EGFR 돌연변이와 ROS1 전위를 동시에 가진 폐선암 환자의 Erlotinib 치료 1예

김민환,박예현,박혜정,지아영,송창호,진무년,김영주,김선욱,이중희,김인수,김혜련,김주항,조병철 Ewha Womans University School of Medicine 2014 EMJ (Ewha medical journal) Vol.37 No.1

The rearrangement of c-ros oncogene 1 (ROS1) has been recently identified as an important molecular target in non small cell lung cancer (NSCLC). ROS1 rearrangement and epidermal growth factor receptor (EGFR) mutation were mutually exclusive each other in previous studies, and the clinical implication of co-existence of the two genetic alterations has not been determined. We report a case of 46-year-old female never-smoker NSCLC patient whose tumor harbored ROS1 rearrangement and EGFR mutation concomitantly. She had undergone curative surgery for stage IIIA NSCLC, and the recurrence in left pleura and brain occurred at 2 years after the surgery. She received several lines of chemotherapy including docetaxel plus carboplatin, erlotinib, pemetrexed, and gemcitabine. Erlotinib therapy showed a favorable treatment response with progression-free survival of 9.5 months and partial response of tumor on radiologic evaluations. This case represents a successful erlotinib treatment in a NSCLC patient with concurrent ROS1 rearrangement and EGFR mutation.

근적외선 유도 약물방출을 위한 키토산 미세입자의 제조와 평가

김민아 ( Min Ah Kim ),김미리 ( Miri Kim ),이창문 ( Chang-moon Lee ) 한국키틴키토산학회 2016 한국키틴키토산학회지 Vol.21 No.4

본 연구에서는 근적외선 레이저의 감응성 물질인 멜라닌과 5-FU를 함유한 키토산 미세입자를 제조하고 광열효과와 약물방출실험을 진행하고 다음과 같은 결과를 얻었다. 멜라닌과 5-FU를 함유한 키토산 미세입자는 W/O/W 방법을 통해 성공적으로 제조할 수 있었고, 미세입자는 구형이었으며 비교적 균일하였다. 키토산 미세입자를 농도별로(0.55~2.75 mg/mL) 증류수에 분산시켜 레이저(808 nm, 1.5 W/cm², 5 min)를 조사한 결과, 샘플의 농도와 조사시간이 증가할수록 온도의 변화가 크게 나타났다. 키토산 미세입자로부터 5-FU의 방출실험을 진행한 결과, 레이저를 조사하지 않은 그룹에 비해 레이저를 조사한 그룹에서 약물방출 속도가 증가하는 것을 알 수 있었고, pH 5.0에서 보다 큰 차이를 보였다. 위의 결과를 통해 근적외선을 이용하여 멜라닌을 함유한 키토산 미세입자로부터 약물 방출 속도를 조절할 수 있고 더 나아가 in vivo에서의 국소적 약물 전달 및 효과적인 치료방법으로 사용될 수 있을 것으로 기대할 수 있다. In this study, melanin and 5-fluorouracil (5-FU)-loaded chitosan microparticles were prepared and the drug release profiles from the microparticles were investigated under near infrared (NIR) 808 nm laser irradiation at 1.5 W/cm ² for 5 min. The chitosan microparticles were uniform and spherical in shape. After irradiation of NIR 808 nm laser at 1.5 W/cm² for 5 min, the temperature of the chitosan microparticle solution increased. As the concentration of the chitosan microparticles increases from 0.55 mg/mL to 2.75 mg/mL, the temperature of the microparticle solution increased with irradiation time. Under NIR 808 nm laser irradiation, 32.1±2.3% and 53.7±1.1% of 5-FU from the chitosan microparticles were released at pH 7.4 and 5.0, respectively. In other hand, without laser irradiation 23.9±1.6% and 26.9±2.0% of 5-FU were released from the chitosan microparticles at pH 7.4 and 5.0, respectively. All these results indicate that chitosan microparticles containing melanin could be used as a photo-induced drug release system.

