Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report considers the potential usefulness of adrenocorticotropic hormone (ACTH) determinations in diagnosis and in prognosis for therapy of patients with carcinoma of the lung but without clinical Cushing's syndrome. The report is based on radioimmunoassay data from 129 patients, including 62 with lung cancers and 67 with nonmalignant pulmonary conditions. Elevated plasma ACTH was found in 21 of 24 patients with untreated cancer and the hormone was detected in tumor extracts and/or bronchial washings from the remaining 3. Elevation of plasma ACTH was found in only 10 of 38 treated patients. Absence of clinical Cushing's syndrome in spite of high plasma ACTH concentrations is explained by the observation that the predominant form of ectopic ACTH in plasma is immunoreactive but nonbioactive 'big' ACTH. Prolonged survival, for longer than 19 months, was observed in only 5 patients: all patients with low plasma ACTH after resection of the lung tumor and 2 of 3 patients with low plasma ACTH without therapy. ACTH was found in all available malignant tissue, primary and metastatic, from the lung carcinoma group,but not in normal lung or in 5 tumors metastatic to the lung. Of the 39 patients diagnosed initially to have chronic obstructive pulmonary disease, 14 showed plasma ACTH elevation. However, 3 of these patients with the highest concentrations subsequently manifested carcinoma or carcinoma in situ.
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PMID:Ectopic production of big ACTH in carcinoma of the lung. Its clinical usefulness as a biologic marker. 16 43

Big corticotropin (adrenocroticotropic hormone, ACTH), an immunoreactive form of ACTH with low biological activity and which elutes in the void volume on Sephadex G-50 gel filtration, is found in plasma and extracts of human pituitary and tumour. Controlled tryptic digestion of big ACTH releases a product with full corticotropic activity which is indistinguishable from the (1-39) ACTH with respect to size, charge and susceptibility to tryptic digestion. Immunoreactive ACTH, predominantly in the big form, is found in virtually all tissue extracts of carcinoma primary to or metastatic from the lung, but not of carcinoma metastatic to the lung, and even in precancerous lung lesions. The absence of clinical Cushing syndrome in patients with carcinoma of the lung and moderate elevation of plasma concentrations of ACTH is due to the low biological activity of big ACTH. Prolonged survival (for more than two years) of patients with lung carcinoma has been observed only in those whose plasma ACTH is low before therapy or after resection of the lung tumour. Rabbit, rat and mouse pituitaries contain an intermediate sized ACTH but the usual 1-39 peptide predominates in the pituitaries of monkey, sheep, dog, cat and guinea pig, as well as man. The hormonal form of ACTH appears to be an important factor regulating the cortisol/corticosterone ratio in mammalian adrenal corticoid secretion because administration of porcine ACTH to rabbits alters the adrenal secretory pattern so as to decrease corticosterone production and increase cortisol production.
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PMID:Multiple forms of corticotropin (adrenocorticotropic hormone, ACTH) and their significance. 18 Dec 23

Ninety-one human tumors, including various common carcinomas, low-grade malignant tumors, and benign tumors, were transplanted into athymic nude mice. Tumor take was confirmed histologically for 22 neoplasms at the initial transplantation, and 14 serially transplantable tumors were established, including some hitherto unestablished or unreported, such as lung and hepatic cell carcinomas. Among the 91 tumors were 21, 14, and 13 carcinomas of the lung, stomach, and breast, respectively. Transplantability was highest in lung carcinomas (10/21), followed by gastric carcinomas (2/14) and breast carcinomas (1/13). Morphology of original tumors was retained well in most transplanted tumors, but desmoplastic or scirrhous tumors, such as gastric and breast carcinomas, tended to become medullary with a decrease in amount of tumor stroma. The ability to produce mucin in gastric carcinomas or melanin in malignant melanoma was maintained in serially transplantable tumors. In addition, ectopic production of adrenocorticotropin and beta melanocyte-stimulating hormone continued in a transplanted small cell carcinoma of the lung. Preliminary results were obtained on hormone dependency of the transplantable breast carcinoma and on alpha1-fetoprotein in the transplantable hepatic cell carcinoma.
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PMID:Transplantation of human tumors in nude mice. 18 24

Two cases of small cell carcinoma of the lung associated with the ectopic production of multiple hormones are reported. Both tumors were shown to contain significant amounts of ADH, ACTH, and beta-MSH. Biologic, immunologic, and gel chromatographic properties of these ectopic hormones were found to be very similar to those of pituitary origin. The effect of excessive secretion of antidiuretic hormone (ADH) dominated the clinical manifestations in both cases, i.e., syndrome of inappropriate secretion of ADH (SIADH). The clinical manifestations of the ectopic ACTH-MSH syndrome were minimal. These data suggest that multiple hormone production without clinically overt sequelae of excess hormone is not uncommon in small cell (oat cell) carcinoma of the lung.
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PMID:Two cases of multiple hormone-producing small cell carcinoma of the lung: coexistence of tumor ADH, ACTH, and beta-MSH. 18 19

