PEL-FREEZ DR4 TEST-SSP UNITRAY^TM를 이용한 HLA-DR 검사

최수진,원진연,오흥범 대한임상검사정도관리학회 1999 臨床檢査와 精度管理 Vol.21 No.1

HCV, Acute, LT : Hepatitis C Virus Infection Elevates TRAIL-DR4/DR5-Induced Apoptosis via Caspase-8 Activation

( Jae Young Jang ),( Seong Jun Kim ),( Eun Kyung Cho ),( Soung Won Jeong ),( Yun Nah Lee ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Sang Woo Cha ),( Young Seok Kim ),( Young Deok Cho ),( Hong Soo Kim ),( 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Persistent hepatitis C virus (HCV) infection induces apoptosis of human hepatocytes. We and others have recently shown that HCV infection sensitizes host cells to mito- chondrial apoptosis via TRAIL death receptor-R1 (DR4)/-R2 (DR5). However, critical determinants of TRAIL-DR4/DR5- mediated apoptosis induced by HCV infection still remain to be clarified. Here we extend our study to examine if HCV infection elevates TRAIL-DR4/DR5-mediated apoptosis via caspase- 8 activation. Methods: Using HCV JFH-1 cell-culture system (HCVcc), the expression level of DR4 and DR5 in HCV-infected Huh7.5.1 cells was analyzed by qRT-PCR and Western blotting. Caspase activity assay and Western blotting were conducted for analysis of TRAIL-DR4/DR5-mediated caspase activation cascade in infected cells by using recombinant TRAIL, caspase inhibitors, and siRNAs specific to DR4 and DR5. Results: HCV infection stimulates DR4 and DR5 gene expression at both levels of transcription and translation. HCV-induced apoptosis via DR4/DR5 was evidenced by the reduction of caspase-3/7 activity by both DR4 and DR5 silencing and the increase of cleavage of caspases including caspase-8, caspase-9, and caspase-3 by TRAIL treatment. Treatment of infected cells with caspase-8 specific inhibitor resulted in the decline of HCV-induced cleavage of PARP and Bid, a pro-apoptotic protein. Conclusions: Our data identify that HCV infection elevates- TRAIL-DR4/DR5-mediated apoptosis of human hepatoma cells via caspase-8 activation. Given the importance of apoptosis in promoting hepatic fibrogenesis, these results suggest potential utility for TRAIL inhibition in chronic hepatitis C.

한국인에서 류마토이드 관절염과 제 2 형 조직적합항원과의 연관성에 관한 연구

유대현(Dae Hyun Yoo),서정대(Jeong Dai Suh),배상철(Sang Cheol Bae),김성윤(Seong Yoon Kim),김목현(Mok Hyun Kim),김신규(Thin Kyou Kim),주경빈(Kyung Bin Joo) 대한내과학회 1991 대한내과학회지 Vol.40 No.5