VIP를 분비하며 신경절신경종의 분화를 가지는 갈색 세포종 1예

나민아,김상수,김동욱,최재훈,이태근,공옥녀,안준협,김지연,성한동,정철호,손석만,김인주,김용기 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.2

갈색 세포종은 신경내분비종양의 하나로 VIP를 포함한 다양한 신경내분비 펩타이드를 분비할 수 있다. 저자들은 만성 설사와 체중 감소를 주소로 내원한 환자에서 좌측 부신에 VIP를 생성하는 갈색 세포종을 진단하여 성공적으로 제거한 후 증상이 모두 호전된 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide, which may cause secretory diarrhea by stimulating the production of adenylate cyclase. Neuroendocrine tumors, secreting vasoactive intestinal peptide (VIP), are almost always of a pancreatic in origin. However, a pheochromocytoma may produce several neuropeptides, containing VIP, as they are considered to be neuroendocrine tumors. A 57-year-old woman, who presented with chronic watery diarrhea, hypokalemia, weight loss and a left adrenal mass, is described. Histologically, the tumor was diagnosed as a pheoch-romocytoma, with ganglioneuronal differentiation, and was histochemically confirmed to produce a vasoactive intestinal polypeptide. A left adrenal VIP-producing pheochromocytoma was successfully resected. After surgery, her diarrhea subsided and the electrolytes, affected neuroendocrine hormone levels, blood pressure and blood sugar level were normalized (J Kor SOC Endocrinol 18:227-231, 2003).

근적외선 레이저 반응성 광열-기포 생성 알지네이트 나노입자로부터 제어된 약물 방출

김현지 ( Hyunji Kim ),김민아 ( Min Ah Kim ),이창문 ( Chang-moon Lee ) 한국키틴키토산학회 2021 한국키틴키토산학회지 Vol.26 No.3

본 연구에서는 근적외선에 반응하는 알지네이트 기반 나노복합체를 제조하여 광열효과 및 버블생성으로 인한 약물 방출을 효과적으로 조절하고자 하였다. 제조된 AMP NPs의 평균 크기는 252.52 ± 0.39 nm로 측정되었고 구형의 형태를 나타내었다. 수용액 내에서의 침전이나 응집이 관찰되지 않았으며 7일 동안 사이즈의 큰 변화가 관찰되지 않았다. AMP NPs에 808 nm 레이저 조사 시 조사 시간 및 레이저 세기가 증가할수록 효과적인 온도 상승을 보였다. 생성된 열로 인해 PFH의 상전이를 유도하여 이에 따른 AMP NPs의 극적인 버블 생성을 초음파 영상으로 확인하였다. 약물 방출 평가에서 AMP NPs에 레이저 조사 시 약물 방출 속도를 향상시켰으며 반복적인 레이저 조사 시 순간적으로 약물의 방출이 증가하였다. 이러한 결과로부터, AMP NPs는 근적외선 반응성 약물 방출 조절제제로서의 가능성을 확인하였고, 이는 병변에서 테라노스틱 제제로 활용 될 수 있을 것으로 기대된다. In order to maximize the therapeutic effect of a drug, it is necessary to control the release rate of the drug or efficiently deliver it to an accurate target site. In this study, alginate-melanin-methotrexate-perfluorohexane nanoparticles (AMP NPs) were proposed for controlling the drug release by near-infrared (NIR) laser-responsive photothermalbubbling effect. AMP NPs had a uniform spherical shape with a size of 252.52 ± 0.39 nm and did not show precipitation in PBS buffer for 7 days. Based on the unique light-to-heat conversion properties of melanin, the temperature of AMP NPs rose to about 52.9℃ after irradiation with an 808 nm NIR laser with an intensity of 1.5 W/㎠ for 10 min. As the exotherm of melanin reached the phase transition temperature of perfluorohexane (PFH), microbubbles from the AMP NPs solution were generated dramatically. The release rate of methotrexate from AMP NPs increased to 61% after 24 h of laser irradiation due to the heat generation of melanin and bubble generation of PFH in AMP NPs. From these results, it is expected that AMP NPs can be utilized as promising carriers for controlled drug release.

