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https://www.readbyqxmd.com/read/29212260/bioenergetics-of-acquired-cisplatin-resistant-h1299-non-small-cell-lung-cancer-and-p31-mesothelioma-cells
#1
Fintan Geoghegan, Robert J Buckland, Eric T Rogers, Karima Khalifa, Emma B O'Connor, Mary F Rooney, Parviz Behnam-Motlagh, Torbjörn K Nilsson, Kjell Grankvist, Richard K Porter
Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209144/targeting-the-long-noncoding-rna-malat1-blocks-the-pro-angiogenic-effects-of-osteosarcoma-and-suppresses-tumour-growth
#2
Zhi-Chang Zhang, Chun Tang, Yang Dong, Jing Zhang, Ting Yuan, Shi-Cong Tao, Xiao-Lin Li
Osteosarcoma (OS), the commonest primary malignant tumour originating from bone, affects a substantial number of people, mostly during adolescent growth, and leads to a very poor prognosis as a result of the high rate of early metastases. Consequently, there is urgent demand for a novel treatment for this disease. There are growing concerns focused on OS-induced pro-angiogenic effects, but to date, the mechanism of OS-induced pro-angiogenesis is still insufficiently well-understood. Long noncoding RNAs (lncRNAs) have attracted increasing interest due to their strong correlation with a variety of diseases and their powerful capacity for epigenetic regulation...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29207631/tetrahydrocurcumin-induces-mesenchymal-epithelial-transition-and-suppresses-angiogenesis-by-targeting-hif-1%C3%AE-and-autophagy-in-human-osteosarcoma
#3
Yan Zhang, Ying Liu, Jilong Zou, Lixin Yan, Wei Du, Yafeng Zhang, Hanliang Sun, Peng Lu, Shuo Geng, Rui Gu, Hongyue Zhang, Zhenggang Bi
Human osteosarcoma is considered a malignant tumor with poor prognosis that readily metastasizes. Tetrahydrocurcumin (THC) has been reported to have anti-tumor activity in numerous tumors. In addition, hypoxia-inducible factor-1α (HIF-1α) has been demonstrated to be associated with tumor metastasis by regulating epithelial-mesenchymal transition (EMT). However, the role of THC in osteosarcoma remains uncertain. Therefore, this study aimed to elucidate the potential mechanisms. We found that THC significantly reduced the growth of osteosarcoma cells and suppressed migration and invasion, as tested in a nude mouse lung metastasis model...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207023/macrophage-migration-inhibitory-factor-promotes-warburg-effect-via-activation-of-the-nf%C3%A2-%C3%AE%C2%BAb-hif%C3%A2-1%C3%AE-pathway-in-lung-cancer
#4
Jun Li, Junhua Zhang, Fengjiao Xie, Jiangzhou Peng, Xu Wu
Macrophage migration inhibitory factor (MIF) is upregulated in various solid tumors, a process that is associated with tumor progression and metastasis. The present study aimed to investigate the role and the underlying mechanism of MIF in human lung cancer. Human lung cancer H358, H460, H524, H1650, H838, H1975 and A549 cell lines were used to examine the expression of MIF by real time‑quantitative polymerase chain reaction and western blotting. The lentivirus was used to overexpress MIF and the expression of MIF and hypoxia‑inducible factor 1‑α (HIF‑1α) were knocked down by shRNA or siRNA...
November 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29194316/tubastatin-a-prevents-hemorrhage-induced-endothelial-barrier-dysfunction
#5
Peter J Bruhn, Vahagn C Nikolian, Ihab Halaweish, Zhigang Chang, Martin Sillesen, Baoling Liu, Yongqing Li, Hasan B Alam
BACKGROUND: Microvascular hyperpermeability resulting from endothelial barrier dysfunction (EBD) is associated with worse clinical outcomes in trauma-induced hemorrhagic shock. We have previously shown that treatment with Tubastatin A (TubA), a histone deacetylase 6 inhibitor, improves outcomes in animal models of shock. In this study, we investigate whether TubA treatment may prevent trauma-related EBD. METHODS: Wistar-Kyoto rats subjected to 40% hemorrhage were treated with TubA or vehicle control...
