Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transient pulmonary neuroendocrine cell hyperplasia and non-neuroendocrine lung tumors develop in nitrosaminetreated hamsters, which we hypothesized might modulate epithelial cell phenotype by expressing gene(s) homologous to human chromosome 3p gene(s) deleted in small cell carcinoma of the lung (SCLC). We differentially screened a chromosome 3 library using nitrosamine-treated versus normal hamster lung cDNAs and identified hepatocyte growth factor-like/macrophage-stimulating protein (HGFL/MSP) in injured lung. HGFL/MSP mRNA is low to undetectable in human SCLC and carcinoid tumors, but the HGFL/MSP tyrosine kinase receptor, RON, is present and functional on many of these neuroendocrine tumors. In H835, a pulmonary carcinoid cell line, and H187, a SCLC cell line, HGFL/ MSP induced adhesion/flattening and apoptosis. Using viable cell counts to assess proliferation after 14 d of treatment with HGFL/MSP, there is growth inhibition of H835 but not H187. Nitrosamine-treated hamsters also demonstrate pulmonary neuroendocrine cell apoptosis in situ during the same time period as expression of the endogenous HGFL/ MSP gene, immediately preceding the spontaneous regression of neuroendocrine cell hyperplasia. These observations suggest that HGFL/MSP might regulate neuroendocrine cell survival during preneoplastic lung injury, which could influence the ultimate tumor cell phenotype.
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PMID:Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival. 918 22

Although all forms of smoking are harmful, smoking pipes or cigars is associated with lower exposure to the lethal products of tobacco products and lower levels of morbidity and mortality than smoking cigarettes. Cytochrome P-450-1A (CYP1A) is a major pathway activating carcinogens from tobacco smoke. Our primary aim was to compare CYP1A2 activity in individuals smoking pipes or cigars only, cigarettes only and in non-smokers. We studied 30 smokers of pipes or cigars only, 28 smokers of cigarettes only, and 30 non-smokers male subjects matched for age. CYP1A2 activity was assessed as the caffeine metabolic ratio in plasma. One-day urine collection was used for determining exposure to products of tobacco metabolism. Nitrosamine and benzo[a]pyrene DNA adducts were measured in lymphocytes. CYP1A2 activity was greater (p<0.0001) in cigarette smokers (median: 0.61; interquartile range: 0.52-0.76) than in pipe or cigar smokers (0.27; 0.21-0.37) and non-smokers (0.34; 0.25-0.42) who did not differ significantly. Urinary cotinine and 1-hydroxypyrene levels were higher in cigarette smokers than in pipe or cigar smokers and higher in the later than in non-smokers. DNA adducts levels were significantly lower in pipe or cigar smokers than in cigarette smokers. In multivariate analysis, cigarette smoking was the only independent predictor of CYP1A2 activity (p<0.0001) and of 1-hydroxypyrene excretion in urine (p=0.0012). In this study, pipe or cigar smoking was associated with lower exposure to products of tobacco metabolism than cigarette smoking and to an absence of CYP1A2 induction. Cigarette smoking was the only independent predictor of CYP1A2 activity in smokers. However, inhalation behaviour, rather than the type of tobacco smoked, may be the key factor linked to the extent of tobacco exposure and CYP1A2 induction. Our results provide a reasonable explanation for the results of epidemiological studies showing pipe or cigar smoking to present fewer health hazards than cigarette smoking.
Lung Cancer 2006 Oct
PMID:Effects of type of smoking (pipe, cigars or cigarettes) on biological indices of tobacco exposure and toxicity. 1688 17

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). N-Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen found in tobacco smoke, induces lung tumors in A/J mice. NNK induces cellular transformation resulting in the over-expression of EGFR. Accordingly, EGFR may be a target for cancer prevention. In this study, we investigated the effect of gefitinib on NNK-induced tumorigenesis and the carcinogenicity of gefitinib in A/J mice. A total of 180 four-week-old female A/J mice were randomly divided into six groups: group 1 (controls), treated with deionized water; group 2, treated with 5 mg/kg p.o. gefitinib; group 3, treated with 50 mg/kg p.o. gefitinib (to test the carcinogenicity of gefitinib); group 4 (controls for NNK treatment), treated with deionized water; group 5, treated with 5 mg/kg p.o. gefitinib; and group 6, treated with 50 mg/kg p.o. gefitinib and injected with NNK once at 8 weeks of age to test the chemopreventive activity of gefitinib. Gefitinib was given once a day, 5 days a week by gavage, beginning at 4 weeks of age and continuing for 26 weeks. All mice were sacrificed at 30 weeks of age. The multiplicities of the NNK-induced lung tumors were significantly suppressed in a dose-dependent manner. Gefitinib had no effect on body weight at a low dose. The administration of gefitinib alone for 26 weeks did not induce tumorigenesis; instead, it significantly suppressed the incidence of spontaneous tumors in the mice, in contrast with other anti-cancer agents. Gefitinib did not induce lung fibrosis when compared with control mice by Azan-Mallory staining. Our results suggest that gefitinib has a weak but significant chemopreventive effect with no carcinogenicity or pulmonary toxicity in A/J mice.
Lung Cancer 2009 Sep
PMID:Effect of gefitinib on N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J mice. 1915 84

E-cigarettes remain controversial because the scientific evidence of short term and long term effects on tolerance and the health value of a switch from tobacco to e-cigarettes is contested and controversial. Nevertheless the quality of e-cigarettes and e-liquids has improved. The main ingredients, propylene glycol, vegetable glycerine and nicotine are pharmaceutical-grade quality in most e-liquids. Flavors are almost all food grade. The high quality of ingredients has decreased the presence of impurities in e-liquids. The emissions of e-cigarettes do not contain solid particles or carbon monoxide. Nitrosamine content is at least one hundred times lower than in tobacco smoke. E-cigarette emissions in normal use do not contain any harmful constituents at significant levels except nicotine. UK public health authorities have stated that e-cigarette use is likely to be at least 95% less toxic than cigarette use. There are benefits from having a well-regulated legal market. In countries where e-liquid containing nicotine is not allowed, "do-it-yourself" liquids are common and have handling risks and may sometimes contain toxic impurities. Though e-cigarettes should never be assumed safe products for non-smokers, for smokers, the e-cigarette is at least 20 times less dangerous than the cigarette. Tobacco cessation specialists in countries where nicotine containing e-cigarettes are available increasingly provide counselling for e-cigarette use to stop smoking or to reduce smoking at the request of patients. Based on current knowledge, for patients with lung or other forms of cancer who would otherwise continue to smoke, e-cigarettes offer an alternative way to quit smoking while they undergo medical treatment.
Lung Cancer 2017 03
PMID:Patients with lung cancer: Are electronic cigarettes harmful or useful? 2776 28