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Hypoxia induce factor

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https://www.readbyqxmd.com/read/29158891/overexpression-of-hypoxia-inducible-factor-and-metabolic-pathways-possible-targets-of-cancer
#1
REVIEW
Davinder Singh, Rohit Arora, Pardeep Kaur, Balbir Singh, Rahul Mannan, Saroj Arora
Cancer, the main cause of human deaths in the modern world is a group of diseases. Anticancer drug discovery is a challenge for scientists because of involvement of multiple survival pathways of cancer cells. An extensive study on the regulation of each step of these pathways may help find a potential cancer target. Up-regulated HIF-1 expression and altered metabolic pathways are two classical characteristics of cancer. Oxygen-dependent (through pVHL, PHDs, calcium-mediated) and independent (through growth factor signaling pathway, mdm2 pathway, HSP90) regulation of HIF-1α leads to angiogenesis, metastasis, and cell survival...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29158812/enhanced-radiotherapy-using-bismuth-sulfide-nanoagents-combined-with-photo-thermal-treatment
#2
Xiaju Cheng, Yuan Yong, Yiheng Dai, Xin Song, Gang Yang, Yue Pan, Cuicui Ge
Nanotechniques that can improve the effectiveness of radiotherapy (RT) by integrating it with multimodal imaging are highly desirable. Results In this study, we fabricated Bi2S3 nanorods that have attractive features such as their ability to function as contrast agents for X-ray computed tomography (CT) and photoacoustic (PA) imaging as well as good biocompatibility. Both in vitro and in vivo studies confirmed that the Bi2S3 nanoagents could potentiate the lethal effects of radiation via amplifying the local radiation dose and enhancing the anti-tumor efficacy of RT by augmenting the photo-thermal effect...
2017: Theranostics
https://www.readbyqxmd.com/read/29158549/hypoxia-inducible-factor-1%C3%AE-mediates-the-profibrotic-effect-of-albumin-in-renal-tubular-cells
#3
Junping Hu, Weili Wang, Fan Zhang, Pin-Lan Li, Krishna M Boini, Fan Yi, Ningjun Li
Proteinuria is closely associated with the progression of chronic kidney diseases (CKD) by producing renal tubulointerstitial fibrosis. Over-activation of hypoxia inducible factor (HIF)-1α has been implicated in the progression of CKD. The present study tested the hypothesis that HIF-1α mediates albumin-induced profibrotic effect in cultured renal proximal tubular cells. Incubation of the cells with albumin (40 μg/ml) for 72 hrs significantly increased the protein levels of HIF-1α, tissue inhibitor of metalloproteinase (TIMP)-1 and collagen-I, which were blocked by HIF-1α shRNA...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157834/16-hydroxycleroda-3-13-dien-15-16-olide-inhibits-the-proliferation-and-induces-mitochondrial-dependent-apoptosis-through-akt-mtor-and-mek-erk-pathways-in-human-renal-carcinoma-cells
#4
Cheng Liu, Wei-Chang Lee, Bu-Miin Huang, Yi-Chen Chia, Yu-Chi Chen, Yung-Chia Chen
BACKGROUND: Renal cell carcinoma (RCC) is well known that it cannot be treated with traditional chemotherapy or radiotherapy. 16-Hydroxycleroda-3,13-dien-15,16-olide (CD), isolated from Polyalthia longifolia Benth. & Hook. f. var. pendula had been reported to display significant efficacy against cancer cell lines. PURPOSE: To determine the anti-tumour activities of CD in two clear cell type RCC (ccRCC) cell lines (A-498 and 786-O). In addition, the underlying mechanisms were also examined...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29156834/oncolytic-reovirus-inhibits-angiogenesis-through-induction-of-cxcl10-ip-10-and-abrogation-of-hif-activity-in-soft-tissue-sarcomas
#5
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Monica M Mita, Alain C Mita, Steffan T Nawrocki
The tumor-selective viral replication capacity and pro-apoptotic effects of oncolytic reovirus have been reported to be dependent on the presence of an activated RAS pathway in several solid tumor types. However, the mechanisms of selective anticancer efficacy of the reovirus-based formulation for cancer therapy (Reolysin, pelareorep) have not been rigorously studied in soft tissue sarcomas (STS). Here we report that Reolysin triggered a striking induction of the anti-angiogenic chemokine interferon-γ-inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) in both wild type and RAS mutant STS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156796/downregulation-of-dna-repair-proteins-and-increased-dna-damage-in-hypoxic-colon-cancer-cells-is-a-therapeutically-exploitable-vulnerability
