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)

Expression of glutathione S-transferase placental form (GST-pi) in human lung carcinoma tissue taken at autopsy or biopsy was investigated immunohistochemically. All of 34 cases of squamous cell carcinomas, including poorly, moderately and well-differentiated examples were shown to stain positively for GST-pi. Poorly differentiated adenocarcinomas were, however, negatively stained (0/5 cases), while moderately and well differentiated adenocarcinomas were found to stain with GST-pi at rates of 69% (9/13 cases) and 71% (5/7 cases), respectively. Six cases of small cell carcinomas examined were all negative. The results indicate that GST-pi may be a useful marker for non-small cell type lung cancer, especially squamous cell carcinoma which is in agreement with findings for rat lung neoplastic lesions reported previously.
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PMID:Expression of the glutathione S-transferase placental form in human lung carcinomas. 284 80

Glutathione levels were measured in 30 human lung cancer lines. Lower levels were detected in cell lines derived from small cell lung cancer specimens compared to non-small cell lines (mean 42 vs. 130 nmol mg-1 protein, P = 0.005). However, no difference were detected between cell lines derived from previously untreated patients, compared to those derived from patients who had received chemotherapy. Non-small cell lines were found to have increased activity of 4 detoxification enzymes compared to small cell lines, although these differences did not reach statistical significance: glutathione transferase activity (69 vs. 36 units, P = 0.137), glutathione reductase (139 vs. 82 units, P = 0.05), gamma-glutamyl transpeptidase (9.39 vs. 3.03 units, P = 0.072) and superoxide dismutase (20 vs. 13.6 units, P = 0.137). As the cell lines exhibit a similar chemosensitivity pattern to that observed in clinical practice, these differences in glutathione and detoxification enzyme levels may prove to be important indicators of intrinsic drug resistance often seen in patients with non-small cell lung cancer.
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PMID:Glutathione and related enzyme activity in human lung cancer cell lines. 290 63

Lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (LC, n = 54) or a nonneoplastic lung disease (n = 20). Aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECDE), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities and glutathione and malondialdehyde contents were determined in 12,000 X g supernatant fractions from nontumorous parenchymal tissues. Interindividual differences in enzyme activities ranged from 11- to 440-fold, and glutathione content varied by 17-fold; the values showed unimodal distributions. AHH, ECDE, EH, and UDPGT activities were significantly and positively correlated to each other; a significant negative correlation was found between GST and the other enzymes. A relationship between enzyme activity and number of cigarettes smoked (pack-years) was found only for GST. Ignoring detailed smoking histories in the 6-month period preceding surgery, no difference was found in enzyme activities or glutathione content between LC and nonneoplastic lung disease patients or between smokers and nonsmokers. However, when the number of days since stopping smoking was considered, in smokers a significant increase was found for AHH, EH, and UDPGT activities and a significant decrease was found for GST activity, as compared to nonsmokers. LC patients who had smoked until the day before surgery had higher activities of AHH, ECDE, EH, and UDPGT than nonsmokers, while GST activity was reduced by one-third. The activities of these enzymes returned to the basal level found in nonsmokers within 59 (AHH), 108 (EH), 67 (UDPGT), and 40 (GST) days. LC patients who were recent smokers (within 30 days prior to surgery) had significantly induced AHH and ECDE activities when compared with smoking nonneoplastic lung disease patients. These results show that pulmonary drug metabolism can be altered by tobacco smoking and that these effects can last 40 to 108 days after cessation of smoking. These new findings should be considered in studies on the role of carcinogen-metabolizing enzymes in determining susceptibility to lung cancer.
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PMID:Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: a case-control study on lung cancer patients. 313 17

