Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine cells are thought to have a regulatory role in prostatic epithelial growth and may be prognostically useful in prostatic adenocarcinoma. To determine the extent of neuroendocrine differentiation in high-grade prostatic intraepithelial neoplasia (PIN), a putative precursor of cancer, we studied the immunohistochemical expression of 10 markers in 26 radical prostatectomy specimens with PIN and adenocarcinoma. Expression was measured as mean percent of positive cases and positive high-power (x40) fields. The highest percentage of cases showed immunoreactivity for serotonin (73%, PIN; 54%, carcinoma), neuron-specific enolase (NSE) (67%, PIN; 46%, carcinoma), chromogranin (62%, PIN; 65%, carcinoma), and human chorionic gonadotropin (hCG) (30%, PIN; 22%, carcinoma); the remaining markers showed immunoreactivity in fewer than 5% of cases (somatostatin, calcitonin, corticotropin) or in no cases (thyrotropin, prolactin, and glucagon). At least one of the markers was present in 88% of cases of PIN and 92% of carcinoma. Non-neoplastic epithelial cells expressed serotonin, NSE, chromogranin, and hCG in every case, and the expression was significantly greater than in PIN and cancer. Stepwise regression analysis revealed the following positive correlations: chromogranin expression in PIN and patient age, NSE expression in cancer and number of lymph node metastases, and hCG expression in cancer and percentage of Gleason pattern 5; serotonin expression in PIN and cancer did not correlate with any of the clinical and pathologic factors. Neuroendocrine differentiation is downregulated in prostatic carcinogenesis, with intermediate levels of expression in PIN compared with normal cells and carcinoma.
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PMID:Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma. 797 47

Carcinoid of the thymus rarely occurs during childhood. The authors identified eight cases in patients younger than 17 years of age. All were associated with Cushing syndrome. Adrenocorticotropic hormone (ACTH) produced by the tumor may be released intermittently, delaying the findings of Cushing syndrome. The authors describe a case of ectopic ACTH production in a teenaged boy who had longstanding hyperpigmentation, increased ACTH levels, and normal cortisol levels. Magnetic resonance imaging of the pituitary had normal findings. Subsequently, severe Cushing syndrome developed. Computed tomography (CT) scans of the chest showed a mediastinal mass that proved to be a thymic carcinoid. The lesion was inoperable. Radiation and chemotherapy were of limited benefit. Metyrapone was used to control hypercortisolism. The patient died with extensive metastases 6 years after initial presentation. CT scans of the chest should be performed in an attempt to localize ectopic ACTH-producing tumors. Surgical excision of the lesion is the treatment of choice. Control of hypercortisolism is essential.
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PMID:Adrenocorticotropic hormone--producing thymic carcinoid in a teenager. 838 Jan 12

The effects of somatostatin and its analogs have been studied in different subclasses of patients with Cushing's syndrome (due to Cushing's disease, ectopic corticotropin [ACTH]- and/or corticotropin-releasing hormone [CRH]-secreting tumors, or ACTH-independent Cushing's syndrome) and in patients with Nelson's syndrome. In most patients with untreated Cushing's disease, octreotide does not suppress ACTH release, a finding that is supported by in vitro studies. However, octreotide or somatostatin inhibits pathological ACTH secretion in Nelson's syndrome. Short-term octreotide treatment has caused a significant initial response (decreased serum cortisol, ACTH, and cortisoluria) in 24 of 38 (64%) patients with ectopic ACTH/CRH Cushing's syndrome, and long-term treatment caused a persistent response in 10 of 14 (71%) cases. Pentetreotide scintigraphy may help to identify those patients with ectopic ACTH/CRH tumors who will have an initial response to octreotide, and is useful for locating ectopic ACTH/CRH-secreting tumors and their metastases. To date, octreotide has been shown to temporarily suppress gastric inhibitory peptide (GIP)-induced cortisol secretion in GIP-dependent (ACTH-independent) Cushing's syndrome, but has not shown any therapeutic benefit in other forms of ACTH-independent Cushing's syndrome.
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PMID:Is there a role for somatostatin and its analogs in Cushing's syndrome? 876 91

