tbuckley/cabot-search huggingface dataset:
Association of Serum Levels of Adipokines and Insulin With Risk of Barrett's Esophagus: A Systematic Review and Meta-Analysis
Authors: Apoorva Krishna Chandar, Swapna Devanna, Chang Lu, Siddharth Singh, Katarina Greer, Amitabh Chak, Prasad G. Iyer
Journal: Clinical Gastroenterology and Hepatology (2015)
The WT1 tumor gene in FLT3-signaling
Authors: Karina Vidovic, Tor Olofsson, Urban Gullberg
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1781 

The Wilms tumor gene 1 (WT1) is highly expressed in most acute myeloid and lymphoid leukemias and expression increases during progression of chronic myeloid leukemia (CML) into blast crisis, suggesting a role of WT1 in leukemogenesis. Consistently, repression of WT1 levels leads to increased apoptosis of some leukemic cell lines. Moreover, WT1 induces acute leukemia in cooperation with the leukemia-associated fusion protein AML1-ETO in mice. Our data show that signaling from the oncogenic fusion tyrosine kinase BCR/ABL1, via PI3K/Akt, leads to increased transcription of the WT1 gene. Interestingly, forced expression of WT1 in cells from chronic myeloid leukemia, harbouring the BCR/ABL1 fusion gene, leads to resistance to apoptosis induced by imatinib, an inhibitor of BCR/ABL1. We hypothesize that also other leukemia associated oncogenic tyrosine kinases signals for high expression of WT1, thus contributing to increased resistance to apoptosis. The FLT3 tyrosine kinase signaling pathway is activated in a large number of acute myeloid leukemias; 30% of cases show an internal tandem duplication (ITD) in the cytosolic part of the FLT3 receptor protein leading to constitutive activation of FLT3 signaling. Inhibitors of FLT3 are currently in clinical trials. The FLT3-ITD expressing cell line MV4-11 is sensitive to inhibitors of FLT3 in vitro. Consistent with our hypothesis, inhibition of FLT3-ITD with the FLT3 inhibitor AG1296 resulted in rapid and specific downmodulation of WT1 mRNA levels. Downmodulation of WT1 in MV4-11 was later followed by decreased proliferation and viability. WT1 levels and viability of the FLT3 negative cell line HL60 remained unaffected after AG1296 treatment. The direct role and mechanisms of WT1 in apoptosis following inhibition of FLT3-ITD is currently investigated.
Phase 2 Study Of Bendamustine, Bortezomib (Velcade) and Prednisone (BVP) For Newly Diagnosed Multiple Myeloma (MM)
Authors: Maria-Victoria Mateos, Albert Oriol, Laura Rosiñol, Felipe de Arriba, Jesús Martín, Joaquín Martínez-López, Maria Asuncion Echeveste, Josep Sarrá, Gemma Ramirez, Enrique M. Ocio, Rafael Martinez, Luis Palomera, Angel Payer, Rebeca Iglesias, Javier De La Rubia, Adrian Alegre, Anabelle Chinea, Joan Bladé, Juan José Lahuerta, Jesús F San Miguel
Journal: Blood (2013)
pH-sensitive polymer-liposome-based antigen delivery systems potentiated with interferon-γ gene lipoplex for efficient cancer immunotherapy
Authors: Eiji Yuba, Yuhei Kanda, Yuta Yoshizaki, Ryoma Teranishi, Atsushi Harada, Kikuya Sugiura, Takeshi Izawa, Jyoji Yamate, Naoki Sakaguchi, Kazunori Koiwai, Kenji Kono
Journal: Biomaterials (2015)
Structure-activity relationships of acridine derivatives via click chemistry: A novel class of G-quadruplex binding ligands
Authors: Silvia Sparapani, Filippo Doria, Mekala Gunaratnam, Stephen Neidle
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1313 

