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https://www.readbyqxmd.com/read/28240549/small-molecule-inhibition-of-microrna-210-reprograms-an-oncogenic-hypoxic-circuit
#1
Matthew G Costales, Christopher L Haga, Sai Pradeep Velagapudi, Jessica L Childs-Disney, Donald G Phinney, Matthew D Disney
A hypoxic state is critical to the metastatic and invasive characteristics of cancer. Numerous pathways play critical roles in cancer maintenance, many of which include noncoding RNAs such as microRNA (miR)-210 that regulates hypoxia inducible factors (HIFs). Herein, we describe the identification of a small molecule named Targapremir-210 that binds to the Dicer site of the miR-210 hairpin precursor. This interaction inhibits production of the mature miRNA, derepresses glycerol-3-phosphate dehydrogenase 1-like enzyme (GPD1L), a hypoxia-associated protein negatively regulated by miR-210, decreases HIF-1α, and triggers apoptosis of triple negative breast cancer cells only under hypoxic conditions...
February 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28238855/mkp-1-negatively-regulates-lps-mediated-il-1%C3%AE-production-through-p38-activation-and-hif-1%C3%AE-expression
#2
Harvinder Talwar, Christian Bauerfeld, Mohamad Bouhamdan, Pershang Farshi, Yusen Liu, Lobelia Samavati
Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine that plays a major role in inflammatory diseases as well as cancer. The inflammatory response after Toll-like receptor (TLR) 4 activation is tightly regulated through phosphorylation of MAP kinases, including p38 and JNK pathways. The activation of MAP kinases is negatively regulated by MAPK phosphatases (MKPs). MKP-1 preferentially dephosphorylates p38 and JNK. IL-1β is regulated through the activation of MAPK, including p38 as well as several transcription factors...
February 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28238093/role-of-hif-1%C3%AE-and-caspase-3-in-cystogenesis-of-odontogenic-cysts-and-tumors
#3
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/28236705/protective-effects-of-total-flavonoids-in-caragana-against-hypoxia-reoxygenation-induced-injury-in-human-brain-microvascular-endothelial-cells
#4
Qian-Song He, Li Zhang, Zi-Yuan Fan, Guo Feng, Fu-Jiang Wang, Zheng-Qi Liu, Ting Tang, Shi-Xiang Kuang
This study aimed to explore the protective effect of total flavonoids in Caragana against hypoxia/reoxygenation (H/R)-induced injury in human brain microvascular endothelial cells (BMECs). Human BMECs were selected and assigned into control, H/R, H/R+NMP, H/R+Low dose, H/R+Moderate dose, H/R+High dose groups. MTT and Transwell assays were used to detect cell viability and migration, respectively. Cell adhesion rate and tube formation were also detected. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to test HIF-1α, VEGF and Notch1 mRNA and protein expressions...
February 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28236660/gene-regulatory-networking-reveals-the-molecular-cue-to-lysophosphatidic-acid-induced-metabolic-adaptations-in-ovarian-cancer-cells
#5
Upasana Ray, Shreya Roy Chowdhury, Madavan Vasudevan, Kiran Bankar, Susanta Roychoudhury, Sib Sankar Roy
Extravasation and metastatic progression are two main reasons behind the high mortality rate associated with cancer. The metastatic potential of cancer cells depends on a plethora of metabolic challenges prevailing in the tumor microenvironment. To achieve higher proliferative rates, cancer cells reprogram their metabolism, increasing glycolysis and biosynthetic activities. Just why this metabolic reprogramming predisposes cells towards increased oncogenesis remains elusive. The accumulation of myriad oncolipids in the tumor microenvironment has been shown to promote the invasiveness of cancer cells, with lysophosphatidic acid (LPA) being one such critical factor enriched in ovarian cancer (OC) patients...
February 25, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28228417/oxygen-sensitive-regulation-and-neuroprotective-effects-of-growth-hormone-dependent-growth-factors-during-early-postnatal-development
#6
Susan Jung, Gudrun Boie, Helmuth-Guenther Doerr, Regina Trollmann
Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIF) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyse effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (ELISA) and mRNA levels (quantitative RT PCR) of growth factors in plasma and brain between normoxic and hypoxic mice (8% O2, 6 h; postnatal day 7, P7) at P14...
