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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 12 (1984), S. 10-12 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Aminoglutethimide (AG) has recently been introduced for endocrine therapy in patients with advanced breast and endometrial cancer. In this study two patients being treated with both AG and the anticoagulant agent warfarin are described. An important drug interaction was observed, resulting in a decrease in the anticoagulant effect of warfarin. This was shown by means of thrombotest measurements and pharmacokinetic evaluation of warfarin. A 3- to 5-fold increase in warfarin clearance was found. This interaction is probably due to an AG-promoted induction of hepatic microsomal enzymes accelerating warfarin metabolism.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of two progestins, medroxyprogesterone acetate (MPA) and megestrol acetate (MA), given orally in high doses, on the pharmacokinetics of antipyrine, digitoxin, and warfarin were studied in patients with advanced breast cancer. Antipyrine and warfarin were given as a single test dose before and after 5 weeks of progestin treatment. The pharmacokinetics of digitoxin was investigated at steady state in patients receiving this drug therapeutically before and during treatment with progestins. Small changes in clearance rates for antipyrine, warfarin, and digitoxin were found. A minor decrease observed in warfarin clearance however may be of clinical importance. Half-lives decreased by 13% for antipyrine and increased by 71% for warfarin. High-dose progestins given orally do not seem to have a major influence on drug metabolism, probably reflecting a minor effect on drug and steroid-metabolizing microsomal mono-oxygenases in the liver.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 42 (1974), S. 333-344 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Estradiol was found to stimulate the activity of adenylate cyclase in the cervicovaginal epithelium of neonatal mice, demonstrated with adenylyl-imidodiphosphate and also with adenosine triphosphate (ATP) as substrate. Measures were taken to exclude interference by other ATP-degrading enzymes. The deposits of the reaction product, indicating enzyme activity, were localized on the plasma membrane of all sides of the epithelial cells. A similar distribution of enzyme activity was recorded in both controls and estradiol-stimulated animals with either of the two substrates; however, the deposits appeared most prominent after estradiol-treatment. In view of a previous report on increased activity of the cyclic AMP-degrading enzyme phosphodiesterase after estradiol-treatment, it was concluded that the parallel elevation in activity of both adenylate cyclase and cyclic AMP-phosphodiesterase indicates a role of cyclic AMP in the action mechanism of estradiol.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 9 (1987), S. 123-128 
    ISSN: 1573-7217
    Keywords: breast cancer ; prognostic factors ; progesterone binding cyst protein ; tumor markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Different secretory proteins have been evaluated as possible tumor markers in breast cancer. In this study progesterone binding cyst protein (PBCP) has been quantitated in breast tumor tissue. We report on a correlation of PBCP in cytosols of primary breast cancer, with known prognostic factors. A significant difference (p 〈 0.001, Chi-square) in the frequency of PBCP-negative patients in clinical Stage I and Stage II is found. This was mainly attributed to a difference between T1 and T2 tumors, with less contribution from nodal status. A biological function of PBCP in breast cancer is not known. The distribution of PBCP in our patients has a close resemblance with expected number of node positive patients, suggesting that PBCP as a tumor marker may aid in providing prognostic information in breast cancer patients.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; cAMP binding capacity ; endocrine treatment ; estrogen receptor ; hormone sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Estrogen receptor (ER) and total binding capacity for cyclic AMP (cAR) were measured in cytosols from human mammary tumors. Patients with advanced, evaluable breast cancer were biopsied before the start of endocrine treatment, and ER and cAR measurements were performed. All patients included in this study were ER positive. Sixteen of 30 patients (53%) had an objective response to endocrine treatment. When ER and cAR were expressed as a ratio and this ratio was related to treatment response, it was found that all objective responders had ratio values above 2.5 × 10−3. Nine of 14 nonresponders had ER/cAR ratios below this value. In our limited series of patients a threshold limit of 2.5 × 10−3 would have correctly predicted the response to endocrine treatment in 25 of 30 patients (83%). In patients with ER values below 100 fmol/mg protein and PgR negative or unknown, cAR might strengthen the predictive value of steroid receptor measurements.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7217
    Keywords: advanced breast cancer ; aminoglutethimide ; previous response ; sequential treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the last 2 years we have treated 24 patients (23 females and 1 male) with aminoglutethimide plus glucocorticoid for advanced breast cancer. More than half of the patients had received more than 3 systemic treatments before start of aminoglutethimide (AG), and at least half of the patients had been given more than 2 different endocrine regimens. There were 8 previous responders to endocrine therapy and in 10 patients steroid receptor status predicted response to therapy. Nine of 22 patients (two had to stop after less than 1 month due to acute toxicity) had an objective response; there were 2 complete responders. Most side effects were not serious, subsiding within a few weeks. In one patient agranulocytosis was observed. AG with glucocorticoid replacement seems to be an effective treatment as a late endocrine alternative in a sequence of different endocrine regimens.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-7217
