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https://www.readbyqxmd.com/read/28713928/upregulation-of-wnt-signaling-under-hypoxia-promotes-lung-cancer-progression
#1
Chun-Fu Hong, Wei-You Chen, Cheng-Wen Wu
The hypoxic tumor microenvironment induces epithelial-mesenchymal transition (EMT) in tumor cells and increases tumor cell malignancy. Previous studies indicated that malfunction of Wnt signaling is observed in some lung cancer patients. Athough crosstalk between hypoxia and Wnt signaling in tumor cells has recently been revealed, the detailed underlying mechanisms have not been well defined. In the present study, we demonstrated that hypoxia in lung adenocarcinoma cells can enhance Wnt signaling activity by stabilizing β-catenin and altering its localization into the nucleus...
July 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28711911/human-steroid-sulfatase-induces-wnt-%C3%AE-catenin-signaling-and-epithelial-mesenchymal-transition-by-upregulating-twist1-and-hif-1%C3%AE-in-human-prostate-and-cervical-cancer-cells
#2
Sangyun Shin, Hee-Jung Im, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Donghak Kim, Hyung-Kyoon Choi, Young-Jin Chun
Steroid sulfatase (STS) catalyzes the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) to their unconjugated biologically active forms. Although STS is considered a therapeutic target for estrogen-dependent diseases, the cellular functions of STS remain unclear. We found that STS induces Wnt/β-catenin s Delete ignaling in PC-3 and HeLa cells. STS increases levels of β-catenin, phospho-β-catenin, and phospho-GSK3β. Enhanced translocation of β-catenin to the nucleus by STS might activate transcription of target genes such as cyclin D1, c-myc, and MMP-7...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705232/hypoxia-inducible-factor-2%C3%AE-promotes-tumor-progression-and-has-crosstalk-with-wnt-%C3%AE-catenin-signaling-in-pancreatic-cancer
#3
Qi Zhang, Yu Lou, Jingying Zhang, Qihan Fu, Tao Wei, Xu Sun, Qi Chen, Jiaqi Yang, Xueli Bai, Tingbo Liang
BACKGROUND: Pancreatic cancer is a devastating disease that is characterized by persistent hypoxia. The roles of hypoxia-inducible factor-2α (hif-2α) are different to those of hif-1α, although both are critical for tumor cells to adapt to the hypoxic microenvironment. However, unlike the well-studied hif-1α, the role of hif-2α in tumors, including pancreatic cancer, is poorly understood. METHODS: Herein, we used a mutated hif-2α (A530T) to figure out the problem that wild-type hif-2α is quickly degraded which limits the study of its function...
July 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28704917/the-role-of-hypoxia-on-the-acquisition-of-epithelial-mesenchymal-transition-and-cancer-stemness-a-possible-link-to-epigenetic-regulation
#4
REVIEW
Chang Dong Yeo, Nahyeon Kang, Su Yeon Choi, Bit Na Kim, Chan Kwon Park, Jin Woo Kim, Young Kyoon Kim, Seung Joon Kim
A hypoxic microenvironment leads to cancer progression and increases the metastatic potential of cancer cells within tumors via epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. The hypoxic response pathway can occur under oxygen tensions of < 40 mmHg through hypoxia-inducible factors (HIFs), which are considered key mediators in the adaptation to hypoxia. Previous studies have shown that cellular responses to hypoxia are required for EMT and cancer stemness maintenance through HIF-1α and HIF-2α...
July 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28704726/bnip3-induction-by-hypoxia-stimulates-fasn-dependent-free-fatty-acid-production-enhancing-therapeutic-potential-of-umbilical-cord-blood-derived-human-mesenchymal-stem-cells
#5
Hyun Jik Lee, Young Hyun Jung, Gee Euhn Choi, So Hee Ko, Sei-Jung Lee, Sang Hun Lee, Ho Jae Han
Mitophagy under hypoxia is an important factor for maintaining and regulating stem cell functions. We previously demonstrated that fatty acid synthase (FASN) induced by hypoxia is a critical lipid metabolic factor determining the therapeutic efficacy of umbilical cord blood-derived human mesenchymal stem cells (UCB-hMSCs). Therefore, we investigated the mechanism of a major mitophagy regulator controlling lipid metabolism and therapeutic potential of UCB-hMSCs. This study revealed that Bcl2/adenovirus E1B 19kDa protein-interacting protein 3 (BNIP3)-dependent mitophagy is important for reducing mitochondrial reactive oxygen species accumulation, anti-apoptosis, and migration under hypoxia...
