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https://www.readbyqxmd.com/read/28214893/the-role-of-netrins-and-their-receptors-in-epithelial-mesenchymal-plasticity-during-development
#1
Michael J Murray
Transitions between mesenchymal and epithelial cells are underpinned by changes in motility, adhesion, and polarity. Netrins and their receptors can control each of these cellular properties, and are emerging as important regulators of epithelial mesenchymal plasticity (EMP). Netrins were first identified in the worm Caenorhabditis elegans as secreted chemoattractants/repellents that could guide migrating mesodermal cells and axonal growth cones. Orthologues were subsequently found to play conserved roles in vertebrates and in the vinegar fly Drosophila...
February 20, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28214878/mirna-26a-contributes-to-the-acquisition-of-malignant-behaviors-of-doctaxel-resistant-lung-adenocarcinoma-cells-through-targeting-ezh2
#2
Jing Chen, Yuejuan Xu, Leilei Tao, Yan Pan, Kai Zhang, Rui Wang, Long-Bang Chen, Xiaoyuan Chu
BACKGROUND/AIMS: Accumulating evidence revealed that microRNAs (miRNAs) have been demonstrated as critical molecules in tumor development and progression. MiR-26a, located in a fragile chromosomal region associated with various human cancer, has been reported to be involved in regulating various cellular process, such as proliferation, apoptosis and invasion through targeting multiple oncogene. Docetaxel-mediated chemotherapy has been applied in improving the survival and prognosis of patients with advanced lung adenocarcinoma (LAD)...
February 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214844/autophagy-activation-by-rapamycin-before-hypoxia-reoxygenation-reduces-endoplasmic-reticulum-stress-in-alveolar-epithelial-cells
#3
Tao Fan, Lei Chen, Zhixin Huang, Wei Wang, Boyou Zhang, Yao Xu, Zhangfan Mao, Hao Hu, Qing Geng
BACKGROUND: To determine potential effects of autophagy activation on hypoxia-reoxygenation (H/R) induced damage of a rat alveolar epithelial cell line. METHODS: CCL149 cells were subjected to autophagy agonist (rapamycin, Rap), autophagy inhibitor (3-methyladenine, 3-MA) or PBS for 1 h before H/R treatment for 2 h, 4 h and 6 h. The optimal concentration of Rap (150 nM, 200 nM and 250 nM) or 3-MA (5 mM, 10 mM and 15 mM) was obtained from MTT assay. Autophagy was determined by fluorescence microscopy of eRFP-LC3 positive cells, transmission electron microscopy of autophagosome, western blot of LC3, AMPK, Beclin-1, HDAC6 and p62 proteins...
January 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214209/expression-and-promoter-dna-methylation-of-mlh1-in-colorectal-cancer-and-lung-cancer
#4
Yunxia Ma, Yuan Chen, Iver Petersen
AIMS: Aberrant DNA methylation is a common molecular feature in human cancer. The aims of this study were to analyze the methylation status of MLH1, one of the DNA mismatch repair (MMR) genes, in human colorectal and lung cancer and to evaluate its clinical relevance. METHODS: The expression of MLH1 was analyzed in 8 colorectal cancer (CRC) and 8 lung cancer cell lines by real-time RT-PCR and western blotting. The MLH1 protein expression was evaluated by immunohistochemistry on tissue microarrays including 121 primary CRC and 90 lung cancer patient samples...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213726/pd-1-and-pd-l1-antibodies-in-cancer-current-status-and-future-directions
#5
REVIEW
Arjun Vasant Balar, Jeffrey S Weber
Immunotherapy has moved to the center stage of cancer treatment with the recent success of trials in solid tumors with PD-1/PD-L1 axis blockade. Programmed death-1 or PD-1 is a checkpoint molecule on T cells that plays a vital role in limiting adaptive immune responses and preventing autoimmune and auto-inflammatory reactivity in the normal host. In cancer patients, PD-1 expression is very high on T cells in the tumor microenvironment, and PD-L1, its primary ligand, is variably expressed on tumor cells and antigen-presenting cells within tumors, providing a potent inhibitory influence within the tumor microenvironment...
