• BMB Reports
• /
• v.36 no.1
• /
• pp.95-109
• /
• 2003

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.17
• /
• pp.7467-7471
• /
• 2014

SCY1-like 1-binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is very important for the development of human cancer. However, the effects of SCYL1BP1 on human lung squamous carcinoma cell biological behavior remain poorly understood. In this study, we present evidence that SCYL1BP1 can promote the degradation of MDM2 protein and further inhibit the G1/S transition of lung squamous carcinoma cell lines. Functional assays found that reintroduction of SCYL1BP1 into lung squamous carcinoma cell lines significantly inhibited cell proliferation, migration, invasion and tumor formation in nude mice, suggesting strong tumor suppressive function of SCYL1BP1 in lung squamous carcinoma. Taken together, our data suggest that the interaction of SCYL1BP1/MDM2 could accelerate MDM2 degradation, and may function as an important tumor suppressor in lung squamous carcinomas.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3143-3147
• /
• 2012

Background: Previous studies investigating the association of physical activity with risk of lung cancer reported conflicting results. In order to update and improve available evidence on any link, a meta-analysis was performed. Method: We searched the PubMed database for prospective cohort studies investigating the relation of physical activity with risk of lung cancer. The pooled relative risk (RR) with its 95% confidence intervals (95%CI) was used to assess the association. Results: We included 14 prospective studies with a total of 1,644,305 participants, with 14,074 incident lung cancer cases documented during follow-up. Meta-analysis of all 14 studies suggested both high and medium levels of physical activity to be associated with decreased risk of lung cancer compared to the reference group with low level of physical activity (for high level, RR = 0.77, 95%CI 0.73-0.81, P < 0.001; for medium level, RR = 0.87, 95%CI 0.83-0.90, P < 0.001). Subgroup analyses by gender found obvious associations in both men and women. No publication bias was observed. Conclusion: Our findings suggest that high and medium levels of physical activity have a beneficial effect on lung cancer by reducing the overall risk of tumour development among both men and women.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.8
• /
• pp.4819-4822
• /
• 2013

Background: Lung cancer is the leading cause of cancer mortality in the world. Many factors can protect against or facilitate its development. A TNF family member TRAIL, has a complex physiological role beyond that of merely activating the apoptotic pathway in cancer cells. Vitamin D is converted to its active form locally in the lung, and is also thought to play an important role in lung health. Our goal was to investigate the possible clinical significance of serum sTRAIL and 1,25-dihydroxyvitamin D(3) levels in patients with non-small cell lung cancer (NSCLC). Materials and Methods: Totals of 18 consecutive adenocarcinoma and 22 squamous cell carcinoma patients with stage-IV non-small cell lung cancer referred to our institute were included in this study. There were 12 men and 6 women, with ages ranging from 38 to 97 (mean 60.5) years with adenocarcinoma, and 20 men and 2 women, with ages ranging from 46 to 80 (mean 65) years with squamous cell carcinoma. Serum levels of sTRAIL and 1,25-dihydroxyvitamin D(3) were measured in all samples at the time of diagnosis. Results: sTRAIL levels in NSCLC patients were higher than in the control group. Although there was no correlation between patient survival and sTRAIL levels, the highest sTRAIL levels were correlated with age and cigarette smoking in the adenocarcinoma patients. sTRAIL level in healthy individuals were correlated with serum 1,25-dihydroxyvitamin D(3). Conclusions: Serum sTRAIL concentrations were increased in NSCLC patients, and correlated with age and smoking history, but not with overall survival.

• Biomolecules & Therapeutics
• /
• v.20 no.6
• /
• pp.513-519
• /
• 2012

Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

• Development and Reproduction
• /
• v.24 no.3
• /
• pp.197-205
• /
• 2020

Diabetes mellitus is a common heterogeneous metabolic disorder, characterized by deposition of extracellular matrix, oxidative stress, and vascular dysfunction, thereby leading to gradual loss of function in multiple organs. However, little attention has been paid to gene expression changes in the lung under hyperglycemic conditions. In this study, we found that diabetes inuced histological changes in the lung of streptozotocin-induced diabetic mice. Global gene expression profiling revealed a set of genes that are up- and down-regulated in the lung of diabetic mice. Among these, expression of Amigo2, Adrb2, and Zbtb16 were confirmed at the transcript level to correlate significantly with hyperglycemia in the lung. We further evaluated the effect of human umbilical cord-derived perivascular stem cells (PVCs) on these gene expression in the lung of diabetic mice. Our results show that administration of PVC-conditioned medium significantly suppressed Amig2, Adrb2, and Zbtb16 upregulation in these mice, suggesting that these genes may be useful indicators of lung injury during hyperglycemia. Furthermore, PVCs offer a promising alternative cell therapy for treating diabetic complications via regulation of gene expression.

• Journal of Biomedical Engineering Research
• /
• v.44 no.5
• /
• pp.303-314
• /
• 2023

