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排序方式: 共有182条查询结果,搜索用时 765 毫秒
131.
Yoshiko Yasuda Mitsugu Fujita Eiji Koike Koshiro Obata Mitsuru Shiota Yasushi Kotani Terunaga Musha Sachiyo Tsuji-Kawahara Takao Satou Seiji Masuda Junko Okano Harufumi Yamasaki Katsumi Okumoto Tadao Uesugi Shinichi Nakao Hiroshi Hoshiai Masaki Mandai 《PloS one》2015,10(4)
The aim of this study is to explore a cause-oriented therapy for patients with uterine cervical cancer that expresses erythropoietin (Epo) and its receptor (EpoR). Epo, by binding to EpoR, stimulates the proliferation and differentiation of erythroid progenitor cells into hemoglobin-containing red blood cells. In this study, we report that the HeLa cells in the xenografts expressed ε, γ, and α globins as well as myoglobin (Mb) to produce tetrameric α2ε2 and α2γ2 and monomeric Mb, most of which were significantly suppressed with an EpoR antagonist EMP9. Western blotting revealed that the EMP9 treatment inhibited the AKT-pAKT, MAPKs-pMAPKs, and STAT5-pSTAT5 signaling pathways. Moreover, the treatment induced apoptosis and suppression of the growth and inhibited the survival through disruption of the harmonized hemoprotein syntheses in the tumor cells concomitant with destruction of vascular nets in the xenografts. Furthermore, macrophages and natural killer (NK) cells with intense HIF-1α expression recruited significantly more in the degenerating foci of the xenografts. These findings were associated with the enhanced expressions of nNOS in the tumor cells and iNOS in macrophages and NK cells in the tumor sites. The treated tumor cells exhibited a substantial number of perforations on the cell surface, which indicates that the tumors were damaged by both the nNOS-induced nitric oxide (NO) production in the tumor cells as well as the iNOS-induced NO production in the innate immune cells. Taken together, these data suggest that HeLa cells constitutively acquire ε, γ and Mb synthetic capacity for their survival. Therefore, EMP9 treatment might be a cause-oriented and effective therapy for patients with squamous cell carcinoma of the uterine cervix. 相似文献
132.
Diana Zahnleiter Steffen Uebe Arif B. Ekici Juliane Hoyer Antje Wiesener Dagmar Wieczorek Erdmute Kunstmann André Reis Helmuth-Guenther Doerr Anita Rauch Christian T. Thiel 《PLoS genetics》2013,9(3)
Human growth has an estimated heritability of about 80%–90%. Nevertheless, the underlying cause of shortness of stature remains unknown in the majority of individuals. Genome-wide association studies (GWAS) showed that both common single nucleotide polymorphisms and copy number variants (CNVs) contribute to height variation under a polygenic model, although explaining only a small fraction of overall genetic variability in the general population. Under the hypothesis that severe forms of growth retardation might also be caused by major gene effects, we searched for rare CNVs in 200 families, 92 sporadic and 108 familial, with idiopathic short stature compared to 820 control individuals. Although similar in number, patients had overall significantly larger CNVs (p-value<1×10−7). In a gene-based analysis of all non-polymorphic CNVs>50 kb for gene function, tissue expression, and murine knock-out phenotypes, we identified 10 duplications and 10 deletions ranging in size from 109 kb to 14 Mb, of which 7 were de novo (p<0.03) and 13 inherited from the likewise affected parent but absent in controls. Patients with these likely disease causing 20 CNVs were smaller than the remaining group (p<0.01). Eleven (55%) of these CNVs either overlapped with known microaberration syndromes associated with short stature or contained GWAS loci for height. Haploinsufficiency (HI) score and further expression profiling suggested dosage sensitivity of major growth-related genes at these loci. Overall 10% of patients carried a disease-causing CNV indicating that, like in neurodevelopmental disorders, rare CNVs are a frequent cause of severe growth retardation. 相似文献
133.
Genotoxicity of gamma-irradiation in L5178Y mouse lymphoma cells 总被引:1,自引:0,他引:1
The ability of gamma-irradiation to induce gene mutation at the thymidine kinase locus and gross chromosome aberrations in L5178Y TK+/- 3.7.2C mouse lymphoma cells was evaluated. Positive results were obtained for both end-points. The majority of mutants were found to be small-colony mutants which correlated with the induction of gross chromosome aberrations. 相似文献
134.
Ca2+-stimulated respiration in mitochondria isolated from different fiber types of normal chick muscle and from dystrophic muscle 总被引:1,自引:0,他引:1
135.
