Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of "soft" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, "scirrhous" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.
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PMID:Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer. 16 44

Case reports of benign hepatoma in young women taking oral contraceptives (OCs) are known to exist. A benign hepatic adenoma was discovered in a young woman who had been taking an OC (Ortho-Novum 2) for 7 years. Although hepatic adenoma is a rare tumor, the increasing number of reports of its occurrence strongly suggest an association between OCs and benign hepatic adenoma. Diagnosis must be suspected in any young woman taking OCs and developing signs of acute cholecystitis with hepatomegaly or mass, or presenting with signs and symptoms of nontraumatic intraabdominal hemorrage. Rupture of the tumor is life-threatening. Treatment should be removal of the tumor whenever possible.
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PMID:Benign liver cell adenoma associated with use of oral contraceptive agents. 17 59

Nine ovarian Sertoli-Leydig tumors, showing varying degrees of differentiation, one pure ovarian Sertoli cell tumor, and one poorly differentiated stromal tumor of the testis, were examined for the presence of testosterone, estradiol and progesterone with an indirect immunoperoxidase method on formalin fixed paraffin embedded tissue. Clinically all nine patients with Sertoli-Leydig tumors had evidence of increased androgen production, manifested by either hirsutism or virilization; elevated serum testosterone was found in all four patients in whom it was measured. The patients with the pure ovarian Sertoli cell and testicular tumors were asymptomatic except for the presence of a mass. Testosterone was identified in Leydig cells in nine instances, in Sertoli cells in six, and in poorly differentiated spindle cells resembling the mesenchyme of the embryonic gonad in two. Cells with vacuolated cytoplasm, both Sertoli and Leydig cells, though positive for lipid were consistently negative for testosterone. Estradiol was present in Leydig cells in nine instances, in Sertoli cells in five, and in primitive gonadal stomal cells in two. The pattern of distribution was similar to that of testosterone but the intensity of the reaction for estradiol was generally less than that for testosterone. Progesterone was identified in Sertoli cells in one instance and was weakly positive in Leydig cells in three instances. The presence of testosterone and estradiol in both Sertoli and Leydig cells as well as in primitive spindle cells resembling those found in the embryonic gonad suggests that the latter cell is the precursor for both Sertoli and Leydig cells.
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PMID:An immunohistological study of steroid localization in Sertoli-Leydig tumors of the ovary and testis. 36 Dec 11

The hamster ductus deferens cloned tumor cell line (DDT1) has been shown to contain both androgen and glucocorticoid binding activity. The androgen receptor binding site concentration is 1.07 x 10(-13) mol of testosterone/mg protein, and testosterone (T) binds with a Kd of 4.3 x 10(-10) M. Dihydrotestosterone (DHT) is also bound to the receptor with a Kd of 2.99 x 10(-10) M and the binding site concentration is 1.33 x 10(-13) mol/mg protein. The order of steroid binding affinity is DHT greater than T greater than Estradiol greater than Progesterone. Cortisol, dexamethasone, and triamcinolone acetonide do not inhibit the androgen binding in vivo or in vitro. In a cell free system antiandrogens inhibit the binding of DHT. The DDT1 cells have a separate receptor for cortisol which binds at saturation 3.44 x 10(-13) mol cortisol/mg protein and has a Kd of 4.54 x 10(-9) M. These studies provide evidence that these endocrine target cells contain specific high affinity receptors for more than one type of steroid. The glucocorticoid receptor may be important for maintaining essential undifferentiated functions while the DHT receptor gives the specific characteristics of sex hormone responsive tissues.
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PMID:The coexistence of androgen and glucocorticoid receptors in the DDT1 cloned cell line. 40 58

A vast literature reports on the ability of some tumor tissues to preserve the receptorial system of the original cells, which can be an indication of hormonal dependence of tumors. The authors tried to determine in quantitative term the receptorial capacity of beta Estradiol 17 of the normal and of the pathological endometrium. 23 postmenopausal patients were investigated, 10 with adenocarcinoma of the uterus, 6 with uterine fibroleiomioma, 4 with genital prolapse, and 3 with recurrent metrorrhagia. The maximal receptorial concentration was found in the 10 patients with adenocarcinoma, with concentrations going from 39.8 to 86.3 femtomoli/mg proteins. The normal value of a normal endometrium would be from 22 to 60.2 femtomoli/mg proteins. Some hypotheses are advanced about the receptorial capacity of the pathological tissues studied.
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PMID:[17-beta estradiol receptors in the normal and pathological human uterus]. 42 39

Young women who use oral contraceptives over a period of years are prone to the development of hepatic tumors, which must be correctly diagnosed and treated. A 24-year old woman who had used various oral contraceptives (Neogynon 21, Lyndiol, Microgynon) for over 5 years developed a hepatocellular carcinoma of the left hepatic lobe. The diagnosis was reached on the basis of laboratory tests as well as the results of laparoscopic, angiographic, x-ray, sonographic, and scintigrammic examinations. An attempt to remove the tumor surgically resulted in a fatal mass bleeding. No metastiasis of the carcinoma could be established. An examination of the liver revealed an Australia-antigen-positive, chronic-aggressive hepatitis.
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PMID:[Malignant liver tumor after oral contraception]. 45

