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https://www.readbyqxmd.com/read/29346507/activity-and-safety-of-afatinib-in-a-window-pre-operative-eortc-study-in-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-scchn
#1
J P Machiels, P Bossi, J Menis, M Lia, C Fortpied, Y Liu, R Lhommel, M Lemort, S Schmitz, S Canevari, L De Cecco, M Guzzo, R Bianchi, P Quattrone, F Crippa, T Duprez, Y Lalami, M Quiriny, N de Saint Aubain, P M Clement, R Coropciuc, E Hauben, L F Licitra
Background: To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29346139/blood-biomarkers-for-evaluation-of-perinatal-encephalopathy-state-of-the-art
#2
Ernest M Graham, Allen D Everett, Jean-Christophe Delpech, Frances J Northington
PURPOSE OF REVIEW: The rapid progress in biomarker science is on the threshold of significantly changing clinical care for infants in the neonatal ICU. Infants with neonatal brain injuries will likely be the first group whose management is dramatically altered with point-of-care, rapidly available brain biomarker analysis. Providing an interim update on progress in this area is the purpose of this review. RECENT FINDINGS: Highlighted findings from the past 18 months of publications on biomarkers in neonatal brain injury include; Specific nonbrain markers of cardiac health and global asphyxia continue to provide information on brain injury after hypoxic-ischemic encephalopathy (HIE)...
January 17, 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29345294/hypoxia-stimulates-the-cytoplasmic-localization-of-oncogenic-long-noncoding-rna-linc00152-in-colorectal-cancer
#3
Yujiro Nishizawa, Masamitsu Konno, Ayumu Asai, Jun Koseki, Koichi Kawamoto, Norikatsu Miyoshi, Hidekazu Takahashi, Naohiro Nishida, Naotsugu Haraguchi, Daisuke Sakai, Toshihiro Kudo, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Recent studies have indicated that long noncoding RNAs (lncRNAs) play a pivotal role in almost all physiological cellular processes, including every stage of cancer development. Given that hypoxia in the tumor microenvironment is involved in the malignant behavior of tumors, such as invasion and metastasis, we investigated the cytoplasmic and nuclear localization of lncRNAs in colorectal cancer cells. A cell culture under hypoxic conditions revealed several lncRNAs, such as LINC00152, whose levels were increased in the cytoplasm of colorectal cancer cells...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345289/no-erythropoietin-induced-growth-is-observed-in-non-small-cell-lung-cancer-cells
#4
Armin Frille, Katharina Leithner, Andrea Olschewski, Horst Olschewski, Christoph Wohlkönig, Andelko Hrzenjak
Lung cancer patients have the highest incidence of anemia among patients with solid tumors. The use of recombinant human erythropoietin (Epo) has consistently been shown to reduce the need for blood transfusions and to increase hemoglobin levels in lung cancer patients with chemotherapy-induced anemia. However, clinical and preclinical studies have prompted concerns that Epo and the presence of its receptor, EpoR, in tumor cells may be responsible for adverse effects and, eventually, death. The question has been raised whether Epo promotes tumor growth and inhibits the death of cancer cells...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345199/pulmonary-vascular-dysfunction-secondary-to-pulmonary-arterial-hypertension-insights-gained-through-retrograde-perfusion
#5
Chun Zhou, Edward S Crockett, Lynn Batten, Ivan F McMurtry, Troy Stevens
Here, we tested the hypothesis that severe pulmonary arterial hypertension impairs retrograde perfusion. To test this hypothesis, pulmonary arterial hypertension was induced in Fischer rats using a single injection of Sugen 5416 followed by 3 weeks of exposure to 10% hypoxia and then 2 weeks of normoxia. This Sugen 5416 and hypoxia regimen caused severe pulmonary arterial hypertension, with a Fulton Index of 0.73+0.07, reductions in both the pulmonary arterial acceleration time and pulmonary arterial acceleration to pulmonary arterial ejection times ratio, and extensive medial hypertrophy and occlusive neointimal lesions...
