• Title/Summary/Keyword: TARGETED

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Natural Products for Cancer-Targeted Therapy: Citrus Flavonoids as Potent Chemopreventive Agents

  • Meiyanto, Edy;Hermawan, Adam;Anindyajati, Anindyajati
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.427-436
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    • 2012
  • Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction.Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer.

Cost-Effectiveness Analysis of HPV Vaccination: Comparing the General Population with Socially Vulnerable Individuals

  • Han, Kyu-Tae;Kim, Sun Jung;Lee, Seo Yoon;Park, Eun-Cheol
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8503-8508
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    • 2014
  • Background: After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. Materials and Methods: Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. Results: In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. Conclusions: The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea.

Long-term Clinical Course of a Korean Girl with β-ureidopropionase Deficiency (β-ureidopropionase 결핍증의 장기간의 임상경과 1례)

  • Song, Woo Sun;Park, Youngjin;Lee, Jun Hwa
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.17 no.1
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    • pp.18-23
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    • 2017
  • ${\beta}$-ureidopropionase deficiency (${\beta}$-UPD; OMIM # 613161) is a rare autosomal recessive inborn error of pyrimidine metabolism caused by mutations in the UPB1 gene and approximately 30 cases have been reported in the world. The clinical features of patients with ${\beta}$-UPD have been reported to vary from asymptomatic to severe developmental delays. However, the long-term clinical courses of patients with ${\beta}$-UPD have not yet been reported. A Korean girl was diagnosed with ${\beta}$-UPD at the age of 8 years and 10 months by targeted next-generation sequencing which was subsequently confirmed by Sanger sequencing. She had many clinical features such as poor oral feeding, failure to thrive, global developmental delay, microcephaly, frequent infection, and intractable epilepsy. She died suddenly of an unknown cause at the age of 11 years and 5 months. Here we report the long-term (i.e. lifelong) clinical aspects of a Korean patient with ${\beta}$-UPD.

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The Effects of Expectation-Performance, Experience and Feelings on the Festival Visitor's Satisfaction (지역축제의 기대성과, 체험 및 감정이 방문자 만족에 미치는 영향)

  • Jung, Hyung-Shik;Choi, Soow-A;Kim, Young-Shim
    • CRM연구
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    • v.2 no.1
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    • pp.33-52
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    • 2009
  • This research focused on the moderating role of the influence an expectation exerts on a performance by a regional festival and the experience to get visitor's feeling and satisfaction. A survey design was used for the last analysis targeted for the respondent who experienced an experience directly targeted for the regional where a regional festival is promoted actively targeted for the visitor. Results are show a positive influence on the expectation exerts on a performance of festival. In addition, it was confirmed that festival experience activity the role important to feeling and satisfaction of a visitor. We suggest, therefore, that it has to raise the efficiency of the strengthening of an experience program to raise an performance of festival participants and the festival manage to draw out the various feeling formation and satisfaction through participation customers' segmentation.

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A Research on Projects of Rental Housing and Vacant Housing Remodeling for Invigoration of the Small-scale Schools in Rural Villages, Jeju-do (제주도 농촌지역의 소규모학교 살리기를 위한 마을임대주택사업과 빈집 정비사업 현황고찰)

  • Byun, Kyeonghwa;Kim, Seung-Geun
    • Journal of the Korean Institute of Rural Architecture
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    • v.20 no.4
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    • pp.85-95
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    • 2018
  • This research aimed to identify transition process of invigoration project of the small-scale schools and status of promoting project of multi-family housing for rental and vacant housing remodeling in Jeju-do, Korea. The results are followings. First, invigoration project of the small-scale schools had been started in villages communities themselves and was institutionalized to local government. To invigorate the small-scale schools was started vacant housing remodeling first in the village itself from 1992. After twenty years had passed, the project was institutionalized to local government in 2013. Second, to enact ordinances about invigoration project of the small-scale schools is the accomplishment of participations and activities of residents who predicted decreasing the number of students in elementary schools. These activities have influenced their communities positively. Finally, to supply multi-family housing for rental or to remodel vacant housing is more effective in increasing residents through influx of students of elementary schools. The average number of students increased from 56.8 in 2013 to 73 in 2018 in 30 elementary schools targeted for invigoration project of the small-scale schools. In particular, the effect in schools targeted the project of rental housing is shown more than schools targeted the project in vacant housing remodeling. In addition, low ratio in the number of closed school is shown in Jeju-do.