#6
Jennifer M J Jongen, Lizet M van der Waals, Kari Trumpi, Jamila Laoukili, Niek A Peters, Susanne J Schenning-van Schelven, Klaas M Govaert, Inne H M Borel Rinkes, Onno Kranenburg
Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156740/improvement-of-therapeutic-effects-of-mesenchymal-stem-cells-in-myocardial-infarction-through-genetic-suppression-of-microrna-142
#7
Liu-Xue Yang, Chun-Ling Wei, Man-Li Guo, Yong Zhang, Feng Bai, Shao-Gang Ma
Transplanted mesenchymal stem cells (MSCs) have been shown to contribute to myocardial repair after myocardial infarction (MI), primarily through production and secretion some growth factors and cytokines related to cell survival and regeneration. Further improvement of the therapeutic potential of MSCs appears to be an attractive strategy for MI treatment. CXC chemokine receptor (CXCR) 7 is the receptor for stromal cell-derived factor-1 (SDF-1), an important chemokine that is essential for tissue repair and angiogenesis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156717/oligomer-procyanidins-f2-repress-hif-1%C3%AE-expression-in-human-u87-glioma-cells-by-inhibiting-the-egfr-akt-mtor-and-mapk-erk1-2-signaling-pathways-in-vitro-and-in-vivo
#8
Hong-Li Zheng, Li-Hui Wang, Bao-Shan Sun, Yi Li, Jing-Yu Yang, Chun-Fu Wu
Hypoxia-inducible factor-1 (HIF-1) is over-expressed in gliomas and has become one of the most compelling tumor targets. In this study, we found that oligomer procyanidins (F2) can suppress the expressions of HIF-1α and its target genes in U87 cells, and also down-regulate the EGFR/PI3K/AKT/mTOR and MAPK/ERK1/2 pathways in vitro and in vivo. Furthermore, hypoxia-induced formation of tubular structures by human umbilical vascular endothelial cells and the migration and invasion of U87 cells could be inhibited by F2 in a HIF-1 dependent manner...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156557/the-invasive-region-of-glioblastoma-defined-by-5ala-guided-surgery-has-an-altered-cancer-stem-cell-marker-profile-compared-to-central-tumour
#9
Stuart J Smith, Mohammed Diksin, Saachi Chhaya, Shwetha Sairam, Maria A Estevez-Cebrero, Ruman Rahman
Glioblastoma, a WHO grade IV astrocytoma, is a highly aggressive and heterogeneous tumour that infiltrates deeply into surrounding brain parenchyma, making complete surgical resection impossible. Despite chemo-radiotherapy, the residual cell population within brain parenchyma post-surgery causes inevitable recurrence. Previously, the tumour core has been the focus of research and the basis for targeted therapeutic regimes, which have failed to improve survival in clinical trials. Here, we focus on the invasive margin as defined by the region with 5-aminolevulinic acid (5ALA) (GliolanTM) fluorescence at surgery beyond the T1 enhancing region on magnetic resonance imaging (MRI)...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#10
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29155477/oxidized-low-density-lipoprotein-suppresses-mouse-granulosa-cell-differentiation-through-disruption-of-the-hypoxia-inducible-factor-1-pathway
#11
Xiaoliang Chen, Yanhong Liu, Yanhong Shan, Xingyi Jin, Qingyang Shi, Chunshu Jia
Obesity predisposes women to reproductive disorders. One symptom of obesity in women is higher levels of oxidized Low-density lipoprotein (oxLDL) in serum and preovulatory follicles. The present study was designed to test the hypothesis that oxLDL might impair follicle differentiation and luteinization. Given that Hypoxia-inducible factor 1 (HIF1) plays crucial roles in supporting follicle differentiation and luteinization in mammals, we focused on oxLDL-mediated events that may affect the HIF1 pathway. We report that exposure to oxLDL diminished the expression of HIF1α and its target genes and suppressed the differentiation of mouse luteinized granulosa cells following induction by human Chorionic gonadotophin (hCG) under hypoxic conditions (1% oxygen)...
