• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2915-2921
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• 2015

Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI with chemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trials are inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods: We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS), overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis, covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68-1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05-2.21], p=0.03). However, combination therapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62-0.88], p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic and predictive factors to find the group with the highest benefit of the combination strategy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9319-9325
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• 2014

Alkaloids are the most extensively featured compounds of natural anti-tumor herbs, which have attracted much attention in pharmaceutical research. In our previous studies, a mixture of major three alkaloid components (5, 6-dihydrobicolorine, 7-deoxy-trans-dihydronarciclasine, littoraline) from Hymenocallis littoralis were extracted, analyzed and designated as AHL. In this paper, AHL extracts were added to human liver hepatocellular cells HepG-2, human gastric cancer cell SGC-7901, human breast adenocarcinoma cell MCF-7 and human umbilical vein endothelial cell EVC-304, to screen one or more AHL-sensitive tumor cell. Among these cells, HepG-2 was the most sensitive to AHL treatment, a very low dose ($0.8{\mu}g/ml$) significantly inhibiting proliferation. The non-tumor cell EVC-304, however, was not apparently affected. Effect of AHL on HepG-2 cells was then explored. We found that the AHL could cause HepG-2 cycle arrest at G2/M checkpoint, induce apoptosis, and interrupt polymerization of microtubules. In addition, expression of two cell cycle-regulated proteins, CyclinB1 and CDK1, was up-regulated upon AHL treatment. Up-regulation of the Fas, Fas ligand, Caspase-8 and Caspase-3 was observed as well, which might imply roles for the Fas/FsaL signaling pathway in the AHL-induced apoptosis of HepG-2 cells.

• International Journal of Advanced Culture Technology
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• 제9권1호
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• pp.16-21
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• 2021

As the average age of national veterans has increased from 69 years old(2011) to 71 years old(since 2015) over the past five years, the overall medical service cost of veterans has increased by about 20%. The main cause of this phenomenon is 'ultra-aging', which accounts for 67% of veterans, while the proportion of health insurance patients aged 70 or older is 9%. Therefore, it is judged that the analysis of the trend of use of medical services at veterans hospitals in each region that is in charge of severe medical services of national veterans can serve as an opportunity to seek countermeasures for the severe medical system of national veterans. First of all, based on the details of major medical expenses (hospitalization, outpatient, pharmaceutical expenses) by region for the last 10 years(2010-2019), data significance was performed through a chi-square test, and the Central Veterans Hospital and Non-Central Veterans Hospital using EXCEL. 'Expected frequency' was calculated by year. By applying the CHITEST(observation frequency, expected frequency) function again, the p-value(p<0.05) was calculated, and the profit bias of each region's veterans hospital could be determined. The specific research method is for the last 10 years(2010-2019) for state-sponsored patients_outpatient treatment income, state-sponsored patients_hospitalization income, exempt patients_outpatients at the Central Veterans Hospital, Busan Veterans Hospital, Gwangju Veterans Hospital, Daegu Veterans Hospital, and Daejeon Veterans Hospital. A one-way analysis of variance was conducted to verify the significance of the difference between group averages on the status of 5 medical revenues of veterans hospitals in each of the 5 regions, including medical treatment income, reduced patients_hospitalization income, and reduced patients_medicine expenses. It was found to be significant(p<0.05) at all levels, including region and type. Finally, the bias in the profit structure of regional veterans hospitals was the highest in 2017(p=0.0004) and the lowest in 2013(p=0.0349). In addition, in the profit structure of the Veterans Hospital, the year in which the'regional' variable worked the most was 2019, and the year with the least affected was 2010. The order of the former is Jungang(=31,674,713), Busan(=12,314,614), Gwangju(=11,957,038), Daegu(=10,168,015), and Daejeon(=6,991,034), and the order of the latter is Jungang(=57,868,791), and Busan(=19,183,194). Gwangju(=17,904,712), Daegu(=15,656,034), and Daejeon(=14,377,395). In conclusion, the profit bias of veterans hospitals repeatedly raced the lowest(p=0.01986) and highest(p=0.03499) for the past five years(2010-2014) year by year, with the 'regional' variable being the most in the veterans hospital's profit structure It was identified as a major influence factor. On the other hand, for the last 5 years (2015-2019), the influence factors of the'regional' variable every year were in 2015(p=0.02015), 2016(p=0.01741), 2017(p=0.00045), and 2018(p=0.00394). in 2019(p=0.00227), a significant difference was confirmed at a very low level.

