tbuckley/cabot-search huggingface dataset:
Abstract 887: The effect of anticancer chemotherapeutics on immune microenvironment of lung adenocarcinoma with EGFR mutation in vivomicroenvironment of lung adenocarcinoma with EGFR mutationin vivo
Authors: Young-Ah Suh, Hyemin Mun, Sun-Hye Lee, Se-Young Jo, Ju-Hee Oh, Chu-Hee Lee
Journal: Cancer Research (2018)

Abstract Lung cancer is the leading cause of cancer related deaths worldwide. Molecular targeting therapy is an attractive treatment for lung cancer, although it eventually develops resistance in most cases. In this report, we tested taxan antitumor effect on lung adenocarcinomas in vitro and in vivo. It could inhibit cell growth of many NSCLC cells tested, exhibiting reduced expression of c-MET and STAT3. The nascent effect of taxan on lung tumor cells were also proved on patient-derived primary lung tumor cells and patient-derived xenograft model that highly expresses c-MET. The antitumor effect of this chemotherapeutics was also observed on T790M mutant cells. Interestingly, the antitumor effect of taxan was synergistic in combination of c-Met inhibitor on lung tumor cells as well as patient-derived primary lung tumor cells. However, single treatment of taxan was sufficient for halting tumor growth in vivo, as no combinational effect of c-Met inhibitor was obvious. Not only c-Met inhibitor but also taxan reduced phosphorylated c-MET and STAT3, although cytokines on downstream of c-MET and STAT3 were explosively increased in vitro setting resulting in high expression of chemokines/cytokines. Importantly, the effect was not true in in vivo setting, in which the expressions of chemokines/cytokines as well as phosphorylated c-MET and STAT3 were influenced with this agent. These results suggest that taxane is one of the comparative adjuvant for lung tumors exhibiting targeted drug resistance, especially for enhanced signaling of MET-STAT-immuno-microenvironment. Citation Format: Young-Ah Suh, Hyemin Mun, Sun-Hye Lee, Se-Young Jo, Ju-Hee Oh, Chu-Hee Lee. The effect of anticancer chemotherapeutics on immune microenvironment of lung adenocarcinoma with EGFR mutation in vivomicroenvironment of lung adenocarcinoma with EGFR mutation in vivo [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 887.
Cardiovascular Magnetic Resonance in the Oncology Patient
Authors: Jennifer H. Jordan, Ryan M. Todd, Sujethra Vasu, W. Gregory Hundley
Journal: JACC. Cardiovascular imaging (2018)

Patients with or receiving potentially cardiotoxic treatment for cancer are susceptible to developing decrements in left ventricular mass, diastolic function, or systolic function. They may also experience valvular heart disease, pericardial disease, or intracardiac masses. Cardiovascular magnetic resonance may be used to assess cardiac anatomy, structure, and function and to characterize myocardial tissue. This combination of features facilitates the diagnosis and management of disease processes in patients with or those who have survived cancer. This report outlines and describes prior research involving cardiovascular magnetic resonance for assessing cardiovascular disease in patients with or previously having received treatment for cancer.
Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement
Authors: Tim Lahm, Ivor S. Douglas, Stephen L. Archer, Harm J. Bogaard, Naomi C. Chesler, Francois Haddad, Anna R. Hemnes, Steven M. Kawut, Jeffrey A. Kline, Todd M. Kolb, Stephen C. Mathai, Olaf Mercier, Evangelos D. Michelakis, Robert Naeije, Rubin M. Tuder, Corey E. Ventetuolo, Antoine Vieillard-Baron, Norbert F. Voelkel, Anton Vonk-Noordegraaf, Paul M. Hassoun
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsDefinition, Development, ...Topic Domain 1: Optimizin...Topic Domain 2: Analyzing...Topic Domain 3: Decipheri...ConclusionsReferencesCITING ARTICLES
Red Wine Inhibits Monocyte Chemotactic Protein-1 Expression and Modestly Reduces Neointimal Hyperplasia After Balloon Injury in Cholesterol-Fed Rabbits
Authors: An-NingFeng, Yuh-LienChen, Ya-TingChen, Yaw-ZonDing, Shing-JongLin
Journal: Circulation (1999)

