Home > Cancer Types > Lung Cancer > Risk Factors and Prevention of Lung Cancer

Risk Factors and Prevention of Lung Cancer

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Lung Cancer
Smoking and Smoking Cessation
Cancer Prevention

Information Patients and the Public (8 links)

Information for Health Professionals / Researchers (6 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Liu YH, Liu GH, Mei JJ, Wang J
The preventive effects of hyperoside on lung cancer in vitro by inducing apoptosis and inhibiting proliferation through Caspase-3 and P53 signaling pathway.
Biomed Pharmacother. 2016; 83:381-391 [PubMed] Related Publications
Though advanced surgical operation and chemotherapy have been under taken, lung cancer remains one of the most aggressive and fatal human malignancies with a low survival rate. Thus, novel therapeutic strategies for prevention and remedy are urgently needed in lung cancer. Hyperoside, known as quercetin-3-O-β-d-galactopyranoside, is a natural flavonol glycoside discovered in plants of genera Hypericum, displaying anti-oxidant, anticancer, and anti-inflammatory properties. In the study, we attempted to investigate whether hyperoside could inhibit lung cancer progression via Caspase-3- and P53-regulated cell death. In in vitro and in vivo experiments, we explored hyperoside at three different dosages on cell apoptosis, cell proliferation, cell migration, cell invasion, cell cycle distribution, the related signalling pathways, as well as xenograft tumor growth. Our data suggested that hyperoside exerted inhibitory role in lung cancer development. Inhibition of NF-κB transcriptional activity, Caspase-9/Caspase-3 activation, the cell cycle arrest, and suppression of cell proliferation-related signaling pathway led to the lung cancer inhibition. Further, via mice xenograft model in vivo, we indicated that hyperoside completely impeded tumor growth through angiogenesis inhibition. Our study illustrated that hyperoside might provide a synergistic anticancer effects that warrant further study and investigation due to its potential role in clinical applications.

Nicholls L, Keir GJ, Murphy MA, et al.
Prophylactic cranial irradiation in small cell lung cancer: A single institution experience.
Asia Pac J Clin Oncol. 2016; 12(4):415-420 [PubMed] Related Publications
AIM: To compare patient demographics, prophylactic cranial irradiation (PCI) utilization and overall survival (OS) of patients with small cell lung cancer (SCLC) referred to a large tertiary center with those reported in large clinical trials.
PATIENTS AND METHODS: A retrospective review was conducted of consecutive patients with limited stage (LS) and extensive stage (ES) SCLC diagnosed at the Princess Alexandra Hospital between January 2008 and December 2013.
RESULTS: Two hundred and three patients with a mean age of 65.4 (±10.7) years were followed for a median duration of 7.6 months (range 0.5-76.5). At diagnosis, 129 (64%) patients had ES-SCLC, including 39 (19.2%) with cerebral metastases. Median OS in LS-SCLC patients receiving PCI was 18.8 months (0.9-69.4), compared with 8.2 months (0.1-34.4) in patients who did not receive PCI (P < 0.001). Median OS in the ES-SCLC cohort receiving PCI was 13.6 months (5.2-37.5) compared to 5.6 months (0.1-73.6) in patients who did not receive the therapy (P < 0.001). There was a significant improvement in intracranial disease-free survival of 7.1 months in patients with ES-SCLC who received PCI. Forty-two LS-SCLC patients (57%) did not receive PCI due to patient suitability.
CONCLUSIONS: In our SCLC cohort, median OS following PCI in LS-SCLC and ES-SCLC is comparable to published data. PCI use at our institution was lower than utilization rates in large meta-analyses, predominately due to poor chemotherapy tolerance and patient suitability. This may be more representative of patients treated in clinical practice rather than those recruited into large phase III trials.

Katki HA, Kovalchik SA, Berg CD, et al.
Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening.
JAMA. 2016; 315(21):2300-11 [PubMed] Free Access to Full Article Related Publications
IMPORTANCE: The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations.
OBJECTIVE: Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations.
DESIGN, SETTING, AND PARTICIPANTS: Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST.
EXPOSURES: Annual CT lung screening for 3 years beginning at age 50 years.
MAIN OUTCOMES AND MEASURES: For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death).
RESULTS: Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US ever-smokers aged 50 to 80 years (NHIS 1997-2001: estimated/observed = 0.94 [95%CI, 0.84-1.05]; AUC, 0.78 [95%CI, 0.76-0.80]). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung cancer screening and 46,488 (95% CI, 43,924-49,053) lung cancer deaths were estimated as screen-avertable over 5 years (estimated NNS, 194 [95% CI, 187-201]). In contrast, risk-based selection screening of the same number of ever-smokers (9.0 million) at highest 5-year lung cancer risk (≥1.9%) was estimated to avert 20% more deaths (55,717 [95% CI, 53,033-58,400]) and was estimated to reduce the estimated NNS by 17% (NNS, 162 [95% CI, 157-166]).
CONCLUSIONS AND RELEVANCE: Among a cohort of US ever-smokers aged 50 to 80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung cancer deaths prevented over 5 years, along with a lower NNS to prevent 1 lung cancer death.

