Kim, Gi-Beom;Kim, Jae-Ryong;Ahn, Myun-Hwan;Seo, Jae-Sung
Journal of Yeungnam Medical Science
/
v.24
no.2
/
pp.262-274
/
2007
Purpose : Bone morphogenetic proteins (BMPs) play an important role in the formation of cartilage and bone, as well as regulating the growth of chondroblasts and osteoblasts. In this study, we investigated whether recombinant human BMP adenoviruses are available for ex vivo gene therapy, using human fibroblasts and human bone marrow stromal cells in an animal spinal fusion model. Materials and Methods : Human fibroblasts and human bone marrow stromal cells were transduced with recombinant BMP-2 adenovirus (AdBMP-2) or recombinant BMP-7 adenovirus (AdBMP-7), referred to as AdBMP-7/BMSC, AdBMP-2/BMSC, AdBMP-7/HuFb, and AdBMP-2/HuFb. We showed that each cell secreted active BMPs by alkaline phosphatase staining. Since AdBMP-2 or AdBMP-7 tranducing cells were injected into the paravertebral muscle of athymic nude mice, at 4 weeks and 7 weeks, we confirmed that new bone formation occurred by induction of spinal fusion on radiographs and histochemical staining. Results : In the region where the AdBMP-7/BMSC was injected, new bone formation was observed in all cases and spinal fusion was induced in two of these. AdBMP-2/BMSC induced bone formation and spinal fusion occurred among one of five. However, in the region where AdBMP/HuFb was injected, neither bone formation nor spinal fusion was observed. Conclusion : The osteoinductivity of AdBMP-7 was superior to that of AdBMP-2. In addition, the human bone marrow stromal cells were more efficient than the human fibroblasts for bone formation and spinal fusion. Therefore, the results of this study suggest that AdBMP-7/BMSC would be the most useful approach to ex vivo gene therapy for an animal spinal fusion model.
Background: TRAIL is a cytokine that selectively induces apoptosis in various cancer cell lines. Gefitinib is new targeted drug applied in lung cancer that selectively inhibits EGFR tyrosine kinase. However, lung cancers have shown an initial or acquired resistance to these drugs. This study examined the effect of IGF-1R and its blockade on enhancing the sensitivity of lung cancer cell lines to TRAIL and gefitinib. Methods: Two lung cancer cell lines were used in this study. NCI H460 is very sensitive to TRAIL and gefitinib. On the other hand, A549 shows moderate resistance to TRAIL and gefitinib. The IGF-1R blockade was performed using adenoviruses expressing the dominant negative IGF-1R and shRNA to IGF-1R and AG1024 (IGF-1R tyrosine kinase inhibitor). Results: The adenovirus expressing dominant negative IGF-1R(950st) induced the increased expression of defective IGF-1R on the lung cancer cell surface, and the adenovirus-shIGF-1R effectively decreased the level of IGF-1R expression on cell surface. The genetic blockade of IGF-1R by the adenovirus-dnIGF-1R and AG1024 increased the sensitivity of A549 cells to TRAIL. The reduction of IGF-1R by transduction with ad-shIGF-1R also increased the sensitivity of the A549 cells to gefitinib. Conclusion: The blockade of IGF-1R through various mechanisms increased the sensitivity of the lung cancer cell line that was resistant to TRAIL and gefitinib. However, further studies using other cell lines showing acquired resistance as well as in vivo animal experiments will be needed.
