Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In postmenopausal women with breast cancer, aromatase, which is the enzyme converting androstenedione to estrone and testosterone to estradiol, is the rate-limiting step in estrogen biosynthesis. The currently available aromatase inhibitor, aminoglutethimide, effectively blocks estrogen production and products tumor regression in patients previously treated with tamoxifen. This drug, however, produces frequent side effects and blocks steroidogenic steps other than the aromatase enzyme. Thus, newer aromatase inhibitors with greater potency and specificity are under intense study. More than 20 such compounds have recently been developed. In several clinical trials, 4-hydroxyandrostenedione, given parenterally, has been highly active and specific for aromatase inhibition in patients with breast cancer. In two large recent studies, one-third of heavily pretreated woman experienced objective tumor regression with this therapy. CGS 16949A, a newer agent, is also in Phase III clinical trials. This compound is an imidazole derivative with nearly 1000-fold greater potency than aminoglutethimide. An initial Phase I study compared the potency of 0.6-16 mg daily in 12 postmenopausal women and found maximal suppression of urinary and plasma estrogens with 2 mg daily. The degree of inhibition was similar to that induced by aminoglutethimide or by surgical adrenalectomy. No CNS, hematologic or biochemical toxicity was observed. A larger Phase II study in 54 patients confirmed this high degree of potency of CGS since a plateau effect was observed at the 1.8, 2 and 4 mg daily doses. The endocrine effects were not absolutely specific as a blunting of ACTH-stimulated but not basal aldosterone levels were observed. This and other emerging aromatase inhibitors offer promise as pharmacologic methods to inhibit estrogen production specifically and without side effects.
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PMID:Recent progress in development of aromatase inhibitors. 214 3

Adenomas of the adrenal cortex which produce aldosterone (APA) are among the surgically correctible causes of hypertension accounting for 0.5 to 1.0% of all hypertensive etiologies. The adenomas have a 5:1 predilection for women and generally present with hypertension or profound hypokalemia. A low plasma renin activity completes the triad for primary hyperaldosteronism which could be caused by adrenocortical cancer, a neoplasm with an average diameter of 12 cm, or idiopathic hyperaldosteronism (IHA), a bilateral hyperplasia of the zona glomerulosa of the adrenal cortex which responds poorly to surgical resection. The adenomas are small (2 cm) but can be localized by imaging or selective venous sampling. Resection has a high success rate with minimal morbidity.
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PMID:Aldosterone-producing tumors (Conn's syndrome). 218 43

To identify tissue- and hormonal-specific DNA control cis-elements in the rat gene, we have constructed fusion genes consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone (hGH) reporter gene and have introduced them into a subclone of rat pancreatic islet tumor cell line (1056A) which expresses the highest level of angiotensinogen mRNA. As a negative control, we have also introduced them into a human choriocarcinoma cell line (JEG-3), which does not express the endogenous angiotensinogen gene. The level of the expression of these fusion genes in these cells was determined by the level of immunoreactive hGH secreted into the culture medium. The expression of angiotensinogen-growth hormone (ANG-GH) fusion genes, pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), and pOGH (ANG N-35/+18) was 1.0, 1.8, 1.5, 12.0 and 3.0-fold higher, respectively, than the promoterless growth hormone expression vector (pOGH). The addition of dexamethasone (10(-6) M), aldosterone (10(-5) M), and thyroid hormone, L-T3 (10(-7) M), stimulated the expression of pOGH (ANG N-1498/+18) by 4.0-, 2.5-, and 2.0-fold above the control level, respectively. Combination of dexamethasone (10(-6) M), L-T3 (10(-7) M), and ethinyl-estradiol (10(-6) M) stimulated the expression of the pOGH (ANG N-1498/+18) to greater than 10-fold over the control. Ethinyl-estradiol (10(-6) M) or progesterone (10(-6) M) alone had no effect on the expression of the pOGH (ANG N-1498/+18).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular cloning and expression of the rat angiotensinogen gene. 220 13

The case of a 39-year-old woman with Cushing's syndrome, hypertension and severe hypokalemia, caused by a unilateral adrenal adenoma composed of cells of the zona fasciculata histological type, is described. Plasma renin activity, plasma levels of mineralocorticoids and the aldosterone secretion rate were determined before and after surgical removal of the adenoma. The tumor appeared to produce autonomously cortisol as well as corticosterone, 18-hydroxycorticosterone and aldosterone. This condition has not previously been described in the literature and might be explained by strong expression of the full spectrum of activities of the mitochondrial enzyme P450 C11 by the tumor cells. Interestingly, despite hyperaldosteronism, plasma renin activity was not suppressed.
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PMID:Concurrent hypercortisolism and hyperaldosteronism due to an adrenal adenoma. 223 30

A cDNA clone encoding human aldosterone synthase cytochrome P-450 (P-450aldo) has been isolated from a cDNA library derived from human adrenal tumor of a patient suffering from primary aldosteronism. The insert of the clone contains an open reading frame encoding a protein of 503 amino acid residues together with a 3 bp 5'-untranslated region and a 1424 bp 3'-untranslated region to which a poly(A) tract is attached. The nucleotide sequence of P-450aldo cDNA is 93% identical to that of P-450(11) beta cDNA. Catalytic functions of these two P-450s expressed in COS-7 cells are very similar in that both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. However, they are distinctly different from each other in that P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone while P-450(11)beta substantially fails to catalyze the reaction to form aldosterone. These results suggest that P-450aldo is a variant of P-450(11)beta, but this enzyme is a different gene product possibly playing a major role in the synthesis of aldosterone at least in a patient suffering from primary aldosteronism.
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PMID:Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism. 225 20