Bain AA, Abbott AL, Miller LL
Successes and Challenges in Implementation of Radon Control Activities in Iowa, 2010-2015.
Prev Chronic Dis. 2016; 13:E50 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Radon gas has recently become more prominent in discussions of lung cancer prevention nationally and in Iowa. A review in 2013 of cancer plans in the National Comprehensive Cancer Control Program found that 42% of cancer plans, including Iowa's, had terminology on radon. Plans included awareness activities, home testing, remediation, policy, and policy evaluation.
COMMUNITY CONTEXT: Iowa has the highest average radon concentrations in the United States; 70% of homes have radon concentrations above the Environmental Protection Agency's action levels. Radon control activities in Iowa are led by the Iowa Cancer Consortium, the Iowa Department of Public Health, and the Iowa Radon Coalition.
METHODS: A collaborative approach was used to increase levels of awareness, testing, and (if necessary) mitigation, and to introduce a comprehensive radon control policy in Iowa by engaging partners and stakeholders across the state.
OUTCOME: The multipronged approach and collaborative work in Iowa appears to have been successful in increasing awareness: the number of radon tests completed in Iowa increased by 20% from 19,600 in 2009 to 23,500 in 2014, and the number of mitigations completed by certified mitigators increased by 108% from 2,600 to more than 5,400.
INTERPRETATION: Through collaboration, Iowa communities are engaged in activities that led to increases in awareness, testing, mitigation, and policy. States interested in establishing a similar program should consider a multipronged approach involving multiple entities and stakeholders with different interests and abilities. Improvements in data collection and analysis are necessary to assess impact.

Ordóñez-Mena JM, Schöttker B, Mons U, et al.
Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium.
BMC Med. 2016; 14:62 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.
METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.
RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.
CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

Lin Y, He F, Zhang X, et al.
Polymorphism rs144848 in BRCA2 may reduce lung cancer risk in women: a case-control study in southeast China.
Tumori. 2016 Mar-Apr; 102(2):150-5 [PubMed] Related Publications
PURPOSE: Whereas lung cancer incidence among men has declined in recent years, the incidence rate among women has increased rapidly. Sex could affect DNA repair capacity. Although BRCA2 is important in DNA repair, few data are available on the association between BRCA2 polymorphisms and lung cancer in women. Therefore, we investigated this in a case-control study among Chinese women.
METHODS: We enrolled 226 women with lung cancer and 269 age-matched healthy controls in our study. Polymorphisms studied were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
RESULTS: Unconditional logistic regression showed no association between rs1799943 or rs1799944 and cancer risk. However, the AC and CC genotypes of rs144848 were significantly associated with reduced risk after adjustment for age and education, with adjusted odds ratios (ORs) of 0.66 (95% confidence interval [CI] 0.45-0.97) and 0.37 (95% CI 0.16-0.78), respectively. The adjusted OR of carriers with the C allele was 0.62 (95% CI 0.44-0.81) compared with the A allele.
CONCLUSIONS: The rs144848 mutation may have a protective effect against lung cancer among women.

Sun Y, Li Z, Li J, et al.
A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis.
Nutrients. 2016; 8(3):134 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear.
OBJECTIVE: Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk.
METHODS: We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed.
RESULTS: Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75-0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63-1.27), 0.74 (95% CI: 0.62-0.89) and 0.86 (95% CI: 0.79-0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis.
CONCLUSIONS: The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population.

Cruz A, Castillo Z, Pérez J, Abeledo A
A Woman-centered Educational Program for Primary Prevention of Lung Cancer in a Cuban Municipality, 2012--2013.
MEDICC Rev. 2015; 17(4):44-7 [PubMed] Related Publications
Lung cancer educational programs seek the involvement of different groups in efforts to promote healthier habits and lifestyles. Women are primary agents for targeting prevention actions because of their ability to foster healthy lifestyles within their families. The purpose of this study was to develop a woman-centered educational program to strengthen knowledge and promote responsible behavior aimed at primary prevention of lung cancer. Based on identified learning needs in 133 female participants concerning lung cancer self care, healthy habits and communication skills about self care, a ten-workshop series was designed and validated by specialists and users. Before intervention, 82% of participants were highly aware of smoking-related harm, but only 26% were highly aware of healthy environmental management practices at home and 14% were knowledgeable about self care. Differences in both awareness and practice of health-promoting behaviors were observed by the end of the training: those highly aware of smoking-related harm rose to 86.5%, and those highly aware of environmental management and self care increased to 66.2% and 83.5%, respectively. The proportions reporting acceptable levels of environmental management and self-care practices increased to 86.5% (from 0%) and 91% (from 3.8%), respectively. One year later, a positive impact on families was confirmed, predominantly on children. We conclude that such a woman-centered educational program can increase awareness and promote healthy behaviors aimed at lung cancer prevention. Women's ability to communicate and share lessons learned within their families should be considered in designing community health education programs. KEYWORDS Lung cancer, health education, disease prevention, primary prevention, health promotion, Cuba.

