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https://www.readbyqxmd.com/read/28425047/can-anti-vascular-endothelial-growth-factor-antibody-reverse-radiation-necrosis-a-preclinical-investigation
#1
Chong Duan, Carlos J Perez-Torres, Liya Yuan, John A Engelbach, Scott C Beeman, Christina I Tsien, Keith M Rich, Robert E Schmidt, Joseph J H Ackerman, Joel R Garbow
Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife Perfexion™ and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4-12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment...
April 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28423052/inflammation-induced-fetal-growth-restriction-in-rats-is-associated-with-increased-placental-hif-1%C3%AE-accumulation
#2
Kevin P Robb, Tiziana Cotechini, Camille Allaire, Arissa Sperou, Charles H Graham
INTRODUCTION: Hypoxia-inducible factor 1-alpha (HIF-1α) is the oxygen-sensitive subunit of the transcription factor HIF-1, and its expression is increased in placentas from pregnancies complicated by pre-eclampsia (PE). Fetal growth restriction (FGR) and PE often share a common pathophysiology; however, it is unknown whether increased placental HIF-1α occurs in FGR. We previously demonstrated that aberrant maternal inflammation in rats resulted in altered utero-placental perfusion and FGR, both of which were prevented by administration of the nitric oxide mimetic glyceryl trinitrate (GTN)...
2017: PloS One
https://www.readbyqxmd.com/read/28421447/inhibition-of-p-glycoprotein-stimulates-cell-death-under-hypoxia-mimicking-conditions
#3
A S Vdovin, P V Maximchik, A V Kulikov, B D Zhivotovsky, V G Gogvadze
The most common drug resistance mechanism in tumor cells is expression on their surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels chemotherapeutic agents from the interior. An imitation of the hypoxic condition by the iron chelator deferoxamine caused Hypoxia-inducible factor 1-alpha (HIF-1α) stabilization and inhibition of doxorubicin-induced apoptosis in colon cancer НСТ116 cells. P-gp blocker verapamil suppressed doxorubicin accumulation leading to cell death induction. Considering these results, P-gp may be used as a potential target to stimulate chemotherapeutic drugs activity that will contribute to more efficient tumor cells elimination...
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28420787/activation-of-nlrp3-inflammasome-complex-potentiates-venous-thrombosis-in-response-to-hypoxia
#4
Neha Gupta, Anita Sahu, Amit Prabhakar, Tathagata Chatterjee, Tarun Tyagi, Babita Kumari, Nilofar Khan, Velu Nair, Nitin Bajaj, Manish Sharma, Mohammad Zahid Ashraf
Venous thromboembolism (VTE), caused by altered hemostasis, remains the third most common cause of mortality among all cardiovascular conditions. In addition to established genetic and acquired risk factors, low-oxygen environments also predispose otherwise healthy individuals to VTE. Although disease etiology appears to entail perturbation of hemostasis pathways, the key molecular determinants during immediate early response remain elusive. Using an established model of venous thrombosis, we here show that systemic hypoxia accelerates thromboembolic events, functionally stimulated by the activation of nucleotide binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome complex and increased IL-1β secretion...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28418093/hypoxia-inducible-factor-1-alpha-does-not-regulate-osteoclastogenesis-but-enhances-bone-resorption-activity-via-prolyl-4-hydroxylase-2
#5
Philippa A Hulley, Tammie Bishop, Aude Vernet, Jurgen E Schneider, James R Edwards, Nick A Athanasou, Helen J Knowles
Osteogenic-angiogenic coupling is promoted by the Hypoxia-Inducible Factor 1-alpha (HIF-1α) transcription factor, provoking interest in HIF activation as a therapeutic strategy to improve osteoblast mineralisation and treat pathological osteolysis. However, HIF also enhances the bone resorbing activity of mature osteoclasts. It is therefore essential to determine the full effect(s) of HIF on both the formation and bone-resorbing function of osteoclasts in order to understand how they might respond to such a strategy...
