Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of receptor cytoplasmic proteins to bind estrogens and androgens was studied in 25 biopsies obtained from cases of squamous-cell carcinoma and leukoplakia of oral cavity mucosa. Androgen receptors were more frequently identified in cancer than in leukoplakia whereas the estrogen receptor situation was reverse.
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PMID:[Cytoplasmic receptors of steroid sex hormones in malignant tumors amd precancerous processes of the human oral mucosa]. 381 7

The contribution of adrenal androgens to the maintenance and progression of so-called hormone-unresponsive prostatic carcinoma was studied in 20 patients with advanced relapsed disease. The role played by testicular androgens had been negated by prior orchiectomy or concurrent LHRH analogue therapy. Ketoconazole, an antifungal agent which inhibits adrenal and testicular androgenesis, administered in a dose of 400 mg 8-hourly, resulted in optimal suppression of adrenal androgens. The mean serum androstenedione concentration fell from 8.01 +/- 0.84 nMol/l to 1.55 +/- 0.25 nMol/l, P less than 0.001, and serum testosterone from 1.25 +/- 0.14 nMol/l to 0.36 +/- 0.06 nMol/l, P less than 0.01, after 6 months treatment. There was, however, no significant difference between patients receiving 400 and those receiving 200 mg. Androgen suppression resulted in six objective and ten subjective clinical responses. Ablation of both testicular and adrenal androgens can now be achieved using ketoconazole in combination with orchiectomy or LHRH analogues, but the high incidence of side effects may preclude its use in all patients with prostatic cancer. The results of this study support the concept of "total androgen ablation" as primary therapy in advanced prostatic cancer as a possible means of improving survival in this common malignancy.
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PMID:Objective responses to ketoconazole therapy in patients with relapsed progressive prostatic cancer. 394 56

Quantitative analyses of cytosolic steroid hormone receptors were performed on nine tumors from the transplantable rat prostatic adenocarcinoma R-3327H. Androgen receptors and estrogen receptors were found in eight of nine and five of six tumors, respectively. None of the tumours analyzed contained detectable progestin or glucocorticoid receptors (four and seven tumors, respectively). The apparent equilibrium dissociation constants for the androgen and estrogen receptors were 0.7-4.3 nM and 0.6-1.8 nM, respectively. The apparent equilibrium Bmax values (maximum number of binding sites) were 1,500-25,000 fmoles/gm tissue for the androgen receptor and 640 to 5,800 fmoles/gm tissue for the estrogen receptor. A comparison between the receptor contents of the R-3327H rat tumor and human benign prostatic hyperplasia and metastatic carcinoma of the prostate showed that the rat tumor was different from the human tissues in several respects. Hence, the search for an optimal animal model for prostatic carcinoma in man must be continued.
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PMID:Comparison of the R-3327H rat prostatic adenocarcinoma to human benign prostatic hyperplasia and metastatic carcinoma of the prostate with regard to steroid hormone receptors. 616 71

Testosterone and its active metabolite dihydrotestosterone exert their influence on target cells through a specific intracellular protein receptor. Structural abnormalities of this receptor lead to a diminished androgen action within the cell and result in the syndrome of androgen insensitivity. Androgen insensitivity is classified on the basis of whether the insensitivity is complete or partial and whether the androgen receptor is normally present (AR(+)), absent (AR(-)) or diminished (AR(+/-)). All patients with androgen insensitivity have normal or high plasma levels of testosterone and elevated serum LH. Patients with complete androgen insensitivity are phenotypically female. The clinical presentation of partial androgen insensitivity is variable, ranging from a minimal amount of virilization to a completely masculine appearance. All patients described with a syndrome of androgen insensitivity are infertile. The influence of androgen receptor function in the pathogenesis of benign prostatic hypertrophy is being investigated. Androgen receptor content is also being studied as a possible marker of responsiveness to hormonal therapy in prostatic carcinoma.
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PMID:Androgen receptors. 618 53