Zhang Z, Ren X, Lu X, et al.
GZD856, a novel potent PDGFRα/β inhibitor, suppresses the growth and migration of lung cancer cells in vitro and in vivo.
Cancer Lett. 2016; 375(1):172-8 [PubMed] Related Publications
Platelet-derived growth factor receptors (PDGFRα/β) play critical roles in the autocrine-stimulated growth and recruitment of cancer-associated fibroblasts (CAFs) of human lung cancer cells. We have identified GZD856 as a new PDGFR inhibitor that potently inhibits PDGFRα/β kinase activity and blocks this signaling pathway in lung cancer cells both in vitro and in vivo. GZD856 strongly suppresses the proliferation of PDGFRα-amplified H1703 (PDGFRβ(-)) human lung cancer cells and demonstrates significant in vivo antitumor efficacy in a xenograft mouse model. Although GZD856 displays only limited in vitro antiproliferative efficiency against PDGFRα(-)/PDGFRβ(+) A549 lung cancer cells, it efficiently inhibits the in vivo growth and metastasis of A549 cancer cells in xenograft and orthotopic models, respectively. The promising in vivo antitumor activity of GZD856 in A549 models may result from its suppression of PDGFR-related microenvironment factors, such as recruitment of CAFs and collagen content in stromal cells. GZD856 may be considered as a promising new candidate for anti-lung cancer drug development.

Fucito LM, Czabafy S, Hendricks PS, et al.
Pairing smoking-cessation services with lung cancer screening: A clinical guideline from the Association for the Treatment of Tobacco Use and Dependence and the Society for Research on Nicotine and Tobacco.
Cancer. 2016; 122(8):1150-9 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
Smoking cessation is crucial for reducing cancer risk and premature mortality. The US Preventive Services Task Force (USPSTF) has recommended annual lung cancer screening with low-dose computed tomography (LDCT), and the Center for Medicare and Medicaid Services recently approved lung screening as a benefit for patients ages 55 to 77 years who have a 30 pack-year history. The Society for Research on Nicotine and Tobacco (SRNT) and the Association for the Treatment of Tobacco Use and Dependence (ATTUD) developed the guideline described in this commentary based on an illustrative literature review to present the evidence for smoking-cessation health benefits in this high-risk group and to provide clinical recommendations for integrating evidence-based smoking-cessation treatment with lung cancer screening. Unfortunately, extant data on lung cancer screening participants were scarce at the time this guideline was written. However, in this review, the authors summarize the sufficient evidence on the benefits of smoking cessation and the efficacy of smoking-cessation interventions for smokers ages 55 to 77 years to provide smoking-cessation interventions for smokers who seek lung cancer screening. It is concluded that smokers who present for lung cancer screening should be encouraged to quit smoking at each visit. Access to evidence-based smoking-cessation interventions should be provided to all smokers regardless of scan results, and motivation to quit should not be a necessary precondition for treatment. Follow-up contacts to support smoking-cessation efforts should be arranged for smokers. Evidence-based behavioral strategies should be used at each visit to motivate smokers who are unwilling to try quitting/reducing smoking or to try evidence-based treatments that may lead to eventual cessation.

Ledford CJ, Gawrys BL, Wall JL, et al.
Translating New Lung Cancer Screening Guidelines into Practice: The Experience of One Community Hospital.
J Am Board Fam Med. 2016 Jan-Feb; 29(1):152-5 [PubMed] Related Publications
INTRODUCTION: In December 2013 the US Preventive Services Task Force issued a recommendation for lung cancer screening with annual low-dose computed tomography (LDCT). As screening guidelines emerge and change, this creates an environment for studying the translation of these guidelines into practice. This study assessed how these guidelines were implemented in a community hospital setting and the resulting radiologic findings.
METHODS: This observational study examined the radiologic outcomes of LDCT lung cancer screening guidelines and the resulting notification.
RESULTS: During the first year after publication of the guidelines, 94 screening LDCT scans were ordered. Of these, 21 (22.3%) did not meet the criteria outlined by the US Preventive Services Task Force. Among the 72 cases that did met published criteria, 65.3% of scans detected nodules, and among the remaining 35.6%, half had another clinically significant finding.
DISCUSSION: This study shows that new lung cancer screening guidelines, as implemented at a community hospital, resulted in radiologic findings that required follow-up in more than half of patients. Clinicians must be aware of these potential incidental findings when talking to patients about the decision to order screenings.

Choi SH, Nam JK, Kim BY, et al.
HSPB1 Inhibits the Endothelial-to-Mesenchymal Transition to Suppress Pulmonary Fibrosis and Lung Tumorigenesis.
Cancer Res. 2016; 76(5):1019-30 [PubMed] Related Publications
The endothelial-to-mesenchymal transition (EndMT) contributes to cancer, fibrosis, and other pathologic processes. However, the underlying mechanisms are poorly understood. Endothelial HSP1 (HSPB1) protects against cellular stress and has been implicated in cancer progression and pulmonary fibrosis. In this study, we investigated the role of HSPB1 in mediating the EndMT during the development of pulmonary fibrosis and lung cancer. HSPB1 silencing in human pulmonary endothelial cells accelerated emergence of the fibrotic phenotype after treatment with TGFβ or other cytokines linked to pulmonary fibrosis, suggesting that HSPB1 maintains endothelial cell identity. In mice, endothelial-specific overexpression of HSPB1 was sufficient to inhibit pulmonary fibrosis by blocking the EndMT. Conversely, HSPB1 depletion in a mouse model of lung tumorigenesis induced the EndMT. In clinical specimens of non-small cell lung cancer, HSPB1 expression was absent from tumor endothelial cells undergoing the EndMT. Our results showed that HSPB1 regulated the EndMT in lung fibrosis and cancer, suggesting that HSPB1-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases.

