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 human monoclonal antibody (MAb) AE6F4 is secreted by a human-human hybridoma line established from the in vitro immunization of normal human peripheral blood lymphocytes with the human lung adenocarcinoma cell line, A549. This MAb is strongly reactive to lung cancer tissues. In the previous study, the antigens recognized by the MAb AE6F4 were purified from A549 cells and identified as 14-3-3 protein and 31 kDa cytosolic phospholipase A2 (cPLA2). The MAb AE6F4 also binds two kinds of antigens (53 kDa and 40 kDa), which are not related to 14-3-3 protein or 31 kDa cPLA2, in the human breast adenocarcinoma cell line, MCF-7. We purified a 38 kDa antigen, which is a degradation product of 53 kDa antigen from breast adenocarcinoma MCF-7 cells using ion-exchange and hydroxyapatite column chromatography. Two partial amino acid sequences of the purified 38 kDa antigen showed 95-100% homology to human cytokeratin 8 (CK8). Two-dimensional gel electrophoresis and immunoblot analysis of intermediate filament fraction separated from MCF-7 cells demonstrated that the 53 kDa and 40 kDa antigens were CK8 and CK19, respectively. Antigenic determinants on CK8 and CK19 recognized by the MAb AE6F4 were resistant to sodium periodate treatment, although antigenic determinant on 31 kDa antigen (14-3-3 protein and(or) cPLA2) was sensitive to this treatment. These results suggest that the MAb AE6F4 reacts with both carbohydrate and peptide antigenic determinants.
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PMID:Cytokeratin 8 and 19 as antigens recognized by adenocarcinoma-reactive human monoclonal antibody AE6F4. 939 22

Cisplatin is the most active anticancer agent for lung cancer. It has been reported that intracellular accumulation of cisplatin is important in determining resistance to cisplatin, which may be modulated by Na+, K(+)-ATPase activity. On the other hand, it is well-known that sorbitol, a metabolite of glucose mediated by aldose reductase, reduces Na+, K(+)-ATPase in diabetic neuropathy. In this study, the effect of exogenous sorbitol on Na+, K(+)-ATPase activity and sensitivity to cisplatin was evaluated using human non-small-cell lung cancer (NSCLC) cell lines. In the NSCLC cell lines, EBC-1, PC-3, and RERF-LC-MS the cytotoxicities of cisplatin were impaired by exposure to sorbitol in these cell lines. Na+, K(+)-ATPase was inactivated and intracellular accumulation of cisplatin was decreased by the exposure. These results suggest that accumulation of sorbitol may induce resistance to cisplatin in NSCLC cells, and diabetes poorly controlled may be one of the determinants of the antitumor effect of cisplatin in NSCLC.
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PMID:Exposure to sorbitol induces resistance to cisplatin in human non-small-cell lung cancer cell lines. 941 70

Recombinant methioninase (rMETase) is a homotetrameric pyridoxal 5'-phosphate enzyme of 172-kda molecular mass derived from Pseudomonas putida and cloned in Escherichia coli. rMETase has been found previously to be an effective, anti-tumor agent in vitro and in vivo. The enzyme targets the elevated minimal methionine requirement seen in all tumor types. In order to prevent immunological reactions which might be produced by multiple dosing of rMETase and to prolong the serum half-life of rMETase, the N-hydroxysuccinimidyl ester of methoxypolyethylene glycol propionic acid (M-SPA-PEG 5000) has been coupled to rMETase. Molar ratios of M-SPA-PEG-5000 (PEG) to rMETase from 10 to 40 were used for PEGylation of rMETase. PEGylation reactions were run at 20 degrees C for 30 to 60 min in reaction buffer (20 mM sodium phosphate buffer, pH 8.3). The PEGylated molecules (PEG-rMETase) were purified from unreacted PEG with Amicon 30 K centriprep concentrators or by Sephacryl S-300 HR gel-filtration chromatography. Unreacted rMETase was removed by DEAE Sepharose FF anion-exchange chromatography. The resulting PEG-rMETase subunit, from a PEG/rMETase ratio of 30/1 in the synthetic reaction, had a molecular mass of approximately 53 kda determined by matrix-assisted laser desorption/ionization mass spectrometry, indicating the conjugation of two PEG molecules per subunit of rMETase and eight per tetramer. PEG-rMETase molecules obtained from reacting ratios of PEG /rMETase of 30/1 had enzyme activities of 70% of unmodified rMETase. PEGylation of rMETase increased the serum half-life of the enzyme in rats to approximately 160 min compared to 80 min for unmodified rMETase. PEG-rMETase could deplete serum methionine levels to less than 0.1 microM for approximately 8 h compared to 2 h for rMETase in rats. Efficacy studies of PEG-rMETase on human lung cancer and kidney cancer cells in vitro demonstrated a 50% inhibitory concentration (IC50) of 0.04 and 0.06 units/ml, respectively. These IC50 values were almost identical to unmodified rMETase, thus indicating maintenance of antitumor efficacy in the PEGylated enzyme. PEG-rMETase had an IC50 for normal lung and kidney cells of 0.8 and 1.5 units/ml, respectively, similar to rMETase. The efficacy data indicated that PEG-rMETase maintained the high level tumor selectivity of rMETase. PEG-rMETase injected intravenously in mice demonstrated a tumor/blood retention ratio of approximately 1/6 compared to 1/10 of unmodified enzyme, indicating that PEG-rMETase distributes to the tumor at least as effectively as rMETase.
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PMID:Polyethylene glycol conjugation of recombinant methioninase for cancer therapy. 947 56

