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Caspase-9 (CASP-9) is an initiator CASP in the apoptosome-driven apoptosis pathway and plays an important role in the development and progression of cancer. Polymorphisms in the promoter region of the CASP-9 gene may influence the promoter activity of this gene, thereby modulating susceptibility to lung cancer. To test this hypothesis, we examined the association of four polymorphisms [-1263A>G, -905T>G, -712C>T and -293_-275delCGTGAGGTCAGTGCGGGGA (-293del)] in the CASP-9 promoter with the risk of lung cancer in a Korean population. The CASP-9 genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and gender. The -1263 GG genotype was associated with a significantly decreased risk of lung cancer compared with the -1263 AA genotype or combined -1263 AA+AG genotype [adjusted odds ratio (OR)=0.64, 95% confidence interval (95% CI)=0.42-0.98, P=0.04 and adjusted OR=0.67, 95% CI=0.46-0.97, P=0.01, respectively]. For the -712C>T polymorphism, individuals with at least one -712T allele were at a significantly increased risk of lung cancer compared with those harboring the -712 CC genotype (adjusted OR=1.42, 95% CI=1.06-1.89, P=0.02). Consistent with the results of genotype analyses, the -1263G/-712C (G-C) haplotype was associated with a significantly decreased risk of lung cancer [adjusted OR=0.59, 95% CI=0.47-0.75, P and Bonferroni corrected P (Pc)

Polymorphisms in DNA repair genes may be associated with differences in the capacity to repair DNA damage and thereby influence an individual's susceptibility to smoking-related cancer. To test this hypothesis, we investigated the potential association of 7 XPC polymorphisms (-449G-->C, -371G-->A, -27G-->C, Val499Arg, PAT-/+, IVS11-5C-->A and Lys939Gln) and their haplotypes with lung cancer risk in a Korean population. XPC genotypes were determined in 432 lung cancer patients and 432 healthy controls frequency-matched for age and sex. XPC haplotypes were predicted using a Bayesian algorithm in the Phase program. The combined -27CG+CC genotype was associated with a significantly increased risk for overall lung cancer compared to the -27GG genotype (adjusted OR = 1.97, 95% CI 1.22-3.17, p = 0.005). The other 6 polymorphisms were not significantly associated with overall risk of lung cancer. When lung cancer cases were categorized by tumor histology, the -371AA genotype was associated with a significantly increased risk of squamous cell carcinoma compared to the combined -371GG and GA genotype (adjusted OR = 2.08, 95% CI 1.09-4.00, p = 0.03). The PAT-/+, IVS11-5C-->A and Lys939Gln polymorphisms were associated with a significantly decreased risk of small cell carcinoma (SM) under a dominant model for the polymorphic allele (adjusted OR = 0.49, 95% CI 0.29-0.82, p = 0.006; adjusted OR = 0.60, 95% CI 0.36-1.00, p = 0.05; and adjusted OR = 0.58, 95% CI 0.35-0.97, p = 0.04, respectively). Consistent with genotyping analyses, haplotype 4 (1112222) containing the PAT+/IVS11-5A/939Gln alleles was associated with a significantly decreased risk of SM (adjusted OR = 0.56, 95% CI 0.37-0.85, p = 0.007 and Bonferroni-corrected p = 0.049), whereas haplotype 5 (1122111) containing the -27C allele was associated with a significantly increased risk of SM (adjusted OR = 2.88, 95% CI 1.41-5.87, p = 0.004 and Bonferroni-corrected p = 0.028). These results suggest that XPC polymorphisms/haplotypes may contribute to genetic susceptibility for lung cancer.