The captopril test was used to make a differential diagnosis of various types of primary aldosteronism. After captopril, there was no change in the activity of the renin-angiotensin-aldosterone system only in the group of patients with aldosterone-producing adenomas in a histological variant of "adenoma and atrophy". The findings suggest that aldosterone secretion regulation is autonomic in the adenoma unassociated with the function of the renin-angiotensin-aldosterone system only in the case of isolated adenoma with a histological variant of adenoma and atrophy. In patients with aldosterone-producing adenomas in the presence of the variant "adenoma and hyperplasia", aldosterone secretion retains sensitivity to the renin-angiotensin-aldosterone system as in patients with idiopathic hyperplasia and hypertensive disease, which indicates that it is possible to differentiate isolated "adenoma and atrophy" from hypertensive disease and idiopathic hyperplasia, despite its combination with tumor by using the captopril test.
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PMID:[Significance of single-dose captopril test in the differential diagnosis of primary aldosteronism]. 229 Feb 81

The adrenal function mainly cortical one, was evaluated in 16 patients with incidentally discovered adrenal masses. Pathological examination was possible in 15 cases. The finding consisted of adrenocortical adenoma in 9, adrenocortical nodular hyperplasia in 1, adrenal medullary hyperplasia in 1, metastatic tumor in 2 and adrenal cyst in 2. Another case of adrenal cyst was diagnosed by percutaneous puncture. In all cases peripheral levels of plasma cortisol, plasma aldosterone concentration and plasma renin activity were normal. Plasma catecholamine levels were also normal except in a case of adrenal medullary hyperplasia. On the other hand, the cases of adrenocortical adenoma displayed elevation of urinary 17-hydroxycorticosteroids in 6/9 (67%), a loss of plasma cortisol circadian rhythm in 3/7 (43%) and insufficient suppression on dexamethasone (DXM) suppression test in 6/9 (67%). Their adrenal scintigraphy (with 131I-6 beta-iodomethyl-9-nor-cholest-5 (10)-en-3 beta-ol) revealed an increased ipsilateral up-take and insufficient suppression after DXM in all, while a diminished contralateral up-take in 4/9 (44%). These data suggested that a considerable number of adrenal incidentalomas may not be truly "non-functioning". Two patients with cortical adenoma experienced post operative adrenal insufficiency (25%). It was suggested that a pre-operative loss of plasma cortisol circadian rhythm was the most prognosticating of the post operative adrenal insufficiency, rather than insufficient DXM suppression or scintigraphic absence of contralateral up-take. Among the patients with malignancy, differentiation of incidental adrenal adenoma from metastasis by size alone may not be reliable.
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PMID:[Clinical experience of adrenal incidentaloma with particular reference to adrenal cortical function]. 229 17

A 58-yr-old man presented with gynecomastia and elevated serum estrogens. The diagnosis of an estrogen-secreting adrenal tumor was made based upon the finding of a 4-cm left adrenal mass, elevated levels of estradiol in peripheral and left adrenal venous blood, and increased urinary 17-ketosteroids. In addition to marked elevations in estradiol and 17-ketosteroids there was an increased baseline level of 11-deoxycorticosterone and a slightly decreased level of 18-hydroxycorticosterone, suggesting the possibility of impaired P450c11 activity. The effect of ketoconazole administration (600 mg/day) for 4 weeks was studied. Urinary free cortisol and 17-ketosteroid excretion and serum testosterone levels fell acutely (1 week). Serum estradiol levels decreased gradually over the 4-week course. Plasma aldosterone levels were essentially unaltered and 18-hydroxcorticosterone levels fell gradually, but there were marked increases in 11-deoxycorticosterone and corticosterone. Coincident with the increase in 11-deoxycorticosterone there was an increase in blood pressure and a transient fall in serum potassium. We conclude that ketoconazole administration may result in a hypermineralocorticoid state. Therefore, the usefulness of ketoconazole therapy for steroid hormone-producing neoplasms will depend upon the individual tumor's steroidogenic profile.
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PMID:Feminizing adrenocortical tumor: steroid hormone response to ketoconazole. 229 65

An ectopic adrenal cortical adenoma containing high levels of androstenedione but without clinically detectable virilizing effects was found in the spinal intradural space of an 8-year-old girl. The tumor, which was located at the L2 level, manifested itself clinically by a short history of bilateral leg pain. It was well encapsulated; therefore, total surgical removal was accomplished. The light microscopic appearance of the tumor was typical of adenomatous adrenal cortical tissue. Ultrastructurally, it also showed characteristic features of steroid-producing tumors, including very abundant smooth endoplasmic reticulum and giant mitochondria with tubulovesicular and circular cristae. Frozen tissue analyzed by radioimmunoassay was found to contain almost 20 times the normal tissue level of androstenedione. There was no elevation of cortisol or aldosterone levels in the tumor. Postoperative magnetic resonance imaging (MRI) scan of the retroperitoneum showed no abnormalities in the patient's adrenal glands. Serum androstenedione levels were normal. We postulate that the adenoma developed from congenital ectopic rests of intraspinal adrenal tissue. Although ectopic occurrence of adrenal cortical tissue has been recorded in other areas, neither such rests nor tumors developing from them have been previously reported within the spinal canal.
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PMID:Adrenal cortical adenoma in the spinal canal of an 8-year-old girl. 232 53

The case of a young woman with primary aldosteronism originating extraadrenally--ovarian tumor--is reported. Clinically she presented with uncontrolled hypertension. Biochemical and hormonal profiles showed features of aldosteronism. The primary was found in the left ovary. Following excision of the tumor, aldosteronism regressed completely. Microscopically, the tumor was of the lipid cell type. Nine months after surgery she is asymptomatic and well. Review of the literature uncovered three previous reports of aldosterone-secreting ovarian tumors.
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PMID:Autonomous aldosterone-secreting ovarian tumor. 234 75


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