排序方式: 共有12条查询结果,搜索用时 15 毫秒
1.
Moreira DF Strauss BE Vannier E Belizário JE 《Genetics and molecular research : GMR》2008,7(3):925-932
Dermcidin (DCD) is a human gene mapped to chromosome 12q13 region, which is co-amplified with multiple oncogenes with a well-established role in the growth, survival and progression of breast cancers. Here, we present a summary of a DNA microarray-based study that identified the genes that are up- and down-regulated in a human MDA-361 pLKO control clone and three clones expressing short hairpin RNA against three different regions of DCD mRNA. A list of 235 genes was differentially expressed among independent clones (> 3-fold change and p < 0.005). The gene expression of 208 was reduced and of 27 was increased in the three DCD-RNAi clones compared to pLKO control clone. The expression of 77 genes (37%) encoding for enzymes involved in amino acid metabolism, glucose metabolism and oxidoreductase activity and several genes required for cell survival and DNA repair were decreased. The expression of EGFR/ErbB-1 gene, an important predictor of outcome in breast cancer, was reduced together with the genes for betacellulin and amphiregulin, two known ligands of EGFR/ErbB receptors. Many of the 27 genes up-regulated by DCD-RNAi expression have not yet been fully characterized; among those with known function, we identified the calcium-calmodulin-dependent protein kinase-II delta and calcineurin A alpha. We compared 132 up-regulated and 12 down-regulated genes in our dataset with those genes up- and down-regulated by inhibitors targeting various signaling pathway components. The analysis showed that the genes in the DCD pathway are aligned with those functionally influenced by the drugs sirolimus, LY-294002 and wortmannin. Therefore, DCD may exert its function by activating the PI3K/AKT/mTOR signaling pathway. Together, these bioinformatic approaches suggest the involvement of DCD in the regulation of genes for breast cancer cell metabolism, proliferation and survival. 相似文献
2.
Daniela Takeshita Fernanda Mara Bento Roger Chammas José Ernesto Belizário Adriana Karaoglanovic Carmona Katsuhiro Konno Robson Lopes de Melo Gustavo Molina Bianca Cristina Garcia Lisboa Sang Won Han 《Biochimie et biologie cellulaire》2007,85(5):573-581
Transduction of the retroviral vector LBmSN, which expresses the blasticidin S resistance gene bsrm in the murine keratinocyte cell line BALB/MK, induces death in these cells. Cell death is caused by a factor called DOKEB (death factor obtained from keratinocytes expressing bsrm), which is released before the cells' death. In this report we describe and discuss the purification and characterization of DOKEB. Our results were as follows. (i) The 5-day-old medium from the modified BALB/MK cells with LBmSN was used for purification and characterization by filtration and chromatography: DOKEB was a stable and highly hydrophilic compound, with a molecular mass less than that of 1 amino acid. (ii) The conditioned medium containing DOKEB was reactive against thiobarbituric acid and dichlorofluorescein diacetate. (iii) DOKEB activity was neutralized by the incubation of the conditioned medium with catalase. Therefore, our conclusion is that the BALB/MK cells expressing bsrm produce a large amount of hydrogen peroxide, which catalyzes the process of apoptosis of those cells. 相似文献
3.
4.
Belizário JE Akamini P Wolf P Strauss B Xavier-Neto J 《Journal of applied genetics》2012,53(3):295-315
Transgenesis refers to the molecular genetic techniques for directing specific insertions, deletions and point mutations in the genome of germ cells in order to create genetically modified organisms (GMO). Genetic modification is becoming more practicable, efficient and predictable with the development and use of a variety of cell and molecular biology tools and DNA sequencing technologies. A collection of plasmidial and viral vectors, cell-type specific promoters, positive and negative selectable markers, reporter genes, drug-inducible Cre-loxP and Flp/FRT recombinase systems are available which ensure efficient transgenesis in the mouse. The technologies for the insertion and removal of genes by homologous-directed recombination in embryonic stem cells (ES) and generation of targeted gain- and loss-of function alleles have allowed the creation of thousands of mouse models of a variety of diseases. The engineered zinc finger nucleases (ZFNs) and small hairpin RNA-expressing constructs are novel tools with useful properties for gene knockout free of ES manipulation. In this review we briefly outline the different approaches and technologies for transgenesis as well as their advantages and disadvantages. We also present an overview on how the novel integrative mouse and human genomic databases and bioinformatics approaches have been used to understand genotype-phenotype relationships of hundreds of mutated and candidate disease genes in mouse models. The updating and continued improvements of the genomic technologies will eventually help us to unraveling the biological and pathological processes in such a way that they can be translated more efficiently from mouse to human and vise-versa. 相似文献
5.
6.
7.
Scutti JA Matsuo AL Pereira FV Massaoka MH Figueiredo CR Moreira DF Belizário JE Travassos LR 《Translational oncology》2011,4(2):101-109
Melanoma is the most aggressive form of skin cancer, and its incidence has increased dramatically over the years. The murine B16F10 melanoma in syngeneic C57Bl/6 mice has been used as a highly aggressive model to investigate tumor development. Presently, we demonstrate in the B16F10-Nex2 subclone that silencing of SOCS-1, a negative regulator of Jak/Stat pathway, leads to reversal of the tumorigenic phenotype and inhibition of melanoma cell metastasis. SOCS-1 silencing with short hairpin RNA affected tumor growth and cell cycle regulation with arrest at the S phase with large-sized nuclei, reduced cell motility, and decreased melanoma cell invasion through Matrigel. A clonogenic assay showed that SOCS-1 acted as a modulator of resistance to anoikis. In addition, downregulation of SOCS-1 decreased the expression of epidermal growth factor receptor (mainly the phosphorylated-R), Ins-Rα, and fibroblast growth factor receptor. In vivo, silencing of SOCS-1 inhibited subcutaneous tumor growth and metastatic development in the lungs. Because SOCS-1 is expressed in most melanoma cell lines and bears a relation with tumor invasion, thickness, and stage of disease, the present results on the effects of SOCS-1 silencing in melanoma suggest that this regulating protein can be a target of cancer therapy. 相似文献
8.
9.
10.
ObjectiveTo study the impact of interpregnancy interval on maternal morbidity and mortality.DesignRetrospective cross sectional study with data from the Perinatal Information System database of the Latin American Centre for Perinatology and Human Development, Montevideo, Uruguay.SettingLatin America and the Caribbean, 1985-97.Participants456 889 parous women delivering singleton infants.ResultsShort (<6 months) and long (>59 months) interpregnancy intervals were observed for 2.8% and 19.5% of women, respectively. After adjustment for major confounding factors, compared with those conceiving at 18 to 23 months after a previous birth, women with interpregnancy intervals of 5 months or less had higher risks for maternal death (odds ratio 2.54; 95% confidence interval 1.22 to 5.38), third trimester bleeding (1.73; 1.42 to 2.24), premature rupture of membranes (1.72; 1.53 to 1.93), puerperal endometritis (1.33; 1.22 to 1.45), and anaemia (1.30; 1.18 to 1.43). Compared with women with interpregnancy intervals of 18 to 23 months, women with interpregnancy intervals longer than 59 months had significantly increased risks of pre-eclampsia (1.83; 1.72 to 1.94) and eclampsia (1.80; 1.38 to 2.32).Conclusions Interpregnancy intervals less than 6 months and longer than 59 months are associated with an increased risk of adverse maternal outcomes. 相似文献