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diethylstilbestrol diethylstilbestrol [keywords]
- Clear Cell Carcinoma of Cervix in a 60- year-old Woman: A Case Report. [Journal Article]
- J Clin Diagn Res 2014 Aug; 8(8):OD01-2.
Clear cell carcinoma of cervix is a rare entity amongst cervical neoplasms especially post diethylstilbestrol era. It is hypothesised to have a bimodal distribution with spontaneous cases unrelated to DES exposure observed in elderly age group. We report a rare case of clear cell carcinoma of cervix (CCCC) in a 60-year-old Asian female with no history of diethylstilbestrol (DES) ingestion. She underwent radical hysterectomy and adjuvant radiotherapy and showed no signs of recurrence even after 6 moths of follow up. Review of relevant literature was done including possible aetiology, appropriate treatment and prognostic factors.
- [Clear cell adenocarcinoma of the uterine cervix in a 17-year-old girl.] [JOURNAL ARTICLE]
- Ugeskr Laeger 2014 Sep 1; 176(36)
Clear cell adenocarcinoma of the uterine cervix (CCEA) is a rare disease, accounting for only 1% of all cervical cancers. The disease in young women is linked to diethylstilbestrol (DES) exposure in utero. Following the ban of DES in 1979, CCEA rarely occurs in young women, but still remains a challenge in diagnosis and fertility preservation. We report on a 17-year-old girl, unexposed to DES, diagnosed with clear cell adenocarcinoma in a cervical polyp.
- Assessment of estrogen disrupting potency in animal foodstuffs of China by combined biological and chemical analyses. [Journal Article]
- J Environ Sci (China) 2014 Oct 1; 26(10):2131-7.
Food has been documented as one of major routes for human exposure to environmental estrogens (EEs), but information on the occurrence of EEs in animal foodstuffs is still scarce. This study analyzed estrogenic activity in 16 types of animal foodstuffs (n=142) collected from four cities (Wuhan, Guangzhou, Wenzhou and Yantai) of China by combined yeast estrogen screen (YES) bioassay and chemical analysis. By bioassay, all samples' extracts were found to induce estrogenic activities and the bioassay-derived 17β-estradiol equivalent (EEQbio) ranged from 8.29 to 118.32ng/g. In addition, the samples were analyzed by liquid chromatography coupled to tandem mass spectrometry for further chemical analysis. 17β-Estradiol was found in all samples in this survey at levels of 0.44 to 15.04ng/g. All samples had 33.1% detection rate of 17α-ethinylestradiol (EE2), and the maximum concentration was 2.80ng/g. Bisphenol A and 4-nonylphenols were detected in 83.8% and 83.1% of samples, with concentrations up to 12.56ng/g and 35.76ng/g, respectively. However, the concentrations of estrone, diethylstilbestrol and 4-t-octylphenol were found to be below the limit of detection. A comparison of EEQbio measured from the YES assay and EEQchem calculated from chemical analysis showed good correlation (R(2)=0.84). Based on the results, the YES assay can be used as a rapid pre-screening method for monitoring the levels of estrogenic activity in large numbers of animal foodstuffs, and chemical analysis used in combination can be used for the identification of specific EEs.
- Diallyl sulfide inhibits diethylstilbestrol induced DNA damage in human breast epithelial cells (MCF-10A). [JOURNAL ARTICLE]
- Steroids 2014 Sep 30.
Breast cancer is the second leading cause of cancer deaths in women in the United States. Diethylstilbestrol (DES) is a synthetic estrogen that has been shown to cause cancer in animals and humans, altering cell viability as well as inducing DNA damage. Diallyl sulfide (DAS) is a garlic organosulfide that has been shown to inhibit both the initiation and promotion phases of cancer in vivo and in vitro, as well as reduce the risk of cancer in epidemiological studies. MCF-10A cells, regarded as a normal breast epithelial cell line, were treated with varying concentrations of DES, DAS or various dose combinations of DES and DAS concomitantly, and assessed for cell viability, DNA strand breaks, and lipid peroxidation. DES (10μM) in combination with 1, 10, or 100μM DAS resulted in a 31%, 34%, or 36% respective increase in cell viability compared to the DES treatment alone, after 24h. At the same time point, 1, 10, and 100μM DAS were all effective in significantly reducing DES (100μM)-induced strand breaks to near that of the vehicle control. Additionally, 1μM DAS was effective in significantly reducing DES (100μM)-induced lipid peroxidation after 3h. The results of this research suggest that DAS is effective in recovering cell viability, attenuating DNA strand breaks, and decreasing lipid peroxidation in MCF-10A cells.
