tbuckley/cabot-search huggingface dataset:
EphA2 Expression Regulates Inflammation and Fibroproliferative Remodeling in Atherosclerosis
Authors: Alexandra C. Finney, Steven D. Funk, Jonette M. Green, Arif Yurdagul, Mohammad Atif Rana, Rebecca Pistorius, Miriam Henry, Andrew Yurochko, Christopher B. Pattillo, James G. Traylor, Jin Chen, Matthew D. Woolard, Christopher G. Kevil, A. Wayne Orr
Journal: Circulation (2017)

Atherosclerotic plaque formation results from chronic inflammation and fibroproliferative remodeling in the vascular wall. We previously demonstrated that both human and mouse atherosclerotic plaques show elevated expression of EphA2, a guidance molecule involved in cell-cell interactions and tumorigenesis.Here, we assessed the role of EphA2 in atherosclerosis by deleting EphA2 in a mouse model of atherosclerosis (Apoe-/-) and by assessing EphA2 function in multiple vascular cell culture models. After 8 to 16 weeks on a Western diet, male and female mice were assessed for atherosclerotic burden in the large vessels, and plasma lipid levels were analyzed.Despite enhanced weight gain and plasma lipid levels compared with Apoe-/- controls, EphA2-/-Apoe-/- knockout mice show diminished atherosclerotic plaque formation, characterized by reduced proinflammatory gene expression and plaque macrophage content. Although plaque macrophages express EphA2, EphA2 deletion does not affect macrophage phenotype, inflammatory responses, and lipid uptake, and bone marrow chimeras suggest that hematopoietic EphA2 deletion does not affect plaque formation. In contrast, endothelial EphA2 knockdown significantly reduces monocyte firm adhesion under flow. In addition, EphA2-/-Apoe-/- mice show reduced progression to advanced atherosclerotic plaques with diminished smooth muscle and collagen content. Consistent with this phenotype, EphA2 shows enhanced expression after smooth muscle transition to a synthetic phenotype, and EphA2 depletion reduces smooth muscle proliferation, mitogenic signaling, and extracellular matrix deposition both in atherosclerotic plaques and in vascular smooth muscle cells in culture.Together, these data identify a novel role for EphA2 in atherosclerosis, regulating both plaque inflammation and progression to advanced atherosclerotic lesions. Cell culture studies suggest that endothelial EphA2 contributes to atherosclerotic inflammation by promoting monocyte firm adhesion, whereas smooth muscle EphA2 expression may regulate the progression to advanced atherosclerosis by regulating smooth muscle proliferation and extracellular matrix deposition.
LUME-Meso: Randomised phase II/III study of nintedanib (N) + pemetrexed/cisplatin (PEM/CIS) followed by maintenance N or placebo (P) in chemo-naïve patients with malignant pleural mesothelioma (MPM)
Authors: S. Popat, R. Gaafar, A. Nowak, A. Tsao, J. Van Meerbeeck, N. Vogelzang, T. Nakano, D. Velema, N. Morsli, G. Scagliotti
Journal: Annals of Oncology (2017)
Abstract 384: Leucine, Serine and Methionine Differentially Affect Protein Synthesis in Rat Heart
Authors: Anja Karlstaedt, Hernan Vasquez, Heinrich Taegtmeyer
Journal: Circulation Research (2015)

Alternating flux through metabolic pathways enables the heart to rapidly adapt to stress. As a consequence, compensatory mechanisms are often associated with changes in mitochondrial function and cellular redox state. The collective importance of these metabolic changes to energy provision and protein turnover remains unknown. We therefore integrated radioactive tracer studies with a mathematical model of cardiac metabolism - CardioNet. We assessed through flux rate analysis the impact of altered amino acid supply on mitochondrial metabolism. In combination with leucine, both serine and methionine resulted in a two- to threefold increased variance of mitochondrial flux rates. Next we used the isolated working rat heart to determine whether supply of glucose and leucine, in combination with either serine or methionine at different concentrations, affects cardiac protein turnover and energy provision. While glucose remained the major energy source, oxidation of leucine contributed to ATP production. Methionine, but not serine, markedly increased both myocardial oxygen consumption and cardiac power at normal physiologic concentrations. Protein synthesis rates (units given in μmol/min/g dry wt) did not significantly differ from leucine alone (0.037±0.001) or leucine in combination with serine (0.038±0.003) or methione (0.045±0.007). However, with increased serine supply, protein synthesis significantly increased (0.0907±0.009) compared to methionine (0.059±0.006, p=0.024) or leucine only (0.015±0.002, p=0.031). The results suggest that myocardial protein synthesis is differentially regulated by specific amino acids.
