tbuckley/cabot-search huggingface dataset:
Abstract 305: AAV9 Mediated Cardiac Bin1 Gene Therapy Attenuates Pressure Overload-induced Heart Failure in Mice
Authors: Kang Zhou, Sosse Agvanian, Yan Liu, Tara Hitzeman, Robin M Shaw, Tingting Hong
Journal: Circulation Research (2018)

Rationale: Pressure overload-induced myocardial hypertrophy can progress to heart failure (HF), along with a decline in myocardial expression of cardiac BIN1 (cardiac isoform of bridging integrator 1, cBin1). T-tubule cBIN1-microdomains are critical in maintaining normal cardiac contractility and electrical stability. Objective: To examine whether cBin1 gene transfer can prevent or postpone HF induced by severe pressure overload in a mouse model with transverse aortic constriction (TAC). Methods and Results: Two sets of experiments were designed. In Set 1, TAC was performed in adult male wild type (WT-TAC) and cardiac specific heterozygous Bin1 deleted mice ( Bin1 HT-TAC). In Set 2, TAC was performed in adult male C57BL/6J mice three weeks after retro-orbital injection of adeno-associated virus 9 transducing cBIN1-V5 or GFP-V5 (cBIN1-TAC or GFP-TAC) and compared to sham controls. The primary endpoint measured was survival at 8 weeks with left ventricular ejection fraction &gt;=35% by echocardiogram. The Bin1 HT-TAC group (less cBIN1) and the cBIN1-TAC group (more cBIN1) had significantly less and more endpoint achievement than their respective set controls, indicating a robust protective effect of cBIN1. Left ventricular (LV) hypertrophy occurred in all TAC groups, yet cBIN1-TAC mice had attenuated LV dilation by echocardiogram, improved contractile reserve by pressure-volume loop, reduced pulmonary edema and less HF development. Exploring myocardial remodeling, exogenous cBIN1 retained t-tubule membrane microdomains with organized L-type calcium channels (LTCC) and ryanodine receptors (RyRs) in cBIN1-TAC mice, which otherwise were significantly disrupted in GFP-TAC mice. However, the total LTCC and RyRs protein levels were not significantly altered among groups by Western blotting. Conclusions: Normalization of cBIN1 level can postpone, if not prevent, the transition from compensated LV hypertrophy to dilated cardiomyopathy following pressure overload. The protective mechanism is linked to cBIN1-mediated preservation of dyads at t-tubule membrane microdomains, limiting pathologic remodeling of the calcium handling apparatus during HF progression.
Alemtuzumab activity and CD52 expression in human CD52 transgenic mice
Authors: Yanping Hu, Jacqueline Shields, Sam Rao, Michael Lamorte, Lisa Woodworth, Bill Kennedy, Elizabeth Hutto, Bruce Roberts, William M. Siders, Johanne Kaplan
Journal: Cancer Research (2007)

