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

Suramin, a drug known to have antiparasitic effects, has been previously shown to have adrenocorticolytic activity in primates. We now confirm preferential accumulation of this compound in the normal adrenal gland, evaluate its in vitro effect against two human adrenocortical carcinoma cell lines (SW-13 and NCI-H295), and report the clinical activity of suramin in 17 patients with metastatic adrenocortical carcinoma. Inhibition of colony formation occurred in both adrenal cell lines in vitro at concentrations that are clinically achievable in humans. In addition, suramin concentrations as low as 100 micrograms/mL were able to inhibit glucocorticoid, mineralocorticoid, and androgen production by the NCI-H295 cell line. Of 16 patients with adrenocortical carcinoma now evaluable for tumor response, 2 achieved a partial response, 2 had a minor response, and 5 remained with stable disease for periods ranging from 3-10 months; the remainder progressed. One of 7 patients with excessive steroid hormone production achieved a partial normalization of her steroid levels for the duration of suramin therapy in the setting of radiographic disease stabilization. An additional patient treated off-study for lack of radiographically measurable disease, achieved complete normalization of plasma aldosterone levels. We conclude that suramin preferentially accumulates in adrenal cells, induces cytotoxicity and significant down-regulation of steroid hormone production in vitro, and has some therapeutic efficacy as a single agent in patients with metastatic adrenocortical carcinoma.
 ...
PMID:Suramin in adrenal cancer: modulation of steroid hormone production, cytotoxicity in vitro, and clinical antitumor effect. 238 Mar 44

A 62-year-old man was admitted to our hospital in Oct. 1986, because of easy fatigability, generalized pigmentation and lymph node swelling. Radiological examination showed massive adrenal tumor and two lung tumors. Endocrinological findings showed cortisol 8.3 micrograms/dl, aldosterone 35.3 ng/dl, ACTH 348 pg/ml, and non reacting pattern was observed in ACTH-overloading test, suggesting a presence of Addison's disease. A diagnosis of malignant lymphoma (Non-Hodgkin's lymphoma, diffuse large cell type) was made by lymph node biopsy, and radiotherapy to bulky bilateral adrenal tumors and cervical lymph nodes was performed with some response. Then, treatment with VEPA and PEP-VP regimens were carried out, and adrenal tumor became remarkably small in size. However, adrenal function did not recover. He relapsed in Jan. 1987 and died of multiple organ failure.
 ...
PMID:[Malignant lymphoma associated with Addison's disease]. 238 Oct 61

Adrenal venous sampling of blood was performed for nine patients with aldosterone-producing adenoma (APA). Measurement of adrenal venous aldosterone is useful for localization of APA but difficult, because catheterization of the right adrenal vein is not easy, and the blood is diluted by nonadrenal flow. To solve these problems, levels of aldosterone (A; ng/dl) and cortisol (C; micrograms/dl) were measured in samples from the left adrenal vein (LAV) and the inferior vena cava (IVC), and the LAV A/C and (LAV A/C)/(IVC A/C) ratios were calculated. These ratios were also obtained for 16 patients with essential hypertension. The adenoma could be localized in three of the nine cases by the measurement of aldosterone alone, but the use of a LAV A/C ratio greater than 5 x 10(-3) and a (LAV A/C)/(IVA A/C) ratio less than 1.0 as criteria separated the patients into those with a left APA, right APA, or essential hypertension. Consequently, adrenal venous sampling and the calculation of these ratios enables preoperative localization of APA with more accuracy, especially when the tumor is small or the result of CT and adrenal scintigraphy is not consistent.
 ...
PMID:Localization of aldosterone-producing adenoma: venous sampling in primary aldosteronism. 238 50

A 64-year-old man with sudden onset of quadriplegia due to marked hypokalemia was referred to our clinic with suppressed plasma renin activity in the presence of a low aldosterone level. Computerized tomography demonstrated a left adrenal adenoma, shown on adrenal scintigraphy to be functioning. The elevated basal level of plasma corticosterone and its increased response to 1-24 adrenocorticotropic hormone suggested the tumor produced corticosterone. The surgical specimen was a benign adrenocortical adenoma with excess content of corticosterone and 18-hydroxycorticosterone.
 ...
PMID:Adrenal adenoma with excess secretion of corticosterone and 18-hydroxycorticosterone. 238 39