Besides Watson-Crick duplex structures, DNA can adopt other topologies during replication, transcription, recombination and damage repair processes. Of particular interest are the higher-order topologies, termed G-quadruplexes, formed by the planar arrangement of four hydrogen bonded guanine bases. These G-rich sequences are found at the ends of telomeric DNA in eukaryotic chromosomes and have the potential to cause instability at chromosome ends, leading to senescence and apoptopsis in cancer cells. A number of small molecules are capable of trapping and stabilizing the 3’ single-stranded overhang of telomeric DNA as these G-quadruplex structures disrupt the binding of telomerase and associated telomere maintenance. G-quadruplex forming motifs are also found in the promoter regions of many oncogenes (for example in the genes c-myc and c-kit ) and they may be involved in the control of cell growth and proliferation.    A large number of small molecules, based on planar tricyclic chromophores, have previously been shown to be effective stabilisers of quadruplex DNA and inhibitors of telomerase activity in vitro . We have been developing ligands based on the acridine moiety, a proven quadruplex-binding motif, since acridines typically have favourable pharmacological features, especially good cellular uptake. A novel library of acridine derivatives has been devised, using click chemistry as a strategic synthetic approach, for the obtainment of readily available complex molecules in high yield. The introduction of the triazole ring, generated by the Huisgen 1,3-dipolar cycloaddition click reaction of acridine bis-azides and a library of substituted alkynes, was designed to enhance, along with the acridine scaffold, favourable π-stacking interactions with the central area of the G-tetrad plane in a quadruplex.    Compounds have been evaluated for quadruplex selectivity by a FRET-based binding assay, and by surface plasmon resonance (SPR) methods. Their effects on a panel of cancer cell lines, known to express telomerase, and a normal fibroblast cell line, will also be reported.
Polytrauma induces increased expression of pyruvate kinase in neutrophils
Authors: Rudolf Oehler, Gertrude Weingartmann, Nicole Manhart, Ulrich Salzer, Michael Meissner, Werner Schlegel, Andreas Spittler, Michael Bergmann, Daniela Kandioler, Christiane Oismüller, Heidi M. Struse, Erich Roth
Journal: Blood (2000)
Abstract 94: Difference of Clinical Characteristics of Sudden Cardiac Arrest and Syncope Related to Coronary Vasospasm
Authors: Ikuko Togashi, Toshiaki Sato, Kyoko Soejima, Shunichiro Miyoshi, Koujiro Tanimoto, Hirotaka Yada, Koutaro Fukumoto, Hikaru Nakamizo, Satoshi Ogawa
Journal: Circulation (2007)

Patients with coronary vasospasm generally have a good prognosis although lethal arrhythmia can result in sudden cardiac arrest (SCA) or syncope. Clinical predictors of SCA related to coronary vasospasm were not clear. We investigated the differences of clinical characteristics and outcome of pts with SCA and syncope related to coronary vasospasm. Method and results; Out of consecutive 47 pts with coronary vasospasm, pts presented SCA(n=13) and syncope(n=26) were enrolled in the study. Pts complicated with 5 idiopathic VF/VT and 3 neurally-mediated syncope were excluded. All pts had a normal LV function except 1 pt with ACS. One pt had coronary artery disease. SCA was experienced during first cardiac event in 77% of SCA group, whereas syncope in 31% of syncope group (p=0.04, as shown in Table ). In SCA group, 2 pts resulted in hospital death after DC-resistant VF, 1 pt died suddenly at home after medical-refractory angina. ICD was implanted in 3 survivors. Ca channel blockers were administered in all pts of each group. After discharge of hospital, during a follow-up period of 3.7±4.1yrs, survivors of SCA group did not experience any additional arrhythmic events and all pts of syncope group were alive while 1 pt had recurrent syncope. Conclusion; Coronary vasospasm can results in SCA during a first cardiac event. The prognosis of the survivors and pts with a history of syncope may be favorable under good medical control of spasm.
Abstract 898: The Kruppel-Like Factor KLF15 is a Novel Regulator of Cardiomyocyte Hypertrophy
Authors: Sudeshna Fisch, Susan J Gray, Stephane Heymans, Baiqiu Wang, Saptarshi Haldar, Otmar Pfister, Lei Cui, Ajay Kumar, Zhiyong Lin, Sucharita Sen-Banerjee, Hiranmoy Das, Christy Petersen, Ulrike Mende, Barbara Burleigh, Yan Zhu, Yigal Pinto, Ronglih Liao, Mukesh K Jain
Journal: Circulation (2006)