February 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28228260/chemotherapy-induced-ca-2-release-stimulates-breast-cancer-stem-cell-enrichment
#7
Haiquan Lu, Ivan Chen, Larissa A Shimoda, Youngrok Park, Chuanzhao Zhang, Linh Tran, Huimin Zhang, Gregg L Semenza
Breast cancer stem cells (BCSCs) play a critical role in tumor recurrence and metastasis. Exposure of breast cancer cells to chemotherapy leads to an enrichment of BCSCs. Here, we find that chemotherapy induces the expression of glutathione S-transferase omega 1 (GSTO1), which is dependent on hypoxia-inducible factor 1 (HIF-1) and HIF-2. Knockdown of GSTO1 expression abrogates carboplatin-induced BCSC enrichment, decreases tumor initiation and metastatic capacity, and delays tumor recurrence after chemotherapy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28225095/high-index-hk0-faceted-platinum-concave-nanocubes-with-enhanced-peroxidase-like-activity-for-an-ultrasensitive-colorimetric-immunoassay-of-the-human-prostate-specific-antigen
#8
Zhuangqiang Gao, Shuzhen Lv, Mingdi Xu, Dianping Tang
Developing simple, high-efficiency non-enzyme bioassays is of great importance for modern analytical systems, but remains a significant challenge. One promising route is to utilize highly efficient nanocatalysts with the exposure of active crystal facets. Herein, we for the first time propose a novel colorimetric immunoassay for the ultrasensitive detection of the human prostate-specific antigen (PSA) based on using a unique type of nanolabel - high-index {hk0} faceted platinum concave nanocubes (HIF-Pt-CNCs)...
February 22, 2017: Analyst
https://www.readbyqxmd.com/read/28225008/anticancer-osmium-complex-inhibitors-of-the-hif-1%C3%AE-and-p300-protein-protein-interaction
#9
Chao Yang, Wanhe Wang, Guo-Dong Li, Hai-Jing Zhong, Zhen-Zhen Dong, Chun-Yuen Wong, Daniel W J Kwong, Dik-Lung Ma, Chung-Hang Leung
The hypoxia inducible factor (HIF) pathway has been considered to be an attractive anti-cancer target. One strategy to inhibit HIF activity is through the disruption of the HIF-1α-p300 protein-protein interaction. We report herein the identification of an osmium(II) complex as the first metal-based inhibitor of the HIF-1α-p300 interaction. We evaluated the effect of complex 1 on HIF-1α signaling pathway in vitro and in cellulo by using the dual luciferase reporter assay, co-immunoprecipitation assay, and immunoblot assay...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223135/cell-physiology-regulation-by-hypoxia-inducible-factor-1-targeting-oxygen-related-nanomachineries-of-hypoxic-cells
#10
REVIEW
Morteza Eskandani, Somayeh Vandghanooni, Jaleh Barar, Hossein Nazemiyeh, Yadollah Omidi
Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions...
February 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28219680/the-regulation-of-transcriptional-repression-in-hypoxia
#11
Miguel A S Cavadas, Alex Cheong, Cormac T Taylor
A sufficient supply molecular oxygen is essential for the maintenance of physiologic metabolism and bioenergetic homeostasis for most metazoans. For this reason, mechanisms have evolved for eukaryotic cells to adapt to conditions where oxygen demand exceeds supply (hypoxia). These mechanisms rely on the modification of pre-existing proteins, translational arrest and transcriptional changes. The hypoxia inducible factor (HIF; a master regulator of gene induction in response to hypoxia) is responsible for the majority of induced gene expression in hypoxia...
February 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28218996/hypoxia-stimulated-membrane-trafficking-requires-t-plastin
#12
Marieke Wottawa, Stephanie Naas, Johannes Böttger, Gijsbert J van Belle, Wiebke Möbius, Natalia H Revelo, Doris Heidenreich, Melanie von Ahlen, Anke Zieseniss, Katharina Kröhnert, Susanne Lutz, Christof Lenz, Henning Urlaub, Silvio O Rizzoli, Dörthe M Katschinski
Traffic between the plasma membrane and the endomembrane compartments is an essential feature of eukaryotic cells. The secretory pathway sends cargoes from biosynthetic compartments to the plasma membrane. This is counterbalanced by a retrograde endocytotic route and is essential for cell homeostasis. Cells need to adapt rapidly to environmental challenges like the reduction of pO2 which, however, has not been analyzed in relation to membrane trafficking in detail. Therefore we determined changes in the plasma membrane trafficking in normoxia, hypoxia, and after reoxygenation METHODS: Membrane trafficking was analyzed by using the bulk membrane endocytosis marker FM 1-43, the newly developed membrane probe mCLING, wheat germ agglutinin as well as fluorescently labeled choleratoxin subunit B...
