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)

Phosphodiesterase I (EC 3.1.4.1) activity was detected in normal human blood serum. The enzyme is stable at laboratory temperature for three days, but is inactivated at pH less than 7. The pH for optimum activity increases with the substrate concentration (under the conditions used, from pH 9.0 to 10.2) and, conversely, the Km increases with pH and buffer concentration. The enzyme is inhibited by ethylenediaminetetraacetate but not by phosphate (0.1 mol/liter). We developed a simple quantitative method for its determination, based on hydrolysis of the p-nitrophenyl ester of thymidine 5'-monophosphate and subsequent measurement of the liberated p-nitrophenol at 400 nm in NaOH (0.1 mol/liter). Normal values (mean +/- 2 SD) were determined to be 33 +/- 6.4 U/liter. Preliminary studies indicate that phosphodiesterase I activity is greater than normal in serum of patients with necrotic changes in the liver or kidney or in cases of breast cancer, but not in that of patients with myocardial infarction, bone cancer, lung cancer, or chronic liver cirrhosis.
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PMID:Determination of phosphodiesterase I activity in human blood serum. 16 91

During pregnancy, calcium is continuously transferred directly from the maternal intestine to the fetal bone, a transfer that is mainly induced by the interrelated actions of the calcium-regulating hormones parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D) and calcitonin. It has recently been demonstrated in animals that PTH-related protein (PTHrP) is the fetal equivalent of PTH. Human PTHrP, originally described as a product of a human lung cancer cell line and implicated in the pathogenesis of humoral hypercalcemia of malignancy, is a protein with 141 amino acids, and it has biochemical actions similar to PTH. It is believed that fetal PTHrP is mainly derived from the placenta during early gestation and from the fetal parathyroid glands during further development and that this protein has the role of maintaining the maternal-fetal calcium gradient either alone or in concert with 1,25(OH)2D. With birth, the placental supply of calcium ceases abruptly, stimulating the increase of PTH and 1,25(OH)2D, which are the main regulators of postnatal calcium metabolism. Alterations in the placental calcium (and phosphate) gradient may be caused by maternal hypo- or hypercalcemia and placental insufficiency and may be followed by transient disorders of calcium metabolism in the newborn. Due to abrupt cessation of the calcium and phosphate supply after delivery at a time when mineral demands are the highest, preterm infants are especially prone to hypocalcemia and osteopathy. If bone disease of prematurity is to be prevented, the amounts of calcium and phosphate must be adequate, as demonstrated by laboratory tests, the most important being calcium and phosphate in urine and alkaline phosphatase activity in serum.
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PMID:[Perinatal calcium metabolism. Physiology and pathophysiology]. 143 20

Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer.
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PMID:Skin test reactivity in patients suffering from lung and breast cancer. 171 Jun 31

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

Thymidylate synthase was identified at the cellular level using anti-thymidylate synthase monoclonal antibody (M-TS-4) developed against HeLa cell line. HeLa cells, 9L rat gliosarcoma cells, and some of human brain tumor cells (medulloblastoma, metastatic brain tumors from lung cancer and osteosarcoma) were cultured in complete medium for 72 hr and fixed with 10% buffered formalin. These were covered with 1:20 dilution of M-TS-4 in Burridge buffer and 1% bovine serum albumin for 4 or 24 hr. After rinsing twice with phosphate-buffered saline solution (PBS), the cell staining was made with avidin-biotin peroxidase complex (ABC). In addition, HeLa cells were exposed to 2 microCi/ml of tritiated thymidine for 30 min, cultured again for 0 to 5 hr, and subjected to autoradiography after M-TS-4 staining with ABC. All cells were stained satisfactorily with ABC except 9L rat gliosarcoma cells. Autoradiography revealed that 38% of the cells were stained with ABC, 28% were labeled with tritiated thymidine, while only 8% of the cells were stained simultaneously at 0 hr specimen. However, the cells labeled with both agents subsided when the cells were incubated in complete medium for 1 or 2 hr before fixation. Therefore, thymidylate synthase appears to exist mainly in G1-phase and to subside in early S-phase. Although the number of thymidylate synthase positive cells was greater than that of the cells labeled with tritiated thymidine, the ratio was constant (r = 0.99). The fraction of S-phase can be estimated from that of thymidylate synthase positive cells. Thymidylate synthase positive cell fraction may become another important segment for cell cycle analysis.
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PMID:[Cell kinetic studies using monoclonal antibody to thymidylate synthase]. 244 34

