• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7045-7056
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• 2013

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

• 정신신체의학
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• 제7권2호
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• pp.263-273
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• 1999

두통은 인류의 가장 흔한 호소 중의 하나로 임상에서 흔히 보는 장애이다. 두통은 뇌막염, 뇌출혈, 또는 뇌종양과 같은 다른 질환의 증상일수 있으나, 또한 편두통이나 군발두통 등과 같은 질병 자체로 표현된다. 일차적으로 두통 장애의 역학이나 국제 두통학회의 진단기준을 이해하고 흔치 않으나 심각한 이차적인 두통장애와 감별에 관심을 둬야 한다. 환자가 일차 두통장애의 기준에 맞으면 신경학적 진단검사의 보충이 없어도 치료를 시작한다. 두통 유형, 표현 양상, 동통기간과 강도 등에 따라 진통소염제나 혼합진통제, 혈관작용의 항편두통 약물 또는 신경이완제나 corticosteroid등을 선택한다. 편두통의 빈도와 강도에 따라 예방치료가 보통 4~6개월간 조절한다. 긴장형 두통은 발작성과 만성두통으로 구분되나 치료적으로는 급성완화와 예방치료로 시도된다. 많은 만성매일두통 환자들이 진통제나 ergotamine을 과용하고 있으며 그들의 의존성과 내재된 갈등조절, 수면장애, 우울등으로 과용된 약물의 제한이 쉽지 않다. 치료의 첫단계는 약물을 끊고 조심스럽게 대치요법을 시행한다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제30권2호
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• pp.143-149
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• 2004

Background: Some clinical trials have reported that a new analgesic combination of tramadol and acetaminophen provides good efficacy in various pain models. For the more clinical uses of this agent, comparisons about the onset of analgesia and analgesic efficacy in the acute state of pain with the other drugs known as strong analgesics were needed. Purpose: The goal of this study was to compare the times to onset of analgesia and the other analgesic efficacy of 75 mg tramadol/650 mg acetaminophen and 20 mg codeine/500 mg acetaminophen/400 mg ibuprofen in the treatment of acute pain after oral surgery. Patients and Methods: Using a randomized, single-dose, parallel-group, single-center, and active-controlled test design, this clinical study compared the times to onset of analgesia using a two-stopwatch technique and the other analgesic efficacy of the single-dose tramadol/acetaminophen and codeine/acetaminophen/ibuprofen. These were assessed in 128 healthy subjects with pain from oral surgical procedures involving extraction of one or more impacted third molars requiring bone removal. From the time of pain development, the times to onset of perceptible and meaningful pain relief, pain intensity, pain relief, an overall assessment, and adverse events of the study medications were recorded for 6 hours. Results: The demographic distribution and baseline pain data in the two groups were statistically similar. The median times to onset of perceptible pain relief were 21.0 and 24.4 minutes in the tramadol/acetaminophen and codeine/acetaminophen/ibuprofen groups respectively and those to onset of meaningful pain relief were 56.4 and 57.3 minutes, which were statistically similar. The other efficacy variables such as mean total pain relief (TOTPAR) and the sum of pain intensity differences (SPID) were also similar in the early period after pain development and drug dosing. The safety of tramadol/acetaminophen was well tolerated and very comparable to that of codeine/acetaminophen/ibuprofen. Conclusions: In this acute dental pain model, the onset of analgesia and analgesic efficacy of tramadol/acetaminophen was comparable to that of codeine/acetaminophen/ibuprofen. These results showed that tramadol/acetaminophen was recommendable for fast and effective treatment in the management of postoperative acute pain.

• 한국의사학회지
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• 제26권2호
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• pp.175-185
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• 2013

Purpose : The current Medical Law and the Pharmaceutical Affairs Act, which are incapable of utilizing the research results and the advanced academic, clinical, and pharmaceutical system of the present-day Korean (Oriental) medicine, have limitations and create a paradox by provoking social conflict among the professionals in the field. The aim of this study was to find out the legal and systematic problems that contributed to a complicated conflict amongst Korean (Oriental) medicine doctors, doctors, pharmacists, and Korean (Oriental) pharmacists regarding the classification of their functions. Methods : We reviewed the history and characteristics of the legislation regarding the duties of Korean (Oriental) medicine doctors and Korean (Oriental) pharmacists as well as the relevant and important public health policies since the enactment of the National Medical Services Law in 1951. We focused on the laws and regulations that are made in the process of the separating functions of physicians and pharmacists and the dispute between the Korean (Oriental) medicine doctors and the Korean (Oriental) pharmacists in the 1990s and 2000s. Results : The legislations and amendments of the medical and pharmaceutical laws and regulations that reflect the modern academic, clinical, and pharmaceutical system of the Korean (Oriental) medicine and the research results could be summarized as follows: 1) A partial amendment of the Medical Law in 1987, which added the provision of "Oriental health guidance" as one of the duties of Korean (Oriental) medicine doctors, assured a place for Korean (Oriental) medicine doctors in the field of public health. 2) A partial revision of Pharmaceutical Affairs Act in 1994 established a new system for Korean (Oriental) pharmacists, bringing about the creation of dualistic pharmaceutical system that complements the dualistic medical system. 3) The Promotion of the Research and Development of Wonder Drugs by Using Natural Substances Act was legislated in 2000 in order to stimulate research and development of Korean (Oriental) medicine and its industrialization. 4) Oriental Medicine Promotion Act in 2003 was enacted to lay foundation to specify and promote technology and industry that are related to Korean (Oriental) medicine. Discussions and conclusions : Although the dualistic medical and pharmaceutical system is set up by the Medical Law and Pharmaceutical Affairs Act, it is shown that the relevant regulations have been developed from a perspective of the western medicine.