Conditions for Selection of Targeted Colonies in the Primary Cells

  • Chang, Mi-Ra;Oh, Keon-Bong;Lee, Kyung-Kwang;Han, Yong-Mahn
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.55-55
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    • 2003
  • The random insertion of useful gene in genome has been a common method to produce transgenic animals. This method is inefficient for induction of high levels gene expression in transgenic animals. To improve this limit, we tried to develop the system which target the gene at the specific genomic region. Thus, in our experiment, the vector system to target the human thrombopoietin (TPO) gene was developed. Targeting vector including TPO, neo and DT genes was transfrcted into bovine embryonic fibroblasts (bEF) or bovine ear skin fibroblasts (bESF). First of all, we determined concentration of the geneticin (G418) for selection of transfected cell lines. Our results showed that 1200 and 900 $\mu\textrm{g}$/ml of G418 were the most proper for selection of transfscted bEF and bESF cells. In this study, lipofectamine was used as a transfection reagent. Thus, the proper ratio of DNA:lipofectamine for transfection was also required to elevate targeting efficiency in primary mammalian cells. Our result indicates that the most proper ratios of DNA:lipofectamine were 4:2 and 1:2 in bEF and bESF cells. According to the optimized these conditions, single colonies were picked following transfection and were analyzed by PCR. More than 90% of the single colonies have TPO gene. However, there were no colonies with targeted TPO at the specific genomic region. Therefore, further experiments to select the specifically targeted colonies and to find more efficient methods such as reducing selection time and shortening a size of TPO gene are required.

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Research Trends in University Library Information Services in Korea (국내 대학도서관 정보서비스 연구동향)

  • Rhee, Hey Young;Park, Hyun Young
    • Journal of the Korean Society for information Management
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    • v.33 no.3
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    • pp.219-238
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    • 2016
  • With the purpose of looking into the information service study tendency, targeted at university library, this performed a content analysis of the articles in print from 2006 to 2015 on major four academic journals of Library and Information Science. Investigation items were study number of information services, subsidiary themes classified with information service functions, study method, collection method, user object, and theory study vs. service study in reality. As a result, information service studies were performed more than other areas. Information service functions targeted at the study were that of information supply. Major subsidiary themes were electronic information service, information literacy instruction, and information (reference) services general. Major study methods were survey research method,, case study, and major material collection methods were questionnaire and web-based research methods. Major user studies were targeted at undergraduates, and service study in reality took a great share.

Online Gaming Regulations and Teenagers' Viewpoint : Examining reactance & Peer-Culture of the targeted group (온라인 게임 규제와 청소년의 시선 : 규제 대상자들의 반발심과 또래문화를 중심으로)

  • Yoon, Yeohong;Jo, Wooyong;Choi, Jeonghye;Chung, Yerim
    • The Journal of the Korea Contents Association
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    • v.16 no.11
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    • pp.223-239
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    • 2016
  • We study online gaming regulations and examine the reactance and attitude of the targeted group. To be specific, we focus on the 'Shutdown Law' due to its scope and magnitude of its influence. The Shutdown Law was enforced to prevent adolescence's immersion in or addiction to online gaming; however, its effectiveness has yet to reach a consensus. Our empirical findings show that the reactance to the regulation is stronger as game usage increases; surprisingly the effect of game usage on reactance weakens among the affected adolescence's group, compared to the adult counterpart. Furthermore, heavy users in the targeted group are more likely to play online gaming to mingle with their peers, and thus more likely to play other activities that friends participate in. These results suggest that online games play a role to cultivate peer-culture among adolescence and facilitate their communication.

Identification of causative mutations in patients with Leigh syndrome and MERRF by mitochondrial DNA-targeted next-generation sequencing

  • Hong, Hyun Dae;Kim, Eunja;Nam, Soo Hyun;Yoo, Da Hye;Suh, Bum Chun;Choi, Byung-Ok;Chung, Ki Wha
    • Journal of Genetic Medicine
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    • v.12 no.2
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    • pp.109-117
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    • 2015
  • Purpose: Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make their exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mitochondrial DNA (mtDNA) mutations in 2 Korean families with myoclonic epilepsy with ragged-red fibers (MERRF) and Leigh syndrome, respectively. Materials and Methods: Whole mtDNAs were sequenced by the method of mtDNA-targeted next-generation sequencing (NGS). Results: Two causative mtDNA mutations were identified from the NGS data. An m.8344A>G mutation in the tRNA-Lys gene (MT-TK) was detected in a MERRF patient (family ID: MT132), and an m.9176T>C (p.Leu217Pro) mutation in the mitochondrial ATP6 gene (MT-ATP6) was detected in a Leigh syndrome patient (family ID: MT130). Both mutations, which have been reported several times before in affected individuals, were not found in the control samples. Conclusion: This study suggests that mtDNA-targeted NGS will be helpful for the molecular diagnosis of genetically heterogeneous mitochondrial diseases with complex phenotypes.

Genetic Characterization of Molecular Targets in Korean Patients with Gastrointestinal Stromal Tumors

  • Park, Joonhong;Yoo, Han Mo;Sul, Hae Jung;Shin, Soyoung;Lee, Seung Woo;Kim, Jeong Goo
    • Journal of Gastric Cancer
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    • v.20 no.1
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    • pp.29-40
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    • 2020
  • Purpose: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST. Materials and Methods: Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs. Results: Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications. Conclusions: Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.