Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The examination of over 150 human subjects failed to reveal any differences in the basal excretion of CAMP between breast cancer and lung cancer patients and the corresponding control. But breast cancer patients show certain disorders in the diurnal rhythm of CAMP production and also in the response of CAMP to euphylline, especially insulin. Moreover, a peculiar impairment of the coordination was noted between the state of fat-carbohydrate metabolism and the character of SAMP excretion in breast and lung cancer. The authors stress the necessity to study not only CAMP basal production in oncological patients but also its synthesis against the background of different functional stimuli and in measures aimed at the correction of disorders in fat-carbohydrate metabolism.
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PMID:[Excretion of cyclic adenosine monophosphate in breast and lung cancer]. 18 54

Methadone was found to significantly inhibit the in vitro and in vivo growth of human lung cancer cells. The in vitro growth inhibition (occurring at 1-100 nM methadone) was associated with changes in cell morphology and viability detectable within 1 hr and was irreversible after a 24-hr exposure to the drug. These effects of methadone could be reversed in the first 6 hr by naltrexone, actinomycin D, and cycloheximide, suggesting involvement of opioid-like receptors and the requirement for de novo mRNA and protein synthesis. The inhibitory effects of methadone on the growth of lung cancer cells also could be achieved by the less addictive (+) isomer of methadone. Characterization of the methadone binding to lung cancer cell membranes revealed high-affinity (nM), saturable binding sites for (+/-)-[3H]methadone, which cross-reacted with ligands for kappa, phencyclidine, sigma, but not mu, and delta opioid receptors, and the binding characteristics appeared to be different from methadone sites present in rat brain. Methadone decreases cAMP levels in lung cancer cells, but the receptors are not coupled to a pertussis toxin-sensitive guanine nucleotide-binding regulatory protein. We conclude that the lung cancer growth inhibitory effects of methadone are significant, occur at low concentrations, and are mediated by a nonconventional type of opioid binding site distinct from methadone receptors found in the brain.
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PMID:Nonconventional opioid binding sites mediate growth inhibitory effects of methadone on human lung cancer cells. 131 Oct 82

Using specific ligands, we find that lung cancer cell lines of diverse histologic types express multiple, high-affinity (Kd = 10(-9)-10(-10) M) membrane receptors for mu, delta, and kappa opioid agonists and for nicotine and alpha-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations (approximately 100 nM) found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas mu, delta, and kappa opioid agonists at low concentrations (1-100 nM) inhibited lung cancer growth in vitro. We also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides (beta-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, we tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a "tumor suppressor" system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.
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PMID:Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines. 215 43

Studies on humoral hypercalcemia of malignancy have shown that tumors produce a protein that acts through the parathyroid hormone (PTH) receptor but is immunologically distinct from PTH. We have recently purified and cloned a parathyroid hormone-related protein (PTHrP) from a human lung cancer cell line. Full length cDNA clones were isolated and found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino terminal residues are identical with human PTH, although antisera directed at the amino terminus of PTHrP do not recognize PTH. A 34-amino acid synthetic peptide, PTHrP(1-34), was several times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of cAMP and plasminogen activity in osteogenic sarcoma cells and activation of adenylate cyclase in chick kidney membranes. PTHrP(1-34) was also more potent than PTH(1-34) in stimulating cAMP and phosphate excretion and reducing calcium excretion in the isolated perfused rat kidney. PTHrP has been consistently demonstrated by immunohistochemistry in squamous cell carcinomas and in keratinocytes present in normal skin, but not in normal or hyperplastic parathyroid tissues or other tumors. PTHrP-like activity has been extracted from ovine placenta and fetal parathyroid tissue, suggesting that PTHrP may play a role in fetal calcium homeostasis.
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PMID:Humoral hypercalcemia of malignancy. 233 5

