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排序方式: 共有265条查询结果,搜索用时 15 毫秒
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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
3.
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
4.
Walter J. Jakubas Bernard C. Wentworth William H. Karasov 《Journal of chemical ecology》1993,19(10):2353-2377
Various plant secondary metabolites related to cinnamic acid are of interest because of their repellency to birds and their occurrence in ecologically important food items. Coniferyl benzoate (CB), a phenylpropanoid ester that occurs in quaking aspen (Populus tremuloides) is of particular ecological interest because of its effect on ruffed grouse (Bonasa umbellus) feeding behavior and its possible influence on the population dynamics of this bird. During detoxification processes, CB and other analogous compounds are metabolized into by-products, such as ferulic acid (FA), that can cause anti-reproductive effects. We tested whether consumption of CB produces antire-productive effects similar to FA using male and female Japanese quail (Coturnix coturnix) as avian models for ruffed grouse. The parameters we investigated included: the production, morphology, and development of eggs; reproductive characteristics influenced by estrogen; serum prolactin levels; and male reproductive behavior. Dietary CB did not produce antireproductive effects similar to FA at intake levels that Japanese quail and ruffed grouse would freely consume. Consumption of CB by Japanese quail significantly reduced egg production and body mass but did not affect male reproductive performance. Coniferyl benzoate's effect on egg production may be explained by lower energy acquisition and retention rather than endocrine changes per se. Contrary to previous reports, it is unlikely that FA, or similar compounds act directly as estrogen mimics or antagonists. Although, CB did reduce egg production in quail, it is unlikely that it would affect egg production in wild ruffed grouse. Detoxification costs and the effects of CB on nutrient utilization may explain why ruffed grouse avoid high dietary levels of CB. 相似文献
5.
Gahr M 《Microscopy research and technique》2001,55(1):1-11
Developmental and seasonal changes in the production of androgens, estrogens, and progestins seem to control sex-specific differentiation and seasonal changes in appetitive and consummatory sexual behaviors of birds. This results in profound sex differences in the quality (sex-specific) or quantity (sex-typical) of behaviors such as courtship, territoriality, or copulation. Steroids affect the brain by binding to intracellularly located receptors. The same brain areas express androgen, estrogen, and progesterone receptors in male and female brains. Sex differences in these genetically determined patterns occur in the size of neuron populations that intrinsically express sex steroid receptors. Further permanent sex differences are subsequent to degenerative fates of receptor expressing neuron populations during ontogeny. Transient sex differences in receptor expression appear to be due to area-specific up- and down-regulation of receptor levels, reflecting transient changes in the level of circulating steroids, changes in environmental conditions, or in the physiological status of the individuals. In particular, intrinsic sex differences in the expression pattern of sex steroid receptors and steroid-independent regulation of the expression level of these receptors in the brain are limiting mechanisms for gonad-dependent sexual development and activities. 相似文献
6.
Salvatore Ulisse Enke Baldini Daniele Pironi Federica Gagliardi Domenico Tripodi Augusto Lauro Sabino Carbotta Danilo Tarroni Matteo DArmiento Aldo Morrone Flavio Forte Flaminia Frattaroli Severino Persechino Teresa Odorisio Vito DAndrea Eleonora Lori Salvatore Sorrenti 《International journal of molecular sciences》2022,23(17)
Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic–pituitary–thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients. 相似文献
7.
