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Xiaoli Xu, Yue Wu, Mingyang Hu, Xiang Li, Qichao Bao, Jinlei Bian, Qidong You, Xiaojin Zhang
DDO-6101, a simplified structure obtained from the Garcinia natural product (NP) gambogic acid (GA), has been previously shown to possess high cytotoxicity to a variety of human tumour cell lines. To improve its physicochemical properties and in vivo cytotoxic potency, a series of novel carbamate-bearing derivatives based on DDO-6101 was synthesized and characterized. The structural modifications revealed that the presence of a carbamate moiety was useful for obtaining comparable cytotoxicity and improved aqueous solubility and permeability...
October 21, 2016: Scientific Reports
Jung Min Kim, In-Hu Hwang, Ik-Soon Jang, Min Kim, In Seok Bang, Soo Jung Park, Yun-Jo Chung, Jong-Cheon Joo, Min-Goo Lee
Houttuynia cordata Thunb (H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells...
October 3, 2016: Integrative Cancer Therapies
M Lan, T Xu, J Yue, J Yang, D R Gomez, M D Jeter, Q N Nguyen, Q Shi, S M Hahn, R U Komaki, X Wang, Z Liao
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Jose V Lafuente, G Bermudez, L Camargo-Arce, S Bulnes
Cerebral syndromes related to high altitude exposure are becoming more frequent as the number of trips to high altitudes has increased in the last decade. The commonest symptom is headache, followed by acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), which can be fatal. The pathophysiology of these syndromes is not fully comprehended. The classical "tight-fit hypothesis" defends the fact that there are some anatomical variations that would obstruct the sinovenous outflow and worsen the vasogenic edema and intracranial hypertension reactive to hypoxia...
September 20, 2016: CNS & Neurological Disorders Drug Targets
Jingxin Zhang, Lili Qiao, Ning Liang, Jian Xie, Hui Luo, Guodong Deng, Jiandong Zhang
Vasculogenic mimicry (VM), a microvascular channel made up of nonendothelial cells, has been accepted as a new model of neovascularization in aggressive tumors, owning to the specific capacity of malignant cells to form vessel-like networks which provide sufficient blood supply for tumor growth. Multiple molecular mechanisms, especially vascular endothelial (VE)-cadherin, erythropoietin-producing hepatocellular receptor A2 (EphA2), phosphatidyl inositol 3-kinase (PI3K), matrix metalloproteinases (MMPs), vascular endothelial growth factor receptor (VEGFR1), and hypoxia inducible factor (HIF)-1a, have been reported to participate in VM formation which is associated with tumor migration and invasion...
May 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Wei-Wen Sung, Yi-Chih Chu, Peir-Rong Chen, Ming-Hui Liao, Jeng-Woei Lee
Latent membrane protein 1 (LMP1) is a pivotal viral oncoprotein that contributes to the carcinogenesis of Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC). We investigated the regulation of hypoxia-inducible factor 1-α (HIF-1α) by LMP1. In NPC cells, we found that LMP1 significantly enhanced the HIF-1α mRNA level, and not only the protein amount as described previously. Mechanistically, the stability of the HIF-1α transcript was remarkably prolonged by LMP1 via reduced expressions of RNA-destabilizing proteins tristetraprolin (TTP) and pumilio RNA-binding family member 2 (PUM2) through C-terminal activation region 1 (CTAR1) and CTAR3 interaction with the ERK1/2 and STAT3 signaling pathways, respectively, in parallel with hindrance of PUM2 binding to the HIF-1α mRNA 3'-untranslated region (3'-UTR)...
November 1, 2016: Cancer Letters
Sung Hoon Cho, Ariel L Raybuck, Kristy Stengel, Mei Wei, Thomas C Beck, Emmanuel Volanakis, James W Thomas, Scott Hiebert, Volker H Haase, Mark R Boothby
Germinal centers (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen (Ag)-activated B lymphocytes proliferate, are selected for high affinity antibody (Ab), promote Ab class switching, and yield B cell memory1,2. Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class 3,4, both cell-autonomous5 and extrinsic6,7 metabolic programming have emerged as modulators of T cell-mediated immunity8. We now show that GC light zones are hypoxic and low oxygen (pO2) alters B cell physiology and function...
August 8, 2016: Nature
Jun Wan, Wei Wu
BACKGROUND: Hyperthermia is a promising treatment for human lung cancer, but recurrence of the primary lesion is common, as the residual tumor becomes adapted to heat treatment and growth is induced by hypoxia-triggered HIF-1a expression. Here, we explored the effects of hyperthermia on HIF-1a expression, proliferation, and lung cancer angiogenesis. METHODS: Human NSCLC NCI-H1650 and SCLC NCI-H446 cell lines were used to examine cell viability, apoptosis, and HIF-1a expression level under a gradient of thermal conditions (37, 42 and 47 °C for 40 min)...