November 20, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29155422/secretion-mediated-stat3-activation-promotes-self-renewal-of-glioma-stem-like-cells-during-hypoxia
#12
D A Almiron Bonnin, M C Havrda, M C Lee, H Liu, Z Zhang, L N Nguyen, L X Harrington, S Hassanpour, C Cheng, M A Israel
High-grade gliomas (HGGs) include the most common and the most aggressive primary brain tumor of adults and children. Despite multimodality treatment, most high-grade gliomas eventually recur and are ultimately incurable. Several studies suggest that the initiation, progression, and recurrence of gliomas are driven, at least partly, by cancer stem-like cells. A defining characteristic of these cancer stem-like cells is their capacity to self-renew. We have identified a hypoxia-induced pathway that utilizes the Hypoxia Inducible Factor 1α (HIF-1α) transcription factor and the JAK1/2-STAT3 (Janus Kinase 1/2 - Signal Transducer and Activator of Transcription 3) axis to enhance the self-renewal of glioma stem-like cells...
November 20, 2017: Oncogene
https://www.readbyqxmd.com/read/29155093/histone-acetylation-of-oligodendrocytes-protects-against-white-matter-injury-induced-by-inflammation-and-hypoxia-ischemia-through-activation-of-bdnf-trkb-signaling-pathway-in-neonatal-rats
#13
Jichong Huang, Li Zhang, Yi Qu, Yan Zhou, Jianghu Zhu, Yafei Li, Tingting Zhu, Fengyan Zhao, Jun Tang, Dezhi Mu
The major pathological damage in encephalopathy of prematurity is white matter injury (WMI). Perinatal hypoxic-ischemia (HI) and inflammation are two major risk factors in the development of WMI. To study the cellular and molecular mechanisms of WMI, we set up a WMI model using lipopolysaccharide-sensitized HI injury in 2-day postnatal rats. Immunofluorescence staining was used to measure the expression of acetylated histone H3 (AH3) in oligodendrocytes, the target cells of WMI; the oligodendrocyte protein markers, NG2, O4, MBP, PLP, and MAG, were detected at different developmental stages...
November 16, 2017: Brain Research
https://www.readbyqxmd.com/read/29155012/litopenaeus-vannamei-notch-affects-lipopolysaccharides-induced-reactive-oxygen-species
#14
Pei Ning, Zhihong Zheng, Jude Juventus Aweya, Defu Yao, Shengkang Li, Hongyu Ma, Fan Wang, Yueling Zhang
Notch signaling pathway was originally discovered in the development stage of drosophila but has recently been found to play essential roles in innate immunity. Most previous studies on Notch have focused on mammals, whereas, in this study, we employed the shrimp Litopenaeus vannamei as a model to study the functions of Notch in invertebrate innate immune system. Our results showed that LvNotch was highly expressed in hemocytes and could be strongly induced by lipopolysaccharides (LPS) injection. Small interfering RNA (siRNA)-mediated knockdown of LvNotch could significantly increase LPS induced L...
November 15, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29154474/intracrine-prostaglandin-e2-pro-tumoral-actions-in-prostate-epithelial-cells-originate-from-non-canonical-pathways
#15
Antonio Madrigal-Martínez, Ana B Fernández-Martínez, Francisco J Lucio Cazaña
Prostaglandin E2 (PGE2 ) increases cell proliferation and stimulates migratory and angiogenic abilities in prostate cancer cells. However, the effects of PGE2 on non-transformed prostate epithelial cells are unknown, despite the fact that PGE2 overproduction has been found in benign hyperplastic prostates. In the present work we studied the effects of PGE2 in immortalized, non-malignant prostate epithelial RWPE-1 cells and found that PGE2 increased cell proliferation, cell migration, and production of vascular endothelial growth factor-A, and activated in vitro angiogenesis...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29154146/multiple-administrations-of-64-cu-atsm-as-a-novel-therapeutic-option-for-glioblastoma-a-translational-study-using-mice-with-xenografts
#16
Yukie Yoshii, Hiroki Matsumoto, Mitsuyoshi Yoshimoto, Ming-Rong Zhang, Yoko Oe, Hiroaki Kurihara, Yoshitaka Narita, Zhao-Hui Jin, Atsushi B Tsuji, Keiichiro Yoshinaga, Yasuhisa Fujibayashi, Tatsuya Higashi
Glioblastoma is the most aggressive malignant brain tumor in humans and is difficult to cure using current treatment options. Hypoxic regions are frequently found in glioblastoma, and increased levels of hypoxia are associated with poor clinical outcomes of glioblastoma patients. Hypoxia plays important roles in the progression and recurrence of glioblastoma because of drug delivery deficiencies and induction of hypoxia-inducible factor-1α in tumor cells, which lead to poor prognosis. We focused on a promising hypoxia-targeted internal radiotherapy agent, (64)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) ((64)Cu-ATSM), to address the need for additional treatment for glioblastoma...