Polymorphisms in DNA repair genes may be associated with differences in the repair capacity of DNA damage and may thereby influence an individual's susceptibility to smoking-related cancer. We investigated the association between the -93G--A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 -93G--A polymorphism was typed in 372 lung cancer patients and 371 healthy controls that were frequency-matched for age and sex. There was no significant association between the hMLH1 -93G--A genotype and the risk for adenocarcinoma or small cell carcinoma. However, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma compared with both the GG genotype (adjusted OR=2.02; 95% CI=1.15-3.55; p=0.014) and the combined GG and GA genotype (adjusted OR=1.83; 95% CI=1.24-2.71; p=0.003). When the subjects were stratified by smoking exposure, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma in lighter smokers (or = 39 pack-years; adjusted OR=1.95; 95% CI=1.03-3.66; p=0.039) compared with the combined GG and GA genotype, whereas there was no significant association in heavier smokers (39 pack-years; adjusted OR=1.47; 95% CI=0.82-2.61). These results suggest that the hMLH1 -93G--A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung.

LER of an acetal-type photoresist (PR) and an annealing-type PR was measured by Atomic Force Microscopy, with which LER is more quantitatively measurable than using SEM. The annealing-type PR showed smaller LER than acetal-type did. Acid diffusion length measurement of these two types of KrF photoresists with a practical method that is a measurement of the thickness loss in a resist film after development which follows placement of exposed resist powder on the surface and applying PEB was also executed. The annealing-type PR has been found to show longer acid diffusion length than that of acetal-type PR. Considering deblocking temperature, acetal group is cleaved right upon exposure before PEB due to its relatively low activation energy. This means that there would be more hydroxystyrene units in acetal-type PR at the beginning of PEB than in annealing-type one. T g of photoresist samples before and after deblocking reaction was also measured by DSC. After deblocking reaction, it was found that T g of acetal-type PR is much higher than that of annealing-type PR. This relatively high T g will make acetal-type PR to have shorter acid diffusion length in conjunction with relatively low PEB temperature comparing with annealing-type in general. The absolute T g value and T g change with deblocking reaction depending on types of PRs were correlated to explain the inherent difference in LER performance in different types of PRs.

The shrinkage of resist pattern during in-line SEM measurement has been argued and studied as one of the problems unsettled for manufacturing with ArF photolithography. Many of attempts to solve this problem have focused their attentions on the improvement of resist and inspection equipment. We bring up BARC (bottom anti-reflective coating) as a new impact factor on SEM shrinkage of resist. Practically, although the same resist was employed, our shrinkage tests gave the results depending on the kind of BARC. Feature size and depth of focus also affect SEM shrinkage of resist. Effect of reflectivity on SEM shrinkage was evaluated by changing thickness of BARCs and resultantly was somewhat significant. In this paper, the BARC-dependent results of SEM shrinkage are analyzed and discussed to provide a possibility that BARC may have another function of reducing SEM shrinkage.

The ArF resist has been evaluated focusing on resin character such as molecular weight, monomer composition and polydispersity (Pd). The resin properties were investigated to elucidate that which parameter was affected to the line edge roughness (LER). The Pd was correlated with LER. As the Pd was large, the LER was small. The resin molecular weight and monomer composition were affected to their vertical profile. Low molecular weight portion rich resin resulted in round and t-top profile, whilst high molecular weight rich resin resulted in square profile. The amount of lower molecular weight fraction was changed by purification method. The lower molecular weight resin caused severe tapered profile. It was concluded that 1) shift of Mw to smaller and 2) higher content of low molecular size fraction lead to rounded and tapered pattern profile. Lot-to-lot stable good pattern profile has achieved by controlling polymer molecular weight and content of low molecular size fraction in small variation range.

