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diethylstilbestrol diethylstilbestrol [keywords]
- Primary Intestinal-type Glandular Lesions of the Vagina: Clinical, Pathologic, and Immunohistochemical Features of 14 Cases Ranging From Benign Polyp to Adenoma to Adenocarcinoma. [Journal Article]
- Am J Surg Pathol 2014 May; 38(5):593-603.
Primary intestinal-type glandular lesions of the vagina are rare. We report a series of 14 lesions, including 1 intestinal-type polyp without neoplastic features, 3 adenomas (2 with high-grade dysplasia), and 10 adenocarcinomas. Patients ranged in age from 20 to 86 years (mean 60 y) and presented with vaginal bleeding or a mass. No history of diethylstilbestrol exposure, adenosis, or endometriosis was elicited in any patient. The lesions were mostly polypoid, small (0.8 to 2.0 cm), and located in the posterior (6 cases) and lower (7 cases) vagina. One carcinoma metastasized to a para-aortic lymph node; the others were confined to the vagina. The neoplasms exhibited histologic features identical to those seen in primary large intestinal tumors, including variable numbers of goblet cells and in 1 case neuroendocrine cells. Five of the adenocarcinomas contained areas consistent with a precursor adenoma. In 3 cases, a benign urothelium-lined duct was adjacent to the lesion, and in 2 patients benign intestinal-type epithelium was present; no other potential benign precursor lesions were seen. Immunohistochemical analysis was performed on 6 cases; the tumors were positive for CDX-2 (6/6), CK20 (5/6), CEA (5/5), CK7 (4/6), and CA-125 (2/4) and were negative for ER (0/6) and p16 (0/2). Clinical outcome data were available in 3 patients with adenocarcinomas; 1 died of disease in <1 year, and 2 were alive with no evidence of disease at 2 and 7 years. The pertinent literature is reviewed, and the potential origin and differential diagnosis of these lesions are discussed.
- [Diethylstilbestrol story]. [English Abstract, Journal Article]
- Therapie 2014 Jan-Feb; 69(1):101-14.
This story, that has been going on for 75 years begins with an infatuation for a "miraculous" drug supposed to, according to a theory and without scientific proof of effectiveness, reduce the pregnancy complications, especially the number of miscarriages. The next steps are painful with the discovery during the seventies, for the in utero exposed daughters, of particular cancers (clear cells adenocarcinoma) of the uterus cervix or the vagina, then during the eighties infertility and pregnancy accidents. This story is exemplary because it involves the different society actors whose roles will be analysed: health professionals, health authorities, patients associations, media and pharmaceutical companies. We will propose lessons for the future.
- Stable Reporter Gene Assay Based on Gal4-Vitamin D Receptor β Fusion Proteins in Medaka (Oryzias latipes), and Its Transactivational Properties. [Journal Article]
- Zoolog Sci 2014 Apr; 31(4):195-201.
The transactivational property of natural and synthetic chemicals via medaka vitamin D receptor β subtype (VDRβ) was investigated after the development of a stable cell line expressing a Gal4-VDRβ fusion protein for reporter gene assay. Members of vitamin D class, including 1α, 25- dihydroxyvitamin D3 (1,25VD3) were specifically detected as agonists in our system. Although other steroids and chemicals used in the present estimation induced no agonistic response, 10 compounds displayed antagonistic or synergistic activity. Spironolactone, which is an antagonist of corticoid receptors in mammals, competitively inhibited the transactivity of 1,25VD3 by over 80% in a dosedependent manner. Mifepristone and cyproterone acetate were also detected as antagonists, but they significantly acted only at 10µ. Pregnenolone and raloxifene dose-dependently enhanced the activity of 1,25VD3 at EC50 to the maximum level. Diethylstilbestrol, 17α-ethynylestradiol, genistein, and stanozolol were also synergists, but their potency was low. Interestingly, dibutyltin dichloride, which is used as a stabilizer in the production of polyvinyl chloride plastics, produced greater response than maximum effect of 1,25VD3 although the concentration-response curve was not typically sigmoidal. In the present study, we successfully developed a stable reporter gene assay, which allows assessment of the vitamin D-like chemicals toward the medaka VDRβ.
- Primary non-clear-cell adenocarcinoma of the vagina in a diethylstilbestrol exposed woman. [Journal Article]
- Mil Med 2014 Apr; 179(4):e461-2.
A 54-year-old woman with a history of in-utero diethylstilbestrol (DES) exposure, who had a prior hysterectomy for symptomatic leiomyomata and dysmenorrhea, presented for vaginal bleeding. Vaginal biopsies showed a non-clear-cell adenocarcinoma, and the patient was subsequently treated with radiation therapy. We present a case of primary vaginal non-clear-cell adenocarcinoma in a patient with in-utero DES exposure. Continued monitoring of older DES-exposed women for vaginal lesions is warranted because of reported cases of non-clear-cell adenocarcinoma and persistent risk of clear cell adenocarcinoma.
- Differing Species Responsiveness of Estrogenic Contaminants in Fish Is Conferred by the Ligand Binding Domain of the Estrogen Receptor. [JOURNAL ARTICLE]
- Environ Sci Technol 2014 Apr 14.
