• 대한의용생체공학회:의공학회지
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• 제9권1호
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• pp.73-78
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• 1988

The polymer electrolyte complex hydrogels consisting of poly (methacrylic acid) and poly (4-vinylpyrridine) were formed and 5-flurouracil and pilocarpine drugs were loaded on their hydrogels. Cumulative 5-FU released from PEC hydrogel was affected by the degree of loading and release rate of 5-FU was followed by the monolithic type. Cumulative pilocarpine released from PEC hydrogel increased by ionic interaction between cationic pilocarpine and anionic PMA. Release rate showed the zero order after burst effect.

• Radiation Oncology Journal
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• 제30권4호
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• pp.189-196
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• 2012

Purpose: To investigate the safety of high dose hypofractionated radiotherapy (RT) in patients with small hepatocellular carcinoma (HCC) in terms of liver volumetric changes and clinical liver function. Materials and Methods: We retrospectively reviewed 16 patients with small HCC who were treated with high dose hypofractionated RT between 2006 and 2009. The serial changes of the liver volumetric parameter were analyzed from pre-RT and follow-up (FU) computed tomography (CT) scans. We estimated linear time trends of whole liver volume using a linear mixed model. The serial changes of the Child-Pugh (CP) scores were also analyzed in relation to the volumetric changes. Results: Mean pre-RT volume of entire liver was 1,192.2 mL (range, 502.6 to 1,310.2 mL) and mean clinical target volume was 14.7 mL (range, 1.56 to 70.07 mL). Fourteen (87.5%) patients had 4 FU CT sets and 2 (12.5%) patients had 3 FU CT sets. Mean interval between FU CT acquisition was 2.5 months. After considering age, gender and the irradiated liver volume as a fixed effects, the mixed model analysis confirmed that the change in liver volume is not significant throughout the time course of FU periods. Majority of patients had a CP score change less than 2 except in 1 patient who had CP score change more than 3. Conclusion: The high dose hypofractionated RT for small HCC is relatively safe and feasible in terms of liver volumetric changes and clinical liver function.

• Journal of Pharmaceutical Investigation
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• 제25권3호
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• pp.249-264
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• 1995

Although liposome has many advantages as a pharmaceutical dosage form, its application in the industrial field has been limited because of some problems such as preparation method, reproducibility, scale-up, stability and sterilization etc. Liposomes prepared by microemulsification method had defined size, narrow size distribution, reproducibility and high entrapment efficiency. For enhancing the stability, the dry form of liposome was recommended. These types of liposome are proliposome and freeze-dried liposome. The liposome must have some properties for preparing of freeze-dried liposome; small size $(50{\sim}200\;nm)$, narrow size distribution and cryoprotectant. In this experiment, the liposomes containing 5-Fluorouracil(5-FU) and its prodrug(pentyl-5-FU-1-acetate; PFA, hexyl-5-FU-1-acetate; HFA) were made with soybean phosphatidylcholine, cholesterol, stearylamine(SA) and dicetyl phosphate(DCP) employing hydration method or microemulsification method using $Microfluidizer^{TM}$. Both or liposome types were MLV and MEL. After preparation, freeze drying and rehydration were performed. In the process of freezing, trehalose(Tr) was added as a cryoprotectant. Their evaluation methods were as follows; entrapment efficiency, mean particle size and size distribution, dissolution test, retain of entrapment efficiency and turbidity after freeze-drying. The results are summarized as belows. The entrapment efficiency of 5-FU was dependent on total lipid concentration and cholesterol content but that of PFA and HFA was decreased when cholesterol was added. When DCP and SA were added, entrapment efficiency was decreased. As the partition coefficient of drug was increased, entrapment efficiency was increased. Under the same condition, entrapment efficiency of MEL is similar to that of MLV. The mean particle size and size distribution of MEL were smaller than those of MLV. Dissolution rates of drug from both liposome types were comparatively similar. Dissolution rates of drugs with serum and liver homogenate were faster than without these material. After preparation of liposome, free drug was removed efficiency by Dowex 50W-X4. When liposome was freeze-dried and then rehydrated in the presence of Tr, characteristics of liposome were maintained well in MEL than MLV. Tr Was used successfully as a cryoprotectant in the process of freeze drying and the optimal ratio of Tr:Lipid was 4:1(g/g).

