Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer

1997 ◽  
Vol 16 (7) ◽  
pp. 356-360 ◽  
Author(s):  
DJ Harrison ◽  
AM Cantlay ◽  
F. Rae ◽  
D. Lamb ◽  
Cad Smith
Keyword(s):  
Lung Cancer ◽  
Lung Disease ◽  
Cigarette Smoke ◽  
Lung Tissue ◽  
Odds Ratio ◽  
Homozygous Deletion ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Gstm1 Gene ◽  
Wide Range

1 Genetic variation at the glutathione S-transferase M1 locus (GSTM1) has been associated with a number of apparently unrelated cancers, including lung cancer. Emphysema is a common lung disease often found concomitant with lung cancer. Both emphysema and lung cancer may result from chemical and oxidative damage caused by reactive species present in cigarette smoke or released from neutrophils recruited follow ing cigarette smoke induced injury. GSTM1 may protect against such damage through detoxification of cigarette smoke components. Polymorphism of this gene may thus influence susceptibility not just to lung cancer, but to other forms of lung disease. 2 Resection specimens from a group of 168 lung cancer patients were assessed for the presence of macro scopic centriacinar and panacinar emphysema. DNA was extracted from archival material and genotyped for the GSTM1 polymorphism using the polymerase chain reaction. A control group of 384 anonymous blood donations was used to determine the frequency of the GSTM1 gene deletion in a random control population. Reverse transcription on lung tissue was performed to investigate mRNA expression of GSTM1 and GSTM4. 3 In 57 lung cancer cases with no emphysema there was no association with homozygous deletion of the GSTM1 gene (51% null in cancer and 53% null in control groups). However in 111 patients with emphysema and lung cancer there was an increase in the frequency of deletion (65%, P=0.032) giving an odds ratio of 1.36(0.32-2.40). In 43 cases there was evidence of both centriacinar and panacinar emphy sema. The frequency of GSTM1 deletion was 70% (Odds ratio 2.11, 0.97 - 3.25). Both GSTM1 and GSTM4 mRNAs were expressed in lung tissue. 4 These findings suggest that GSTM1 has a general but rather small protective effect against toxicological injury in the lung which is not specific to cancer. This is of relevance in considering the health effects of exposure to a wide range of reactive chemicals in the environment.

scholarly journals FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoshan Su ◽  
Junjie Chen ◽  
Xiaoping Lin ◽  
Xiaoyang Chen ◽  
Zhixing Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Migration ◽  
Cigarette Smoke ◽  
Epithelial Mesenchymal Transition ◽  
Control Group ◽  
Data Set ◽  
Mesenchymal Transition

Abstract Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial–mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated. Methods The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT. Results Based on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling. Conclusions In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

scholarly journals The time pattern of selenomethionine administration in preventing free radicals due to exposure to electric cigarette smoke

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Rivan Virlando Suryadinata ◽  
Bambang Wirjatmadi ◽  
Amelia Lorensia
Keyword(s):  
Free Radicals ◽  
Cigarette Smoke ◽  
Lung Tissue ◽  
Cell Damage ◽  
Control Group ◽  
Early Application ◽  
Control Group Design ◽  
Time Pattern ◽  
Negative Effect ◽  
Male Wistar Rats

Background: Most people believe that electric cigarettes have no negative effect on health,  which causes them to use it more. However, exposure to the smoke from these cigarettes is bad for the health and causes cell damage. Antioxidants play an important role in preventing cell damage, and they can be obtained through the oral administration of selenomethionine.Design and methods: This study used an experimental method and a post-test control group design. Male Wistar rats, which were exposed to cigarette smoke were given selenomethionine orally and then tested for the presence of free radicals. The measurement of lung tissue damage was conducted by assessing the level of malondialdehyde in the blood and immunohistochemistry (IHC) of the lung tissue.Result: The study showed that differences in the time of administration of selenomethionine affect the levels of malondialdehyde in the blood and expression of malondialdehyde in the lung tissue (p<0.05). Consequently, the two groups showed a strong (r=0.861) and significant (p=0.000) relationship with each other.Conclusion: The early application of selenomethionine can prevent increased levels of malondialdehyde in the blood and lung tissue due to exposure to e-cigarette smoke.