Rheumatoid arthritis is a chronic inflammatory disease characterized as destructive polyarthritis and has evidence of immunogenetic and environmental elements in its etiologic factors. Many studies document that one of the key genetic elements is closely linked to the class II major histocompatibility complex located in chromosome 6. Although it is not. known precisely how HLA genes contribute to disease susceptibility, many studies document a close association between rheumatoid arthritis and the specific histocompatibility marker, HLA-DR4. However, studies of HLA-DR4 in disease severity have yielded conflictiing results. Association between HLA- DR4 and the rheumatoid factor, earlier age of onset, increased general disease severity and more erosive radiographic changes have been reported, but these associations have not been confirmed in other studies. In addition, there has been no report regarding the association between rheumatoid arthritis and class II MHC in Koreans. Therefore this is the first epidemiologic study regarding the association between rheumatoid arthritis and class II MHC. The disrtibution of class II major histocompatibility complex and association between HLA- DR4 and disease severity were analyzed in 206 Korean patients with rheumatoid arthritis in this study. The results were as follows: 1) HLA-DR4 was associated with rheumatoid arthritis in 61.6% of the patients studied. The relative risk and etiologic fraction of HLA-DR4 were 2.47 and 0.367, respectively. HLA-DR1 was positive in 11.1% and the etiologic fraction of HLA-DR1 was 0.008. Therefore HLA-DR4 was associated strongly with rheumatoid arthritis in Koreans, similar to other ethnic populations, but HLA-DR1 was not associated with rheumatoid arthritis in Koreans. 2) HLA-DR2 was positive in 19.9% and the preventive fraction of HLA-DR2 was 0.205. HLA-DR7 was positive in 4.3% and the preventive fraction of HLA- DR7 was 0.011. Hence HLA-DR2 was the most preventive class II MHC against the development of rheumatoid arthritis in this study. 3) HLA-Dgw3 was positive in 62.1% and the relative risk of HLA-DQw3 was 1.65, HLA-DQw7, which was known as HLA-DQw3.1, was positive in 20.5% and HLA-DR4 Dgw7 haplotype was positive in 15% of the total number of patients. 4) HLA-DR4 was significantly associated with a more advanced ARA anatomical grade and more severe radiographic changes, including bony erosion, joint space, narrowing and total radiographic score. 5) The rheumatoid facor was positive in 84.3% of the HLA-DR4 positive patients and positive in 82.3% of the HLA-DR4 negative patients. HLA-DR4 v as positive in 62.2% of the 172 seropositive patients and positive in 58.8% of the 34 seronegative patients. Therefore HLA-DR4 was not associated significantly with the presence of a rheumatoid factor in this study. 6) HLA-DR4 was not associated significantly with joint count (Ritchie index), ARA functional class, ESR, C-reactive protein or other demographic data. HLA-DR4 was not associated significantly with the positive rate of ANA, cryoglobulin. 7) Homozygous HLA-DR4 patients were 31 out of 127 DR4-positive patients and showed more advanced ARA anatomical stage and radiographic changes than heterozygous DR4 patients, but the difference was statistically insignificant. In summary, HLA-DR4 was significantly associated with rheumatoid arthritis in Koreans, similar to other ethnic populations, Also HLA-DR4 was significantly associated with more destructive arthritis, but not associated with rheumatoid factor positivity and the parameters representing disease activity of rheumatoid arthritis.

Growth Inhibitory Effect of (E)-2,4-bis(p-hydroxyphenyl)-2-Butenal Diacetate through Induction of Apoptotic Cell Death by Increasing DR3 Expression in Human Lung Cancer Cells

( Ung Soo Lee ),( Jung Ok Ban ),( Eung Tae Yeon ),( Hee Pom Lee ),( Venkatareddy Udumula ),( Young Wan Ham ),( Jin Tae Hong ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.6

The Maillard Reaction Products (MRPs) are chemical compounds which have been known to be effective in chemoprevention. Death receptors (DR) play a central role in directing apoptosis in several cancer cells. In our previous study, we demonstrated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal, a MRP product, inhibited human colon cancer cell growth by inducing apoptosis via nucle-ar factor-κB (NF-κB) inactivation and G2/M phase cell cycle arrest. In this study, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate, a new (E)-2,4-bis(p-hydroxyphenyl)-2-butenal derivative, was synthesized to improve their solubility and stability in water and then evaluated against NCI-H460 and A549 human lung cancer cells. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate reduced the viability in both cell lines in a time and dose-dependent manner. We also found that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate increased apoptotic cell death through the upregulation of the expression of death receptor (DR)-3 and DR6 in both lung cancer cell lines. In addition to this, the transfection of DR3 siRNA diminished the growth inhibitory and apoptosis inducing effect of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate on lung cancer cells, however these effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate was not changed by DR6 siRNA. These results indicated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate inhibits human lung cancer cell growth via increasing apoptotic cell death by upregulation of the expression of DR3.