January 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29344970/carbon-allocation-to-major-metabolites-in-illuminated-leaves-is-not-just-proportional-to-photosynthesis-when-gaseous-conditions-co2-and-o2-vary
#6
Cyril Abadie, Camille Bathellier, Guillaume Tcherkez
In gas-exchange experiments, manipulating CO2 and O2 is commonly used to change the balance between carboxylation and oxygenation. Downstream metabolism (utilization of photosynthetic and photorespiratory products) may also be affected by gaseous conditions but this is not well documented. Here, we took advantage of sunflower as a model species, which accumulates chlorogenate in addition to sugars and amino acids (glutamate, alanine, glycine and serine). We performed isotopic labelling with 13 CO2 under different CO2 /O2 conditions, and determined 13 C contents to compute 13 C-allocation patterns and build-up rates...
January 18, 2018: New Phytologist
https://www.readbyqxmd.com/read/29344729/sodium-bicarbonate-supplementation-improves-severe-intensity-intermittent-exercise-under-moderate-acute-hypoxic-conditions
#7
Sanjoy K Deb, Lewis A Gough, S Andy Sparks, Lars R McNaughton
Acute moderate hypoxic exposure can substantially impair exercise performance, which occurs with a concurrent exacerbated rise in hydrogen cation (H+) production. The purpose of this study was therefore, to alleviate this acidic stress through sodium bicarbonate (NaHCO3) supplementation and determine the corresponding effects on severe-intensity intermittent exercise performance. Eleven recreationally active individuals participated in this randomised, double-blind, crossover study performed under acute normobaric hypoxic conditions (FiO2% = 14...
January 17, 2018: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/29341045/approach-to-infants-born-through-meconium-stained-amniotic-fluid-evolution-based-on-evidence
#8
Munmun Rawat, Sushma Nangia, Praveen Chandrasekharan, Satyan Lakshminrusimha
Meconium-stained amniotic fluid (MSAF) during delivery is a marker of fetal stress. Neonates born through MSAF often need resuscitation and are at risk of meconium aspiration syndrome (MAS), air leaks, hypoxic-ischemic encephalopathy, extracorporeal membrane oxygenation (ECMO), and death. The neonatal resuscitation approach to MSAF has evolved over the last three decades. Previously, nonvigorous neonates soon after delivery were suctioned under the vocal cords with direct visualization technique using a meconium aspirator...
January 16, 2018: American Journal of Perinatology
https://www.readbyqxmd.com/read/29341043/can-neonatal-brain-mri-be-performed-during-active-cooling
#9
Marisa J Pacella, Dhanashree A Rajderkar, Nicole Copenhaver, Kristine Boykin, Michael D Weiss
OBJECTIVE:  Due to logistical constraints, physicians traditionally delay diagnostic imaging for neonatal hypoxic-ischemic encephalopathy (HIE) until the neonate has completed all 72 hours of therapeutic hypothermia and rewarming. In some cases, neonates may require neuroimaging before 72 hours has passed. STUDY DESIGN:  We present a case in which an MRI was acquired during active hypothermia. RESULTS:  Upon return to the NICU, Baby X's temperature probe read 33...
January 16, 2018: American Journal of Perinatology
https://www.readbyqxmd.com/read/29339541/phd3-controls-lung-cancer-metastasis-and-resistance-to-egfr-inhibitors-through-tgf%C3%AE
#10
Higinio Dopeso, Hui-Ke Jiao, Angel M Cuesta, Anne-Theres Henze, Liane Jurida, Michael Kracht, Amparo Acker-Palmer, Boyan K Garvalov, Till Acker
Lung cancer is the leading cause of cancer-related death worldwide, in large part due to its high propensity to metastasize and develop therapy resistance. Adaptive responses to hypoxia and epithelial-mesenchymal transition (EMT) are linked to tumor metastasis and drug resistance, but little is known about how oxygen sensing and EMT intersect to control these hallmarks of cancer. Here we show that the oxygen sensor PHD3 links hypoxic signaling and EMT regulation in the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT and acted as a negative regulator of EMT, metastasis and therapeutic resistance...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29339479/hif-signaling-in-osteoblast-lineage-cells-promotes-systemic-breast-cancer-growth-and-metastasis-in-mice
#11
Claire-Sophie Devignes, Yetki Aslan, Audrey Brenot, Audrey Devillers, Koen Schepers, Stéphanie Fabre, Jonathan Chou, Amy-Jo Casbon, Zena Werb, Sylvain Provot
Bone metastasis involves dynamic interplay between tumor cells and the local stromal environment. In bones, local hypoxia and activation of the hypoxia-inducible factor (HIF)-1α in osteoblasts are essential to maintain skeletal homeostasis. However, the role of osteoblast-specific HIF signaling in cancer metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are located in hypoxic niches in the bone marrow and that activation of HIF signaling in these cells increases bone mass and favors breast cancer metastasis to bone locally...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339404/hif-1%C3%AE-and-hif-2%C3%AE-regulate-hemogenic-endothelium-and-hematopoietic-stem-cell-formation-in-zebrafish
#12
Claudia Gerri, Michele Marass, Andrea Rossi, Didier Y R Stainier
During development, hematopoietic stem cells (HSCs) derive from specialized endothelial cells (ECs), called hemogenic endothelium (HE), via a process called endothelial-to-hematopoietic transition (EHT). While hypoxia inducible factor-1α (HIF-1α) has been reported to positively modulate EHT in vivo, current data indicate the existence of other regulators of this process. Here we show that in zebrafish Hif-2α also positively modulates HSC formation. Specifically, HSC marker gene expression is strongly decreased in hif-1aa;hif-1ab (hif-1α) and in hif-2aa;hif-2ab (hif-2α) zebrafish mutants and morphants...
