disease undergoing coronary angiography (CAG)....
Oxygen desaturation is associated with diabetes mellitus in patients with obstructive sleep apnoea
Authors: Mohammed Al-Abri, Hussain Al-Lawati, Yousef Al-Alawi, Abdullah Al-Manairi
Journal: European Respiratory Journal (2011)

Objective:  Obstructive sleep apnoea (OSA) is associated with impaired glycaemic control. The aim of the study was to evaluate the contribution of oxygen desaturation in the association of diabetes mellitus (DM) OSA.   Methods:  The study was conducted retrospectively between January 2008 and May 2010 in sultan Qaboos University Hospital, department of clinical physiology. The data were collected using electronic medical records and sleep study report. Desaturation index (DI) was calculated by the number of desaturation dips from wakefulness level in addition to SaO 2     Results:  The total number of cases was 180 (116 males & 64 females) with mean age of 43±17 years. Female patients were more obese than males (BMI= 37.2±10.3 kg/m 2 , 32.7±8.2 kg/m 2  respectively, P=0.005). The mean apnea/hypopnea index (AHI) was 31±31 and mean Epworth sleepiness scale (ESS) was 11±5. There was significant association between diabetes mellitus (DM) and AHI (median for diabetic 39 Vs 18 for non-diabetic, p=0.03). Furthermore, there was significant association between diabetes and oxygen desaturation index (median for diabetic 25 Vs 9.6 for non diabetic p=0.02) and it becomes more significant with severe desaturation (SaO 2   0.05).   Conclusion:  The study showed that Obstructive sleep apnoea is associated with diabetes mellitus. OSA patients with more severe Oxygen desaturation are at greater risk of developing diabetes.
Abstract 2195: Significant Relation of Arterial Stiffening to Hyperventilatory Response to Exercise in Patients with Coronary Artery Disease
Authors: Kenki Enko, Satoru Sakuragi, Kengo Kusano
Journal: Circulation (2008)

Exercise intolerance is a common feature of patients with coronary artery disease (CAD). Enhanced ventilatory response is determinants of exercise capacity and marker of a poor prognosis irrespective of LV systolic function. Pulse wave velocity (PWV), which is a reliable marker of arterial stiffness, modulates left ventricular (LV) function and is related to exercise capacity in CAD patients; however, the relationship of PWV to ventilatory response to exercise in CAD patients has not been fully elucidated. In this study, we examined PWV and cardiopulmonary exercise testing (CPX) in CAD patients and evaluated the relationship between PWV and ventilatory response to exercise. We studied 81 CAD patients (69±8yo, 64men). All subjects underwent symptom limited CPX. Ventilatory response to exercise was determined by VE/VCO 2 slope. We also measured PWV using an automated device (form ABI/PWV, Colin, Japan) prior to CPX. LV function was assessed by echocardiogram. In univariate analysis, PWV was related to VE/VCO 2 slope (r=0.34, p&lt;0.01). PWV was also associated with exercise time (r=−0.22, p&lt;0.05), time to ST depression (r=−0.32, p&lt;0.01) and peak VO 2 (r=−0.44, p&lt;0.01). The relationship between PWV and VE/VCO 2 was still significant after adjustment for age, sex and blood pressure. Patients with high PWV (over 1800cm/sec, n=29) had higher BNP (140±214 vs 59±66 pg/ml, p&lt;0.05) and lower E/A ratio (0.7±0.2 vs. 0.9±0.3, p&lt;0.05) than those with low PWV (under 1800cm/sec, n=52). In exercise testing, patients with high PWV had higher VE/VCO 2 slope (30.9±2.6 vs. 29.0±3.4, p&lt;0.01), shorter time to ST depression than patients with low PWV (352±79 vs. 403±59 sec, p&lt;0.01), whereas severity of CAD, defined as number of diseased vessels, was comparable between the two groups. Arterial stiffening is associated with enhanced ventilatory response to exercise in CAD patients. Diastolic dysfunction and lowered threshold of myocardial ischemia associated with arterial stiffening are probably involved in the hyperventilatory response to exercise in CAD patients.