Relationship of Vitamin D Binding Protein Polymorphisms and Lung Function in Korean Chronic Obstructive Pulmonary Disease

PURPOSE: Multiple genetic factors are associated with chronic obstructive pulmonary disease (COPD). The association of gene encoding vitamin D binding protein (VDBP, GC) with COPD has been controversial. We sought to investigate the types of GC variants in the Korean population and determine the association of GC variants with COPD and lung function in the Korean population. MATERIALS AND METHODS:The study cohort consisted of 203 COPD patients and 157 control subjects. GC variants were genotyped by the restriction fragment-length polymorphism method. Repeated measures of lung function data were analyzed using a linear mixed model including sex, age, height, and pack-years of smoking to investigate the association of GC genetic factors and lung function. RESULTS:GC1F variant was most frequently observed in COPD (46.1%) and controls (42.0%). GC1S variant (29.0% vs. 21.4%; p=0.020) and genotype 1S-1S (8.3% vs. 3.4%; p=0.047) were more commonly detected in control than COPD. According to linear mixed model analysis including controls and COPD, subjects with genotype 1S-1S had 0.427 L higher forced expiratory volume in 1 second (FEV₁) than those with other genotypes (p=0.029). However, interaction between the genotype and smoking pack-year was found to be particularly significant among subjects with genotype 1S-1S; FEV₁ decreased by 0.014 L per smoking pack-year (p=0.001). CONCLUSION:This study suggested that GC polymorphism might be associated with lung function and risk of COPD in Korean population. GC1S variant and genotype 1S-1S were more frequently observed in control than in COPD. Moreover, GC1S variant was more common in non-decliners than in rapid decliners among COPD.ope

Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions

BACKGROUND: The development of chemo-resistance in non-small lung cancer is a major obstacle in treating patients. Hypoxia is a commonly faced microenvironment in solid tumor and suggested to be related to both autophagy and chemo-resistance. METHODS: In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue RESULTS: Hypoxic exposure (1 % O2) of A549 cell stimulated autophagic induction in cancer cells, shown by increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 in Western blot, increased GFP-LC puncta in confocal microscopy, and increased number of double-membrane autophagic vacuoles in electron micrographs. Hypoxic exposure also induced resistance of cancer cells to cisplatin, and LC3B siRNA restored the sensitivity of cancer cells to chemotherapy. Furthermore, Human lung cancer tissues that experienced chemotherapy showed increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 compared with chemo-naïve cancer tissue in Western blot. CONCLUSION: Autophagy may play an important role in acquiring resistance to chemotherapy in lung cancer and hypoxia related pathway seems to be involved in autophagy induction.ope

Autophagy Activity in Pulmonary Metastatic Tumor Tissues from Colorectal Cancer: A Pilot Study

PURPOSE: Autophagy has been reported to be involved in treatment failure in tumor. We aimed to evaluate autophagy activity in tumor tissue and compare them between the recurrence and non-recurrence groups. MATERIALS AND METHODS: We analyzed expressions of autophagy-related proteins in tumor tissues which were obtained from pulmonary metastases of colorectal cancer patients by Western blot. We also analyzed autophagosomes by transmission electron microscopy. RESULTS: Tumor tissues from recurrence group showed increased levels of LC3B-II, decreased levels of p62/SQSTM1, and also a marked accumulation of autophagosomes compared with tissues from non-recurrence group. CONCLUSION: The present study suggests that autophagy may be associated with treatment failure of metastatic colorectal cancer.ope

Identification of Tumor Suppressor Loci on the Short Arm of Chromosome 16 in Primary Small Cell Lung Cancers

Background : Loss of the short arm of chromosome 16 is a frequent event in various cancers, which suggests the presence of tumor suppressor gene(s) there. To map precise tumor suppressor loci on the chromosome arm for further positional cloning efforts, we tested 23 primary small cell lung cancers. Method : The DNAs extracted from paraffin embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Twenty polymorphic microsatellite markers located in the short arm of chromosome 16 were used in the microsatellite analysis. Results : We found that six (26.1%) of 23 tumors exhibited LOH in at least one of tested microsatellite markers. Two (8.7%) of 6 tumors exhibiting LOH lost a larger area in chromosome 16p. LOH was observed in five common deleted regions at 16p. Among those areas, LOH between D16S668 and D16S749 was most frequent (21.1%). LOH was also observed at four other regions, between D16S3024 and D16S748, D16S405, D16S420, and D16S753. Six of 23 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 3.3% (15 of 460) of the loci tested. Conclusion : Our data demonstrated that at least five tumor suppressor loci might exist in the short arm of chromosome 16 and that they may play an important role in small cell lung cancer tumorigenesis.ope

인슐린양 성장 인자 결합 단백-3 유전자-202 좌위의 다형성에 따른 비소세포폐암의 위험도

인슐린양 성장 인자 결합 단백-3(Insulin-like growth factor (IGF) binding protein-3 (IGFBP- 는 혈액 내에서 와 3)) IGF 결합하여 복합체 혹은 저장소로 작용함으로써 가 수용체에 결합하는 것을 방해하여 의 항세포사멸 , IGF IGF (anti-및 세포분열 촉진의 기능을 억제한다 하지만 특정 상황에서는 도리어 apoptosis) . , IGFBP- 가 의 파괴를 억제하여 3 IGF 에 의한 암세포의 분화 및 성장을 촉진할 수도 있다는 것이 알려져 있다 대부분의 환자에서 혈액내 IGF . IGFBP- 수치는 3IGFBP- 유전자의 3 - 좌위 의 다형성 에 의해 크게 영향을 받는다 따라서 저자 등은 제한 효소 202 (locus) (polymorphism) 를 이용하여 비소세포폐암 환자의 (restriction enzyme) IGFBP- 유전자 3 - 좌위의 다형성을 분석함으로써 이 좌위의 202 ,다형성이 비소세포폐암의 위험도와 연관되어 있는지 조사하였다 본 연구는 명의 비소세포폐암 환자군과 연령 성별 . 104 흡연력이 비슷한 명의 대조군을 비교 분석하였다 대조군에서 104 . - 좌위 유전자 다형성의 빈도는 202 AA형 명 48 (46.2%),AC형 명 45 (43.3%), CC형 명 이었고 비소세포폐암 환자군에서 11 (10.5%) , - 좌위 유전자 다형성의 빈도는 202 AA형 명 67(64.4%), AC형 명 35 (33.7%), CC형 명 이었다 2 (1.9%) . - 좌위의 유전자 다형성에 있어서 대조군과 비소세포폐암 환자 202 군 사이에 유의한 빈도 차이가 있었으며 ( p< 0.05, Pearson’s χ2 비소세포폐암의 위험도는 test), – -좌위의 202 AA형에서 가장 높고 CC형에서 가장 낮았다. CC형을 기준으로 하면 AC형의 비교 위험도는 신뢰구간 2.60 (95% : 0.89 - 이었으 8.60) 며 AA형의 비교 위험도는 신뢰구간 5.89 (95% : 1.92 - 이었다 본 연구 결과는 21.16) . , IGFBP- 유전자의 3 - 좌위 202 (locus) 의 다형성 이 비소세포폐암의 위험인자 중의 하나일 가능성을 제시하며 따라서 비소세포폐암에 대한 항암 (polymorphism) , 치료 개발에 있어서 새로운 표적이 될 가능성을 시사한다.ope