Isoprostanes, novel markers of oxidative injury, are generated by the free radical-mediated peroxidation of arachidonic acid (AA). They are thought to be important in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Using gas chromatography-mass spectrometry (GC-MS), we investigated the alteration of urinary F(2)-isoprostanes in AD patients compared to that of healthy subjects. Our results show that the levels of urinary F(2)-isoprostanes, sum of the prostaglandin F(2 alpha) isomer; prostaglandin F(2 alpha) (PGF(2 alpha)), prostaglandin F(2 beta) (PGF(2 beta)), and 8-isoprostaglandin F(2 alpha) (8-isoPGF(2 alpha)), significantly increased in AD patients (P0.05). The concentration of urinary 8-isoPGF(2 alpha), one of the biomarkers of oxidative stress, was not significantly different between 34 AD patients and 20 age-matched controls (P0.05). The PGF(2 alpha), formed by endoperoxide reductase from PGH(2), was significantly increased in AD patients, when compared with the levels of the normal controls (P0.05). The PGF(2 alpha), an enzymatic product of arachidonic acid, may affect the pathogenesis of AD. In addition, urinary F(2)-isoprostanes can play an important role as a biomarker in AD.

To explore the possible involvement of a relationship between steroids and polyunsaturated fatty acids (PUFAs) in thyroid cancer, we studied the concentration levels of 21 endogenous urinary androgens and glucocorticoids, and 6 urinary PUFAs in female patients with thyroid cancer (n=29, 49.4+/-12.6 years) and in normal female subjects (n=20, 48.3+/-11.9 years). Using gas chromatography-mass spectrometry in selected ion-monitoring mode, we performed quantification of androgens, glucocorticoids, and PUFAs. In the case of the urinary androgens and the glucocorticoids, the concentration of androgens was not altered between patients with thyroid cancer and normal controls. However, the concentration of glucocorticoid significantly decreased in patients with thyroid cancer compared to that of the normal controls. Also, in case of urinary PUFAs, the precursor of cholesterol, the concentration of linoleic acid, arachidonic acid, and docosahexaenoic acid (DHA) were decreased in patient with thyroid cancer (P

The risk of cancer of the cervix is linked with sexual behavior. Although infectious agents, such as human papillomaviruses (HPVs) are implicated, these alone may be insufficient to induce the disease. We investigated the potential role of estrogen, androgen, and polyamine metabolism as co-factors in the development of cervical cancer. We obtained urine samples from patients with benign cervical disease (n=18) and cervical cancer (n=18) and from age-matched normal female subjects (n=25). For 11 polyamine determination, an improved and sensitive gas-chromatographic with nitrogen/phosphorus-detection (GC/NPD) procedure was used. The urinary levels of 25 androgens and corticoids and 16 estrogens were quantitatively determined by gas chromatography-mass spectrometry-selected ion-monitoring (GC/MS/SIM). In the patients with cervical cancer, the ratio of 16alpha-hydroxy estrone (16alpha-OH E1)/2-hydroxy estrone (2-OH E1), putrescine (Put)/N(1)-acetylspermidine (N(1)-acSpd) and 5beta-tetrahydrocortisol (THF)/5alpha-tetrahydrocortisol (5alpha-THF) were significantly increased in comparison to the values of the normal controls. These data suggest: (1) an increase of 16alpha-hydroxylation in estrogen metabolism; (2) the high activity of polyamine oxidase (PAO) in polyamine metabolism; and (3) the low activity of 5alpha-reductase in androgen metabolism may play a significant role in the development of cervical cancer. Although additional research is necessary, the combination of 16alpha-OH E1/2-OH E1 and THF/5alpha-THF may provide a dual marker for the discrimination of benign cervical disease and cervical cancer.