Efficacy and safety of sofosbuvir and daclatasvir for 8 weeks in treatment-naïve non-cirrhotic patients with chronic hepatitis C virus Genotype 3 Infection
Authors: C. Hezode, V. Leroy, I. Rosa, F. Roudot-Thoraval, J.-M. Pawlotsky, V. de Ledinghen, J.-P. Bronowicki
Journal: Journal of Hepatology (2017)
Identificaiton of an hot integration area for hepatitis B viral genome in the tenth intron of DEP Domain-Containing 5 gene in hepatoma patients with unfavorable postoperative prognosis
Authors: C.-T. Yeh, C.-W. Hsu, C.-L. Lin, K.-H. Liang, M.-W. Lai, M.-L. Chang, W.-R. Lin, Y.-C. Chen, Y.-H. Huang, T.-H. Wang
Journal: Journal of Hepatology (2017)
Nicotinamide Increases the Megakaryocytic Maturation of Human Hematopoietic Stem Cells Primarily Due to SIRT Inhibition
Authors: Swapna Panuganti, Lisa M. Giammona, Jan M. Kemper, Pani Apostolidis, Stephan Lindsey, Eleftherios Papoutsakis, William M. Miller
Journal: Blood (2008)
Favorable clinical outcome and response to immunotherapy share a common PD-L1/PD-1 based NSCLC immune contexture
Authors: G. Mazzaschi, D. Madeddu, G. Bocchialini, L. Gnetti, G. Armani, F. Sogni, M. Tiseo, A. Ardizzoni, F. Aversa, F. Quaini
Journal: Annals of Oncology (2017)
Impact of sustained virological response with DAAs in patients with compensated HCV cirrhosis and endoscopic esophageal varices study
Authors: M. Puigvehí, M.-C. Londoño, R.M. Morillas, M. Miquel, A. Gallego, S. Lens, Z. Mariño, M. Vergara, S. Lorente, X. Torras, R. Planas, R. Solà, J.A. Carrión
Journal: Journal of Hepatology (2017)
Estimates of total body iron indicate 19 mg and 38 mg oral iron are equivalent for the mitigation of iron deficiency in individuals experiencing repeated phlebotomy
Authors: Walter Bialkowski, Joseph E. Kiss, David J. Wright, Ritchard Cable, Rebecca Birch, Pam D'Andrea, Barbara J. Bryant, Bryan R. Spencer, Alan E. Mast
Journal: American Journal of Hematology (2017)

Iron deficiency anemia is a common clinical condition often treated with tablets containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side effects lowering patient compliance. Oral iron supplements also increase hepcidin production causing decreased fractional absorption of subsequent doses. Frequent blood donors often become iron deficient. Therefore, they were enrolled in a two-year study involving continued blood donations and randomization to receive no pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI) did not change for the subset of donors in the no pill and placebo groups who completed both enrollment and final visits (P = .21 and P = .28, respectively). However, repeated measures regression analysis on the complete dataset estimated a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (P = .001). The effects of 19 and 38 mg iron supplementation on TBI were indistinguishable (P = .54). TBI increased by 229 mg after the initial 60 days of iron supplementation (P < .0001) and was maintained at this higher level with continued iron supplementation following each subsequent donation. The TBI increase was apportioned 51 mg to red cell iron (P < .0001) and 174 mg to storage iron (P < .0001). Changes in storage iron were negatively impacted by 57 mg due to concurrent antacid use (P = .04). These findings in blood donors suggest that much lower doses of iron than are currently used will be effective for clinical treatment of iron deficiency anemia.
