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Hypoxia

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https://www.readbyqxmd.com/read/30175155/a-novel-approach-to-target-hypoxic-cancer-cells-via-combining-%C3%AE-oxidation-inhibitor-etomoxir-with-radiation
#1
Arpit Dheeraj, Chapla Agarwal, Isabel R Schlaepfer, David Raben, Rana Singh, Rajesh Agarwal, Gagan Deep
Background: Hypoxia in tumors is associated with resistance towards various therapies including radiotherapy. In this study, we assessed if hypoxia in cancer spheres could be effectively reduced by adding etomoxir (a β-oxidation inhibitor) immediately after cell irradiation. Methods: We employed cancer cells' sphere model to target hypoxia. Confocal imaging was used to analyze hypoxia and expression of specific biomarkers in spheres following various treatments (radiation and/or etomoxir)...
2018: Hypoxia
https://www.readbyqxmd.com/read/29862306/effects-of-human-relaxin-2-serelaxin-on-hypoxic-pulmonary-vasoconstriction-during-acute-hypoxia-in-a-sheep-model
#2
René Schiffner, Marius Nistor, Sabine Juliane Bischoff, Georg Matziolis, Martin Schmidt, Thomas Lehmann
Purpose: Hypoxia induces pulmonary vasoconstriction with a subsequent increase of pulmonary artery pressure (PAP), which can result in pulmonary hypertension. Serelaxin has shown an increase of pulmonary hemodynamic parameters after serelaxin injection. We therefore investigated the response of pulmonary hemodynamic parameters after serelaxin administration in a clinically relevant model. Methods: Six controls and six sheep that received 30 μg/kg serelaxin underwent right heart catheterization during a 12-minute hypoxia period (inhalation of 5% oxygen and 95% nitrogen) and subsequent reoxygenation...
2018: Hypoxia
https://www.readbyqxmd.com/read/29392150/a-multichannel-computer-driven-system-to-raise-aquatic-embryos-under-selectable-hypoxic-conditions
#3
Sanjeeva Metikala, Herbert Neuhaus, Thomas Hollemann
The formation of a functional cardiovascular system is an essential step in the early vertebrate embryo. Nevertheless, the effect of hypoxia on the developmental program of organisms was studied rarely. In particular, this holds true for vertebrate embryos that depend on a functional placenta for proper development and had not been studied in this respect due to the obvious limitation. We established a protocol to culture aquatic embryos, which enabled us to culture a high number of Xenopus embryos until tadpole stage under defined hypoxic conditions in four hypoxia chambers simultaneously, employing a computerized system...
2018: Hypoxia
https://www.readbyqxmd.com/read/28770235/respiratory-muscle-dysfunction-in-animal-models-of-hypoxic-disease-antioxidant-therapy-goes-from-strength-to-strength
#4
REVIEW
Ken D O'Halloran, Philip Lewis
The striated muscles of breathing play a critical role in respiratory homeostasis governing blood oxygenation and pH regulation. Upper airway dilator and thoracic pump muscles retain a remarkable capacity for plasticity throughout life, both in health and disease states. Hypoxia, whatever the cause, is a potent driver of respiratory muscle remodeling with evidence of adaptive and maladaptive outcomes for system performance. The pattern, duration, and intensity of hypoxia are key determinants of respiratory muscle structural-, metabolic-, and functional responses and adaptation...
2017: Hypoxia
https://www.readbyqxmd.com/read/28770234/snps-linkage-disequilibrium-and-chronic-mountain-sickness-in-tibetan-chinese
#5
Norman E Buroker, Xue-Han Ning, Zhao-Nian Zhou, Kui Li, Wei-Jun Cen, Xiu-Feng Wu, Wei-Zhong Zhu, C Ronald Scott, Shi-Han Chen
Chronic mountain sickness (CMS) is estimated at 1.2% in Tibetans living at the Qinghai-Tibetan Plateau. Eighteen single-nucleotide polymorphisms (SNPs) from nine nuclear genes that have an association with CMS in Tibetans have been analyzed by using pairwise linkage disequilibrium (LD). The SNPs included are the angiotensin-converting enzyme (rs4340), the angiotensinogen (rs699), and the angiotensin II type 1 receptor (AGTR1) (rs5186) from the renin-angiotensin system. A low-density lipoprotein apolipoprotein B (rs693) SNP was also included...