Background: Cardiac hypertrophy is a common response to injury and hemodynamic stress and an important harbinger of heart failure and death. The molecular mechanisms underlying this disease process...
Measuring clinically significant chemotherapy-related toxicities using Medicare claims from CALGB breast and lung cancer trial participants
Authors: E. B. Lamont, J. E. Herndon, J. C. Weeks, I. C. Henderson, R. Lilenbaum, R. L. Schilsky, N. A. Christakis
Journal: Journal of Clinical Oncology (2007)

6595 Background: Because the elderly are numerically underrepresented in cancer clinical trials, the benefits and toxicities of cancer therapies in the general population of elderly patients is not known. Nevertheless, clinicians need such information. A solution may be found in analyses of observational data. Specific Aim: We performed a criterion validation study to determine the accuracy with which observational Medicare claims data measure clinically significant chemotherapy-related toxicities in elderly Medicare beneficiaries with cancer. Methods: We created a cohort of 175 elderly clinical trial patients treated on two Cancer and Leukemia Group B (CALGB) trials (i.e., 9,344 adjuvant breast and 9,730 advanced lung cancer trials) and merged participants’ CALGB data with their Centers for Medicare and Medicaid Services (CMS) data. From CALGB data, we identified all grade III/IV toxicities with a frequency of ≥3%. We reviewed diagnostic and procedure codes from CMS coding manuals, developed initial algorithms to measure the toxicities and then finalized the algorithms after empiric review of individual patients’ actual CMS codes incurred during the observation period (i.e., date of first trial treatment through 90 days following last trial treatment). We compared results of each of our CMS toxicity algorithms to gold-standard of CALGB grade III/IV toxicity information in order to calculate the CMS algorithms’ test characteristics. Results: The following 15 grade III /IV chemotherapy-related toxicities occurred in ≥3% of the 175 patients: white blood cell, hemoglobin, platelets, anorexia, nausea, vomiting, diarrhea, stomatitis, sensory neuropathy, motor neuropathy, motor or sensory neuropathy, dyspnea, hyperglycemia, infection, and malaise. Of these, only the CMS-based algorithm measuring ‘grade III/IV vomiting‘ had a sensitivity, specificity, and area under the ROC of ≥ 80%. Conclusions: The results of this preliminary study suggest that CMS claims data may be of only limited value in measuring clinically significant chemotherapy- related toxicities in elderly Medicare beneficiaries with cancer. Future research will focus on confirming these findings in a larger and more diverse patient sample. No significant financial relationships to disclose.
Abstract P120: Long-Term Adherence to Heart Healthy Behaviors in Older Adults: A Theory-Based Approach
Authors: Kathleen M Michael, Margaret Hammersla, Jennifer Klinedinst, Barbara Resnick
Journal: Circulation (2015)