scholarly journals Immunotherapy causing pneumonitis in a patient with non-small cell lung cancer (NSCLC)

2019 ◽  
Vol 12 (3) ◽  
pp. e226044 ◽  
Author(s):  
Rui Li ◽  
Gina Lee ◽  
Ahmed El-Sherief
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Lung Disease ◽  
Cell Lung Cancer ◽  
Respiratory Symptoms ◽  
Oral Prednisone ◽  
Small Cell ◽  
Architectural Distortion ◽  
Small Cell Lung ◽  
Wide Range

Our patient, who had been previously diagnosed with non-small cell lung cancer, presented with progressive dyspnoea after receiving second-line immunotherapy treatment with atezolizumab. Chest CT scan showed bilateral lung architectural distortion, bronchial dilatation, consolidative opacities, ground-glass opacities and linear opacities concerning for either infectious lung disease or treatment-related lung disease. A diagnostic bronchoscopy was performed and no evidence of malignancy or infection was detected. Discontinuing atezolizumab with the addition of oral corticosteroid improved the patient’s respiratory symptoms but the patient required continuous oxygen supplementation. Later, the patient was found to have radiologic findings suggestive of further progression of his pneumonitis after completion of a course of corticosteroid treatment and required another course of oral prednisone. Immune-mediated pneumonitis could present with mild to severe respiratory symptoms with a wide range of clinical and radiologic features and physicians should be aware of this diagnosis of exclusion. Although patients may experience progressive disease with or without immunotherapy rechallenge, most of these cases can be managed successfully with favourable outcomes.

scholarly journals Glutathione S-transferase T1 and M1 polymorphisms and risk of thyroid neoplasms

2003 ◽  
Vol 11 (3) ◽  
pp. 185-185
Author(s):  
Karmen Stankov ◽  
Stefano Landi ◽  
Marco Volante ◽  
Mauro Papotti
Keyword(s):  
Confidence Interval ◽  
Thyroid Carcinoma ◽  
Odds Ratio ◽  
Follicular Adenoma ◽  
Follicular Carcinoma ◽  
Thyroid Neoplasms ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Gstt1 Null Genotype ◽  
Increased Risk

Background: In order to test the possibility of association between GSTT1 and M1 (glutathione S-transferase) null allele variant, in which the entire gene is absent, and the risk of TCO (thyroid carcinoma with cell oxyphilia), the case-control study was carried out. Methods: Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR in the DNA from 108 healthy individuals and in DNA from samples of thyroid tumors from 130 patients of the same race and origin as the control group (Caucasian, Italian). The following types of NMTC were analyzed: oxyphilic adenoma (OA), oxyphilic carcinoma (OC) papillary thyroid carcinoma with oxyphilic features (PTCof), follicular adenoma (FA), follicular carcinoma (FC), follicular variant of PTC (fvPTC) and classical PTC. Associations between prevalence of particular genotypes and the occurrence of TCO (versus controls) and other subtypes of NMTC were tested. Associations were quantified by calculating OR (odds ratio) with 95% confidence interval. StatGraphics Plus v. 5 software (Manugistics) was used for statistical analysis. Results: In this study of the association between the GSTT1 and M1 null genotype and the increased risk of TCO, the frequency of GSTT1 null genotype of 19.2% in cases and 15.7% in controls was found with an adjusted odds ratio (OR) of 1.4 (95% confidence interval (CI) 0.70-2.81), and the frequency of GSTM1 null genotype of 59% in cases with oxyphilic tumors and of 55.6% in controls (OR 1.24; 95% CI, 0.62-2.48). Conclusion: These results indicate that the GSTT1 and M1 null genotypes do not increase the risk of development of oxyphilic tumors, as well as other types of NMTC that have been included in this study.

scholarly journals Inhibitory Effects of GGX on Lung Injury of Chronic Obstructive Lung Disease (COPD) Mice Model

2021 ◽  
Vol 42 (3) ◽  
pp. 56-71
Author(s):  
Tae Hyeon Kim ◽  
Won Kyung Yang ◽  
Su Won Lee ◽  
Seung Hyung Kim ◽  
Yee Ran Lyu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Disease ◽  
Lung Tissue ◽  
Obstructive Lung Disease ◽  
Chronic Obstructive Lung Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Chronic Obstructive ◽  
Mice Model ◽  
Tnf Α