Lee, Na Young;Park, Ji Hyun;Kim, Gil Hyun;Jung, Jin Hwa;Cho, Kyung Soon;Kim, Sung Mi
Pediatric Infection and Vaccine
/
v.10
no.1
/
pp.87-94
/
2003
Purpose : Respiratory viruses are one of the most infectious agent in human. Acute lower respiratory tract infection(ALRTIs) is associated with significant morbidity and mortality in children. This study is performed to investigate the etiologic organism, age and sex distribution, clinical manifestations and seasonal occurrence of ALRTIs in children. Methods : Viral agent was evaluated with nasopharyngeal aspirates, rhinorrhea and saliva collected from 568 patients. We confirmed viral agents in 54 patients who were younger than 15 year old. They had visited Maryknoll Hospital, Busan in Korea from January, 2002 to December, 2002 for ALRTIs. Results : The viral pathogens identified were Influenza A virus(59.3%), Enterovirus(33.3%), Adenovirus(5.6%), and Influenza B virus(1.9%). Parainfluenza virus and Respiratory syncytial virus were not detected. The occurrence of acute lower respiratory infections was high between 3 & 6 years old. The clinical patterns include pneumonia(51.9%), bronchitis(31.5%), croup(9.3%), bronchiolitis(7.4%). The respiratory viral agents had their characteristic seasonal patterns. Conclusion : Influenza A virus was the most common cause of acute lower respiratory tract infections in Busan area during the 2002. ALRTIs had high occurrence between 3 to 6 years old. And the most common clinical patterns were pneumonia and bronchitis.
Kim, Chang-Hyen;Kim, Jin-Woo;Kim, Myung-Jin;Pyo, Sung-Woon
Maxillofacial Plastic and Reconstructive Surgery
/
v.27
no.2
/
pp.103-109
/
2005
In spite of the ongoing advances, standard therapies for oral cancer still has some limitations in efficacy and in ability to prolong survival rate of advanced disease and result in significant functional defect and severe cosmetic deformity. Currently gene therapy using tumor suppressor gene is considered as a potent candidate for new therapeutic approaches that can improve efficacy and reduce complications. The purpose of this research is to identify the role of adenoviral vector to transfer HCCS-1 tumor suppressor gene in oral cancer cells and to find out whether there is a possibility for it to serve in the field of gene therapy. The human SCC-25 cell line was used for transfection. To determine the efficiency of the adenovirus as a gene delivery vector cell line was transduced with LacZ gene and analysed with X-gal staining. Northern blot was performed to confirm the tranfection with HSCC-1 gene and cell viability was assessed by cell cytotoxicity assay. We had successfully construct the recombinant HSCC-1 adenovirus(Ad5CMV-HCCS-1). DNA extracted from Ad5CMV-HCCS-1 revealed HCCS-1 gene is incorporated. The transduction efficiencies were over than 50% of SCC-25 cells with a MOI of 2 and over 95% with a MOI of 50. Northern blot analysis showed that a single 0.6kb mRNA transcript was expressed in Ad5CMV-HCCS-1 transduced SCC-25 cells. There was no or very low transcription HCCS-1 mRNA in wild and Ad5CMV-LacZ transduced SCC-25 cells. Cells transduced with Ad5CMV-HCCS-1 showed significant growth inhibition. By day 6, Ad5CMV-HCCS-1 treated cell count was decreased to 30% of mock-infected cells, while that of Ad5CMV-LacZ treated cells was 90% of mock-infected cells (p<0.05). Finally, these result suggest that the Ad5CMV-HCCS-1 has potential as a gene therapy tool for oral cancer.
Kim, Mi-Suk;Kwon, Hee-Chung;Kang, Hee-Seog;Park, In-Chul;Rhee, Chang-Hun;Kim, Chang-Min;Lee, Choon-Taek;Hong, Seok-Il;Lee, Seung-Hoon
Journal of Korean Neurosurgical Society
/
v.29
no.4
/
pp.471-476
/
2000
Objective : p16/INK4a, a kind of tumor suppressor genes, encodes a specific inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. This prevents the association of CDK4 with cyclin D1, and subsequently inhibits phosphorylation of retinoblastoma tumor suppressor protein(pRb), thus preventing exit from the G1 phase. According to previous reports, over 50% of glioma tissue and 80% of glioma cell lines have been demonstrated inactivation of p16/INK4a gene. The purpose of this study was to determine whether recombinant adenovirus-p16 virus is a suitable candidate for gene replacement therapy in cases of glioma. Methods : Three human glioma cell lines(U251MG, U87MG and U373MG) that express mutant p16 protein were used. Replication-deficient adenovirus was utilized as an expression vector to transfer exogenous p16 cDNA into the cells ; control cells were infected with the Ad-${\beta}$-gal expressing ${\beta}$-galactosidase. To monitor gene transfer and the expression of exogenous genes, we used Western Blotting analysis. Flow cytometry studies of cellular DNA content were performed to determine the cell cycle phenotype of the glioma cells before and after treatment. Results : We showed here that restoration of p16/INK4a expression in p16 negative U87MG, U251MG and partially deleted U373MG by Ad-CMV-p16 induced growth suppression in vitro. Flow cytometric study revealed that Ad-CMV-p16 infected U87MG cells were arrested during the G0-G1 phase of the cell cycle. Expression of p16 transferred by Ad-CMV-p16 in glioma cells was highly efficient and maintained for more than seven days. Conclusions : Our results suggest that Ad-CMV-p16 gene therapy strategy is potentially useful and warrants further clinical investigation for the treatment of gliomas.