In this study, we investigate how oxidative stress alters the urinary F2-isoprostanes' level and we examine the correlation between 8-isoPGF(2alpha) and thyroid hormones in female patients with Graves' hyperthyroidism. We quantitatively determined the concentrations of urinary F2-isoprostanes using gas chromatography-mass spectrometry in the selected ion-monitoring mode. We recruited individuals in the following three groups of subjects for this study: (1) female hyperthyroidism patients (n = 14, 21-71 years), (2) female hypothyroidism patients (n = 16, 16-66 years), and (3) female age-matched normal controls (n = 10, 20-61 years). The average concentration of 8-iso prostaglandin F(2alpha) (8-isoPGF(2alpha)) in hyperthyroidism patients was significantly higher than that in the healthy controls (P0.05). The concentration of 8-isoPGF(2alpha) in hypothyroidism patients was similar to that in normal controls. Although the level of 8-isoPGF(2alpha) in two of the patients was slightly elevated, the P value was not significant (NS). Our data suggest that the increased level of urinary 8-isoPGF(2alpha) may reflect possible oxidation injuries in hyperthyroidism patients due to the high level of thyroid hormones. Therefore, the elevated 8-isoPGF(2alpha) in patients could be used as an important biomarker for hyperthyroidism disease.

F(2)-isoprostanes are derived in vivo principally from the following: (1) the formation of positional peroxyl radicals of arachidonic acid, (2) endocyclization to prostaglandin G(2)-like structures, and (3) reduction to PGF(2)-like compounds. F(2)-isoprostanes have been proposed as biomarkers of lipid peroxidation, oxidative stress status, and the oxidation of low-density lipoprotein (LDL). Using gas chromatography-ion trap-mass spectrometry, we studied how hemodialysis (HD) affects plasma total F(2)-isoprostanes. We examined the plasma total F(2)-isoprostanes in end-stage renal disease (ESRD) patients, before HD, after HD, between HD, and in control subjects. Plasma concentrations of total F(2)-isoprostanes were significantly higher in the after HD ESRD patients than the before hemodialysis ESRD patients (P0.05). There is no difference between before HD ESRD patients and normal controls. Moreover, a positive or negative correlation was seen between LDL and plasma total F(2)-isoprostanes (P0.001), and between age and plasma total F(2)-isoprostanes (P0.001). This study indicates HD treatment may be the major contributor of oxidative stress in ESRD patients.

DNA repair plays a critical role in protecting the genome from insults of cancer-causing agents, such as those found in tobacco smoke. Therefore, reduced DNA repair capacity can increase the susceptibility to smoking-related cancers. Recently, several polymorphisms have been identified in the xeroderma pigmentosum group G (XPG) gene, and it is possible that these polymorphisms may affect the DNA repair capacity, thereby modulating cancer susceptibility. We investigated the relationship between the His1104Asp polymorphism in the XPG gene and the risk of lung cancer. The study population consisted of 310 lung cancer patients and 311 healthy controls who were frequency (1:1) matched based on age and sex. The Asp/Asp genotype was more frequent in the controls (28.9%) than in the cases (18.7%) and associated with a significantly decreased risk of lung cancer [adjusted odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37-0.80] when the combined His/His and His/Asp genotype was used as the reference. The protective effect of the Asp/Asp genotype against lung cancer was statistically significant in the older subjects (adjusted OR = 0.51, 95% CI = 0.37-0.80), males (adjusted OR = 0.54, 95% CI = 0.35-0.83), and lighter smokers (adjusted OR = 0.48, 95% CI = 0.25-0.94) in a stratification analysis. When the lung cancers were analyzed by histologic type, the Asp/Asp genotype was associated with a significantly decreased risk of squamous cell carcinoma (adjusted OR = 0.55, 95% CI = 0.34-0.88) and small cell lung cancer (adjusted OR = 0.44, 95% CI = 0.20-0.97), but non-significant decreased risk of adenocarcinoma (adjusted OR = 0.64, 95% CI = 0.36-1.12). These results suggest that the XPG codon 1104 polymorphism contributes to genetic susceptibility to lung cancer.