4133  Alemtuzumab (Campath) is a recombinant humanized IgG1 monoclonal antibody directed against the 28 kD cell surface glycoprotein CD52. CD52 is expressed on the surface of several cell types including normal and malignant B and T lymphocytes as well as on NK cells, and macrophages. Currently, Campath is approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). The exact mechanisms by which Campath mediates its biological effect in vivo are not clearly defined. To explore this issue, a transgenic mouse was created that expresses human CD52 under the control of the endogenous CD52 promoter. In these mice, human CD52 is expressed on B-cells and T-cells and to a lesser extent on NK-cells of peripheral blood, lymph nodes, and spleen as determined by FACS analysis. Preliminary immunohistochemical staining indicates that human CD52 is expressed in lymphoid organs such as spleen and inguinal lymph nodes. Pharmacokinetic experiments revealed that Campath displays a half-life of approximately one and a half days in these mice. Treatment with a single i.p. dose of Campath resulted in a transient increase in the circulating levels of TNF-α, IFN-γ and IL-6 within four hours following administration. Campath depleted CD4+ and CD8+ T-cells, CD19+ B-cells as well as NK cells in a dose- and time-dependent manner in the peripheral blood and reduced these same cell populations in the lymphoid organs of the transgenic mice. Following lymphocyte depletion with a single dose of Campath, B-cells appear to recover to the level of untreated controls prior to T-cells. Taken together, these data suggest that the human CD52 transgenic mouse may serve as a promising animal model to investigate in vivo efficacy and the mechanism of action of Campath.
Clinical Effectiveness Of Omalizumab In Severe Allergic Asthma Above The Recommended Dosing Range: The Australian Xolair Registry
Authors: M. Hew, A. Gillman, M. Sutherland, P. Wark, J. Bowden, V. McDonald, M. Guo, H. Reddel, C. Jenkins, G. Marks, J. Upham, F. Thien, J. Rimmer, G. P. Katsoulotos, M. Cook, I. Yang, C. Katelaris, S. Bowler, D. Langton, P. G. Gibson, P. D. Robinson, C. Wright, M. Bint, V. Yozghatlian, S. Burgess, P. Sivakumaran, A. Jaffe, K. Yan, M. Peters, V. Kritikos, M. Baraket, A. Aminazad
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
CHANGES IN EJECTION FRACTION AND GLOBAL LONGITUDINAL STRAIN ASSESSMENT IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION AFTER THERAPY WITH SACUBITRIL/VALSARTAN
Authors: Amitabh C. Pandey, Megan Pelter, Paul Montgomery, Ruth Kuo, Christine Shen, Rajbir Sidhu, David Lerner, Kristin Billick, Brooke Hay, Alyssa Loveday, Ashley Duckett, Siddharth Suresh, Ajay Srivastava, David Rubenson, J. Thomas Heywood, Rajeev Mohan
Journal: Journal of the American College of Cardiology (2019)
INCREASED BODYWEIGHT AND INADEQUATE RESPONSE TO ASPIRIN IN INDIVIDUALS WITH CORONARY ARTERY DISEASE
Authors: Remo Holanda de Mendonca Furtado, Flavia Arantes, Carlos Barbosa, Andre Franci, Fernando Menezes, Rocio Salsoso, Talia Dalcoquio, Carlos Nakashima, Marco Scanavini Filho, Aline Ferrari, Paulo Genestreti, Luciano Baracioli, Jose C. Nicolau
Journal: Journal of the American College of Cardiology (2019)
ENDOTHELIAL FUNCTION PREDICTS 5-YEAR ADVERSE CLINICAL OUTCOME IN PATIENTS HOSPITALIZED IN THE EMERGENCY DEPARTMENT CHEST PAIN UNIT
Authors: Michael Shechter, Amir Lerman, Megha Prasad, Orly Goitein, Ronen Goldkorn, Michael Naroditsky, Nira Koren-Morag, Shlomi Matetzky
Journal: Journal of the American College of Cardiology (2019)
UTILITY OF BASELINE AND FOLLOW-UP CARDIOVASCULAR PHYSICAL EXAMS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: TOPCAT
Authors: Senthil Selvaraj, Brian Claggett, Sanjiv Jayendra Shah, Inderjit Ananda, Jean L. Rouleau, Akshay S. Desai, Eldrin F. Lewis, Bertram Pitt, Nancy K. Sweitzer, Marc A. Pfeffer, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2019)
PRE-ABLATION LEFT ATRIAL FUNCTION AND FIBROSIS PREDICTS ATRIAL FIBRILLATION RECURRENCE: CARDIAC MAGNETIC RESONANCE STUDY
Authors: Ibolya Csecs, Takanori Yamaguchi, Mobin Kheirkhahan, David Peritz, Alan Morris, Eugene Kholmovski, Gagandeep Kaur, Bosten Loveless, Benjamin Hardisty, Bela Merkely, Brent Wilson, Nassir Marrouche
Journal: Journal of the American College of Cardiology (2019)
Abstract 283: Parkin Fails to Rescue Age-Dependent Cardiomyopathy in Mitochondrial DNA Mutator Mice
Authors: Benjamin P Woodall, Amabel M Orogo, Ajit S Divakaruni, Melissa Q Cortez, Hongxia Wang, Anne N Murphy, Åsa B Gustafsson
Journal: Circulation Research (2018)

