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)

The lethal effect of high-dose melphalan in mice could be offset by pretreatment with cyclophosphamide, cytosine arabinoside or low-dose melphalan. The reason for improved survival is unclear. Althoug animals given high-dose melphalan died with symptoms of gut death, in only one instance, that with low-dose melphalan itself, did pretreatment protect the intestinal epithelium as measured by the microcolony assay. A small enhancement in the recovery of the haemopoietic tissue in pretreated animals was noted, although this on its own is unlikely to explain the phenomenon. Experiments in tumour-bearing mice showed that pretreatment with cyclophosphamide did not reduce the toxicity of melphalan to the Lewis lung carcinoma.
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PMID:Effect of high-dose melphalan on marrow and intestinal epithelium in mice pretreated with cyclophosphamide. 68 11

Severe gastrointestinal dysmotility is a newly recognized paraneoplastic syndrome that occurs with small-cell lung carcinoma. Thirty-four patients with small-cell carcinoma, of whom 5 had chronic intestinal pseudoobstruction and 29 had no digestive symptoms, were studied serologically. Four of the 5 patients with gut dysmotility had immunoglobulin G antibodies reactive with neurons of the myenteric and submucosal plexuses of jejunum and stomach in an indirect immunofluorescence assay. Antibodies of this type were not found in any of the 29 patients who had no gut dysmotility, nor were they found in patients with chronic idiopathic intestinal pseudoobstruction (n = 8), ovarian cancer (n = 20), or epilepsy (n = 4) or in normal subjects (n = 9). In 4 of the patients with paraneoplastic pseudoobstruction, antibodies in highly diluted serum (1:4000-1:8000) bound selectively to nuclei and cytoplasm of neuronal elements in the gut. This novel autoantibody activity suggests that intestinal pseudoobstruction occurring in patients with small-cell carcinoma may have an autoimmune basis. From a clinical standpoint, serological testing offers a simple means for determining which patients with gut dysmotility syndromes may have associated small-cell carcinoma, thereby enabling earlier diagnosis and treatment of the tumor.
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PMID:Enteric neuronal autoantibodies in pseudoobstruction with small-cell lung carcinoma. 165 50

Recent progress in cancer research revealed that gut hormones have the activity to regulate the cellular growth of cancer cells. Gastrin, cholecystokinin and vasoactive intestinal peptide were demonstrated to stimulate the growth of gastric cancer cells, pancreatic cancer cells and colon cancer cells, respectively. Accordingly, it is possible to assume that these gut hormones may play an important role in the progression of these cancers. Further studies will be required to clarify the role of gut hormones as physiological growth factors in gastrointestinal tissues. The other aspect of gut hormones related with cellular growth is their role as autocrine growth factors. Gastrin-releasing peptide (GRP) is classified as a gut hormone with the structural similarity with amphibian bombesin. Several reported findings indicate that GRP functions as an autocrine growth factor for human small cell lung carcinoma; a monoclonal antibody for GRP is now applied for the therapy of this cancer. It is important to find out other gut hormones functioning as autocrine growth factors.
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PMID:[Gut hormones with activity to modulate cellular growth]. 208 20

This report documents the occurrence of chronic intestinal pseudoobstruction in association with a small cell carcinoma of the lung with evidence of pre- and postganglionic sympathetic dysfunction in one patient with brain metastases, and with sympathetic and parasympathetic postganglionic dysfunction in a second patient. A strategy is outlined for the identification and characterization of disordered neural control of gut motility. This strategy utilizes gastrointestinal motility studies to confirm gut neuropathy, autonomic function tests, and plasma norepinephrine responses to intravenous edrophonium to identify the level of dysfunction. These cases are compared with others in the literature, and the occult nature of these cancers, the spectrum of symptoms suggesting autonomic dysfunction on presentation, and the occasional response of the neurologic deficit to treatment of the malignancy are highlighted.
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PMID:Autonomic function and motility in intestinal pseudoobstruction caused by paraneoplastic syndrome. 255 92

