Exposure to Tobacco Smoking Induces a subset of Activated Tumor-resident Tregs in Non-Small Cell Lung Cancer.
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ABSTRACT:
SUBMITTER: Hu Y
PROVIDER: S-EPMC8591366 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions.
| S-EPMC5004964 | biostudies-literature
Project description:Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
| S-EPMC2880489 | biostudies-literature
Project description:Cancer is driven by mutation. Worldwide, tobacco smoking is the major lifestyle exposure that causes cancer, exerting carcinogenicity through 60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. 22,910 somatic substitutions were identified, including 132 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in-frame, and another two lines carrying PVT1-CHD7 fusion genes, suggesting that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
| EGAS00000000051 | EGA
Project description:BACKGROUNDClear cell renal cell carcinoma (ccRCC) is the most common histologically defined renal cancer. However, it is not a uniform disease and includes several genetic subtypes with different prognoses. ccRCC is also characterized by distinctive metabolic reprogramming. Tobacco smoking (TS) is an established risk factor for ccRCC, with unknown effects on tumor pathobiology.METHODSWe investigated the landscape of ccRCCs and paired normal kidney tissues using integrated transcriptomic, metabolomic, and metallomic approaches in a cohort of white males who were long-term current smokers (LTS) or were never smokers (NS).RESULTSAll 3 Omics domains consistently identified a distinct metabolic subtype of ccRCCs in LTS, characterized by activation of oxidative phosphorylation (OXPHOS) coupled with reprogramming of the malate-aspartate shuttle and metabolism of aspartate, glutamate, glutamine, and histidine. Cadmium, copper, and inorganic arsenic accumulated in LTS tumors, showing redistribution among intracellular pools, including relocation of copper into the cytochrome c oxidase complex. A gene expression signature based on the LTS metabolic subtype provided prognostic stratification of The Cancer Genome Atlas ccRCC tumors that was independent of genomic alterations.CONCLUSIONThe work identified the TS-related metabolic subtype of ccRCC with vulnerabilities that can be exploited for precision medicine approaches targeting metabolic pathways. The results provided rationale for the development of metabolic biomarkers with diagnostic and prognostic applications using evaluation of OXPHOS status. The metallomic analysis revealed the role of disrupted metal homeostasis in ccRCC, highlighting the importance of studying effects of metals from e-cigarettes and environmental exposures.FUNDINGDepartment of Defense, Veteran Administration, NIH, ACS, and University of Cincinnati Cancer Institute.
| S-EPMC7773408 | biostudies-literature
Project description:IntroductionLung cancer survivors are at high risk of developing a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined the risk factors for SPLC across multiple epidemiologic cohorts and evaluated the impact of smoking cessation on reducing SPLC risk.MethodsWe analyzed data from 7059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 3423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (N = 4731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta-analysis.ResultsOverall, 163 MEC cases (2.3%) developed SPLC. Smoking pack-years (hazard ratio [HR] = 1.18 per 10 pack-years, p < 0.001) and smoking intensity (HR = 1.30 per 10 cigarettes per day, p < 0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force's screening criteria at IPLC diagnosis also had an increased SPLC risk (HR = 1.92; p < 0.001). Validation studies with the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and European Prospective Investigation into Cancer and Nutrition revealed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (pmeta < 0.001), 1.25 per 10 cigarettes per day (pmeta < 0.001), and 1.99 (pmeta < 0.001) for meeting the U.S. Preventive Services Task Force's criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR = 0.17; p < 0.001).ConclusionsTobacco smoking is a risk factor for SPLC. Smoking cessation may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted.
| S-EPMC8159872 | biostudies-literature
Project description:Tobacco smoking is a research topic of high interest to the public health in Iraq. Although Iraq is a country with a high percentage of smokers, we noticed the dearth of adequate studies and programs to deal with this problem. The percentage of smokers exceed 30% of the population and smoking problem becomes a permanent habit in adults and young people. The problems associated with tobacco smoking behavior related to individuals' post-traumatic stress disorder following post-war conflicts, and the social and cultural environment. The health consequences of tobacco smoking can harm almost every organ in the body, and there are reports confirmed the tobacco smoking is a high-risk factor for lung cancer and other diseases. The relative risk of lung cancer increases with increasing duration and intensity of smoking. Also, smoking associated with bladder, prostate, and head and neck cancers, in addition to respiratory diseases. Intervention efforts should focus on reducing the prevalence of cigarette smoking, introduce effective treatments for cancer and quit smoking. In this perspective article, we present our viewpoint and three scenarios to deal with the problem of tobacco smoking in Iraq. We recommend introducing educational, health and legislative policies for quitting smoking and using effective treatments for cancer.
