The preventative effects of statin on lung cancer development in patients with idiopathic pulmonary fibrosis using the National Health Insurance Service Database in Korea.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

A ketogenic diet rich in fish oil is superior to other fats in preventing NNK-induced lung cancer in A/J mice.

Given that ketogenic diets (KDs) are extremely high in dietary fat, we compared different fats in KDs to determine which was the best for cancer prevention. Specifically, we compared a Western and a 15% carbohydrate diet to seven different KDs, containing either Western fats or fats enriched in medium chain fatty acids (MCTs), milk fat (MF), palm oil (PO), olive oil (OO), corn oil (CO) or fish oil (FO) for their ability to reduce nicotine-derived nitrosamine ketone (NNK)-induced lung cancer in mice. While all the KDs tested were more effective at reducing lung nodules than the Western or 15% carbohydrate diet, the FO-KD was most effective at reducing lung nodules. Correlating with this, mice on the FO-KD had low blood glucose and the highest ß-hydroxybutyrate level, lowest liver fatty acid synthase/carnitine palmitoyl-1a ratio and a dramatic increase in fecal Akkermansia. We found no liver damage induced by the FO-KD, while the ratio of total cholesterol/HDL was unchanged on the different diets. We conclude that a FO-KD is superior to KDs enriched in other fats in reducing NNK-induced lung cancer, perhaps by being the most effective at skewing whole-body metabolism from a dependence on glucose to fats as an energy source.

Ganoderma lucidum spore oil synergistically enhances the function of cyclophosphamide in the prevention of breast cancer metastasis.

BACKGROUND: Ganoderma lucidum ( G . lucidum ) is a traditional Chinese herbal medicine that has shown potential as an alternative adjuvant therapy for cancer patients. However, the mechanisms and adjuvant therapeutic effects of G . lucidum in cancer treatment remain unclear. METHODS: In this work, G . lucidum spore oil (GanoOil), a newly developed oily G . lucidum spore extract was used to investigate the mechanisms and adjuvant therapeutic effects of GanoOil in conjunction with the chemotherapeutic drug cyclophosphamide (CTX) for preventing breast cancer metastasis. RESULTS: In the model of lung metastasis, orally administered GanoOil increased the population of CD8 + T cells and interleukin (IL)-6 cytokine levels in mouse blood, whereas also enhancing the activity of natural killer cells in the spleen. Furthermore, the combination of GanoOil and CTX effectively suppressed the lung metastasis of circulating breast cancer cells, alleviated CTX-induced weight loss, and reduced the ratio of lung and spleen weight to body weight in mice. Moreover, high concentrations of GanoOil exhibited no significant toxicity or side effects in both in vitro and in vivo experiments. CONCLUSION: In conclusion, GanoOil is a safe drug that can enhance immune activity in mice to achieve therapeutic effects on cancer, and can also synergistically inhibit tumor metastasis with CTX.

Euglena gracilis Extract Protects From Tobacco Smoke Carcinogen-Induced Lung Cancer by Altering Gut Microbiota Metabolome.

Extracts from Euglena gracilis have been shown to prevent cancer growth in mouse models. However, the molecular mechanism of this anti-cancer activity has not been determined nor has the effect of Euglena extracts on tobacco smoke carcinogen-induced carcinogenesis. Here, we investigate the hypothesis that this anti-cancer activity is a result of changes in the intestinal microbiota induced by oral administration of the extract. We found that a Euglena gracilis water extract prevents lung tumorigenesis induced by a tobacco smoke-specific carcinogen (NNK) in mice treated either 2 weeks before or 10 weeks after NNK injection. Both of these treatment regimens are associated with significant increases in 27 microbiota metabolites found in the mouse feces, including large increases in triethanolamine, salicylate, desaminotyrosine, N-acetylserine, glycolate, and aspartate. Increases in the short-chain fatty acids (SCFAs) including acetate, propionate and butyrate are also observed. We also detected a significant attenuation of lung carcinoma cell growth through the induction of cell cycle arrest and apoptosis caused by low levels of SCFAs. This study provides strong evidence of anti-cancer activity in Euglena gracilis extracts against tobacco smoke carcinogen-induced tumorigenesis and demonstrates that this activity is linked to increased production of specific gut microbiota metabolites and the resultant induction of cell cycle arrest and apoptosis of lung carcinoma cells.