November 16, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29153134/phd-in-the-foxd1-lineage-cells-links-hypoxia-to-inappropriate-nephrogenesis
#17
Tetsuhiro Tanaka
Insufficient oxygenation during pregnancy negatively influences kidney development, which likely serves as a predisposing factor in chronic kidney disease at later stages in life. In this issue of Kidney International, Kobayashi et al. demonstrate that deletion of prolyl hydroxylase 2 and 3, 2 of the major oxygen sensors, in the FoxD1 lineage cells reduces kidney size and inhibits nephrogenesis in mice. Temporospatial expression pattern and studies on additional knockouts suggest the involvement of hypoxia-inducible factor 2...
December 2017: Kidney International
https://www.readbyqxmd.com/read/29153032/evaluation-of-the-carcinogenic-potential-of-roxadustat-fg-4592-a-small-molecule-inhibitor-of-hypoxia-inducible-factor-prolyl-hydroxylase-in-cd-1-mice-and-sprague-dawley-rats
#18
James Beck, Carroll Henschel, James Chou, Al Lin, Ughetta Del Balzo
The carcinogenic potential of roxadustat (FG-4592), a novel orally active, heterocyclic small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) enzymes in clinical development for treatment of anemia, was evaluated in CD-1 mice and Sprague Dawley rats. Inhibition of HIF-PH by roxadustat leads to a rapid increase in cytoplasmic HIF-α concentrations, followed by translocation of HIF-α to the nucleus and upregulation of HIF-responsive genes, including erythropoietin. Roxadustat was dosed by oral gavage 3 times weekly (TIW) for up to 104 weeks in mice at 0, 15, 30, and 60 mg/kg and in rats at 0, 2...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/29152251/oxygen-the-forgotten-nutrient
#19
Paul Trayhurn
O2 is essential for the maintenance and growth of aerobic animals, similar to the essentiality of what are classically considered nutrients. Nevertheless, O2 is not customarily regarded as a nutrient, this reflecting the route by which it enters the body - through the lungs or gills in vertebrates, rather than via the mouth and gastrointestinal tract. A relative deficiency of O2 occurs at high altitudes and during deep-sea diving, to which distinct adaptations occur. Deficiency is also evident in lung diseases such as emphysema...
2017: Journal of Nutritional Science
https://www.readbyqxmd.com/read/29152147/microrna-370-inhibits-the-growth-and-metastasis-of-lung-cancer-by-down-regulating-epidermal-growth-factor-receptor-expression
#20
Xin Liu, You-Guang Huang, Cong-Guo Jin, Yong-Chun Zhou, Xiao-Qun Chen, Jia Li, Yan Chen, Mei Li, Qian Yao, Ke Li, Min Lan, Jia-Gui Ye, Xi-Cai Wang
Abnormal microRNA-370 (miR-370) expression has been frequently reported in several types of cancers, including lung cancer. However, the role and molecular mechanisms of miR-370 in regulating the growth and metastasis of lung cancer have not been clarified. Here, we show higher levels of epidermal growth factor receptor (EGFR), but lower levels of miR-370 expression in most human lung cancer cells and non-tumor cells. Induction of miR-370 over-expression significantly reduced the levels of EGFR expression and the EGFR 3'untranslated region (UTR)-regulated luciferase activity in XWLC-05 and H157 cells, suggesting that miR-370 may bind to the 3'UTR of EGFR mRNA...
October 20, 2017: Oncotarget
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