Dina Kata Ilona Grf Zsfia Hoyk Eszter Ducza Mria A. Deli Istvn Zupk Imre Fldesi 《International journal of molecular sciences》2022,23(16)
Estrogens regulate a variety of neuroendocrine, reproductive and also non-reproductive brain functions. Estradiol biosynthesis in the central nervous system (CNS) is catalyzed by the enzyme aromatase, which is expressed in several brain regions by neurons, astrocytes and microglia. In this study, we performed a complex fluorescent immunocytochemical analysis which revealed that aromatase is colocalized with the nuclear stain in glial fibrillary acidic protein (GFAP) positive astrocytes in cell cultures. Confocal immunofluorescent Z-stack scanning analysis confirmed the colocalization of aromatase with the nuclear DAPI signal. Nuclear aromatase was also detectable in the S100β positive astrocyte subpopulation. When the nuclear aromatase signal was present, estrogen receptor alpha was also abundant in the nucleus. Immunostaining of frozen brain tissue sections showed that the nuclear colocalization of the enzyme in GFAP-positive astrocytes is also detectable in the adult rat brain. CD11b/c labelled microglial cells express aromatase, but the immunopositive signal was distributed only in the cytoplasm both in the ramified and amoeboid microglial forms. Immunostaining of rat ovarian tissue sections and human granulosa cells revealed that aromatase was present only in the cytoplasm. This novel observation suggests a new unique mechanism in astrocytes that may regulate certain CNS functions via estradiol production. 相似文献
8.
以自来水为试验原水,投加雌酮(E1)、雌二醇(E2)和乙炔雌二醇(EE2),考察了颗粒活性炭去除水中雌激素的效果及动力学.结果表明,活性炭吸附能快速有效地去除水中雌激素.接触10 min后,即达到吸附平衡.平衡质量浓度与雌激素起始质量浓度有关.初始质量浓度为500 ng/L时,E1、E2和EE2的去除率分别为74.7%、89.5%和82.8%.E1、E2和EE2同时存在时,活性炭对E2的吸附效果显著变差(初始质量浓度为500 ng/L时,吸附平衡质量浓度由44.65 ng/L增加到195.03 ng/L),而对E1和EE2的吸附效果没有影响.不同初始质量浓度的等温吸附数据可用Freundlich等温吸附方程来描述. 相似文献
9.
目的建立超高效液相色谱-串联质谱(ultra performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)测定饮料中双酚A(bisphenol A,BPA)、双酚S(bisphenol S,BPS)、辛基酚(octylphenol,OP)和壬基酚(nonylphenol,NP)残留量的分析方法。方法样品经过HLB固相萃取柱净化后,用ZORBAX SB-Aq柱(3.0 mm×100 mm,1.8μm)分离,以甲醇和5 mmol/L乙酸铵溶液作为流动相进行梯度洗脱,电喷雾负离子模式(ESI-)电离,多反应监测模式(multiple reaction monitoring,MRM)进行检测。结果 BPA、BPS在2~100μg/L范围内线性关系良好(r0.999),方法的检出限(S/N=3)为0.3、0.01μg/L,在0.25、2、8μg/L添加水平的回收率分别为78.6%~88.0%,相对标准偏差(n=6)为1.1%~6.0%;OP、NP在10~500μg/L范围内线性关系良好(r0.999),方法的检出限(S/N=3)为0.7、0.9μg/L,在1.25、10、40μg/kg添加水平的回收率分别为85.5%~107%,相对标准偏差(n=6)为2.1%~6.6%。结论该方法简单、灵敏、准确可靠,适用于饮料中BPA、BPS、OP和NP等环境类雌激素的测定。 相似文献
10.
To explore novel synthetic routes of 16-epiestriol (Estra-1, 3, 5(10)-triene-3, 16β, 17β-triol), we used the estrone as the starting material. After some simple synthetic steps, 16-epiestriol was yielded. Identification and purity of intermediates in the synthetic routes were characterized by melting point and 1H NMR spectrum analysis, respectively. In addition, the structure of 16-epiestriol was modified and radiolabeled with18F-fluoride to yield18F-FES. The corresponding quality control analysis of the injection were performed. The yield of two synthetic routes of 16-epiestriol were about 20% starting from estrone. Radiosynthesis of18F-FES was finished in 60 minutes with a radiochemical yield of (30±4)% and radiochemical purity greater than 99%. The18F-FES injection was colorless and clear and the pH value was 6.5-7.5. The specific activity of the injection saline was (1.75±0.25) Ci/μmol. In this study, 16-Epiestriol was yielded with a relatively high yield in two novel routes.18F-FES was finally yielded after structure modification of 16-epiestriol and the corresponding radiolabeling procudure. The quality control results of the18F-FES injection could meet the need in clinical examination. 相似文献