Leg size and muscle functions associated with leg compliance 总被引:2,自引:0,他引:2
Convertino V. A.; Doerr D. F.; Flores J. F.; Hoffler G. W.; Buchanan P. 《Journal of applied physiology》1988,64(3):1017-1021
136.
137.
Ogbomo H Hahn A Geiler J Michaelis M Doerr HW Cinatl J 《Biochemical and biophysical research communications》2006,339(1):375-379
The measurement of natural killer (NK) cells toxicity against tumor or virus-infected cells especially in cases with small blood samples requires highly sensitive methods. Here, a coupled luminescent method (CLM) based on glyceraldehyde-3-phosphate dehydrogenase release from injured target cells was used to evaluate the cytotoxicity of interleukin-2 activated NK cells against neuroblastoma cell lines. In contrast to most other methods, CLM does not require the pretreatment of target cells with labeling substances which could be toxic or radioactive. The effective killing of tumor cells was achieved by low effector/target ratios ranging from 0.5:1 to 4:1. CLM provides highly sensitive, safe, and fast procedure for measurement of NK cell activity with small blood samples such as those obtained from pediatric patients. 相似文献
138.
Charles T. Driscoll Steven W. Effler Martin T. Auer Susan M. Doerr Michael R. Penn 《Hydrobiologia》1993,253(1-3):61-72
Onondaga Lake is a hypereutrophic, industrially polluted lake located in Syracuse, NY. High hypolimnetic concentrations of H2S that develop after anoxia restrict the accumulation of total Fe2+ due to the formation of FeS, and may limit Fe-PO4 interactions. High water column concentrations of Ca2+ and high rates of CaCO3 deposition occur due to inputs of Ca2+ from an adjacent soda ash manufacturing facility. Patterns of P concentration and other water chemistry parameters in the lower waters, and results from chemical equilibrium calculations, suggest that Ca-PO4 minerals may regulate the supply of P from sediments to the water column in Onondaga Lake. These findings have important management implications for Onondaga Lake. First, declines in water column Ca2+ concentrations due to reductions in industrial CaCl2 input may result in conditions of undersaturation with respect to Ca-PO4 mineral solubility and increases in the release of P from sediments to the water column. Second, introduction of O2 from hypolimnetic oxygenation, as a lake remediation initiative, may enhance P supply from sediments, because of increased solubility of Ca-PO4 minerals at lower pH. 相似文献
139.
Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 μg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 μg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease. 相似文献
140.
M Michaelis F Rothweiler S Barth J Cinatl M van Rikxoort N L?schmann Y Voges R Breitling A von Deimling F R?del K Weber B Fehse E Mack T Stiewe H W Doerr D Speidel J Cinatl jr 《Cell death & disease》2011,2(12):e243
Six p53 wild-type cancer cell lines from infrequently p53-mutated entities (neuroblastoma, rhabdomyosarcoma, and melanoma) were continuously exposed to increasing concentrations of the murine double minute 2 inhibitor nutlin-3, resulting in the emergence of nutlin-3-resistant, p53-mutated sublines displaying a multi-drug resistance phenotype. Only 2 out of 28 sublines adapted to various cytotoxic drugs harboured p53 mutations. Nutlin-3-adapted UKF-NB-3 cells (UKF-NB-3rNutlin10 μM, harbouring a G245C mutation) were also radiation resistant. Analysis of UKF-NB-3 and UKF-NB-3rNutlin10 μM cells by RNA interference experiments and lentiviral transduction of wild-type p53 into p53-mutated UKF-NB-3rNutlin10 μM cells revealed that the loss of p53 function contributes to the multi-drug resistance of UKF-NB-3rNutlin10 μM cells. Bioinformatics PANTHER pathway analysis based on microarray measurements of mRNA abundance indicated a substantial overlap in the signalling pathways differentially regulated between UKF-NB-3rNutlin10 μM and UKF-NB-3 and between UKF-NB-3 and its cisplatin-, doxorubicin-, or vincristine-resistant sublines. Repeated nutlin-3 adaptation of neuroblastoma cells resulted in sublines harbouring various p53 mutations with high frequency. A p53 wild-type single cell-derived UKF-NB-3 clone was adapted to nutlin-3 in independent experiments. Eight out of ten resulting sublines were p53-mutated harbouring six different p53 mutations. This indicates that nutlin-3 induces de novo p53 mutations not initially present in the original cell population. Therefore, nutlin-3-treated cancer patients should be carefully monitored for the emergence of p53-mutated, multi-drug-resistant cells. 相似文献