Despite evidence-based recommendations, long-term adherence to heart-healthy behaviors is generally low in older adults. Many behavioral strategies have induced short term improvements in physical activity, diet adherence, and medication use, but sustained change in health behaviors beyond six months remains a challenge. No single approach seems to result in durable, long-term lifestyle change. We hypothesized that a Social-Ecological Model incorporating Social Cognitive Theory, combined with Diffusion of Innovation would increase long term heart-healthy behaviors in community-dwelling older adults. We conducted a single group study using repeated measures at baseline, 3, 6, 12 and 24 months to evaluate adherence to exercise, diet, and prescribed medications. We evaluated the effects of a two phase theory-based behavioral intervention on overall physical activity, physical performance, fat and sodium intake, prescribed medication use, blood pressure, self-efficacy (exercise, diet, medications), resilience, depression, and pain. Twenty-nine low income seniors with cardiovascular risk factors completed the intervention, which consisted of a 12-week education and initiation phase led by a nurse and lay exercise trainer in the participants’ congregate residence. The second phase focused on motivation and dissemination. Ongoing health behaviors were facilitated by 1) group intervention with social support, 2) extended intervention exposure over 24 months, with twice-weekly exercise classes continued with the lay trainer and within-community champions, 3) eminders and cues, and 4) monthly inoculation visits by healthcare providers to reinforce motivation and target behaviors. Across the study, 50% of the participants consistently attended the classes and engaged in exercise activities. The percentage of individuals participating in at least 10 minutes of exercise per week increased. Although below recommended guidelines, the trend toward greater exercise participation is encouraging given the challenges to adherence noted in this population. In addition we found that outcome expectations for exercise increased significantly (p = 0.05). Dietary intake showed significant decreases in fat consumption (p = 0.001), and medication adherence was consistently strong. Results of the study demonstrate the feasibility of using this model to successfully engage participants within their own environment over 24 months, and to use lay trainers and community champions to sustain the exercise and education intervention with periodic inoculations by healthcare providers. While individual improvements were modest, they nonetheless provide support for the efficacy of theory-based interventions to facilitate long-term adherence to heart-healthy behaviors, and may guide future work to develop and test robust efficacy-enhancing interventions.
Abstract 15562: Cost-Effectiveness of STEMI Management Strategies for Patients Presenting to Non-Urban Centers: A Model-Based Analysis
Authors: Brian J Potter, Milton C Weinstein, Thomas A Gaziano
Journal: Circulation (2013)

Introduction: Despite great efforts and expense to transfer patients to existing cardiac catheterization laboratories (CCL’s) for primary PCI, real-world data have shown that door-to-balloon object...
Abstract 19348: Reduced Cx43 Expression Leads to Increased Fibrosis and Pro-arrhythmia due to Enhanced Fibroblast Activity in Aged and Pressure Overloaded Mice
Authors: John A Jansen, Toon A van Veen, Sanne de Jong, Roel van der Nagel, Helen E Driessen, Ronald p Labzowski, Astrid A Bosch, Carolin M Oefner, Marc A Vos, Jacques M de Bakker, Harold V van Rijen
Journal: Circulation (2010)

Background:  Arrhythmogenic ventricular remodeling is hallmarked by both reduced gap junction (Connexin43, Cx43) expression and increased collagen deposition (fibrosis). We hypothesized that reduced Cx43 expression is responsible for enhanced fibrosis in the remodeled heart, resulting in an arrhythmogenic substrate. Therefore, we investigated the effect of normal or reduced Cx43 expression on the formation of fibrosis in a physiological (aging) and pathophysiological (Transverse Aortic Constriction, TAC) mouse model.   Methods:  Cx43fl/fl (control) and Cx43CreER(T)/fl mice (Cx43HZ) were aged to 20 months, or at the age of 3 months either TAC- or SHAM-operated and sacrificed after 16 weeks. Hearts were Langendorff-perfused, and epicardial mapping of LV and RV was performed to determine epicardial conduction velocity (CV), effective refractory period (ERP), and susceptibility for arrhythmias. Cx43 expression, fibroblast proliferation (DDR-2) and activity (pro-collagen peptide III) was determined by Western Blotting and immunohistochemistry. Sirius Red staining was performed to determine collagen content.   Results:  Cx43 expression was reduced by half in all Cx43HZ mice compared to their control. Collagen deposition was significantly increased in aged Cx43HZ mice compared to aged control mice (7.38 vs 1.10%). TAC-operation increased fibrosis in control (4.0%) compared to SHAM (0.4%), but was significantly higher in Cx43HZ (10.77%). DDR-2 expression appeared unchanged, but pro-collagen peptide III expression was higher in TAC-operated Cx43HZ mice. Arrhythmia vulnerability was high in aged Cx43HZ mice (67%), in contrast to aged control mice (0%). Aged Cx43HZ mice with arrhythmias had significantly higher levels of fibrosis and conduction heterogeneity than aged Cx43HZ mice without. TAC-operation increased arrhythmia susceptibility (35%) in both Cx43HZ and control mice compared to SHAM (0%), and significantly increased heterogeneity of conduction in RV of Cx43HZ mice.   Conclusions:  Reduced cellular coupling resulted in more excessive collagen deposition during aging or pressure overload in mice due to enhanced fibroblast activity, leading to increased conduction inhomogeneity and pro-arrhythmia.
Abstract 755: Adoptive Transfer of RAGE-Deficient T lymphocytes Attenuates Atherosclerosis in Diabetic Apolipoprotein E Null Mice
Authors: De-xiu Bu, Janine Lee, Rosa H Rosario, Yan Lu, Ann Marie Schmidt, Raphael A Clynes
Journal: Circulation (2007)