April 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28410378/metabolic-changes-and-inflammation-in-cultured-astrocytes-from-the-5xfad-mouse-model-of-alzheimer-s-disease-alleviation-by-pantethine
#6
Manuel van Gijsel-Bonnello, Kévin Baranger, Philippe Benech, Santiago Rivera, Michel Khrestchatisky, Max de Reggi, Bouchra Gharib
Astrocytes play critical roles in central nervous system homeostasis and support of neuronal function. A better knowledge of their response may both help understand the pathophysiology of Alzheimer's disease (AD) and implement new therapeutic strategies. We used the 5xFAD transgenic mouse model of AD (Tg thereafter) to generate astrocyte cultures and investigate the impact of the genotype on metabolic changes and astrocytes activation. Metabolomic analysis showed that Tg astrocytes exhibited changes in the glycolytic pathway and tricarboxylic acid (TCA) cycle, compared to wild type (WT) cells...
2017: PloS One
https://www.readbyqxmd.com/read/28410215/cardiac-glycosides-suppress-the-maintenance-of-stemness-and-malignancy-via-inhibiting-hif-1%C3%AE-in-human-glioma-stem-cells
#7
Dae-Hee Lee, Sang Cheul Oh, Amber J Giles, Jinkyu Jung, Mark R Gilbert, Deric M Park
Tissue hypoxia contributes to solid tumor pathogenesis by activating a series of adaptive programs. We previously showed that hypoxia promotes the preferential expansion and maintenance of CD133 positive human glioma stem cells (GSC) in a hypoxia inducible factor 1 alpha (HIF-1α)-dependent mechanism. Here, we examined the activity of digitoxin (DT), a cardiac glycoside and a putative inhibitor of HIF-1α, on human GSC in vitro and in vivo. During hypoxic conditions (1% O2), we observed the effect of DT on the intracellular level of HIF-1α and the extracellular level of vascular endothelial growth factor (VEGF) in human GSC...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376567/hypoxia-inducible-factor-1%C3%AE-potentiates-jagged-1-mediated-angiogenesis-by-mesenchymal-stem-cell-derived-exosomes
#8
Hernán Gonzalez-King, Nahuel A García, Imelda Ontoria-Oviedo, María Ciria, José Anastasio Montero, Pilar Sepúlveda
Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)-1α in MSCs improves their therapeutic potential by inducing angiogenesis in transplanted tissues. Here, we studied the contribution of exosomes released by HIF-1α-overexpressing donor MSCs (HIF-MSC) to angiogenesis by endothelial cells. Exosome secretion was enhanced in HIF-MSC...
April 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28320353/genome-independent-hypoxic-repression-of-estrogen-receptor-alpha-in-breast-cancer-cells
#9
Mercè Padró, Raymond J Louie, Brian V Lananna, Adam J Krieg, Luika A Timmerman, Denise A Chan
BACKGROUND: About 75-80% of breast tumors express the estrogen receptor alpha (ER-α) and are treated with endocrine-target therapeutics, making this the premier therapeutic modality in the breast cancer clinic. However, acquired resistance is common and about 20% of resistant tumors loose ER-α expression via unknown mechanisms. Inhibition of ER-α loss could improve endocrine therapeutic efficacy, benefiting a significant number of patients. Here we test whether tumor hypoxia might commonly produce ER-α loss...
March 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28295343/epithelial-membrane-protein-2-emp2-deficiency-alters-placental-angiogenesis-mimicking-features-of-human-placental-insufficiency
#10
Carmen J Williams, Alison Chu, Wendy N Jefferson, David Casero, Deepthi Sudhakar, Nevil Khurana, Claire P Hogue, Chinmayi Aryasomayajula, Priya Patel, Peggy Sullivan, Elizabeth Padilla-Banks, Shabnam Mohandessi, Carla Janzen, Madhuri Wadehra
Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2(-/-) ) were generated. Emp2(-/-) females are fertile but have reduced litter sizes when carrying Emp2(-/-) but not Emp2(+/-) fetuses...