한국인 류마티스 관절염 환자에서 질병 중증도 표지자로서의 HLA-DR4 유용성

임미경 ( M. K. Lim ),이창근 ( C. K. Lee ),최승원 ( S. W. Choi ),주용선 ( Y. S. Ju ),주유숙 ( Y. S. Cho ),김성문 ( S. M. Kim ),신명진 ( M. J. Shin ),오흥범 ( H. B. Oh ),유빈 ( B. Yoo ),문희범 ( H. B. Moon ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.1

Objective: To investigate HLA-DR4, its subtype and shared epitope as a severity marker in Korean patients with rheumatoid arthritis. Methods: One hundred thirty-six RA patients were typed for HLA DR4 and HLA-DRB1 alleles by the polymerase chain reaction-sequence specific probe method. The patients were retrospectively evaluated for extra-articular features, presence of remission, and joint failure. Bony erosion score was assessed by Sharp`s method with modification. Results: Patients with HLA-DR4 had significantly higher prevalence of extra-articular features compared to those without the allele. However, there was no association of HLA-DR4, HLA-DRB1*0405 and shared epitope with rate of remission, joint failure, and bony erosion score. Eighty-two percent of patients were rheumatoid factor positive. With seropositive patients only, the results were the same as those above. Conclusion: HLA-DR4, HLA-DRB1*0405 and shared epitope are not a severity marker in Korean patients with RA in terms of radiological score, rate of joint failure, and rate of clinical remission. Data from this study do not support the clinical use of HLA-DR4 typing as a prognostic marker in Korean patients with RA.

반영구 특수메이크업 Dr. Eye 4S기법 개발의 타당성과 신뢰성 검증

진현숙,황혜주 한국인체미용예술학회 2022 한국인체미용예술학회지 Vol.23 No.3

The purpose of this study is to verify the validity and reliability of the semi-permanent make-up, Dr. Eye 4S Technique, which has been standardized and developed through mathematical formulation, to ensure that it is convenient for anyone to learn to use. We conducted two surveys at a two week interval. Those who participated in this study have more than 15 years of experience at plastic surgery and dermatology clinics in the Seoul metropolitan area, and 5 to 10 years of experience using semi-permanent make-up techniques. The results of compiling and analyzing data revealed the following: (i) The Correlation of Perceived Usability produced significant results in ‘convenience for the cosmetic procedure,’ ‘availability of information about the procedure’, ‘streamlining the process’, and ‘usefulness in general use’. (ii) The Correlation of Perceived Easiness produced significant results in ‘easiness to use’ ‘less effort’, and ‘easiness to perform’. (iii) The Correlation of Intention to Use produced significant results in willingness ‘to use,’ ‘to continue using’, ‘to talk positively about the 4S Technique,’ and ‘to perform the procedure using the 4S Technique’. (iv) The Correlation of Recognized Usability produced significant results in expecting ‘quick procedure,’ ‘improved result,’ and ‘to be helpful for a procedure’. (v) The Correlation of Work Efficiency produced significant results in ‘easier use,’ and ‘helpfulness in performing a procedure’. (v) The Correlation of Satisfaction Level of Training Content produced significant results in the satisfaction with the basic training about ‘drawing eyebrow sketches,’ ‘drawing eyebrow lines,’ and the ‘4S Technique.’ Lastly, (vi) The Correlation of Satisfaction Level of Training produced significant results in ‘willingness to recommend the 4S Technique’. This study verified the validity and reliability of the semi-permanent make-up, Dr. Eye 4S Technique, which is convenient for anyone to learn to use, and therefore will guide effective traning for semi-permanent make-up in the future.

Overexpression of Par-4 sensitizes TRAIL-induced apoptosis via inactivation of NF-κB and Akt signaling pathways in renal cancer cells

Lee, Tae-Jin,Jang, Ji-Hoon,Noh, Hyo-Jeong,Park, Eun-Jung,Choi, Kyeong-Sook,Kwon, Taeg-Kyu Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of cellular biochemistry Vol.109 No.5