Atherosclerosis is an inflammatory disease, associated with immune responses and other metabolic factors such as diabetes. Receptor for advanced glycation end products (RAGE) plays a central role in diabetic atherosclerosis. However, the impact of immune cell RAGE on lesion development in atherosclerosis-prone mice has not yet been studied. Here, we tested the hypothesis that T lymphocyte RAGE contributed to lesion progression in established atherosclerosis in diabetic Apolipoprotein E (apoE) null mice.   Methods and Results : Male apoE null mice, apoE null/RAGE null (all in the C57BL/6 background) age 6 weeks, were rendered diabetic with streptozotocin; at 14 weeks of age, mice were sacrificed and aortas were collected for lesion analysis. The aortic mean lesion area in apoE null/RAGE null mice was 2.3-fold lower compared to that in apoE null mice, 61,120.87±4,258.86 μm 2  (n=6) verus142,367.02 ±7,621.08 μμ 2  (n=6), respectively, p 2  (n=7) verus 304,275.20±76,797.69 μm 2  (n=6), p 0.05.   Conclusions:  These data provide definitive evidence that RAGE contributes significantly to the acceleration of atherosclerosis in diabetes, and that T lymphocyte RAGE is critically involved in this process. Therefore, cell-specific targeting RAGE might be a potential therapeutic strategy for treating atherosclerosis in diabetes.
Abstract 1289: Activation of the Transient Receptor Potential V4 Channel Causes Cardiovascular Collapse Mediated by Endothelial Failure
Authors: Robert N Willette, Weike Bao, Sandhya Nerurkar, Tian-li Yue, Chris P Doe, Gerald Stankus, Haisong Ju, Ross Bentley, Anthony Sulpizio, David Behm, Hoffman Sandra, Kristeen Maniscalco, Zuojun Lin, Casillas N Linda, Min Lin, Robert E Trout, Bartholomew J Votta, Robert W Marquis, Xu Xiaoping
Journal: Circulation (2007)

Transient receptor potential V4 (TRPV4), is an osmo/mechano-sensitive ligand-gated non-selective cationic channel that contributes to intracellular Ca 2+ homeostasis and regulation of cell volume. TRPV4 is highly expressed in endothelial and various epithelial cells and to a lesser extent in vascular smooth muscle. The purpose of the present study was to evaluate the cardiovascular effects of a potent novel small molecule TRPV4 activator (TRPV4A; EC 50 = 19, 8 or 1 nM in mouse, rat or dog, respectively) and to examine its mechanism of action. In the three species (mouse, rat and dog) examined, the intravenous administration of TRPV4A in anesthetized preparations induced a dose-dependent reduction in blood pressure, followed by cardiovascular collapse at doses ≤300 ug/kg. TRPV4A had no acute cardiovascular effects in the TRPV4 −/− null mouse (&gt;5 mg/kg, iv). Hemodynamic analysis in the dog suggested that the terminal event was related to a profound reduction in cardiac output (decreased SV followed by decreased HR). However, TRPV4A had no effect on rate or contractility in the isolated, buffer-perfused rat heart. In contrast, TRPV4A produced potent endothelial-dependent relaxation of rodent isolated vascular ring segments that was abolished by NOS inhibition (L-NAME) and eNOS gene deletion. Surprisingly, the in vivo cardiovascular collapse induced by TRPV4A was not altered by NOS inhibition (L-NAME), eNOS gene deletion or by treatment with anticoagulant or antiplatelet agents. Cardiovascular collapse induced by TRPV4A was correlated (concentration and time appropriate) with profound fluid extravasation (Evans Blue) and tissue hemorrhage in the lung, intestine and kidney. Consistent with these results, TRPV4A induced a ruthenium-red sensitive non-selective cation current, reduction in cell volume and subsequent cell death in cultured endothelial cells. These results provide the first characterization of the cardiovascular effects of a potent and selective TRPV4 channel activator and suggest that inappropriate activation of TRPV4 produces acute cardiovascular collapse associated with endothelial activation/injury and failure of the microvascular permeability barrier.
Abstract 20995: Early and Mid-term Results of Ablation for Atrial Fibrillation (AF) Concomitant to Isolated CACB Surgery
Authors: Ardawan Rastan, Kristin Badel, Anne Simon, Anne-Kathrin Funkat, Nicolas K Doll, Sven Lehmann, Martin Misfeld, Friedrich W Mohr
Journal: Circulation (2010)