Opportunities and Challenges of Kava in Lung Cancer Prevention.

Lung cancer is the leading cause of cancer-related deaths due to its high incidence, late diagnosis, and limited success in clinical treatment. Prevention therefore is critical to help improve lung cancer management. Although tobacco control and tobacco cessation are effective strategies for lung cancer prevention, the numbers of current and former smokers in the USA and globally are not expected to decrease significantly in the near future. Chemoprevention and interception are needed to help high-risk individuals reduce their lung cancer risk or delay lung cancer development. This article will review the epidemiological data, pre-clinical animal data, and limited clinical data that support the potential of kava in reducing human lung cancer risk via its holistic polypharmacological effects. To facilitate its future clinical translation, advanced knowledge is needed with respect to its mechanisms of action and the development of mechanism-based non-invasive biomarkers in addition to safety and efficacy in more clinically relevant animal models.

Carotenoids for lung cancer chemoprevention and chemotherapy: Promises and controversies.

BACKGROUND: Lung cancer is one of the leading causes of malignancy in the world. Several therapeutical and chemopreventive approaches have been practised to mitigate the disease. The use of phytopigments including carotenoids is a well-known approach. However, some of the prominent clinical trials interrogated the efficacy of carotenoids in lung cancer prevention. METHODS: A elaborate literature survey have been performed investigating in vitro, in vivo, and clinical studies reported on the administration of carotenoids for chemoprevention and chemotherapy. RESULTS: Tobacco consumption, genetic factors, dietary patterns, occupational carcinogens, lung diseases, infection, and sex disparities are some of the prominent factors leading to lung cancer. Significant evidence has been found underlining the efficiency of carotenoids in alleviating cancer. In vitro studies have proven that carotenoids act through PI3K/ AKT/mTOR, ERK-MAPK pathways and induce apoptosis through PPAR, IFNs, RAR, which are p53 intermediators in lung cancer signaling. Animal models and cell lines studies showed promising results, while the outcomes of clinical trials are contradictory and require further verification. CONCLUSION: The carotenoids exert chemotherapeutic and chemopreventive effects on lung tumors which has been evidenced in numerous investigations. However, further analyses are necessary to the answer the uncertainties raised by several clinical trials.

Dietary Phytochemicals as Potential Chemopreventive Agents against Tobacco-Induced Lung Carcinogenesis.

Lung cancer is the second most common cancer in the world. Cigarette smoking is strongly connected with lung cancer. Benzo[a]pyrene (BaP) and 4-(N-methyl-N-nitrosamine)-1-(3-pyridyl)-butanone (NNK) are the main carcinogens in cigarette smoking. Evidence has supported the correlation between these two carcinogens and lung cancer. Epidemiology analysis suggests that lung cancer can be effectively prevented through daily diet adjustments. This review aims to summarize the studies published in the past 20 years exploring dietary phytochemicals using Google Scholar, PubMed, and Web of Science databases. Dietary phytochemicals mainly include medicinal plants, beverages, fruits, vegetables, spices, etc. Moreover, the perspectives on the challenges and future directions of dietary phytochemicals for lung cancer chemoprevention will be provided. Taken together, treatment based on the consumption of dietary phytochemicals for lung cancer chemoprevention will produce more positive outcomes in the future and offer the possibility of reducing cancer risk in society.

Reducing tobacco-associated lung cancer risk: a study protocol for a randomized clinical trial of AB-free kava.