Saturable binding of androgens, glucocorticoids, and triiodothyronine was found in the 64-24 hormone-responsive rat mammary carcinoma cell line. Androgen receptors had a dissociation content (Kd) for methyltrienolone of 3.4 X 10(-10) M and a binding capacity of approximately 10,000 sites/cell in whole cells. 5 alpha-[3H]dihydrotestosterone (DHT) was specifically taken up into approximately 2,150 nuclear sites with an affinity of 8.3 X 10(-10) M when nuclei were isolated from whole cells incubated with [3H]DHT. Sucrose gradient centrifugation of cytosol prepared from these cells revealed a displaceable [3H]DHT-binding component which migrated at 8S. Sedimentation analysis with high salt gradients of nuclear extracts from cells incubated with [3H]DHT revealed a peak of radioactivity in the 4S region which was abolished by coincubation of the cells with excess nonradioactive methyltrienolone. Receptors for [3H]dexamethasone were more abundant (approximately 50,000 sites/cell) in whole cells and had a Kd of 7.5 X 10(-9) M, but the number of nuclear binding sites was similar to that for androgens. Specificity studies using unlabeled steroids showed that each of the two classes of steroid receptors had greater affinities for their appropriate hormones. High affinity receptors for estrogens and progestins were not detectable in these cells. Triiodothyronine receptors were demonstrable but at a very low binding capacity (1,100 sites/cell). The Kd of these receptors was 0.6 X 10(-10) M. Cytogenetic studies revealed 44 chromosomes/mitosis with several unique markers. These receptor and karyotypic features suggest that the 64-24 cells may be useful in studying androgen action on breast cancer independently of estrogen or progestin influence, as well as the effects of thyroid hormone and glucocorticoids on breast cancer cells.
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PMID:Receptor characteristics of the rat mammary carcinoma cell line 64-24. 625 64

Androgen receptors (AR) were studied in seminiferous tubule cytosol and testicular nuclear extracts prepared from testes of previously untreated elderly men undergoing orchiectomy as therapy for prostatic carcinoma. Cytosol exhibited high affinity (Kd = 0.8 nM), saturable binding of [3H]methyltrienolone; however, the synthetic progestin, promegestone was a stronger competitor for MT binding sites than were 5 alpha-dihydrotestosterone (DHT) or testosterone (T), suggesting the presence of progesterone-like binding sites. Addition of triamcinolone acetonide (TA) produced the usual relative steroid specificity for AR binding and reduced the measured AR binding capacity by 19 +/- 8% (Mean +/- SD, n = 3). The umber of MT binding sites was 30-40 fmol/mg protein, or an average of 65 fmol/g testis, and the equilibrium dissociation constant at 0 degrees C was 0.6-1.4 nM. In the presence of sodium molybdate, binding was stable for 40 h at 0 degrees C and the half-time of dissociation of the MT-AR complex was 12-16 h. The binding of salt extractable (600 mM KCl) nuclear sites to MT was saturable and was specific for androgens. The number of binding sites in nuclear extracts was 170 fmol/g testis and the apparent equilibrium dissociation constant was 4.2 nM. Thus, the binding of MT to human seminiferous tubule cytosol and testicular nuclear extract exhibits properties which are nearly identical to those of the prostate AR. Further study of this androphilic protein may provide insight into the role of androgen in normal and abnormal spermatogenesis in man.
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PMID:Evidence for an androgen receptor in the seminiferous tubules of the human testis. 633 54

Surgical adrenalectomy produces objective tumour regression in 50-60% of estrogen receptor-positive women with metastatic breast carcinoma. Additional responses to antiestrogens or further suppression of estrogens with aminoglutethimide after adrenalectomy suggest the possibility of continued adrenal steroid secretion even after surgical ablation. The use of sensitive and specific RIAs allows precise determination of the degree of hormone suppression after adrenalectomy and could provide documentation of nonsuppression or escape from suppression in individual patients. To evaluate the possibility of continued hormone secretion, we measured 14 hormones in 26 postmenopausal women with breast carcinoma before and after adrenalectomy. While the mean levels of androgens were markedly suppressed [dehydroepiandrosterone sulfate (DHEA-S), 99%, androstenedione, 94%; testosterone, 77%; dihydrotestosterone, 73%] after adrenalectomy, estrogen concentrations fell to a much lesser extent (plasma estrone, 73%; urinary estrone, 86%; plasma estradiol, 53%; urinary estradiol, 67%). Examination of data in individual patients revealed incomplete suppression in several women (less than 50% suppression of plasma estradiol in 14 of 25 patients, of urinary estradiol in 4 of 22, and of urinary estrone in 1 of 22). Androgen concentrations also fell incompletely after adrenalectomy in a few patients. Androstenedione concentrations were greater than 2 SD above the group mean in 2 of 23 patients, and in 2 of 25 patients, DHEA-S concentrations were also greater that 2 SD above the group mean. Serial measurements of hormones over a 1- to 3-yr period following surgery revealed escape from suppression over time (i.e. greater than 2-fold increase in hormone levels) in 7 of 26 women. The practical significance of the lack of suppression or of escape from inhibition was assessed by comparing estrogen levels in responders vs. nonresponders to surgical adrenalectomy. Of all steroids measured, greater suppression of only 1 hormone (urinary estrone) was observed in responders vs. nonresponders. These data indicate that adrenalectomy does not uniformly suppress circulating androgen and estrogen levels in postmenopausal patients. Women who initially suppress after adrenalectomy may show recovery of either androgen or estrogen levels with time.
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PMID:How effective is surgical adrenalectomy in lowering steroid hormone concentrations? 645 36