• 의료법학
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• 제13권2호
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• pp.11-38
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• 2012

The Supreme Court stand in the position in specific lawsuit that it doesn't allow the discretionary not covered service, but recently in revocation suit of fine disposal that is imposed on medical fee of leukemia patient, it altered the existing adjudgement and admitted the discretionary not covered service exceptionally. It put forward the allowable condition roughly in that case. According as this alteration, it has become more important to embody the allowance conditions of exceptions. The Supreme Court presented three things, which are procedural condition, medical condition and subscriber's agreement. Concerning procedural condition, several present conciliation procedures are as follows: medical care benefit arret request, relative value conciliation etc, prior request on anti-cancer drug among chemicals which exceed acceptance criteria, request of non benefit object on common drugs. To be granted the existence of those system, there should be no obstacle to use that. Even if it were so, we should take circumstances into consideration; individual situation is unescapable concerning substance and urgency of the discretionary not covered service, process of the procedure, time required etc. Regarding medical condition, safety and effectiveness will be verified through evaluation procedures of new medical skill. About the necessity, the Supreme Court made clear through a sentence that it allow the discretionary not covered service, in case that needs to treat a patient out of the standard of medical benefit. Strict interpretation is right and it answer the purpose of the sentence that the supreme court permit the discretionary not covered service, exceptionally. We need to differentiate medical necessity and medical validity. Subscriber's agreement should holds true if it entails full explanation, and if it is preliminary, explicit and individual. On this account, it should be difficult to admit that someone agree effectively when he call for the affirmation that he is recipient of medical care. Reasonable expense needs to be a part of review whether the agreement is valid. Meanwhile If we adjust system of medical expense and eventually reorganize a fee for consultation payment system (Fee-for-service controlled by item to DRG (Diagnosis Related Groups)), controversial area of the discretionary not covered service will be decreased and that will guarantee the discretion of the doctor.

• 융합보안논문지
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• 제17권4호
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• pp.69-78
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• 2017

2001년 9월 11일 테러 이후 초국가적 범죄와 테러리즘의 증가로 인해 국경안보의 중요성이 강조됨에 따라 통합적인 CIQ 역량강화가 요구되고 있다. 미국, 캐나다, 호주는 CIQ를 통합하여 여행자 물품 출입국통제 강화 및 공항만 육로 국경보안에 중점을 둔 국경안보 활동을 강화하고 있다. 미국은 2003년 국토안보부 산하에 관세국경관리청(CBP)을 신설하였다. 캐나다도 2003년 공공안전부 산하에 국경보안청(CBSA)을 창설하였다. 호주도 2015년 이민국경보호부(DIBP) 산하로 관세국경보호청을 통합하고, 국경수비대(ABF)를 신설하였다. 그러나 CIQ 업무별 분산된 국경관리체계를 운영하고 있는 한국은 공항만 육로 국경에서 발생하는 불법 출입국, 테러분자 입국, 밀수입, 마약 총기류 밀거래 등 복합적인 국경위협에 통합적으로 대응하기 어렵다. 이를 해결하기 위해서 유사성이 높은 세관 및 검역 업무부터 순차적으로 통합하고, 중장기적으로 관세청이 출입국관리 업무를 위임받아 CIQ 업무 전체를 통합하는 방안도 검토해볼 수 있다. 또는 미국, 캐나다, 호주의 CIQ 단일책임기관을 한국의 실정에 맞게 벤치마킹하여 새로운 통합국경안보조직을 신설하는 방안도 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1001-1006
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• 2015