De Flora S, Ganchev G, Iltcheva M, et al.
Pharmacological Modulation of Lung Carcinogenesis in Smokers: Preclinical and Clinical Evidence.
Trends Pharmacol Sci. 2016; 37(2):120-42 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
Many drugs in common use possess pleiotropic properties that make them capable of interfering with carcinogenesis mechanisms. We discuss here the ability of pharmacological agents to mitigate the pulmonary carcinogenicity of mainstream cigarette smoke. The evaluated agents include anti-inflammatory drugs (budesonide, celecoxib, aspirin, naproxen, licofelone), antidiabetic drugs (metformin, pioglitazone), antineoplastic agents (lapatinib, bexarotene, vorinostat), and other drugs and supplements (phenethyl isothiocyanate, myo-inositol, N-acetylcysteine, ascorbic acid, berry extracts). These drugs have been evaluated in mouse models mimicking interventions either in current smokers or in ex-smokers, or in prenatal chemoprevention. They display a broad spectrum of activities by attenuating either smoke-induced preneoplastic lesions or benign tumors and/or malignant tumors. Together with epidemiological data, these findings provide useful information to predict the potential effects of pharmacological agents in smokers.

Predina JD, Keating J, Patel N, et al.
Clinical implications of positive margins following non-small cell lung cancer surgery.
J Surg Oncol. 2016; 113(3):264-9 [PubMed] Related Publications
Positive margins following pulmonary resection of non-small cell lung cancer (NSCLC) occur in approximately 5-15% of patients undergoing a curative procedure. The presence of positive margins negatively impacts long-term outcomes by setting the stage for local and potentially distant disease recurrence. Despite major clinical ramifications, there are very few dedicated reports that examine the implications of positive margins following surgery for NSCLC. Furthermore, published series are typically retrospective studies from single institutions. In this review we analyze published data with special consideration of four pertinent questions: (i) what are the long term outcomes of a positive margin following pulmonary resection?, (ii) is intraoperative margin assessment by frozen section reliable?, (iii) what is the optimal distance of the tumor margin to the surgical margin?, and (iv) should adjuvant chemotherapy and/or radiation therapy be used in the setting of a positive surgical margin?

Field JK, Devaraj A, Duffy SW, Baldwin DR
CT screening for lung cancer: Is the evidence strong enough?
Lung Cancer. 2016; 91:29-35 [PubMed] Related Publications
The prevailing questions at this time in both the public mind and the clinical establishment is, do we have sufficient evidence to implement lung cancer Computed Tomography (CT) screening in Europe? If not, what is outstanding? This review addresses the twelve major areas, which are critical to any decision to implement CT screening and where we need to assess whether we have sufficient evidence to proceed to a recommendation for implementation in Europe. The readiness level of these twelve categories in 2015 have been with colour coded, where green indicates we have sufficient evidence, amber is borderline evidence and red requires further evidence. Recruitment from the 'Hard to Reach' community still remains at red, while mortality data, cost effectiveness and screening interval are all categorised as amber. The integration of smoking cessation into CT screening programmes is still considered to be category amber. The US Preventive Services Task Force have recommended that CT screening is implemented in the USA utilising the NLST criteria, apart from continuing screening to 80 years of age. The cost effectiveness of the NLST was calculated to be $81,000/QALY, however, its well recognised that the costs of medical care in the USA, is far higher than that of Europe. Medicare have agreed to cover the cost of screening but have stipulated a number of stringent requirements for inclusion. To date we do not have good CT screening mortality data available in Europe and eagerly await the publication of the NELSON trial data in 2016 and then the pooled UKLS and NELSON data thereafter. However in the meantime we should start planning for implementation in Europe, especially in the areas of the radiological service provision and accreditation, as well as identifying novel mechanisms to recruit from the hardest to reach communities.

Wu X, Liu T, Fang O, et al.
MicroRNA-708-5p acts as a therapeutic agent against metastatic lung cancer.
Oncotarget. 2016; 7(3):2417-32 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
MicroRNAs (miRNAs) have recently been recognized as targets for anti-metastatic therapy against cancer malignancy. Development of effective miRNA mediated therapies remains a challenge to both basic research and clinical practice. Here we presented the evidence for a miR-708-5p mediated replacement therapy against metastatic lung cancer. Expression of miR-708-5p was substantially reduced in metastatic lung cancer samples and cancer cell lines when compared to non-metastatic counterparts. Expression of the miRNA suppressed cell survival and metastasis in vitro through its direct target p21, and inhibited the PI3K/AKT pathway and stem cell-like characteristics of lung cancer cells. Systemic administration of this miRNA in a mouse model of NSCLC using polyethylenimine (PEI)-mediated delivery of unmodified miRNA mimics induced tumor specific apoptosis. It also effectively protected the tested animals from developing metastatic malignancy without causing any observed toxicity. The findings strongly support miR-708-5p as a novel and effective therapeutic agent against metastatic malignancy of non-small cell lung cancer.

