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Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer 总被引:2,自引:0,他引:2
R H Wiltrout M R Boyd T C Back R R Salup J A Arthur R L Hornung 《Journal of immunology (Baltimore, Md. : 1950)》1988,140(9):3261-3265
The investigational drug flavone-8-acetic acid (FAA) potently augments NK activity in the spleen, liver, lungs, and peritoneum in a dose-dependent manner after i.v. or i.p. administration. Augmented NK activity peaks by 24 h after FAA injection and returns to normal after 6 days. Combined treatment of established murine renal cancer with FAA and rIL-2 results in up to 80% long term survival whereas FAA or rIL-2 alone were unable to induce any long term survivors. The optimal dose of rIL-2 required for use with FAA was in the range of 10,000 to 30,000 U/day. Further studies demonstrated that the regimen of FAA plus rIL-2 administration that was effective in treating established murine renal cancer also induced a more potent augmentation of NK activity than did either FAA or rIL-2 alone. Subsequent studies revealed that the therapeutic effectiveness of FAA plus rIL-2 was significantly reduced when tumor-bearing mice were treated with anti-asialo GM1 serum. These results are consistent with a role for augmented NK activity in the therapeutic effects of FAA plus rIL-2 murine renal cancer. In addition, these studies demonstrate that FAA and rIL-2 is a useful approach for cancer treatment in that subtoxic doses of rIL-2 can be used and significant anti-tumor efficacy occurs even without accompanying adoptive immunotherapy. 相似文献
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Human migration is nonrandom. In small scale societies of the past, and in the modern world, people tend to move to wealthier, safer, and more just societies from poorer, more violent, less just societies. If immigrants are assimilated, such nonrandom migration can increase the occurrence of culturally transmitted beliefs, values, and institutions that cause societies to be attractive to immigrants. Here we describe and analyze a simple model of this process. This model suggests that long run outcomes depend on the relative strength of migration and local adaptation. When local adaption is strong enough to preserve cultural variation among groups, cultural variants that make societies attractive always predominate, but never drive alternative variants to extinction. When migration predominates, outcomes depend both on the relative attractiveness of alternative variants and on the initial sizes of societies that provide and receive immigrants. 相似文献
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Davide Danovi Amos Folarin Sabine Gogolok Christine Ender Ahmed M. O. Elbatsh P?r G. Engstr?m Stefan H. Stricker Sladjana Gagrica Ana Georgian Ding Yu Kin Pong U Kevin J. Harvey Patrizia Ferretti Patrick J. Paddison Jane E. Preston N. Joan Abbott Paul Bertone Austin Smith Steven M. Pollard 《PloS one》2013,8(10)
Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF−/−, or p53−/−), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value. 相似文献
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Methylation patterns at the hypervariable X-chromosome locus DXS255 (M27 beta): correlation with X-inactivation status. 总被引:4,自引:0,他引:4
Methylation patterns surrounding a hypervariable X-chromosome locus, DXS255, have been analyzed with the restriction enzyme MspI and its methylation-sensitive isoschizomer HpaII. HpaII sites flanking the hypervariable region were found to be methylated on 41 active X chromosomes and unmethylated on 11 inactive X chromosomes present in a range of male, female, and hybrid cells and tissues. This differential methylation pattern coupled with the previously described high level (greater than 90%) of heterozygosity at the DXS255 locus can therefore be applied to determine the inactivation status of X chromosomes in females heterozygous for X-linked disease and in tumor clonality studies. 相似文献
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The 24-h time budget of a takh harem stallion (Equus ferus przewalskii) pre- and post-reintroduction
Lee Boyd 《Applied animal behaviour science》1998,60(4):291-299
Focal animal sampling was used to determine the 24-h time budget of a takh harem stallion (Equus ferus przewalskii) during the 2 weeks prior to, and the two weeks following, reintroduction into the Hustain Nuruu Steppe Reserve, Mongolia. Both before and after release, the stallion spent approximately 47% of his time grazing, 6% standing, and 5% in recumbent rest. The biggest changes to the time budget after release were a 4-fold increase in the amount of time spent moving, and a 50% decrease in the amount of time spent resting in a standing position. During the middle of the day when the temperatures were hottest, the stallion exhibited less grazing and more standing resting behaviour than in the morning or evening hours. Recumbent rest invariably occurred in the hours before dawn. 相似文献
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