2017: Hypoxia
https://www.readbyqxmd.com/read/28580363/targeted-metabolomics-in-colorectal-cancer-a-strategic-approach-using-standardized-laboratory-tests-of-the-blood-and-urine
#6
Katarzyna J Jerzak, Marissa Laureano, Radwa Elsharawi, Peter Kavsak, Kelvin Kw Chan, Sukhbinder K Dhesy-Thind, Kevin Zbuk
BACKGROUND: Glycolytic markers have been detected in colorectal cancer (CRC) using advanced analytical methods. METHODS: Using commercially available assays, by-products of anaerobic metabolism were prospectively measured in the blood and urine of 20 patients with metastatic colorectal cancer (mCRC) and 20 patients with local disease. Twenty-four-hour urine citrate, plasma lactate, ketones, venous blood gas, anion gap, and osmolar gap were investigated. Results of patients with metastatic and local CRC were compared using two-sample t-tests or equivalent nonparametric tests...
2017: Hypoxia
https://www.readbyqxmd.com/read/28580362/kemtub012-ni2-a-novel-potent-tubulysin-analog-that-selectively-targets-hypoxic-cancer-cells-and-is-potentiated-by-cytochrome-p450-reductase-downregulation
#7
Paolo Lazzari, Marco Spiga, Monica Sani, Matteo Zanda, Ian N Fleming
PURPOSE: There is an urgent need to develop effective therapies and treatment strategies to treat hypoxic tumors, which have a very poor prognosis and do not respond well to existing therapies. METHODS: A novel hypoxia-targeting agent, KEMTUB012-NI2, was synthesized by conjugating a 2-nitroimidazole hypoxia-targeting moiety to a synthetic tubulysin, a very potent antimitotic. Its hypoxic selectivity and mode of action were studied in breast cancer cell lines. RESULTS: KEMTUB012-NI2 exhibited a similar selectivity for hypoxic cells to that of tirapazamine, a well-established hypoxia-targeting agent, but was >1,000 times more potent in cell cytotoxicity assays...
2017: Hypoxia
https://www.readbyqxmd.com/read/28580361/neuroprotection-via-rna-binding-protein-rbm3-expression-is-regulated-by-hypothermia-but-not-by-hypoxia-in-human-sk-n-sh-neurons
#8
Lisa-Maria Rosenthal, Giang Tong, Christoph Walker, Sylvia J Wowro, Jana Krech, Constanze Pfitzer, Georgia Justus, Felix Berger, Katharina Rose Luise Schmitt
OBJECTIVE: Therapeutic hypothermia is an established treatment for perinatal asphyxia. Yet, many term infants continue to die or suffer from neurodevelopmental disability. Several experimental studies have demonstrated a beneficial effect of mild-to-moderate hypothermia after hypoxic injury, but the understanding of hypothermia-induced neuroprotection remains incomplete. In general, global protein synthesis is attenuated by hypothermia, but a small group of RNA-binding proteins including the RNA-binding motif 3 (RBM3) is upregulated in response to cooling...
2017: Hypoxia
https://www.readbyqxmd.com/read/28443291/a-review-of-the-development-of-tumor-vasculature-and-its-effects-on-the-tumor-microenvironment
#9
REVIEW
Jake C Forster, Wendy M Harriss-Phillips, Michael Jj Douglass, Eva Bezak
BACKGROUND: The imbalance of angiogenic regulators in tumors drives tumor angiogenesis and causes the vasculature to develop much differently in tumors than in normal tissue. There are several cancer therapy techniques currently being used and developed that target the tumor vasculature for the treatment of solid tumors. This article reviews the aspects of the tumor vasculature that are relevant to most cancer therapies but particularly to vascular targeting techniques. MATERIALS AND METHODS: We conducted a review of identified experiments in which tumors were transplanted into animals to study the development of the tumor vasculature with tumor growth...