Li H, Hu J, Wu S, et al.
Auranofin-mediated inhibition of PI3K/AKT/mTOR axis and anticancer activity in non-small cell lung cancer cells.
Oncotarget. 2016; 7(3):3548-58 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
Auranofin, a gold complex that has been used to treat rheumatoid arthritis in clinics and has documented pharmacokinetic and safety profiles in humans, has recently been investigated for its anticancer activity in leukemia and some solid cancers. However, auranofin's single agent activity in lung cancer is not well characterized. To determine whether auranofin has single agent activity in lung cancer, we evaluated auranofin's activity in a panel of 10 non-small cell lung cancer (NSCLC) cell lines. Cell viability analysis revealed that auranofin induced growth inhibition in a subset of NSCLC cell lines with a half maximal inhibitory concentration (IC50) below 1.0 μM. Treatment with auranofin elicited apoptosis and necroptosis in auranofin-sensitive cell lines. Moreover, the susceptibility of NSCLC cells to auranofin was inversely correlated with TXNRD1 expression in the cells. Transient transfection of the TXNRD1-expressing plasmid in auranofin-sensitive Calu3 cells resulted in partial resistance, indicating that high TXNRD level is one of causal factors for resistance to auranofin. Further mechanistic characterization with proteomic analysis revealed that auranofin inhibits expression and/or phosphorylation of multiple key nodes in the PI3K/AKT/mTOR pathway, including S6, 4EBP1, Rictor, p70S6K, mTOR, TSC2, AKT and GSK3. Ectopic expression of TXNRD1 partially reversed auranofin-mediated PI3K/AKT/mTOR inhibition, suggesting that TXNRD1 may participate in the regulation of PI3K/AKT/mTOR pathway. Administration of auranofin to mice with xenograft tumors derived from NSCLC cells significantly suppressed tumor growth without inducing obvious toxic effects. Our results demonstrated feasibility of repurposing auranofin for treatment of lung cancer.

Bodduluru LN, Kasala ER, Madhana RM, et al.
Naringenin ameliorates inflammation and cell proliferation in benzo(a)pyrene induced pulmonary carcinogenesis by modulating CYP1A1, NFκB and PCNA expression.
Int Immunopharmacol. 2016; 30:102-10 [PubMed] Related Publications
Lung cancer is the major cause of cancer-related mortality and is a growing economic burden worldwide. Chemoprevention has emerged as a very effective preventive measure against carcinogenesis and several bioactive compounds in diet have shown their cancer curative potential on lung cancer. Naringenin (NRG), a predominant flavanone found in citrus fruits has been reported to possess anti-oxidative, anti-inflammatory and anti-proliferative activity in a wide variety of cancer. The aim of the present study is to divulge the chemopreventive nature of NRG against benzo(a)pyrene (B[a]P) induced lung carcinogenesis in Swiss albino mice. Administration of B[a]P (50mg/kg, p.o.) to mice resulted in increased lipid peroxidation (LPO), proinflammatory cytokines (TNF-α, IL-6 and IL-1β) with subsequent decrease in activities of tissue enzymic antioxidants (SOD, CAT, GPx, GR, GST) and non-enzymic antioxidants (GSH and Vit-C). Treatment with NRG (50mg/kg body weight) significantly counteracted all these alterations thereby showing potent anti-cancer effect in lung cancer. Moreover, assessment of protein expression by immunoblotting and mRNA expression by RT-PCR revealed that NRG treatment effectively negates B[a]P-induced upregulated expression of CYP1A1, PCNA and NF-κB. Further, the antiproliferative effect of NRG was confirmed by histopathological analysis and PCNA immunostaining in B[a]P induced mice which showed increased PCNA expression that was restored upon NRG administration. Overall, these findings substantiate the chemopreventive potential of NRG against chemically induced lung cancer in mice.

Tian L, Shen D, Li X, et al.
Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4.
Oncotarget. 2016; 7(2):1619-32 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 μg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer.

Eberth JM
Lung Cancer Screening With Low-Dose CT in the United States.
J Am Coll Radiol. 2015; 12(12 Pt B):1395-402 [PubMed] Related Publications
The findings of the landmark National Lung Screening Trial (NLST)-showing a 20% reduction in lung cancer mortality when screening with low-dose CT (LDCT), compared with chest radiography-marked a turning point in the field of lung cancer screening, influencing organizational recommendations and leading to increasing acceptance of LDCT for screening of individuals at high risk for lung cancer. However, many practices and institutions have experienced barriers in their attempts to implement successful screening programs; these include challenges in maintaining the same high caliber of screening programs as those in the NLST, confusion regarding insurance reimbursement protocols, and a lack of resources to help physicians discuss the specifics of LDCT screening with their patients. To address these challenges, standards are being established to ensure consistent quality of screening programs, including certification standards and protocols maintained by the ACR. In addition, the US Preventive Services Task Force's "B" rating, given to LDCT screening in late 2013, resulted in mandated private insurance coverage beginning in 2015 and the 2015 CMS coverage determination has spurred previously reluctant organizations to prepare for population-based screening. Despite these successes, protocols for billing and claims processing are still evolving and organizations are considering how best to implement the shared decision-making process required by CMS. Despite some procedural setbacks that have yet to be resolved, LDCT screening for individuals at high risk of lung cancer has grown substantially since its effectiveness was shown by the NLST in 2011.