cis-Diamminedichloroplatinum(II) (CDDP) is a key anticancer agent. It has been reported that intracellular accumulation of CDDP is an important step as a determinant for resistance to CDDP, which may be modulated by Na+, K(+)-ATPase activity. In this study, the significance of membrane Na+, K(+)-ATPase activity and the role of thromboxane (TX) receptors were evaluated using human lung cancer cell lines. In the non-small-cell lung cancer (NSCLC) cell line, EBC-1, sensitivity to CDDP was improved by treatment with two different selective thromboxane receptor antagonists, calcium 5(z)-[1R,2S,3S,4S-7-[3-phenylsulfonylaminobicyclo [2.2.1]hept-2-yl]-5-heptenoate hydrate (S-1452), and (3R)-3-(4-fluorophenyl sulfonamido)-1,2,3,4-tetrahydro-9-carbazolepropanoic acid (BAYu3405). Na+, K(+)-ATPase was activated and intracellular accumulation of CDDP increased with treatment in EBC-1. In the small-cell lung cancer (SCLC) cell lines, SBC-1, sensitivity to CDDP and Na+, K(+)-ATPase activity did not change significantly, and intracellular accumulation of CDDP was not modulated. These results suggest the importance of the TX receptors as determinants of the sensitivity to CDDP in NSCLC cell lines. However, Na+, K(+)-ATPase activity and the role of TX receptors may not be so significant in the resistance mechanisms to CDDP in SCLC cell lines. In EBC-1 cells, the specific binding of S-145 was evident, but not in SBC-1 cells. The difference in TX receptors in NSCLC and SCLC cell lines may be one of the reasons for the variety of the antitumor effects of CDDP in chemotherapy for lung cancer.
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PMID:Role of thromboxane receptor on the intracellular accumulation of cis-diamminedichloroplatinum(II) in non-small-cell but not in small-cell lung cancer cell lines. 961 69

cis-Diamminedichloroplatinum(II) (CDDP) is the most active anticancer agent. It has been reported that intracellular accumulation of CDDP is an important step as a determinant for resistance to CDDP, which may be modulated by Na+, K(+)-ATPase activity. In this study, the significance of membrane Na+, K(+)-ATPase activity in the intracellular accumulation of CDDP were evaluated using human lung cancer cell lines. Na+, K(+)-ATPase was active in each cell line, not only non-small-cell lung cancer (NSCLC) but also in small-cell lung cancer (SCLC) cell lines. In NSCLC cell lines, there were significant correlations between Na+, K(+)-ATPase activities and intracellular accumulation of CDDP and the accumulation significantly decreased by ouabain, an inhibitor of Na+, K(+)-ATPase in each cell line. However, the correlation between enzyme activity and intracellular accumulation of CDDP were not significant in SCLC cell lines where sensitivity to CDDP was better than in NSCLC cell lines. These results suggest Na+, K(+)-ATPase are active in both NSCLC and SCLC cells, however, the importance of the enzyme as an active transporter of CDDP may be limited only to NSCLC cells. The mechanisms of intracellular accumulation may not be so important as a determinant of sensitivity to CDDP in SCLC cells.
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PMID:Significance of Na+, K(+)-ATPase on intracellular accumulation of cis-diamminedichloroplatinum(II) in human non-small-cell but not in small-cell lung cancer cell lines. 961 70