We previously demonstrated that an acidic variant (B1) of lysosomal arylsulfatase B from transplanted human lung cancer is phosphorylated on its protein and carbohydrate moieties (Gasa, S., and Makita, A. (1983) J. Biol. Chem. 258, 5034-5039). The present study identifies that a cAMP-dependent protein kinase is responsible for phosphorylation of arylsulfatase B. The protein kinase activity toward the sulfatase was considerably higher in the transplanted lung cancer than in normal lung in the presence of cAMP. B enzyme purified from normal human liver was found to contain 0.6 mol/mol B enzyme, and protein kinase treatment added further 1.3 mol of Pi to give a single phosphopeptide (X). On the other hand, B1 enzyme purified from the transplanted human lung cancer which had been labeled in vivo with 32Pi revealed at least two phosphopeptides (X and Y). Assuming that the sulfatase from normal liver and lung cancer possesses the same number of available phosphorylation sites, phosphorylation of site X which was available only by deliberate phosphorylation of the native, ordinary B enzyme appears to be cancer-associated. Increasing phosphorylation of the sulfatase resulted in a maximum 50% elevation in arylsulfatase activity, followed by a decrease of the activity upon overphosphorylation, using an artificial substrate.
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PMID:Phosphorylation of human lysosomal arylsulfatase B by cAMP-dependent protein kinase. Different sites of phosphorylation between normal and cancer tissues. 243 76

The results are reported of a multidisciplinary diagnostic and therapeutic program applied to 381 patients with lung carcinoma from 1983 through 1985 at Mestre General Hospital. Cytologic and/or histologic diagnosis was established in 95% and staging accomplished in 96% of the patients. One-hundred-twenty-nine patients with non-small cell cancer were primarily treated by surgery (lobectomy or pneumonectomy); 3-year survival of this group was 48%. Of the 45 patients with pN1 or pN2 disease, 23 were treated with postoperative adjunctive mediastinal radiotherapy (50Gy/25 F/5Wk); however, survival showed no significant difference in the two groups. Ninety-seven inoperable patients were treated by radiotherapy alone; among those receiving doses of 50-60 Gy in 5 to 6 weeks, 3-year survival was 10%. Chemotherapy (CAMP), used in 23 cases (22 stage IV, 1 stage III), showed no improvement in survival, as compared with a similar series of patients submitted to symptomatic treatment alone. Of the 27 patients affected by small-cell carcinoma, 14 were treated with an aggressive radiochemotherapy protocol and 13 with palliative radiotherapy or low-dose chemotherapy: median survival in the two groups was respectively 45 and 60 weeks. Our study demonstrates the clinical feasibility of interdisciplinary programs routinely applied to a large population of lung cancer patients, and confirms its rationale in terms of early diagnosis, improved staging, and adequate treatment.
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PMID:[Diagnostic and therapeutic approach to lung neoplasms. Departmental experience at the Mestre Hospital]. 245 97

Studies of humoral hypercalcemia of malignancy (HHM) have provided evidence that tumors produce a protein that acts through the parathyroid (PTH) receptor but is immunologically distinct from PTH. We have recently purified and cloned a parathyroid hormone-related protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino-terminal residues are identical with human PTH, although antisera directed to the amino-terminus of PTHrP do not recognize PTH. The striking homology with PTH about the amino-terminal region is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone. A 34-amino acid synthetic peptide, PTHrP(1-34) was 2-4 times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of cAMP and plasminogen activity in osteogenic sarcoma cells and activation of adenylate cyclase in chick kidney membranes. Like PTH, PTHrP peptides of less than 30 residues from the amino-terminus showed substantially reduced activity. PTHrP(1-34) was also more potent than hPTH(1-34) in stimulating cAMP and phosphate excretion and reducing calcium excretion in the isolated perfused rat kidney. Immunohistochemical localization of PTHrP was consistently demonstrated in squamous cell carcinomas. In normal tissues PTHrP has been immunohistochemically localized in keratinocytes and PTHrP-like activity has been extracted from ovine placenta and fetal ovine parathyroids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Humoral hypercalcemia of malignancy. 269 18