Background—Wine consumption decreases the risk of myocardial infarction. Intimal hyperplasia contributes to restenosis after angioplasty. Local ethanol delivery inhibits intimal hyperplasia after balloon injury in rabbit iliac and pig coronary arteries. The effects of wine consumption on intimal response and monocyte chemotactic protein-1 (MCP-1) expression were studied in cholesterol-fed rabbits. Methods and Results—Male rabbits were fed a 2% cholesterol diet together with red wine (12.5% vol, 5 mL/kg body wt per day; n=7), white wine (13.3% vol, 5 mL/kg body wt per day; n=7), or no wine as a control (n=8) for 6 weeks. A balloon injury of the abdominal aorta was performed at the end of the third week. Abdominal aortas were harvested at the end of 6 weeks. Neointimal hyperplasia was measured morphometrically. MCP-1 expression was determined by Northern blot, in situ hybridization, and immunohistochemistry. Rabbits fed red wine had significantly less neointimal hyperplasia than did control rabbits (intima/...
Abstract 19466: Preliminary Experience Using Multiplexed Imaging of the Sympathetic Autonomic Nervous System - Impact on Outcome of Catheter Ablation of Atrial Fibrillation
Authors: SabineErnst, FrancescaMenichetti, RafaelBaavour, NathanielRoth, JamshedBomanji, SimonaBen-Haim
Journal: Circulation (2014)

Introduction: Catheter ablation of ganglionated plexi (GP) as an add on to pulmonary vein (PV) isolation has been reported to significantly improve outcome of atrial fibrillation (AF) ablation. In order to facilitate localization of these GPs, a novel imaging study is proposed, assessing the uptake of iodine-123 metaiodobenzylguanidine (mIBG, an analog of norepinephrine)in combination with 3D surface reconstruction from contrast computed tomography (cCT) or cardiac magnetic resonance (CMR). Methods: A total of 8 patients (5 male, median age 58 yrs) underwent mIBG SPECT using a dedicated cardiac camera (D-SPECT, SUMO, Spectrum Dynamics). This data was merged with 3D CMR or cCT and finally imported into CARTO (Biosense Webster). Using the individual mediastinum uptake as a normalizing factor, high uptake sites in the epicardial fat pads around the left atrium (LA) were identified. Five patients had paroxysmal AF whilst 3 present in persistent (n=2) or longstanding persistent (n=1) AF. Only 3 patients were t...
Abstract 2726: In vitro functional activity of OMP-336B11, a GITRL-Fc fusion protein, on primary human immune cells
Authors: Ivan H. Chan, Ming-Hong Xie, Andrew Lam, Fumiko T. Axelrod, Jennifer Elechko, Angie I. Park, Austin Gurney
Journal: Cancer Research (2018)

Abstract Glucocorticoid-induced TNFR-related protein (GITR) is a member of the TNF receptor superfamily. GITR, a co-stimulatory surface receptor, is activated upon binding to GITR Ligand (GITRL) and mediates co-stimulation of T-cell and NK responses and inhibits the suppressive activity of regulatory T-cells (Tregs). As such, GITR is an attractive immuno-oncology target for activation via GITR agonists. OMP-336B11 is a single-gene recombinant fusion protein consisting of two trimeric human GITRLs and a human immunoglobulin (IgG1) Fc domain. Murine preclinical studies using a surrogate GITRL-Fc fusion protein demonstrated robust antitumor efficacy. Functional characterization of OMP-336B11 in various human immune cell assays is presented here. In human peripheral blood mononuclear cells (PBMC), OMP-336B11 stimulated IL-2 cytokine release in a dose-dependent manner. In activated human T-cells, OMP-336B11 enhanced cell proliferation in a dose-responsive fashion. OMP-336B11 also augmented IL-2 induced IFNγ from human NK cells. To elicit NK mediated cytotoxicity of high GITR expressing cells (i.e., Tregs), OMP-336B11 is designed with an IgG1 Fc domain. Co-incubation of primary human NK cells (effector) and GITR expressing cells (target) resulted in an OMP-336B11 dependent dose-titratable increase in target cytotoxicity. Furthermore, OMP-336B11 agonistic activity was compared to anti-GITR agonist antibodies. By measuring cell proliferation and IFNγ from activated T-cells, OMP-336B11 demonstrated superior activity compared to the other agonist anti-GITR antibodies. In conclusion, OMP-336B11 is designed to induce effective GITR activation and also to mediate depletion of GITR-high cells. OMP-336B11 is currently undergoing phase I clinical study. Citation Format: Ivan H. Chan, Ming-Hong Xie, Andrew Lam, Fumiko T. Axelrod, Jennifer Elechko, Angie I. Park, Austin Gurney. In vitro functional activity of OMP-336B11, a GITRL-Fc fusion protein, on primary human immune cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2726.
Treatment of young adults with Philadelphia‐negative acute lymphoblastic leukemia and lymphoblastic lymphoma: Hyper‐CVAD vs. pediatric‐inspired regimens
Authors: Stuart E. Siegel, Anjali Advani, Nita Seibel, Lori Muffly, Wendy Stock, Selina Luger, Bijal Shah, Daniel J. DeAngelo, David R. Freyer, Dan Douer, Rebecca H. Johnson, Brandon Hayes‐Lattin, Mark Lewis, Jerry J. Jaboin, Peter F. Coccia, Archie Bleyer
Journal: American Journal of Hematology (2018)

