Antitumor Activity of LB42907, a Potent and Selective Farnesyltransferase Inhibitor: Synergistic Effect in Combination with Other Anticancer Drugs

김세미,Ji Hyun Park,Sun-Young Koo,김동명,Kwihwa Kim,Shin Wu Jeong,Hyun-Ho Chung,Heung-Soo Cho,Joonghoon Park,Hyeon Joo Yim,Jinho Lee,Jong Sung Koh 대한화학회 2008 Bulletin of the Korean Chemical Society Vol.29 No.7

Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

세프질$^{(R)}$ 정 250밀리그람 (세프프로질 250밀리그람)에 대한 프로세질 정 250밀리그람의 생물학적동등성

김세미,강민선,조혜영,이용복,Kim, Se-Mi,Kang, Min-Sun,Cho, Hea-Young,Lee, Yong-Bok 한국임상약학회 2010 한국임상약학회지 Vol.20 No.3

Cefprozil is a broad-spectrum oral beta-lactam cephalosporin consisting of cis- and trans-isomeric mixture whose ratio is approximately 90:10. Cefprozil is used to treat certain infections caused by bacteria such as bronchitis and ear, skin, and throat infections. The purpose of the present study was to evaluate the bioequivalence of two cefprozil tablets, $Cefzil^{(R)}$ tablet 250 mg (BMS Pharmaceutical Korea., Ltd.) and Procezil tablet 250 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of cefprozil from the two cefprozil formulations were tested using KP VIII Apparatus I method with water dissolution media. Thirty five healthy male subjects, $24.00{\pm}1.53$ years in age and $69.77{\pm}9.99$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After four tablets containing 1000 mg as cefprozil were orally administered, blood samples were taken at predetermined time intervals and the concentrations of cefprozil in serum were determined using HPLC/UV detector. The dissolution profiles of two formulations were similar in water tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ on the basis of total-cefprozil were calculated, and computer program (K-BE Test 2002) was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Cefzil^{(R)}$ tablets, were -0.81%, -3.00% and -6.83% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.9515~log 1.0454 and log 0.9613~log 1.0465 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Procezil tablet was bioequivalent to $Cefzil^{(R)}$ tablet.

가바펜틴 400밀리그람 캡슐의 생물학적동등성시험

김세미,강현아,조혜영,신새벽,류희두,윤화,이용복,Kim, Se-Mi,Kang, Hyun-Ah,Cho, Hea-Young,Shin, Sae-Byeok,Yoo, Hee-Doo,Yoon, Hwa,Lee, Yong-Bok 대한약학회 2008 약학회지 Vol.52 No.3

Gabapentin, [1-(aminomethyl) cyclohexaneacetic acid], a structural analog of $\gamma$-aminobutyric acid (GABA), is being developed for the treatment of epilepsy. Unlike GABA, gabapentin crosses the blood-brain barrier after systemic administration. Gabapentin is an effective antiepileptic drug in patients with partial and secondarily generalized seizures who are uncontrolled with use of existing anticonvulsant drug therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin 400 mg capsules, $Neurontin^{(R)}$ capsule 400 mg (Pfizer Inc.) and Gabatin capsule 400 mg (Korean Drug Co. Ltd), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, 23.58$\pm$1.50 years in age and 66.74$\pm$8.31 kg in body weight, were divided into two groups and a randomized 2$\times$2 cross-over study was employed. After one capsule containing 400 mg as gabapentin were orally administered, blood was taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Neurontin^{(R)}$ capsule 400 mg, were 2.04, -3.68 and 16.79% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.91$\sim$log 1.16 and log 0.87$\sim$log 1.11 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabatin capsule 400 mg was bioequivalent to $Neurontin^{(R)}$ capsule 400 mg.