Predictors of retention in a cervical cancer survivorship study.
Authors: Lari B. Wenzel, Kathryn Osann, Susie Hsieh, Sandra Sappington, Diana Marquez, Dana Meredith Chase, Edward L. Nelson
Journal: Journal of Clinical Oncology (2012)

6132 Background: Women with cervical cancer experience numerous quality of life (QOL) disruptions. A completed pilot study indicated that QOL and key biomarkers could be improved with psychosocial telephone counseling (PTC). A confirmatory trial has recently completed accrual.The purpose of this study is to identify predictors of retention in this large biobehavioral trial, and examine retention differences between the pilot and confirmatory trial. Methods: Women with stage I – III cervical cancer diagnosed 9 – 30 months earlier were randomized to either PTC or usual care. PROs and biological specimens were collected prior to randomization (N=204), and 3 (T2) and 9 months post baseline. Sociodemographic, clinical and QOL variables were evaluated from baseline to T2 to identify predictors of study retention. Multiple measures, including the PROMIS Depression and Anxiety scales were entered into a multivariate stepwise logistic regression model to predict study retention. Results: In the multivariate model, being randomized to counseling (OR=4.4, 95% CI: 1.5-12.6), having clinically significant depression, defined as &gt;1 SD above the 50 th percentile (OR=4.2, 95% CI:1.7-10.5) and being single (OR=3.4, 95% CI: 1.3-9.2) were the most significant predictors of drop-out in the study overall. Among those in the counseling arm, depression is the strongest predictor of dropout, with a five times higher dropout rate (OR=5.2, 95% CI:1.9-15.6) than those with low to moderate levels of depression, or no depression. However, retention rates improved substantially overall from the pilot study (72%) to the confirmatory study (84%), in both study arms, and retention increased among Latinas from 60% in the pilot study to 83% in the current study, and from 52% to 81% among those with less than a high school education. Conclusions: Results from this analysis of predictors of retention indicate that enhanced attention to sociocultural disparities can improve study retention. Attending to baseline clinical depression may be a further consideration.
Abstract B46: Activation of TWIST1 by COL11A1 decreases cell sensitivity to paclitaxel by modulating NFκB -mediated Iκκβ expression
Authors: Yi-Hui Wu, Cheng-Yang Chou
Journal: Cancer Research (2017)

Abstract Background: We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian tumorigenesis via upregulating the Transforming growth factor beta 1 (TGF-β)/ Matrix metalloproteinases 3 (MMP3) axis and upregulated COL11A1 expression enhanced metastatic potential to the lungs. COL11A1 expression is also associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. In this study, we verified how COL11A1 to regulate twist-related protein 1 (TWIST1) in ovarian cancer cells. Methods: ES2 and TOV-21G cells transfected with a small interference RNA of COL11A1 (shCOL11A1) and OVCAR3 and OVCAR4 cells transfected with a COL11A1 expression plasmid. Site-directed mutagenesis assay, luciferase assay, chromatin immunoprecipitation assay, immunofluorescence assay, anchorage-independent soft-agar assay, invasion assay and xenograft animal study were performed in this study. COL11A1 and TWIST1 mRNA expression levels of 104 ovarian tumors were determined by real-time RT-PCR. Results: We found that the level of COL11A1 expression in a panel of ovarian cancer cells was positively correlated with the expressions of TWIST1 and Iκκβ. Mechanistic studies indicated that a decrease in TWIST1 caused by COL11A1-suppressed Iκκβ transcription was achieved by derepression of binding of Sp1 to the Iκκβ promoter. COL11A1-mediated nuclear factor-kappaB (NF-κB) activation, via the activation of Iκκβ transcription, promoted anchorage-independent soft-agar growth, invasion and xenograft tumor formation, which was associated with epithelial-to-mesenchymal transition. In addition, TWIST1 messenger RNA level was positively associated with COL11A1 messenger RNA expression level in ovarian tumors. Conclusions: COL11A1 activates NF-κB signaling by increasing Iκκβ transcription, which results in progression of ovarian cancer and poorer patient outcomes. We suggest that Iκκβ may potentially be targeted in patients with COL11A1-positive tumors. Citation Format: Yi-Hui Wu, Cheng-Yang Chou. Activation of TWIST1 by COL11A1 decreases cell sensitivity to paclitaxel by modulating NFκB -mediated Iκκβ expression. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B46.
