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)

Typical carcinoid, atypical carcinoid, and small cell lung cancer (SCLC) fall within the spectrum of neuroendocrine lung neoplasms. This paper investigates the immunohistochemical expression of the products of tumour suppressor genes p53 and retinoblastoma (RB), together with proliferation (PCNA and Ki67) and neuroendocrine differentiation markers, in 14 typical carcinoids, ten atypical carcinoids, four borderline atypical carcinoid/SCLC, and 11 SCLC. We demonstrated that the phosphoprotein p53 and RB product can be immunolocalized on routine histological material. p53 protein was absent in all typical and atypical carcinoids, while it was abnormally expressed in eight SCLC and one borderline case. RB product was detected in all typical carcinoids and in two atypical carcinoids, while it was consistently absent in the other cases. PCNA-labelled cells were less than 4 per cent in typical carcinoids, about 40 per cent in atypical carcinoids, and over 70 per cent in SCLC. PCNA labelling index discriminates between typical and atypical carcinoids. Neuroendocrine differentiation was evaluated by a semi-quantitative method: a mean score value was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data show that the decrease in neuroendocrine features from typical carcinoid to SCLC is paralleled by an increase in proliferative activity and by an altered expression of tumour suppressor gene products. The above findings have diagnostic relevance.
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PMID:Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms. 135 31

The molecular forms of ACTH secreted by established human small cell lung cancer (SCLC) cells and primary cultures derived from a bronchial carcinoid tumour, a pituitary adenoma and hyperplastic pituitary tissue have been characterized by Sephadex G-75 chromatography and quantified with two novel immunoradiometric assays for ACTH and ACTH precursor peptides. Pro-opiomelanocortin (POMC; Mr 31,000) and pro-ACTH (Mr 22,000) were secreted by all cell types. No smaller peptides were identified in the culture media from SCLC and bronchial carcinoid cells, implying a deficiency in the enzymes and/or intracellular organelles required for extensive POMC processing. A more heterogeneous profile of ACTH-containing peptides was produced by cells of pituitary origin, indicating more extensive proteolytic processing of POMC. However, the major peptide secreted by cells from a large aggressive pituitary adenoma was unprocessed POMC (Mr 31,000). These results suggest that both lung and pituitary cells in vitro retain their in-vivo pattern of POMC processing and provide valuable models in which to study the regulation of ACTH synthesis and secretion.
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PMID:Comparison of ACTH and ACTH precursor peptides secreted by human pituitary and lung tumour cells in vitro. 215 69

Synaptophysin is a Mr 38,000 integral membrane glycoprotein expressed by a variety of normal and neoplastic neuroendocrine cells. We studied synaptophysin as an immunocytochemical marker for neuroendocrine differentiation in lung cancer and compared it to the immunocytochemical expression of chromogranin A, a marker for dense core (endocrine) granules, and the biochemical activity of L-dopa decarboxylase (DDC), the key amine-handling enzyme. Of the 250 cell lines available to us, we selected examples representative of the following cell types: bronchial carcinoids (n = 4), small cell lung cancer (SCLC) (n = 7), extrapulmonary small cell carcinomas (n = 4), and non-small cell lung cancers (n = 18) whose neuroendocrine status had been previously determined on the basis of electron microscopy and DDC activity. We demonstrated (a) there was a higher incidence of synaptophysin than chromogranin A immunoreactivity in carcinoid (100 versus 75%), classic SCLC (70 versus 50%), and variant SCLC (57 versus 29%) cell lines; (b) 3 of the 4 (75%) extrapulmonary small cell lung cancer cell lines expressed synaptophysin and chromogranin A; (c) 5 of the 7 (71%) non-small cell lung cancer cell lines previously shown to express multiple neuroendocrine markers were positive for synaptophysin, chromogranin A, and DDC activity; (d) none of the other 11 non-small cell lung cancer cell lines expressed synaptophysin or chromogranin A; and (e) formalin fixation and paraffin embedding reduced synaptophysin immunoreactivity in 11 of 14 (79%) of the cell lines, as compared to freshly prepared specimens fixed in 95% ethanol. Western blot analysis using the synaptophysin antibody (SY38) demonstrated immunoreactive proteins ranging from Mr 43,000 to 45,000 in five representative cell lines. The concordance of expression of all three neuroendocrine markers was statistically significant when values for all cell lines were totalled. Synaptophysin was a more commonly expressed marker for variant SCLC cell lines, which rarely showed DDC activity. We conclude that synaptophysin may be a more sensitive and specific marker for neuroendocrine differentiation, when compared to chromogranin A and DDC in lung cancer cell lines which express only part of the neuroendocrine program.
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PMID:A comparison of synaptophysin, chromogranin, and L-dopa decarboxylase as markers for neuroendocrine differentiation in lung cancer cell lines. 216 88