가바펜틴 800밀리그람 정제의 생물학적동등성시험

김세미,신새벽,강현아,조혜영,이용복,Kim, Se-Mi,Shin, Sae-Byeok,Kang, Hyun-Ah,Cho, Hea-Young,Lee, Yong-Bok 대한약학회 2008 약학회지 Vol.52 No.4

Gabapentin, 1-(aminomethyl) cyclohexaneacetic acid, is a amino acid derivative, and is clinically effective in the treatment of neuropathic pain and partial seizures of epilepsy as a complementary therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin tablets, $Neurontin^{R}$ tablet 800 mg (Pfizer Pharmaceuticals Co., Ltd.) and Gabapenin tablet 800 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with 0.06 M HCI dissolution media. Twenty six healthy male subjects, $23.85{\pm}2.24$ years in age and $69.40{\pm}11.11$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 800 mg as gabapentin was orally administered, blood samples were taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution media. The pharmacokinetic parameters such as $AUC_{t}$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{t}$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Neurontin^{R}$, were 1.28%, 0.63% and 0.62% for $AUC_{t}$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log0.9097{\sim}log1.1598$ and $log0.8919{\sim}log1.1262$ for $AUC_{t}$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabapenin tablet 800 mg was bioequivalent to $Neurontin^{R}$ tablet 800 mg.

한국인에 있어서 MDRI 유전자(exon 12, 21 및 26)의 일배체형 분석

김세미,박선애,조혜영,이용복,Kim, Se-Mi,Park, Sun-Ae,Cho, Hea-Young,Lee, Yong-Bok 한국약제학회 2008 Journal of Pharmaceutical Investigation Vol.38 No.6

The aim of this study was to investigate the frequency of the SNPs on MDR1 exon 12, 21 and 26 in Korean population and to analyze haplotype frequency on MDR1 exon 12, 21 and 26 in Korean population. A total of 426 healthy subjects was genotyped for MDR1, using polymerase chain reaction-based diagnostic tests. Haplotype was statistically inferred using an algorithm based on the expectation-maximization (EM). MDR1 C1236T genotyping revealed that the frequency for homozygous wild-type (C/C), heterozygous (C/T) and for homozygous mutant-type (T/T) was 20.19%, 46.48% and 33.33%, respectively. MDR1 G2677T/A genotyping revealed that the frequency for homozygous G/G, heterozygous G/T, homozygous T/T, heterozygous G/A, heterozygous T/A and for homozygous A/A type was 30.75%, 42.26%, 9.86%, 7.51 %, 7.04% and 2.58%, respectively. MDR1 C3435T genotyping revealed that the frequency for homozygous wild-type (C/C), heterozygous (C/T) and for homozygous mutant-type (T/T) was 38.73%, 50.24% and 11.03%, respectively. Twelve haplotypes were observed. Of the three major haplotypes identified (CGC, TTT and TGC), the CGC haplotype were mainly predominant in the Korean populations and accounted for 29.96% of total haplotype in Korean.

단보 : 딜라트렌 정 12.5밀리그람(카르베딜롭 12.5밀리그람)에 대한 카딜란 정 12.5밀리그람의 생물학적동등성

김세미 ( Se Mi Kim ),신새벽 ( Sae Byeok Shin ),김주환 ( Ju Hwan Kim ),권인호 ( In Ho Kwon ),김용희 ( Yong Hee Kim ),이상노 ( Sang No Lee ),조혜영 ( Hea Young Cho ),이용복 ( Yong Bok Lee ) 한국약제학회 2008 Journal of Pharmaceutical Investigation Vol.38 No.6

Fatty Acid 추출제를 사용한 용매추출법에 의한 Praseodymium과 Dysprosium의 분리

김세미 ( Se Mi Kim ),이은수 ( Eun Su Lee ),김정훈 ( Jeong Hoon Kim ),김영운 ( Young Wun Kim ),박종목 ( Jong Mok Park ),허남호 ( Nam Ho Heo ),강호철 ( Ho Cheol Kang ) 한국환경분석학회 2013 환경분석과 독성보건 Vol.16 No.2

The separation of praseodymium and dysprosium has been studied by solvent extraction using fatty acid series such as hexanoic acid, octanoic acid, 2-ethylhexanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, and oleic acid as an extractant in kerosene as a diluent. In this study, we want to know extractive trend depending on the carbon chain length and the pH of aqueous phase. The results obtained from solvent extraction of praseodymium and dysprosium using fatty acids are as follows; the pH0.5 of dysprosium is from 4.93 to 5.94, and that of praseodymium is from 4.24 to 5.34. The pH0.5 of them is increased with increasing the length of the carbon chain of the fatty acid. Using 1.5 M octanoic acid as an extractant, we can get the highest separation factor of praseodymium and dysprosium that is 49.