Exposure to estrogenic endocrine disrupting chemicals (EDCs) induces a range of adverse effects, notably on reproduction and reproductive development. These responses are mediated via estrogen receptors (ERs). Different species of fish may show differences in their responsiveness to environmental estrogens but there is very limited understanding on the underlying mechanisms accounting for these differences. We used custom developed in vitro ERα reporter gene assays for nine fish species to analyze the ligand- and species-specificity for 12 environmental estrogens. Transcriptonal activities mediated by estradiol-17β (E2) were similar to only a 3-fold difference in ERα sensitivity between species. Diethylstilbestrol was the most potent estrogen (∼10-fold that of E2) in transactivating the fish ERαs, whereas equilin was about 1 order of magnitude less potent in all species compared to E2. Responses of the different fish ERαs to weaker environmental estrogens varied, and for some considerably. Medaka, stickleback, bluegill and guppy showed higher sensitivities to nonylphenol, octylphenol, bisphenol A and the DDT-metabolites compared with cyprinid ERαs. Triclosan had little or no transactivation of the fish ERαs. By constructing ERα chimeras in which the AF-containing domains were swapped between various fish species with contrasting responsiveness and subsequent exposure to different environmental estrogens. Our in vitro data indicate that the LBD plays a significant role in accounting for ligand sensitivity of ERα in different species. The differences seen in responsiveness to different estrogenic chemicals between species indicate environmental risk assessment for estrogens cannot necessarily be predicted for all fish by simply examining receptor activation for a few model fish species.
- Our stolen figures: The interface of sexual differentiation, endocrine disruptors, maternal programming, and energy balance. [REVIEW]
- Horm Behav 2014 Mar 28.
This article is part of a Special Issue "Energy Balance". The prevalence of adult obesity has risen markedly in the last quarter of the 20th century and has not been reversed in this century. Less well known is the fact that obesity prevalence has risen in domestic, laboratory, and feral animals, suggesting that all of these species have been exposed to obesogenic factors present in the environment. This review emphasizes interactions among three biological processes known to influence energy balance: Sexual differentiation, endocrine disruption, and maternal programming. Sexual dimorphisms include differences between males and females in body weight, adiposity, adipose tissue distribution, ingestive behavior, and the underlying neural circuits. These sexual dimorphisms are controlled by sex chromosomes, hormones that masculinize or feminize adult body weight during perinatal development, and hormones that act during later periods of development, such as puberty. Endocrine disruptors are natural and synthetic molecules that attenuate or block normal hormonal action during these same developmental periods. A growing body of research documents effects of endocrine disruptors on the differentiation of adipocytes and the central nervous system circuits that control food intake, energy expenditure, and adipose tissue storage. In parallel, interest has grown in epigenetic influences, including maternal programming, the process by which the mother's experience has permanent effects on energy-balancing traits in the offspring. This review highlights the points at which maternal programming, sexual differentiation, and endocrine disruption might dovetail to influence global changes in energy balancing traits.
- [Simultaneous determination of six estrogens in different water bodies by solid phase extraction and ultra performance liquid chromatography coupled with triple quadrupole mass spectrometry]. [English Abstract, Journal Article]
- Se Pu 2013 Dec; 31(12):1176-81.
A method has been developed for the simultaneous determination of six estrogens: (estriol, 17-beta-estradiol, 17-alpha-estradiol, estrone, ethinyloestradiol, diethylstilbestrol) in water environment by solid phase extraction and ultra performance liquid chromatography couple with triple quadrupole mass spectrometry. After enriched and purified by an HLB solid phase extraction column, the six estrogens were separated by a BEH C18 column and then determined by MS/MS with multiple reaction monitoring (MRM) mode. The quantification was achieved by internal standard method, with estriol-D3, estradiol-D2 and diethylstilbestrol-D8 as the internal standards. Good linear relationships were obtained in the mass concentration range of 1.0-100 microg/L with high correlation coefficients over 0. 998 2. The limits of detection and quantification for the six estrogens were 0.27-0.45 ng/L and 1.08-1.78 ng/L, respectively. The recoveries were in the range of 68.3%-97.4% at the three spiked levels and with the relative standard deviations below 15%. The method shows high sensitivity, good precision, extensive analytical range and high analytical speed. It was successfully applied to the simultaneous detection of the six estrogens in four different water bodies including surface water, waste water, source water of drinking and domestic water.
- Neurobehavioral evaluation of mouse newborns exposed prenatally to low-dose bisphenol A. [Journal Article]
- J Toxicol Sci 2014; 39(2):231-5.
There have been few neurobehavioral toxicology studies on newborn animals. Thus, we developed a mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants, by means of determining the newborn's motor activity applying the tare function of an analytical balance. Motor activities including crawling, pivoting, righting or tremors of mouse newborns were evaluated. Tremors of newborns of dams exposed to bisphenol A at 2, 20 or 200 µg/kg/day on days 5 through 18 of gestation were significantly increased when evaluated on postnatal day 1, as well as those of newborns exposed prenatally to diethylstilbestrol at 0.5 µg/kg/day. We suggest that our developed testing method may provide a useful addition to neurobehavioral assessment in very young rodents exposed to environmental hormone mimics.
- Packed-fiber solid-phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry for determination of diethylstilbestrol, hexestrol, and dienestrol residues in milk products. [Journal Article]
- J Chromatogr B Analyt Technol Biomed Life Sci 2014 Apr 15.:7-13.
A sensitive analytical method based on packed-fiber solid-phase extraction and high performance liquid chromatography-tandem mass spectrometry (PF SPE-HPLC-MS/MS) has been developed for determination of three synthetic stilbenes in milk. The stilbenes are extracted with acetonitrile, using sodium chloride, and purified with PF SPE using a cartridge containing electrospun polystyrene nanofibers. Parameters affecting the efficiency of PF SPE, such as pH and amount of salt, were optimized. Under optimal conditions, the limits of detection and quantification were 5-13pg/g and 15-37pg/g, respectively. Absolute recoveries varied between 60% and 85% at three different levels. The method was successfully applied for the determination of estrogenic stilbenes in a total of 69 milk samples. The method is sensitive and cost-effective in stilbene detection, and has potential in quality control of dairy products.