• 의료법학
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• 제15권1호
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• pp.123-164
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• 2014

Under the new system of 'Separation of pharmaceutical prescription and dispensing' in Korea, which was implemented in 2000, physician could not dispense a medicine, and outpatient should have a physician's prescription filled at a drugstore. After pharmacist makes up outpatient's prescription, National Health Insurance Service(NHIS) pay for outpatient's medicine to pharmacist, except an outpatient's own medicine charge. And NHIS only pay for outpatient's prescription fee to physician and, physician doesn't derive profit from dispensing medicine in itself. Nevertheless, if physician writes out a prescription with violation of 'Criteria for the Medical Care Benefits', NHIS clawed back the payment of outpatient's prescription and medicine from the physician or the medical institution which the physician belongs to. In the past, NHIS's confiscation was in accordance with 'the National Health Care Insurance Act, Article 52, Clause 1'. But, since 2006 when the Supreme Court declared that there was no legal basis on the NHIS's confiscation of outpatient's medicine payment, NHIS had put in a claim for illegal prescriptions on the basis 'the Korean Civil law, Article 750(tort)'. So, Many medical institutions filed civil actions against NHIS. The key point of this actions was whether the issuing outpatient prescriptions with violations of Criteria for the Medical Care Benefits constitute of the law of tort. On this point, the first trial and the second trial took different position. Finally the Supreme Court acknowledged the constitution of the law of tort in 2013. In this paper, the author will review critically the decision of the Supreme Court, and consider the relativeness between the legal effect of Criteria for the Medical Care Benefits and the constitution of the issuing outpatient prescriptions with violations of Criteria for the Medical Care Benefits as the law of tort.

• 대한예방한의학회지
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• 제12권2호
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• pp.13-25
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• 2008

The purpose of this study was to investigate extract from mixed culture with Trichloloma matsutake mycelium in oriental medicine and cereal medium(OCM) to develop new material for pharmaceutical products and medicinal food for diabetes mellitus. To evaluate of hypoglycemic activity of OCM extracts, we examined the inhibitory activity of ${\alpha}$-glucosidasein OCM, blood glucose level and liver function of streptozotocin(STZ) induced diabetic rat. Experimental group was divided into 6 groups: first, it was divided into normal control group(hereafter NC group) and diabetes-induced group, and diabetes-induced group was subdivided into diabetic control group(DC group), treated by hot water extracts group(HE), ultra sonic waves, micro waves, and micro bubble extracts g roup(UE), crude polysaccharide of HE group (HEE) and crude polysaccharide of UE group(UEE) at a dose of 300mg/kg/body weight, respectively. In diabetic-induced groups, after streptozotocin was melted in 0.01M citrate buffer at 50mg/kg/body weight, when the non-fasting blood glucose levelwas 300 mg/dl or more in blood collected from the tail vein, it was regarded as diabetic induction and then such diabetic-induced experimental animals were used in this experiment. At the end of the experiment, blood glucose level increased by 4.19% in DC group but significantly decreased by 32.34%, 19.19%, 17.81% and 17.64%, respectively in UEEE, UE, HE, and HEE groups. In the cases of AST, ALT, and ALP, the experiment group treated with extracts showed significantly lowerblood glucose level than DC group. The levels of BUN and uric acid were found to be lower in the UMPM extract group(UE) than HW extract group(HE), which implies that herb medicine medium extracts in which Tricholoma matsutake mycelia were cultured are effective in reducing impaired liver function as well as high blood glucose level caused by diabetes. In addition, the administration of low temperature UMPM extracts was found to produce better results than that of high temperature hot water extracts. In this regard, it is expected that extracts from herb medicine obtained by cultivating Tricholoma matsutake mycelia will be widely used as new ingredients for foods and medicines for prevention and treatment of diabetes.