The truncated myc and max proteins, only containing basic regions and helix-loop-helix/zipper (b/HLH/Zip) regions were over-expressed in E. coli and used for the determination of the binding constant and of the inhibitory mechanism on myc-max (or max-max)-DNA complex formation. The association kinetic constants (k(1) and k(-1)) of truncated max-max or myc-max dimer and DNA were determined as k(1)=(1.7+/-0.6)x10(5) M(-1) s(-1), k(-1)=(3.4+/-1.2)x10(-2) s(-1) for max-max and DNA or k(1)=(2.1+/-0.7)x10(5) M(-1) s(-1), k(-1)=(3.2+/-1.4)x10(-2) s(-1) for myc-max and DNA. The equilibrium binding constant (K(1)) was determined using these kinetic parameters [K(XXD)=(7.8+/-2.6)x10(6) M(-1) for max-max and DNA or K(XYD)=(6.9+/-2.2)x10(6) M(-1) for myc-max and DNA]. The binding constants of myc-max or max-max dimer formation were K(XX)=(2.6+/-0.9)x10(5) M(-1) or K(XY)=(1.3+/-0.4)x10(4) M(-1), respectively. When truncated proteins were used, the max-max dimer formation was easier than the myc-max dimer formation, contrary to the physiologically determined case. This leads us to deduce that domains other than b/HLH/Zip are very important for the transcriptional regulatory activity in physiological conditions. The truncated myc and max proteins, which were expressed in E. coli and contained only b/HLH/Zip regions were also used for the screening of inhibitors of myc-max-DNA complex formation. A synthesized curcuminoid, 1,7-bis(4-methyl-3-nitrophenyl)-1,6-heptadiene-3,5-dione (curcuminoid 004), showed the most potent inhibition out of the synthesized curcuminoids, in competition with DNA. The dissociation constant of max-max dimer and the inhibitor was 9 microM, when investigated using in vitro expressed b/HLH/Zip dimer proteins. The curcuminoid 004 showed an inhibitory effect on the binding of myc-max protein to the E-box element in SNU16 cells, and suppressed the expression of myc target genes including ornithine decarboxylase (ODC), cdc25a and c-myc in myc over-expressed human stomach cancer cell line SNU16.

Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be involved in the development of NHL and that such mutations may be responsible for the allelic losses of 8p21-22 in NHL. In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-R1 gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1 gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.