Lee, Hyeon Seung;Choe, Young June;Cho, Eun Young;Lee, Hyunju;Choi, Eun Hwa;Lee, Hoan Jong
Pediatric Infection and Vaccine
/
v.21
no.3
/
pp.207-213
/
2014
Purpose: This study aimed to investigate the association between respiratory virus infection and pneumococcal colonization in children. Methods: From May 2009 to June 2010, nasopharyngeal (NP) aspirates were obtained from patients under 18 years old who visited Seoul National University Children's Hospital for respiratory symptoms. NP samples were used to detect respiratory viruses (influenza virus A and B, parainfluenza virus 1, 2 and 3, respiratory syncytial virus A and B, adenovirus, rhinovirus A/B, human metapneumovirus, human coronavirus 229E/NL63 and OC43/HKU1) by RT-PCR and pneumococcus by culture. Results: Median age of the patients was 27 months old. A total of 1,367 NP aspirates were tested for respiratory viruses and pneumococcus. Pneumococcus was isolated from 228 (16.7%) of samples and respiratory viruses were detected from 731 (53.5%). Common viruses were rhinovirus (18.4%), respiratory syncytial virus (RSV) A (10.6%), adenovirus (6.9%), influenza virus A (6.8%). Pneumococcal isolation rate was significantly higher in the cases of positive virus detection than negative detection [21.3% (156/731) vs. 11.3% (72/636), P <0.001]. For individual viruses, pneumococcal isolation rate was positively associated with detection of influenza virus A [24.7% (23/93) vs 16.1% (205/1274), P=0.001], RSV A [28.3% (41/145) vs 15.3% (187/1222), P=0.001], RSV B [31.3% (10/32) vs 16.3% (218/1335), P=0.042], rhinovirus A/B [22.6% (57/252) vs 15.3% (171/1115), P=0.010]. Conclusion: The study revealed that pneumococcal isolation from NP aspirates is related with respiratory virus detection. The result of this study could be used to investigate how respiratory viruses and pneumococcus cause clinical diseases.
Kim, Hye-Ran;Yang, Eun Ju;Chang, Jeong Hyun;Chang, Kyung-Soo
Journal of Life Science
/
v.30
no.3
/
pp.221-229
/
2020
Distylium racemosum is an evergreen tree growing wild on Jeju Island, which has been reported to exert biological activity. Obesity is induced by genetic, metabolic, environmental, and other factors. Among these, certain bacterial and viral infections have been shown to cause obesity, which is known as infectobesity. Human adenovirus (HAdV)-36 is one of the viruses that are known to cause infectobesity in humans. Unlike extensive research on preventing obesity and developing anti-obesity drugs, little research has been conducted specifically on the prevention and treatment of infectobesity. Therefore, this study aimed to evaluate the effects of phytochemicals from D. racemosum on the replication of HAdV-36. A549 cells infected with HAdV-36 were treated with an ethyl acetate fraction of a D. racemosum leaf extract (DRE), and the virus titer was calculated based on the hemagglutination (HA) titer. The results showed a concentration-dependent inhibitory effect of DRE treatment on HA titers. DRE treatment was also found to inhibit the cytopathic effects of the virus and the expression of viral genes. Quercitrin was identified as the constituent of DRE exerting an inhibitory effect on HAdV-36 replication. This study shows that DRE can be used as a candidate substance for the development of treatment for HAdV-36 infections. In addition, this study provides a basis to further investigate DRE for the development of anti-infectobesity medication.