• 대한환경공학회지
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• 제28권11호
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• pp.1192-1197
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• 2006

입상 활성탄을 이용한 회분식 흡착실험과 연속식 흡착 컬럼 실험을 통해 이온성 및 비이온성 의약품의 제거특성을 평가하였다. 초기 혼합 의약품을 10 ${\mu}g/L$로 주입한 회분식 흡착실험의 경우 입상 활성탄을 500 mg/L로 하였을 때 대상 의약품은 $94{\sim}98%$ 이상의 높은 제거율을 보였다. 이온성 의약품은 pH가 감소할수록 흡착능이 증가하였으나 비이온성 의약품의 흡착능은 pH변화에 큰 영향을 받지 않았다. 이온성 의약품은 pH가 이온화 상수(pKa) 이하로 낮아짐에 따라 COOH형태로 비이온화되어 흡착이 용이하게 되지만 pH가 pKa 이상에서는 이온 상태의 $COO^-$로 존재하게 되어 흡착이 저하되기 때문이다. 또한 pH저하는 액상내 $H^+$ 증가 및 활성탄 표면에 양하전을 증가시켜 용액으로부터 이온성 의약품을 이온 결합에 의해 제거시킬 수 있기 때문이다. 40일간 흡착 컬럼을 연속 운전한 결과 15분의 공탑체류시간(EBCT)에서는 활성탄과 의약품의 충분한 접촉시간으로 대상 의약품에 대해 $93{\sim}99%$의 제거율을 얻었다. 짧은 EBCT의 운전조건에서는 이온성 의약품 가운데 CA, IBP 및 GFZ가 다른 이온성 및 비이온성 의약품에 비해 빠르게 파과에 도달했고 EBCT의 변화에 따른 흡착특성의 변화는 비이온성 의약품에서 더 크게 나타났다. 본 연구를 통해 기존 정수 처리공정을 통해 제거되기 어려운 의약품을 입상 활성탄 흡착공정을 통해 효과적으로 제어할 수 있음을 알 수 있었다.

• 한국응용과학기술학회지
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• 제36권2호
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• pp.592-599
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• 2019

This study is to stabilize insoluble and unstable active ingredient which is Idebenone (INCI name: hydroxydecyl ubiquinone) in a multi-lamellar vesicle (MLV) and to stabilize it in the skin care cosmetics. Idebenone is good effective raw material in the treatment of Alzheimer's disease in the medical field and a powerful antioxidant in dermatology. It is well known as a substance that inhibits the formation of melanin and cleans the skin pigment. However, it did not dissolve in any solvent and it was difficult to apply in cosmetic applications. Niosome vesicle was able to develop a nano-particle by making a multi-layer of idebenone encapsulated with a nonionic surfactant, hydrogenated lecithin and glycine soja (soybean) sterols and passing it through a high pressure microfluidizer. Idebenone niosome vesicle (INV) has been developed to have the ability to dissolve transparently in water and to promote transdermal penetration. The appearance of the INV was a yellowish liquid having specific odor, and the particle size distribution of INV was about 10~80 nm. The pH was 5~8 (mean=6.8). This capsulation with idebenone was stored in a $45^{\circ}C$ incubator for 3 months and its stability was observed and quantitatively measured by HPLC. As a result, the stability of the sample encapsulated in the niosome vesicle (97.5%) was about 66.3% higher than that of the non-capsule sample of 32.5%. Idebenone 1% INV was used for the efficacy test and clinical trial evaluation as follows. The anti-oxidative activity of INV was 38.2%, which was superior to that of 12.8% tocopherol (control). The melanin-reducing effect of B16 melanoma cells was better than INV (17.4%) and Albutin (control) (9.6%). Pro-collagen synthesis rate was 128.2% for INV and 89.3% for tocopherol (control). The skin moisturizing effect was 15.5% better than the placebo sample. The elasticity effect was 9.7% better than the placebo sample. As an application field, INV containing 1% of idebenone is expected to be able to develop various functional cosmetic formulations such as skin toner, ampoule essence, cream, eye cream and sunblock cream. In addition, it is expected that this encapsulated material will be widely applicable to emulsifying agents for skin use in the pharmaceutical industry as well as the cosmetics industry.