This study aimed to assess the practical feasibility of advanced deformable image registration (DIR) algorithms in radiotherapy by employing two distinct datasets. The first dataset included 14 4D lung CT scans and 31 head and neck CT scans. In the 4D lung CT dataset, we employed the DIR algorithm to register organs at risk and tumors based on respiratory phases. The second dataset comprised pre-, mid-, and post-treatment CT images of the head and neck region, along with organ at risk and tumor delineations. These images underwent registration using the DIR algorithm, and Dice similarity coefficients (DSCs) were compared. In the 4D lung CT dataset, registration accuracy was evaluated for the spinal cord, lung, lung nodules, esophagus, and tumors. The average DSCs for the non-learning-based SyN and NiftyReg algorithms were 0.92±0.07 and 0.88±0.09, respectively. Deep learning methods, namely Voxelmorph, Cyclemorph, and Transmorph, achieved average DSCs of 0.90±0.07, 0.91±0.04, and 0.89±0.05, respectively. For the head and neck CT dataset, the average DSCs for SyN and NiftyReg were 0.82±0.04 and 0.79±0.05, respectively, while Voxelmorph, Cyclemorph, and Transmorph showed average DSCs of 0.80±0.08, 0.78±0.11, and 0.78±0.09, respectively. Additionally, the deep learning DIR algorithms demonstrated faster transformation times compared to other models, including commercial and conventional mathematical algorithms (Voxelmorph: 0.36 sec/images, Cyclemorph: 0.3 sec/images, Transmorph: 5.1 sec/images, SyN: 140 sec/images, NiftyReg: 40.2 sec/images). In conclusion, this study highlights the varying clinical applicability of deep learning-based DIR methods in different anatomical regions. While challenges were encountered in head and neck CT registrations, 4D lung CT registrations exhibited favorable results, indicating the potential for clinical implementation. Further research and development in DIR algorithms tailored to specific anatomical regions are warranted to improve the overall clinical utility of these methods.

• 대한예방의학회:학술대회논문집
• /
• 1993.10a
• /
• pp.14-15
• /
• 1993

• Tuberculosis and Respiratory Diseases
• /
• v.58 no.4
• /
• pp.367-374
• /
• 2005

Background : The fact that only 10-20% of chronic cigarette smokers develop chronic obstructive pulmonary disease (COPD) reflects the presence of genetic factors associated with the susceptibility to COPD. Recently, it was reported that the surfactant protein A increases the secretion of matrix metalloprotease 9, which degrades extracellular matrices of the lung, through a Toll-like receptor 2 (TLR2). In this context, possible role of TLR2 in the pathogenesis of COPD was postulated, and a functional dinucleotide repeat polymorphism in intron II of TLR2 was evaluated for any association with COPD. Method : Male patients with COPD and male smokers with a normal pulmonary function were enrolled in this study. The number of Guanine-Thymine repeats in intron II of the TLR2 gene were counted. Because the distributions of the repeats were trimodal, the alleles were classified into three subclasses, 12-16 repeats: short (S) alleles; 17-22 repeats: medium length (M) alleles; and 23-27 repeats: long (L) alleles. Result : 125 male patients with COPD and 144 age- and gender-matched blood donors with a normal lung function were enrolled. There were no differences in the distribution of each allele subclass (S, M and L) between the COPD and control group (p=0.75). The frequencies of the genotypes with and without each allele subclass in the COPD and control group were similar. Conclusion : A microsatellite polymorphism in intron II of TLR2 gene was not associated with the development of COPD in Koreans.

• The Journal of Korean Medicine
• /
• v.23 no.2
• /
• pp.211-224
• /
• 2002

Background and Objective : In order to investigate the effects of Gilgyunglwedok-tang (GRT) on antitumor activity and antimetastatic activity, studies were done experimentally. Materials and Methods : Experimental studies were perfonned for the cytotoxic effect on BALB/c mouse lung fibroblast cells, the proliferating effect of splenic lymphocyte, the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclear cells (PBMCs), the cytotoxic effect on A549, SK-OV-3, SK-MEL-2, MCF-7 cells, the inhibitory effect on the activity of DNA topoisomerase I, the T/C% in ICR mice bearing S-180, the inhibitory effect of Cell adhesive of A549 Cells and SK-OY-3 Cells to complex extracellular matrix, the inhibitory effect on lung colonies, the change of lung tissue, the antiangiogenic activity, and the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line. Results and Conclusion : The results were obtained as follows : 1. In the cytotoxic effect on BALB/C mouse lung fibroblast Cell, GHT didn't show the significant cytotoxic effect on BALB/C mouse lung fibroblast cell compared to the control group. 2. In thymidine uptake assay, GHT showed the significant proliferating effect of splenic lymphocyte in proportion to the concentration. 3. In the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclea cells (PBMCs) of mice, GRT had no significant change to the normal group in CD4. However, GRT showed an increase to the normal group in CD8 and GHT in the only $1\mu\textrm{g}/ml$ category showed an increase to the normal group in B220. 4. In the cytotoxic effect of GRT on A549, SK-OY-3, SK-MEL-2 and MCF-7 cells, there was no significant cytotoxic effect compared to the control group. 5. In the inhibitory effect on the activity of DNA topoisomerase I, GHT in the $10\mu\textrm{g}/ml$ category showed the inhibitory effect on the activity of DNA topoisomerase I in proportion to the concentration. 6. In the T/C% in ICRmice bearing S-180, GHTtreated group showed 123.7% of T/C% compared to the control group. 7. In the inhibitory effect of cell adhesive of A549 Cells and SK-OV-3 Cells to complex extracellular matrix, GRT in the only $100\mu\textrm{g}/ml$ category showed the significant inhibitory effect compared to the control group. 8. In the inhibitory effect on lung colonies, GHT showed the significant inhibitory effect on lung colonies compared to the control group. 9. In the change of lung tissue, GHT showed a significant decrease of lung cancer growth, interalveolar fibrosis and hyaline material compared to the control group. In the development of lymphocyte around lung cancer cells and lung parenchymal, GHT showed the significant inducement efficacy compared to the control group. 10. In CAM assay, the antiangiogenic activity of GHT showed 30%. 11. In the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line, GHT had no significant inhibitory effect on MMP-2 and MMP-9 gene expression compared to the control group. According to the above results, it could be suggested that GHT has an antitumor activity and antimetastatic activity.