July 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28699703/a-positive-feedback-loop-promotes-hif-1%C3%AE-stability-through-mir-210-mediated-suppression-of-runx3-in-paraquat-induced-emt
#6
Yong Zhu, Jinfeng Wang, Xiaoxiao Meng, Hui Xie, Jiuting Tan, Xinkun Guo, Peng Han, Ruilan Wang
Irreversible pulmonary fibrosis induced by paraquat (PQ) poisoning is the major cause of death in patients with PQ poisoning. The epithelial-mesenchymal transition (EMT) is postulated to be one of the main mechanisms of pulmonary fibrosis. Here, we investigated the role of miR-210 in PQ-induced EMT and its relationship with hypoxia-inducible factor-1α (HIF-1α). Western blotting, immunofluorescence, immunoprecipitation and other methods were used in this study. We found that miR-210 expression was significantly increased after PQ poisoning, and it may be regulated by HIF-1α...
July 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28689812/ibmx-protects-human-proximal-tubular-epithelial-cells-from-hypoxic-stress-through-suppressing-hypoxia-inducible-factor-1%C3%AE-expression
#7
Arif Ul Hasan, Wararat Kittikulsuth, Fuminori Yamaguchi, Tuba Musarrat Ansary, Asadur Rahman, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Masaaki Tokuda, Akira Nishiyama
Hypoxia predisposes renal fibrosis. This study was conducted to identify novel approaches to ameliorate the pathogenic effect of hypoxia. Using human proximal tubular epithelial cells we showed that a pan-phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX) dose and time dependently downregulated hypoxia-inducible factor 1α (HIF-1α) mRNA expression, which was further augmented by addition of a transcriptional inhibitor, actinomycin D. IBMX also increased the cellular cyclic adenosine monophosphate (cAMP) level...
July 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28687790/chronic-inflammation-triggered-by-the-nlrp3-inflammasome-in-myeloid-cells-promotes-growth-plate-dysplasia-by-mesenchymal-cells
#8
Chun Wang, Can-Xin Xu, Yael Alippe, Chao Qu, Jianqiu Xiao, Ernestina Schipani, Roberto Civitelli, Yousef Abu-Amer, Gabriel Mbalaviele
Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684234/roflumilast-treatment-inhibits-lung-carcinogenesis-in-benzo-a-pyrene-induced-murine-lung-cancer-model
#9
Chang Dong Yeo, Young Ae Kim, Hwa Young Lee, Jin Woo Kim, Seung Joon Kim, Sang Haak Lee, Young Kyoon Kim
Roflumilast, a potent and selective inhibitor of phosphodiesterase-4 (PDE4), has been used in treatment of COPD. PDE4 inhibitor is associated with inhibition of chronic airway inflammation, oxidative stress, and mesenchymal markers in B(a)P-induced lung tumors. The aim of this study was to assess whether roflumilast alone or added to inhaled budesonide might have dose-dependent inhibition on lung carcinogenesis induced by carcinogen B(a)P in mice. Female A/J mice were given a single dose of benzo(a)pyrene. Administration of roflumilast (1mg/kg or 5mg/kg) via oral gavage and aerosolized budesonide (2...
July 3, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28674216/microrna-200c-increases-radiosensitivity-of-human-cancer-cells-with-activated-egfr-associated-signaling
#10
Taeryool Koo, Bong Jun Cho, Dan Hyo Kim, Ji Min Park, Eun Jung Choi, Hans H Kim, David J Lee, In Ah Kim
MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c...