<P>The prostate-apoptosis-response-gene-4 (Par-4) is up-regulated in prostate cells undergoing programmed cell death. Furthermore, Par-4 protein has been shown to function as an effector of cell death in response to various apoptotic stimuli that trigger mitochondria and membrane receptor-mediated cell death pathways. In this study, we investigated how Par-4 modulates TRAIL-mediated apoptosis in TRAIL-resistant Caki cells. Par-4 overexpressing cells were strikingly sensitive to apoptosis induced by TRAIL compared with control cells. Par-4 overexpressing Caki cells treated with TRAIL showed an increased activation of the initiator caspase-8 and the effector caspase-3, together with an enforced cleavage of XIAP and c-FLIP. TRAIL-induced reduction of XIAP and c-FLIP protein levels in Par-4 overexpressing cells was prevented by z-VAD pretreatment. In addition, the surface DR5 protein level was increased in TRAIL-treated Par-4 overexpressing cells. Interestingly, even though a deletion of leucine zipper domain in Par-4 recovered Bcl-2 level to basal level induced by wild type Par-4, it partly decreased sensitivity to TRAIL in Caki cells. In addition, exposure of Caki/Par-4 cells to TRAIL led to reduction of phosphorylated Akt levels, but deletion of leucine zipper domain of Par-4 did not affect these phosphorylated Akt levels. In conclusion, we here provide evidence that ectopic expression of Par-4 sensitizes Caki cells to TRAIL via modulation of multiple targets, including DR5, Bcl-2, Akt, and NF-κB. J. Cell. Biochem. 109: 885–895, 2010. © 2010 Wiley-Liss, Inc.</P>

Association of DR4 (TRAIL-R1) Polymorphisms with Cancer Risk in Caucasians: an Updated Meta-analysis

Chen, Wei,Tang, Wen-Ru,Zhang, Ming,Chang, Kwenjen,Wei, Yun-Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Death receptor 4 (TRAIL-R1 or DR4) polymorphisms have been associated with cancer risk, but findings have been inconsistent. To estimate the relationship in detail, a meta-analysis was here performed. A search of PubMed was conducted to investigate the association between DR4 C626G, A683C and A1322G polymorphisms and cancer risk, using odds ratios (ORs) with 95% confidence intervals. The results suggested that DR4 C626G and A683C polymorphisms were indeed associated with cancer risk (for C626G, dominant model, OR 0.991, 95%CI 0.866-1.133, p=0.015; for A683C, additive model, OR=1.140, 95%CI: 0.948-1.370, p=0.028; dominant model, OR=1.156, 95%CI: 0.950-1.406, p=0.080) in the Caucasian subgroup. However, the association was not significant between DR4 polymorphism A1322G with cancer risk in Caucasians (For A1322G, additive model: OR 1.085, 95%CI 0.931-1.289, p=0.217; dominant model: OR 1.379, 95%CI 0.934-2.035, p=0.311; recessive model: OR 1.026, 95%CI 0.831-1.268 p=0.429.). In summary, our finding suggests that DR4 polymorphism C626G and A683 rather than A1322G are associated with cancer risk in Caucasians.

Association between Laryngeal Squamous Cell Carcinoma and Polymorphisms in Tumor Necrosis Factor Related Apoptosis Induce Ligand (TRAIL), TRAIL Receptor and sTRAIL Levels

Verim, Aysegul,Turan, Saime,Farooqi, Ammad Ahmad,Kahraman, Ozlem Timirci,Tepe-Karaca, Cigdem,Yildiz, Yemliha,Naiboglu, Baris,Ozkan, Nazli Ezgi,Ergen, Arzu,Isitmangil, Gulbu Aydinoglu,Yaylim, Ilhan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurring in the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway. Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngeal carcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution of DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotype in patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patients with early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might be associated with progression of laryngeal cancer in the Turkish population.

Inhibitory Effect of Snake Venom Toxin on Colorectal Cancer HCT116 Cells Growth through Induction of Intrinsic or Extrinsic Apoptosis

김경태,송호섭 대한침구의학회 2013 대한침구의학회지 Vol.30 No.1

I investigated whether snake venom toxin(SVT) from Vipera lebetina turanica enhances the apoptosis ability of tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) in cancer cells. TRAIL inhibited HCT116 cell growth in a dose-dependent manner. Consistent with cell growth inhibition, the expression of TRAIL receptors; DR4 and DR5 was significantly increased as well as apoptosis related proteins such as cleaved caspase-3, 8, 9 and Bax. However, the expression of survival proteins(eg, cFLIP, survivin, XIAP and Bcl2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the reactive oxygen species(ROS) scavenger N-acetylcysteine reduced the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the apoptosis related protein such as caspase-3 and-9 as well as cell growth inhibitory effects. The collective results suggest that SVT facilitates TRAIL-induced apoptosis in human colorectal cancer HCT116 cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS pathway signals.