Abstract For young adults with acute lymphoblastic leukemia, pediatric‐based regimens are likely to provide the following when compared to hyper‐CVAD regimens: better disease control, less hospitalization time, diminished acute toxicities, decreased financial cost, more quality‐adjusted life years, and fewer adverse late effects, such as infertility, myelodysplasia, and second malignant neoplasms. There are also reasons to expect less cardiac and cognitive dysfunction after pediatric regimens. The improved quality and quantity of life associated with pediatric regimens renders them preferable to hyper‐CVAD regimens for the treatment of Philadelphia‐negative B‐precursor or T‐cell acute lymphoblastic leukemia and lymphoblastic lymphoma in young adults.
Periostin as a Novel Factor Responsible for Ventricular Dilation
Authors: NarutoKatsuragi, RyuichiMorishita, NorikoNakamura, TayehitoOchiai, YoshiakiTaniyama, YasuhiroHasegawa, KayokoKawashima, YasufumiKaneda, ToshioOgihara, KeijiroSugimura
Journal: Circulation (2004)

Background— Periostin is highly expressed in the myocardium in patients with heart failure. However, no report has documented the function of periostin. To identify the function of periostin in the pathophysiology of heart failure, overexpression or loss of function of the periostin gene was examined by direct transfection into the rat heart. Methods and Results— Rats transfected with the periostin gene by the HVJ-liposome method showed left ventricular (LV) dilation as assessed by echocardiography, accompanied by an increase in periostin expression. Consistently significant differences were observed in LV pressure, LV end-diastolic pressure, LV dP/dtmax, and LV dP/dtmin at 6 and 12 weeks after transfection in rats transfected with the periostin gene, accompanied by a decrease in cardiac myocytes and an increase in collagen deposition. Importantly, periostin has the ability to inhibit the spreading of myocytes and the adhesion of cardiac fibroblasts with or without fibronectin. Markers of cardiac dysfunct...
Ca2+ Waves in Lung Capillary Endothelium
Authors: XiaoyouYing, YoshihiroMinamiya, ChenzhongFu, JaharBhattacharya
Journal: Circulation Research (1996)

Although cytosolic Ca2+ importantly regulates organ function, lung microvascular [Ca2+]i regulation remains poorly understood because of the lack of direct in situ quantification. In the present study, we report the first endothelial [Ca2+]i quantification by the fura 2 method in microscopically imaged venular capillaries of the isolated blood-perfused rat lung. Sequential images indicated the presence of intercellular Ca2+ waves that spontaneously originated from pacemaker endothelial cells and then spread for short distances along the capillary wall, inducing synchronous endothelial [Ca2+]i oscillations. Fast Fourier analyses of the oscillations revealed a dominant wave component with an amplitude of 37 nmol/L, frequency of 0.4 min−1, and velocity of 5 μm/s. The intracellular Ca2+ wave was unaffected by blood flow stoppage or by infusions of Ca2+-containing or Ca2+-free dextran. Inhibition of the wave by thapsigargin in Ca2+-free dextran and by the gap junction uncoupler, heptanol, indicated that it was...
Abstract 2435: ST6Gal-I sialylation potentiates hypoxia adaptation by enhancing HIF-1a signaling
Authors: Robert B. Jones, Kaitlyn A. Dorsett, Anita B. Hjelmeland, Susan L. Bellis
Journal: Cancer Research (2018)