166 Sprague-Dawley Rats (148 males and 118 females) submitted to different hormonal conditions were exposed to 3 repeated whole-body irradiations of 14.8 MeV neutrons or sham-irradiated between 50 and 65 days of age (total absorbed doses: 3 x 2 rad and 3 x 8 rad). They were observed for 11 months. In the male group, a small number of tumors was obtained. In the female group, 75 breast neoplasms were scored in 41 of 78 irradiated animals (54 fibroadenomas, 20 adenocarcinomas and 1 fibrosarcoma). A second group of benign and malignant tumors was observed from 200 days on. The neoplastic response to fast neutron fractionated irradiations was increased by pregnancy with subsequent lactation. Estradiol and progesterone receptors were measured in 34 tumor samples. Fibroadenomas (1;5) and adenocarcinomas (1;3) bound labelled steroids. Like in human breast cancer metastases, steroid receptors are found in recurrences only if present in the primary tumor.
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PMID:Mammary carcinogenesis in Sprague--Dawley rats following 3 repeated exposures to 14.8 MeV neutrons and steroid receptor content of these tumor types. 55 71

Tamoxifen (ICI 46474), an antiestrogen, was given to 89 selected patients with stage IV breast cancer at a dose of 20 mg orally every 12 hours. Forty-seven percent of the patients had objective tumor regression averaging 11+ months with 25 of 42 women still in remission. In the first 39 patients where the minimum follow-up period is 16 months the average duration of remission is more than 15 months with 8 of 19 patients still in remission. These results are approaching those of surgical hypophysectomy, where, in our experience the average remission lasts about 18 months. Thus, Tamoxifen is a highly effective antitumor agent and is probably the initial treatment of choice for women with hormone responsive breast cancer. Antiestrogen induced objective remissions in 5 of 19 patients who had previously responded to surgical hypophysectomy, and 5 additional patients showed no progression of disease lasting 15+ months. Estradiol and estrone were detectable in the serum of these patients whereas, prolactin and growth hormone were not detectable. Thus, antiestrogen can induce remissions in some patients in the absence of the pituitary gland, and this constitutes additional palliation and provides evidence that estrogens can directly stimulate tumor growth. Four of 7 patients who obtained remissions from Tamoxifen obtained further improvement from hypophysectomy, and 1 of 8 patients who failed to benefit from antiestrogen improved after hypophysectomy. These results suggest that prolactin and growth hormone may also play a role in stimulating tumor growth in some patients.
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PMID:Treatment of breast cancer with antiestrogen: approach to medical hypophysectomy? 61 66

Estradiol receptors and glucose-6-phosphate dehydrogenase, an enzyme induced by estrogens, were measured in both benign and malignant human breast tumors. The mean glucose-6-phosphate dehydrogenase activity was higher in the malignant tumors than in the benign tumors. Tumors containing estradiol receptors contained higher activities of glucose-6-phosphate dehydrogenase than tumors without receptors. In breast carcinomas with and without estradiol receptors glucose-6-phosphate dehydrogenase gave 3 isoenzymes with very similar electrophoretic pattern after polyacrylamide gel electrophoresis. The results showed that although glucose-6-phosphate dehydrogenase was higher in estradiol receptor positive than in estradiol receptor negative tumors there was no significant correlation between the estradiol receptor concentration and glucose-6-phosphate dehydrogenase activity in human breast tumors.
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PMID:Estradiol receptors and glucose-6-phosphate dehydrogenase activity in human breast tumors. 83 20

A case report on an unusual hormone producing ovarian tumor in a 3 year old girl with sexual precocity is given. The serum values of Estradiol and Progesterone were similar to those of mature women during the luteal phase. The LH values were normal, the 17-Ketosteroids and 17-Hydroxycorticosteroids were near the upper limit of the normal range. At laparotomy a smooth, encapsulated tumor of the left ovary, 12 cm in diameter, was removed by unilateral salpingo-oophorectomy. Hormone analyses of the blood of the ovarian vein as well as of necrotic parts of the tumor showed values of 3450 and 2750 pg/ml Estradiol, and 70 000 and 75 000 pg/ml Progesterone respectively. Histiologically the tumor cells were growing in nests and broad columns, showing bizarre nuclei, abundant pathologic mitoses and patchy calcification. In places the tumor cells were forming follicle-like structures. Both the fat stain and the glycogen stain were positive. Histochemically the tumor showed a strong activity of 3beta-ol-Steroiddehydrogenase. Postoperatively the signs of sexual precocity disappeared soon. The patient is now without complaints for 3 years. The diagnosis of a juvenile granulosa cell tumor (Scully) was given. The endocrine relations between sexual steroids and gonadotropin before and after surgery are discussed.
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PMID:[An unusual hormone-active avarian tumor in a 3-year-old girl]. 101 97


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