Temporal decline in mitochondrial function is widely considered to be a driver of cardiomyocyte aging, which in turn contributes to the prevalence of cardiovascular disease in the aging population. The accumulation of dysfunctional mitochondria appears to be a direct consequence of reduced autophagy and mitochondrial quality control in the aging heart. Parkin, an E3 ubiquitin ligase, plays a critical role in this process, marking dysfunctional mitochondria for degradation by autophagosomes; however, whether Parkin functions to prevent cardiac aging by maintaining a healthy population of mitochondria is still unclear. To examine the role of Parkin in the context of mtDNA damage and myocardial aging, we used a mouse model carrying a proofreading defective mitochondrial DNA polymerase gamma (POLG). We observed a significant decrease in Parkin protein levels in the hearts of aged (6 months) POLG mice, in spite of elevated Parkin mRNA. Seahorse analysis revealed a decrease in cardiac mitochondrial respiration in 6-month POLG mice. While cardiac structure and function were similar in both genotypes, POLG mice displayed modest but significant cardiac hypertrophy at this age. Next, we generated mice with concomitant Parkin deletion or cardiac specific Parkin overexpression with the mutant POLG. However, loss of Parkin did not exacerbate the accelerated cardiac aging phenotype observed in the POLG mice, and enhancing cardiac Parkin protein levels did not rescue the mitochondrial dysfunction or the cardiac hypertrophy observed in POLG mice up to 12 months of age. Surprisingly, we found that Parkin levels were reduced in POLG hearts, even with cardiac specific overexpression of Parkin. Translation of Parkin was unperturbed in 12-month POLGxParkin TG hearts, suggesting instead that Parkin protein stability is compromised in aged POLG hearts, a hypothesis we are currently testing. We also found both diminished protein ubiquitination and reduced degradation of Mfn1, a known Parkin substrate, in POLGxParkin TG hearts compared to Parkin TG hearts. These results provide new insights into mitophagy and aging, and suggest that Parkin plays a minor role in baseline mitochondrial maintenance and that overexpression of Parkin fails to prevent the cardiac aging process.
NATRIURETIC PEPTIDES VERSUS A CLINICAL HISTORY OF HEART FAILURE FOR RISK PREDICTION IN PATIENTS WITH DIABETES
Authors: Brian Bergmark, David Morrow, Deepak L. Bhatt, Itamar Raz, Philippe Steg, Ofri Mosenzon, Yared Gurmu, Eugene Braunwald, Benjamin M. Scirica
Journal: Journal of the American College of Cardiology (2019)
Abstract 414: Transcriptome Analysis by RNA Sequencing of Left Ventricular Tissue From Mice Fed a High-Fat Diet
Authors: Stephen W Luckey, Jesse Riordan, Courtney Olson, Joseph Nadeau
Journal: Circulation Research (2018)

A high-fat diet induces obesity and is associated with heart disease characterized by cardiac hypertrophy, diastolic dysfunction, fibrosis, and mitochondrial dysfunction. However, the molecular mechanisms involved in the pathogenesis of cardiac disease are not known. Therefore, the objective of this study was to investigate the molecular changes in the heart associated with a high-fat diet at early time points in the progression of cardiac disease. To do this, male C57BL/6 mice were fed either a chow diet or a high-fat (58 kcal%), low-sucrose (HFLS) diet starting at 5 weeks of age for 14 days and 100 days. At each time point, hearts were extracted and morphometric measurements were recorded. HFLS diet had no effect on weight gain at 14 days but did significantly increase body weight by two-fold at 100 days. At 14 days, there was no significant difference in cardiac size as measured by heart weight-to-tibia length ratio (HW/TL) between mice on HFLS diet and chow diet. However, there was a 24% increase in HW/TL following 100 days on the HFLS diet. Total RNA was extracted from left ventricular tissue from each group and gene expression was determined by RNA-Seq transcriptome analysis. DAVID functional pathway analysis of the top 50 genes with differential expression between diets at 14 days and 100 days identified significant enrichment for mitochondrial proteins and lipid metabolism at both time points on the HFLS diet. Moreover, there was enrichment for hypoxia response genes following 100 days on the HFLS diet. Analysis of genes with differential expression between 14 days and 100 days on HFLS diet identified enrichment for actin binding proteins/Z disc, glutathione transferase activity, and oxidation/reduction activity. These findings demonstrate significant differences in gene regulation in the hearts of mice fed a high fat diet at early time points. It is possible that these early molecular changes play a role in the progression of cardiac disease.
婴儿 AD 中的角质层和系统生物标志物
Authors: M.A. McAleer, I. Jakasa, G. Hurault, P. Sarvari, W.H.I. McLean, R.J. Tanaka, S. Kezic, A.D. Irvine
Journal: British Journal of Dermatology (2019)

