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https://www.readbyqxmd.com/read/29140182/tgf-%C3%AE-1-and-cxcl12-modulate-proliferation-and-chemotherapy-sensitivity-of-acute-myeloid-leukemia-cells-co-cultured-with-multipotent-mesenchymal-stromal-cells
#1
Roland Christian Schelker, Sabine Iberl, Gunnar Müller, Christina Hart, Wolfgang Herr, Jochen Grassinger
OBJECTIVES: Multipotent mesenchymal stromal cells (MSCs) play a central role within the bone marrow (BM) niche, supporting hematopoiesis via soluble factors like cytokines and chemokines. In our study, we sought to investigate the effect of blocking transforming growth factor beta 1 (TGF-β1) and C-X-C motif chemokine 12 (CXCL12) receptor CXCR4 on acute myeloid leukemia (AML) cells in an MSC co-culture system. METHODS: Human MSCs were obtained by BM aspirates and their phenotype and functional properties were confirmed in vitro...
November 15, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29122692/blockade-of-platelet-activating-factor-receptor-attenuates-abnormal-behaviors-induced-by-phencyclidine-in-mice-through-down-regulation-of-nf-%C3%AE%C2%BAb
#2
The-Vinh Tran, Se Jin Park, Eun-Joo Shin, Hai-Quyen Tran, Ji Hoon Jeong, Choon-Gon Jang, Yu Jeung Lee, Seung-Yeol Nah, Toshitaka Nabeshima, Hyoung-Chun Kim
Accumulating evidence suggests that neuroinflammation is one of the important etiologic factors of abusive and neuropsychiatric disorders. Platelet-activating factor (PAF) is potent proinflammatory lipid mediat1or and plays a pivotal role in neuroinflammatory disorders through the specific PAF receptor (PAF-R). Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Here, we investigated the role of PAF-R in the abnormal behaviors induced by PCP in mice. Repeated treatment with PCP resulted in a significant increase in PAF-R gene expression in the prefrontal cortex (PFC) and in the hippocampus...
November 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29121280/continuing-chronic-beta-blockade-in-the-acute-phase-of-severe-sepsis-and-septic-shock-is-associated-with-decreased-mortality-rates-up-to-90-days
#3
C Fuchs, S Wauschkuhn, C Scheer, M Vollmer, K Meissner, S-O Kuhn, K Hahnenkamp, A Morelli, M Gründling, S Rehberg
Background: There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. Methods: The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively...
October 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29118031/neurohormonal-blockade-and-circulating-cardiovascular-biomarkers-during-anthracycline-therapy-in-breast-cancer-patients-results-from-the-prada-prevention-of-cardiac-dysfunction-during-adjuvant-breast-cancer-therapy-study
#4
Geeta Gulati, Siri L Heck, Helge Røsjø, Anne H Ree, Pavel Hoffmann, Tor-Arne Hagve, Jon Norseth, Berit Gravdehaug, Kjetil Steine, Jürgen Geisler, Torbjørn Omland
BACKGROUND: Anthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on-treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines...
November 8, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29114413/perioperative-factors-affecting-ambulatory-outcomes-following-laparoscopic-adjustable-gastric-banding
#5
Mirsad Dupanovic, Ron Krebill, Iris Dupanovic, John Nachtigal, Melissa Rockford, Walter Orr
Objective: Morbidly obese patients are traditionally hospitalised following bariatric surgery. However, laparoscopic-adjustable gastric banding (LAGB) is amenable for ambulatory care. We hypothesised that the majority of patients can receive an ambulatory LAGB and that both surgical and anaesthetic perioperative factors will significantly affect non-ambulatory LAGB outcomes. Methods: Medical records of 201 consecutive LAGB patients performed at the University of Kansas Medical Centre during a 3-y period were reviewed...
October 2017: Turkish Journal of Anaesthesiology and Reanimation
https://www.readbyqxmd.com/read/29106497/effect-of-candesartan-and-metoprolol-on-myocardial-tissue-composition-during-anthracycline-treatment-the-prada-trial
#6
Siri Lagethon Heck, Geeta Gulati, Pavel Hoffmann, Florian von Knobelsdorff-Brenkenhoff, Tryggve Holck Storås, Anne Hansen Ree, Berit Gravdehaug, Helge Røsjø, Kjetil Steine, Jürgen Geisler, Jeanette Schulz-Menger, Torbjørn Omland
Aims: Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade. Methods and results: PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol...