Infection with the human immunodeficiency virus (HIV) is associated with a high incidence of cancers. This relationship does not appear to be due to a direct effect of the virus, and may be mediated by neuroimmune interactions since the HIV glycoprotein, gp120, enters the brain soon after infection with HIV, and intracerebroventricular (i.c.v.) infusion of gp120 suppresses aspects of cellular and tumor immunity. It has been speculated that this suppression may be attributed to the release of interleukin-1 (IL-1) in the brain induced by gp120. Using an in vivo tumor model, we examined the effect of centrally administered gp120 on tumor metastasis and lung clearance of mammary adenocarcinoma (MADB106) tumor cells in rats, and the role played by brain IL-1 in mediating these effects. We demonstrate that central administration of gp120 (4 microg) significantly (p<0.05) increased the retention of tumor cells in the lungs and significantly (p<0.02) enhanced the development of tumor metastases. Central administration of IL-1beta (10 ng) also significantly (p<0.05) increased retention of tumor cells in the lungs. The effect of gp120 on lung retention of tumor cells was blocked by co-administration of alpha-melanocyte stimulating hormone (alpha-MSH, 20 ng), a hormone that blocks many of the biological effects of IL-1, or the IL-1 receptor antagonist (50 microg). Given that systemic administration of gp120 or IL-1beta had no effect on the retention of tumor cells in the lungs, these findings indicate that gp120-induced secretion of IL-1 within the brain most likely mediates the effects of gp120 on tumor metastasis. These findings suggest a possible neuroimmune mechanism to account for the increased incidence and aggressiveness of tumors in HIV-infected patients.
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PMID:Intracerebral HIV glycoprotein (gp120) enhances tumor metastasis via centrally released interleukin-1. 950 52

We have examined the effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on invasive ability of murine melanoma cell lines with different metastatic potential in a Matrigel invasion assay. alpha-MSH potently blocked the invasion of B16-BL6 cells with highly metastatic potential in a concentration-dependent manner, whereas it was less effective in inhibiting the invasion of weakly metastatic B16-F1 cells. Pretreatment of B16-BL6 cells with alpha-MSH resulted in a decrease of the adhesiveness to fibronectin and laminin substrates in a time-dependent fashion. As assessed by zymographic analysis, alpha-MSH partially inhibited the production of matrix metalloproteinase (MMP)-2 and -9 from both cell lines to a similar degree without affecting the degradative activity of these MMPs. alpha-MSH was more potent in inhibiting the migration of B16-BL6 cells towards both fibronectin- and laminin-coated substrates than that of B16-F1 cells. The growth and morphology of B16-BL6 cells were not changed after a 7-day incubation with alpha-MSH. The number of lung tumor colonies markedly decreased when B16-BL6 cells were coinjected intravenously with 10(-6) M alpha-MSH. However, alpha-MSH had no effect on the experimental lung metastases by B16-F1 cells. These results suggest that alpha-MSH suppressed the invasive and metastatic properties of B16 melanoma cells, and the degree of inhibition was associated with metastatic potential of B16 melanoma cells.
Invasion Metastasis 1997
PMID:Alpha-melanocyte-stimulating hormone blocks invasion of reconstituted basement membrane (Matrigel) by murine B16 melanoma cells. 956 Oct 27

We have previously reported high immunoreactive alpha-MSH (IR-alpha-MSH) concentrations in melanoma patients' plasma, as well as significant amounts in melanoma metastases and cells grown in culture. Necrosis within the melanoma tumour leads to a massive proteolysis of intracellular proteins and release of cell content: this might significantly contribute to the elevated IR-alpha-MSH plasma levels measured in melanoma patients. To test this hypothesis, we studied the necrosis-related release of MSH from human melanoma cells, using a specific radioimmunoassay. The studies of fine-needle biopsies indicated that most of the human melanoma tumour exudates tested contained very high MSH concentrations (> 500 pg/ml; 14/15), while plasma levels were generally normal (< or = 25 pg/ml; 10/15). The level in an exudate from a non-melanoma tumour type was < 40 pg/ml. In vitro studies showed that release of the IR-alpha-MSH was time- and temperature-dependent, and related to cell death.
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PMID:alpha-Melanotropin immunoreactivity in human melanoma exudate is related to necrosis. 964 Feb 35