    Keywords: aromatase inhibitor ; breast cancer ; endocrine therapy ; NMR spectroscopy ; plasma lipids ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Side-effects following long-term endocrine therapy might have clinical implications. The aim of this study was to study potential methods to detect effects on plasma induced by hormonal therapies. The composite methylene (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) aliphatic peaks of the1H magnetic resonance spectrum (500 MHz) were analyzed in consecutive plasma samples of 23 cancer patients drawn before and during treatment with hormonally acting drugs. The aliphatic peaks were analyzed for line width at half-height and then averaged. In addition,13C magnetic resonance spectroscopy (125 MHz) analyses were done in selected patients. The blood samples were analyzed for triglyceride, cholesterol, apolipoprotein A1 (apo A1), and apolipoprotein B (apo B) levels. The methylene line width increased significantly after 9 weeks of tamoxifen (41.4 vs. 37.6 Hz). A trend of differences was observed in the saturated part of the13C magnetic resonance spectrum. A significant decrease in total cholesterol (mean decrease, 13%), increases in apo A1 (9%) and in the ratio of apo A1 to apo B (28%), but unchanged total triglycerides were found, indicating a decrease in LDL and increase in HDL lipoproteins in these patients following tamoxifen therapy. During dose escalation with the aromatase inhibitor exemestane, the methylene line width seemed to decrease (31.9 vs. 38.8 Hz, at 12 weeks and baseline, respectively). Significant decreases in total (13%) and HDL (32%) cholesterol, apo A1 (25%), and total triglyceride (16%) levels were found during the same interval. The apo A1/apo B ratio decreased by 25%. For patients on dexamethasone, the proton aliphatic line widths increased one day after the initiation of therapy. The changes in line shape observed during dexamethasone therapy indicated lower levels of triglyceride-rich relative to triglyceride-poor lipoproteins, consistent with results from the lipid analyses. In conclusion, nuclear magnetic resonance spectroscopy might have potential to detect effects on plasma induced by endocrine therapy. The lipid analyses in these patients were in support of the changes in lipid profile as evaluated by nuclear magnetic resonance spectroscopy.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 136 (1973), S. 263-275 
    ISSN: 1432-0878
    Keywords: Vaginal epithelium ; Cell differentiation ; Mouse ; Estradiol sensitive antigen ; Immunocytology, Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of an antigenic material specific for the cervicovaginal epithelium (CVA) was studied in the vaginal epithelium of the adult mouse with immunofluorescence and immunoferritin techniques. The antigen localization has been correlated to the fine structure of the vaginal epithelium in various states of functional activity. The antigen distribution in adult ovariectomized mice and in ovariectomized mice treated with estradiol was compared with that in normal cycling mice. CVA was found to be associated with the exterior of the cell membrane of vaginal epithelium cells, being part of the glycocalyx. Two cell types, mucous or keratinized, are derived from the germinative cell layer of the vaginal epithelium, depending on the hormonal environment. Mucous cells with morphological features that characterize cells about to cornify have been demonstrated. Fluorescence as well as ferritin particles, indicating the presence of antigen-antibody complexes, were seen within the mucous droplets of the mucous cells. The CVA production is apparently connected with vaginal mucus formation. The CVA distribution in the adult vaginal epithelium is discussed in relation to the distribution demonstrated earlier in the cervicovaginal epithelium of neonatal mice.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular histology 11 (1979), S. 669-684 
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Synopsis A cytochemical method for the demonstration of adenylate cyclase activity has been evaluated. Enzyme activity in the epithelium of the Müllerian part of the vaginal anlage in neonatal, oestradiol-treated mice has been studied under different experimental conditions. The effects of fixation, incubation conditions and post-fixation have been studied. Variations in the amount of impurities and acid content of the glutaraldehyde do not seem to influence the enzyme activity. High Pb2+ ion concentration seems to promote unspecific staining. Under standard conditions [2 mM Pb (NO3)2, pH 7.2, and incubation temperature 30°C], neither non-enzymatic nor nonsubstrate-dependent lead trapping in the tissue could be observed. The possible contribution of other enzymes utilizing ATP and AMP-P(NH)P as the formation precipitate, has been evaluated. Both ATP and AMP-P(NH)P have been used as substrates in this study. Provided the appropriate control experiments are performed, this cytochemical method is reliable for demonstration of adenylate cyclase activity.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-7217
    Keywords: HPV 16 ; breast cancer ; CIN III ; PCR ; southern blot ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Women with both a history of high grade cervical intraepithelial neoplasia (CIN III) and breast carcinoma as second primary cancer were selected for studying the presence of HPV in breast carcinomas. Paraffin embedded material from 38 patients with 41 breast carcinoma cases after CIN III were examined by polymerase chain reaction (PCR) and in situ hybridization. By PCR we detected HPV 16 DNA in 19 out of 41 cases (46%) of the breast carcinomas. One case proved to be HPV 16 positive also by in situ hybridization. HPV 16 was also detected in 32 out of the 38 patients with CIN III (84%). All HPV 16 positive breast carcinomas were HPV 16 positive in their corresponding CIN III lesions. Eight patients with diagnosed breast cancer before the CIN III lesions were used as controls. None of these had HPV positive breast carcinomas. No cases were positive for HPV 11, 18, or 33. HPV 16 was detected in the primary tumours, in local metastases from HPV 16 positive tumours, in a distant HPV 16 positive breast carcinoma metastasis to the colon, and in other primary cancers in patients with HPV 16 positive breast carcinomas and HPV 16 positive CIN III. Estrogen and progesterone receptors were quantified in the HPV positive and HPV negative breast carcinomas, and there was no significant difference in the fraction positive in the two groups. Oncogenic HPV DNA might be transported from an original site of infection to other organs by blood or lymph, and possibly be a factor in the development of cancer in different organs.
    Type of Medium: Electronic Resource
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