Background: With development and application of new and effective anti-cancer drugs, the median survival post-progression (SPP) is often prolonged, and the role of the median SPP on surrogacy performance should be considered. To evaluate the impact of the median SPP on the correlation between progression-free survival (PFS) and overall survival (OS), we performed simulations for treatment of four types of cancer, advanced gastric cancer (AGC), metastatic colorectal cancer (MCC), glioblastoma (GBM), and advanced non-small-cell lung cancer (ANSCLC). Materials and Methods: The effects of the median SPP on the statistical properties of OS and the correlation between PFS and OS were assessed. Further, comparisons were made between the surrogacy performance based on real data from meta-analyses and simulation results with similar scenarios. Results: The probability of a significant gain in OS and HR for OS was decreased by an increase of the SPP/OS ratio or by a decrease of observed treatment benefit for PFS. Similarly, for each of the four types of cancer, the correlation between PFS and OS was reduced as the median SPP increased from 2 to 12 months. Except for ANSCLC, for which the median SPP was equal to the true value, the simulated correlation between PFS and OS was consistent with the values derived from meta-analyses for the other three kinds of cancer. Further, for these three types of cancer, when the median SPP was controlled at a designated level (i.e., < 4 months for AGC, < 12 months for MCC, and <6 months for GBM), the correlation between PFS and OS was strong; and the power of OS reached 34.9% at the minimum. Conclusions: PFS is an acceptable surrogate endpoint for OS under the condition of controlling SPPs for AGC, MCC, and GBM at their limit levels; a similar conclusion cannot be made for ANSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1809-1817
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• 2012

Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.

• 대한의생명과학회지
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• 제13권4호
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• pp.251-261
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• 2007

A myofiber of skeletal muscle is composed of myofibrils, sarcolemma (plasma membrane), and constameres, which anchor the myofibrils to the sarcolemma. Achvillin is a recently identified F-actin binding muscle protein, co-isolates with dystrophin and caveolin-3 in low-density sarcolemma of striated muscle, and colocalizes with dystrophin at costameres, the specialized adhesion sites in muscle. Archvillin also binds to nebulin and localizes at myofibrillar Z-discs, the lateral boundaries of the sarcomere in muscle. However other roles of archvillin on the dynamics of myofibrillogenesis remain to be defined. The goal of this study is, by using siRNA-mediated gene silencing technique, to investigate the effect of archvillin on the dynamics of myofibrillogenesis in cell culture of a mouse skeletal myogenic cell line (C2C12), where presumptive myoblasts withdraw from the cell cycle, fuse, undergo de novo myofibrillogenesis, and differentiate into mature myotubes. The roles of archvillin in the assembly and maintenance of myofibril and during the progression of myofibrillogenesis induced in skeletal myoblast following gene silencing in the cell culture were investigated. Fluorescence microscopy demonstrated that the distribution of archvillin was changed along the course of myofibril assembly with nebulin, vinculin and F-actin and then located at Z-lines with nebulin. Fluorescence microscopy demonstrated that knockdown of mouse archvillin expression led to an impaired assembly of new myofibrillar clusters and delayed fusion and myofibrillogenesis although the mouse archvillin siRNA did not affect those expressions of archvillin binding proteins, such as nebulin and F-actin. This result is corresponded with that of RT-PCR and western blots. When the perturbed archvillin was rescued by co-transfection with GFP or Red tagged human archvillin construct, the inhibited cell fusion and myotube formation was recovered. By using siRNA technique, archvillin was found to be involved in early stage of myofibrillogenesis. Therefore, the current data suggest the idea that archvillin plays critical roles on cell fusion and dynamic myofibril assembly.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2002년도 추계학술대회
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• pp.162-172
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• 2002

Schizosaccharomyces pombe is suited for the study of cytokinesis as it divides by forming a septum in the middle of the cell at the end of mitosis. To enhance our understanding of the cytokinesis, we have carried out a genetic screen for temperature-sensitive S. pombe mutants that show defects in septum formation and cell division. Here we present the isolation and characterization of a new temperature-sensitive mutant, sun1(septum uncontrolled), which undergoes uncontrolled septation during cell division cycle at restrictive temperature $(37^{\circ}C)$. In sun1 mutant, actin ring and septum are positioned at random locations and angles, and nuclear division cycle continues. These observations suggest that the sun] gene product is required for the proper placement of the actin ring as well as precise septation. The sun] mutant is monogenic recessive mutation unlinked to previously known various cdc genes of S. pombe. In a screen for $sunl^+$ gene to complement the sun] mutant, we have cloned a gene, $susl^+$(suppressor of sun1 mutant), that encodes a protein of 689 amino acids. The predicted amino acid sequence of $susl^+$ gene is similar to the human hMadlp and Saccharomyces cerevisiae Mad1p, a component of the spindle checkpoint in eukaryotic cells. The null mutant of $susl^+$ gene grows normally at various temperatures and has the increased sensitivity to anti-microtubule drug, while $susl^+$ mutant shows no sensitivity to microtubule destabilizing drugs. The putative S. pombe Sus1p directly interacts with S. pombe Mad2p in yeast two-hybrid assays. These data suggest that the newly isolated susr gene encodes S. pombe Mad1p and suppresses sun] mutant defective in controlled septation in a cell division cycle.