Objectives: This study is aimed to evaluate the protective effects of GGX on lung injury of Chronic Obstructive Lung Disease (COPD) mice model. Materials and Methods: C57BL/6 mice were challenged with lipopolysaccharide (LPS) and cigarette smoke extract (CSE) and then treated with vehicle only (Control group), dexamethasone 3 ㎎/㎏ (Dexa group), gam-gil-tang 200 ㎎/㎏ (GGT group), GGX 100, 200, and 400 ㎎/㎏ (GGX group). After sacrifice, its bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed with cytospin, Enzyme-Linked Immunosorbent Assay (ELISA), real-time polymerase chain reaction (PCR) and hematoxylin & eosin (H&E), and Masson’s trichrome staining. Results: In the COPD model, GGX significantly inhibited the increase of neutrophils, TNF-α, IL-17A, CXCL-1, MIP2 in BALF and TNF-α, IL-1β, IL-10 mRNA expression in lung tissue. It also decreased the severity of histological lung injury. Conclusion: This study suggests the usability of GGX for COPD patients by controlling lung tissue injury.

Effect of cigarette smoke on TNF-a and IL-1b mRNA expression in lung tissues and cells of rats

2015 ◽  
Author(s):  
Mingli Ji ◽  
Yuxia Wang ◽  
Xiaopeng Li ◽  
Zhibi Qian
Keyword(s):  
Carbon Dioxide ◽  
Mrna Expression ◽  
Cigarette Smoke ◽  
Lung Tissue ◽  
Control Group ◽  
Expression Levels ◽  
Arterial Partial Pressure ◽  
Experimental Group ◽  
Mrna Expression Levels ◽  
Pro Inflammatory Cytokines

We investigated lung tissue expression of the pro-inflammatory cytokines TNF-a and IL-1b in response to cigarette smoke exposure and the ensuing effects on arterial oxygen and carbon dioxide as indices of respiratory function. Experimental group rats were exposed to cigarette smoke twice daily (30 min per exposure) for 28 consecutive days. Arterial partial pressure of oxygen (PO2), arterial partial pressure of carbon dioxide (PCO2), and both mRNA and protein expression levels of TNF-a and IL-1b were compared to a control group. Contents of TNF-a and IL-1b in bronchoalveolar lavage fluid (BALF) and lung homogenate were detected by enzyme linked immunosorbent assays while TNF-a mRNA and IL-1b mRNA expression levels in lung tissue were detected by reverse transcription-polymerase chain reaction. Arterial PO2 was significantly lower in the experimental group than the control group, while the arterial PCO2 was significantly higher. BALF levels of TNF-a and IL-1b were significantly higher in the experimental group than the control group, as were TNF-a mRNA and IL-1b mRNA expression levels in lung tissue. Cigarette smoke may activate inflammatory cells in the pulmonary circulation and increase the expression of the pro-inflammatory cytokines TNF-a and IL-1b in lung tissue, leading to lung injury and respiratory dysfunction.

scholarly journals GSTT1 Gene Deletion Is Associated with Lung Cancer in Mexican Patients

2004 ◽  
Vol 19 (6) ◽  
pp. 259-261 ◽  
Author(s):  
M. P. Gallegos-Arreola ◽  
B. C. Gómez-Meda ◽  
G. Morgan-Villela ◽  
M. R. Arechavaleta-Granell ◽  
L. Arnaud-López ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Gene Deletion ◽  
Lung Cancer Risk ◽  
Homozygous Deletion ◽  
Glutathione S Transferase ◽  
Gstt1 Null Genotype ◽  
Lung Cancer Patients ◽  
Gstt1 Gene ◽  
Gst Activity

Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking.We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer.

scholarly journals High frequency of infection of lung cancer patients with the parasite Toxoplasma gondii