Previous studies from this laboratory have demonstrated that arylsulfatase B (ASB) is phosphorylated by a protein kinase, which is the first finding of phosphorylation in lysosomal hydrolases. The present study was undertaken to characterize the sites of phosphorylation in ASB from transplanted human lung cancer and from normal human tissues, and to identify type of tumor protein kinase responsible for the phosphorylation of ASB. When ASB purified from liver and placenta was phosphorylated in vitro by a cAMP-dependent protein kinase, it gave a single tryptic phosphopeptide (X) and phosphothreonine. On the other hand, the tumor ASB which had been phosphorylated in vivo demonstrated two phosphopeptides X and Y. Since the tumor ASB had been shown to be phosphorylated both at threonine and serine residues, phosphorylation at threonine residue of peptide X, which is phosphorylated by a cAMP-dependent protein kinase, will be cancer-associated. Through photoaffinity labeling with a labeled cAMP analogue to detect regulatory subunits of cAMP-dependent protein kinase subtypes, it was found that the cAMP-dependent protein kinase in the transplanted lung tumor was largely type II which can be ascribed to the appearance of highly phosphorylated ASB in the tumor.
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PMID:Protein phosphorylation of human lysosomal arylsulfatase B from normal and cancer tissues. 338 98

Many lysosomal hydrolases in cases of human cancer were found to be accompanied by acidic variant forms together with the major hydrolase components. Such variants were found to be phosphorylated not only at their carbohydrate moiety which contributes largely to their acidic property, but also at the protein moiety. We identified a cAMP-dependent protein kinase which is responsible for phosphorylation of arylsulfatase B. The protein kinase activity toward the sulfatase was considerably higher in transplanted lung cancer than in normal lung in the presence of cAMP. The B enzyme purified from normal human liver was found to contain 0.6mol of Pi/mol of B enzyme, and protein kinase treatment added a further 1.3mol Pi to give a single phosphopeptide (X) containing phosphothreonine. On the other hand, the B1 enzyme purified from transplanted human lung cancer which had been labeled in vivo with [32P] Pi revealed at least two phosphopeptides (X and Y). Assuming that the sulfatase from liver and lung cancer possesses the same number of available phosphorylation sites, phosphorylation of site X (Thr) which is available only by deliberate phosphorylation of the native, ordinary B enzyme, appears to be cancer-associated. Increased phosphorylation of the sulfatase resulted in a maximum 50% elevation in arylsulfatase activity, followed by a decrease in the activity upon overphosphorylation, using an artificial substrate.
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PMID:[Phosphorylation of lysosomal hydrolases in human cancer and its significance]. 360 35

Type I and type II cAMP receptor proteins participate in cell growth regulation, differentiation and neoplastic transformation of neoplasms. In this paper the growth regulatory effects of cAMP analogs, DBcAMP (non-site-selective) and 8-Cl-cAMP (site-selective) on a highly metastatic human lung cancer cell line PG were studied. By MTT assay, DBcAMP at 1mmol/L was found to inhibit PG growth by 30% on the day 8, while 8-CL-cAMP at 10-20 mumol/L inhibited the growth by 75%-80%. When phosphodiesterase inhibitor isobutyl-1-methyl-xanthine (IBMX) was added the inhibitory effect of 8-Cl-cAMP was not enhanced, whereas that of DBcAMP was significantly enhanced. The invasiveness and colony-forming ability of the treated cells decreased. The cAMP level as determined by RIA was much more increased in DBcAMP-treated than in 8-Cl-cAMP-treated PG cells. The result suggests that 8-Cl-cAMP and DBcAMP exert their effects on tumor cell growth and invasion by defferent mechanisms.
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PMID:[Effects of site-selective 8-Cl-cAMP on the growth regulation of human lung giant cell cancer]. 765 98


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