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

Small cell lung carcinoma (SCLC) is histologically simple, and shows a characteristic ultrastructure and very complex functions. Recently, a large amount of information has been accumulated by fundamental research, largely involving studies on many cultured cell lines. Now their potential application to the therapy of SCLC is being sought. A characteristic ultrastructural feature is the presence of dense-cored neurosecretory-type granules 100-200 nm in diameter. In addition, epithelial cell characteristics are noted. Predominance of either a neurosecretory or epithelial nature may affect the responsiveness of tumors to therapy. Many kinds of brain-gut hormones are produced by SCLC. Gastrin-releasing peptide (GRP) has attracted much attention as an autocrine growth factor for SCLC. Aromatic L-amino acid decarboxylase (AADC), neuron-specific enolase (NSE) and creatine kinase BB (CK-BB) are rather specific to SCLC. NSE and CK-BB together with GRP are good monitoring markers during treatment. Amplification of c-myc, N-myc and L-myc is seen in SCLCs. Areas both with and without N-myc amplification are found in both the primary site and metastatic sites in a single case. Del 3p(14-23) is characteristic for SCLC but SCLCs without such deletion are also present. A cytologically "variant" type is composed of cells simulating "large cells", in which the doubling time is short, AADC and GRP are undetectable, granules are rare, and the cells are resistant to radiation. However, one cell line of the classic type has revealed reversible squamous cell change in the absence of retinoic acid, becoming radioresistant without showing any remarkable changes in AADC, NSE or CK-BB. Since SCLC mixed with "large cells" or "small cell carcinoma of undifferentiated type" is resistant to therapy and possesses a more epithelial nature, small cell carcinoma with a large cell component has been proposed as a subtype. The question of whether this subclassification is practical should be confirmed by prospective study.
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PMID:[Pathology and biology of small cell lung cancer]. 283 14

Peptides corresponding closely in structure to the biologically active carboxyl terminal region of the amphibian peptide bombesin have now been isolated from several mammalian species, including man. Two principal forms have been found: one contains 27 amino acids and exhibits variations in amino acid sequence in the amino terminal region; the other is the carboxyl terminal decapeptide and probably does not vary among mammals. These peptides exhibit full immunoreactivity with most bombesin antisera and account for "bombesin-like immunoreactivity" that has been described in mammalian brain, sympathetic ganglia, and nerve fibers in the gut as well as in fetal lung endocrine cells and certain lung tumors, especially small cell lung carcinoma. The name gastrin releasing peptide (GRP) was given to the porcine and avian heptacosapeptides by McDonald and Mutt. The larger and smaller mammalian peptides now often are called GRP27 and GRP10. Both forms exhibit the full spectrum of activity shown by bombesin. Evidence has been obtained that neural release of mammalian bombesin-like peptides is physiologically important in regulation of gastrin release from the stomach. Lung tumors that produce bombesin-like peptides also have receptors for bombesin. These receptors appear to be involved in the autocrine regulation of tumor cell proliferation.
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PMID:Mammalian bombesin-like peptides: neuromodulators of gastric function and autocrine regulators of lung cancer growth. 300 26

A 58-year-old woman who had presented with intestinal pseudo-obstruction died 9 months later from rapidly progressive neurologic symptoms and autonomic insufficiency. Her gastric emptying had been markedly delayed and transit of markers had been slowed throughout the small bowel. A 5-hour manometric recording of the antrum and duodenum had shown absence of the normal interdigestive motor complex, which was replaced by irregular contractile activity of reduced amplitude. A small-cell carcinoma of the lung was found at autopsy. Pathologic study of the gut showed widespread degeneration of the myenteric plexus, which was infiltrated by plasma cells and lymphocytes and contained significantly reduced numbers of neurons. The extra-intestinal nervous system had neuronal loss and lymphocytic infiltrates in dorsal root ganglia. Thus, a gastrointestinal neuropathy causing intestinal pseudo-obstruction may be the presenting manifestation of a paraneoplastic syndrome associated with small-cell carcinoma.
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PMID:Intestinal pseudo-obstruction as the presenting manifestation of small-cell carcinoma of the lung. A paraneoplastic neuropathy of the gastrointestinal tract. 629 44