November 21, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29190880/enhancement-of-the-anti-tumor-activity-of-fgfr1-inhibition-in-squamous-cell-lung-cancer-by-targeting-downstream-signaling-involved-in-glucose-metabolism
#6
Claudia Fumarola, Daniele Cretella, Silvia La Monica, Mara A Bonelli, Roberta Alfieri, Cristina Caffarra, Federico Quaini, Denise Madeddu, Angela Falco, Andrea Cavazzoni, Graziana Digiacomo, Giulia Mazzaschi, Valentina Vivo, Elisabetta Barocelli, Marcello Tiseo, Pier Giorgio Petronini, Andrea Ardizzoni
Fibroblast Growth Factor Receptor (FGFR) signaling is a complex pathway which controls several processes, including cell proliferation, survival, migration, and metabolism. FGFR1 signaling is frequently deregulated via amplification/over-expression in NSCLC of squamous histotype (SQCLC), however its inhibition has not been successfully translated in clinical setting. We determined whether targeting downstream signaling implicated in FGFR1 effects on glucose metabolism potentiates the anti-tumor activity of FGFR1 inhibition in SQCLC...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29183009/hypoxia-induced-mesenchymal-stromal-cells-exhibit-an-enhanced-therapeutic-effect-on-radiation-induced-lung-injury-in-mice-due-to-an-increased-proliferation-potential-and-enhanced-antioxidant-ability
#7
Bailong Li, Cheng Li, Mo Zhu, Youjun Zhang, Jicong Du, Yang Xu, Bin Liu, Fu Gao, Hu Liu, Jianming Cai, Yanyong Yang
BACKGROUND/AIMS: Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage...
November 29, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29177004/active-fraction-hs7-from-taiwanofungus-camphoratus-inhibits-akt-mtor-erk-and-stat3-pathways-and-induces-cdk-inhibitors-in-cl1-0-human-lung-cancer-cells
#8
I-Chun Lai, Gi-Ming Lai, Jyh-Ming Chow, Hsin-Lun Lee, Chuan-Feng Yeh, Chi-Han Li, Jiann-Long Yan, Shuang-En Chuang, Jacqueline Whang-Peng, Kuan-Jen Bai, Chih-Jung Yao
Background: The non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. In NSCLC, the oncogenic AKT-mTOR, ERK and STAT3 pathways are commonly dysregulated and have emerged as attractive targets for therapeutic developments. In a relatively limited subset of NSCLC, these pathways driven by mutant EGFR can be treated by the tyrosine kinase inhibitors (TKIs)-mediated targeted therapy. However, for the most NSCLC, more novel targeted agents are imperatively needed...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/29173495/inflammation-and-the-chemical-carcinogen-benzo-a-pyrene-partners-in-crime
#9
REVIEW
Q Shi, R W L Godschalk, F J van Schooten
Exposure to benzo[a]pyrene (B[a]P) is known to play a role in lung carcinogenesis and the underlying processes can be modified by the presence of inflammation. The inflammatory process can for instance enhance the concentration of reactive metabolites that bind to DNA and may also diminish DNA repair. Additionally, during the inflammatory process mediators are released that create a microenvironment which is suitable for further stimulation of cancer development. Various transcriptional pathways are activated by inflammation, including pathways that are mediated via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), signal transducer and activator of transcription 3 (STAT-3), and hypoxia-inducible factor-1 (HIF-1)...
October 2017: Mutation Research
https://www.readbyqxmd.com/read/29167681/mir-200b-downregulates-cftr-during-hypoxia-in-human-lung-epithelial-cells
#10
Sylwia Bartoszewska, Wojciech Kamysz, Bogdan Jakiela, Marek Sanak, Jarosław Króliczewski, Zsuzsa Bebok, Rafal Bartoszewski, James F Collawn
Background: Hypoxic conditions induce the expression of hypoxia-inducible factors (HIFs) that allow cells to adapt to the changing conditions and alter the expression of a number of genes including the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a low abundance mRNA in airway epithelial cells even during normoxic conditions, but during hypoxia its mRNA expression decreases even further. Methods: In the current studies, we examined the kinetics of hypoxia-induced changes in CFTR mRNA and protein levels in two human airway epithelial cell lines, Calu-3 and 16HBE14o-, and in normal primary bronchial epithelial cells...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/29167125/mesenchymal-stem-cells-reduce-hypoxia-induced-apoptosis-in-alveolar-epithelial-cells-by-modulating-hif-and-ros-hypoxic-signalings
#11
Olivier Bernard, Florence Jeny, Yurdagul Uzunhan, Elisabetta Dondi, Rahma Terfous, Rabab Label, Angela Sutton, Jérôme Larghero, Valérie Vanneaux, Hilario Nunes, Emilie Boncoeur, Carole Planès, Nicolas Dard
Distal lung diseases such as pulmonary fibrosis or acute lung injury are commonly associated with local alveolar hypoxia that may be deleterious through the stimulation of alveolar epithelial cell (AEC) apoptosis. In various murine models of alveolar injury, administration of allogenic human mesenchymal stem cells (hMSC) exerts an overall protective paracrine effect limiting lung inflammation and fibrosis. However, the precise mechanisms on lung cells themselves remain poorly understood. Here we investigated whether hMSC conditioned medium (hMSC-CM) would protect AECs from hypoxia-induced apoptosis and the mechanisms involved in this cytoprotective effect...