Molecular mechanisms of interplay between reactive oxygen (superoxide, hydroxyl radical, H2O2 etc.) and nitrogen (nitric oxide - NO, ONOO-, NO2-, NO3- etc.) forms are proposed to be of key importance for cell and tumor biology. Considering NO as a signal molecule we have studied the impact of NO release on processes of generation of H2O2 in different experimental systems including pleural effusions (PE) of lung cancer patients, human polymorphonuclear leukocytes (PMNs), and rat thymocytes. It was found that PE of lung cancer patients contain a high level of [NO2-+NO3-], i.e. 43.4 25.6 microM (n=15), and PE cells could effectively generate H2O2 in response to lectins from Viscum album (VAA), Phaseolus vulgaris (PHA), and Pisum sativum (PSA) as well as to menadione. A positive correlation between the [NO2-+NO3-] concentration and menadione-induced H2O2 generation (r=0.1964) was found, whereas the [NO2-+NO3-] concentration and lectin-induced H2O2 generation (PHA, r=-0.4099; PSA, r=-0.3949; VAA, r=-0.3225) were negatively correlated. Notably, an increase of H2O2 generation by PE cells was determined in the range of 20-35 microM [NO2-+NO3-]. When PMNs and rat thymocytes were treated with a donor of NO (sodium nitroprusside), the release of H2O2 in response to lectins or menadione was decreased in a dose-dependent manner. The end products of NO biochemistry, assayed as KNO2 and KNO3, were not able to affect significantly the H2O2 generation processes. In conclusion, the data indicate that the potential for triggered H2O2-generation of cells is modulated markedly by the presence of NO or derived reaction compounds. This relation may play an important role in the pathogenesis of PE malignancies with potential relevance for therapeutic strategies.
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PMID:NO-dependent regulation of lectin- and menadione-induced H2O2 production by cells from pleural effusions of lung cancer patients and by immune cells. 1008 31

Technical standardization on randomly chosen samples of tissue specimen is essential for the validity of interpretations derived from measurements on the presence of asbestos fibers in lung in combination with further features of the patients. Fixed non-tumorous lung tissue (2-3 g) of 150 patients after surgery for various lung diseases were either digested in 45 ml of 13% solution with sodium hypochlorite (NaClO; wet ashing) or heated in an oven at 600 degrees C for 15 min (hot ashing). After tissue disintegration asbestos and asbestos-like fibers were counted by visual inspection, and the fiber concentration in the lung parenchyma was computed. In addition, the patients' survival, and the occupational and social history were analyzed. As a result, the mean concentrations of fibers were found to be 55 f/g (fibers/gram, hot ashing) and 46 f/g (wet ashing). The difference is statistically not significant. Mesotheliomas contributed 49% (73 patients), non-small cell lung carcinomas 32% (59 patients) to the entire cohort. Eighteen patients had a non-malignant lung disease. Analysis of living habits revealed that 73 (49%) patients were heavy smokers, and 99 (66%) patients had a history of occupational asbestos exposure which lasted for 18 years on average. A statistically significant difference of the asbestos fiber concentration between the group with professional exposure and that without detectable asbestos exposure could be obtained in mesothelioma patients and non-malignant lung diseases only, and a tendency for elevated fiber presence was seen in non-small cell lung carcinoma patients. In tissue specimen of patients with non-malignant lung diseases the highest fiber concentration was measured (median 104 f/g) followed by mesothelioma patients (77 f/g), and lung carcinoma patients (62 f/g wet tissue). The difference in the fiber concentration between smokers and ex-smokers versus non-smokers was particularly high in patients with non-malignant lung diseases (103 f/g in smokers versus 33 f/g in non-smokers), still statistically significant in mesothelioma patients (100 f/g smokers versus 61 f/g non smokers), and negligible in lung carcinoma patients (58 f/g smokers versus 62 f/g non-smokers). Only 5/70 mesothelioma patients were not exposed to asbestos at work, and nearly half of the patients (36) were non-smokers. The median survival of mesothelioma patients was significantly shortened for patients with a high intrapulmonal fiber concentration greater than 70 f/g (35 weeks versus 60 weeks). This correlation was also true for lung carcinoma patients (110 weeks versus 230 weeks).
Lung Cancer 1999 May
PMID:Quantitation of asbestos and asbestos-like fibers in human lung tissue by hot and wet ashing, and the significance of their presence for survival of lung carcinoma and mesothelioma patients. 1044 59