Liver steatosis and fibrosis in at-risk European HIV-monoinfected patients
Authors: M. Lemoine, L. Assoumou, P. Ingiliz, P.-M. Girard, S. De Wit, M.-A. Valantin, A. Huefner, J. Schulze zur Wiesch, S. Mauss, Y. Menu, P. Bedossa, J. Capeau, D. Costagliola, G. Behrens
Journal: Journal of Hepatology (2017)
Extent of portal invasion in patients with hepatocellular carcinoma: the more, the worse?
Authors: R. Kloeckner, V. Steinle, S. Koch, D.P. dos Santos, A. Mähringer-Kunz, C. Düber, H. Lang, M. Sprinzl, J.U. Marquardt, P.R. Galle, A. Weinmann
Journal: Journal of Hepatology (2017)
Abstract 17169: The Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial
Authors: Erin A Bohula, Robert P Giugliano, Christian T Ruff, Julia F Kuder, Sabina A Murphy, Elliott M Antman, Eugene Braunwald
Journal: Circulation (2015)

Background: Edoxaban (edox), an oral factor Xa inhibitor with 50% renal clearance, was non-inferior to warfarin for prevention of thromboembolic events and significantly reduced bleeding in pts with AF. However, a detailed analysis of the impact of creatinine clearance (CrCl) on clinical outcomes with edox has not been described. Purpose: We evaluated the safety, efficacy and net clinical outcome of edox vs warfarin (warf) across the range of baseline CrCl in the ENGAGE AF-TIMI 48 trial. Methods: 14,071 AF pts at moderate-to-high risk of stroke were randomized to edox 60mg QD or warf. Severe renal dysfunction (CrCl&lt;30ml/min) was exclusionary and a CrCl 30-50 resulted in a 50% dose reduction of edox (30mg QD). Endpoints of stroke or systemic embolism (SSE), ISTH major bleeding (MB) and the primary net clinical outcome of SSE/MB and all-cause mortality (ACM) were evaluated by intention-to-treat analysis by the pre-specified singular CrCl cutpoint of 50ml/min and additional exploratory cutpoints. Results: The relative risk of SSE with edox vs warf in the pre-specified analysis in those with CrCl≤50 (HR 0.87, 0.65-1.18) was similar to those with CrCl&gt;50 (HR 0.87, 0.72-1.04; p-int=0.94). Evaluation by more granular, exploratory cutpoints demonstrated higher rates of SSE (Fig 1a; p-int&lt;0.001) and ischemic stroke (p-int=0.05) with edox vs warf in the upper range of CrCl, but lower rates of bleeding were observed at all levels of CrCl with edox (Fig 1a; p-int=0.39). For the net clinical outcome (SSE/MB/ACM), there was no significant difference between edox and warf at higher levels of renal function due to the preserved effect on bleeding and mortality (Fig 1b; p-int 0.17). An on-treatment analysis with plasma drug levels will be shown. Conclusion: While there is a trend towards decreasing efficacy with increasing CrCl for edox compared to well-managed warfarin, the overall safety and net clinical benefit of edox compared to warfarin is consistent across renal function groups.