November 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29152147/microrna-370-inhibits-the-growth-and-metastasis-of-lung-cancer-by-down-regulating-epidermal-growth-factor-receptor-expression
#12
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
https://www.readbyqxmd.com/read/29148169/antitumor-and-anti-metastatic-mechanisms-of-rhizoma-paridis-saponins-in-lewis-mice
#13
Shuli Man, Hongyan Chai, Jingxia Cui, Jingwen Yao, Long Ma, Wenyuan Gao
Lung cancer is one of the most common causes of death in the world. Rhizoma paridis saponins (RPS) have been found to show inhibition of pulmonary adenoma in previous research. However, the detailed mechanisms of RPS from a holistic view have not been established. In this study, Lewis pulmonary adenoma mice were successfully established to analyze the pathways involved in RPS intervening tumor formation and progression. As a result, RPS inhibited levels of cytokines or receptors such as VEGFD, VEGFR3, RAGE, IL6R, IL17BR, and CXCL16 which were regarded as the initiators induced tumor cell proliferation, adhesion, angiogenesis, and invasion...
November 17, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29134361/sonic-hedgehog-agonist-protects-against-complex-neonatal-cerebellar-injury
#14
Vien Nguyen, Khalida Sabeur, Emin Maltepe, Kurosh Ameri, Omer Bayraktar, David H Rowitch
The cerebellum undergoes rapid growth during the third trimester and is vulnerable to injury and deficient growth in infants born prematurely. Factors associated with preterm cerebellar hypoplasia include chronic lung disease and postnatal glucocorticoid administration. We modeled chronic hypoxemia and glucocorticoid administration in neonatal mice to study whole cerebellar and cell type-specific effects of dual exposure. Chronic neonatal hypoxia resulted in permanent cerebellar hypoplasia. This was compounded by administration of prednisolone as shown by greater volume loss and Purkinje cell death...
November 13, 2017: Cerebellum
https://www.readbyqxmd.com/read/29119942/18f-faza-pet-ct-in-the-preoperative-evaluation-of-nsclc-comparison-with-18f-fdg-and-immunohistochemistry
#15
Paola Mapelli, Valentino Bettinardi, Federico Fallanca, Elena Incerti, Antonia Compierchio, Francesca Rossetti, Angela Coliva, Annarita Savi, Claudio Doglioni, Giampiero Negri, Luigi Gianolli, Maria Picchio
PURPOSE: To assess the capability of 18F-FAZA PET/CT in identifying intratumoral hypoxic areas in early and locally advanced non-small cell lung cancer (NSCLC) patients and to compare 18F-FAZA PET/CT with 18F-FDG PET/CT and histopathological biomarkers and to investigate whether the assessment of tumour to blood (T/B) and tumour to muscle (T/M) ratios provides comparable information regarding the hypoxic fractions of the tumour. MATERIALS AND METHODS: Seven patients with NSCLC were prospectively enrolled (3 men, 4 women; median age: 71 years; range 63-80)...
November 8, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/29115513/lncrna-pvt1-regulate-expression-of-hif1%C3%AE-via-functioning-as-cerna-for-mir%C3%A2-199a%C3%A2-5p-in-non%C3%A2-small-cell-lung-cancer-under-hypoxia
#16
Chunhong Wang, Chunfang Han, Yibo Zhang, Fengqin Liu
Non‑small cell lung cancer (NSCLC) represents one of the most important causes of cancer mortality in the world, and leads to the largest number of deaths in all kinds of lung cancer. Hypoxia has been confirmed to be a characteristic feature of NSCLC and has been shown to decrease the therapeutic efficacy of radiotherapy and some forms of chemotherapy. Previous studies revealed that many miRNAs have been proven to be involved in the molecular regulation of hypoxia and to affect the protein expression level of HIF‑1α...