Objective:  Results of surgical AF ablation in combination with isolated CABG were evaluated with regard to different AF pathologies and applied energy sources.   Methods:  During 2002–2009 a total of 268 patients received isolated CABG and surgical AF therapy. For endocardial approach cryotechnology and for epicardial approach predominantely bipolar radiofrequency was applied. All patients received 24h Holter before discharge and after 12 months. During yearly telephone follow-up all medication and clinical symptoms were determined accompanied by SF-12 and AF severity score questionnaires.   Results:  Age was 70.6±6.7y with 20.0% female. Ejection fraction was 54.4±12.5%. Paroxysmal AF was present in 47.3%, 32.5% had preoperatively oral anticoagulation. LA size was 46.8±8.2mm, AF history was 3.7±3.1y. 2.9±0.9 distal anastomoses were performed with 96.2% LIMA and 31.5% BIMA use and 28.0% OPCAB. Endocardial approach was used in 33.8%. Hospital mortality was 4.2% and varied significant between paroxysmal (1.6%) vs. persistent AF (6.6%, p=0.03). SR at discharge was present in 86.2% of paroxysmal and 63.5% of persistent AF (p   Conclusions:  Concomitant AF ablation for atrial fibrillation in ischemic heart disease is highly effective especially in paroxysmal AF. For patients with persistent AF endocardial cryoablation is more successful but is associated with a higher perioperative adverse event rate.
Abstract 16498: AMP-Activated Protein Kinase Plays an Essential Role in Sildenafil-Induced Cardioprotection against Ischemia-Reperfusion Injury
Authors: Anindita Das, Fadi N Salloum, Sai S Koka, Lei Xi, Rong Tian, Rakesh C Kukreja
Journal: Circulation (2012)

Background:  Sildenafil (SIL), a inhibitor of phosphodiesterase-5 induces powerful protection against myocardial ischemia/reperfusion (I/R) injury through nitric oxide (NO) and protein kinase G (PKG). AMP-activated protein kinase (AMPK) is a key regulator of myocardial energy metabolism and plays a protective role in ischemic myocardium. Since the catalytic subunit α2 of AMPK is highly expressed in heart and AMPK interacts with both NO and PKG, we tested the hypothesis that AMPK mediates sildenafil-induced cardioprotection against I/R injury, using the transgenic mice with cardiac-specific overexpression of a dominant-negative AMPKα2 subunit (dn-AMPKα2).   Methods & Results:  Adult male dn-AMPKα2 and wild-type (WT) mice were pretreated with saline or SIL (0.7 mg/kg i.p.). One hour later, the hearts were subjected to I/R by occlusion of coronary artery for 30 min followed by reperfusion for 24 hours. As shown in Fig. A, myocardial infarct size was significantly reduced in SIL-treated WT mice as compared to saline treated mice (P   Conclusion:  The loss of protective effects of SIL in the dn-AMPKα2 mice strongly suggests that activation AMPK is essential for SIL-induced cardioprotection against I/R injury.