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Melo e Silva, M.C.M. Cristina; Patricio, Luciana; Gano, Lurdes; Sa e Melo, M. Luisa; Inohae, Eiko; Mataka, Shuntaro; Thiemann, Thies, E-mail: lucianap@itn1.itn.pt2001
AbstractAbstract
[en] The synthesis of two novel radiolabelled estrogen derivatives, [125I](E)-3-methoxy-17α-iodovinylestra-1,3,5(10),6-tetraen-17β-ol (E[125I]IVDE) and [125I](Z)-3-methoxy-17α-iodovinylestra-1,3,5(10),6-tetraen-17β-ol (Z[125I]IVDE), was carried out aiming to study the influence of the introduction of a C6-C7 double bond on the biological properties of the estradiol molecule. 3-Methoxyestra-1,3,5(10),6-tetraen-17-one was synthesised starting from a suitably protected estrone and subsequently converted into the 17α-ethynyl derivative. The radioiodinated derivatives were stereoselectively formed by radioiododestannylation of the corresponding tributylstannyl precursors. The biodistribution of the novel [125I]iodovinylestradiol derivatives was evaluated in immature female mice. Biological data indicated that the Z-isomer, owing to its higher in vivo uptake by the target tissue, has the preferable configuration for further development of similar compounds for estrogen receptor detection.
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S0969804399002584; Copyright (c) 2001 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; This record replaces 33037053; Country of input: Belgium
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[en] Over the past decade, educational programmes have been the main focus of the activities of the International Union of Toxicology (IUTOX). The IUTOX educational programmes are dynamic and have been growing in scope and frequency each year. It is envisaged that this growth will continue with guidance from our member societies and the continuing support of our sponsors. Presently, IUTOX is engaged in the following educational programmes: (1) International congresses that provide the opportunity for direct communication of current toxicological information. Fellowships are sponsored to facilitate attendance at these congresses for toxicologists in need. (2) Workshops that permit interaction on a more localised level of topics of more regional interest. Workshops have served to help stimulate formation of toxicology societies by bringing together sufficient scientists to facilitate these discussions. (3) Continuing educational (CE) programmes at member society meetings. Topics are prioritised based on input received from the local societies. Programmes often are those from CE courses given at meetings, such as conferences of the US Society of Toxicology (US SOT) and EUROTOX from the previous year. (4) Biennial Risk Assessment Summer School (RASS), an intensive week-long interaction between senior toxicologists who serve as faculty with attendees providing individual training. (5) Dissemination of donated printed toxicological books from publishers and syllabi from continuing education courses to regional locations. (6) Web-based interactive training programmes in regions where formal toxicological educational programmes are limited or lacking. (7) Preparation and distribution of monographs on selected topics of very current interest. Monographs on environmental oestrogens and genetically-modified foods have been published. The recent activities in each of these programmes are reviewed in this paper
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ICT X 2004: 10. international congress of toxicology: Living in a safe chemical world; Tampere (Finland); 11-15 Jul 2004; S0041-008X(05)00239-5; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
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[en] Highlights: • Autophagy was crucially connective with endometriosis. • The role of autophagy in endometriosis is controversial. • Autophagy is a friend in endometriosis. • Autophagy is a foe in endometriosis. Endometriosis is a chronic, estrogen-dependent disease and characterized by the implantation of endometrial glands and stroma deep and haphazardly into the outside the uterine cavity. It affects an estimated 10% of the female population of reproductive age and results in obvious reduction in health-related quality of life. Unfortunately, there is no a consistent theory for the etiology of endometriosis. Furthermore, the endometriosis is hard to diagnose in early stage and the treatment methods are limited. Importantly, emerging evidence has investigated that there is a close relationship between endometriosis and autophagy. However, autophagy is a friend or foe in endometriosis is puzzling, the precise mechanism underlying autophagy in endometriosis has not been fully elucidated yet. Here, we provide an integrated view on the acquired findings of the connections between endometriosis and autophagy. We also discuss which may contribute to the abnormal level of autophagy in endometriosis.