2019 ◽  
Vol 5 (2) ◽  
pp. 00143-2018 ◽  
Author(s):  
Jaroslav Bajnok ◽  
Muyassar Tarabulsi ◽  
Helen Carlin ◽  
Kevin Bown ◽  
Thomas Southworth ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Toxoplasma Gondii ◽  
Cancer Patients ◽  
Lung Tissue ◽  
Specific Gene ◽  
Infection Prevalence ◽  
Tissue Samples ◽  
Gene Markers ◽  
Lung Cancer Patients ◽  
Wide Range

BackgroundToxoplasma gondii is an intracellular protozoan parasite that can cause a wide range of clinical conditions, including miscarriage and pneumonia. The global prevalence is 30% in humans, but varies by locality (e.g. in the UK it is typically 10%). The association between lung cancer and T.  gondii infection was investigated by direct detection in lung tissue samples.MethodsLung tissue samples were taken from patients undergoing lung resection surgery (n=72) for suspected lung cancer (infection prevalence 100% (95% CI: 93.9–100%)). All 72 participants were confirmed as having lung cancer following subsequent diagnostic tests. In addition, bronchial biopsy samples were collected from non-lung cancer healthy control subjects (n=10). Samples were tested for T.  gondii using PCR amplification of T.  gondii specific gene markers and T.  gondii specific immunohistochemistry.ResultsAll 72 lung cancer patients were infected with T.  gondii (prevalence 100% (95% CI: 93.9–100%)). Of which, 95.8% (n=69) of patients showed evidence of active parasite stages. Infection prevalence in the controls (10%) was significantly lower (p<0.0001).ConclusionsClinicians treating lung cancer patients should be aware of the potential presence of the parasite, the potential for induction of symptomatic complications and interference with treatment success.

scholarly journals Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle,

2014 ◽  
Vol 40 (4) ◽  
pp. 411-420 ◽  
Author(s):  
Samanta Portão de Carlos ◽  
Alexandre Simões Dias ◽  
Luiz Alberto Forgiarini Júnior ◽  
Patrícia Damiani Patricio ◽  
Thaise Graciano ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Cigarette Smoke ◽  
Lung Tissue ◽  
Mammalian Target Of Rapamycin ◽  
Thiobarbituric Acid ◽  
Lung Parenchyma ◽  
Diaphragm Muscle ◽  
Cigarette Smoke Exposure ◽  
Control Group ◽  
Control Value

OBJECTIVE: To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation) and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively]) in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS) for 7, 15, 30, 45, or 60 days. METHODS: Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group): a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively. RESULTS: Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice), the greatest differences (increases) in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases) in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle. CONCLUSION: Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily) in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD.

ANALYSIS FOR CASCADING FAILURES WITH DNA REPAIR FUNCTION OF GENE NETWORK AND ITS APPLICATION

2012 ◽  
Vol 24 (03) ◽  
pp. 237-244 ◽  
Author(s):  
Yu-Lin Zhang ◽  
Shu-Dong Wang ◽  
Long-Xiao Sun ◽  
Yuan-Yuan Zhang ◽  
Da-Zhi Meng
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Lung Adenocarcinoma ◽  
Gene Networks ◽  
Cascading Failures ◽  
Control Group ◽  
Cancer Occurrence ◽  
Wide Range ◽  
Cancer Related Gene ◽  
Experimental Group

Gene networks research has grown steadily because of its potential to represent, characterize and model a wide range of systems and phenomena on the molecular level. Especially the studies on the cancer-related gene networks through complex interactions can help to provide better understanding of the formation and development of cancer. In this work, using the expressions data of normal and lung adenocarcinoma stage, mutual information networks of cancer-related genes are constructed first. Then a model for cascading failures with DNA repair function of weighted gene networks is built. Furthermore, comparisons of numerical experiments show that deleting nodes in the networks of adenocarcinoma experimental group is more likely to cause larger scales of cascading failure than the one of control group. In addition, we find that 13 genes of control group and 12 genes of experimental group are of very strong destructibility for the two networks, respectively. The failures of these genes can lead to the paralysis of the whole network. Therefore, we conclude that these genes might play important roles in keeping normal level or developing lung adenocarcinoma of organisms. The results may have certain significance for the interpretation of lung cancer development and provide beneficial inspirations to clarify lung cancer occurrence of biological mechanism.

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