BACKGROUND: Tobacco use is the leading cause of many preventable diseases, resulting in premature death or disease. Given that the majority of adult who smoke want to stop, this health burden could be significantly reduced if the success rate of tobacco cessation can be improved. In addition, most adults planning to quit were interested in trying complementary approaches to facilitating tobacco cessation, which is currently lacking. Therefore, there is an unmet and urgent need for novel interventions to improve the success of tobacco cessation. If such an intervention can reduce tobacco-associated lung carcinogenesis, that will be more desirable. The goal of this project is to develop a safe and effective kava-based intervention to enable tobacco cessation and reduce lung cancer risk, which will improve the health of smokers. METHODS: A randomized controlled trial will enroll 80 adults who currently smoke at least 10 cigarettes daily and randomize 1:1 into the placebo and AB-free kava arms, being exposed for 4 weeks, with a total of six visits (weeks 0, 1, 2, 4, 8, and 12) to evaluate the compliance and potential issues of AB-free kava use among the participants, explore the potential effect of the AB-free kava intervention on tobacco dependence, tobacco use, and lung carcinogenesis biomarkers. Participants will be enrolled during their primary care clinic visit. DISCUSSION: Primary care settings play a critical role in tobacco-related disease screening, counseling, and early intervention, as the majority of adults who smoke visit their physicians annually. Building upon our promising pilot human trial results in conjunction with ample compelling lab animal results, and consistent with evidence of kava's benefits from epidemiological data, this trial will evaluate the compliance of AB-free kava among adults who currently smoke with no intention to quit. The other exploratory aims include (1) whether AB-free kava intervention can reduce tobacco use and tobacco dependence; (2) whether AB-free kava use suppresses tobacco-induced carcinogenesis; and (3) the potential of the mechanism-based noninvasive biomarkers in precision AB-free kava intervention. The positive results from this study are expected to provide a great opportunity to effectively reduce smoking rates and tobacco-related diseases. TRIAL REGISTRATION: ClinicalTrials.gov with the identifier: NCT05081882. Registered on October 18, 2021.

Association between ß-carotene supplementation and risk of cancer: a meta-analysis of randomized controlled trials.

CONTEXT: ß-Carotene, which is derived from most fruits and vegetables, is the most common type of carotenes. Existing studies have demonstrated that ß-carotene is associated with some positive health outcomes. However, results about the effects of supplemental ß-carotene on cancer are inconsistent. OBJECTIVE: To determine the association between supplemental ß-carotene intake and the risk of cancers. DATA SOURCES: Eight databases (PubMed, Web of Science, Embase, Cochrane, China National Knowledge Infrastructure, Wangfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) were systematically searched until September 2022. DATA EXTRACTION: Only reports from randomized controlled trials in which an association between supplemental ß-carotene intake and the risk of cancer was found were included in the meta-analysis. DATA ANALYSIS: A total of 18 eligible studies based on 8 different randomized controlled trials were included in the meta-analysis, with varying sample sizes from 391 to 39 876 participants. There was no significant association between supplemental ß-carotene intake and overall cancer incidence rate after synthesizing all the results (risk ratio [RR]: 1.02; 95% confidence interval [CI], 0.99-1.05). Results from subgroup analysis indicated that intake of supplemental ß-carotene significantly increased the risk of lung cancer (RR: 1.19; 95%CI: 1.08-1.32), whereas no significant associations were observed for other site-specific cancers. In addition, smokers and the subgroup of participants with only low-dose ß-carotene intake had a risk increment of cancer if they took supplemental ß-carotene (RR: 1.16; 95%CI: 1.05-1.29). CONCLUSION: ß-Carotene supplementation has no beneficial or harmful effect on cancer incidence; moreover, it might have potentially harmful effects on lung cancer, especially for people who smoke. On the basis of the evidence from this study, supplemental intake of ß-carotene is not recommended for preventing cancer, and the establishment of a tolerable upper intake level of ß-carotene should be considered.

Regular Glucosamine Use May Have Different Roles in the Risk of Site-Specific Cancers: Findings from a Large Prospective Cohort.

