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

To ascertain whether the content of endocrine markers is constant in small-cell carcinoma of the lung, levels of three markers of medullary thyroid carcinoma were studied in this tumor. Histaminase was increased in six of six primary tumors (three to 14,000 times), L-dopa decarboxylase in four of six (six to 30 times), and calcitonin in one of one (eight times) over levels in adjacent lung. Marker levels in mediastinal metastases reflected those in primary tumors in four of five patients. However, in four of seven, multiple hepatic metastases contained low to absent levels despite simultaneously high values in chest lesions. Immunohistochemical studies of histaminase revealed that within each primary tumor different cells contained different amounts of the enzyme. Since marker content varied between tumor cells, between primary tumors and between metastases in individual patients we conclude that circulating levels of these three markers cannot be expected necessarily to mirror tumor burden in patients with small-cell lung tumors.
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PMID:Variable content of histaminase, L-dopa decarboxylase and calcitonin in small-cell carcinoma of the lung. Biologic and clinical implications. 2 72

Twenty-seven small cell carcinomas of the lung and three tumors of the large intestine with combined adenocarcinomatous and small cell and/or anaplastic carcinoid-type histologic features were studied by light and electron microscopy. It was shown that the small cells have morphologic characteristics of APUD cells. Also presented are the histologic features of a carcinoma of the lung with large cell undifferentiated carcinoma, adenocarcinoma, squamous cell carcinoma, and giant cell carcinoma areas in the primary site and in several metastatic foci. Two of the renal metastases showed small cell carcinoma. The combined tumors and the numerous other similar neoplasms described in the literature and reviewed here suggest an endodermal origin for digestive and respiratory tract APUD cells based on the hypothesis that cancer is a clonal proliferation, and mucous and squamous cell differentiation is an endodermal rather than neural crest characteristic. The ultrastructural features of tumors of cells of known neural crest origin, including a medullary carcinoma of the thyroid, three carotid body tumors, a pheochromocytoma, and two cutaneous melanomas were compared with those of other APUD cell tumors including small cell carcinomas of the lung, two bronchial carcinoids, a carcinoid of the appendix, and a carcinoid of the kidney. Cells of the latter group sometimes possessed cytoplasmic tonofibrils, round compact masses of cytoplasmic microfilaments, and ductal lumina. These features were lacking in the former group and may signify a different embryologic origin. The histologic, histopathologic, and embryologic evidence regarding the origin of digestive and respiratory tract APUD cells is reviewed, showing that the former are, and the latter probably are, of endodermal and not neuroectodermal origin.
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PMID:The endodermal origin of digestive and respiratory tract APUD cells. Histopathologic evidence and a review of the literature. 3 40

To investigate the possible embryologic relation between small-cell carcinoma of the lung and medullary thyroid carcinoma, we measured plasma histaminase (an enzyme found in medullary carcinoma tissue) in 25 patients with small-cell tumors. The assays used histamine and putrescine as substrates. Thirty-two per cent of the patients by the histamine assay, and 31 per cent by the putrescine, had values greater than +2 S.D. from the mean for 63 normal persons. In contrast, among 20 patients with squamous and large-cell lung tumors, one (by the histamine assay), and two (by the putrescine) had elevated values. In four of five autopsy cases, histaminase was high in small-cell carcinoma tissue. The enzyme in plasma and in tumor behaved as classic histaminase in substrate specificity, and in response to inhibitors. The data support the proposed embryologic relation between small-cell lung carcinoma and medullary thyroid carcinoma, and further associate histaminase with some neural crest tumors.
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PMID:Elevated histaminase (diamine oxidase) activity in small-cell carcinoma of the lung. 17 75