- Estrogens in the wrong place at the wrong time: fetal BPA exposure and mammary cancer. [JOURNAL ARTICLE]
- Reprod Toxicol 2014 Sep 29.
Iatrogenic gestational exposure to diethylstilbestrol (DES) induced alterations of the genital tract and predisposed individuals to develop clear cell carcinoma of the vagina as well as breast cancer later in life. Gestational exposure of rodents to a related compound, the xenoestrogen bisphenol-A (BPA) increases the propensity to develop mammary cancer during adulthood, long after cessation of exposure. Exposure to BPA during gestation induces morphological alterations in both the stroma and the epithelium of the fetal mammary gland at 18 days of age. We postulate that the primary target of BPA is the fetal stroma, the only mammary tissue expressing estrogen receptors during fetal life. BPA would then alter the reciprocal stroma-epithelial interactions that mediate mammogenesis. In addition to this direct effect on the mammary gland, BPA is postulated to affect the hypothalamus and thus in turn affect the regulation of mammotropic hormones at puberty and beyond.
- Liquid-phase exfoliated graphene as highly-sensitive sensor for simultaneous determination of endocrine disruptors: Diethylstilbestrol and estradiol. [JOURNAL ARTICLE]
- J Hazard Mater 2014 Sep 18.:157-163.
It is quite important to develop convenient and rapid analytical methods for trace levels of endocrine disruptors because they heavily affect health and reproduction of humans and animals. Herein, graphene was easily prepared via one-step exfoliation using N-methyl-2-pyrrolidone as solvent, and then used to construct an electrochemical sensor for highly-sensitive detection of diethylstilbestrol (DES) and estradiol (E2). On the surface of prepared graphene film, two independent and greatly-increased oxidation waves were observed at 0.28V and 0.49V for DES and E2. The remarkable signal enlargements indicated that the detection sensitivity was improved significantly. The influences of pH value, amount of graphene and accumulation time on the oxidation signals of DES and E2 were discussed. As a result, a highly-sensitive and rapid electrochemical method was newly developed for simultaneous detection of DES and E2. The values of detection limit were evaluated to be 10.87nM and 4.9nM for DES and E2. Additionally, this new method was successfully used in lake water samples and the accuracy was satisfactory.
- Hepatotoxicity induced by neonatal exposure to diethylstilbestrol is maintained throughout adulthood via the nuclear receptor SHP. [JOURNAL ARTICLE]
- Expert Opin Ther Targets 2014 Sep 29.:1-10.
Background: Liver physiology is sensitive to estrogens, which suggests that the liver might be a target of estrogenic endocrine disrupters (EED). However, the long-term consequences of neonatal exposure to EED on liver physiology have rarely been studied. The nuclear receptor small heterodimer partner (SHP) mediates the deleterious effects of neonatal exposure to diethylstilbestrol (DES) on male fertility. Objectives: As SHP is involved in liver homeostasis, we aimed to determine whether neonatal estrogenic exposure also affected adult liver physiology through SHP. Male mouse pups were exposed to DES in the first 5 days of life. Results: DES exposure leads to alterations in the postnatal bile acid (BA) synthesis pathway. Neonatal DES-exposure affected adult liver BA metabolism and subsequently triglyceride (TG) homeostasis. The wild-type males neonatally exposed to DES exhibited increased liver weight and altered liver histology in the adult age. The use of deficient male mice revealed that SHP mediates the deleterious effects of DES treatment. These long-term effects of DES were associated with differently timed alterations in the expression of epigenetic factors. Conclusions: However, the molecular mechanisms by which neonatal exposure persist to affect the adult liver physiology remain to be defined. In conclusion, we demonstrate that neonatal DES exposure alters adult hepatic physiology in an SHP-dependent manner.