Decreased hypercoagulable state in hepatitis C virus-cirrhotic patients treated with DAA: the outcome revolution
Authors: A. Zanetto, E. Campello, L. Spiezia, S. Shalaby, E. Franceschet, M. Tessari, A. Ferrarese, A.C. Frigo, I. Bortoluzzi, M. Gambato, G. Germani, A. Floreani, F. Farinati, M. Senzolo, P. Burra, P. Simioni, F.P. Russo
Journal: Journal of Hepatology (2017)
Slower Engraftment in Patients with High Expression of miRNA-15a, miRNA-16, miRNA-126, miRNA-146a, miRNA-223 Prior to Autologous Stem Cell Transplantation and at Early Time after Transplantation
Authors: Mateusz Nowicki, Janusz Szemraj, Agnieszka Wierzbowska, Małgorzata Misiewicz, Roman Małachowski, Agnieszka Pluta, Olga Grzybowska-Izydorczyk, Tadeusz Robak, Anna Szmigielska-Kaplon
Journal: Blood (2016)
Phase I dose escalating study of hypoxia-activating agent tirapazamine in combination with trans-arterial embolization in patients with intermediate stage hepatocellular carcinoma
Authors: N. Abi-Jaoudeh, D. Fernando, K. Nelson, H. Javan, R. Guzman, T. Seery, P.-C. Liang, P.-J. Chen, J.-I Hwang, D.K. Imagawa
Journal: Journal of Hepatology (2017)
Tropical Australia is a potential reservoir of non-tuberculous mycobacteria in cystic fibrosis
Authors: Laura J. Sherrard, George T. Tay, Claire A. Butler, Michelle E. Wood, Stephanie Yerkovich, Kay A. Ramsay, David W. Reid, Vanessa L. Moore, Timothy J. Kidd, Scott C. Bell
Journal: European Respiratory Journal (2017)

Improved survival rates and increased treatment intensity of people with cystic fibrosis have been accompanied by a rising incidence of multi-antibiotic resistant and difficult-to-treat respiratory pathogens, including non-tuberculous mycobacteria (NTM) [1]. NTM epidemiology in cystic fibrosis varies globally, with a prevalence of >20% in some geographical locations [2]. In particular, there are concerns that active NTM disease from rapidly growing mycobacteria ( Mycobacterium abscessus complex) may be increasing and causing accelerated pulmonary decline [3, 4]. NTM are found naturally in ecological niches such as soil and water, and susceptible individuals may also acquire infection from potable water in their homes [5, 6]. Recent reports demonstrate person-to-person transmission [7, 8], which might occur via fomites and cough aerosols [8] and further emphasise the potential clinical importance of these organisms. Living in tropical Australia is associated with NTM acquisition, whilst long-term azithromycin is protective in CF <http://ow.ly/FrJi309W8DK>
Retrospective Treatment Analysis of a Series of 104 Patients with Adult Onset Hemophagocytic Lymphohistiocytosis in a Single Institution of China
Authors: Xiao Shuai, Juan Xu, Xushu Zhong, Yan Li, Wenjiao Tang, Huanling Zhu, Ting Niu, Yu Wu, Yongqian Jia, Xu Cui, Ling Pan, Hong Chang, Yuping Gong, Bing Xiang, Jie Huang, Jianjun Li, Chuan He, Xinchuan Chen, Liping Xie, Hongbing Ma, Jie Ji, Yang Dai, Zhigang Liu, Ting Liu
Journal: Blood (2016)
Factors associated with tumor recurrence after liver transplantation for hepatocellular carcinoma: prospective cohort on 371 patients
Authors: T. Decaens, R. Adam, S. Dharancy, L. Sulpice, D. Samuel, E. Boleslawski, M. Latournerie, G.-P. Pageaux, O. Scatton, S. Radenne, E. Savier, J. Belghiti, C. Vanlemens, N. Oubaya, C. Duvoux
Journal: Journal of Hepatology (2017)
Abstract 14014: Early Detection of Myocardial Involvement in Idiopathic Inflammatory Myopathies Assessed by Cardiac Magnetic Resonance Imaging
Authors: Dominik Buckert, Angela Rosenbohm, Jan Kassubek, Wolfgang Rottbauer, Albert Ludolph, Peter Bernhardt
Journal: Circulation (2015)