An increasing body of evidence suggests that glutathione-dependent enzymes are an important factor in determining the sensitivity of tumours to cytotoxic drugs. Ten randomized normal and tumour samples from individuals with lung cancer were analysed for glutathione S-transferase isoenzyme (GST) content and glutathione peroxidase (Gpx) activity. The normal tissue samples exhibited a 5.1- and 7.0-fold variation in GST and Gpx activity respectively. High levels of the pi class, acidic Yf, GST subunit were found in all the samples, with little variation between individuals. The concentration of alpha and mu class subunits was 5- to 10-fold lower and were subject to significant individual variability. The mu class subunit identified had a faster mobility on SDS-PAGE than the hepatic GST mu standard and did not appear subject to the genetic polymorphism associated with certain members of this gene family. This suggests the presence of a novel pulmonary protein which may correspond to the rat Yn Yn protein. The normal to tumour ratio for GST activity varied significantly between the samples and tended to follow the relative expression of the mu class subunit, and to a lesser extent the alpha class GST subunit. The pi subunit was present in the normal and tumour cells in very similar concentration. The expression of the mu class GST appeared to follow the differences in GST enzymic activity and although the numbers were small appeared to segregate according to tumour type. Gpx activity was also elevated in certain tumours. Of particular interest were the two adenocarcinomas which had a 20- to 30-fold higher tumour Gpx activity.
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PMID:Glutathione S-transferase isoenzymes and glutathione peroxidase activity in normal and tumour samples from human lung. 340 65

Leukocyte isozyme(s) of glutathione transferase (GT-tSBO) has been shown to be dominantly inherited. The frequency of the phenotypes of this isozyme in bronchial carcinoma and control patients matched for age and smoking history is reported here. Control smokers showed an increased likelihood of having GT-tSBO (59%) compared with lung cancer patients (35%). The lack of GT-tSBO was related to the extent of smoking by the lung cancer patients but not to the pathology of the lung tumor. It was concluded that the gene expressing this isozyme(s) may be a host genetic determinant of susceptibility to lung cancer in smokers.
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PMID:A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. 369 3

It has been reported human lung has cytochrome P-450 dependent monooxygenase activity which is necessary for the formation of mutagenic and carcinogenic metabolites of polycyclic aromatic hydrocarbons, such as benzo[a]pyrene. We now report epoxide hydratase and glutathione S-transferase, enzymes important in the further metabolism of certain benzo[a]pyrene metabolites formed by the monooxygenase system, have been detected in human lung tissues from patients undergoing surgery for lung cancer.
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PMID:Epoxide hydratase and glutathione S-transferase activities in human lungs. 722 44

Cytogenetic alterations have been associated with the occurrence of many cancers. However, limited data exist to address whether increased chromosomal changes in surrogate normal tissue are similarly associated with malignancy. As part of an ongoing case-control study of lung cancer, we have studied the factors that affect sister chromatid exchange (SCE) frequency in lymphocytes from lung cancer patients. Further, we sought to investigate whether the factors that affect SCE frequencies were comparable in lung cancer cases and controls. Cases had newly diagnosed, operable primary lung cancer. Controls were friends and spouses of cases. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was obtained in an interviewer-administered questionnaire. Intake of antioxidants was also determined through the administration of a validated semiquantitative food frequency questionnaire. Metabolic traits studied included the polymorphic glutathione-S-transferase class mu (GST-mu) and variants of P450 isoenzymes CYP1A1 and CYP 2D6. Overall, 78 cases and 78 controls were included in the analysis. Although there was a small number of lung cancer patients who had never smoked in the study (9% of cases), these patients had higher SCE frequencies than current or former smokers. This suggests that factors associated with genomic instability may also play a role in the pathogenesis of lung cancer. The best fit model for SCE frequency, which had been previously generated from control data alone, included age, gender, smoking, GST-mu, and vitamin A intake. However, when this model was applied to lung cancer patients, smoking was not associated with an elevated SCE frequency. Thus, it is not clear that SCE frequency data in prevalent lung cancer cases and controls are comparable.
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PMID:Comparison of sister chromatid exchange frequency in peripheral lymphocytes in lung cancer cases and controls. 747 55