Endocrine and immunohistochemical studies were performed in a patient with lung cancer associated with gynecomastia. Elevated level of human chorionic gonadotropin (hCG) in plasma and mild hyperadrenocorticism were demonstrated by hormone assays. Postmortem examination proved the existence of anaplastic small cell carcinoma of the lung mixed with a feature of chorioepithelioma. The presence of significant amounts of adrenocorticotropic hormone (ACTH), beta-melanocyte stimulating hormone (beta-MSH), calcitonin, gastrin, hCG, hCG-alpha, hCG-beta and human chorionic somatomammotropin (hCS) in tumor tissues was demonstrated by radioimmunoassays, bioassay and immunohistochemical techniques. We present here a unique case of multiple hormones producing tumor elaborating both hormones of amine precursor uptake and decarboxylation (APUD) series (ACTH, beta-MSH, calcitonin and gastrin) and of placental origin (hCG, hCG-alpha, hCG-beta and hCS).
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PMID:Multiple-hormone producing lung carcinoma. 22 25

The capacity which the cells of some tumors have of synthesizing, storing, and releasing hormonal polypetides constitutes the basic characteristic of the neoplasms of the APUD system. On many occasions these polypeptides are released as hormonal precursors of high molecular weight, with a minimal biological action in comparison with the real hormone (big ACTH, big gastrin, etc.), and they have no clinical expressivity. On other occasions they reproduce, however, the clinical syndrome of the hormone released in excess. The production of multiple hormones by a single tumor is not a common event. Here we present the case of a patient with an oat-cell carcinoma of the lung and a carcinoma of the pancreas, both histopathologically primitive. In this patient a syndrome of inadequate secretion of antidiuretic hormone was detected. By means of radioimmunoassay techniques, the existence of antidiuretic hormone, ACTH with a predominance of the components of high molecular weight (big ACTH and beta-LPH) and MSH was demonstrated in the tumoral extracts from the lung, pancreas, and from a mediastinal metastatic lymph node. While the concentrations of ACTH were much greater in the lung than in the pancreas, the opposite occurred for the antidiuretic hormone. The synthesis of MSH by the hypophyseal gland or by tumors is not at present recognized, but rather is considered as a degradation product during the process of extraction. The APUD system makes up the morphologic substrate of the syndromes of familiar multiple endocrine adenomatosis. The present case could represent a variant of sporadic multiple endocrine neoplasms which would have the same anatomical basis.
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PMID:[Hormonal multiplicity of an apudoma of the lung and pancreas. Characterization of the different peptides in the tumoral extracts (author's transl)]. 22 76

The DMS-79 continuous line of human small cell lung carcinoma cells, which produces immunoreactive (IR)-corticotropin (ACTH), -lipotropin (LPH), and -beta-endorphin (beta END), was found to produce IR-calcitonin (CT). Two major high molecular weight (HMW) forms of IR-CT were observed after gel exclusion chromatography under denaturing conditions (mol wt. approximately 7,000 and approximately 14,000), as well as a minor HMW IR-CT component (mol. wt. approximately 70,000). None of these IR-CT materials was extracted from DMS-79 medium by affinity chromatography using an ACTH antibody covalently bound to agarose. These results demonstrate ectopic production of HMW forms of CT and ACTH/LPH/beta END by human lung tumor cells in tissue culture, but do not support the existence of a common CT/ACTH/LPH/beta END precursor molecule.
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PMID:Ectopic production of high molecular weight calcitonin and corticotropin by human small cell carcinoma cells in tissue culture: evidence for separate precursors. 23 96

The most common ectopic production of a pituitary hormone is the one of ACTH leading to Cushing's syndrome. Ectopic ACTH-hypersecretion is the cause of Cushing's syndrome in 10-15% of all cases. The ACTH-secreting tumours are often oat-cell carcinomas of the lung, less frequently pancreatic cancers, hypernephromas, or C-cell carcinomas of the thyroid. Some of these tumours may be benign or semi-benign as the rare carcinoid tumours and cause great problems in the differential diagnosis of ACTH-dependent hypercortisolism. Out of 173 of our patients with Cushing's syndrome observed in the last 12 years 21 were caused by ectopic ACTH-production. Of these 21 patients 13 have a small cell carcinoma of the lung. The ectopic ACTH-syndrome often has typical clinical features caused by the levels of ACTH and cortisol leading to hypocalcemic alkalosis with muscle weakness and wasting, carbohydrate intolerance, and hypertension with oedema. The survival time in many of these patients is not long enough to allow them to develop typical signs of Cushing's syndrome though they are often highly pigmented. These patients are easily diagnosed. However, patients with small tumours which do not cause very elevated ACTH-levels and who have the more typical clinical signs of full-blown Cushing's syndrome are difficult to recognize. For the differential diagnosis of ACTH-dependent Cushing's syndrome the corticotropin-releasing hormone (CRH) stimulation test and dexamethasone suppression test with high doses are helpful. In special cases the venous sampling procedure for ACTH-measurements is necessary, also CT or NMR is helpful. Ectopic CRH-production is a rare cause of ACTH-dependent Cushing's syndrome. Patients with ectopic CRH-production and consecutive ACTH-hypersecretion from the pituitary have not been studied extensively. There are especially no well documented results of the use of the CRH-stimulation test in vivo in this group of patients with Cushing's syndrome. On the other hand, in the documented cases, not only CRH-, but also ACTH-production was found in the tumours. So far, this rare cause of ACTH-dependent Cushing's syndrome has to be excluded or confirmed by the measurement of endogenous CRH-levels. But until now we have not been able to detect one single case of ectopic CRH-production using a sensitive homologous CRH-radioimmunoassay over a period of more than 8 years in which we have seen nearly 120 newly diagnosed patients with ACTH-dependent Cushing's syndrome. Only in the plasma and tumour tissue of two patients of other groups have we found high CRH-levels.
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PMID:Ectopic production of ACTH and corticotropin-releasing hormone (CRH). 132 73