BACKGROUND: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. METHODS: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. RESULTS: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01-1.06], skin cancer (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01-1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses. CONCLUSIONS: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. IMPACT: The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Integrating network pharmacology and transcriptomic validation to investigate the efficacy and mechanism of Mufangji decoction preventing lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Mufangji decoction (MFJD), a famous traditional Chinese medicine formula in Synopsis of Golden Chamber (Jingui yaolue), has been utilized to treat cough and asthma and release chest pain over 2000 years in China. Chinese old herbalist doctor use MFJD to treat lung cancer and cancerous pleural fluid, but the preventive effect of MFJD on lung cancer and the underlying mechanism are indefinite. AIM OF THE STUDY: The goal of this study is to explore the efficacy and mechanism of Mufangji decoction preventing lung cancer referring to the traditional use. MATERIALS AND METHODS: Tumor allograft experiment and host versus tumor experiment were used to observe the direct anti-tumor effect and indirect anti-tumor immune effect, the mouse lung carcinogenic model was used to evaluate the dose-response and the preventive effect of MFJD on lung cancer. The active ingredients of MFJD were obtained by UPLC-MS/MS. The potential targets of MFJD were screened by network pharmacology and transcriptomics. The therapeutic targets and pathways of MFJD on lung cancer were obtained by protein-protein interaction, molecular docking and David database. The predicted results were verified in vitro and in vivo. RESULTS: MFJD could significantly prevent tumor growth in host versus tumor experiment but could not in tumor allograft experiment, indicating an anti-tumor immune effect against lung cancer. MFJD could reduce lung nodules with a dose-response in mouse lung carcinogenic model. Myeloperoxidase (MPO) was selected as the core target due to the highest degree value in Protein-Protein interaction network and had potently binding activity to sinomenine and dehydrocostus lactone in molecular docking. In vivo, MPO-expressed neutrophils are negatively correlated with lung cancer progression and MFJD could promote the neutrophil-related immune surveillance. In vitro, sinomenine and dehydrocostus lactone could promote neutrophil phagocytosis, MPO and ROS production in a dose dependent manner. The major compounds from MFJD were identified to regulate 36 targets for lung cancer prevention by UPLC-MS/MS, network pharmacology and transcriptomics. David database exhibited that MFJD plays an important role in immunoregulation by modulating 4 immune-related biological processes and 3 immune-related pathways. CONCLUSIONS: MFJD prevents lung cancer by mainly promoting MPO expression to maintain neutrophil immune surveillance, its key compounds are sinomenine and dehydrocostus lactone.

Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Cardiovascular disease and cancer are the 2 leading causes of death in the US, and vitamin and mineral supplementation has been proposed to help prevent these conditions. Objective: To review the benefits and harms of vitamin and mineral supplementation in healthy adults to prevent cardiovascular disease and cancer to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed (publisher-supplied records only), Cochrane Library, and Embase (January 2013 to February 1, 2022); prior reviews. Study Selection: English-language randomized clinical trials (RCTs) of vitamin or mineral use among adults without cardiovascular disease or cancer and with no known vitamin or mineral deficiencies; observational cohort studies examining serious harms. Data Extraction and Synthesis: Single extraction, verified by a second reviewer. Quantitative pooling methods appropriate for rare events were used for most analyses. Main Outcomes and Measures: Mortality, cardiovascular disease events, cancer incidence, serious harms. Results: Eighty-four studies (N=739 803) were included. In pooled analyses, multivitamin use was significantly associated with a lower incidence of any cancer (odds ratio [OR], 0.93 [95% CI, 0.87-0.99]; 4 RCTs [n=48 859]; absolute risk difference [ARD] range among adequately powered trials, -0.2% to -1.2%) and lung cancer (OR, 0.75 [95% CI, 0.58-0.95]; 2 RCTs [n=36 052]; ARD, 0.2%). However, the evidence for multivitamins had important limitations. Beta carotene (with or without vitamin A) was significantly associated with an increased risk of lung cancer (OR, 1.20 [95% CI, 1.01-1.42]; 4 RCTs [n=94 830]; ARD range, -0.1% to 0.6%) and cardiovascular mortality (OR, 1.10 [95% CI, 1.02-1.19]; 5 RCTs [n=94 506] ARD range, -0.8% to 0.8%). Vitamin D use was not significantly associated with all-cause mortality (OR, 0.96 [95% CI, 0.91-1.02]; 27 RCTs [n=117 082]), cardiovascular disease (eg, composite cardiovascular disease event outcome: OR, 1.00 [95% CI, 0.95-1.05]; 7 RCTs [n=74 925]), or cancer outcomes (eg, any cancer incidence: OR, 0.98 [95% CI, 0.92-1.03]; 19 RCTs [n=86 899]). Vitamin E was not significantly associated with all-cause mortality (OR, 1.02 [95% CI, 0.97-1.07]; 9 RCTs [n=107 772]), cardiovascular disease events (OR, 0.96 [95% CI, 0.90-1.04]; 4 RCTs [n=62 136]), or cancer incidence (OR, 1.02 [95% CI, 0.98-1.08]; 5 RCTs [n=76 777]). Evidence for benefit of other supplements was equivocal, minimal, or absent. Limited evidence suggested some supplements may be associated with higher risk of serious harms (hip fracture [vitamin A], hemorrhagic stroke [vitamin E], and kidney stones [vitamin C, calcium]). Conclusions and Relevance: Vitamin and mineral supplementation was associated with little or no benefit in preventing cancer, cardiovascular disease, and death, with the exception of a small benefit for cancer incidence with multivitamin use. Beta carotene was associated with an increased risk of lung cancer and other harmful outcomes in persons at high risk of lung cancer.