2016: Journal of Experimental & Clinical Cancer Research: CR
Valeria A Kostevich, Alexey V Sokolov, Stanislav O Kozlov, Anna Yu Vlasenko, Nikolay N Kolmakov, Elena T Zakharova, Vadim B Vasilyev
Strongly pronounced argyrosis caused by adding AgCl to the feed of laboratory rats efficiently mimics the deficiency of ceruloplasmin (CP) ferroxidase activity. Bringing the concentration of AgCl in the feedstuff of lactating rats to 250 mg % and keeping their progeny (Ag-rats) for 3 months on the same silver-containing feed provided the serum iron content 1.4 times lower than that in the control group. Besides, the ferroxidase activity of CP dropped to zero. In CP purified from sera of Ag-rats two copper ions were substituted with two silver ions...
August 2016: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Jun-Hai Tang, Zhi-Xiong Ma, Guo-Hao Huang, Qing-Fu Xu, Yan Xiang, Ningning Li, Kastytis Sidlauskas, Eric Erquan Zhang, Sheng-Qing Lv
PURPOSE: The aim of this study was to investigate the effect of downregulation of HIF-1α gene on human U251 glioma cells and examine the consequent changes of TMZ induced effects and explore the molecular mechanisms. METHODS: U251 cell line stably expressing HIF-1α shRNA was acquired via lentiviral vector transfection. The mRNA and protein expression alterations of genes involved in our study were determined respectively by qRT-PCR and Western blot. Cell proliferation was measured by MTT assay and colony formation assay, cell invasion/migration capacity was determined by transwell invasion assay/wound healing assay, and cell apoptosis was detected by flow cytometry...
May 1, 2016: Experimental Cell Research
Caroline C da Guarda, Rayra P Santiago, Thassila N Pitanga, Sanzio S Santana, Dalila L Zanette, Valéria M Borges, Marilda S Goncalves
The sickle cell disease (SCD) is a hemolytic genetic anemia characterized by free heme and hemoglobin release into intravascular spaces, with endothelial activation. Heme is a proinflammatory molecule able to directly activate vascular endothelium, thus, endothelial dysfunction and vascular disease are major chronic events described in SCD. The aim of this study was to evaluate the production of endothelial nitric oxide synthase (eNOS), nitrite and hypoxia inducible factor alpha (HIF-α) in HUVECs (human umbilical vein endothelial cells) activated by heme in response to simvastatin, hydroxyurea (HU), and ascorbic acid therapies...
July 2016: Microvascular Research
Naga Suresh Adapala, Harry K W Kim
OBJECTIVE: Ischemic osteonecrosis of the femoral head (ONFH) in piglets results in an ischemic injury to the immature articular cartilage. The molecular changes in the articular cartilage in response to ONFH have not been investigated using a transcriptomic approach. The purpose of this study was to perform a genome-wide transcriptomic analysis to identify genes that are upregulated in the immature articular cartilage following ONFH. METHODS: ONFH was induced in the right femoral head of 6-week old piglets...
2016: PloS One
Qiang Xie, Jing Xie, Juan Zhong, Xiangzhu Cun, Shiyu Lin, Yunfeng Lin, Xiaoxiao Cai
OBJECTIVES: This study aimed to investigate the influence of hypoxia on angiogenesis in a 3D gel, with co-culturing adipose-derived stromal cells (ASCs) and endothelial cells (ECs). MATERIALS AND METHODS: ASCs from green fluorescent protein-labeled mice and ECs from red fluorescent protein-labeled mice were co-cultured in 3D collagen gels at 1:1 ratio, in normal and hypoxic oxygen conditions, and morphology of angiogenesis was observed using confocal laser scanning microscopy...
April 2016: Cell Proliferation
Anna Janaszak-Jasiecka, Sylwia Bartoszewska, Kinga Kochan, Arkadiusz Piotrowski, Leszek Kalinowski, Wojciech Kamysz, Renata J Ochocka, Rafał Bartoszewski, James F Collawn
Hypoxia-inducible factors (HIF) are heterodimeric transcription factors that allow cells to adapt and survive during hypoxia. Regulation of HIF1A and HIF2A mRNA is well characterized, whereas HIF3A mRNA regulation and function are less clear. Using RNA-Seq analysis of primary human umbilical vein endothelial cells, we found two isoforms of HIF3A were expressed, HIF3A2 and HIF3A3. Comparing HIF3A expression profiles to HIF1A mRNA during 48 hours of hypoxia revealed that HIF1A message peaked at 4 hours, whereas HIF3A expression increased while HIF1A was decreasing...