A mucoepidermoid carcinoma of the lung (ICD classification 8430/3) resected from a patient with no clinical signs of pituitary-adrenal alterations was transplanted into 2-month-old athymic nu/nu nude mice, with the purpose of studying the effects exerted by the human tumour on the host hypothalamo-pituitary-adrenal axis. The tumour produces peptides derived from different regions of pro-opiomelanocortin (POMC: ACTH, 7.6 +/- 0.7; N-terminal POMC, 6.6 +/- 0.6; beta-LPH/endorphin, 7.3 +/- 0.7; and alpha-MSH;3.8 +/- 0.5 pmol/g wet tissue) and the neuropeptides corticotrophin-releasing hormone and arginine vasopressin (CRH: 3.6 +/- 0.4 and AVP: 1.1 +/- 0.2 pmol/g wet tissue). Immunohistochemical staining of consecutive sections of the tumour indicated that staining of tumour cells for the different peptides was not uniform and although some cells co-stained with CRH and AVP, POMC-positive cells appeared to be distinct from CRH and AVP cells. Tumour extracts were chromatographed on Sephadex G-75 and fractions monitored for POMC-derived peptides. A single peak with characteristics of alpha-MSH was detected. The ACTH, N-POMC and beta-LPH/endorphin radioimmunoassays (RIA) detected a peak at large molecular weight, eluting at the position expected for POMC. These RIA systems also revealed an ACTH(1-39) peak and another peak which probably correspond to 13 kDa ACTH, a peak eluting at the position of hN-POMC(1-48), a beta-LPH-like peak, and a smaller sized peak which may represent alpha- or gamma-endorphin. The ACTH, N-POMC and beta-LPH/endorphin contents of anterior lobe (AL) extracts, but not neutrointermediate lobe (NIL) extracts, showed a striking decrease in tumour-bearing (TB) nude mice. However, while no difference was seen in the alpha-MSH content of AL extract between TB and control (C) nude mice, it decreased in NIL extracts of TB animals. The contents of CRH and AVP in stalk-median eminence extracts of TB nude mice was significantly lower than that of C nude mice. Basal plasma corticosteroids were raised in TB nude mice at levels comparable to those in stressed C nude mice, and although adrenal weights did not vary between TB and C nude mice, morphological changes indicating hypertrophy were found in the adrenal glands of the host animals. It was concluded that the tumour dramatically alters the hypothalamo-pituitary-adrenal axis of the host, and that it may be a useful model for studying tumour-host interactions in ectopic hormone-producing tumours.
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PMID:Neuroendocrine alterations in nude mice with a human lung carcinoma producing pro-opiomelanocortin, corticotrophin-releasing hormone and arginine vasopressin. 216 Aug 74

Bombesin (BN), a tetradecapeptide neuropeptide growth factor, is shown to be a potent (ED50 of 5 X 10(-12) M) chemoattractant for human monocytes and small cell lung carcinoma cells (SCCL). These effects are BN receptor-mediated since potencies of several BN analogs to induce chemotaxis and to inhibit [125I-tyr4] BN binding activity correlate well (P less than 0.001). As has been demonstrated for other BN receptor-mediated effects, carboxy-terminal amino acids are required for optimum biological activity. BN is not an exclusive chemoattractant for SCCL cells but was also active in promoting migration of other, but not all, lung tumor cells. Other neuropeptides, such as beta-endorphin, substance P, and arg-vasopressin, are also shown to be chemoattractants for SCCL cells, with EC50's also in the 10(-12) M range. The ability of these ligands to effect monocyte and some tumor cell migration suggest a role for neuropeptides in inflammation and metastasis. In the latter case, tumor cells, in response to neuropeptide chemical gradients, may become localized at specific body sites. Neuropeptide release, in response to cognitive or other stimuli, may thereby modify cell migratory patterns. Additionally, such hormones may influence early developmental events such as tissue organization and histogenesis.
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PMID:Neuropeptides are chemoattractants for human tumor cells and monocytes: a possible mechanism for metastasis. 241 46


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