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Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
Beata Filip-Psurska Mateusz Psurski Artur Anisiewicz Patrycja Libako Ewa Zbrojewicz Magdalena Maciejewska Micha Chodyski Andrzej Kutner Joanna Wietrzyk 《International journal of molecular sciences》2021,22(5)
1,25-Dihydroxycholecalciferol, the hormonally active vitamin D3 metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)2D3 analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR. 相似文献
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电磁波在包含各向异性媒质多层介质中传播的分析 总被引:1,自引:0,他引:1
对电磁波在包含各向异性媒质多层介质中的传播进行分析,给出了闭合形式的解,该结构可用作法拉第旋转器,与其它准光元件组合构成的准光环行器或隔离器。也可用作辐射口径,通过改变磁化场方向和强度实现波束扫描或极化变化,给出了法拉第旋转角计算结果和实验结果。 相似文献
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This study compared the effects of estrogen (E) on the hyperactivity induced by (+)-3,4-methylenedioxymethamphetamine (MDMA) with E effects on cocaine-evoked hyperactivity in female rats. Sprague-Dawley rats were ovariectomized (OVX); half of them received a 17β-estradiol (E?) implant (OVX + E). Three weeks later, rats received saline, (+)-MDMA (1, 2, or 4 mg/kg) or cocaine (5, 10, or 20 mg/kg), and locomotor activity was monitored. OVX + E rats exhibited greater locomotor hyperactivity in response to both psychostimulants than did OVX rats. The enhanced response to cocaine appeared within 5 min following drug injection whereas the enhanced response to (+)-MDMA was delayed for approximately 30 min. The differential effects of E on hyperactivity may be due to the unique profiles of dopamine (DA) and serotonin (5-HT) in response to (+)-MDMA and cocaine. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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本文提出了依缓冲库调速CIMS可靠性分析的位相结构方法,从闭环排队网络出发,利用准生灭过程理论,给出了系统的各种可靠性指标和生产指标,讨论了系统局部运行期的们相特征,最后给出了两个数据算例。 相似文献
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Asako Yamamoto Lingli Yang Yasutaka Kuroda Jiao Guo Lanting Teng Daisuke Tsuruta Ichiro Katayama 《International journal of molecular sciences》2021,22(1)
As the outermost barrier of the body, skin is a major target of oxidative stress. In the brain, estrogen has been reported synthesized locally and protects neurons from oxidative stress. Here, we explored whether estrogen is also locally synthesized in the skin to protect from oxidative stress and whether aberrant local estrogen synthesis is involved in skin disorders. Enzymes and estrogen receptor expression in skin cells were examined first by quantitative real-time PCR and Western blot analyses. Interestingly, the estrogen synthesis enzyme was mainly localized in epidermal keratinocytes and estrogen receptors were mainly expressed in melanocytes among 13 kinds of cultured human skin cells. The most abundant estrogen synthesis enzyme expressed in the epidermis was 17β-hydroxysteroid dehydrogenase 1 (HSD17β1) localized in keratinocytes, and the most dominant estrogen receptor expressed in the epidermis was G protein-coupled estrogen receptor 1 (GPER1) in melanocytes. To investigate whether keratinocyte-derived estradiol could protect melanocytes from oxidative stress, cultured human primary epidermal melanocytes (HEMn-MPs) were treated with H2O2 in the presence or absence of 17β estradiol or co-cultured with HSD17β1 siRNA-transfected keratinocytes. Keratinocyte-derived estradiol exhibited protective effects against H2O2-induced cell death. Further, reduced expression of HSD17β1 in the epidermis of skin from vitiligo patients was observed compared to the skin from healthy donors or in the normal portions of the skin in vitiligo patients. Our results suggest a possible new target for interventions that may be used in combination with current therapies for patients with vitiligo. 相似文献
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Olga A. Sukocheva Dong Gui Hu Robyn Meech Anupam Bishayee 《International journal of molecular sciences》2021,22(9)
Breast cancer MCF-7 cell-line-derived mammospheres were shown to be enriched in cells with a CD44+/CD24– surface profile, consistent with breast cancer stem cells (BCSC). These BCSC were previously reported to express key sphingolipid signaling effectors, including pro-oncogenic sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 3 (S1P3). In this study, we explored intracellular trafficking and localization of SphK1 and S1P3 in parental MCF-7 cells, and MCF-7 derived BCSC-enriched mammospheres treated with growth- or apoptosis-stimulating agents. Intracellular trafficking and localization were assessed using confocal microscopy and cell fractionation, while CD44+/CD24- marker status was confirmed by flow cytometry. Mammospheres expressed significantly higher levels of S1P3 compared to parental MCF-7 cells (p < 0.01). Growth-promoting agents (S1P and estrogen) induced SphK1 and S1P3 translocation from cytoplasm to nuclei, which may facilitate the involvement of SphK1 and S1P3 in gene regulation. In contrast, pro-apoptotic cytokine tumor necrosis factor α (TNFα)-treated MCF-7 cells demonstrated increased apoptosis and no nuclear localization of SphK1 and S1P3, suggesting that TNFα can inhibit nuclear translocation of SphK1 and S1P3. TNFα inhibited mammosphere formation and induced S1P3 internalization and degradation. No nuclear translocation of S1P3 was detected in TNFα-stimulated mammospheres. Notably, SphK1 and S1P3 expression and localization were highly heterogenous in mammospheres, suggesting the potential for a large variety of responses. The findings provide further insights into the understanding of sphingolipid signaling and intracellular trafficking in BCs. Our data indicates that the inhibition of SphK1 and S1P3 nuclear translocation represents a novel method to prevent BCSCs proliferation. 相似文献
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Abstract. We propose the quasi‐maximum likelihood method to estimate the parameters of an RCA(1) process, i.e. a random coefficient autoregressive time series of order 1. The strong consistency and the asymptotic normality of the estimators are derived under optimal conditions. 相似文献