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 5-year survival of lung cancer patients is about 30% in Japan. One of the reasons for the poor prognosis seems to be drug resistance. It has been reported that certain types of oncogenes, such as ras, myc and fos, may play an important role in drug resistance. The myc protein forms a sequence-specific DNA-binding complex with Max and may act as a transcription factor; thus, it may be possible that myc family oncogenes are involved in DNA synthesis and repair processes mediating drug resistance. We report here that L-myc oncogene may be involved in the transition from drug-sensitive to drug-resistant phenotype of a certain small cell lung cancer cell line.
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PMID:[Relationship between drug resistance and oncogenes in lung cancer cell lines]. 133 94

DNA index (DI) was studied with flow cytometry in surgical samples from 35 patients with lung cancer, 10 patients with benign lesions, 10 normal persons. The results showed that DI of lung cancer is significantly higher than that of benign pathological lesion and normal lung (P < 0.001). Aneuploid lung cancer was 88.57%, diploid was 11.43%. The DNA content of benign and normal lung was diploid. In the meantime, A significant positive correlation between the lung cancer DI and histopathological grade and cancer cell type was also observed, but there is not correlation between the TNM staging and lung cancer DI. Our results suggest that the flow cytometric analysis of DNA is useful for clinical pathologic diagnosis of lung cancer.
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PMID:[Flow cytometric analysis of DNA content in lung cancer]. 133 10

The knowledge of prognostic factors such as TNM, performance status, and sex is essential for predicting patient outcome and optimal trial design and analysis. Recent advances in cytogenetics and molecular biology have yielded new prognostic factors such as DNA ploidy, oncogenes and oncogene product. New prognostic factors can predict patient outcome and should be incorporated for the multivariate analysis of prognostic factors. They can provide a guideline for selecting special patient population suitable for adjuvant chemotherapy even in the early stage of lung cancer.
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PMID:[An overview of new prognostic factors in lung cancer]. 134 85

Radon increases the risk of lung cancer in smoking and non-smoking underground miners. To investigate the mutational spectrum associated with exposure to high levels of radon, we sequenced exons 5-9 of the p53 tumour suppressor gene and codons 12-13 of the Ki-ras protooncogene in 19 lung cancers from uranium miners exposed to radon and tobacco smoke. Mutations were not found in Ki-ras, but 9 p53 mutations, including 2 deletions, were found in 7 patients by direct DNA sequencing after polymerase chain reaction amplification of DNA from formalin-fixed, paraffin-embedded tissue. In tumours from 5 patients, the mutation produced an aminoacid change and an increased nuclear content of p53 protein. The tumours with either a stop codon or frame-shift deletion in the p53 gene were negative by immunohistochemistry. None of the mutations were G:C to T:A transversions in the coding strand of the p53 gene, which are the most frequent base substitutions associated with tobacco smoking, and none were found at the hotspot codons described in lung cancer. The observed differences from the usual lung cancer mutational spectrum may reflect the genotoxic effects of radon.
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PMID:Mutations of p53 and ras genes in radon-associated lung cancer from uranium miners. 134 94

The doxorubicin-selected lung cancer cell line H69AR is resistant to many chemotherapeutic agents. However, like most tumor samples from individuals with this disease, it does not overexpress P-glycoprotein, a transmembrane transport protein that is dependent on adenosine triphosphate (ATP) and is associated with multidrug resistance. Complementary DNA (cDNA) clones corresponding to messenger RNAs (mRNAs) overexpressed in H69AR cells were isolated. One cDNA hybridized to an mRNA of 7.8 to 8.2 kilobases that was 100- to 200-fold more expressed in H69AR cells relative to drug-sensitive parental H69 cells. Overexpression was associated with amplification of the cognate gene located on chromosome 16 at band p13.1. Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression. The mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.
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PMID:Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. 809 49

Taxol, an agent with a unique mechanism of action, has been shown to be highly active in patients with refractory ovarian cancer and may well have significant activity in other malignancies such as breast and lung cancer. The camptothecin analogs, another unique class of agents, have demonstrated antitumor activity in phase I and II trials. Finally, the anthrapyrazoles are intercalating agents with clinical activity in breast cancer and a toxicity profile that may permit increased dose intensity using colony-stimulating factor support. While this review focuses on these three drug classes, a number of other agents with apparently unique mechanisms of antitumor activity and unusual dose-limiting toxicities are in earlier development. These include antimetabolites; inhibitors of DNA, RNA, or protein synthesis; differentiating agents; agents that inhibit tumor growth by binding to growth factors; and agents whose mechanism of action is best classified as unknown.
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PMID:New anticancer agents: taxol, camptothecin analogs, and anthrapyrazoles. 136 58