特应性皮炎 (AD) 也称为湿疹,是一种常见的炎症性皮肤病,通常在生命早期出现。估计英国有大约 1500 万人目前患有 AD,受此病影响的儿童高达 20%。指标(如患者体内与此病存在或严重性相关的某种特定蛋白的水平)可能在确保治疗得当方面有重要意义。已针对成人描述了 AD的 严重性指标,但需要能够用于定义婴儿 AD 严重性的相似指标,因为婴儿期通常是此病开始的时间。这项研究旨在鉴定易于从婴儿皮肤中获得的可用于预测 AD 的指标。作为此研究的一部分,从 100 名刚发生中重度 AD 但尚未接受治疗的儿童和 20 名无 AD 的儿童中进行了采样。 在研究开始时对受影响儿童 AD 的严重性水平进行评级,从所有参与者采集最外层的皮肤。66 个测量的指标中共有 31 个在 AD 婴儿和无 AD 婴儿中的水平存在差异。已知这些指标与不同的过程有关,包括身体天然防御和新血管的形成。这项研究的作者得出结论称,这些结果显示,易于获得的指标可以用于预测婴儿 AD,皮肤最外层的天然防御反应在防止婴儿 AD 发生中至关重要。
Abstract 218: Biofunctional Tissue-engineered Vascular Grafts Induce Vascular Regeneration
Authors: Yiwa Pan, Yifan Wu, Kang Qin, Yongzhen Wei, Deling Kong, Qiang Zhao
Journal: Circulation Research (2018)

Vascular graft has proven to be an effective strategy for the treatment of cardiovascular diseases. However grafts made solely from synthetic polymers cannot satisfy the clinic requirements in terms of low long-term patency, because they only provide a simple structural or physical replacement without the biological functions. In order to address the issue, we aim to fabricate vascular grafts which could mimic native extracellular matrix (ECM) in terms of both physiological structure and bio-functions. Different types of strategies and techniques have been explored to realize this purpose, including graft structure optimization, surface/interface functionalization, and controlled delivery of vascoactive molecules.Up to now, we have successfully fabricated a kind of vascular grafts with dual surface functions of anti-thrombogenicity and rapid endothelialization. Through structural optimization, the problem of limited cellularization in vascular grafts has been effectively resolved, and thus the vascular regeneration as well as the homeostasis has been improved. Furthermore, incorporation of some specific cytokines (such as Dickkopf-3) into the micro/nano- fibrous vascular grafts could enhance the migration vascular progenitor cells (VPCs) into the grafts and further induce the differentiation of them, contributing to endothelialisation and intima/media formation. In addition, vascular grafts loaded with exosomes derived from mesenchymal stem cells have been successfully prepared, and delivered exosomes exhibited immunomodulation function which is very important for the vascular regeneration and inhibition of calcification.
GLYCATED ALBUMIN IS A PREDICTOR OF MAJOR ADVERSE CARDIO-CEREBRAL EVENTS IN NONDIABETIC PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UNDERWENT PERCUTANEOUS CORONARY INTERVENTION
Authors: Qingbo Liu, Bing Hua, Hehe Cui, Xiaosong Ding, Siwen Liang, Li Zhou, Hui Chen, Hongwei Li
Journal: Journal of the American College of Cardiology (2019)
FACTORS ASSOCIATED WITH ELEVATED N: TERMINAL PRO: BRAIN NATRIURETIC PEPTIDE LEVELS AT THE CONVALESCENT STAGE IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Bolrathanak Oeun, Daisaku Nakatani, Shungo Hikoso, Takayuki Kojima, Takahisa Yamada, Yoshio Yasumura, Masaaki Uematsu, Yoshiharu Higuchi, Toshiaki Mano, Hisakazu Fuji, Haruhiko Abe, Yusuke Nakagawa, Tomoharu Dohi, Akihiro Sunaga, Hirota Kida, Tetsuhisa Kitamura, Fusako Sera, Kei Nakamoto, Yasushi Sakata
Journal: Journal of the American College of Cardiology (2019)
COST-EFFECTIVENESS OF IMPLANTABLE CARDIAC MONITOR FOR THE DETECTION OF ARRHYTHMIA IN UNEXPLAINED SYNCOPE PATIENTS IN THE UNITED STATES
Authors: Brad Sutton, Sarah Bermingham, Alex Diamantopoulos, Kate Lindborg, Mirko De Melis, Sarah Rosemas, Stylianos Tsintzos, Ying Xia, Matthew Reynolds
Journal: Journal of the American College of Cardiology (2019)
Abstract 427: Inhibition of Myocardial Romk Channels Blocks Ischemic Preconditioning Induced Cardio-protection
Authors: Mohun Ramratnam, Warren Linnerooth, John W Kyle, Brandi A Weidmeyer, Emily D Lacount, Nihal Ahmad, Alexander Pasternak, Elizabeth M McNally, Jonathan C Makielski
Journal: Circulation Research (2018)