November 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109913/comparative-analysis-of-the-microrna-transcriptome-between-yak-and-cattle-provides-insight-into-high-altitude-adaptation
#17
Jiuqiang Guan, Keren Long, Jideng Ma, Jinwei Zhang, Dafang He, Long Jin, Qianzi Tang, Anan Jiang, Xun Wang, Yaodong Hu, Shilin Tian, Zhi Jiang, Mingzhou Li, Xiaolin Luo
Extensive and in-depth investigations of high-altitude adaptation have been carried out at the level of morphology, anatomy, physiology and genomics, but few investigations focused on the roles of microRNA (miRNA) in high-altitude adaptation. We examined the differences in the miRNA transcriptomes of two representative hypoxia-sensitive tissues (heart and lung) between yak and cattle, two closely related species that live in high and low altitudes, respectively. In this study, we identified a total of 808 mature miRNAs, which corresponded to 715 pre-miRNAs in the two species...
2017: PeerJ
https://www.readbyqxmd.com/read/29109255/hif-and-hoil-1l-mediated-pkc%C3%AE-degradation-stabilizes-plasma-membrane-na-k-atpase-to-protect-against-hypoxia-induced-lung-injury
#18
Natalia D Magnani, Laura A Dada, Markus A Queisser, Patricia L Brazee, Lynn C Welch, Kishore R Anekalla, Guofei Zhou, Olga Vagin, Alexander V Misharin, G R Scott Budinger, Kazuhiro Iwai, Aaron J Ciechanover, Jacob I Sznajder
Organisms have evolved adaptive mechanisms in response to stress for cellular survival. During acute hypoxic stress, cells down-regulate energy-consuming enzymes such as Na,K-ATPase. Within minutes of alveolar epithelial cell (AEC) exposure to hypoxia, protein kinase C zeta (PKCζ) phosphorylates the α1-Na,K-ATPase subunit and triggers it for endocytosis, independently of the hypoxia-inducible factor (HIF). However, the Na,K-ATPase activity is essential for cell homeostasis. HIF induces the heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), which leads to PKCζ degradation...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29074488/endothelial-hif-2%C3%AE-contributes-to-severe-pulmonary-hypertension-by-inducing-endothelial-to-mesenchymal-transition
#19
Haiyang Tang, Aleksandra Babicheva, Kimberly M McDermott, Yali Gu, Ramon J Ayon, Shanshan Song, Ziyi Wang, Akash Gupta, Tong Zhou, Xutong Sun, Swetaleena Dash, Zilu Wang, Angela Balistrieri, Qiu Yu Zheng, Arlette G Cordery, Ankit A Desai, Franz Rischard, Zain Khalpey, Jian Wang, Stephen M Black, Joe G N Garcia, Ayako Makino, Jason X-J Yuan
Pulmonary vascular remodeling characterized by concentric wall thickening and intraluminal obliteration contributes to the elevated PVR in patients with IPAH. Here we report that increased HIF-2α in lung vascular endothelial cells (LVEC) under normoxic conditions is involved in the development of pulmonary hypertension (PH) by inducing endothelial-to-mesenchymal transition (EndMT), which subsequently results in vascular remodeling and occlusive lesions. We observed significant EndMT and markedly increased expression of SNAI, an inducer of EndMT, in LVEC from IPAH patients and PH animals compared with controls...
October 26, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29072684/plod2-regulated-by-transcription-factor-foxa1-promotes-metastasis-in-nsclc
#20
Hongzhi Du, Yulong Chen, Xiaoying Hou, Yue Huang, Xiaohui Wei, Xiaowen Yu, Shuyun Feng, Yao Wu, Meixiao Zhan, Xin Shi, Sensen Lin, Ligong Lu, Shengtao Yuan, Li Sun
In multiple types of tumors, fibrotic collagen is regarded as the 'highway' for cancer cell migration, which is mainly modified by lysyl hydroxylase 2 (PLOD2). The previous findings have demonstrated that the expression of PLOD2 was regulated by multiple factors, including HIF-1α, TGF-β and microRNA-26a/b. Although PLOD2 was confirmed to be related to poor prognosis in lung adenocarcinoma, the regulatory mechanism and function of PLOD2 in human lung adenocarcinoma is poorly understood. On the other hand, upregulation or hyperactivation of epidermal growth factor receptor is considered as a prognostic marker in many cancers, especially in non-small-cell lung cancer (NSCLC)...
October 26, 2017: Cell Death & Disease
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