July 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28655873/synergistic-effect-of-human-bone-morphogenic-protein-2-and-mesenchymal-stromal-cells-on-chronic-wounds-through-hypoxia-inducible-factor-1-%C3%AE-induction
#11
Sabine François, Véronique V Eder, Karim Belmokhtar, Marie-Christine Machet, Luc Douay, Norbert-Claude Gorin, Marc Benderitter, Chapel A Alain
Chronic skin ulcers and burns require advanced treatments. Mesenchymal Stromal Cells (MSCs) are effective in treating these pathologies. Bone Morphogenic Protein-2 (BMP-2) is known to enhance angiogenesis. We investigated whether recombinant human hBMP-2 potentiates the effect of MSCs on wound healing. Severe ulceration was induced in rats by irradiation and treated by co-infusion of MSCs with hBMP-2 into the ulcerated area which accelerated wound healing. Potentiation of the effect of MSCs by hBMP-2 on endothelial repair improved skin healing...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28635661/hypoxic-preconditioning-promotes-the-bioactivities-of-mesenchymal-stem-cells-via-the-hif-1%C3%AE-grp78-akt-axis
#12
Jun Hee Lee, Yeo Min Yoon, Sang Hun Lee
Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survival; however, the mechanisms underlying such effects remain unclear. This study aimed to uncover the potential mechanism involving 78-kDa glucose-regulated protein (GRP78) to explain the enhanced MSC bioactivity and survival in hindlimb ischemia. Under hypoxia (2% O₂), the expression of GRP78 was significantly increased via hypoxia-inducible factor (HIF)-1α...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28602136/in-situ-forming-hydrogels-with-long-lasting-mir-21-enhances-the-therapeutic-potential-of-msc-by-sustaining-stimulation-of-target-gene
#13
Xianwei Zhang, Yufa Sun, Jianfeng Liu, Zhiyong Yi, Feng Gao, Qiaowei Liu, Yundai Chen
Regulating stem cells by microRNA (miRNA) is promising in regenerative medicine. However, non-viral transfection is usually transient while stably lentiviral transfection is accompanied with oncogenic risk. In the study, we explored the feasibility to retain the microRNAs within biopolymer hydrogels for their long-lasting working and sustaining stimulation of target gene. miRNA-21 (MiR-21), a reported microRNA enhancing the therapeutic potential of mesenchymal stem cells (MSCs) was used. We demonstrated that miR-21 could be efficiently retained within collagen hydrogel after forming complex with cationic polymer polyethylenimine (PEI)...
June 10, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28599281/hif-2%C3%AE-promotes-the-formation-of-vasculogenic-mimicry-in-pancreatic-cancer-by-regulating-the-binding-of-twist1-to-the-ve-cadherin-promoter
#14
Jian Yang, Dong-Ming Zhu, Xiao-Gang Zhou, Ni Yin, Yi Zhang, Zi-Xiang Zhang, De-Chun Li, Jian Zhou
Vasculogenic mimicry (VM) is a blood supply modality that occurs independently of endothelial cell angiogenesis. Hypoxia and the epithelial-mesenchymal transition (EMT) induce VM formation by remodeling the extracellular matrix. Our previous study demonstrated that hypoxia-inducible factor-2 alpha (HIF-2α) promotes the progress of EMT in pancreatic cancer; however, whether HIF-2α promotes VM formation in pancreatic cancer remains unknown. In this study, we investigated HIF-2α expression and VM by immunohistochemistry in 70 pancreatic cancer patients as well as the role of Twist1and Twist2 in HIF-2α-induced VM in vitro and in vivo...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28576310/the-paracrine-effect-of-cobalt-chloride-on-bmscs-during-cognitive-function-rescue-in-the-hibd-rat
#15
Ying Dai, Wendi Li, Min Zhong, Jie Chen, Qian Cheng, Youxue Liu, Tingyu Li
Hypoxia-ischemia (HI)-induced perinatal encephalopathy frequently causes chronic neurological morbidities and acute mortality. Bone mesenchymal stem cell (BMSC) transplantation could potentially promote functional and anatomical recovery of ischemic tissue. In vitro hypoxic preconditioning is an effective strategy to improve the survival of BMSCs in ischemic tissue. In this study, cobalt chloride (CoCl2) preconditioned medium from BMSC cultures was injected into the left lateral ventricle of HI rats using a micro-osmotic pump at a flow rate 1...