Background: Prior evidence has shown that the renal outer medullary potassium channel (Kir 1.1 or ROMK) may be the pore forming subunit of the mitochondrial KATP channel (mitoKATP). However, it is unknown if ROMK inhibition affects myocardial function after ischemia reperfusion injury or cardio-protection from ischemic preconditioning. Methods: C57/BL6J mice were subjected to ex vivo ischemia (45 min) and then reperfusion (60 min) with or without ischemic preconditioning (3 cycles of 3 min). Mice were treated throughout the protocol with either 5 μM of compound A, a potent ROMK inhibitor, or vehicle, in a modified Krebs Henseliet buffer. Results: WT mice hearts subjected to ischemia reperfusion injury and perfused with 5 μM compound A recovered 73% of baseline left ventricular developed pressure (LVDP) while mouse hearts perfused with vehicle recovered 50% of baseline LVDP (P=0.07, N=3). Infarct size was not significantly different between hearts perfused with 5 μM compound A or vehicle (32% ± 7% vs. 46% ± 10%, P =0.18, N=3). In vehicle perfused mice, IPC significantly improved % recovery of LVDP (IPC 87% ± 9% vs. no IPC 50% ± 7%, P =0.014, N=3) and infarct size (IPC 22% ± 4% vs no IPC 46% ± 11%, P =0.02, N=3). However, IPC did not improve % recovery of LVDP (IPC 69% ± 6% vs no IPC 73% ± 4%, P =0.33, N=3) or infarct size (IPC 46% ± 14% vs no IPC 32% ± 7%, P =0.22, N=3) in mouse hearts perfused with compound A. Conclusions: Myocardial ROMK inhibition does not increase IR injury in an ex vivo mouse preparation, but does block cardio-protection from IPC further supporting ROMK as the potential pore forming channel of mitoKATP.
Generics companies colluded to keep drug price high, says watchdog
Authors: Clare Dyer
Journal: BMJ (2019)

The Competition and Markets Authority (CMA) has accused two UK generic drug companies of entering into an anti-competitive “pay for delay” agreement which may have cost the NHS an extra £2m (€2.3m; $2.7m) a year.

The CMA alleges in provisional findings, called a statement of objections (SO), that Auden McKenzie paid its rival Waymade to stay out of the market for 20 mg hydrocortisone pills for four years, leaving it the sole supplier.

From 2011 to 2015, the cost of a pack of 30 pills rose from £46 to £90 and NHS spending on hydrocortisone rose from £1.7m to £3.7m a year, the authority said.

“The CMA …
COMPARISON OF THE TIMI, GRACE, PAMI AND CADILLAC RISK SCORES FOR PREDICTION OF CARDIOVASCULAR OUTCOMES IN DIABETIC PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: DATA FROM TSOC ACS-DM REGISTRY
Authors: Yung-Ta Kao, Chien-Yi Hsu, Chun-Yao Huang, Yi-Chen Hsieh, Jong-Shiuan Yeh
Journal: Journal of the American College of Cardiology (2019)
VENOUS THROMBOEMBOLISM IN TRANSWOMEN AS COMPARED TO CISGENDER MEN AND WOMEN: AN 8-YEAR NATIONAL INPATIENT SAMPLE ANALYSIS
Authors: Bishoy Hanna, Rupak Desai, Sonu Gupta, Kapil Bhatia, Samuel Ogbuchi, Obiora Egbuche, Timir Paul, Gautam Kumar, Rajesh Sachdeva
Journal: Journal of the American College of Cardiology (2019)
Angiogenesis Induced By Aminoacyl-tRNA Synthetase Deficiency Is Dependent on Amino Acid Response (AAR) but Not Unfolded Protein Response (UPR) Pathways
Authors: Fan Zhang, Yi Chen, Yi Jin, Chun-Hui Xu, Dian-Jia Liu, Ai-Ning Xu, Yuan-Liang Zhang, Yin-Yin Xie, Jing-Yi Shi, Lan Wang, Qiu-Hua Huang, Zhu Chen, Sai-Juan Chen, Xiao-Jian Sun
Journal: Blood (2018)
THE CONTROL RATE FOR PATIENTS WITH ESSENTIAL HYPERTENSION IN CHINESE ADULTS: A REAL WORD STUDY BASED ON THE ELECTRONIC HEALTH RECORDS OF 544,892 COMMUNITY RESIDENTS
Authors: Ying Wang, Zhiliang Wang, Xin Liu, Chunxiao Xing, Zemin Kuang, Xiangyu Guo, Lijun Wang
Journal: Journal of the American College of Cardiology (2019)
VERY LONG-TERM FOLLOW-UP OF DIABETIC PATIENTS WITH CORONARY ARTERY DISEASE UNDERGOING ANGIOPLASTY WITH CONVENTIONAL AND DRUG-ELUTING STENTS
Authors: Mauricio Mocha, Matheus Oliveira Laterza Ribeiro, Guilherme Fernandes Carvalho, Jaime Linhares Filho, Eduardo Lima, Whady Hueb, Paulo Rezende, Daniel Valente Batista, Eduardo Martins, Diogo Freitas Cardoso Azevedo, Cibele Garzillo, Jose Ramires, Roberto Kalil-Filho
Journal: Journal of the American College of Cardiology (2019)
GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca<sup>2+</sup> signalling in a GABA-independent manner
Authors: Shu-Heng Jiang, Li-Li Zhu, Man Zhang, Rong-Kun Li, Qin Yang, Jiang-Yu Yan, Ce Zhang, Jian-Yu Yang, Fang-Yuan Dong, Miao Dai, Li-Peng Hu, Jun Li, Qing Li, Ya-Hui Wang, Xiao-Mei Yang, Yan-Li Zhang, Hui-Zhen Nie, Lei Zhu, Xue-Li Zhang, Guang-Ang Tian, Xiao-Xin Zhang, Xiao-Yan Cao, Ling-Ye Tao, Shan Huang, Yong-Sheng Jiang, Rong Hua, Kathy Qian Luo, Jian-Ren Gu, Yong-Wei Sun, Shangwei Hou, Zhi-Gang Zhang
Journal: Gut (2019)