June 29, 2017: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/29105118/v1b-receptor-antagonist-ssr149415-and-naltrexone-synergistically-decrease-excessive-alcohol-drinking-in-male-and-female-mice
#7
Yan Zhou, Marcelo Rubinstein, Malcolm Low, Mary Jeanne Kreek
BACKGROUND: A recent clinical trial found that pharmacological blockade of V1b receptors reduces alcohol relapse in alcohol-dependent patients. SSR149415 is a selective V1b receptor antagonist that has potential for development as an alcohol dependency treatment. In this study, we investigated whether SSR149415 alone or in combination with the mu-opioid receptor [MOP-r] antagonist naltrexone (NTN) would alter excessive alcohol drinking in mice. METHODS: Both sexes of C57BL/6J (B6) mice were subjected to a chronic intermittent access (IA) drinking paradigm (two-bottle choice, 24-h access every other day) for 3 weeks...
November 3, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29103968/anti-pd-l1-tgf%C3%AE-r2-m7824-fusion-protein-induces-immunogenic-modulation-of-human-urothelial-carcinoma-cell-lines-rendering-them-more-susceptible-to-immune-mediated-recognition-and-lysis
#8
Italia Grenga, Renee N Donahue, Morgan L Gargulak, Lauren M Lepone, Mario Roselli, Marijo Bilusic, Jeffrey Schlom
BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis...
November 2, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29079516/pharmacological-blockade-of-the-wnt-beta-catenin-signaling-a-possible-first-in-kind-dmoad
#9
EDITORIAL
F Dell'Accio, F Cailotto
No abstract text is available yet for this article.
October 25, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29070816/resistance-to-checkpoint-blockade-therapy-through-inactivation-of-antigen-presentation
#10
Moshe Sade-Feldman, Yunxin J Jiao, Jonathan H Chen, Michael S Rooney, Michal Barzily-Rokni, Jean-Pierre Eliane, Stacey L Bjorgaard, Marc R Hammond, Hans Vitzthum, Shauna M Blackmon, Dennie T Frederick, Mehlika Hazar-Rethinam, Brandon A Nadres, Emily E Van Seventer, Sachet A Shukla, Keren Yizhak, John P Ray, Daniel Rosebrock, Dimitri Livitz, Viktor Adalsteinsson, Gad Getz, Lyn M Duncan, Bo Li, Ryan B Corcoran, Donald P Lawrence, Anat Stemmer-Rachamimov, Genevieve M Boland, Dan A Landau, Keith T Flaherty, Ryan J Sullivan, Nir Hacohen
Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29...
October 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/29069238/urinary-cytokine-profiles-according-to-the-site-of-blockade-of-the-renin-angiotensin-system-in-nephrectomized-rats
#11
Nilo César do Vale Baracho, Kátia Daniela da Silveira, Natália Pessoa Rocha, Thiago Macedo Cordeiro, Victor Feracin, Regina Maria Pereira, Marconi Augusto Aguiar Dos Reis, Mauro Martins Teixeira, Ana Cristina Simões E Silva
INTRODUCTION: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. OBJECTIVE: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). METHODS: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control)...
April 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29061963/%C3%AE-v-integrins-on-mesenchymal-cells-regulate-skeletal-and-cardiac-muscle-fibrosis
#12
I R Murray, Z N Gonzalez, J Baily, R Dobie, R J Wallace, A C Mackinnon, J R Smith, S N Greenhalgh, A I Thompson, K P Conroy, D W Griggs, P G Ruminski, G A Gray, M Singh, M A Campbell, T J Kendall, J Dai, Y Li, J P Iredale, H Simpson, J Huard, B Péault, N C Henderson
Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRβ) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRβ(+) cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRβ(+) cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29055392/sleep-apnea-an-overlooked-cause-of-lipotoxicity
#13
Chenjuan Gu, Haris Younas, Jonathan C Jun
Obstructive sleep apnea (OSA) is a common sleep disorder associated with diabetes and cardiovascular disease. However, the mechanisms by which OSA causes cardiometabolic dysfunction are not fully elucidated. OSA increases plasma free fatty acids (FFA) during sleep, reflecting excessive adipose tissue lipolysis. In animal studies, intermittent hypoxia simulating OSA also increases FFA, and the increase is attenuated by beta-adrenergic blockade. In other contexts, excessive plasma FFA can lead to ectopic fat accumulation, insulin resistance, vascular dysfunction, and dyslipidemia...
October 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29041004/impact-of-beta-blockade-on-cardiac-events-in-patients-with-chronic-severe-nonischemic-mitral-regurgitation
#14
Phyllis G Supino, Ofek Y Hai, Abhishek Sharma, Joshua Lampert, Clare Hochreiter, Edmund M Herrold, Jeffrey S Borer
OBJECTIVES: The aim of this study was to examine the impact of beta-blockade on cardiac events among patients with initially asymptomatic chronic severe nonischemic mitral valve regurgitation (MR). METHODS: Data from 52 consecutive patients in our prospective natural history study of isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of chronic beta-blockade use to subsequent cardiac events (death or indications for mitral valve surgery, MVS)...