May 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28560067/inhibition-of-hif-1%C3%AE-by-px-478-suppresses-tumor-growth-of-esophageal-squamous-cell-cancer-in-vitro-and-in-vivo
#16
Yingming Zhu, Yuanwei Zang, Fen Zhao, Zhenxiang Li, Jianbo Zhang, Liang Fang, Minghuan Li, Ligang Xing, Zhonghua Xu, Jinming Yu
The aim of this study is to investigate the clinical significance of hypoxia inducible factor-1α (HIF-1α) expression in esophageal squamous cell cancer (ESCC) and clarify the effects of PX-478, a selective HIF-1α inhibitor, on ESCC both in vitro and in vivo. HIF-1α, cyclooxygenase-2 (COX-2) and programmed death ligand-1 (PD-L1) were markedly overexpressed in ESCC tissue and associated with poorer survival. In vitro, both COX-2 and PD-L1 expression of ESCC cells were significantly induced by CoCl2 treatment, but inhibited by HIF-1α knock-down or PX-478 treatment...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28560008/gc7-blocks-epithelial-mesenchymal-transition-and-reverses-hypoxia-induced-chemotherapy-resistance-in-hepatocellular-carcinoma-cells
#17
Qing-Yun Zhou, Chao-Yong Tu, Chu-Xiao Shao, Wu-Ke Wang, Jing-De Zhu, Ying Cai, Jia-Yan Mao, Wei Chen
Hypoxia is common in solid tumors and results in the activation of hypoxia-response genes. Hypoxia-inducible factor-1α (HIF-1α) is thought to reflect major cellular adaptation to hypoxia and contributes to chemoresistance in various tumors including hepatocellular carcinoma (HCC). N1-guanyl-1,7-diaminoheptane (GC7) is an inhibitor which suppresses the active eukaryotic translation initiation factor 5A-2 (eIF5A2), preventing epithelial-mesenchymal transition (EMT) in chemoresistance. In this study, we investigated the role of GC7 in the therapeutic effect of doxorubicin in hypoxia in HCC...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28559999/hypoxia-inducible-factor-1-%C3%AE-protects-mesenchymal-stem-cells-against-oxygen-glucose-deprivation-induced-injury-via-autophagy-induction-and-pi3k-akt-mtor-signaling-pathway
#18
Bingke Lv, Tian Hua, Feng Li, Jianbang Han, Jie Fang, Limin Xu, Chengmei Sun, Zhongfei Zhang, Zhiming Feng, Xiaodan Jiang
Mesenchymal stem cell (MSC) transplantation is a promising therapeutic strategy for myocardial infarction. The survival rate of the grafted MSCs is limited by the conditions of hypoxia and low nutrient levels. In this study, we investigated the role of hypoxia-inducible factor 1 alpha (Hif-1α) in oxygen-glucose deprivation (OGD)-induced injury in MSCs. Hif-1α was overexpressed or suppressed in MSCs by transfection with a Hif-1α expressing vector or Hif-1α-specific siRNA, respectively. Then MSCs were exposed to OGD, and the changes in cell viability, cell cycle distribution and apoptosis were respectively monitored by MTT assay and flow cytometry...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28552861/effects-of-pentosan-polysulfate-and-polysulfated-glycosaminoglycan-on-chondrogenesis-of-canine-bone-marrow-derived-mesenchymal-stem-cells-in-alginate-and-micromass-culture
#19
Eugene C Bwalya, Sangho Kim, Jing Fang, H M Suranji Wijekoon, Kenji Hosoya, Masahiro Okumura
Mesenchymal stem cells (MSC) are a potential alternative source of differentiated chondrocytes for cartilage tissue regeneration and repair of osteoarthritic (OA) joints. We investigated the effects of pentosan polysulfate (PPS) and polysulfated glycosaminoglycan (PSGAG) on chondrogenesis of canine bone marrow-derived mesenchymal stem cells (cBMSC) in alginate and micromass cultures (MMC). Chondrogenic differentiation medium (CDM) was supplemented with PPS or PSGAG at concentrations of 0 (positive control; PC), 1, 3 and 5 μg/ml...
May 27, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28550976/cultivation-and-characterization-of-pterygium-as-an-ex-vivo-study-model-for-disease-and-therapy
#20
Natasha Josifovska, Dóra Júlia Szabó, Richárd Nagymihály, Zoltán Veréb, Andrea Facskó, Ketil Eriksen, Morten C Moe, Goran Petrovski
PURPOSE: Development of ex vivo model to study pathogenesis, inflammation and treatment modalities for pterygium. METHODS: Pterygium obtained from surgery was cultivated (3 months). Gravitational attachment method using viscoelastic facilitated adherence of graft and outgrowing cells. Medium contained serum as the only growth supplement with no use of scaffolds. Surface profiling of the multi-layered cells for hematopoietic- and mesenchymal stem cell markers was performed...
May 24, 2017: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
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