February 20, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28216300/boronic-acid-tethered-amphiphilic-hyaluronic-acid-derivative-based-nanoassemblies-for-tumor-targeting-and-penetration
#13
Jae Young Jeong, Eun-Hye Hong, Song Yi Lee, Jae-Young Lee, Jae-Hyoung Song, Seung-Hak Ko, Jae-Seong Shim, Sunghwa Choe, Dae-Duk Kim, Hyun-Jeong Ko, Hyun-Jong Cho
(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and > 90% drug encapsulation efficiency were fabricated...
February 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28214471/che-1-sustains-hypoxic-response-of-colorectal-cancer-cells-by-affecting-hif-1%C3%AE-stabilization
#14
Tiziana Bruno, Mariacristina Valerio, Luca Casadei, Francesca De Nicola, Frauke Goeman, Matteo Pallocca, Valeria Catena, Simona Iezzi, Cristina Sorino, Agata Desantis, Cesare Manetti, Giovanni Blandino, Aristide Floridi, Maurizio Fanciulli
BACKGROUND: Solid tumours are less oxygenated than normal tissues. Consequently, cancer cells acquire to be adapted to a hypoxic environment. The poor oxygenation of solid tumours is also a major indicator of an adverse cancer prognosis and leads to resistance to conventional anticancer treatments. We previously showed the involvement of Che-1/AATF (Che-1) in cancer cell survival under stress conditions. Herein we hypothesized that Che-1 plays a role in the response of cancer cells to hypoxia...
February 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28214453/reciprocal-regulation-of-enos-h2s-and-co-synthesizing-enzymes-in-human-atheroma-correlation-with-plaque-stability-and-effects-of-simvastatin
#15
Fragiska Sigala, Panagiotis Efentakis, Dimitra Karageorgiadi, Konstadinos Filis, Paraskevas Zampas, Efstathios K Iliodromitis, George Zografos, Andreas Papapetropoulos, Ioanna Andreadou
The molecular and cellular mechanisms underlying plaque destabilization remain obscure. We sought to elucidate the correlation between NO, H2S and CO-generating enzymes, nitro-oxidative stress and plaque stability in carotid arteries. Carotid atherosclerotic plaques were collected from 62 patients who had undergone endarterectomy due to internal artery stenosis. Following histological evaluation the plaques were divided into stable and unstable ones. To investigate the impact of simvastatin we divided patients with stable plaques, into those receiving and to those not receiving simvastatin...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-receptor-expression-to-promote-metastasis
#16
Julia A Ju, Ines Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
: Metastasis is the leading cause of breast cancer (BCa)mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM binding receptors in this process was explored. Using a bioinformatics approach the expression of all integrin receptor subunits, in two independent BCa patient data sets, were analyzed to determine if integrin status correlates with a validated hypoxiainducible gene signature...
February 17, 2017: Molecular Cancer Research: MCR
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/28209257/synthesis-and-evaluation-of-n-benzofuran-5-yl-aromaticsulfonamide-derivatives-as-novel-hif-1-inhibitors-that-possess-anti-angiogenic-potential
#18
Jinlian Wei, Yingrui Yang, Yali Li, Xiaofei Mo, Xiaoke Guo, Xiaojin Zhang, Xiaoli Xu, Zhengyu Jiang, Qidong You
Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis, and poor patient prognosis has been recognized as an important cancer drug target. A novel series of N-(benzofuran-5-yl)aromaticsulfonamide derivatives were synthesized and evaluated as HIF-1 inhibitor. Among these compounds, 7q exhibited specific inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. It inhibited the HIF-1 transcriptional activity (IC50=12.5±0.7μM) and secretion of VEGF (IC50=18...
June 11, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28208156/oncogenic-role-of-pdk4-in-human-colon-cancer-cells
#19
D Leclerc, D N T Pham, N Lévesque, M Truongcao, W D Foulkes, C Sapienza, R Rozen
BACKGROUND: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model. Decreased methylation of four consecutive PDK4 CpGs was observed in normal mucosa of patients. Although other members of the PDK family have been investigated for transformation potential, PDK4 has not been extensively studied...
February 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28203649/increased-iron-export-by-ferroportin-induces-restriction-of-hiv-1-infection-in-sickle-cell-disease
#20
Namita Kumari, Tatiana Ammosova, Sharmin Diaz, Xionghao Lin, Xiaomei Niu, Andrey Ivanov, Marina Jerebtsova, Subhash Dhawan, Patricia Oneal, Sergei Nekhai
The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1)...
December 27, 2016: Blood Adv
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