802.11 WLAN 방송 패킷을 이용한 신뢰성 있는 실시간 멀티미디어 데이터 전송 방법

김세미 ( Se-mi Kim ),김동현 ( Dong-hyun Kim ),김종덕 ( Jong-deok Kim ) 한국정보처리학회 2011 한국정보처리학회 학술대회논문집 Vol.18 No.1

최근 IEEE 802.11 WLAN(Wireless Local Area Network)에서 실시간 멀티미디어 서비스가 증가하고 있다. WLAN 의 패킷 전송방식은 Unicast 또는 Broadcast 방식이 있다. Unicast 방식은 재전송을 포함하여 유실율이 적으나 사용자가 증가할수록 AP 에서 필요한 무선 자원의 크기가 증가한다. 무선 자원의 크기가 증가하면 AP 부하가 증가하여 서비스 수용에 한계가 있다. Broadcast 방식은 사용자 수에 상관 없이 무선 자원의 크기가 일정하나, 패킷 유실율이 높다. 본 논문에서는 이러한 문제점을 해결하기 위해 Broadcast 와 FEC(Forward Error Correction) Erasure Code 기반 기술을 적용하는 것을 제안한다. 방송 패킷을 이용 AP 의 부하를 줄이고, Reed Solomon Erasure Code 를 적용하여 패킷 유실 복구율을 높인다. 이러한 방법을 통하여 다수의 사용자에게 안정적인 실시간 멀티미디어 방송 서비스를 제공 할 수 있다. 제안한 방법을 검증하기 위해 Android Platform 에서 FEC 적용 유무에 따른 수신율을 측정하였다. 그 결과 유실율 30%미만인 Broadcast 환경에서 96.4% 이상의 수신율을 보였다.

집단지성을 활용한 예비교사들의 과학지식형성과정탐색

김세미 ( Semi Kim ),김은진 ( Eunjin Kim ),김성원 ( Sung Won Kim ) 한국과학교육학회 2013 한국과학교육학회지 Vol.33 No.5

The purpose of this study was to investigate the process of constructing pre-service teachers` scientific knowledge information through collective intelligence. We selected the` Appropriate Technology` (A.T.) as the subject for formation of scientific knowledge. Twenty nine pre-service teachers of the course `Scientific Thinking and Writing in Science Education` were allowed to freely post information whenever they wanted. They presented their full opinions, interacted with each other, and assessed the other` information on the website for a month. The way of posting was as follows. After one pre-service teacher had written the information about A.T. on the website, the other assessed the text and added or modified the writing. This process continued. We analyzed every writing they posted and questionnaire which contained the reason why they modified the text. The result was as follows. Pre-service teachers formed collective intelligence through four stages. First, pre-service teachers started to find the information related to the subject and they just added the information behind the other`s writing. In the second stage, information was added, too. But me difference was that the information they selected carried values for having certain views. Third, they organized their writings with logical and critical thinking. Finally, they revised their overall writing. The results showed that students could develop their critical thinking and they could learn the way of communication from the process of collective intelligence. We found the forming process of knowledge by collective intelligence, and explored the various involving patterns and thinking activities in the process. Based on this research, we expect the improvement of students` logical and critical thinking through the various classes using collective intelligence.

원보 : 염산레르카니디핀 체내동태 연구를 위한 혈청 중 레르카니디핀의 LC/MS/MS 정량법 검증

김세미 ( Se Mi Kim ),김환호 ( Hwan Ho Kim ),신새벽 ( Sae Byeok Shin ),강현아 ( Hyun Ah Kang ),윤화 ( Hwa Yoon ),조혜영 ( Hea Young Cho ),김윤균 ( Yoon Gyoon Kim ),양찬우 ( Chan Woo Yang ),용철순 ( Chul Soon Yong ),이용복 ( Yong B 한국약제학회 2007 Journal of Pharmaceutical Investigation Vol.37 No.4