2017: Hypoxia
https://www.readbyqxmd.com/read/28352643/update-on-hypoxia-inducible-factors-and-hydroxylases-in-oxygen-regulatory-pathways-from-physiology-to-therapeutics
#10
REVIEW
Peter Ratcliffe, Peppi Koivunen, Johanna Myllyharju, Jiannis Ragoussis, Judith Vmg Bovée, Ines Batinic-Haberle, Claire Vinatier, Valérie Trichet, Florence Robriquet, Lisa Oliver, Betty Gardie
The "Hypoxia Nantes 2016" organized its second conference dedicated to the field of hypoxia research. This conference focused on "the role of hypoxia under physiological conditions as well as in cancer" and took place in Nantes, France, in October 6-7, 2016. The main objective of this conference was to bring together a large group of scientists from different spheres of hypoxia. Recent advances were presented and discussed around different topics: genomics, physiology, musculoskeletal, stem cells, microenvironment and cancer, and oxidative stress...
2017: Hypoxia
https://www.readbyqxmd.com/read/28331872/induction-of-erythropoiesis-by-hypoxia-inducible-factor-prolyl-hydroxylase-inhibitors-without-promotion-of-tumor-initiation-progression-or-metastasis-in-a-vegf-sensitive-model-of-spontaneous-breast-cancer
#11
Todd W Seeley, Mark D Sternlicht, Stephen J Klaus, Thomas B Neff, David Y Liu
The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neu(ndl)-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592)...
2017: Hypoxia
https://www.readbyqxmd.com/read/27995152/combination-effects-of-sorafenib-with-pi3k-inhibitors-under-hypoxia-in-colorectal-cancer
#12
Dimple R Bhatia, Padma Thiagarajan
AIM: This study reports the influence of hypoxia on response of colorectal cancer cells to anticancer effects of sorafenib in combination with PI3K inhibitors GDC-0941 and BEZ-235. MATERIALS AND METHODS: All hypoxic exposures were carried out at 1% O2/5% CO2. Antiproliferation activity was evaluated by 48 hours propidium iodide and 14 days clonogenic assay. Protein levels were evaluated by fluorescence ELISA. Metabolites lactate and glucose were evaluated biochemically...
2016: Hypoxia
https://www.readbyqxmd.com/read/27933301/the-three-musketairs-lasker-prize-2016-goes-to-the-protagonists-of-hypoxia-research
#13
EDITORIAL
Roland H Wenger, Dörthe M Katschinski
No abstract text is available yet for this article.
2016: Hypoxia
https://www.readbyqxmd.com/read/27878135/control-of-the-heart-rate-of-rat-embryos-during-the-organogenic-period
#14
Helen E Ritchie, Carolina Ragnerstam, Elin Gustafsson, Johanna M Jonsson, William S Webster
The aim of this study was to gain insight into whether the first trimester embryo could control its own heart rate (HR) in response to hypoxia. The gestational day 13 rat embryo is a good model for the human embryo at 5-6 weeks gestation, as the heart is comparable in development and, like the human embryo, has no functional autonomic nerve supply at this stage. Utilizing a whole-embryo culture technique, we examined the effects of different pharmacological agents on HR under normoxic (95% oxygen) and hypoxic (20% oxygen) conditions...
2016: Hypoxia
https://www.readbyqxmd.com/read/27800515/phosphorylation-of-the-pyruvate-dehydrogenase-complex-precedes-hif-1-mediated-effects-and-pyruvate-dehydrogenase-kinase-1-upregulation-during-the-first-hours-of-hypoxic-treatment-in-hepatocellular-carcinoma-cells
#15
Andreas David Zimmer, Geoffroy Walbrecq, Ines Kozar, Iris Behrmann, Claude Haan
The pyruvate dehydrogenase complex (PDC) is an important gatekeeper enzyme connecting glycolysis to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). Thereby, it has a strong impact on the glycolytic flux as well as the metabolic phenotype of a cell. PDC activity is regulated via reversible phosphorylation of three serine residues on the pyruvate dehydrogenase (PDH) E1α subunit. Phosphorylation of any of these residues by the PDH kinases (PDKs) leads to a strong decrease in PDC activity...