Background: Idiopathic inflammatory myopathies are heterogeneous autoimmune systemic diseases characterized by chronic progressive muscle weakness and inflammatory infiltrates in skeletal muscle. The frequency of cardiac involvement varies between 9% and 72%, mainly dependent on patient selection, definition and diagnostic tools applied. Heart failure is the most frequent finding. Cardiac magnetic resonance imaging (CMR) has been shown to provide reliable and valuable information about cardiac function and inflammatory process in one examination. Hypothesis: Aim of our prospective study was to characterize cardiac involvement using a comprehensive CMR protocol. Methods: Fifty-three consecutive patients with histologically proven idiopathic inflammatory myopathy were enrolled into the study. Blood levels of Creatine kinase (CK) and myocardial CK (CK-MB) were analyzed from each patient. All patients underwent CMR examination in a 1.5-T whole body scanner. 3D short-axis functional steady-state free precession and late gadolinium enhancement (LGE) sequences were acquired in all patients covering the entire left and right ventricle. CMR images were analyzed by two experienced and blinded readers in consensus. Besides functional analysis LGE images were analyzed for hyperenhancement and quantified as LGE percentage of myocardial mass. Results: Reduced left ventricular function (ejection fraction &lt; 60%) was present in 9 (17%) patients. These patients exhibited significantly higher blood levels of CK-MB (283±193 vs. 175±221 U/l, p=0.02) than patients with preserved LVEF. Early myocardial enhancement (&gt;45% signal intensity increase) was more often present (6 out of 9 [66.7%] vs. 25 out of 44 [56.8%], p=.014) as well as LGE patterns consistent with myocardial inflammation (9 out of 9 [100%] vs. 24 out of 44 [54.5%], p=.001). LGE was most often observed in the inferior and lateral segments. Conclusion: The results of this study show that CMR is able to detect cardiac involvement in idiopathic inflammatory myopathies. Early diagnosis using CMR could result in early therapy of heart failure, leading to beneficial ventricular remodeling and thus improving living quality and survival in these patients.
Syringaresinol-4- O - β - d -glucoside alters lipid and glucose metabolism in HepG2 cells and C2C12 myotubes
Authors: Shuai Wang, Chongming Wu, Xin Li, Yue Zhou, Quanyang Zhang, Fuchao Ma, Jianhe Wei, Xiaopo Zhang, Peng Guo
Journal: Acta Pharmaceutica Sinica B (2017)

Syringaresinol-4-O-β-d-glucoside (SSG), a furofuran-type lignan, was found to modulate lipid and glucose metabolism through an activity screen of lipid accumulation and glucose consumption, and was therefore considered as a promising candidate for the prevention and treatment of metabolic disorder, especially in lipid and glucose metabolic homeostasis. In this study, the effects of SSG on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were further investigated. Treatment with SSG significantly inhibited lipid accumulation by oil red O staining and reduced the intracellular contents of total lipid, cholesterol and triglyceride in HepG2 cells. No effect was observed on cell viability in the MTT assay at concentrations of 0.1-10 μmol/L. SSG also increased glucose consumption by HepG2 cells and glucose uptake by C2C12 myotubes. Furthermore, real-time quantitative PCR revealed that the beneficial effects were associated with the down-regulation of sterol regulatory element-binding proteins-1c, -2 (SREBP-1c, -2), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC) and hydroxyl methylglutaryl CoA reductase (HMGR), and up-regulation of peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ). SSG also significantly elevated transcription activity of PPARγ tested by luciferase assay. These results suggest that SSG is an effective regulator of lipogenesis and glucose consumption and might be a candidate for further research in the prevention and treatment of lipid and glucose metabolic diseases.