Background and aims Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis. Methods The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to identify differentially expressed neurotransmitter receptors. The expression pattern of gamma-aminobutyric acid type A receptor pi subunit (GABRP) in human and mouse PDAC tissues and cells was studied by immunohistochemistry and western blot analysis. The in vivo implications of GABRP in PDAC were tested by subcutaneous xenograft model and lung metastasis model. Bioinformatics analysis, transwell experiment and orthotopic xenograft model were used to identify the in vitro and in vivo effects of GABRP on macrophages in PDAC. ELISA, co-immunoprecipitation, proximity ligation assay, electrophysiology, promoter luciferase activity and quantitative real-time PCR analyses were used to identify molecular mechanism. Results GABRP expression was remarkably increased in PDAC tissues and associated with poor prognosis, contributed to tumour growth and metastasis. GABRP was correlated with macrophage infiltration in PDAC and pharmacological deletion of macrophages largely abrogated the oncogenic functions of GABRP in PDAC. Mechanistically, GABRP interacted with KCNN4 to induce Ca 2+ entry, which leads to activation of nuclear factor κB signalling and ultimately facilitates macrophage infiltration by inducing CXCL5 and CCL20 expression. Conclusions Overexpressed GABRP exhibits an immunomodulatory role in PDAC in a neurotransmitter-independent manner. Targeting GABRP or its interaction partner KCNN4 may be an effective therapeutic strategy for PDAC.
ELEVATED RESTING HEART RATE IMPROVES RISK STRATIFICATION FOR ADVERSE CARDIOVASCULAR OUTCOMES IN CANCER PATIENTS
Authors: Mohamad Hemu, Parva Bhatt, Megan Randall, Aamir Ahmed, Caleb J. Chiang, Andres Palomo, Jason B. Kramer, Ibtihaj Fughhi, Philip Bonomi, Tochukwu M. Okwuosa
Journal: Journal of the American College of Cardiology (2019)
POST-ACUTE CORONARY SYNDROME PATIENTS WITH POLYVASCULAR DISEASE DERIVE LARGE ABSOLUTE BENEFIT FROM ALIROCUMAB: ODYSSEY OUTCOMES
Authors: Johan Wouter Jukema, Michael Szarek, Matthew Roe, Deepak L. Bhatt, Vera Bittner, H. Asita de Silva, Rafael Diaz, Shaun Goodman, Corinne Hanotin, Jay Edelberg, Robert Harrington, Yuri Karpov, Angele Moryusef, Robert Pordy, Juan Prieto, Harvey White, Andreas Zeiher, Gregory Schwartz, Philippe Steg
Journal: Journal of the American College of Cardiology (2019)