A Comparative Experimental Study of the, In-vitro Efficiency of Hypertonic, Saline-Enhanced Hepatic Bipolar and, Monopolar Radiofrequency Ablation

Lee, Jeong Min,Han, Joon Koo,Kim, Se Hyung,Sohn, Kyu Li,Lee, Kyoung Ho,Ah, Su Kyung,Choi, Byung Ihn Korean Radiological Society 2003 Korean Journal of Radiology Vol.4 No.3

HPLC를 이용한 Alnus속 식물에서의 diarylheptanoids의 정량분석

정동욱,김준식,조수민,이연아,김광호,김세원,이민원 중앙대학교 약학연구소 1999 약학 논총 Vol.13 No.-

Quantitative determination of diarylheptanoids (oregonin and hirsutanonol), which were characteristic components of Alnus spp. has been conducted by High Performance Liquid Chromatography. The HPLC analysis was carried out using an YMC J'sphere ODS-H80 column [150×4.6mm, S-4μm. 80A(particle)] and a combination of acetonitrile and H2O was used as mobile phase in gradient solvent system. The results showed differnce in the species (Alnus japonica, A hirsuta and A. hirsuta var. sibirica)

Comparisons of obstetrical outcomes among vaginal, intramuscular progesterone treatment and conservative management for the prevention of preterm birth in twin pregnancies with a short cervix

( Young Li Kim ),( Young Jae Lee ),( Hee Young Cho ),( Eun Ah Kim ),( Min Jung Baek ),( Young Ran Kim ),( Sukho Kang ),( Ji Yeon Lee ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

목적: To determine the differences in pregnancy outcomes among cases treated by vaginal progesterone, intramuscular(IM) progesterone and conservative management in twin pregnancies with a short cervix. 방법: This is a retrospective study of 273 twin pregnancies complicated by a short cervix(<2.5cm) who delivered from 2007 to 2016 in CHA Bundang Medical Center. Women who received cervical cerclage were excluded. Treatment groups included 1) group I; conservative management group without progesterone treatment(n=174), 2) group II; vaginal progesterone suppository group(n=30), 3) group III; IM progesterone injection group(n=69). Primary outcomes were spontaneous birth at <28, 32, 34, or 36 weeks of gestational age(GA). The secondary outcomes included hospitalized for tocolytics or antenatal corticosteroids, small for gestational age and low APGAR score(<7) at 5 min. 결과: Preterm birth before 36 weeks of GA was different among 3 groups(29.3%[51/174] vs.20.0%[6/30] vs.43.5%[30/69], p=0.034). Low APGAR score(<7) at 5min was significantly different among 3 groups(7.8%[27/348] vs.5.0%[3/60] vs.15.2%[21/138], p=0.018). After multivariate analysis, preterm birth(<36 weeks) occurred more frequently in group III than group I(aOR 6.90 95%CI:1.06-45.04, p=0.044). However, there was no significant difference between group II and III. Meanwhile, there were more cases with low APGAR score(<7) at 5 min in group III than group I(aOR 6.58 95%CI:1.43-30.21, p=0.015) and group II(aOR 17.04 95%CI:1.56-185.74, p=0.020) after multivariate analysis. 결론: In twin pregnancies complicated by short cervical length, IM progesterone group showed significantly greater occurrence of preterm birth before 36 weeks of GA in comparison with vaginal progesterone group and conservative management group.

In vivo study for the hemostatic efficacy and foreign body reaction of a new powder-type polysaccharide hemostatic agent

Yoonhyeong Byun,Eun Jin Kim,Areum Lee,Young-Ah Suh,Hee Ju Sohn,Jung Min Lee,Jae Seung Kang,Yoo Jin Choi,Youngmin Han,Hongbeom Kim,Wooil Kwon,Jin-Young Jang 대한외과학회 2022 Annals of Surgical Treatment and Research(ASRT) Vol.102 No.2