[Equol and its enantiomers inhibited urethane-induced lung cancer in mice].

OBJECTIVE: To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice. METHODS: A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison. RESULTS: A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups. CONCLUSION: Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.

Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression.

Lung cancer is one of the most common neoplasms globally, with about 2.2 million new cases and 1.8 million deaths annually. Although the most important factor in reducing lung cancer risk is lifestyle change, most patients favour the use of supplements, for example, rather than quitting smoking or following a healthy diet. To better understand the efficacy of such interventions, a systematic review was performed of data from randomized controlled trials concerning the influence of beta-carotene supplementation on lung cancer risk in subjects with no lung cancer before the intervention. The search corpus comprised a number of databases and eight studies involving 167,141 participants, published by November 2021. The findings indicate that beta-carotene supplementation was associated with an increased risk of lung cancer (RR = 1.16, 95% CI = 1.06-1.26). This effect was even more noticeable among smokers and asbestos workers (RR = 1.21, 95% CI = 1.08-1.35) and non-medics (RR = 1.18, 95% CI = 1.07-1.29). A meta-regression found no relationship between the beta-carotene supplementation dose and the size of the negative effect associated with lung cancer risk. Our findings indicate that beta-carotene supplementation has no effect on lung cancer risk. Moreover, when used as the primary chemoprevention, beta-carotene may, in fact, increase the risk of lung cancer.

The mechanism of dioscin preventing lung cancer based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea nipponica Makino as a Chinese folk medicine has been used for the treatment of chronic bronchitis, cough, and asthma. Several studies have established the antimetastatic potential of Dioscorea nipponica Makino extract. Dioscin is a major bioactive compound in Dioscorea nipponica Makino and has anti-tumor property in lung cancer cell lines. However, the preventive effect of dioscin against lung cancer and its key mechanism haven't been identified yet. AIM OF STUDY: To identify the prevention effect of dioscin on lung cancer and explore its key mechanism based on network pharmacology and experimental validation. METHODS: The potential targets of dioscin were obtained from the HERB database. The therapeutic targets of lung cancer were acquired from the GeneCards database. Protein-protein interaction network (PPI) was constructed in the STRING 11.0 database. The David database was used for enrichment analysis. Molecular Docking was finished by the AutoDock Vina. NSCLC cell lines and mouse lung cancer model were used to confirm the prevention effect of dioscin on lung cancer and its key mechanism. RESULTS: 76 potential targets of dioscin were identified to be involved in lung cancer treatment, which refer to 512 biological processes, 47 molecular functions, 77 cellular components and 107 signal pathways. The molecular docking suggested that dioscin might bind to AKT1, Caspase3, TP53, C-JUN and IL-6. The DARTS indicated that dioscin could bind to AKT1. In vitro, dioscin could decrease proliferation, invasion and migration in A549 and PC-9 cells with the significant reduction in the expression of p-AKT, MMP2, and PCNA. In vivo, dioscin could reduce lung nodules, lung injury, and mortality in mouse lung cancer model with reducing the expression of p-AKT, MMP2, PCNA and increasing the expression of active-caspase3. CONCLUSION: Dioscin could prevent lung cancer and its key target is AKT1 kinase, a center protein of PI3K/AKT signaling pathway.

A methodological quality evaluation of the published guidelines and recommendations about the lung cancer screening.

BACKGROUND: A project to assess the existing literature and to benchmark the quality of past guidelines and recommendations on lung cancer screening projects was developed with a particular focus on the assessment of the methodology used in producing them. METHODS: Each guideline was assessed in the different items and domains with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and scored on a seven-point scale. RESULTS: Eight guidelines matched the inclusion criteria and were assessed. A multinational collaboration produced three out of five guidelines. The multivariable analysis shows that improved scores of stakeholders' involvement were related to internationally developed guidelines. Improved methodological quality was related to the involvement of scientific societies due to the better rigor of development and editorial independence. Countries with higher expenditure on healthcare produced significantly better guidelines. CONCLUSIONS: Assessed by the AGREE II criteria, the methodological quality of previous guidelines was relatively low. Nevertheless, the National Comprehensive Cancer Network Guidelines should be recommended as a model for the development of best methodological quality guidelines.

