Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An autopsy case of ACTH-producing thymic carcinoid with Cushing's syndrome is reported. The patient was a 63-yr-old man with multiple bone metastases from an undetermined primary site. Hyperpigmentation was observed at the terminal stage. The plasma levels of ACTH, cortisol, chromogranin A, and urinary 17-hydroxy-corticosteroids were extremely high, and ectopic ACTH-producing neuroendocrine tumor was diagnosed. In addition, plasma CRH was high. Autopsy revealed that the patient had primary thymic carcinoid with extensive metastases. Remarkable hyperplasia of the adrenal cortexes and Crooke's hyaline degeneration of the pituitary gland were consistent with Cushing's syndrome by ectopic ACTH production. There were multiple CRH-producing cells without degenerative changes in the hypothalamus. The tumor cells were immunoreactive to ACTH, CRH, and the cleavage enzyme PC2. POMC messenger ribonucleic acid and PC2 messenger ribonucleic acid were detected in the tumor cells by an in situ hybridization method. Expression of PC2 was considered to induce hyperpigmentation by producing alpha MSH. Despite hypercortisolism and ectopic production of CRH by the tumor cells, hypothalamic CRH cells were not atrophic. This case is a good example to demonstrate the correlation between CRH and the hypothalamo-pituitary-adrenal axis as well as hyperpigmentation in Cushing's syndrome.
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PMID:Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-releasing hormone. 855 Jul 83

In order to clarify the expression of prohormone convertase (PC) 1/3 and PC2 in various carcinoids and non-carcinoid endocrine tumors, we performed indirect immunoperoxidase staining on total of 19 cases of carcinoids (9 cases of bronchial carcinoids, 4 cases of rectal carcinoids, 4 cases of gastric carcinoids and 2 cases of bile duct carcinoids). Our study also included 7 non-carcinoid endocrine tumors. Seventy-nine% and 26% of carcinoids highly or strongly expressed positive staining for PC1/3 and PC2, respectively. High and strong expressions (3+ or 4+) of both PC1/3 and PC2 were noted in only bronchial carcinoids. Strong expressions for only PC1/3 were noted in rectal carcinoids. Bile duct carcinoids also demonstrated higher expressions of PC1/3 than those of PC2. These results suggested that high expressions of both PC1/3 and PC2 in bronchial carcinoids might reflect their diverse and frequent peptide production. The expressions of PC1/3 mRNA and PC2 mRNA detected by in situ hybridization in the bronchial carcinoids and rectal carcinoids were correlated with immunoexpressions of both of the antigens. The granular immunoexpression pattern of PC1/3 and PC2 visualized by confocal laser scanning microscopy would suggest the site of post-translational processing in the secretory granules. Non-carcinoid endocrine tumors showed low expressions (+ or 2+) of PC1/3 and PC2, except for thyroid medullary carcinoma showing high immunoexpression of PC1/3. Other non-carcinoid endocrine tumors (parathyroid adenomas and adrenal pheochromocytomas) revealed low immunoexpressions for both PC1/3 and PC2.
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PMID:Immunohistochemical expressions of prohormone convertase (PC)1/3 and PC2 in carcinoids of various organs. 1053 Jun 21

The differential gene expression of proopiomelanocortin (POMC)-related processing enzymes, transcription factors, and receptors responsible for ACTH secretion between non-pituitary and pituitary ACTH-secreting tumors remains obscure. This study was attempted to determine the gene expression profiles of transcription factors (Tpit, NeuroD1 and IKZF1), proprotein convertase (PC) 1/3 and PC2, and several key receptors linked to ACTH secretion, including corticotrophin releasing hormone receptor (CRHR1), vasopressin receptor 1b (V1bR), somatostatin receptor (SSTR) subtype-2, -5 and dopamine receptor type 2 (D2R) in non-pituitary and pituitary ACTH-secreting tumors. Surgical tissue specimens from carcinoid tumors causing ectopic ACTH syndrome (EAS: n=4) and pituitary tumors causing Cushing's disease (CD: n=13), were subjected to real-time RT-PCR for measurements of each mRNA levels. POMC and CRHR1 mRNA levels in CD were far greater than those in EAS, whereas IKZF1, PC2, SSTR-2 and -5 mRNA levels in EAS were significantly greater than those in CD. NeuroD1, Tpit, PC1/3, V1bR and D2R mRNA levels were comparable between EAS and CD. In conclusion, differential gene expression profiles revealed more abundant mRNA expression in EAS than in CD of 1) IKZF1 with its potential implication of cell differentiation and hormone secretion, 2) PC2 with its possible enhanced processing activity of mature ACTH, and 3) SSTR-2 and -5 with their potential therapeutic application of more selective agonists in EAS patients.
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PMID:Differential gene expression profiles of POMC-related enzymes, transcription factors and receptors between non-pituitary and pituitary ACTH-secreting tumors. 2138 26