Abstract Aberrant surface glycosylation is a well-known hallmark of a tumor cell, however the functional role of glycans in cancer cell biology remains unclear. Tumor cells frequently display an increase in surface α2-6 sialylation, a modification added to N-glycosylated proteins by the ST6Gal-I sialyltransferase. ST6Gal-I sialylates a select cohort of surface receptors, which correspondingly modulates receptor-induced intracellular signaling cascades. Emerging evidence suggests that ST6Gal-I-mediated sialylation promotes the survival of tumor cells exposed to a variety of cell stressors. In the current study we identify a new function for ST6Gal-I in protecting against hypoxic stress. In response to low oxygen tension, the hypoxia inducible factor, HIF-1α, becomes stabilized in tumor cells. In turn, HIF-1α stimulates the transcription of genes important for cell survival. To interrogate a role for ST6Gal-I in hypoxic response, we evaluated HIF-1α accumulation in ovarian and pancreatic cancer cells with ST6Gal-I overexpression or knockdown. We find that ST6Gal-I activity augments HIF-1α accumulation in cells treated with chemical hypoxia mimetics (DFO and DMOG), or alternatively grown in a hypoxic environment. Furthermore, hypoxic cells with high ST6Gal-I expression have increased mRNA levels of HIF-1α transcriptional targets including the glucose transporters, GLUT1 GLUT3, and the glycolytic enzyme, PDHK1. Interestingly, cells with high ST6Gal-I expression also have an increased pool of HIF-1α mRNA, suggesting that ST6Gal-I may influence the biosynthesis of HIF-1α. Finally, cells grown in hypoxia for several weeks display an enrichment in ST6Gal-I expression, consistent with the concept that ST6Gal-I acts as a pro-survival factor. Taken together, these findings highlight a novel, glycosylation-dependent mechanism that facilitates tumor cell adaptation to a hypoxic milieu. Citation Format: Robert B. Jones, Kaitlyn A. Dorsett, Anita B. Hjelmeland, Susan L. Bellis. ST6Gal-I sialylation potentiates hypoxia adaptation by enhancing HIF-1a signaling [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 2435.
Deciphering the Role of Lipid Droplets in Cardiovascular Disease
Authors: Ira J. Goldberg, Karen Reue, Nada A. Abumrad, Perry E. Bickel, Sarah Cohen, Edward A. Fisher, Zorina S. Galis, James G. Granneman, E. Douglas Lewandowski, Robert Murphy, Michelle Olive, Jean E. Schaffer, Lisa Schwartz-Longacre, Gerald I. Shulman, Tobias C. Walther, Jue Chen
Journal: Circulation (2018)

Lipid droplets (LDs) are distinct and dynamic organelles that affect the health of cells and organs. Much progress has been made in understanding how these structures are formed, how they interact with other cellular organelles, how they are used for storage of triacylglycerol in adipose tissue, and how they regulate lipolysis. Our understanding of the biology of LDs in the heart and vascular tissue is relatively primitive in comparison with LDs in adipose tissue and liver. The National Heart, Lung, and Blood Institute convened a working group to discuss how LDs affect cardiovascular diseases. The goal of the working group was to examine the current state of knowledge on the cell biology of LDs, including current methods to study them in cells and organs and reflect on how LDs influence the development and progression of cardiovascular diseases. This review summarizes the working group discussion and recommendations on research areas ripe for future investigation that will likely improve our understanding of atherosclerosis and heart function.
Sirtuins and Pyridine Nucleotides
Authors: MahaAbdellatif
Journal: Circulation Research (2012)

The silencer information regulator (Sir) family of proteins has attracted much attention during the past decade due to its prominent role in metabolic homeostasis in mammals. The Sir1–4 proteins were first discovered in yeast as nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, which through a gene silencing effect promoted longevity. The subsequent discovery of a homologous sirtuin (Sirt) family of proteins in the mammalian systems soon led to the realization that these molecules have beneficial effects in metabolism- and aging-related diseases. Through their concerted functions in the central nervous system, liver, pancreas, skeletal muscle, and adipose tissue, they regulate the body's metabolism. Sirt1, -6, and -7 exert their functions, predominantly, through a direct effect on nuclear transcription of genes involved in metabolism, whereas Sirt3–5 reside in the mitochondrial matrix and regulate various enzymes involved in the tricarboxylic acid and urea cycles, oxidative phosphorylation,...
Abstract 2063: <i>SAMD9/SAMD9L</i> mutations in familial monosomy 7
Authors: Victoria Bryant, Jasmine Wong, Jason Schwartz, Tamara Lamprecht, Jing Ma, Charles Mullighan, Mignon Loh, Kevin Shannon, Jeffery Klco
Journal: Cancer Research (2018)