Purpose: Various hemostatic agents have been introduced in therapy as postoperative bleeding is a poor prognostic factor for postoperative outcomes. These products can be divided into those that directly promote the hemostatic cascade and those that physically form a barrier by absorbing blood. The latter, powder-type hemostatic agents have the advantages of being inexpensive and more absorbable with less foreign body reactions (FBRs) and are applicable to a relatively wide area. This study was conducted to verify the safety and efficacy of a newly invented polysaccharide product (OOZFIX, Theracion Biomedical), which improves blood absorption and hemostatic effects. Methods: Two separate animal experiments were performed. The first evaluated FBRs histologically at 3 days, 2 weeks, and 4 weeks, after implantation of OOZFIX in rats, and the second compared hemostatic performance of OOZFIX and Arista AH (Bard) in the porcine liver punch biopsy model. Results: We found minimal FBRs in the 3-day group and no reactions in both the 2-week and 4-week groups after implantation of hemostatic agents. The time to hemostasis of OOZFIX was not significantly different from that of Arista AH (median [interquartile range]: 9 [6–10] minutes vs. 8 [6–10] minutes, respectively; P = 0.522). When comparing the serial bleeding grade tendency, there was no statistical difference between OOZFIX and Arista AH (P = 0.656). Conclusion: OOZFIX caused a minimal FBR that disappeared within 2 weeks in vivo, and its hemostatic performance was comparable with that of an existing agent, Arista AH. Further clinical studies are required in the future.

대황의 항산화 효과 및 타이로시네이즈 저해 활성

김정은 ( Jung Eun Kim ),박찬하 ( Chan Ha Park ),오대석 ( Dae Seok Oh ),이승연 ( Seung Yeon Lee ),장세훈 ( Se Hun Jang ),홍지연 ( Jee Yeon Hong ),민혜진 ( Hye Jin Min ),박수아 ( Su Ah Park ),원두현 ( Doo Hyun Won ),박수남 ( Soo Nam 대한화장품학회 2011 대한화장품학회지 Vol.37 No.4

본 연구에서는 대황 추출물의 항산화 활성, 타이로시네이즈(tyrosinase) 저해 활성을 확인하였다. 대황의 50 % 에탄올 추출물, 에틸아세테이트(ethyl acetate) 분획, 아글리콘(aglycone) 분획으로 실험을 진행하였다. 대황 추출물들의 DPPH (1,1-diphenyl-2-picrylhydrazyl) 소거활성(FSC₅₀)은 대표적인 항산화제인 (+)-α-tocopherol보다 낮은 것으로 나타났다. Luminol 발광법을 이용한 Fe³⁺-EDTA/H₂O₂ 계에서 생성된 활성산소종에 대한 아글리콘 분획의 소거활성(총 항산화능, OSC₅₀)은 0.265 μg/mL로 매우 큰 활성을 나타내었다. 대황 추출물의 rose-bengal로 증감된 ¹O₂에 의한 적혈구 파괴에 대한 세포보호 효과는 모든 분획에서 농도 의존적(1∼50 μg/mL)으로 증가하였으며, 특히 아글리콘 분획은 10 μg/mL 농도에서 τ₅₀이 757.0 min으로 높은 세포 보호 활성을 나타내었다. 대황 추출물 중 아글리콘 분획의 타이로시네이즈 저해활성(IC₅₀)은 11.20 μg/mL으로 226.88 μg/mL인 알부틴(arbutin)보다 큰 활성을 보여주었다. 이상의 결과들로부터 대황 추출물은 활성산소종을 소거하는 항산화제로 이용가능하며, 특히 아글리콘 분획의 현저한 항산화 작용 및 큰 타이로시네이즈 저해 효과로부터 이들 분획 또한 화장품원료로서 응용 가능성이 큼을 알 수 있었다. In this study, the antioxidative effects and inhibitory activities on tyrosinase of Rheum undulatum (R. undulatum) L. extracts were investigated. 50 % ethanol extract, ethyl acetate and aglycone fractions of R. undulatum L. were used in experiments. The DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging activities (FSC₅₀) of R. undulatum L. extracts was lower than (+)-α-tocopherol, known as a typical antioxidant. Reactive oxygen species (ROS) scavenging activities (OSC₅₀) of aglycone fraction on ROS generated in Fe³⁺-EDTA/H₂O₂ system using the luminol-dependent chemiluminescence assay showed the most prominent effect at a concentration of 0.265 μg/mL. The cellular protective effects of extract/fractions of R. undulatum L. on the rose-bengal sensitized photohemolysis of human erythrocytes were increased in a concentration dependent manner (1 ~ 50 μg/mL). Especially, aglycone fraction in 10 μg/mL concentration showed the most protective effect among extracts (τ₅₀, 757.0 min). The inhibitory effects (IC₅₀, 11.20 μg/mL) on tyrosinase of aglycone fraction was much higher than arbutin (226.88 μg/mL), known as a whitening agent. These results indicate that R. undulatum L. extracts can be used as antioxidant. Particularly, aglycone fraction of R. undulatum L. showed superior antioxdative activity and high inhibitory effect on tyrosinase. Therefore, aglycone fraction of R. undulatum L. could be applicable to new functional cosmetics.