Fish Intake, Dietary Polyunsaturated Fatty Acids, and Lung Cancer: Systematic Review and Dose-Response Meta-Analysis of 1.7 Million Men and Women.

To determine the association between fish intake and dietary polyunsaturated fatty acids (PUFA) and incidence of lung cancer. We systematically reviewed and meta-analyzed all available studies to quantify the associations of fish and PUFA consumption with risk of lung cancer. Relative risk (RR) with 95% confidence interval (CI) was calculated. 13 population-based prospective cohort studies involving 1,785,000 participants and two randomized control trials were included. Our study demonstrated that dietary PUFA significant reduced risk of lung cancer for men (RR 0.99, 95%CI 0.98 to 1.00) and the U.S. population (RR 0.99, 95%CI 0.98 to 1.00). Dose-response analysis indicated that a 5 g/day increment of dietary PUFA was associated with 5% lower risk of lung cancer (RR 0.95, 95%CI 0.91 to 0.99). In addition, PUFA supplementation is significant improved overall survival in patients with lung cancer (RR 1.98, 95%CI 1.09 to 3.59). Our study showed an inverse association between dietary PUFA and risk of lung cancer in males and among the U.S. population. Although smoking cessation is the single biggest factor associated with lung cancer risk reduction, this study adds to a growing body of evidence that diet may have a role in modestly reducing lung cancer risk.

Equol and its enantiomers inhibited urethane-induced lung cancer in mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice.@*METHODS@#A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison.@*RESULTS@#A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups.@*CONCLUSION@#Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.

Garlic oil blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis by inducing phase II drug-metabolizing enzymes.

Lung cancer caused one-quarter of all cancer deaths that was more than other cancers. Chemoprevention is a potential strategy to reducing lung cancer incidence and death, and the effective chemopreventive agents are needed. We investigated the efficacy and mechanism of garlic oil (GO), the garlic product, in the chemoprevention of tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice and MRC-5 cell models in the present study. As a result, it was demonstrated that GO significantly inhibited the NNK-induced lung cancer in vivo and protected MRC-5 cells from NNK-induced cell damage. GO could induce the expressions of the phase II drug-metabolizing enzymes, including NAD(P)H: quinone oxidoreductase 1 (NQO-1), glutathione S-transferase alpha 1 (GSTA1), and antioxidative enzymes heme oxygenase-1 (HO-1). These results supported the potential of GO as a novel candidate agent for the chemoprevention of tobacco carcinogens induced lung cancer.

Dietary phytoestrogen intake and lung cancer risk: an analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.

Phytoestrogens (PEs) have estrogen-like activity and were found to lower incidences of several hormone-dependent cancers. Emerging evidence suggests that estrogen may play a role in lung cancer carcinogenesis. We aim to evaluate dietary PE intake and lung cancer risk using data from the Prostate, Lung, Colorectal and Ovarian cancer screening trial. A total of 1706 lung cancer cases were identified. The association between lung cancer risk and PE intake (in quartiles) was calculated using the Cox proportional hazard models adjusting for potential confounders. Stratified analyses by smoking status, sex and histology were also performed. The highest quartile of total PE intake was associated with a reduced risk of lung cancer compared with the lowest quartile [hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.73-0.99 for >1030 µg/day versus <290 µg/day] (P trend = 0.56). Similar patterns were observed among ever smokers (HR = 0.84, 95% CI: 0.71-0.98), non-small cell histology (HR = 0.84, 95% CI: 0.72-0.99), male (HR = 0.84, 95% CI: 0.69-1.03) and female (HR = 0.80, 95% CI: 0.64-0.99 for 510-1030 µg/day, HR = 0.84, 95% CI: 0.67-1.06 for >1030 µg/day versus <290 µg/day) subjects with no significant linear trend observed. Despite a lower consumption compared with the Asian population, increased PE intake still appears to decrease lung cancer risk in a Caucasian-dominant population. Future studies are needed to replicate these results in independent cohorts and shed a light on the potential mechanism of the protective effect of PEs on lung carcinogenesis and the interaction between PEs, smoking and endogenous estrogens.