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S0006291X17321307; Available from http://dx.doi.org/10.1016/j.bbrc.2017.10.145; Copyright (c) 2017 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
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Journal Article
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Biochemical and Biophysical Research Communications; ISSN 0006-291X;
; CODEN BBRCA9; v. 495(1); p. 60-63

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[en] A product is prepared by the action of tritiated methanol on 11β-hydroxy-estra-4,9-dien-3,17-dione, the action of an aromatisation agent on the (11β)-11-methoxy-3H3-estra-4,9-dien-3,17-dione formed and the action of an ethynylation agent on the resulting (11β)-3-hydroxy-11-methoxy-3H3-estra-1,3,5(10)-trien-17-one giving (11β, 17α)-11-methoxy-3H3-19-norpregna-1,3,5(10)-trien-20-yne-3,17 diol, the free hydroxyl function or functions of this product may be etherified or esterified as the case may be. The tritiated methanol acts in the presence of perchloric acid. The aromatisation agent is palladium hydroxide and the operation is carried out in methanol. The ethynylation agent is acetylene and the reaction takes place in the presence of sodium t-amylate in toluene. This product allows the study and determination of the estrogen specific receptor present in the tissue cells of target organs for the action of estrogens: uterus, vagina, hypophysis, hypothalamus and tumours, of the breast and prostate for example, in both animals and man. Not being fixed by the plasma proteins binding such hormones as testosterone and estradiol in women the product is an ideal indicator of the tissular estrogen receptor with which it forms a complex of strong affinity and great stability, especially since it interacts with the tissular receptors of no other steroid hormone groups (glucocorticoids, androgen or progestogen mineralocorticosteroids)
[fr]
Procede de preparation d'un produit caracterise en ce que l'on fait agir le methanol tritie sur la 11β-hydroxy-estra-4,9-dien-3,17-dione, soumet la (11β)-11-methoxy-3H3-estra-4,9-dien-3,17-dione resultant a l'action d'un agent d'aromatisation, fait agir sur la (11β)-3-hydroxy-11-methoxy-3H3-estra-1,3,5(10)-trien-17-one resultant un agent d'ethynylation et obtient le (11β, 17α)-11-methoxy-3H3-19-norpregna-1,3,5(10)-trien-20-yne-3,17-diol, dont on peut, le cas echeant, etherifier ou esterifier la ou les fonctions hydroxyles libres. On fait agir le methanol tritie en presence de l'acide perchlorique. L'agent d'aromatisation est l'hydroxyde de palladium et on opere dans le methanol. L'agent d'ethynylation est l'acetylene et on opere en presence de t-amylate de sodium dans le toluene. Ce produit permet l'etude et le dosage du recepteur specifique estrogene present dans les cellules des tissus des organes cibles de l'action des estrogenes, comme l'uterus, le vagin, l'hypophyse, l'hypothalamus et les tumeurs, comme par exemple du sein, de la prostate, aussi bien chez l'animal que chez l'homme. En effet comme ce produit ne se fixe pas sur les proteines plasmatiques liant les hormones tels que la testosterone et l'estradiol chez la femme c'est un marqueur de choix du recepteur tissulaire des estrogenes avec lequel il forme un complexe de forte affinite et de grande stabilite, d'autant qu'il n'a aucune interaction avec les recepteurs tissulaires des autres classes d'hormones steroidiennes (glucocorticoides, mineralocorticosteroides androgenes ou progestogenes)Original Title
Steroides marques au tritium, leur procede de preparation et leur application pour le dosage et la localisation des recepteurs tissulaires hormonaux des steroides
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19 Jul 1977; 6 p; FR PATENT DOCUMENT 2398076/A/; Available from Institut National de la Propriete Industrielle, Paris (France)
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[en] We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma. We performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients. Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated. Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients. Trial identification number (Clinical Trials.gov): http://www.clinicaltrials.gov/NCT01965080. Nordic Society of Gynecological Oncology: NSGO–EC–0302. EudraCT number: 2004-001103-35
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Available from http://dx.doi.org/10.1186/1471-2407-14-68; Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924910; PMCID: PMC3924910; PUBLISHER-ID: 1471-2407-14-68; PMID: 24498853; OAI: oai:pubmedcentral.nih.gov:3924910; Copyright (c) 2014 Lindemann et al.; licensee BioMed Central Ltd.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0) (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.; Country of input: International Atomic Energy Agency (IAEA)
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BMC cancer (Online); ISSN 1471-2407;
; v. 14; p. 68

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AbstractAbstract