Hagerman CJ, Tomko CA, Stanton CA, et al.
Incorporating a Smoking Cessation Intervention into Lung Cancer Screening Programs: Preliminary Studies.
J Psychosoc Oncol. 2015; 33(6):703-23 [PubMed] Related Publications
Two preliminary studies assessed whether telephone counseling (TC) is a feasible smoking cessation intervention following lung cancer screening. Seven older smokers undergoing lung cancer screening (pack years = 61.5) completed three TC sessions, which incorporated the screening result as motivation to quit. Participation (87.5%) and retention (85.7%) rates were good, and four smokers quit smoking (three of whom received abnormal results). We conducted four focus groups with 16 current and former older smokers (pack years = 55). Most believed that an abnormal scan would motivate them to quit and expressed interest in TC. TC may be feasible and potentially efficacious within lung screening programs.

Liu L, Li H, Guo Z, et al.
The Combination of Three Natural Compounds Effectively Prevented Lung Carcinogenesis by Optimal Wound Healing.
PLoS One. 2015; 10(11):e0143438 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
The tumor stroma has been described as "normal wound healing gone awry". We explored whether the restoration of a wound healing-like microenvironment may facilitate tumor healing. Firstly, we screened three natural compounds (shikonin, notoginsenoside R1 and aconitine) from wound healing agents and evaluated the efficacies of wound healing microenvironment for limiting single agent-elicited carcinogenesis and two-stage carcinogenesis. The results showed that three compounds used alone could promote wound healing but had unfavorable efficacy to exert wound healing, and that the combination of three compounds made up treatment disadvantage of a single compound in wound healing and led to optimal wound healing. Although individual treatment with these agents may prevent cancer, they were not effective for the treatment of established tumors. However, combination treatment with these three compounds almost completely prevented urethane-induced lung carcinogenesis and reduced tumor burden. Different from previous studies, we found that urethane-induced lung carcinogenesis was associated with lung injury independent of pulmonary inflammation. LPS-induced pulmonary inflammation did not increase lung carcinogenesis, whereas decreased pulmonary inflammation by macrophage depletion promoted lung carcinogenesis. In addition, urethane damaged wound healing in skin excision wound model, reversed lung carcinogenic efficacy by the combination of three compounds was consistent with skin wound healing. Further, the combination of these three agents reduced the number of lung cancer stem cells (CSCs) by inducing cell differentiation, restoration of gap junction intercellular communication (GJIC) and blockade of the epithelial-to-mesenchymal transition (EMT). Our results suggest that restoration of a wound healing microenvironment represents an effective strategy for cancer prevention.

Yu N, Su X, Wang Z, et al.
Association of Dietary Vitamin A and β-Carotene Intake with the Risk of Lung Cancer: A Meta-Analysis of 19 Publications.
Nutrients. 2015; 7(11):9309-24 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
Whether dietary β-carotene and vitamin A intake protect against lung cancer risk is not clear. Therefore, we performed this meta-analysis to investigate the association between them. The related articles were searched using the databases PubMed and the Web of Knowledge up to May 2015. We used the random-effect model to estimate the relative risk (RR) and their 95% CI. Small-study effect was assessed using Egger's test. In total, 19 studies comprising 10,261 lung cancer cases met the inclusion criteria. The pooled RR and their 95% CI was 0.855 (0.739-0.989) for higher category of dietary vitamin A intake and lung cancer risk, especially among Asian populations and in the cohort studies. Evidence from 18 studies suggested that higher category of dietary β-carotene intake could reduce lung cancer risk (0.768 (0.675-0.874)).The associations were also significant in American and Asian populations. In conclusions, higher category of dietary β-carotene and vitamin A intakes could reduce the risk of lung cancer. However, the dose-response analysis was not performed due to the limited data in each individual study. Due to this limitation, further studies with detailed dose, cases and person-years for β-carotene and vitamin A of each category are wanted to assess this dose-response association.

Chen Y, Xiao Y, Yang Y, et al.
Decomposing contribution of age and non-age factors to rapid growth of lung cancer in Xuanwei over past 30 years.
BMC Public Health. 2015; 15:1116 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
BACKGROUND: From 1973 to 2005, the lung cancer mortality in Xuanwei had increased constantly. Effect analysis of age and non-age factors on lung cancer is important for local policy-making.
METHODS: Demographic and death data was collected and used. Factors of lung cancer were classified into age and non-age factors. The contribution of the two factors to lung cancer was evaluated by method of decomposing the differences of mortality rate.
RESULTS: For males, the non-age factors were the major contributor to growth of lung cancer mortality, and 78.46% of all growth was attributed to non-age factors. For females, the non-age factors were the absolute contributor to growth of lung cancer in 1973-1992. From 1992 to 2005, the contribution proportion had reduced to 75.39%.
CONCLUSIONS: Aging was one of risk factors for lung cancer in Xuanwei, but not the main factor. It was supposed that multiple environmental risk factors were related with high growth of lung cancer in Xuanwei. Policy-making should focus on the non-age factors.