March 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28278175/pneumococcal-infection-of-respiratory-cells-exposed-to-welding-fumes-role-of-oxidative-stress-and-hif-1-alpha
#11
Jonathan Grigg, Lisa Miyashita, Reetika Suri
Welders are more susceptible to pneumococcal pneumonia. The mechanisms are yet unclear. Pneumococci co-opt the platelet activating factor receptor (PAFR) to infect respiratory epithelial cells. We previously reported that exposure of respiratory cells to welding fumes (WF), upregulates PAFR-dependent pneumococcal infection. The signaling pathway for this response is unknown, however, in intestinal cells, hypoxia-inducible factor-1 α (HIF 1α) is reported to mediate PAFR-dependent infection. We sought to assess whether oxidative stress plays a role in susceptibility to pneumococcal infection via the platelet activating factor receptor...
2017: PloS One
https://www.readbyqxmd.com/read/28263965/l-2-hydroxyglutarate-production-arises-from-noncanonical-enzyme-function-at-acidic-ph
#12
Andrew M Intlekofer, Bo Wang, Hui Liu, Hardik Shah, Carlos Carmona-Fontaine, Ariën S Rustenburg, Salah Salah, M R Gunner, John D Chodera, Justin R Cross, Craig B Thompson
The metabolite 2-hydroxyglutarate (2HG) can be produced as either a D-R- or L-S- enantiomer, each of which inhibits α-ketoglutarate (αKG)-dependent enzymes involved in diverse biologic processes. Oncogenic mutations in isocitrate dehydrogenase (IDH) produce D-2HG, which causes a pathologic blockade in cell differentiation. On the other hand, oxygen limitation leads to accumulation of L-2HG, which can facilitate physiologic adaptation to hypoxic stress in both normal and malignant cells. Here we demonstrate that purified lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) catalyze stereospecific production of L-2HG via 'promiscuous' reduction of the alternative substrate αKG...
May 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28251972/-zinc-induces-normoxic-accumulation-of-transcriptionally-active-hypoxia-inducible-factor-1-alpha-in-mammary-epithelial-cells
#13
S-Y Lee, S Mustafa, Y-W Ching, N Shafee
Both zinc and the α-subunit of hypoxia-inducible factor (HIF-1α) play important roles in the remodelling of mammary gland tissues. In the present study, we examined the level and the transcriptional activity of HIF-1α in mammary cells upon zinc treatment. In MCF-7 mammary adenocarcinoma and MCF-10A mammary epithelial cell lines, the toxicity levels of zinc differ. Interestingly, both cell lines overexpress HIF-1α following zinc treatment. As it was evident from an up-regulation of its specific target gene CA9 that encodes carbonic anhydrase IX, the stabilized HIF-1α translocated to the nucleus and was transcriptionally active...
January 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28243027/effects-of-histone-deacetylase-inhibitor-valproic-acid-on-the-expression-of-hypoxia-inducible-factor-1-alpha-in-human-retinal-m%C3%A3-ller-cells
#14
Young Jun Kim, Sang Jun Park, Na Rae Kim, Hee Seung Chin
PURPOSE: To evaluate the effects of valproic acid (VPA), a histone deacetylase inhibitor (HDACI), on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal Müller cells under hypoxic conditions. METHODS: Chemical hypoxia was induced in human retinal Müller cells (MIO-M1) by treatment with increasing concentrations of cobalt(II) chloride (CoCl2). Müller cells were also treated with a set concentration of CoCl2, along with various concentrations of VPA...