Enolase is a glycolytic enzyme widely distributed in each mammalian tissue and consists of three distinct subunits alpha, beta, and gamma. In the brain enolase exhibits three dimetric isozymic forms: alpha alpha, alpha gamma and gamma gamma. The gamma protein subunit has recently been found to be identical with the nervous system-specific and species-nonspecific protein, 14-3-2; therefore, alpha gamma and gamma gamma types of enolase were characterized as neuron-specific enolase (NSE). NSE has been also detected in the pituitary gland, thyroid gland, adrenal medulla and pancreas, all of which contain neuroendocrine cells. Recently NSE was observed by immunostaining or radioimmunoassay in neuroendocrine tumor such as glucagonomas, insulinomas, gut carcinoids, medullary thyroid carcinomas or neuroblastomas. Furthermore, small cell carcinoma of the lung which has been known to frequently exhibit neuroendocrine properties was found to produce NSE. In this paper NSE as a tumor marker in various cancers was evaluated by immunostaining or enzyme immunoassay which was developed by a co-worker Kato. The data revealed that serum NSE was clinically useful as a tumor marker, especially a monitoring marker of disease extent. NSE productions were also observed in adenocarcinoma of the colon or the lung and large cell carcinoma of the lung as well as small cell carcinoma of the lung and the esophagus, all of which were considered to share the biochemical features of neuroendocrine tumor. The evidence challenges a speculation that small cell carcinoma of the lung has an origin separated from the other histological types of lung carcinoma. In this meaning NSE is an important tumor marker for both clinical medicine and basic research.
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PMID:[Neuron-specific enolase as a new tumor marker]. 634 46

The aims of this study were to investigate, in patients with newly diagnosed small-cell lung carcinoma (SCLC), whether or not there may be a relationship between the presence, type or titer of circulating neuronal autoantibodies and (i) the extent of SCLC dissemination at presentation, (ii) the development of peripheral neuropathy during platinum chemotherapy, (iii) survival time. We studied stored serum from 58 patients with uncomplicated SCLC who had participated in two trials conducted by the North Central Cancer Treatment Group (NCCTG); 29 had extensive disease and 29 had limited disease. No patient had neuropathy or other neurological or paraneoplastic problems at the time of enrollment but each group included 14 or 15 patients respectively who developed peripheral neuropathy in the course of chemotherapy. We tested five consecutive serum specimens from each patient in blinded fashion by (i) an indirect immunofluorescence assay optimized to detect neuron-restricted nuclear and cytoplasmic antibodies (triple substrate of mouse cerebellum, gut and kidney), and (ii) immunoprecipitation assays to detect neuronal Ca2+-channel-binding antibodies (N-type and P/Q-type). Sera that were positive by immunofluorescence were analyzed further by Western blotting. Neuronal autoantibodies were significantly more frequent in patients who had limited SCLC at presentation (12/29 or 41% positive) than in those with extensive SCLC (5/29 or 17% positive, P = 0.02). Neuronal autoantibodies of nuclear or cytoplasmic specificity were found in 50% of the seropositive patients with limited SCLC (21% of the total group), but in no patient with extensive SCLC (P = 0.01). The frequency of neuronal autoantibodies did not differ significantly among patients who did and did not develop peripheral neuropathy. Titers fell progressively during chemotherapy and did not rise again when peripheral neuropathy became clinically evident. This argues against a synergism between drug toxicity and neuronal autoimmunity as the mechanism of platinum-associated peripheral neuropathy. Seropositivity for neuronal autoantibodies did not affect the survival of patients with either limited or extensive SCLC. It is conceivable that the immunosuppression attendant on combined cisplatin/etoposide therapy cancels a pre-existing protective antitumor immune response (presumably cytotoxic-T-cell-mediated) for which the nuclear and cytoplasmic paraneoplastic IgG autoantibodies serve as a surrogate marker. Testing of this hypothesis would require the survival of seropositive and seronegative patients to be compared in a larger trial, using a therapeutic modality that does not compromise immunocompetence.
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PMID:Neuronal autoantibody titers in the course of small-cell lung carcinoma and platinum-associated neuropathy. 1041 61


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