High histaminase [amine:oxygen oxidoreductase (deaminating) (pyridoxal-containing), EC 1.4.3.6] activity is found in certain human tumors and in the placenta of most mammals. The present study explores the relationship of tumor histaminase to histaminases found in placenta and other human, pig, and rat tissues. The electrophoretic mobility and Michaelis constants for the deamination of histimine and putrescine were identical for histaminases from human placenta and from medullary thyroid carcinoma. An antibody was raised in rabbits against human placental histaminase that was highly purified by a new affinity procedure. In separate studies, using inhibitory concentrations of antibody and a second antibody precipitation technique, identical patterns of immunoreactivity were found for histaminases from human placenta, kidney, medullary thyroid carcinoma, and small cell lung carcinoma; human intestinal histaminase crossreacted well but less strongly than did enzymes from these other tissues. Histaminases from pig kidney, pig intestine, and rat intestine showed no crossreaction; histaminases from rat thymus and adrenal gland showed minimal crossreactivity. The findings suggest that placental histaminase activity is not a unique product of a fetal or trophoblastic genome. The presence of histaminase in malignancies does not appear to be an example of ectopic tumor production of a placental trophoblastic protein.
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PMID:Histaminase (diamine oxidase) activity in human tumors: an expression of a mature genome. 19 38

Investigations were performed to evaluate the incidence of increased serum calcitonin and histaminase in 79 patients with untreated small cell carcinoma of the lung (SSC). In addition, serum calcitonin was measured following pentagastrin stimulation in 19 of these patients. Serum calcitonin was elevated in 54 of 79 patients (68%), 20 patients (25%) having a level usually associated with the diagnosis of medullary carcinoma of the thyroid (MCT). The levels of histaminase, on the other hand, did not differ from the distribution in normals. In three of 19 patients undergoing the pentagastrin stimulation test, calcitonin was significantly increased. Thus, serum calcitonin is frequently elevated in patients with SCC and a positive pentagastrin test is not pathognomonic of MCT.
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PMID:Small cell carcinoma of the lung: serum calcitonin and serum histaminase (diamine oxidase) at basal levels and stimulated by pentagastrin. 21 4

The relations of calcitonin concentrations to the presence of bone marrow metastases and to the concentrations of calcium, parathormone and gastrin in serum were investigated in 74 untreated patients with small cell carcinoma of the lung. Calcitonin concentrations were enhanced in two thirds of the patients, while serum calcium concentrations were normal in all. In 19 of 57 patients parathormone concentrations were slightly above the normal range, but the concentrations of parathormone and calcitonin were not correlated. Bone marrow metastases had no influence on the concentration of serum calcitonin. Finally, a small inverse correlation between the concentrations of gastrin and calcitonin in serum was observed. The results resemble those of the calcitonin-producing medullary carcinoma of the thyroid, supporting the suggestion of an ectopic source of hypercalcitoninemia in small cell carcinoma of the lung.
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PMID:Small cell carcinoma of the lung: relation of calcitonin to bone marrow metastases, parathormone and gastrin. 22 33

A subtraction library was constructed from human insulinoma (beta cell tumor) and glucagonoma (alpha cell tumor) cDNA phagemid libraries. Differential screening of 153 clones with end-labeled mRNAs from insulinoma, glucagonoma, and HeLa cells resulted in the isolation of a novel cDNA clone designated IA-1. This cDNA clone has a 2838-base pair sequence consisting of an open reading frame of 1530 nucleotides, which translates into a protein of 510 amino acids with a pI value of 9.1 and a molecular mass of 52,923 daltons. At the 3'-untranslated region there are seven ATTTA sequences between two polyadenylation signals (AATAAA). The IA-1 protein can be divided into two domains based upon the features of its amino acid sequence. The NH2-terminal domain of the deduced protein sequence (amino acids 1-250) has four classical pro-hormone dibasic conversion sites and an amidation signal sequence, Pro-Gly-Lys-Arg. The COOH-terminal domain (amino acids 251-510) contains five putative "zinc-finger" DNA-binding motifs of the form X3-Cys-X2-4-Cys-X12-His-X3-4-His-X4 which has been described as a consensus sequence for members of the Cys2-His2 DNA-binding protein class. Northern blot analysis revealed IA-1 mRNA in five of five human insulinoma and three of three murine insulinoma cell lines. Expression of this gene was undetectable in normal tissues. Additional tissue studies revealed that the message is expressed in several tumor cell lines of neuroendocrine origin including pheochromocytoma, medullary thyroid carcinoma, insulinoma, pituitary tumor, and small cell lung carcinoma. The restricted tissue distribution and unique sequence motifs suggest that this novel cDNA clone may encode a protein associated with the transformation of neuroendocrine cells.
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PMID:A novel human insulinoma-associated cDNA, IA-1, encodes a protein with "zinc-finger" DNA-binding motifs. 163 55

