Abstract 4980: Comparison of gene expression profiles of cigarette smoke-exposed normal human bronchial epithelial (NHBE) to profiles from smokers and patients with chronic obstructive pulmonary disease (COPD) and lung cancer

Background: The morbidity and mortality associated with tobacco smoking is well established. Nicotine is the addictive component of tobacco. Nicotine, through the non-neuronal α7nicotinic receptor, induces cell proliferation, neo-angiogenesis, epithelial to mesenchymal transition, and inhibits drug-induced apoptosis. Objective: To understand the genetic, molecular and cellular biology of addiction, chronic obstructive pulmonary disease and lung cancer. Methods: The search for papers to be included in the review was performed during the months of July- September 2018 in the following databases: PubMed (http://www.ncbi.nlm.nih.gov), Scopus (http://www.scopus.com), EMBASE (http://www.elsevier.com/online-tools/embase), and ISI Web of Knowledge (http://apps.webofknowledge.com/). The following searching terms: “nicotine”, “nicotinic receptor”, and “addiction” or “COPD” or “lung cancer” were used. </P><P> Patents were retrieved in clinicaltrials.gov (https://clinicaltrials.gov/). All papers written in English were evaluated. The reference list of retrieved articles was also reviewed to identify other eligible studies that were not indexed by the above-mentioned databases. </P><P> New experimental data on the ability of nicotine to promote transformation of human bronchial epithelial cells, exposed for one hour to Benzo[a]pyrene-7,8-diol-9-10-epoxide, are reported. Results: Nicotinic receptors variants and nicotinic receptors upregulation are involved in addiction, chronic obstructive pulmonary disease and/or lung cancer. Nicotine through α7nicotinic receptor upregulation induces complete bronchial epithelial cells transformation. Conclusion: Genetic studies highlight the involvement of nicotinic receptors variants in addiction, chronic obstructive pulmonary disease and/or lung cancer. A future important step will be to translate these genetic findings to clinical practice. Interventions able to help smoking cessation in nicotine dependence subjects, under patent, are reported.

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CircRNA Expression Profile in Lung Cancer Complicated with Chronic Obstructive Pulmonary Disease Patients

10.21203/rs.3.rs-47904/v1 ◽

2020 ◽

Author(s):

Fuqiang Wen ◽

Xiaoou Li ◽

Yongchun Shen ◽

Jiahan Cheng ◽

Jun Chen ◽

...

Keyword(s):

Lung Cancer ◽

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Expression Profiles ◽

Circular Rnas ◽

Chronic Obstructive ◽

Biological Processes ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Diagnosis Of Lung Cancer

Abstract Background: Lung cancer complicated with chronic obstructive pulmonary disease (COPD) are major causes of mortality worldwide, and the incidence of lung cancer and COPD increasing significantly. Circular RNAs (circRNAs), have been reported to participate in various biological processes, whereas the role of circRNAs in lung cancer complicated with COPD remains unclear. We aims to identify differentially expressed circRNAs (DEcircRNAs) between lung cancer complicated with COPD and lung cancer without COPD. Method: The circRNAs expression profiles were identified using a high-throughput circRNA microarray in cancer adjacent tissues from 6 lung cancer without COPD patients and 8 lung cancer complicated with COPD patients. Bioinformatic analyses were conducted to identify the functions of DEcircRNAs. Result: A total of 115 up- and 128 down-regulated circRNAs were screened in lung cancer complicated with COPD patients compared with lung cancer without COPD patients. The myD88-dependent toll-like receptor signaling pathway and positive regulation of nitric oxide biosynthetic process ranked the top 2 enriched biological processes in Gene Ontology analysis. Signaling transduction and infectious diseases were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways in both up- and down-regulated circRNAs. Compared with lung cancer without COPD, circRNAs are dysregulated in the adjacent tissues of lung cancer with COPD. Conclusion: The DEcircRNAs might act as potential targets for the diagnosis of lung cancer with COPD.

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P1-192: Bronchial epithelial proliferation measured by Ki-67 is related to current smoking and sex but not to lung cancer or chronic obstructive pulmonary disease

Journal of Thoracic Oncology ◽

10.1097/01.jto.0000284290.70068.88 ◽

2007 ◽

Vol 2 (8) ◽

pp. S813-S814

Author(s):

York E. Miller ◽

Dae S. Hyun ◽

Robert L. Keith ◽

Timothy C. Kennedy ◽

Marina Lewis ◽

...

Keyword(s):

Lung Cancer ◽

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Chronic Obstructive ◽

Epithelial Proliferation ◽

Ki 67 ◽

Obstructive Pulmonary Disease ◽

Bronchial Epithelial ◽

Current Smoking

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Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD)

Biomedicines ◽

10.3390/biomedicines8100398 ◽

2020 ◽

Vol 8 (10) ◽

pp. 398

Author(s):

Kentaro Akata ◽

Kei Yamasaki ◽

Fernando Sergio Leitao Filho ◽

Chen Xi Yang ◽

Hiroto Takiguchi ◽

...

Keyword(s):

Gene Expression ◽

Chronic Obstructive Pulmonary Disease ◽

Bronchoalveolar Lavage ◽

Pulmonary Disease ◽

Expression Profiles ◽

Chronic Obstructive ◽

Phagocytic Function ◽

Pathogen Recognition ◽

Obstructive Pulmonary Disease ◽

Lung Macrophages

Lung macrophages are the key immune effector cells in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Several studies have shown an increase in their numbers in bronchoalveolar lavage fluid (BAL) of subjects with COPD compared to controls, suggesting a pathogenic role in disease initiation and progression. Although reduced lung macrophage phagocytic ability has been previously shown in COPD, the relationship between lung macrophages’ phenotypic characteristics and functional properties in COPD is still unclear. (1) Methods: Macrophages harvested from bronchoalveolar lavage (BAL) fluid of subjects with and without COPD (GOLD grades, I–III) were immuno-phenotyped, and their function and gene expression profiles were assessed using targeted assays. (2) Results: BAL macrophages from 18 COPD and 10 (non-COPD) control subjects were evaluated. The majority of macrophages from COPD subjects were non-polarized (negative for both M1 and M2 markers; 77.9%) in contrast to controls (23.9%; p < 0.001). The percentages of these non-polarized macrophages strongly correlated with the severity of COPD (p = 0.006) and current smoking status (p = 0.008). Non-polarized macrophages demonstrated poor phagocytic function in both the control (p = 0.02) and COPD (p < 0.001) subjects. Non-polarized macrophages demonstrated impaired ability to phagocytose Staphylococcus aureus (p < 0.001). They also demonstrated reduced gene expression for CD163, CD40, CCL13 and C1QA&B, which are involved in pathogen recognition and processing and showed an increased gene expression for CXCR4, RAF1, amphiregulin and MAP3K5, which are all involved in promoting the inflammatory response. (3) Conclusions: COPD is associated with an abundance of non-polarized airway macrophages that is related to the severity of COPD. These non-polarized macrophages are predominantly responsible for the poor phagocytic capacity of lung macrophages in COPD, having reduced capacity for pathogen recognition and processing. This could be a key risk factor for COPD exacerbation and could contribute to disease progression.

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