We reviewed the clinical features, essential laboratory data, pituitary imaging findings (computerized tomography and magnetic resonance imaging), management, and outcome of 353 consecutive patients with the presumptive diagnosis of pituitary tumor investigated from January 1984 through December 1997 at University Hospital, Lausanne, Switzerland. In 18 cases primary empty sella turcica was diagnosed, and in 13 cases of pseudacromegaly there were no endocrine abnormalities. The remaining 322 patients disclosed abnormal pituitary masses, including 275 pituitary adenomas, 18 craniopharyngiomas, 6 cases of primary pituitary hyperplasia, 6 intrasellar meningiomas, 6 cases of distant metastases, 4 intrasellar cysts, 2 chordomas, 1 primary lymphoma, and 1 astrocytoma. Biologic data and immunohistochemical analysis of the excised tissues demonstrated that prolactinomas and nonsecreting adenomas (NSAs) were the most frequent pituitary tumors (40% and 39%, respectively), followed by somatotropic adenomas with acromegaly (11%) and Cushing disease (6%). In contrast with the vast majority of NSAs, which significantly expressed glycoprotein hormones in tissue without secreting them, there was a small group of glycoprotein hormone-secreting adenomas (2%), which had a more severe clinical course after surgery. Thirty-eight pituitary masses were incidentally discovered, most of them NSAs. The expansion of pituitary adenomas into the right cavernous sinus was twice as frequent as to the left cavernous sinus. For the differential diagnosis of hyperprolactinemia, basal prolactin (PRL) levels above 85 micrograms/L, in the absence of renal failure and PRL-enhancing drugs, and a PRL increment of less than 30% after thyrotropin-releasing hormone (TRH) accurately ruled out functional hyperprolactinemia due to NSA, and were typical of prolactinomas. For screening and follow-up of acromegaly, basal growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, as well as the paradoxical GH response to TRH (present in 2/3 acromegalic patients), could be used as convenient tools, but the most accurate test for diagnosis and prediction of outcome after therapy was GH (lack of) suppression during oral glucose tolerance test. In Cushing disease, single evening plasma cortisol was as good as the overnight dexamethasone suppression test for screening, and a combined dexamethasoneovine corticotropin-releasing hormone (oCRH) test was as accurate as the long dexamethasone suppression test to confirm the diagnosis. Bilateral inferior petrosal sinus catheterization coupled with oCRH test confirmed the pituitary origin of excess adrenocorticotropic hormone (ACTH) in all patients, including those with normal pituitary on magnetic resonance imaging (50% of the cases). However, this procedure failed to predict tumor localization correctly within the pituitary in 21% of patients. Pituitary cysts, meningiomas, and craniopharyngiomas with an intrasellar component were correctly diagnosed based on pituitary imaging in 75%, 67%, and 44% of cases, respectively. The remainder, as well as the cases of pituitary hyperplasia, metastases, and other less frequent pathologies, were initially diagnosed as NSAs or as masses of unknown nature. When surgery was indicated, pituitary adenomas and other intrasellar masses were operated on by the transsphenoidal route, with the exception of 100% of meningiomas, 83% of craniopharyngiomas, and 10% of NSAs, which were operated on by the transcranial route. Favorable late surgical outcome of prolactinomas could be predicted by a restored PRL response to TRH. However, dopamine agonist (DA) therapy, usually resulting in satisfactory control of PRL levels and in tumor shrinkage, progressively displaced surgery as primary treatment for prolactinomas throughout the study period. After full-term pregnancy, the size of prolactinoma decreased in 7 of 9 patients, and PRL was normal in 2. Surgery was the first treatment for NSAs, with a tumor rela
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PMID:Diagnosis, treatment, and outcome of pituitary tumors and other abnormal intrasellar masses. Retrospective analysis of 353 patients. 1042 6

Adrenal cortical carcinoma (ACC) is a rare neoplasm that affects all age groups, with a bimodal peak of incidence, in young individuals in the first decade or two of life and in older subjects in the fifth to seventh decades. It may be clinically "functional" with Cushing's syndrome, virilization, or feminization, or it may be "nonfunctional." We report on the case of a 42-yr-old woman who complained of abdominal pain and a large adrenal tumor measuring 20 cm in size. No endocrine symptoms were observed. Laboratory tests showed increased levels of adrenocorticotropic hormone (ACTH), serum cortisol, and urinary free cortisol. Cytohistologic features were typical of ACC. A striking presence of hyaline cytoplasmatic globules was seen in cytologic smears and histologically, being immunoreactive for vimentin, consistent with an intracellular store of intermediate filaments. The tumor showed high proliferative activity (40%) with Ki-67 and negativity for p53, cerbB2, and bcl-2. Although hyaline globules are more frequent in pheochromocytomas and other neoplasms, they may also be present in ACC. These globules may be observed in cytologic smears. Also, the identification and immunohistochemical characterization of these hyaline globules in metastases may be useful in determining the origin of primary occult tumors. Diagn. Cytopathol. 1999;21:394-397.
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PMID:Giant adrenal cortical carcinoma, clinically "nonfunctional": report of a case containing cytoplasmic hyaline globules of vimentin. 1057 70