2016: Hypoxia
https://www.readbyqxmd.com/read/27800514/erythropoietin-and-a-nonerythropoietic-peptide-analog-promote-aortic-endothelial-cell-repair-under-hypoxic-conditions-role-of-nitric-oxide
#16
Lamia Heikal, Pietro Ghezzi, Manuela Mengozzi, Blanka Stelmaszczuk, Martin Feelisch, Gordon Aa Ferns
The cytoprotective effects of erythropoietin (EPO) and an EPO-related nonerythropoietic analog, pyroglutamate helix B surface peptide (pHBSP), were investigated in an in vitro model of bovine aortic endothelial cell injury under normoxic (21% O2) and hypoxic (1% O2) conditions. The potential molecular mechanisms of these effects were also explored. Using a model of endothelial injury (the scratch assay), we found that, under hypoxic conditions, EPO and pHBSP enhanced scratch closure by promoting cell migration and proliferation, but did not show any effect under normoxic conditions...
2016: Hypoxia
https://www.readbyqxmd.com/read/27800513/preconditioning-with-ethyl-3-4-dihydroxybenzoate-augments-aerobic-respiration-in-rat-skeletal-muscle
#17
Charu Nimker, Deependra Pratap Singh, Deepika Saraswat, Anju Bansal
Muscle respiratory capacity decides the amount of exertion one's skeletal muscle can undergo, and endurance exercise is believed to increase it. There are also certain preconditioning methods by which muscle respiratory and exercise performance can be enhanced. In this study, preconditioning with ethyl 3,4-dihydroxybenzoate (EDHB), a prolyl hydroxylase domain enzyme inhibitor, has been investigated to determine its effect on aerobic metabolism and bioenergetics in skeletal muscle, thus facilitating boost in physical performance in a rat model...
2016: Hypoxia
https://www.readbyqxmd.com/read/27800512/chronic-intermittent-hypoxia-and-obstructive-sleep-apnea-an-experimental-and-clinical-approach
#18
REVIEW
Emilia Sforza, Fréderic Roche
Obstructive sleep apnea (OSA) is a prevalent sleep disorder considered as an independent risk factor for cardiovascular consequences, such as systemic arterial hypertension, ischemic heart disease, cardiac arrhythmias, metabolic disorders, and cognitive dysfunction. The pathogenesis of OSA-related consequence is assumed to be chronic intermittent hypoxia (IH) inducing alterations at the molecular level, oxidative stress, persistent systemic inflammation, oxygen sensor activation, and increase of sympathetic activity...
2016: Hypoxia
https://www.readbyqxmd.com/read/27800511/oxygen-dependent-regulation-of-aquaporin-3-expression
#19
David Hoogewijs, Melanie Vogler, Eveline Zwenger, Sabine Krull, Anke Zieseniss
The purpose of this study was to investigate whether aquaporin-3 (AQP3) expression is altered in hypoxia and whether hypoxia-inducible transcription factor (HIF)-1 regulates the hypoxic expression. AQP3 mRNA expression was studied in L929 fibrosarcoma cells and in several tissues derived from mice that were subjected to hypoxia. Computational analysis of the AQP3 promoter revealed conserved HIF binding sites within close proximity to the translational start site, and chromatin immunoprecipitation assays confirmed binding of HIF-1α to the endogenous hypoxia response elements...
2016: Hypoxia
https://www.readbyqxmd.com/read/27800510/sevoflurane-mitigates-shedding-of-hyaluronan-from-the-coronary-endothelium-also-during-ischemia-reperfusion-an-ex-vivo-animal-study
#20
Congcong Chen, Daniel Chappell, Thorsten Annecke, Peter Conzen, Matthias Jacob, Ulrich Welsch, Bernhard Zwissler, Bernhard F Becker
Glycosaminoglycan hyaluronan (HA), a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas) on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C) followed by reperfusion (40 minutes), half with and half without preconditioning by sevoflurane...
2016: Hypoxia
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