Abstract The purpose of this study was to define the mutations causing familial monosomy 7 with myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). We have previously reported frequent germline mutations in the genes SAMD9 and SAMD9L in pediatric MDS. We obtained samples on 32 individuals in 7 families with multiple siblings affected with MDS/AML and monosomy 7. We conducted targeted sequencing of genes frequently mutated in MDS/AML and amplicon sequencing of SAMD9 and SAMD9L. We performed cell cycle analysis assays on SAMD9/9L mutations to study their effects on cell proliferation. Our data show that 5 of the 7 families have germline pathologic mutations in SAMD9 (n=1) and SAMD9L (n=4), with significant clinical variability in the phenotypes displayed, ranging from transient monosomy 7 to overt AML with monosomy 7. Consistent with previous data, the mutant SAMD9 or SAMD9L allele was underrepresented in the bone marrow. This decrease in the mutant allele paralleled the extent of monosomy 7, suggesting that only the wild-type allele was retained in cells with monosomy 7. Functional analysis revealed that all germline SAMD9/9L mutations displayed a gain-of-function ability to suppress cell cycle progression. The patients with more aggressive disease were found to harbor somatic mutations in SETBP1, ETV6 or RUNX1. In many individuals we found additional somatic revertant mutations in cis with the germline mutation, which overcame the growth-suppressive effects of the germline mutation. Our data show that germline mutations in SAMD9/9L represent a new class of predisposition genes for familial monosomy 7 with MDS/AML and should be screened for in all children with MDS. Citation Format: Victoria Bryant, Jasmine Wong, Jason Schwartz, Tamara Lamprecht, Jing Ma, Charles Mullighan, Mignon Loh, Kevin Shannon, Jeffery Klco. SAMD9/SAMD9L mutations in familial monosomy 7 [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 2063.
Abstract 5648: Proteomics analysis of oral cancer cell-derived extracellular vesicles
Authors: Ana K. Oliveira, Ariane F. Busso-Lopes, Jamile Oliveira Sá, César Rivera, Adriana F. Paes Leme
Journal: Cancer Research (2018)

Abstract More than 300,000 new cases of head and neck cancer occur each year around the world, and although it is not one of the most common tumors in the world, has an elevated morbidity rate (37.8%) after five years of diagnosis. The development and progression of the Oral Squamous Cell Carcinoma (OSCC) involve complex cellular mechanisms which contribute to a tumor progression. Recently extracellular vesicles (EVs) have taken a significant physiological and pathological role in cell-cell communication through interactions mediated by receptors or by transfer of bioactive molecules such as receptors, proteins, lipids, mRNA, microRNA, and DNA, by changing the phenotype of the recipient cell. The tumor cells can transfer information to different cell types using EVs as a vehicle, modifying the characteristics of the tumor microenvironment, and contributing to cancer sustaining. The detection of alterations in the EVs proteome may, therefore, contribute to the understanding the cellular mechanisms modulated in OSCC and help to improve the clinical prognosis and potential therapeutic targets in oral cancer. Thus, this study analyzed the cargo proteins of different EVs from less and high aggressive oral cancer cells to understand their possible role in microenvironment modulation and oral cancer progression. Our results indicate that EVs of aggressive cells have exclusive proteins that may contribute to lymph node metastasis, which is the worse prognostic factor in OSCC and can be considered potential targets in OSCC.FAPESP: 2016/19337-3 Citation Format: Ana K. Oliveira, Ariane F. Busso-Lopes, Jamile Oliveira Sá, César Rivera, Adriana F. Paes Leme. Proteomics analysis of oral cancer cell-derived extracellular vesicles [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 5648.
Association Between Insight and Outcome of Psychotherapy: Systematic Review and Meta-Analysis
Authors: Simone Jennissen, Julia Huber, Johannes C. Ehrenthal, Henning Schauenburg, Ulrike Dinger
Journal: American Journal of Psychiatry (2018)

An increased understanding of repetitive dysfunctional patterns and their relationship to an individual's life history is regarded as a key mechanism of change in insight-oriented therapies. At the same time, empirical research on the insight-outcome relationship is rare, and its generalizability is restricted by the use of a wide range of definitions and methods among studies. The authors conducted a meta-analysis to systematically examine the association between patient insight and psychotherapy outcome across a range of treatment modalities.Insight was defined as patients' understanding of associations between past and present experiences, typical relationship patterns, and the relation between interpersonal challenges, emotional experience, and psychological symptoms. From 13,849 initially identified abstracts, the authors extracted 23 independent effect sizes. A random-effects meta-analysis was performed to assess the magnitude of the insight-outcome relationship. Risk of publication bias was assessed with funnel plot inspections, Egger's regression test, and Duval and Tweedie's trim-and-fill procedure as sensitivity analyses.A significant, moderate correlation (r=0.31) was observed between insight and treatment outcome. Sensitivity analyses demonstrated the robustness of the results.The findings support the importance of insight for psychotherapy outcome. Insight may be a relevant mechanism of change across different treatment modalities.