연구배경 : 폐암의 80-90%는 흡연과 관계가 있으나 흡연자의 일부에서만 폐암이 발생하는 현상은 개체의 유전적 소인이 폐암발생을 결정하는 주요 요인임을 시사한다. 저자들은 한국인에서 DNA 회복 유전자인 XPC 유전자의 codon 499와 codon 939 다형성 그리고 intron 9에 존재하는 poly(AT) 삽입/결손 (PAT) 다형성에 따른 폐암의 위험도를 조사하였다. 방 법 :1998년 1월부터 1998년 12월까지 경북대학교병원 내과에서 병리학적으로 폐암으로 확진된 남자 폐암환자 219명을 대상으로 하였으며 악성종양으로 진단받은 과거력이 있는 사람은 제외하였다. 대조군은 1998년 1월부터 1998년 12월까지 경북대학교병원 건강검진센터를 방문한 40세 이상의 검진자들을 대상으로 하였으며 호흡기질환이나 악성종양이 있는 경우는 제외하였다. 대상인의 나이, 성, 흡연력, 과거력 등은 면접이나 병력지를 통해 얻었으며, 시료는 전혈 5cc에서 DNA를 추출하고 PCR 혹은 PCR-RFLP법을 통해 XPC 유전자의 다형성을 조사하였다. 결 과: 조사한 3부위의 XPC 유전자의 유의한 관계가 없었으며 연령, 흡연력, 흡연 인-년등으로 구분한 경우에도 다형성에 따른 폐암의 위험도는 유의한 차이가 없었다. 폐암의 조직형을 구분하여 비교한 경우에도 XPC 유전자의 다형성과 폐암의 위험도는 유의한 관계가 없었다. XPC 유전자의 Va1499Ala, PAT, Lys939Gln 다형성은 다형성간에 연관비평형 (lingkage disequilibrium) 있었으며, 특히 PAT 다형성과 Lys939Gln 다형성은 kappa 치가 0.87로 높았다. XPC 유전자의 3부위다형성의 haplotype도 폐암과 유의한 관계가 없었으며, 연력, 흡연력, 흡연 안-년, 조직형을 구분한 경우에도 haplotype에 따른 폐암의 위험도는 유의차이가 없었다. 결 론: 한국인에서 XPC 유전자의 codon 499와 codon 939 다형성과 PAT 다형성은 폐암의 위험도를 결정하는 주요 인자는 아닌 것으로 생각된다. 【Background : DNA repair plays a crucial role in protection from cancer-causing agents. Therefore, a reduced DNA repair capacity can increase the susceptibility to lung cancer. The XPC gene contains 15 exons and encodes a 940 amino acid protein that plays a central role in DNA damage recognition of the nucleotide excision repair pathway, which is a major DNA repair mechanisim removing the bulky-helix distorting DNA lesions caused by smoking. Recently several polymorphisms in the XPC gene were identified. In addition, it is possible that these polymorphisms may affect the DNA repair capacity, which modulate cancer susceptibility. The relationship between codon 499 and 939 polymorphisms, and a poly(AT) insertion/deletion polymorphism in the XPC gene, and the lung cancer risk were investigated. Materials and Methods : The genotypes were determined using either PCR or PCR-RFLP analysis in 219 male lung cancer patients and 150 healthy males controls. Results : The frequencies of the genotypes (Val499Ala, PAT and Lys939Gln) among the cases were not significantly different from those of the controls. There was no significant associantion between these polymorphi는 and the lung cancer risk when the analyses were stratified according to age, smoking status and the pack-years of smoking. Moreover, the genotypes had no apparent relationship with any of the histological types of lung cancer. There was a linkage disequilibrium among the Val499Ala, PAT and Lys939Gln polymorphisms. The PAT polymorphism had a strong linkage disequilibrium with the Lys939Gln polymorphism (kappa value=0.87). The XPC haplotypes showed no significant association with the lung cancer risk. Conclusion : These results suggest that XPC Val499Ala, PAT and Lys939Gln polymorphisms are not major contributors to the individual lung cancer susceptibility in Koreans.】

In dward nova we assume the primary star as a white dwarf and the secondary as the late type star which filled Roche lobe. Mass flow from the secondary star leads to the formation of thin accretion disk around the white dwarf. We use the α parameter as viscosity to maintain the disk form and propose that the outburst in dwarf nova cause the steep increase of source term. With these assumptions we solve the basic equations of stellar structure using Newton-Raphson method. We show the physical parameters like temperature, density, pressure, opacity, surface density, height and flux to the radius of disk. Changing the value of α, we compare several parameters when mass flow rate is constant with those of when luminosity of disk is brightest. At the same time, we obtain time-dependent variations of luminosity and mass of disk. We propose the suitable range of α is 0.15-0.18 to the difference of luminosity. We compare several parameters of disk with those of the normal late type stars which have the same molecular weight of disk is lower. Maybe the outburst in dwarf nova is due to the variation of the α value instead of increment of mass flow from the secondary star.

For a geostationary satellite north-south station keeping maneuver must control the inclination elements. The effects on the orbit plane of maneuvers and natural perturbations may be represented by a plane plot of Wc versus Ws, since these inclination elements represent the projection of the unit orbit normal onto the equatorial plane. The evolution of the semi-major axis and the inclination elements are obtained.

The present study aimed to explore the use of meaning-making coping (existential, spiritual, and religious coping) among cancer patients in Korea and to investigate the impact of culture on their choice of coping methods. Thirty-three participants with various kinds of cancer were interviewed. Four different kinds of coping resources emerged from analyses of the interview transcripts: (1) belief in the healing power of nature; (2) mind–body connection; (3) relying on transcendent power; and (4) finding oneself in relationships with others. The findings of this study suggest the importance of investigating cultural context when exploring the use of the meaning-making coping strategies in different countries.