February 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28213472/%C3%AE-2-microglobulin-participates-in-development-of-lung-emphysema-by-inducing-lung-epithelial-cells-senescence
#6
Na Gao, Ying Wang, Chun-Ming Zheng, Yan-Li Gao, Hui Li, Yan Li, Ting-Ting Fu, Li-Li Xu, Wei Wang, Sun Ying, Kewu Huang
β2-microglobulin (β2m), the light chain of major histocompatibility complex class 1 (MHC I), has been identified as a pro-aging factors and involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of β2m in development of lung emphysema. Here, we found that concentrations of β2m in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 mg/l vs 1...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213469/insulin-signaling-via-the-pi3k-akt-pathway-regulates-airway-glucose-uptake-and-barrier-function-in-a-cftr-dependent-manner
#7
Samuel A Molina, Hannah K Moriarty, Danny T Infield, Barry R Imhoff, Rachel J Vance, Agnes H Kim, Jason M Hansen, William R Hunt, Michael Koval, Nael A McCarty
Cystic fibrosis-related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF) and correlates with increased rates of lung function decline. Since glucose is a nutrient present in the airways of patients with bacterial airway infections and since insulin controls glucose metabolism, the effect of insulin on CF airway epithelia was investigated to determine the role of insulin receptors and glucose transport in regulating glucose availability in the airway. The response to insulin by human airway epithelial cells was characterized by qPCR, immunoblot, immunofluorescence, and glucose uptake assays...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213007/effect-of-dasatinib-on-emt-mediated-mechanism-of-resistance-against-egfr-inhibitors-in-lung-cancer-cells
#8
Yuichi Sesumi, Kenichi Suda, Hiroshi Mizuuchi, Yoshihisa Kobayashi, Katsuaki Sato, Masato Chiba, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
OBJECTIVE: The epithelial to mesenchymal transition (EMT) is associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor EGFR mutations. Because no currently available drugs specifically kill cancer cells via EMT, novel treatment strategies that overcome or prevent EMT are needed. A recent report suggested that dasatinib (an ABL/Src kinase inhibitor) inhibits EMT induced by transforming growth factor (TGF)-beta in lung cancer cells (Wilson et al...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#9
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209612/microrna-520f-reverses-epithelial-to-mesenchymal-transition-by-targeting-adam9-and-tgfbr2
#10
Jasmijn Gm van Kampen, Onno van Hooij, Cornelius Fj Jansen, Frank P Smit, Paula I van Noort, Iman J Schultz, Roel Qj Schaapveld, Jack A Schalken, Gerald W Verhaegh
Reversing epithelial-to-mesenchymal transition (EMT) in cancer cells has been widely considered as an approach to combat cancer progression and therapeutic resistance, but a limited number of broadly comprehensive investigations of microRNAs involved in this process have been conducted. In this study, we screened a library of 1120 microRNA for their ability to transcriptionally activate the E-cadherin gene CDH1 in a promoter reporter assay as a measure of EMT reversal. By this approach, we defined miR-520f as a novel EMT-reversing microRNA...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209270/crosstalk-between-glucocorticoids-and-il-4-modulates-ym1-expression-in-alternatively-activated-myeloid-cells
#11
Nathalie Ng Kuet Leong, Frank Brombacher, Alexander H Dalpke, Michael Weitnauer
Airway epithelial cells induce a tolerogenic microenvironment by modulating immune cells in the lung. We recently showed that the supernatant of airway epithelial cells induces two marker genes of alternative activation, Ym1 and Ms4a8a, in respiratory myeloid cells. This induction was partially mediated by glucocorticoids, secreted by airway epithelial cells. In this study, we further investigated Ym1 and Ms4a8a regulation in alternatively activated myeloid cells in the presence of the TH2 cytokines IL-4 and IL-13...
February 9, 2017: Immunobiology
https://www.readbyqxmd.com/read/28209205/long-noncoding-agap2-as1-is-activated-by-sp1-and-promotes-cell-proliferation-and-invasion-in-gastric-cancer
#12
Fuzhen Qi, Xianghua Liu, Hao Wu, Xiang Yu, Chenchen Wei, Xiaodan Huang, Guozhong Ji, Fengqi Nie, Keming Wang
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and cancer progression. Recently, the lncRNA AGAP2-AS1 was identified as an oncogenic lncRNA in human non-small cell lung cancer (NSCLC) and its elevated expression was linked to NSCLC development and progression. However, the expression pattern and molecular mechanism of AGAP2-AS1 in gastric cancer (GC) have not been characterized. METHODS: Bioinformatic analysis was performed to determine AGAP2-AS1 expression levels in the GC and normal tissues using gene profiling data from the Gene Expression Omnibus...
February 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28207927/attenuated-airway-hyperresponsiveness-and-mucus-secretion-in-hdm-exposed-igf1r-deficient-mice
#13
S Piñeiro-Hermida, J A Gregory, I P López, R Torrens, C Ruíz-Martínez, M Adner, J G Pichel
BACKGROUND: Asthma is a common chronic lung disease characterized by airflow obstruction, airway hyperresponsiveness (AHR) and inflammation. IGFs have been reported to play a role in asthma but little is known about how the Insulin-like Growth Factor 1 Receptor (IGF1R) affects asthma pathobiology. METHODS: Female Igf1r-deficient and control mice were intranasally challenged with house dust mite (HDM) extract or PBS five days per week for four weeks. Lung function measurements, and bronchioalveolar lavage fluid (BALF), serum and lungs were collected on day 28 for further cellular, histological and molecular analysis...