Chlorpropamide 2-hydroxylation is catalysed by CYP2C9 and CYP2C19 <i>in vitro</i>: chlorpropamide disposition is influenced by CYP2C9, but not by CYP2C19 genetic polymorphism

Shon, Ji-Hong,Yoon, Young-Ran,Kim, Min-Jung,Kim, Kyoung-Ah,Lim, Young-Chae,Liu, Kwang-Hyeon,Shin, Dong-Hoon,Lee, Chung Han,Cha, In-June,Shin, Jae-Gook Blackwell Science Ltd 2005 British journal of clinical pharmacology Vol.59 No.5

<P>Aims</P><P>We evaluated the involvement of cytochrome P450 (CYP) isoforms 2C9 and 2C19 in chlorpropamide 2-hydroxylation <I>in vitro</I> and in chlorpropamide disposition <I>in vivo</I>.</P><P>Methods</P><P>To identify CYP isoforms(s) that catalyse 2-hydroxylation of chlorpropamide, the incubation studies were conducted using human liver microsomes and recombinant CYP isoforms. To evaluate whether genetic polymorphisms of CYP2C9 and/or CYP2C19 influence the disposition of chlorpropamide, a single oral dose of 250 mg chlorpropamide was administered to 21 healthy subjects pregenotyped for CYP2C9 and CYP2C19.</P><P>Results</P><P>In human liver microsomal incubation studies, the formation of 2-hydroxychlorpropamide (2-OH-chlorpropamide), a major chlorpropamide metabolite in human, has been best described by a one-enzyme model with estimated <I>K</I><SUB><I>m</I></SUB> and <I>V</I><SUB>max</SUB> of 121.7 ± 19.9 µ<SMALL>M</SMALL> and 16.1 ± 5.0 pmol min<SUP>−1</SUP> mg<SUP>−1</SUP> protein, respectively. In incubation studies using human recombinant CYP isoforms, however, 2-OH-chlorpropamide was formed by both CYP2C9 and CYP2C19 with similar intrinsic clearances (CYP2C9 <I>vs.</I> CYP2C19: 0.26 <I>vs.</I> 0.22 µl min<SUP>−1</SUP> nmol<SUP>−1</SUP> protein). Formation of 2-OH-chlorpropamide in human liver microsomes was significantly inhibited by sulfaphenazole, but not by <I>S</I>-mephenytoin, ketoconazole, quinidine, or furafylline. In <I>in vivo</I> clinical trials, eight subjects with the <I>CYP2C9</I>*<I>1/</I>*<I>3</I> genotype exhibited significantly lower nonrenal clearance [*<I>1/</I>*<I>3 vs.</I>*<I>1/</I>*<I>1</I>: 1.8 ± 0.2 <I>vs.</I> 2.4 ± 0.1 ml h<SUP>−1</SUP> kg<SUP>−1</SUP>, <I>P</I> < 0.05; 95% confidence interval (CI) on the difference 0.2, 1.0] and higher metabolic ratios (of chlorpropamide/2-OH-chlorpropamide in urine: *<I>1/</I>*<I>3 vs.</I>*<I>1/</I>*<I>1</I>: 1.01 ± 0.19 <I>vs.</I> 0.56 ± 0.08, <I>P</I> < 0.05; 95% CI on the difference − 0.9, − 0.1) than did 13 subjects with <I>CYP2C9</I>*<I>1/</I>*<I>1</I> genotype. In contrast, no differences in chlorpropamide pharmacokinetics were observed for subjects with the <I>CYP2C19</I> extensive metabolizer <I>vs.</I> poor metabolizer genotypes.</P><P>Conclusions</P><P>These results suggest that chlorpropamide disposition is principally determined by CYP2C9 activity <I>in vivo</I>, although both CYP2C9 and CYP2C19 have a catalysing activity of chlorpropamide 2-hydroxylation pathway.</P>