Cisplatin is a key drug in chemotherapy for lung cancer. It has been reported that intracellular accumulation of cisplatin is an important step as a determinant for resistance to cisplatin, which may be modulated by Na+, K+-ATPase activity. And it has been reported that isoproterenol, a beta-adrenoceptor agonist, enhances sensitivity to cisplatin in non-small cell lung cancer (NSCLC) cell lines. In this study, the effects of the selective beta1, beta2, and beta3-adrenoceptor agonists on membrane Na+, K+-ATPase activity and sensitivity to cisplatin were evaluated using human non-small cell lung cancer cell line. In the NSCLC cell line, sensitivity to cisplatin was improved by treatment with procaterol, a selective beta2-adrenoceptor agonist. Na+, K+-ATPase was activated and intracellular accumulation of cisplatin increased with the treatment. However, beta1 or beta3-adrenoceptor agonist did not modulate sensitivity to cisplatin or Na+, K+-ATPase activity. These results suggest that beta2-adrenoceptor may be one of the determinants for sensitivity to cisplatin in NSCLC. Exogenous beta2-adrenoceptor agonists may improve the antitumor effect of chemotherapy involving cisplatin.
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PMID:Selective beta2-adrenoceptor agonist enhances sensitivity to cisplatin in non-small cell lung cancer cell line. 1060 90

We have reviewed the biomedical literature published over the last 25 years in order to try to establish which of four frequently evaluated laboratory parameters (i.e. serum, or plasma, NSE, LDH, sodium or albumin) might, alone or in combination, give the "best" pretreatment prognostic information in small-cell lung cancer (SCLC) patients, independent of the usual radiological and clinical parameters. From the 45 studies included in this review, the only clear conclusion that can be derived is that it has not yet been clearly demonstrated that the "new" tests (NSE or other tumor markers) are superior to the "old" tests (LDH, sodium, albumin etc.). From the only seven studies that used the same powerful statistical methodologies (Cox's models in association with recursive partitioning and amalgamation procedure (RECPAM) analysis) it could be concluded that LDH and albumin might have independent prognostic significance in SCLC and in advanced SCLC respectively. Provided that, in the future, both laboratory and statistical expertises are clearly guaranteed in the primary studies in this field, it might become possible to propose laboratory parameters as additional staging parameters in SCLC.
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PMID:Laboratory variables as additional staging parameters in patients with small-cell lung carcinoma. A systematic review. 1061 46

Occupational exposure to certain particulate hexavalent chromium [Cr(VI)] compounds, such as lead chromate, has been associated with lung cancer and respiratory tract toxicity. We have previously shown that apoptosis is a major mode of death in cultured rodent cells treated with soluble sodium chromate and particulate lead chromate. Here we report the cellular and molecular effects of lead chromate and sodium chromate in normal human lung small airway epithelial (HSAE) cells, which may be one of the targets for Cr(VI)-induced lung cancer and respiratory tract toxicity. Phagocytosed lead chromate particles and intracellular lead-inclusion bodies (LIB) were observed by transmission electron microscopy and confirmed by X-ray analysis. HSAE cells exposed to lead chromate and sodium chromate underwent dose-dependent apoptosis. The cellular uptake and genomic interactions of both Cr and lead (Pb) were examined by inductively coupled plasma mass spectrometry (ICPMS) coupled with a novel, direct-injection high-efficiency nebulizer (DIHEN). Using this approach, we have quantitated a dose-dependent formation of Cr-DNA adducts and DNA-associated Pb in lead chromate-treated HSAE cells. The formation of LIB in normal human lung cells exposed to lead chromate indicates that ionic Pb is released from the particles and thus might contribute to the cell toxicity caused by lead chromate. Internalization and dissolution of lead chromate particles and the interaction of ionic Cr and Pb with DNA, may be components of the mechanism of lead chromate carcinogenesis. Lead chromate-induced apoptosis may be a mechanism to eliminate cells with chromium- and/or lead-damaged DNA.
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PMID:Internalization of carcinogenic lead chromate particles by cultured normal human lung epithelial cells: formation of intracellular lead-inclusion bodies and induction of apoptosis. 1062 Apr 81


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