Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Ectopic production of ACTH and corticotropin-releasing hormone (CRH). 132 73

A forty-one-year-old male who was found to have lung carcinoid tumor showed clinical features of Cushing syndrome. At the age of 38 years during a regular check-up, a chest roentgenogram showed multiple nodular shadows in the bilateral lung, and he was admitted to hospital. By open lung biopsy, he was diagnosed as having malignant carcinoid or small cell carcinoma of the lung. The abnormal lung shadows did not respond to chemotherapy (CDDP + VDS). The clinical course after discharge was uneventful until the age of 41 years, when he was readmitted to our hospital because of brain metastasis. Physical examination revealed moon face and central obesity. Plasma ACTH level was high and dexamethasone suppression test showed no cortisol suppression on 8 mg dexamethasone administration. Therefore, it was thought that the patient had ACTH producing ectopic tumor which led to Cushing syndrome. We measured the molecular weight of ACTH by column chromatography and found he had a big ACTH (molecular weight about 22,000). Reexamining him clinically and histologically, we concluded that the patient had atypical carcinoid tumor in the lung which might produce ACTH causing Cushing syndrome with metastasis to the brain.
 ...
PMID:[A case of Cushing syndrome caused by ACTH producing atypical lung carcinoid tumor]. 132 84

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.
 ...
PMID:Neuroendocrine alterations in nude mice with a human lung carcinoma producing pro-opiomelanocortin, corticotrophin-releasing hormone and arginine vasopressin. 216 Aug 74

Despite all we have learned, the reason why certain tumours and particularly non-pituitary tumours synthesize ACTH remains an enigma. There is no clear theory which links the neoplastic process with the expression of peptide hormones but it is interesting to speculate that the amplification of certain oncogenes may be linked to de-repression of hormone genes. Once the gene has been switched on, there should be some mechanism for preventing continuous expression and in the pituitary the POMC gene is normally inhibited by glucocorticoids. Therefore it is crucial to investigate the role of glucocorticoids in non-pituitary tumours and this requires an understanding of the molecular mechanisms involved in glucocorticoid inhibition of the normal POMC gene in the pituitary. The evidence presented in this chapter describing the glucocorticoid receptor binding site in the promoter region of the POMC gene in rat pituitary gives an exciting insight into the regulatory mechanisms and their potential for aberrant control. Taken with the presence of pituitary-specific regions regulating the POMC gene promoter there appear to be multiple approaches to dissecting out the differences in non-pituitary tumours. Thus in a relatively short period of time there has been a marked increase in our understanding of the molecular mechanisms underlying POMC gene expression. At the level of the peptides, progress has been slower. We are now aware that secretion of ACTH implies that a number of other peptides will be found in the circulation, even though there is limited evidence for a specific role for any of the co-secreted peptides. However, it is hard to understand the conflicting reports that N-POC is synthesized by non-small cell and small cell carcinoma of the lung when ACTH, which we assume to be co-secreted, is thought to be synthesized only by small cell carcinoma. The most likely explanation for this is the difficult nature of the radio-immunoassays for these hormones and the problems associated with studying large groups of clearly defined patients. Development of very simple methods for measuring the ACTH precursors has demonstrated that they are released into the circulation in normal subjects and that the levels are markedly elevated in non-pituitary tumours, suggesting that they are the major circulating forms in the ectopic ACTH syndrome. This implies that these tumours cannot process the precursor molecules suggesting that the processing enzymes are lacking.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The synthesis of ACTH and related peptides by tumours. 216 56

We report a case of ectopic ACTH syndrome in a 50-year old woman with small cell carcinoma of the lung. Ectopic ACTH syndrome from small cell carcinoma often presents with hypokalemia, metabolic alkalosis and muscle wasting. This patient presented with Cushingnoid features which is unusual in such cases.
 ...
PMID:A case of small cell carcinoma with ectopic ACTH syndrome. 216 92

The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit.
 ...
PMID:A clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer. 217 Oct 9

In an attempt to localize hormones in cytocentrifuge-prepared cultured cells of small cell carcinoma of the lung (SCCL), various modifications of the immunoperoxidase (PAP) procedure (Sternberger, 1979) were tested. When using glutaraldehyde, formaldehyde, or p-benzoquinone fixation (Pearse & Polak, 1975) and rabbit antibodies in primary or bridging steps of the PAP procedure, nonspecific staining (false positives) could be elicited with the majority of rabbit antibodies tested, but not with antibodies from other animal sources. This problem could be eliminated by fixation of cells either with formalin-acetone (Mason et al., 1975) or, when using antibodies from a source other than rabbit, glutaraldehyde. It was not possible to localize ACTH in DMS-79, a human SCCL line known to produce this hormone. However, calcitonin was localized in the calcitonin-producing SCCL line DMS-53. Failure to localize ACTH in DMS-79 may be due to the lower levels of this hormone in DMS-79, as compared to the levels of calcitonin in DMS-53. This study emphasizes the importance of proper controls before concluding successful localization in a given immunocytochemical preparation of cultured cells.
 ...
PMID:Immunocytochemical staining of cytocentrifuge prepared cultured cells: nonspecific staining and its elimination. 241 84

We describe a case of adrenal myelolipoma that occurred in a 66-year-old male with an ACTH producing oat cell lung carcinoma. To our knowledge, this is the first case in which myelolipoma has occurred in association with ectopic ACTH-induced Cushing's syndrome. The literature is reviewed and the pathogenesis of myelolipoma is discussed.
 ...
PMID:Ectopic ACTH and adrenal myelolipoma. 253 44

Large cell neuroendocrine (LCNE) carcinomas of the lung are a newly recognized, highly aggressive and frequently misdiagnosed entity. We report a case of stage I LCNE lung carcinoma initially misdiagnosed as large cell undifferentiated carcinoma or poorly differentiated adenocarcinoma. The tumor was very extensively necrotic and its neuroendocrine differentiation was only demonstrable with immunohistochemical staining with PHE-5 monoclonal antibody and with antisera against synaptophysin and calcitonin. ACTH, somatostatin and neurofilaments were not demonstrable. The clinical course was ominous and the patient died within 17 months. The reason for this rapid fatal outcome could be ascribed either to the neuroendocrine phenotype of the tumor, or to the extensive necrosis, or both.
 ...
PMID:Large cell neuroendocrine carcinoma of the lung. 255 26

Radioimmunoassay was used to determine CEA, ACTH, calcitonin (CT), parathyroid hormone (PTH) and cortisol levels in the blood plasma and serum of small-cell lung carcinoma patients before and after chemotherapy. The prognostic value of the determination of CEA, ACTH and CT levels was shown. In 74% of patients, progression of the disease was accompanied by a rise of the CEA level, successful treatment by a decrease in the CEA level. A similar correlation between tumor activity and ACTH, CT and PTH levels was shown in 50.44 and 47% of the patients respectively.
 ...
PMID:[Radioimmunologic evaluation of the prognosis and effective therapy of patients with small cell lung cancer]. 299 53


<< Previous 1 2 3 4 5 6 Next >>