- Diethylstilbestrol Exposure in Neonatal Mice Induces Changes in the Adulthood in the Immune Response to Taenia crassiceps without Modifications of Parasite Loads. [Journal Article]
- Biomed Res Int 2014.:498681.
Industrial growth has increased the exposition to endocrine disruptor compounds (EDC's), which are exogenous agents with agonist or antagonist action of endogenous steroid hormones that may affect the course of parasite infections. We wanted to determine if the exposure to diethylstilbestrol (DES), an estrogen agonist, to both male and female mice affected the immune response and their susceptibility to T. crassiceps cysticercosis. In all infected groups, females showed higher parasite loads than males, and neonatal DES administration did not modify this pattern. In the spleen, noninfected mice showed sex-related differences in the percentage of the CD8+ subpopulation, but DES decreased the percentage of CD3+, CD19+, and CD8+ subpopulations in infected mice. In the mesenteric lymphatic node (MNL), DES showed a dimorphic effect in the percentage of CD19+ cells. Regarding estrogen receptor alpha (ER-α) expression, DES treatment induced a reduction in the expression of this receptor in both noninfected female and male mice in the spleen, which was decreased only in males in CD3+ and CD8+ lymphocytes in MNL cell subpopulations. Our study is the first one to demonstrate that DES neonatal treatment in male and female mice affects the immune cell percentage, without effect on the susceptibility to T. crassiceps cysticercosis.
- Altered Gene Expression Patterns During the Initiation and Promotion Stages of Neonatally Diethylstilbestrol-Induced Hyperplasia/Dysplasia/Neoplasia in the Hamster Uterus. [JOURNAL ARTICLE]
- Reprod Toxicol 2014 Sep 18.
Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: 1) immunoblot analyses and 2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and 3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: 1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and 2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon. Particularly interesting changes included members in the functional categories of nuclear receptors (progesterone receptor), cell-cell interactions (E-cadherin, connexins), cytokine action (IRF-1, Stat5A), growth factor action (IRS-1), extracellular matrix component (tenascin-C), transcription factors (Nrf2, Sp1), and multi-functional nuclear protein (SAFB1).
- Direct estradiol and diethylstilbestrol actions on early- versus late-stage prostate cancer cells. [Journal Article]
- Prostate 2014 Dec; 74(16):1589-603.
Diethylstilbestrol (DES) and other pharmaceutical estrogens have been used at ≥ µM concentrations to treat advanced prostate tumors, with successes primarily attributed to indirect hypothalamic-pituitary-testicular axis control mechanisms. However, estrogens also directly affect tumor cells, though the mechanisms involved are not well understood.LAPC-4 (androgen-dependent) and PC-3 (androgen-independent) cell viability was measured after estradiol (E2 ) or DES treatment across wide concentration ranges. We then examined multiple rapid signaling mechanisms at 0.1 nM E2 and 1 µM DES optima including levels of: activation (phosphorylation) for mitogen-activated protein kinases, cell-cycle proteins, and caspase 3, necroptosis, and reactive oxygen species (ROS).LAPC-4 cells were more responsive than PC-3 cells. Robust and sustained extracellular-regulated kinase activation with E2 , but not DES, correlated with ROS generation and cell death. c-Jun N-terminal kinase was only activated in E2 -treated PC-3 cells and was not correlated with caspase 3-mediated apoptosis; necroptosis was not involved. The cell-cycle inhibitor protein p16(INK4A) was phosphorylated in both cell lines by both E2 and DES, but to differing extents. In both cell types, both estrogens activated p38 kinase, which subsequently phosphorylated cyclin D1, tagging it for degradation, except in DES-treated PC-3 cells.Cyclin D1 status correlated most closely with disrupted cell cycling as a cause of reduced cell numbers, though other mechanisms also contributed. As low as 0.1 nM E2 effectively elicited these mechanisms, and its use could dramatically improve outcomes for both early- and late-stage prostate cancer patients, while avoiding the side effects of high-dose DES treatment. Prostate 74: 1589-1603, 2014. © 2014 Wiley Periodicals, Inc.