Regulation of expression of the human calcitonin gene was found to differ between two tumor lines of different tissue origin, medullary thyroid carcinoma (TT line) and small-cell lung carcinoma (DMS53 line). Distal 5' DNA elements between -750 and -2000 exhibited a stronger basal activity in DMS53 than in TT cells, whereas proximal DNA sequences between -132 and -252 mediated a dramatic cyclic AMP response in TT but not DMS53 cells.
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PMID:Differential utilization of calcitonin gene regulatory DNA sequences in cultured lines of medullary thyroid carcinoma and small-cell lung carcinoma. 215 43

We have found that neuroendocrine tumors (including neuroblastoma, ganglioneuroma, gut carcinoid, pheochromocytoma, medullary thyroid carcinoma, insulinoma, glucagonoma, prolactinoma, carotid body tumor, and small cell lung carcinoma) produce considerable amounts (about 1000-80,000 ng/g tissue) of the alpha subunit of guanine nucleotide-binding protein, GO (GO alpha), whereas nonneuroendocrine tumors contain less than 300 ng of GO alpha/g tissue. GO alpha in the neuroendocrine tumors was present both in the soluble fraction, and cholate-extractable membrane-bound fraction of tissues. Immunoblots of membrane fractions of neuroblastoma and carcinoid tissues confirmed that the immunoreactive substance in the tumor tissues was GO alpha. Immunohistochemically, GO alpha was localized consistently in the cell membrane and occasionally in the cytoplasm of neuroendocrine tumors. GO alpha was also detected in sera of 73% patients with neuroblastoma at diagnosis, whereas serum GO alpha concentrations in control children, or patients with nonneuroendocrine tumors were lower than the detection limit of the immunoassay method employed. Serum GO alpha concentrations in patients with neuroblastoma changed with the clinical course; they fell in patients responding to treatment and increased in patients who relapsed. Since GO alpha, a specific protein in the neural and neuroendocrine cells, was found to be produced in considerable amounts by all types of neuroendocrine tumors but not in nonneuroendocrine tumors, GO alpha might be a useful biomarker for neuroendocrine tumors.
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PMID:Production of the alpha subunit of guanine nucleotide-binding protein GO by neuroendocrine tumors. 282 34

Gastrin-releasing peptide (GRP), the mammalian homolog of the amphibian peptide bombesin, is encoded in man by a single gene located on chromosome 18. Restriction enzyme and DNA sequence analyses establish that the gene is 10 kilobases in size with two introns of 4.8 and 3.9 kilobases. Exon 1 encodes the 5'-untranslated region, the signal peptide, and the first 23 amino acids of GRP. Exon 2 encodes the remaining three complete amino acids of GRP and the first 74 amino acids of the GRP carboxy-terminal extension peptide. Hence, intron 1 interrupts the coding region of the bioactive portion of GRP between the first and second nucleotides for Gly, the 24th amino acid of GRP. Exon 3 encodes the remainder of the GRP-extension peptide and the 3'-untranslated region. Two GC-rich, potential regulatory sequences and a sequence associated with regulation by cAMP lie between the CAAT and TATA boxes; the primary transcriptional start site is located 30 bases downstream from the TATA box. The second intron has an alternate donor site at its 5'-end and an alternate acceptor site at its 3'-end. S1 nuclease mapping demonstrates that differential RNA splicing using these sites results in the similar expression of three GRP mRNAs in GRP-containing neurons (in stomach and brain) as well as in GRP-containing neuroendocrine cells (fetal lung). In addition, the pattern of RNA splicing is similar between normal tissue and neoplastic tissue (small cell carcinoma of the lung and medullary carcinoma of the thyroid).
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PMID:Analysis of the gene and multiple messenger ribonucleic acids (mRNAs) encoding human gastrin-releasing peptide: alternate RNA splicing occurs in neural and endocrine tissue. 284 May 64


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