Chromogranins A, B, and C, proteins that are co-stored and co-released with peptides and amines, have been identified in a variety of neuroendocrine tissues, both normal and neoplastic. We examined the secretion of chromogranin A and chromogranin A + B by hormone-producing tumours in patients with endocrine pancreatic tumours, carcinoid tumours, pheochromocytomas, and small cell lung cancer. The radioimmunoassay determining the plasma concentrations of chromogranin A + B showed a greater sensitivity than that determining chromogranin A alone. All patients with endocrine pancreatic tumours, carcinoids, and pheochromocytomas had increased levels of chromogranin A + B, whereas a small number of the patients (5/18 with endocrine pancreatic tumours and 1/3 with pheochromocytomas) had normal levels of chromogranin A. Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C. We have demonstrated that a polyclonal antiserum against a mixture of chromogranin A and B might be a more sensitive marker than chromogranin A alone for diagnosing neuroendocrine tumours. This is not surprising, since both chromogranins are widely distributed in neuroendocrine cells.
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PMID:A polyclonal antiserum against chromogranin A and B--a new sensitive marker for neuroendocrine tumours. 231 6

The biochemical properties of lung cancer cell lines were investigated. Bombesin-like peptides were present in three small cell lung cancer (SCLC) cell lines examined and three of four lung carcinoids but not in five non-small cell lung cancer (NSCLC) cell lines. Therefore SCLC and some lung carcinoids, but not NSCLC, are enriched in neuroendocrine properties. In contrast, 125I-EGF bound with high affinity to all five NSCLC cell lines and three of four lung carcinoids but not to the three SCLC cell lines examined. For lung carcinoid cell line NCI-H727, 125I-EGF bound with high affinity (Kd = 6 nM) to a single class of sites (Bmax = 110,000/cell). The 125I-EGF bound was rapidly internalized at 37 degrees C but not 4 degrees C. Using Western blot techniques and antiphosphotyrosine antibodies, EGF induced phosphorylation of a major 170 Kd protein. Using immunoprecipitation techniques and anti-EGF receptor antibodies a major 170 Kd protein was labeled. These data indicate that biologically active EGF receptors are present on NSCLC and lung carcinoid cell lines.
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PMID:Lung carcinoid cell lines have bombesin-like peptides and EGF receptors. 238 Feb 59

The expression of cytokeratins (CKs) in human lung cancer was studied using chain-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 18, and 19. When applied to adenocarcinomas (ACs) of the lung, high levels of CKs 7, 8, 18, and 19 were detected in all tumors, while CK 4 was found in high concentrations in some ACs. CK 10 and 13 were completely absent, or only present in low numbers of cells. Small cell lung cancers (SCLCs) and lung carcinoids contained CK 18 and sometimes 8 and 19, but no CK 7 in most cases. Three out of four tumors, histologically classified as SCLC, and expressing CK 7 in a variable number of cells were found by electron microscopic studies to contain regions with AC and/or squamous cell carcinoma (SQC) differentiation. The monoclonal antibody specific for CK 7 can therefore possibly help to distinguish AC differentiation within SCLC. CKs 10 and 13 were completely absent in SCLCs and lung carcinoids, while few CK 4-positive cells were found in some SCLCs and in one lung carcinoid. Within SQCs the monoclonal antibodies revealed a pronounced heterogeneity in CK expression. CKs 4, 7, 8, 10, 13, 18, and 19 could be detected, although not evenly distributed among all tumor cells. Highly differentiated SQCs expressed high levels of the CKs specific for squamoid differentiation, i.e., CKs 4, 10, and 13 in variable numbers of cells. With decreasing histologically detectable SQC differentiation these markers were gradually lost, while the number of cells containing CKs 7, 8, 18, and 19 increased. Application of this panel of monoclonal antibodies can therefore distinguish not only the main subtypes of lung cancer, but can also indicate the degree of differentiation and the degree of heterogeneity. These findings can be used as a diagnostic aid in lung tumor pathology, which may have an impact on treatment and prognosis.
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PMID:Cytokeratins in different types of human lung cancer as monitored by chain-specific monoclonal antibodies. 245 87