Debrisoquine is an antihypertensive drug that is metabolized by cytochrome P4502D6. Deficient metabolism is inherited as an autosomal recessive condition. We previously reported in a case-control study that extensive metabolizers of debrisoquine were at greater risk of lung cancer compared to poor and intermediate metabolizers. Cloning of the gene that encodes P4502D6 (CYP2D6) led to the identification of both wild-type and mutant forms of the gene. Subsequently, a DNA-restriction fragment length polymorphism (RFLP) was identified, and a Southern hybridization-based test was developed in an attempt to define the genotype. When the DNA-RFLP test was applied to stored DNA from our study subjects there was neither a significant association with the metabolic phenotype nor an association with lung cancer. Further work has demonstrated that the wild-type gene, which was characterized by a 29-kb allele, can also contain mutations that result in nonfunctional or absent proteins. When these mutations are present, individuals exhibit the poor or intermediate metabolizer phenotype in spite of the presence of the 29-kb putative wild-type allele. Sequence determination of the mutants led to the development of techniques to exploit the polymerase chain reaction, which, together with Southern analysis, have been reported to detect as many as 95% of poor metabolizers. This technique is being used to examine the association of the extensive metabolizer genotype with lung cancer in the subjects from the case-control study. Preliminary results indicate a weak association between the homozygous wild-type genotype and lung cancer; in contrast, the extensive metabolizer phenotype is strongly associated with lung cancer in this subset.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The debrisoquine metabolic phenotype and DNA-based assays: implications of misclassification for the association of lung cancer and the debrisoquine metabolic phenotype. 136 37

We have examined restriction fragment length polymorphisms of the H-ras-1 gene in germ-line DNA from 214 lung cancer patients and 309 unaffected controls. When DNA samples were digested with MspI/HpaII, Southern blot analysis revealed at least 22 different alleles, grouped according to their frequencies as common, intermediate, and rare. The frequency of rare alleles in lung cancer patients (16/428) is significantly different (p = 0.002) from that in the control group (5/618). Individuals with rare alleles were found to be at 4.7-fold greater risk of lung cancer than those with no rare alleles.
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PMID:Allele diversity of the H-ras-1 variable number of tandem repeats in Norwegian lung cancer patients. 136 38

Human cancer risk assessment at a genetic level involves the investigation of carcinogen metabolism and DNA adduct formation. Wide interindividual differences in metabolism result in different DNA adduct levels. For this and other reasons, many laboratories have considered DNA adducts to be a measure of the biologically effective dose of a carcinogen. Techniques for studying DNA adducts using chemically specific assays are becoming available. A modification of the 32P-postlabeling assay for polycyclic aromatic hydrocarbon DNA adducts described here provides potential improvements in quantification. DNA adducts, however, reflect only recent exposure to carcinogens; in contrast, genetic testing for metabolic capacity indicates the extent to which carcinogens can be activated and exert genotoxic effects. Such studies may reflect both separate and integrated risk factors together with DNA adduct levels. A recently described restriction fragment length polymorphism for the CYP1A1, which codes for the cytochrome P450 enzyme primarily responsible for the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons, has been found to be associated with lung cancer risk in a Japanese population. In a subset of individuals enrolled in a U.S. lung cancer case-control study, no association with lung cancer was found.
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PMID:Polycyclic aromatic hydrocarbon-DNA adducts and the CYP1A1 restriction fragment length polymorphism. 136 39

Human cytochrome P450IIE1 (CYP2E) is involved in the metabolic activation of procarcinogens such as N-nitrosodimethylamine, benzene and ethyl carbamate. We screened DNA from 28 individuals for restriction fragment length polymorphisms (RFLPs) is the human P450IIE1 gene and detected an RFLP for the restriction endonuclease DraI. The distribution of the genotypes of this polymorphisms among lung cancer patients (n = 74) differed from that among controls (n = 73) with statistical significance of p < 0.05. In addition, the distribution among patients with cancers of the digestive system (n = 38) was also different from that among controls. Our findings indicate an association between the DraI polymorphism of the IIE1 gene and susceptibility to cancers of the lung and the digestive system.
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PMID:Human cytochrome P450IIE1 gene: DraI polymorphism and susceptibility to cancer. 136 74


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