Viruses are the most common cause of lower respiratory tract infections (LRTIs) in infants and young children and are a major public health problem in this age group. Viruses were identified in 54.9-70.4% of hospitalized infants and children with LRTIs in Korea. The viral pathogens identified included respiratory syncytial virus (RSV) A and RSV B, influenza (Inf) A, Inf B, parainfluenza (PIV)1, PIV2, human bocavirus (hBoV), human rhinovirus (hRV), adenovirus (ADV), human metapneumovirus (hMPV), human coronavirus (hCoV)-OC 43, hCoV-229E, hCoV-NL63, hCoV-HKU1, and human enterovirus (hEV). Coinfections with ${\geq}$2 viruses were observed in 11.5-22.8% of children. The occurrence of LRTIs was the highest in the first year of life. The specific viruses are frequently associated with specific clinical syndromes of LRTIs. LRTIs caused by RSV were predominant among younger infants. hRV accounted for a larger proportion of LRTIs in young infants than ADV and hBoV. hMPV was frequently detected in children >24 months old. The number of hMPV infections peaked between February and May, whereas hRV was detected throughout the year. Thus far, hCoV is a less common respiratory pathogen in cases of ALRI and URI in Korean children.
We performed RT-nested PCR to study the distribution of human enteric viruses in urban rivers in Korea. During 2002-2003, water samples were collected from four rivers in Gyeonggi Province, South Korea. Among 58 samples, 45 (77.6%), 32 (55.2%), 12 (20.7%), 2 (3.4%), 4 (6.9%), and 4 (6.9%) showed positive results with adenoviruses (AdVs), enteroviruses (EVs), reoviruses (ReVs), hepatitis A viruses (HAVs), rotaviruses (RoVs), and sapoviruses (SVs), respectively. According to the binary logistic regression model, the occurrence of each enteric virus, except ReVs and HAVs, was not statistically correlated with the water temperature and levels of fecal coliforms (P<0.05). AdVs were most often detected; only 4 samples (6.9%) were negative for AdVs while positive for other enteric viruses in the studied sites. Our results indicated that monitoring human enteric viruses is necessary to improve microbial quality, and that AdVs detection by PCR can be a useful index for the presence of other enteric viruses in aquatic environments.
Kim, Jae Kyung;Jeon, Jae-Sik;Kim, Jong Wan;Rheem, Insoo
Journal of Microbiology and Biotechnology
/
v.23
no.2
/
pp.267-273
/
2013
Multiplex RT-PCR was used to detect respiratory viruses in 5,318 clinical samples referred to the laboratory of a tertiary teaching hospital from December 2006 to November 2010. The acquired data were analyzed with respect to types, ratio, and co-infection trends of infected respiratory viruses. Trends in respiratory viral infection according to sex, age, and period of infection were also analyzed. Of the 5,318 submitted clinical samples, 3,350 (63.0%) specimens were positive for at least one respiratory virus. The infection rates were 15.8% for human rhinovirus, 14.4% for human respiratory syncytial virus A, 9.7% for human respiratory syncytial virus B, 10.1% for human adenovirus, 5.4% for influenza A virus, 1.7% for influenza B virus, 4.7% for human metapneumovirus, 2.3% for human coronavirus OC43, 1.9% for human coronavirus 229E/NL63, 3.7% for human parainfluenza virus (HPIV)-1, 1.1% for HPIV-2, and 5.3% for HPIV-3. The co-infection analysis showed 17.1% of double infections, 1.8% of triple infections. The median age of virus-positive patients was 1.3 years old, and the 91.5% of virus-positive patients were under 10 years old. Human respiratory syncytial virus was the most common virus in children < 5 years of age and the influenza A virus was most prevalent virus in children over 5 years of age. These results help in elucidating the tendency of respiratory viral infections.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.