January 16, 2018: Blood
https://www.readbyqxmd.com/read/29339173/neuroprotective-effects-of-topiramate-and-memantine-in-combination-with-hypothermia-in-hypoxic-ischemic-brain-injury-in-vitro-and-in-vivo
#13
Elisa Landucci, Luca Filippi, Elisabetta Gerace, Serena Catarzi, Renzo Guerrini, Domenico E Pellegrini-Giampietro
Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal mortality and subsequent severe neurological sequelae. Mild hypothermia is a standard therapy for HIE, but is used only in selected Reference Centers and in neonates >1800 g. Since neuronal death following HIE occurs by a cascade of events triggered by activation of glutamate receptors, we used in vitro and in vivo models of HIE to examine whether the AMPA/kainate receptor antagonist topiramate and the NMDA receptor antagonist memantine could exert neuroprotective effects, alone or in combination with hypothermia...
January 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29339014/development-of-gpc3-specific-chimeric-antigen-receptor-engineered-natural-killer-cells-for-the-treatment-of-hepatocellular-carcinoma
#14
Min Yu, Hong Luo, Mingliang Fan, Xiuqi Wu, Bizhi Shi, Shengmeng Di, Ying Liu, Zeyan Pan, Hua Jiang, Zonghai Li
Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential utilities have not been explored in hepatocellular carcinoma (HCC). Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study, we developed GPC3-specific NK cells and explored their potential in the treatment of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly cytotoxic NK cell line with second-generation GPC3-specific CAR...
December 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29338840/hydrogen-sulfide-provides-intestinal-protection-during-a-murine-model-of-experimental-necrotizing-enterocolitis
#15
Natalie A Drucker, Amanda R Jensen, Michael Ferkowicz, Troy A Markel
BACKGROUND: Necrotizing enterocolitis (NEC) continues to be a morbid surgical condition among preterm infants. Novel therapies for this condition are desperately needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that has been found to have beneficial properties. We therefore hypothesized that intraperitoneal injection of various H2S donors would improve clinical outcomes, increase intestinal perfusion, and reduce intestinal injury in an experimental mouse model of necrotizing enterocolitis...
December 24, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29338172/activation-of-nrf2-and-hypoxic-adaptive-response-contribute-to-neuroprotection-elicited-by-phenylhydroxamic-acid-selective-hdac6-inhibitors
#16
Irina N Gaisina, Sue H Lee, Navneet A Kaidery, Manel Ben Aissa, Manuj Ahuja, Natalya N Smirnova, Sushama Wakade, Arsen Gaisin, Megan W Bourassa, Rajiv R Ratan, Sergey V Nikulin, Andrey A Poloznikov, Bobby Thomas, Gregory R J Thatcher, Irina G Gazaryan
Activation of HIF-1α and Nrf2 is a primary component of cellular response to oxidative stress, and activation of HIF-1α and Nrf2 provides neuroprotection in models of neurodegenerative disorders, including ischemic stroke, Alzheimer's and Parkinson's diseases. Screening a library of CNS-targeted drugs using novel reporters for HIF-1α and Nrf2 elevation in neuronal cells revealed histone deacetylase (HDAC) inhibitors as potential activators of these pathways. We report the identification of phenylhydroxamates as single agents exhibiting tripartite inhibition of HDAC6, inhibition of HIF-1 prolyl hydroxylase (PHD), and activation of Nrf2...