The acute blockade of the renin-angiotensin system has been made it possible to investigate its role in the maintenance of blood pressure and aldosterone secretion in normotensive and hypertensive subjects. The administration of saralasin or captopril and, in the near future, of renin inhibitors induces a fall in blood pressure that is variable from one subject to the other according to the sodium balance and the level of activation of the system. These blockers also decrease the angiotensin II-dependent aldosterone production and increase renin secretion according to the circulating level of angiotensin II and the functional state of adrenal and juxtaglomerular receptors. In practice the definition of an abnormal response to renin-angiotensin blockade is difficult to define precisely, but the hypotensive effect has been tentatively used for the diagnosis of renin-dependent hypertension, especially renovascular hypertension and primary hyperaldosteronism. In renal artery stenosis the most convincing results mainly concern the lateralization of an abnormal unilateral renin secretion, which is potentiated by an acute blockade of the renin-angiotensin system. The acute administration of converting enzyme inhibitor is also useful to detect the absence of decrease in plasma aldosterone, which is characteristic of a solitary tumor or of other anatomical and functional disorders of the adrenal glands.
 ...
PMID:Acute inhibition of the renin-angiotensin system: interest and limits to detect surgically curable hypertension. 241 19

The effects of synthetic human atrial natriuretic peptide (ANP) on the release of catecholamines, aldosterone, or cortisol were observed in human adrenal tumors obtained surgically from patients with pheochromocytoma, primary aldosteronism, or Cushing's syndrome, respectively. Each tumor tissue or adjacent normal cortical tissue was sectioned into slices, which were incubated in medium-199 in the presence or absence of adrenocorticotrophin (ACTH) and ANP. The amounts of epinephrine, norepinephrine, aldosterone, or cortisol released into the medium were measured. Existence of ANP receptors on the adrenal tissues was examined by binding assays, affinity labeling, and immunohistochemistry. Release of catecholamines from pheochromocytoma tissues was inhibited by ANP, and the presence of the ANP receptor on pheochromocytoma was further demonstrated by both binding assays and affinity labeling; Scatchard analysis revealed a single class of binding sites for ANP with a Kd of 1.0 nM and a Bmax of 0.4 pmol/mg of protein and the molecular size was estimated as 140 and a 70 kDa under nonreducing and reducing conditions, respectively. The presence of ANP receptors in pheochromocytoma was demonstrated by immunohistochemistry. ANP inhibited both basal and ACTH-stimulated aldosterone secretion in the slices of normal cortex, and localization of ANP receptors in zona glomerulosa cells was also demonstrated. However, ANP did not inhibit basal and ACTH-stimulated aldosterone and cortisol secretion in both tissue slices from aldosteronoma and Cushing's adenoma. Consistent with these observations, the absence of ANP receptors in adenoma tissues was determined by binding assays, affinity labeling, and immunohistochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Functional atrial natriuretic peptide receptor in human adrenal tumor. 247 57

A 54-yr-old woman with the symptoms of primary reninism, i.e. hypertension, metabolic alkalosis and elevated levels of plasma renin activity (PRA) and aldosterone, is described. She had an ileal cancer secreting active and inactive renin. The symptoms markedly improved after resection of the tumor. In the tumor active and inactive renin were proved to be present by an assay of angiotensin I formation in the presence and absence of renin antibody, and renin immunoreactivity was found immunohistochemically. The mRNA coding for the renin precursor was identified in the RNA-rich extract of the tumor by blot hybridization analysis with the human renin cDNA as a probe. The mRNA from the tumor was shown to be identical in molecular size to that from the human kidney by agarose gel electrophoresis. This is the first description of an ectopic renin-producing ileal carcinoma and the first demonstration of renin mRNA in the tumor tissue.
 ...
PMID:Ectopic production of renin by ileal carcinoma. 254 46