Modifications of three isolation methods were used to purify nuclei from an androgen-dependent cell line (AD) and two androgen-independent cell lines (AI1 and AI2) of the Shionogi mouse mammary carcinoma. Yields of nuclei, contamination of the nuclei by whole cells, monitoring of cytoplasmic tags by phase-contrast microscopy, and biochemical analyses were used to compare the methods. Purification with the cationic detergent cetylpyridinium chloride (CPC) resulted in greater yields of nuclei than purification of nuclei using Triton N-101. Purification by glycerol loading followed by hypotonic shock, although resulting in somewhat less whole cell contamination of the nuclei, yielded fewer nuclei per gram wet weight starting tissue. Phase-contrast microscopy showed the relative absence of cytoplasmic tags when nuclei were prepared by either the Triton N-101 or CPC methods. However, the yield of protein per nucleus was less when nuclei were prepared using CPC. Androgen uptake by nuclei of three cell lines was markedly reduced in those nuclei prepared by the CPC method as compared with those prepared by the Triton N-101 method. In the case of the AD tumour cell line nuclei prepared by the CPC method, both the affinity of the nuclei for dihydrotestosterone and the number of uptake sites were reduced when compared with AD tumour cell line nuclei prepared by the modified Triton N-101 method.
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PMID:The method used in purification of nuclei from three variant cell lines of the Shionogi mouse mammary carcinoma alters their uptake of dihydrotestosterone. 651 13

Mice bearing the androgen-responsive Shionogi mammary carcinoma SC115 were treated with different concentrations of testosterone to determine if regulation of growth by testosterone would affect the susceptibility of the tumor to eradication by drugs. Following s.c. injection of 2 X 10(6) cells, tumors grew to 3 g by 21 +/- 2.1 days in males (n = seven) and 30 +/- 2.4 days in females administered testosterone (n = ten). If androgen was withdrawn, tumors weighing 1 g regressed temporarily but resumed growing after a delay of 19 +/- 1.7 days in males and 6 +/- 3.2 days in females. A combination of cyclophosphamide (100 mg/kg) and Adriamycin (6.5 mg/kg), three i.p. injections 7 days apart, caused a tumor growth delay (TGD) of 5 +/- 3.8 days in males and 26 +/- 3.2 days in females. The combination of endocrine therapy and chemotherapy was superior to either treatment alone in males. Androgen withdrawal plus chemotherapy was additive; a submaximal dose of testosterone for tumor growth plus drugs was more effective, causing a TGD of 40 +/- 2.7 days. There were no significant differences in TGD in females receiving treatments singly or in combination, possibly due to the fact that tumors in females were more sensitive to drugs alone and less sensitive to testosterone alone than were tumors in males. To ascertain if combination therapy would be effective in females in an adjuvant situation, the same treatment regimens were administered 1 day after injection of 10(6) tumor cells. Under these conditions, hormonal manipulations combined with chemotherapy resulted in a longer TGD than either modality alone. Furthermore, submaximal doses of testosterone for growth plus chemotherapy induced a longer disease-free interval (no palpable tumors by 120 days in 12 of 12 mice) than did complete androgen withdrawal plus drugs (palpable tumors in 4 of 5 mice by 104 +/- 2.7 days). The results demonstrate that endocrine regulation of SC115 mammary tumor growth can alter responsiveness of the tumor to chemotherapy.
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PMID:Effects of endocrine regulation of growth of a mouse mammary tumor on its sensitivity to chemotherapy. 670 51

Effects of neonatal androgenization on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis infemale noninbred Sprague-Dawley rats are reported. Testosterone propionate (1.25 mg) was injected sc into 29 2-day-old rats. At 50 days of age, all rats were given 20 mg of DMBA through a stomach tube. In these androgenized rats, no corpora lutea were found in the ovaries and the induction of mammary carcinoma by DMBA was strongly suppressed, whereas the induction of mammary dysplasia was significantly accelerated in comparison with the neonatally intact controls. Mammary dysplasia in the androgenized group varied widely, with two kinds of macroscopically detectable tumor-forming lesions (solid and cystic) and with microscopic characteristics of acinar adenosis, fibrotic adenosis, fibrosis, intraductal papillary proliferative lesions, and epithelial cysts. The earliest lesions of mammary dysplasia observed were acinar adenosis nodules and microcysts, both of which appeared as multifocal phenomena as early as 25 days after administration of DMBA.
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PMID:Induction of mammary dysplasia and mammary carcinoma in neonatally androgenized female rats by 7,12-dimethylbenz[a]anthracene. 676 73


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