February 2017: Korean Journal of Ophthalmology: KJO
https://www.readbyqxmd.com/read/28238093/role-of-hif-1%C3%AE-and-caspase-3-in-cystogenesis-of-odontogenic-cysts-and-tumors
#15
Natacha M M da Costa, Adriane S de Siqueira, André L R Ribeiro, Maria S da Silva Kataoka, Ruy G Jaeger, Sérgio M de Alves-Júnior, Andrew M Smith, João de Jesus Viana Pinheiro
OBJECTIVES: Odontogenic cysts and tumors are the most relevant lesions that affect the gnathic bones. These lesions have in common the formation of cystic areas and this common feature may suggest involvement of similar mechanisms. The hypoxia inducible factor 1 alpha (HIF-1α), a responsive protein to hypoxia and caspase-3, an irreversible apoptosis marker, may contribute to cyst formation. Thus, this study aimed to investigate the immunoexpression of these proteins in odontogenic cysts and tumors...
February 25, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28230075/oxygen-impairs-oligodendroglial-development-via-oxidative-stress-and-reduced-expression-of-hif-1%C3%AE
#16
Christina Brill, Till Scheuer, Christoph Bührer, Stefanie Endesfelder, Thomas Schmitz
The premature increase of oxygen tension may contribute to oligodendroglial precursor cell (OPC) damage in preterm infants. Fetal OPCs are exposed to low oxygen tissue tensions not matched when cells are cultured in room air. Maturation (A2B5, O4, O1, MBP, CNP, arborization), oxidative stress (nitrotyrosine Western blot, NRF2 and SOD2 expression), apoptosis (TUNEL), proliferation (Ki67), and expression of transcription factors regulated by Hypoxia-Inducible-Factor-1-alpha (Hif-1α) expressed in OPCs (Olig1, Olig2, Sox9, Sox10) were assessed in rat OPCs and OLN93 cells cultured at 5% O2 and 21% O2...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28212880/automatic-detection-of-hypoxia-in-renal-tissue-stained-with-hif-1alpha
#17
Aline Rodrigues Buzin, Nayana Damiani Macedo, Isabela Bastos Binotti Abreu De Araujo, Breno Valentim Nogueira, Tadeu Uggere de Andrade, Denise Coutinho Endringer, Dominik Lenz
OBJECTIVE: The objective of this study was the identification of the stain HIF-alpha using the Image Cytometry, and to help to count the positive cells (with HIF-alpha) and the negative cells (without HIF-alpha) from the same sample. METHOD: 17 images of renal tissues from male rats of Winstar lineage; overall, there were 12.587 objects (cells) in the images for analysis. The acquired images were then analyzed through the free softwares CellProfiler (version 2.1...
February 14, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28198519/correlation-of-hypoxia-inducible-transcription-factor-in-breast-cancer-and-suvmax-of-f-18-fdg-pet-ct
#18
COMPARATIVE STUDY
Young-Ju Jeong, Jae-Won Jung, Yoon-Young Cho, Sung-Hwan Park, Hoon-Kyu Oh, Sungmin Kang
BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed...
2017: Nuclear Medicine Review. Central & Eastern Europe
https://www.readbyqxmd.com/read/28183349/hif-1%C3%AE-inhibitor-echinomycin-reduces-acute-graft-versus-host-disease-and-preserves-graft-versus-leukemia-effect
#19
Yushi Yao, Lei Wang, Jihao Zhou, Xinyou Zhang
BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28183202/mesothelial-cell-autoantibodies-upregulate-transcription-factors-associated-with-fibrosis
#20
John Gilmer, Tanner Harding, Linda Woods, Brad Black, Raja Flores, Jean Pfau
Amphibole asbestos exposure is associated with the production of mesothelial cell autoantibodies (MCAA). These MCAA have been linked with pleural fibrotic disease in the asbestos exposed community of Libby, Montana, and induce collagen deposition by cultured mesothelial cells. However, the exact intracellular mechanism by which these autoantibodies cause an increase in collagen deposition remains unknown. This study sought to gain insight into the transcription factors involved in the collagen production after human mesothelial cells are exposed to MCAA...
January 2017: Inhalation Toxicology
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