Three monoclonal antibodies (mAbs), NCC-LU-243, -244 and -246, detected three different epitopes on a 145-kDa cell membrane antigen, which had been designated as the cluster 1 antigen at the First International Workshop on Small Cell Lung Cancer (SCLC) Antigens. The distribution of the antigen in various tissues, cultured cells and sera was examined by immunohistochemistry and sandwich radioimmunoassay using these mAbs. The antigen is a normal differentiation antigen and is present in neuronal, neuroendocrine and cardiac muscle cells. The level of the antigen was highest in central nervous tissues, while it was undetectable in the liver, kidney and peripheral lung. Among tumor tissues, the antigen was detected only in SCLC, carcinoid tumor and neuroblastoma, indicating its usefulness as a marker for discriminating SCLC from non-SCLC. The level of the antigen varied among SCLC tissues and tended to be lower in variant-type cultured SCLC cells. Although an increase in the antigen level was observed in sera of some patients with advanced SCLC, the antigen did not possess any additional value over neuron-specific enolase as a serum tumor marker for monitoring SCLC patients.
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PMID:Quantitative distribution of cluster 1 small cell lung cancer antigen in cancerous and non-cancerous tissues, cultured cells and sera. 247 55

Chromogranins A, B and C, proteins that are costored and coreleased with peptides and amines, have been identified in a variety of endocrine and nervous tissues, both normal and neoplastic. We examined the secretion of chromogranin A and chromogranin A + B by hormone-producing tumors in patients with endocrine pancreatic tumors (EPT), carcinoid tumors, pheochromocytomas and small cell lung cancer (SCLC). Radioimmunoassay (RIA) of the plasma/serum concentrations of chromogranin A + B showed a greater sensitivity than RIA of chromogranin A alone. All patients with EPT, carcinoids and pheochromocytomas had increased levels of chromogranin A + B, whereas a small number of the patients (5/18 with EPT and 1/3 with pheochromocytomas) had normal levels of chromogranin A. Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C.
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PMID:Chromogranins--new sensitive markers for neuroendocrine tumors. 254 31

Selected neoplastic markers (NSE, gastrin, CEA, calcitonin, keratin) were studied in pulmonary specimens from 5 patients with bronchial carcinoid, 20--with small cell lung cancer (SCLC), and 2 with solid tumors. In patients with carcinoid and SCLC NSE and gastrin markers were found--characteristic for neuroendocrine neoplasia. The author discuss the usefulness of immunohistochemistry in differential diagnostics of pulmonary malignancy.
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PMID:[Bronchial carcinoid and small cell lung cancer--neuroendocrine tumors. Immunohistochemical studies]. 256 12

From January 1955 to April 1987 111 patients with bronchial carcinoid were operated on in our department. There were 62 males and 49 females with a mean age of 45.5 years. Preoperative histological diagnosis was achieved in 22 cases, while in five patients, a false positive diagnosis of small cell lung cancer was reported. Fifteen patients required pneumonectomy, 70 had lobectomy, 16 bilobectomy, and four segmentectomy. One patient required tracheal resection, while in another patient the tumour was removed through bronchotomy. Four patients were completely treated with YAG laser phototherapy. There were three postoperative deaths. The following variables were analysed and discussed in order to evaluate their influence on prognosis: (1) size of the tumour, (2) typical or atypical appearance, (3) endoluminal or extraluminal growth, (4) vascular invasion, (5) node metastases. Atypical onset, node metastases and extraluminal invasion are significant factors in worsening the prognosis.
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PMID:Typical and atypical bronchial carcinoids. 260 51


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