2016: Scientific Reports
Bader Al-Saikan, Jie Ding, Edward Tredget, Peter Metcalfe
INTRODUCTION: Partial bladder outlet obstruction (pBOO) results in significant morbidity and mortality in the pediatric and adult populations. Mesenchymal stem cells (MSC) have been widely studied in many organ systems for the treatment and prevention of fibrotic and inflammatory conditions. Therefore, we hypothesize that systemic administration of MSC will demonstrate short-term biochemical, histological, and urodynamic benefits in an animal model for pBOO. METHODS: After University ethics approval, 5 × 106 green fluorescent protein GFP-labeled MSC were intravenously injected concurrently with pBOO in adult Sprague-Dawley rats...
January 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
Xin Yue, Peiwei Zhao, Kongming Wu, Juan Huang, Wen Zhang, Yaogui Wu, Xiaohui Liang, Xuelian He
Gene associated with retinoid-interferon-induced mortality (GRIM-19), an important subunit of mitochondrial complex I, has been identified as a tumor suppressor, and its reduced expression has been reported to be associated with tumorigenesis and metastasis. Autophagy has been proposed as a protective mechanism for cell survival under various stresses, including chemotherapy. However, it remains unknown whether GRIM-19 is linked to autophagy and chemotherapy resistance. Here, we showed that suppression of GRIM-19 by shRNA enhanced cell-type-dependent autophagy by activating extracellular regulated protein kinase (ERK) and hypoxia inducible factor-1a (HIF-1a) in a reactive oxygen species (ROS)-mediated manner, and thereby conferred resistance to paclitaxel...
July 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Y Liu, S H Man, X Liu, X Y Ding, W L Xiao
PURPOSE OF INVESTIGATION: Cervical cancer markers are not well known for accurate detection of the disease. MATERIALS AND METHODS: In the present study, cervical cancer samples were collected from the 42 patients in the Department of Surgery and Medicine of Weifang People's Hospital and Medical College, Shandong, China. The cDNA subtraction approach was performed to find out the specific transcripts, which are responsible for cervical cancer. The specific differentially expressed transcripts were identified by Basic Local Alignment Search Tool (BLAST) analysis and the results were validated by immunohistochemistry...
2015: European Journal of Gynaecological Oncology
Su-Yan Dong, Yan-Jie Guo, Ya Feng, Xin-Xin Cui, Sheng-Han Kuo, Te Liu, Yun-Cheng Wu
Both silent information regulator 1 (SIRT1) and hypoxia inducible factor 1 (HIF-1) have been found to play important roles in the pathophysiology of Parkinson's disease (PD). However, their mechanisms and their relationship still require further study. In the present study, we focused on the change and relationship of SIRT1 and HIF-1α in PD. PD cell models were established by using methyl-4-phenylpyridinium (MPP(+)), which induced inhibition of cell proliferation, cell cycle arrest and apoptosis. We found that the expression of HIF-1α and its target genes VEGFA and LDHA increased and that SIRT1 expression was inhibited in MPP(+) treated cells...
February 5, 2016: Biochemical and Biophysical Research Communications
Jerzy O Szablowski, Jevgenij A Raskatov, Peter B Dervan
Hypoxic gene expression contributes to the pathogenesis of many diseases, including organ fibrosis, age-related macular degeneration, and cancer. Hypoxia-inducible factor-1 (HIF1), a transcription factor central to the hypoxic gene expression, mediates multiple processes including neovascularization, cancer metastasis, and cell survival. Pyrrole-imidazole polyamide 1: has been shown to inhibit HIF1-mediated gene expression in cell culture but its activity in vivo was unknown. This study reports activity of polyamide 1: in subcutaneous tumors capable of mounting a hypoxic response and showing neovascularization...
April 2016: Molecular Cancer Therapeutics
Z H Zhang, D Z Yin, X S Pang, Z C Wang
Vascular endothelial growth factor (VEGF)-dependent angiogenesis plays a crucial role in corpus luteum formation and its functional maintenance in mammalian ovaries. We recently reported that activation of hypoxia-inducible factor (HIF)-1α signaling contributes to the regulation of VEGF expression in luteal cells (LCs) in response to human chorionic gonadotropin (HCG). We examined whether HIF prolyl-hydroxylase (PHD)-2 gene silencing induces VEGF expression in LCs and enhanced its expression induced by HCG in LCs...
2015: Genetics and Molecular Research: GMR
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