Qin Y, Zhang Q, Lee S, et al.
Doxycycline reverses epithelial-to-mesenchymal transition and suppresses the proliferation and metastasis of lung cancer cells.
Oncotarget. 2015; 6(38):40667-79 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
The gelatinase inhibitor doxycycline is the prototypical antitumor antibiotic. We investigated the effects of doxycycline on the migration, invasion, and metastasis of human lung cancer cell lines and in a mouse model. We also measured the effect of doxycycline on the transcription of epithelial-mesenchymal transition (EMT) markers, and used immunohistochemistry to determine whether EMT reversal was associated with doxycycline inhibition. Doxycycline dose-dependently inhibited proliferation, migration, and invasion of NCI-H446 human small cell lung cancer cells. It also suppressed tumor growth from NCI-H446 and A549 lung cancer cell xenografts without altering body weight, inhibited Lewis lung carcinoma cell migration, and prolonged survival. The activities of the transcription factors Twist1/2, SNAI1/2, AP1, NF-κB, and Stat3 were suppressed by doxycycline, which reversed EMT and inhibited signal transduction, thereby suppressing tumor growth and metastasis. Our data demonstrate functional targeting of transcription factors by doxycycline to reverse EMT and suppress tumor proliferation and metastasis. Thus, doxycycline selectively targets malignant tumors and reduces its metastatic potential with less cytotoxicity in lung cancer patients.

Pinsky PF, Kramer BS
Lung Cancer Risk and Demographic Characteristics of Current 20-29 Pack-year Smokers: Implications for Screening.
J Natl Cancer Inst. 2015; 107(11) [PubMed] Article available free on PMC after 15/04/2017 Related Publications
BACKGROUND: Based on current recommendations, 30+ pack-years of smoking are required for eligibility for low-dose CT (LDCT) lung cancer screening; former smokers must have quit within 15 years. We investigated whether current smokers with 20 to 29 pack-years have similar lung cancer risks as eligible former smokers and also whether they have a different demographic profile.
METHODS: The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) was a randomly assigned screening trial of subjects age 55 to 74 years with chest radiographs (CXR) used for lung cancer. Subjects completed a baseline questionnaire containing smoking history questions. Cox proportional hazards models, adjusted for age and sex, were utilized to estimate hazard ratios (HRs) for various smoking history groups. Next, we utilized the National Health Interview Survey (NHIS), which inquired about smoking history and race/ethnicity, to analyze the demographic profiles of various high-risk smoking history categories. All statistical tests were two-sided.
RESULTS: The PLCO cohort included 18 114 former and 12 243 current LDCT-eligible smokers, plus 2283 20- to 29-pack-year current smokers. The hazard ratio for 20- to 29-pack-year current smokers compared with eligible (30+ pack-year) former smokers was 1.07 (95% confidence interval [CI] = 0.75 to 1.5). Based on the NHIS, 10 million persons in the United States are currently LDCT eligible; an additional 1.6 million (16%, 95% CI = 13.6% to 19.0%) are 20- to 29-pack-year current smokers. The percentage increase in eligibles if 20- to 29-pack-year current smokers were included was substantially greater for women than men (22.2%, 95% CI = 17.9% to 26.7%; vs 12.2%, 95% CI = 9.3% to 15.3%, P < .001) and for minorities than non-Hispanic whites (30.0%, 95% CI = 24.2% to 36.0%; vs 14.1%, 95% CI = 11.1% to 17.0%, P < .001).
CONCLUSION: The potential benefits and harms of recommending LDCT screening for 20 to 29-pack-year current smokers should be assessed.

Stang A, Schuler M, Kowall B, et al.
Lung Cancer Screening Using Low Dose CT Scanning in Germany. Extrapolation of results from the National Lung Screening Trial.
Dtsch Arztebl Int. 2015; 112(38):637-44 [PubMed] Article available free on PMC after 15/04/2017 Related Publications
BACKGROUND: It is now debated whether the screening of heavy smokers for lung cancer with low dose computed tomography (low dose CT) might lower their mortality due to lung cancer. We use data from the National Lung Screening Trial (NLST) in the USA to predict the likely effects of such screening in Germany.
METHODS: The number of heavy smokers aged 55-74 in Germany was extrapolated from survey data obtained by the Robert Koch Institute. Published data from the NLST were then used to estimate the likely effects of low dose CT screening of heavy smokers in Germany.
RESULTS: If low dose CT screening were performed on 50% of the heavy smokers in Germany aged 55-74, an estimated 1 329 506 persons would undergo such screening. If the screening were repeated annually, then, over three years, 916 918 screening CTs would reveal suspect lesions, and the diagnosis of lung cancer would be confirmed thereafter in 32 826 persons. At least one positive test result in three years would be obtained in 39.1% of the participants (519 837 persons). 4155 deaths from lung cancer would be prevented over 6.5 years, and the number of persons aged 55-74 who die of lung cancer in Germany would fall by 2.6%. 12 449 persons would have at least one complication, and 1074 persons would die in the 60 days following screening.
CONCLUSION: The screening of heavy smokers for lung cancer can lower their risk of dying of lung cancer by 20% in relative terms, corresponding to an absolute risk reduction of 0.3 percentage points. These figures can provide the background for a critical discussion of the putative utility of this type of screening in Germany.