A clonal assay to determine the mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in human lymphocytes has been used by a number of investigators to study exposure to mutagens and carcinogens in a variety of populations. We have studied hprt MF in 106 subjects (40 controls and 66 cases) enrolled in a case-control investigation of lung cancer. Epidemiological data collected included smoking history, intake of dietary micronutrients, and occupational and environmental exposures as well as medical history, all obtained from an interviewer-administered questionnaire. All subjects were also genotyped for the known polymorphism in glutathione S-transferase class mu (GST-mu). In analysis of cases and controls, hprt MF was not associated with age, smoking, the polymorphism in GST mu, dietary intake, occupational exposures, family history of cancer or usage of medications. Since MF and cloning efficiency (CE) are not independent when CE is low, further analysis in cases and controls with a CE greater than or equal to 30% (27 cases and 22 controls) was also conducted. In analysis of controls, hprt MF increased with age and was inversely associated with intake of folate and vitamins A and C. The presence of lung cancer was not associated with hprt MF. Thus, our study supports the previous observation that dietary components may affect the MF at the hprt locus.
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PMID:Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer. 750 Sep 85

To obtain cisplatin (CDDP)-resistant cells possessing the clinically induced resistance phenotype, H-460 nonsmall cell lung cancer cells (NSCLC) were pulse treated with 20, 60, 80 microM CDDP for 1 h every week, respectively. Twelve months later, three CDDP-resistant cell lines (H-460/CDDP20, H-460/CDDP60, H-460/CDDP80) were obtained that exhibit different levels of CDDP resistance (6- to 22-fold), and the possible mechanisms of resistance were studied. These resistant cells were cross-resistant to carboplatin and melphalan, but not to adriamycin or 5-fluorouracil. CDDP resistance in these cell lines appeared to be stable even after 6 months of growth in cisplatin-free medium. There was no evidence of drug accumulation differences between parental and resistant cells. Although both intracellular glutathione (GSH) content and glutathione S-transferase (GST) activity increased 1.5- to 2.5-fold in the resistant cells, only a minimal reversal of drug resistance was observed after buthionine sulfoximine (BSO) treatment, which depleted intracellular GSH levels. An enhancement of DNA repair activity was found in the resistant cell lines and played the major role in the cisplatin resistance phenotype. Using H-460/CDDP80 cells as a model, addition of a nontoxic concentration of pentoxifylline (PTX) significantly enhanced CDDP-induced cytotoxicity in a synergistic manner. Furthermore, more prominent reversal of CDDP resistance could be achieved when the resistant cells were pretreated with BSO, followed by PTX and CDDP combined treatment. This provides a rationale for combination therapy in refractory lung cancer using CDDP and two resistance modulators.
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PMID:Modulation of cisplatin resistance in acquired-resistant nonsmall cell lung cancer cells. 754 42

Polymorphisms in inherited metabolic traits and intake of dietary antioxidants have been reported to be associated with risk for the development of lung cancer in smokers. This increased risk of lung cancer is presumably attributable to the accumulation of DNA damage. We conducted a study to investigate whether genetic metabolic variants and antioxidant consumption affected the sister chromatid exchange (SCE) level in lymphocytes. Study subjects were 78 friends and spouses of cases from a case-control study of lung cancer designed to investigate the association of metabolic polymorphisms with lung cancer. The metabolic traits studied included glutathione S-transferase class mu and variants of P-450 isoenzymes CYP1A1 and CYP2D6. Intake of antioxidants including vitamins A, C, and E and selenium was determined through the administration of a validated, semiquantitative food frequency questionnaire. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was also obtained in an interviewer-administered questionnaire. Smoking status was found to be significantly associated with SCE frequency. In addition SCE frequency decreased with the period of time since quitting smoking. The presence of one or more glutathione S-transferase class mu alleles was associated with significantly lower SCE. Higher intake of vitamin A and selenium was also inversely associated with SCE level. Thus, the results suggest that glutathione S-transferase class mu and the intake of vitamin A and selenium may modulate the accumulation of chromosomal damage in lymphocytes.
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PMID:Glutathione S-transferase mu genotype, diet, and smoking as determinants of sister chromatid exchange frequency in lymphocytes. 754 11


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