scholarly journals Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development

2021 ◽  
Vol 22 (22) ◽  
pp. 12179
Author(s):  
Anna Valeria Samarelli ◽  
Valentina Masciale ◽  
Beatrice Aramini ◽  
Georgina Pamela Coló ◽  
Roberto Tonelli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cigarette Smoking ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Cancer Development ◽  
Unknown Aetiology ◽  
Cancer Knowledge ◽  
Agent Based ◽  
Stress Oxidative ◽  
Common Target

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2–4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine–kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.

scholarly journals Relationship of the oxidative damage biomarker 8-epi-prostaglandin F2α to risk of lung cancer development in the Shanghai Cohort Study

2018 ◽  
Vol 39 (7) ◽  
pp. 948-954 ◽  
Author(s):  
Jian-Min Yuan ◽  
Steven G Carmella ◽  
Renwei Wang ◽  
Yu-Ting Tan ◽  
Jennifer Adams-Haduch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Cigarette Smoking ◽  
Oxidative Damage ◽  
Prostaglandin F2α ◽  
Epidemiological Data ◽  
Cancer Development ◽  
Cigarette Smoke Exposure ◽  
Lung Carcinogenesis ◽  
Never Smokers

Abstract It has been hypothesized that the pathogenesis of lung cancer induced by cigarette smoking involves oxidative damage by free radicals. Epidemiological data on biomarkers of oxidative damage and risk of lung cancer development are sparse. A nested case–control study of 610 lung cancer cases and 610 matched controls was conducted within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F2α (8-epiPGF2α), a biomarker of oxidative stress, were determined in baseline urine samples using a validated mass-spectrometry assay. Current smokers had significantly higher level of 8-epiPGF2α than former smokers or never smokers (P < 0.001). 8-epiPGF2α levels were significantly higher in lung cancer cases than their smoking-matched controls in former and current smokers, but not different in never smokers (P for interaction = 0.019). The relative risks of developing lung cancer for former and current smokers in the highest relative to the lowest quartile of 8-epiPGF2α were 5.25 (Ptrend = 0.035) and 1.99 (Ptrend =0.007), respectively. The effect of 8-epiPGF2α and biomarkers of cigarette smoke exposure on lung cancer risk was additive; the relative risk was 5.33 (95% confidence interval = 2.65–7.51) for current smokers with the highest thirds of 8-epiPGF2α and total cotinine compared with their lowest thirds. Smokers with a heightened state of oxidative stress in response to the insults of cigarette smoking may be more susceptible to smoking-induced lung carcinogenesis.

Molecular mechanisms of lung cancer development at its different stages in nuclear industry workers

2015 ◽  
Vol 77 (2) ◽  
pp. 10
Author(s):  
G. G. Rusinova ◽  
N. S. Vyazovskaya ◽  
T. V. Azizova ◽  
V. S. Revina ◽  
I. V. Glazkova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanisms ◽  
Nuclear Industry ◽  
Cancer Development

scholarly journals BIX01294 inhibits EGFR signaling in EGFR-mutant lung adenocarcinoma cells through a BCKDHA-mediated reduction in the EGFR level

2021 ◽  
Author(s):  
Ji Hye Kim ◽  
Jongwook Kim ◽  
Se Seul Im ◽  
Ji Hyeon Lee ◽  
Sein Hwang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Apoptotic Cell ◽  
Energy Levels ◽  
Histone Methyltransferase ◽  
Current Data ◽  
Metabolic Function ◽  
Egfr Signaling ◽  
Egfr Mutant

AbstractBIX01294 (BIX), an inhibitor of the G9a histone methyltransferase, has been reported to have antitumor activity against a variety of cancers. However, the molecular mechanisms underlying its anticancer effects, particularly those against lung cancer, remain unclear. Here, we report that BIX induces apoptotic cell death in EGFR-mutant non-small cell lung cancer (NSCLC) cells but not in their wild-type counterparts. Treatment with BIX resulted in a significant reduction in the EGFR level and inhibition of EGFR signaling only in EGFR-mutant NSCLC cells, leading to apoptosis. BIX also inhibited mitochondrial metabolic function and decreased the cellular energy levels that are critical for maintaining the EGFR level. Furthermore, BIX transcriptionally downregulated the transcription of branched-chain α-keto acid dehydrogenase (BCKDHA), which is essential for fueling the tricarboxylic acid (TCA) cycle. Interestingly, this BCKDHA downregulation was due to inhibition of Jumanji-domain histone demethylases but not the G9a histone methyltransferase. We observed that KDM3A, a Jumonji histone demethylase, epigenetically regulates BCKDHA expression by binding to the BCKDHA gene promoter. BIX exposure also led to a significant decrease in the EGFR level, causing apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Taken together, our current data suggest that BIX triggers apoptosis only in EGFR-mutant NSCLC cells via inhibition of BCKDHA-mediated mitochondrial metabolic function.

Investigation into Cigarette Smoking and Atmospheric Pollution in the Aetiology of Lung Cancer

1963 ◽  
Vol 2 (01) ◽  
pp. 13-19 ◽  
Author(s):  
R. Doll
Keyword(s):  
Lung Cancer ◽  
Cigarette Smoking ◽  
Atmospheric Pollution ◽  
Direct Evidence ◽  
Retrospective Studies ◽  
Common Factor ◽  
Animal Experiments ◽  
Smoking Habits ◽  
Careful Examination ◽  
Ancillary Data

The evidence that cigarette smoking and atmospheric pcllution are causes of lung cancer is largely statistical. The first evidence was indirect; that is, i1. was noticed that in many countries the incidence of lung cancer had increased and that the increase could be correlated with changes in the prevalence of cigarette smoking and of certain types of atmospheric pollution.Since then much direct evidence has been obtained. The relationship between cigarette smoking and lung cancer has been demonstrated retrospectively by comparing the smoking habits of patients with and without lung cancer and prospectively by observing the mortality from lung cancer in groups of persons of known smoking habits. Conclusions can be drawn from these studies only after careful examination of the results. In particular it is important in retrospective studies to test a) the reproducibility of the data, b) the representativeness of the data, and c) the comparability of the special series and their controls. The resul1.s of retrospective studies are all similar and all show a close relationship between cigarette smoking and the disease.The results have been confirmed by pro~pective studies which are lesF. open to bias. The results can be explained if cigarette smoking causes lung cancer or if both are related to some third common factor. Ancillary data (pathological changes in the bronchial mucosa, animal experiments, etc.) support the causal hypothesis.The evidence relating to atmospheric pollution is less definite and it is difficult to get direct evidence of a relationship in the individual. It is clear that pollution has little effect in the absence of smoking, but the mortality associated with a given amount of smoking is generally greater in large towns than in the countryside and among men who have emigrated from Britain than among men who have lived all their lives in less polluted countries.

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