February 16, 2017: Allergy
https://www.readbyqxmd.com/read/28207789/carbapenem-resistance-and-pathogenicity-of-bovine-acinetobacter-indicus-like-isolates
#14
Peter Klotz, Stephan Göttig, Ursula Leidner, Torsten Semmler, Sandra Scheufen, Christa Ewers
The objective of this study was to characterize blaOXA-23 harbouring Acinetobacter indicus-like strains from cattle including genomic and phylogenetic analyses, antimicrobial susceptibility testing and evaluation of pathogenicity in vitro and in vivo. Nasal and rectal swabs (n = 45) from cattle in Germany were screened for carbapenem-non-susceptible Acinetobacter spp. Thereby, two carbapenem resistant Acinetobacter spp. from the nasal cavities of two calves could be isolated. MALDI-TOF mass spectrometry and 16S rDNA sequencing identified these isolates as A...
2017: PloS One
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#15
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
Oxygen is supplied as a supportive treatment for patients suffering from acute respiratory distress syndrome. Unfortunately, high oxygen concentration increases reactive oxygen species generation, which causes DNA damage and ultimately cell death in the lung. Although 8-oxoguanine-DNA glycosylase (OGG-1) is involved in repairing hyperoxia-mediated DNA damage, the underlying molecular mechanism remains elusive. In this study, we report that ogg-1-deficient mice exhibited a significant increase of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the lung after being exposed to 95% oxygen...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28202352/amino-acid-transporter-slc38a3-promotes-metastasis-of-non-small-cell-lung-cancer-cells-by-activating-pdk1
#16
Yanhui Wang, Li Fu, Minqing Cui, Yongbin Wang, Yan Xu, Molin Li, Jun Mi
BACKGROUND: Tumor metastasis is a finely-tuned pathological process coupled to metabolic reprogramming that includes both glutamine and glucose. The solute carrier SLC38A3, a member of amino acid/polyamine/organocation (APC) superfamily, is an L-glutamine transporter. It is not clear whether SLC38A3 involves the metastasis of NSCLC (non small cell lung cancer). METHODS: The scratch test and transwell assay were used to determine the ability of NSCLC to migrate. Cellular amino acids content was determined by mass spectrometry...
February 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28199134/genetic-control-of-fatty-acid-%C3%AE-oxidation-in-chronic-obstructive-pulmonary-disease
#17
Zhiqiang Jiang, Nelson H Knudsen, Gang Wang, Weiliang Qiu, Zun Zar Chi Naing, Yan Bai, Xingbin Ai, Chih-Hao Lee, Xiaobo Zhou
Bioenergetics homeostasis is important for cells to sustain normal functions and defend against injury. Genetics controls on bioenergetics homeostasis, especially lipid metabolism remain poorly understood in chronic obstructive pulmonary diseases (COPD), the third leading cause of death in the world. Additionally, biological function of most susceptible genes identified from genome-wide association studies (GWAS) in COPD remains unclear. Here, we aim to address 1) how fatty acid oxidation, specifically β-oxidation (FAO), a key lipid metabolism pathway that provides energy to cells, contributes to cigarette smoke (CS)-induced COPD; and 2) whether and how FAM13A (family with sequence similarity 13 member A), a well-replicated COPD GWAS gene, modulates FAO pathway...
February 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28199128/sox2-drives-bronchial-dysplasia-in-a-novel-organotypic-model-of-early-human-squamous-lung-cancer
#18
Lúcia L Correia, Jo-Anne Johnson, Peter McErlean, Julien Bauer, Hassan Farah, Doris M Rassl, Robert C Rintoul, Tariq Sethi, Paul Lavender, Emma L Rawlins, Trevor D Littlewood, Gerard I Evan, Frank M McCaughan
Rationale Improving the early detection and chemoprevention of lung cancer are key to improving outcomes. The pathobiology of early squamous lung cancer is poorly understood. We have shown that amplification of SOX2 is an early and consistent event in the pathogenesis of this disease but its functional oncogenic potential remains uncertain. We tested the impact of deregulated SOX2 expression in a novel organotypic system that recreates the molecular and microenvironmental context in which squamous carcinogenesis occurs...
February 15, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28198394/cockroach-protease-allergen-induces-allergic-airway-inflammation-via-epithelial-cell-activation
#19
Sagar L Kale, Komal Agrawal, Shailendra Nath Gaur, Naveen Arora
Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197929/epithelial-mesenchymal-transition-emt-and-non-small-cell-lung-cancer-nsclc-a-mutual-association-with-airway-disease
#20
Malik Quasir Mahmood, Chris Ward, Hans Konrad Muller, Sukhwinder Singh Sohal, Eugene Haydn Walters
NSCLC is a leading cause of morbidity and mortality worldwide. It includes adeno- and squamous cell carcinoma. In the background, COPD and smoking play a vital role in development of NSCLC. Local progression and metastasis of NSCLC has been associated with various mechanisms, but in particular by a process called epithelial mesenchymal transition (EMT), which is implicated in COPD pathogenesis. In this study, we have investigated whether expression of EGFR (activation marker) and S100A4, vimentin and N-cadherin (as EMT) is different both in central and leading edge of NSCLC and to what extent related to EMT activity of both small and large airways, stage and differentiation of NSCLC...
March 2017: Medical Oncology
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