| S-EPMC6212484 | biostudies-other
Project description:OBJECTIVES:There is no safe or risk-free level of tobacco use or tobacco smoke exposure. In this randomized controlled trial, we tested a tobacco control intervention in families and specifically evaluated a tailored cessation intervention for the parents and/or caregivers (Ps/Cs) who were smokers while their children were simultaneously enrolled in tobacco prevention. METHODS:Ps/Cs and children were recruited from 14 elementary schools across rural and urban settings. Approximately one-fourth (24.3%; n = 110) of the total Ps/Cs enrolled in the randomized controlled trial (n = 453) were smokers, predominantly women (80.9%), with a mean age of 37.7 years. (SD 12.2); 62.7% were African American, 44% had less than a high school education, and 58% earned <$20 000 annually. P/C smokers were offered a tailored cessation intervention in years 1 and 2. Self-report smoking status and saliva cotinine were obtained at baseline, the end of treatment (EOT) and/or year 2, and in the year 4 follow-up. RESULTS:Ps/Cs in the intervention group showed a larger increase in self-reported smoking abstinence over time (EOT: 6.5% [SE = 5.7%]; year 4: 40.6% [SE = 5.7%]) than the control group (EOT: 0.0% [SE = 6.5%]; year 4: 13.2% [SE = 6.4%]; F = 4.82; P = .0306). For cotinine, the intervention group showed a decrease from baseline (239.9 [SE = 1.3]) to EOT 99.3 [SE = 1.4]) and then maintenance through year 4 (109.6 [SE = 1.4]), whereas the control group showed increases from baseline (221.1 [SE = 1.4]) to EOT (239.0 [SE = 1.4]) to year 4 (325.8 [SE = 14]; F = 5.72; P = .0039). CONCLUSIONS:This study provides evidence that tailored cessation offered to Ps/Cs in their children's schools during their children's enrollment in tobacco prevention may contribute to more robust success in P/C cessation and a reduction of tobacco smoke exposure in children.
| S-EPMC5745674 | biostudies-literature
Project description:Background: Environmental tobacco smoke (ETS) exposure in children ranks one of the major public health problems in our time. Poor parental knowledge, attitude, and practice (KAP) on ETS often contribute to worse exposure of the kids. Thus, we aimed to document parental KAP regarding tobacco use, smoking cessation and children's ETS exposure, and to analyse how knowledge and attitude relate to practice. Methods: Self-administered KAP questionnaires were distributed to smoking parents recruited from the pediatric unit at the Prince of Wales Hospital, which provides pediatric service to a population of 1.2 million in Hong Kong. The 60-item questionnaire had a range of 0-38 for knowledge, 0-44 for attitude, and 0-40 for practice. Descriptive analyses were performed for KAP response, regression analyses were performed for the exploration of associations and identification of predictive indicators. Results: 145 smoking parents (mean age: 38.0 ± 6.7 yrs.; male: 85.5%) were included. Less than half (39.3%) of them reported a smoke-free policy at home. Among those parents who had private cars, less than half (45.2%) of them had smoke-free policy in their car that they never smoked in the car. Only 25.5% of the participants correctly answered ≥70% of the knowledge questions, and 11.8 % of the participants gave favorable responses to ≥70% of the attitude questions. The total knowledge and the total attitudes score were positively associated (r = 0.49, 95% CI: 0.35-0.79, p < 0.001), yet they were only modestly correlated with parental practice on children's ETS exposure. By multivariate regressions, potential predictive factors for more favorable parental KAP included higher household income, lower parental nicotine dependence level and breastfeeding practice. Conclusions: Parental KAP related to tobacco use and children's ETS exposure needs improvement to address the significant gap between recommended and actual practice. The weak association between knowledge and practice suggested that parental education alone is not adequate to combat ETS exposure in children.
| S-EPMC8653904 | biostudies-literature
Project description:BACKGROUND:Our objective was to assess whether exposure to tobacco in video games is associated with smoking among adolescent gamers from Argentina. METHODS:Cross-sectional data were analysed from students in public and private middle schools in Argentina. Tobacco content in video games was estimated using previously validated methods and adolescents' tobacco exposure was assessed by multiplying tobacco content in the top three video games they play by the hours played per day. The primary outcome was current smoking. Multilevel logistic regression models adjusted for clustering within schools, regressing current smoking on tobacco exposure in video games (ie, none, low, high) after controlling for age, sex, parental education, parenting style, parental rules about the use of video games, rebelliousness, sensation seeking and 'technophilia'. RESULTS:Of the 3114 students who participated, 92% of boys (1685/1802) and 56% of girls (737/1312) played video games and were included in the analytical sample. The prevalence of smoking was 13.8% among boys and 22.0% among girls; 74.5% of boys played video games more than 1?hour per day compared with 47.7% of girls. High exposure to tobacco content in video games compared with no exposure was independently associated with current smoking among girls (OR 1.78; 95% CI 1.02 to 3.09) but not among boys (OR 0.98; 95% CI 0.64 to 1.51). CONCLUSIONS:Greater exposure to tobacco content in video games was associated with higher likelihood of smoking among Argentine girls who play video games, suggesting the need for policies that limit these exposures.
| S-EPMC6339838 | biostudies-literature
Project description:Around 40% of children are exposed to tobacco smoke, increasing their risk of poor health. Previous research has demonstrated misunderstanding among smoking parents regarding children's exposure. The parental perceptions of exposure (PPE) measure uses visual and textual vignettes to assess awareness of exposure to smoke. The study aimed to determine whether PPE is related to biochemical and reported measures of exposure in children with smoking parents. Families with at least one smoking parent and a child ≤ age 8 were recruited. In total, 82 parents completed the PPE questionnaire, which was assessed on a scale of 1-7 with higher scores denoting a broader perception of exposure. Parents provided a sample of their child's hair and a self-report of parental smoking habits. Parents who reported smoking away from home had higher PPE ratings than parents who smoke in and around the home (p = 0.026), constituting a medium effect size. PPE corresponded with home smoking frequency, with rare or no home exposure associated with higher PPE scores compared to daily or weekly exposure (p < 0.001). PPE was not significantly related to hair nicotine but was a significant explanatory factor for home smoking location. PPE was significantly associated with parental smoking behaviour, including location and frequency. High PPE was associated with lower exposure according to parental report. This implies that parental understanding of exposure affects protective behaviour and constitutes a potential target for intervention to help protect children.
| S-EPMC7277295 | biostudies-literature