October 18, 2017: Cardiology
https://www.readbyqxmd.com/read/29035909/dysregulated-myelopoiesis-and-hematopoietic-function-following-acute-physiologic-insult
#15
Tyler J Loftus, Alicia M Mohr, Lyle L Moldawer
PURPOSE OF REVIEW: The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an acute physiologic insult, focusing on the expansion and persistence of myeloid-deriver suppressor cells, the deterioration of lymphocyte number and function, and the inadequacy of stress erythropoiesis. RECENT FINDINGS: Persistent myeloid-derived suppressor cell (MDSC) expansion among critically ill septic patients is associated with T-cell suppression, vulnerability to nosocomial infection, chronic critical illness, and poor long-term functional status...
October 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29032370/an-immunofluorescence-assay-for-extracellular-matrix-components-highlights-the-role-of-epithelial-cells-in-producing-a-stable-fibrillar-extracellular-matrix
#16
Omar S Qureshi, Hélène Bon, Breda Twomey, Gill Holdsworth, Kirsty Ford, Marianne Bergin, Linghong Huang, Mariusz Muzylak, Louise J Healy, Vanessa Hurdowar, Timothy S Johnson
Activated fibroblasts are considered major drivers of fibrotic disease progression through the production of excessive extracellular matrix (ECM) in response to signals from damaged epithelial and inflammatory cells. Nevertheless, epithelial cells are capable of expressing components of the ECM, cross-linking enzymes that increase its stability and are sensitive to factors involved in the early stages of fibrosis. We therefore wanted to test the hypothesis that epithelial cells can deposit ECM in response to stimulation in a comparable manner to fibroblasts...
October 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29031854/angptl-4-induces-diabetic-retinal-inflammation-by-activating-profilin-1
#17
Qianyi Lu, Peirong Lu, Wei Chen, Li Lu, Zhi Zheng
Diabetic retinopathy (DR), the most common cause of irreversible blindness in working-age adults, results in central vision loss that is caused by microvascular damage to the inner lining of the back of the eye, the retina. The aim of this work was to assess the temporal relationships between angiopoietin-like protein-4 (ANGPTL-4), a novel adipocytokine factor, and diabetic retinal inflammation and microvascular dysfunction. The downstream pathway(s) and upstream mediator(s) of ANGPTL-4 were then determined under high glucose (HG) conditions...
October 13, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/29030687/tolerability-of-bisoprolol-on-domiciliary-spirometry-in-copd
#18
Sunny Jabbal, Brian J Lipworth
We investigated if serial domiciliary measures of spirometry were sensitive at detecting subtle effects of beta-2 blockade associated with bisoprolol in (n = 17) patients with COPD. After a two-week run in on inhaled corticosteroid (ICS) and long acting beta-2 agonist (LABA): beclometasone/formoterol 100/6 µg, patients' started additional a long acting muscarinic receptor antagonist: (LAMA) Tiotropium 18 µg, with concomitant weekly dose titration of bisoprolol: 1.25-2.5-5 mg. After a further week of bisoprolol 5 mg, they were stepped back down to (ICS/LABA) for one week...
October 14, 2017: Lung
https://www.readbyqxmd.com/read/29025008/cardiopulmonary-interactions-with-beta-blockers-and-inhaled-therapy-in-copd
#19
S Jabbal, W Anderson, P Short, A Morrison, A Manoharan, B J Lipworth
Background: Beta-blockers remain underused in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Aim: We compared how different inhaled therapies affect tolerability of bisoprolol and carvedilol in moderate to severe COPD. Design: A randomized, open label, cross-over study. Methods: We compared the cardiopulmonary interactions of bisoprolol 5 mg qd or carvedilol 12.5 mg bid for 6 weeks in conjunction with: (i) triple: inhaled corticosteroid/long acting beta-agonist/long acting muscarinic antagonist (ICS + LABA + LAMA), (ii) dual: ICS + LABA and (iii) ICS alone...
July 24, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28966942/beta-adrenergic-receptors-are-expressed-across-diverse-cancers
#20
Steven L Rains, Clarissa N Amaya, Brad A Bryan
Based largely on retrospective analyses and a handful of prospective case reports, pharmacological inhibition of the beta adrenergic receptors using beta blockers has shown clinical anti-cancer efficacy in reproductive cancers, as well as angiosarcoma and multiple myeloma. Because of the potential promise of beta blockers as an adjunct to standard anti-cancer therapy, it is imperative to identify other tumor types expressing beta adrenergic (β-AR) receptors so future preclinical and clinical studies can be directed at the most promising tumor targets...
July 2017: Oncoscience
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