[en] 17α-Ethinylestradiol (EE2) is a synthetic estrogen used primarily in birth control pills and in hormone replacement therapy. Owing to its occurrence in surface waters at concentrations frequently greater than 1 ng/l and its projected future use, EE2 is expected to pose a significant risk to aquatic organisms. This study was conducted to obtain long-term exposure data necessary for the establishment of water quality criteria and to investigate mechanisms associated with toxic effects. In a multigeneration experiment, Chinese rare minnows (Gobiocypris rarus) were constantly exposed to environmentally relevant concentrations of the synthetic estrogen EE2. Mortality, deformities, reproductive parameters, plasma vitellogenin and histopathology were assessed. The results showed that, in the F0 generation, all endpoints were significantly affected at concentrations higher than 0.2 ng/l EE2. No F1 phenotypic males developed to maturity at 0.2 ng/l and, when adult females of this exposure group were crossed with unexposed males, no F2 fertile eggs were produced. Kidney histopathology and ultrastructure suggest anomalies possibly associated with increased vitellogenin accumulation. We concluded that the reproduction of the F1 minnows was completely inhibited at the lowest concentration tested, 0.2 ng/l EE2, a concentration frequently detected in surface waters. Growth effects may be related to increased energy requirements including the energy used in VTG synthesis. Reproductive effects are presumably associated with male feminization and the occurrence of testis-ova in males; however, ovarian degeneration observed in females may also have contributed to reproductive failure
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S0041-008X(07)00445-0; Available from http://dx.doi.org/10.1016/j.taap.2007.10.006; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
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[en] Oestrogen receptors were measured in the cytoplasmic fraction of tummours from patients with breast cancer. Receptors were detected in 48% of patients, and 52% showed no receptors. A follow-up study of a small group of patients on hormone therapy is reported
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Journal Article
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South African Medical Journal; v. 53 (15); p. 577-578
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[en] Although the radioreceptor method is widely used for estrogen receptor assay in human tissue, it has several limitations and a number of alternative methods are being explored. An immunohistochemical method of estrogen receptor assay using a specific antibody to estradiol has been proposed as a suitable alternative. The present study was designed to evaluate the validity of this method in detecting true estrogen receptors in human tumor tissue. Using radioiodinated antibody to estrogen, we have demonstrated that the estrogen antibody can detect the estrogen when it is bound to 4S type receptor but is unable to bind to estrogen when the hormone is bound to 8S type receptor. Our observations suggest that the immunohistochemical method of detection of intracellular cytosolic receptor for estrogen is not a suitable alternative to the currently used radioreceptor method
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[en] An estrogen radioimmunoassay was used to study the problem of blanks in steroid assays. Negligible binding (1.5 percent) in the non-antibody tubes prevailed throughout the study. The assay was validated using accepted procedures. Both water and solvent blanks had estrogen concentrations of 7-9 pg/tube. However, neither water nor solvent blanks showed a dose-related response, indicating that they were 'real' blanks. Exogenous estradiol, when added to water and solvent in quantities less than the estimated blank, was not quantitatively recovered. However, exogenous estradiol added to the water solvent in quantities greater than the blank estimate was quantitatively recovered. The sensitivity of the reference standard curve was 6-10 pg/tube, approximately the same as the blank estimate. These results indicated that the estimates of water and solvent blanks were measures of the assay sensitivity. In such circumstances, it is suggested that blank estimates should not be subtracted from sample values. If the blank estimates are high, attention should be directed towards improving the sensitivity of the assay
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Journal Article
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Canadian Journal of Animal Science; ISSN 0008-3984;
; v. 61(2); p. 363-368

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[en] Gene expression profiling of tumors using DNA microarrays is a promising method for predicting prognosis and treatment response in cancer patients. It was recently reported that expression profiles of sporadic breast cancers could be used to predict disease recurrence better than currently available clinical and histopathological prognostic factors. Having observed an overlap in those data between the genes that predict outcome and those that predict estrogen receptor-α status, we examined their predictive power in an independent data set. We conclude that it may be important to define prognostic expression profiles separately for estrogen receptor-α-positive and estrogen receptor-α-negative tumors
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Available from http://dx.doi.org/10.1186/bcr548; Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC154130; PMCID: PMC154130; PUBLISHER-ID: bcr548; PMID: 12559041; OAI: oai:pubmedcentral.nih.gov:154130; Copyright (c) 2003 Bio Med Central; Country of input: International Atomic Energy Agency (IAEA)
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Breast Cancer Research (Print); ISSN 1465-5411;
; v. 5(1); p. 23-26

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