Fusion of mouse peritoneal macrophages or human blood monocytes with weakly metastatic mouse Cloudman S91 melanoma cells resulted in hybrids with enhanced metastatic potential (Rachkovsky et al., 1998. Clin. Exp. Metastasis, 16: 299-312). With few exceptions, such hybrids also showed increased basal- and MSH-induced pigmentation, at least in part through increased N-glycosylation of melanogenic proteins (Sodi et al., 1998. Pigment Cell Res., 11: 299-309). Here we report analyses regarding expression of the melanocyte-stimulating hormone (MSH) receptor (melanocortin-1 receptor, MC1-R) and the melanogenic proteins, tyrosinase (E.C. 1.14.18.1), tyrosinase-related protein 1 (TRP-1), and the tyrosinase-related protein 2 (TRP-2, E.C. 5.3.2.3), by a panel of cell lines consisting of parental Cloudman S91 melanoma cells, macrophages from DBA/2J mice, artificially derived macrophage x melanoma hybrids of high and low metastatic potential, and a naturally occurring highly metastatic hybrid between a Cloudman S91 tumor cell and a DBA/2J tumor-infiltrating cell. We show that incubation of cells with MSH/isobutylmethylxanthine (IBMX) resulted in strong melanogenic and morphologic responses in high metastatic hybrids compared to parental cells and the low metastatic hybrid, and that high metastatic hybrids exhibit increased mRNA expression for MC1-R accompanied by increased 125I-alphaMSH binding. Although tyrosinase activity and the protein level for tyrosinase and TRP-2, but not for TRP-1, were increased in the high metastatic hybrids versus the other cells, no significant changes in mRNA either for tyrosinase or for TRPs were observed in them. Furthermore, unlike tyrosinase, the abundance and gel mobility pattern of TRP-2 did not correlate with changes in activity in all hybrids and parental melanoma cells. The results suggest that although the activity MC1-R and tyrosinase correlate with enhanced basal as well as MSH-induced melanogenesis in metastatic/melanotic hybrids, their expression is differentially regulated, i.e., regulation of MC1-R while at transcriptional level, the TRPs are primarily regulated via post-transcriptional mechanisms in high metastatic hybrids.
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PMID:Upregulation of mRNA for the melanocortin-1 receptor but not for melanogenic proteins in macrophage x melanoma fusion hybrids exhibiting increased melanogenic and metastatic potential. 1061 75

Ectopic adrenocorticotropic hormone (ACTH) and/or corticotropin-releasing hormone (CRH) are associated with a growing list of tumors. We report a 69-year-old white man with a history of high-grade prostate carcinoma and widely metastatic adenocarcinoma who presented with metabolic alkalosis, hypokalemia, and hypertension secondary to ectopic ACTH and CRH secretion. Laboratory values were consistent with hypokalemia and metabolic alkalosis. Markedly elevated serum cortisol (135 microg/dL), ACTH (1,387 pg/dL), CRH (69 pg/dL), and urine free cortisol (16,276 microg/24 h) levels were found. Chest computed tomographic (CT) scan showed small noncalcified parenchymal densities; however, bronchoscopy and bronchoalveolar lavage washings were unremarkable for a neoplastic process. Abdominal CT scan and magnetic resonance imaging showed multiple small liver lesions and multiple thoracic and lumbar intensities consistent with diffuse metastatic disease. Histological analysis of a biopsy specimen from the thoracic spine showed an undifferentiated adenocarcinoma consistent with a prostate primary tumor. The severe metabolic alkalosis secondary to glucocorticoid-induced excessive mineralocorticoid activity was treated with potassium supplements, spironolactone, and ketoconazole. In this case report, we describe an unusual tumor associated with ectopic ACTH and CRH production and the pharmacodynamic relationship of plasma cortisol levels and urinary cortisol excretion with ketoconazole treatment.
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PMID:Hypokalemia, metabolic alkalosis, and hypertension: Cushing's syndrome in a patient with metastatic prostate adenocarcinoma. 1127 85


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