January 17, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29338076/hypoxia-inducible-transcription-factors-hif1a-and-hif2a-increase-in-aging-mucosal-tissues
#17
J L Ebersole, M J Novak, L Orraca, J Martinez-Gonzalez, S Kirakodu, K C Chen, A Stromberg, O A Gonzalez
Hypoxia (ie. oxygen deprivation) activates the hypoxia-signaling pathway, primarily via hypoxia inducible transcription factors (HIF) for numerous target genes, which mediate angiogenesis, metabolism, coagulation, among other processes to try to replenish tissues with blood and oxygen. Hypoxia signaling dysregulation also commonly occurs during chronic inflammation. We sampled gingival tissues from rhesus monkeys (M. mulatta; 3-25 years old) and total RNA was isolated for microarray analysis. HIF1A, HIF1B, and HIF2A were significantly different in healthy aged tissues, and both HIF1A and HIF3A were positively correlated with aging...
January 16, 2018: Immunology
https://www.readbyqxmd.com/read/29337282/comparative-proteome-analysis-of-monolayer-and-spheroid-culture-of-canine-osteosarcoma-cells
#18
Christiane Gebhard, Ingrid Miller, Karin Hummel, Martina Neschi Née Ondrovics, Sarah Schlosser, Ingrid Walter
Osteosarcoma is an aggressive bone tumor with high metastasis rate in the lungs and affects both humans and dogs in a similar way. Three-dimensional tumor cell cultures mimic the in vivo situation of micro-tumors and metastases and are therefore better experimental in vitro models than the often applied two-dimensional monolayer cultures. The aim of the present study was to perform comparative proteomics of standard monolayer cultures of canine osteosarcoma cells (D17) and three-dimensional spheroid cultures, to better characterize the 3D model before starting with experiments like migration assays...
January 11, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29337222/blockade-of-placental-growth-factor-reduces-vaso-occlusive-complications-in-murine-models-of-sickle-cell-disease
#19
Jian-Ming Gu, Shujun Yuan, Derek Sim, Keith Abe, Perry Liu, Martin Rosenbruch, Peter Bringmann, Katalin Kauser
Vaso-occlusive crisis (VOC) is the most common and debilitating complication of sickle cell disease (SCD); recurrent episodes cause organ damage and contribute to early mortality. Plasma placental growth factor (PlGF) levels are elevated in SCD and can further increase under hypoxic conditions in SCD mice. Treatment with a PlGF-neutralizing antibody (anti-PlGF Ab) in SCD mice reduced levels of monocyte chemoattractant protein-3, eotaxin, macrophage colony-stimulating factor, plasminogen activator inhibitor-1 significantly, and macrophage-derived chemokine and macrophage inflammatory protein-3β moderately; this may contribute to inhibition of leukocyte recruitment, activation, and thrombosis...
January 11, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29335581/role-of-hypoxia-in-diffuse-large-b-cell-lymphoma-metabolic-repression-and-selective-translation-of-hk2-facilitates-development-of-dlbcl
#20
Kavita Bhalla, Sausan Jaber, Nanaji Nahid M, Karen Underwood, Afshin Beheshti, Ari Landon, Binny Bhandary, Paul Bastain, Andrew M Evens, John Haley, Brian Polster, Ronald B Gartenhaus
Published molecular profiling studies in patients with lymphoma suggested the influence of hypoxia inducible factor-1 alpha (HIF1α) targets in prognosis of DLBCL. Yet, the role of hypoxia in hematological malignancies remains unclear. We observed that activation of HIF1α resulted in global translation repression during hypoxic stress in DLBCL. Protein translation efficiency as measured using 35S-labeled methionine incorporation revealed a ≥50% reduction in translation upon activation of HIF1α. Importantly, translation was not completely inhibited and expression of clinically correlated hypoxia targets such as GLUT1, HK2, and CYT-C was found to be refractory to translational repression under hypoxia in DLBCL cells...
January 15, 2018: Scientific Reports
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