Lung carcinogenesis by tobacco smoke

Masonic Cancer Center, University of Minnesota, Minneapolis, MN. .
International Journal of Cancer (Impact Factor: 5.09). 12/2012; 131(12):2724-32. DOI: 10.1002/ijc.27816
Source: PubMed

ABSTRACT Cigarette smoke is a complex mixture of chemicals including multiple genotoxic lung carcinogens. The classic mechanisms of carcinogen metabolic activation to DNA adducts, leading to miscoding and mutations in critical growth control genes, applies to this mixture but some aspects are difficult to establish because of the complexity of the exposure. This article discusses certain features of this mechanism including the role of nicotine and its receptors; lung carcinogens, co-carcinogens and related substances in cigarette smoke; structurally characterized DNA adducts in the lungs of smokers; the mutational consequences of DNA adduct formation in smokers' lungs; and biomarkers of nicotine and carcinogen uptake as related to lung cancer. While there are still uncertainties which may never be fully resolved, the general mechanisms by which cigarette smoking causes lung cancer are well understood and provide insights relevant to prevention of lung cancer, the number one cancer killer in the world, causing 1.37 million deaths per year.

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    • "Spread of the tumor can occur by the lymphatic vessels to lymph nodes located within the lung, mediastinum and thorax. If spread by the blood stream, it can lead to deposits of tumor in the liver, opposite lung, bone and brain [11] [12] [13] [14] [15]. Figure 2 shows the right is that of a cancerous lung post mortem, showing local growth of the tumor. "
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    ABSTRACT: Smog hanging over cities is the most familiar and obvious form of air pollution. The effects of inhaling particulate matter have been studied in humans and animals and include asthma, lung cancer, cardiovascular issues, and premature death. There are, however, some additional products of the combustion process that include nitrogen oxides and sulfur and some un-combusted hydrocarbons, depending on the operating conditions and the fuel-air ratio. Tuning the fuel to air ratio caused to control the lung cancer. Lung cancers are tumors arising from cells lining the airways of the respiratory system. Design of a robust nonlinear controller for automotive engine can be a challenging work. This research paper focuses on the design and analysis of a high performance PID like fuzzy controller for automotive engine, in certain and uncertain condition. The proposed approach effectively combines of design methods from linear Proportional-Integral-Derivative (PID) controller and fuzzy logic theory to improve the performance, stability and robustness of the automotive engine. To solve system’s dynamic nonlinearity, the PID fuzzy logic controller is used as a PID like fuzzy logic controller. The PID like fuzzy logic controller is updated based on gain updating factor. In this methodology, fuzzy logic controller is used to estimate the dynamic uncertainties. In this methodology, PID like fuzzy logic controller is evaluated. PID like fuzzy logic controller has three inputs, Proportional (P), Derivative (D), and Integrator (I), if each inputs have 𝑁 linguistic variables to defined the dynamic behavior, it has 𝑁×𝑁×𝑁 linguistic variables. To solve this challenge, parallel structure of a PD-like fuzzy controller and PI-like fuzzy controller is evaluated. In the next step, the challenge of design PI and PD fuzzy rule tables are supposed to be solved. To solve this challenge PID like fuzzy controller is replaced by PD-like fuzzy controller with the integral term in output. This method is caused to design only PD type rule table for PD like fuzzy controller and PI like fuzzy controller.
    International Journal of Bio-Science and Bio-Technology 09/2015; 7(4):179-202. DOI:10.14257/ijbsbt.2015.7.4.18
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    • "A variety of enzymes metabolize PAHs to more polar and water-soluble metabolites to be excreted from the body. However, during the course of metabolism, some unstable and reactive intermediates are formed, which can bind to DNA to form bulky DNA adducts (Hecht, 2012; DeMarini et al., 2001). At the same time, the cells constantly deal with the formation of DNA adducts by DNA repair processes to eliminate these alterations so that mutation does not occur (Irigaray and Belpomme, 2010). "
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    ABSTRACT: Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G → A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure-genomic mutation relationship at a large scale.
    08/2015; 2(6):583-90. DOI:10.1016/j.ebiom.2015.04.003
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    • "Please cite this article in press as: Gui-Zhen Wang, et al., Tobacco smoke induces production of chemokine CCL20 to promote lung cancer, Cancer Letters (2015), doi: 10.1016/ j.canlet.2015.04.005 is needed to identify biomarkers to screen for those most prone to develop lung cancer, and to uncover targets for development of therapeutic and chemopreventive approaches. The key carcinogens of tobacco smoke are NNK and PAHs [3] [35]. These carcinogens induce chronic inflammation to facilitate carcinogenesis . "
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    ABSTRACT: Tobacco kills nearly 6 million people each year, and 90% of the annual 1.59 lung cancer deaths worldwide are caused by cigarette smoke. Clinically, a long latency is required for individuals to develop lung cancer since they first exposed to smoking. In this study, we aimed to identify clinical relevant inflammatory factors that are critical for carcinogenesis by treating normal human lung epithelial cells with tobacco carcinogen nicotine-derived nitrosaminoketone (NNK) for a long period (60 days) and systematic screening in 84 cytokines/chemokines. We found that a chemokine CCL20 was significantly up-regulated by NNK, and in 78/173 (45.1%) patients the expression of CCL20 was higher in tumor samples than their adjacent normal lung tissues. Interestingly, CCL20 was up-regulated in 48/92 (52.2%) smoker and 29/78 (37.2%) nonsmoker patients (p=0.05), and high CCL20 was associated with poor prognosis. NNK induced production of CCL20, which promoted lung cancer cell proliferation and migration. In addition, an anti-inflammation drug dexamethasone inhibited NNK-induced CCL20 production and suppressed lung cancer in vitro and in vivo. These results indicate that CCL20 is crucial for tobacco smoke-caused lung cancer, and anti-CCL20 could be a rational approach to fight against this deadly disease. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Cancer letters 04/2015; 61(1). DOI:10.1016/j.canlet.2015.04.005 · 5.62 Impact Factor
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