To facilitate understanding of the mechanisms underlying pulmonary diseases, including lung cancer and cystic fibrosis, we have transformed and characterized cultures of human tracheal epithelial cells. Cells were transfected by calcium phosphate precipitation with a plasmid containing a replication-defective simian virus 40 (SV40) genome. Colonies of cells with enhanced growth potential were isolated and analyzed for transformation- and epithelial-specific characteristics. Precrisis cells were observed to express the SV40 large tumor antigen, produce cytokeratins, have microvilli, and form tight junctions. After crisis, cells continued to express the SV40 large tumor antigen as well as epithelial-specific cytokeratins and to display the apical membrane microvilli. Apical membrane Cl channels were opened in postcrisis cells exposed to 50 microM forskolin. These channels showed electrical properties similar to those observed in primary cultures. The postcrisis cells have been in culture for greater than 250 generations and are potentially "immortal." In addition to providing a useful in vitro model for the study of ion transport by human airway epithelial cells, the cells can be used to examine stages of neoplastic progression.
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PMID:Characterization of human tracheal epithelial cells transformed by an origin-defective simian virus 40. 245 4

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

Peripheral blood samples from six cancer patients (five colon cancer, one lung cancer) and six healthy volunteers were tested in vitro for oxygen radical production by phagocytic cells and in assays of mitogen-induced lymphoblastogenesis at physiologic and pharmacologic concentrations of pyridoxine (PN, 1.8-96 nmol/ml) or pyridoxal (PL, 0.08-90 nmol/ml). Plasma levels of pyridoxal-5'-phosphate (PLP), 4-pyridoxic acid (4PA), pyridoxamine phosphate (PMP), and PL were also determined. Phagocytic cells from three patients showed significantly increased capacity for oxygen radical production when incubated in PL-, but not PN-supplemented media. Oxygen burst capacity of cells from healthy subjects was significantly enhanced by PN-, but not PL-enriched media. Lymphocyte responsiveness to phytohemagglutinin or pokeweed mitogen (PWM) stimulation showed a modest increase in cell activation in three patients as the concentration of PN was increased; with concanavalin A, two showed enhanced responsiveness. On the other hand, PL-supplementation resulted in greater cell proliferation only with PWM. The cancer patients had significantly lower plasma PLP, 4PA, and PMP levels when compared with the healthy volunteers. These data indicate that in the cancer patients and in a majority of the healthy volunteers, vitamin B-6 status was marginal or deficient and suggest that increasing PN or PL in vivo levels may augment functions related to cell-mediated immunity.
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PMID:Evaluation of cancer patient leukocyte responses in the presence of physiologic and pharmacologic pyridoxine and pyridoxal levels. 273 45

A case-control study that included 25,398 cases of lung cancer among Florida residents, first diagnosed in 1981-1983, was conducted to determine if residence in the central Florida phosphate mining region was associated with an increased risk of lung cancer. A twofold increase in lung cancer risk was observed among male nonsmokers who lived in the study area. Risks were elevated for all major lung cancer cell types, with the highest risks observed for small cell carcinoma of the lung. Among cigarette smokers, a slight, but not statistically significant, additional increase in risk was associated with residence in the study area. Among women, no significant elevations in risk were observed for persons who lived in the study area. The greatest increase in risk among women was for small cell carcinomas, but the elevations were not statistically significant.
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PMID:Lung cancer in Florida. Risks associated with residence in the central Florida phosphate mining region. 283 99

Estramustine-binding protein has previously been demonstrated in normal rat prostatic tissue, in normal human prostate epithelium, and in prostatic carcinomas. It binds specifically estramustine and estromustine, the cytotoxic metabolites of estramustine phosphate (Estracyt), a drug which is used in the treatment of prostatic carcinoma. In this study we have examined the presence of an estramustine-binding associated protein in a panel of human cell lines, representing the major histopathological types of lung cancer. A mouse (murine) monoclonal antiserum developed against rat estramustine-binding protein was used for immunohistochemical detection. Fast protein liquid chromatography was used for biochemical characterization. As judged from the immunohistochemical investigation, estramustine-binding protein was present in large amounts in five of six non-small cell carcinoma cell lines, while seven of eight small cell carcinoma cell lines were essentially negative. Fast protein liquid chromatography analyses of lysated cells from the lung cancer cell lines, incubated with [3H]estromustine, concurred with the results from the immunohistochemical stainings. These data strongly indicate a convincing connection between the immunoreactivity and ligand-binding properties of estramustine-binding protein in the cell lines examined. The presence of an estramustine-binding associated protein in human lung cancer cell lines has implications for further investigations into the biological relevance and the potential for eventual therapeutic applications.
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PMID:Expression of an estramustine-binding associated protein in human lung cancer cell lines. 284 Jan 98


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