• 멤브레인
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• 제32권2호
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• pp.150-162
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• 2022

수처리 및 의약바이오 분야에서 유효물질 분리에 활용되고 있는 알루미나 중공사 분리막은 얇은 두께로 인해 취급 및 적용시 쉽게 파괴되는 단점이 있기 때문에 분리막의 강도를 100 MPa 이상으로 향상시키기 위한 연구가 필요하다. 본 연구에서는 나노입자의 함량을 0, 1, 3, 5 wt%로 증가시켰을 때 제조된 중공사 분리막의 특성을 평가하였다. 그 결과, 나노입자의 함량이 증가함에 따라 중공사 분리막의 강도는 79 MPa에서 115 MPa로 증가하였으며, 밀도는 1.76 g/m³에서 1.88 g/m³으로 증가하였고 기공률과 평균기공크기는 각각 51%에서 48%로, 416 nm에서 352 nm로 감소한 것을 확인하였다. 스폰지구조가 발달하고 스폰지구조의 기공크기가 향상된 알루미나 중공사 분리막은 100 MPa 이상으로 기계적 강도가 향상되었으며, 약 100000 GPU의 높은 질소 투과도 및 약 3000 L/m²h의 높은 물 투과도를 나타내었다. 따라서, γ-알루미나 나노입자를 소결조제로 첨가하는 것은 α-알루미나 중공사 분리막의 기계적 강도를 효과적으로 증진시키고 높은 투과성능을 유지할 수 있는 매우 유효한 방법임을 확인하였다.

• 생명과학회지
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• 제33권1호
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• pp.91-101
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• 2023

박테리오신은 리보솜에서 합성된 항균 펩타이드로, 박테리아에 의해 생성되어 유사하거나 밀접한 관련이 있는 박테리아 균주의 성장을 억제한다. 니신이 처음 발견된 이래로, 독특한 구조와 다양한 항균활성 방식을 가진 많은 박테리오신들이 기술되었고, 생산, 분비, 면역을 암호화하는 유전자들이 보고되었다. 니신은 치즈와 액체 달걀, 소스, 통조림 식품에 적용되는 박테리오신 중 하나이다. 많은 Bacillus 속 박테리오신들은 변역 후 변형된 펩타이드인 란티바이오틱스에 속한다. 다른 속의 Bacillus는 또한 많은 다른 비-란티바이오틱스 박테리오신을 생산한다. Bacillus 속 박테리오신은 때때로 더 넓은 항균 스펙트럼 때문에 더욱 중요해지고 있다. 박테리오신은 식품 및 제약 산업에서 식품 부패 및 병원성 세균 증식을 방지하기 위한 매력적인 화합물로 간주된다.박테리오신은 식품계에서 다양한 방식으로 생물학적 방부제로 사용될 수 있다. 생물 보존은 미생물 및/또는 그 대사산물을 사용하는 식품의 유통기한 연장 및 안전성 향상을 의미한다. 새로운 항균 화합물에 대한 수요는 식품 미생물학적 안전성을 향상시킬 수 있는 새로운 기술에 대한 큰 관심을 가져왔다. 박테리오신의 응용은 식품에서 인간의 건강으로 확대되고 있다. 오늘날 많은 연구자들은 박테리오신에 대한 관심을 식품보존에서 감염과 항생제 내성 질병을 유발하는 박테리아의 처리로 전환하고 있는 추세이다. 박테리오신 연구의 이 흥미로운 새로운 시대는 의심할 여지없이 새로운 발명과 새로운 응용으로 이어질 것이다. 이 리뷰에서 우리는 Bacillus 속에 의해 생산되는 박테리오신의 다양한 특성과 응용을 요약한다.

• Journal of Ginseng Research
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• 제47권3호
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.