Plasma 18-hydroxycorticosterone (18-OHB) and aldosterone responses to angiotensin II (AII) and ACTH were examined in 2 patients with a 18-OHB-producing tumor (18-OHBPT) versus those in 8 patients with a aldosterone-producing adenoma (APA), 7 patients with low renin essential hypertension (LREH) and 10 normal subjects. Plasma 18-OHB and aldosterone levels and the 18-OHB: aldosterone ratio were high in patients with an APA and normal in patients with LREH. In patients with a 18-OHBPT, plasma 18-OHB and aldosterone levels were high and normal, respectively, resulting in a 2-fold greater 18-OHB: aldosterone ratio than that in patients with an APA. Patients with an APA had a blunted response of plasma 18-OHB and aldosterone to AII and a supranormal response of these corticoids to ACTH. Patients with LREH had a supranormal response of plasma 18-OHB and aldosterone to AII and a normal response of these corticoids to ACTH. In patients with a 18-OHBPT the responses of both plasma 18-OHB and aldosterone to AII and ACTH closely resembled those in patients with an APA but not in patients with LREH. These data suggest that 18-OHBPT may be a variant of aldosteronomas, producing a large amount of 18-OHB and a small amount of aldosterone.
 ...
PMID:Altered responses of plasma 18-hydroxycorticosterone and aldosterone to angiotensin II and adrenocorticotropin in patients with a 18-hydroxycorticosterone-producing tumor. 255 39

Previous studies have suggested a role for glucocorticoids in the differentiation of the acinar pancreas. We have now used the rat tumor cell line AR42J, derived from the acinar pancreas, to directly study this effect of glucocorticoids in vitro. The steroid hormones dexamethasone, corticosterone, aldosterone, and progesterone, but not estrogen, increased both the amylase content and the number of secretory granules of these cells. The potencies of the steroids were directly related to their effectiveness as glucocorticoids; dexamethasone was the most potent hormone and gave maximal effects at 100 nM. Morphometric analyses revealed that dexamethasone increased the volume density of granules 5.5-fold from 0.20 +/- 0.08 to 1.10 +/- 0.20% (n = 4) of the cytoplasmic volume. Dexamethasone treatment also increased the volume density of rough endoplasmic reticulum 2.4-fold from 1.20 +/- 0.09 to 2.86 +/- 0.30% (n = 5) of the cytoplasmic volume. After 48 h of dexamethasone treatment the cellular content of amylase increase eightfold from 2.8 +/- 0.4 to 22.6 +/- 3.8 U/mg protein (n = 6). This effect of dexamethasone was discernible after 12 h of incubation and approached maximal stimulation after 72 h of incubation. The increases in cellular amylase content were due to increased amylase synthesis as shown by specific immunoprecipitation of [35S]methionine-labeled proteins. Moreover, in vitro translation of cellular mRNA indicated that dexamethasone treatment increased amylase mRNA. Dexamethasone treatment also led to increased secretion of amylase in response to the secretagogue cholecystokinin. These data indicate, therefore, that glucocorticoids induce a more highly differentiated phenotype in AR42J pancreatic cells, and they suggest that glucocorticoids act via the enhanced transcription of specific mRNAs for acinar cell proteins.
 ...
PMID:Glucocorticoids increase amylase mRNA levels, secretory organelles, and secretion in pancreatic acinar AR42J cells. 257 57

CT is the imaging procedure of choice for the detection of most suspected adrenal masses. But except for some patients with acute adrenal hemorrhage or fat-containing myelolipoma, the precise histologic nature of an adrenal mass is not apparent from the CT image. MIBG radionuclide scanning is useful in some patients with pheochromocytoma, whereas bilateral adrenal venous sampling for hormone assay is necessary for correct lateralization in some patients with a small aldosterone-producing adenoma. The potential value of MR imaging in the characterization of adrenal masses, especially to distinguish benign adrenal cortical adenomas from metastatic disease, is now under investigation. Currently percutaneous aspiration biopsy is still necessary to make this distinction in patients with an adrenal mass and a known extra-adrenal primary neoplasm.
 ...
PMID:Overview of adrenal imaging/adrenal CT. 269 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>