Vitzthum K, Thielke L, Deter A, et al.
Smoking Lung Cancer Patients and Tobacco Cessation - Is the Current Treatment in Germany Sufficient?
Pneumologie. 2015; 69(11):667-72 [PubMed] Related Publications
Lung cancer is the most preventable neoplastic disease for men and women. The incidence rate per year is 14.000 in Germany. Smoking is the main risk factor for the onset of lung cancer and for a share of 90% of cases, lung cancer is associated with smoking. Recent studies have shown that the time slot of diagnosing lung cancer is a teachable moment for tobacco cessation interventions. The therapy that was rated most effective was a combination of cognitive behavioral therapy and pharmacotherapy (e. g. NRT, Bupropion, Varenicline). We examined the smoking status of all patients undergoing lung cancer surgery in 2011, 2012 and 2013 in this study. A retrospective semi structured interview via telephone was conducted regarding smoking habits and current quality of life. 131 patients (36.6% female, average age of 68.7 years) of an urban German hospital were included.Results showed a relapse rate of 22.3%, while 86.2% used to be highly addicted smokers; A multivariate analysis of covariance (MANCOVA) indicated a significant overall impact of smoking status on quality of life with a medium effect size, controlled for age, gender, living conditions, tumor stage, duration of smoking abstinence, type of cancer therapy, type of resection method, and the time period between the date of surgery and of the survey. Two thirds of all smokers did not see an association between their habit and their disease.So far motivation to quit and long term abstinence rates are not sufficiently established even among seriously sick patients in Germany; further initiatives should focus on new and more intense interventions and educational strategies.

Kasala ER, Bodduluru LN, Barua CC, et al.
Benzo(a)pyrene induced lung cancer: Role of dietary phytochemicals in chemoprevention.
Pharmacol Rep. 2015; 67(5):996-1009 [PubMed] Related Publications
Lung cancer is the major cause of overall cancer deaths, and chemoprevention is a promising strategy to control this disease. Benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is one among the principal constituents of tobacco smoke that plays a key role in lung carcinogenesis. The B(a)P induced lung cancer in mice offers a relevant model to study the effect of natural products and has been widely used by many researchers and found considerable success in ameliorating the pathophysiological changes of lung cancer. Currently available synthetic drugs that constitute the pharmacological armamentarium are themselves effective in managing the condition but not without setbacks. These hunches have accelerated the requisite for natural products, which may be used as dietary supplement to prevent the progress of lung cancer. Besides, these agents also supplement the conventional treatment and offer better management of the condition with less side effects. In the context of soaring interest toward dietary phytochemicals as newer pharmacological interventions for lung cancer, in the present review, we are attempting to give a silhouette of mechanisms of B(a)P induced lung carcinogenesis and the role of dietary phytochemicals in chemoprevention.

Tertil M, Golda S, Skrzypek K, et al.
Nrf2-heme oxygenase-1 axis in mucoepidermoid carcinoma of the lung: Antitumoral effects associated with down-regulation of matrix metalloproteinases.
Free Radic Biol Med. 2015; 89:147-57 [PubMed] Related Publications
Lung mucoepidermoid carcinoma (MEC) is a very poorly characterized rare subtype of non-small-cell lung cancer (NSCLC) associated with more favorable prognoses than other forms of intrathoracic malignancies. We have previously identified that heme oxygenase-1 (HO-1, encoded by HMOX1) inhibits MEC tumor growth and modulates the transcriptome of microRNAs. Here we investigate the role of a major upstream regulator of HO-1 and a master regulator of cellular antioxidant responses, transcription factor Nrf2, in MEC biology. Nrf2 overexpression in the NCI-H292 MEC cell line mimicked the phenotype of HO-1 overexpressing cells, leading to inhibition of cell proliferation and migration and down-regulation of oncogenic miR-378. HMOX1 silencing identified HO-1 as a major mediator of Nrf2 action. Nrf2- and HO-1 overexpressing cells exhibited strongly diminished expression of multiple matrix metalloproteinases and inflammatory cytokine interleukin-1β, which was confirmed in an NCI-HO-1 xenograft model. Overexpression of HO-1 altered not only human MMP levels in tumor cells but also murine MMP levels within tumor microenvironment and metastatic niche. This could possibly contribute to decreased metastasis to the lungs and inhibitory effects of HO-1 on MEC tumor growth. Our profound transcriptome analysis and molecular characterization of the mucoepidermoid lung carcinoma helps to understand the specific clinical presentations of these tumors, emphasizing a unique antitumoral role of the Nrf2-HO-1 axis.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

[Home]    Page last updated: 07 March, 2017     © CancerIndex, Established 1996