• 동의생리병리학회지
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• 제26권2호
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• pp.155-159
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• 2012

The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix and the effects of 5-Fluorouracil (5-FU) in human colorectal adenocarcinoma cells (HT-29). We used human colorectal adenocarcinoma cell line, HT-29 cells. We examined cell death by MTT assay and caspase 3 assay with Sophorae Radix. To examine the inhibitory effects of Sophorae Radix, cell cycle (sub G1) analysis was done the HT-29 cells after three days with Sophorae Radix. The reversibility of Sophorae Radix was examined on one day to five days treatment with $150{\mu}g$ Sophorae Radix. Sophorae Radix inhibited the growth of HT-29 cells in a dose-dependent fashion. Also we showed that Sophorae Radix induced apoptosis in HT-29 cells by MTT assay, caspase 3 assay and sub-G1 analysis. Sophorae Radix combined with 5-FU markedly inhibited the growth of HT-29 cells compared to Sophorae Radix or 5-FU alone. After 3 days treatment of HT-29 cells with Sophorae Radix, the fraction of cells in sub-G1 phase was much higher than that of the control group. Our findings provide insight into unraveling the effects of Sophorae Radix in human colorectal adenocarcinoma cells and developing therapeutic agents against colorectal cancer.

• 한국한의학연구원논문집
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• 제18권1호
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• pp.85-92
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• 2012

Objective : The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix and the effects of 5-Fluorouracil (5-FU) in human gastric adenocarcinoma cells (AGS). Method : We used human gastric adenocarcinoma cell line, AGS cells. We examined cell death by MTT assay and caspase 3 assay with Sophorae Radix. To examine the inhibitory effects of Sophorae Radix, cell cycle (sub G1) analysis was done the AGS cells after three days with Sophorae Radix. The reversibility of Sophorae Radix was examined on one day to five days treatment with 100 ${\mu}g/ml$ Sophorae Radix. Result : Sophorae Radix inhibited the growth of AGS cells in a dose-dependent fashion. Also we showed that Sophorae Radix induced apoptosis in AGS cells by MTT assay, caspase 3 assay and sub-G1 analysis. Sophorae Radix combined with 5-FU markedly inhibited the growth of AGS cells compared to Sophorae Radix or 5-FU alone. After 3 days treatment of AGS cells with Sophorae Radix, the fraction of cells in sub-G1 phase was much higher than that of the control group. Conclusion : Our findings provide insight into unraveling the effects of Sophorae Radix in human gastric adenocarcinoma cells and developing therapeutic agents against gastric cancer.

• Radiation Oncology Journal
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• 제4권2호
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• pp.141-145
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• 1986

1981년 1월부터 1985년 12월까지 서울대학교병원 치료방사선과에서 운2명의 극소적으로 절제 불가능한 췌장암 환자를 방사선과 악물요법으로 치료하였다. 방사선은 2주의 간격을 두고 2000cGy씩 총 4000cGy를 조사하였으며 5-FU (5-fluorouracil)는 방사선 조사의 각 course의 첫 3일에 걸쳐 주입하였다. 방사선치료 종료 4주 후부터 FAM (5-FU, Adriamycin, Mitomycin)을 지속요법으로 사용하였다. 통증 완화는 $22\%(4/18)$에서 완전관해를, $39\%(7/18)$에서 부분관해를 보였다. 생존기간의 중앙치는 31주였으며 치료 전 Performance status가 중요한 예후인자였다. 국소적으로 절제불가능한 췌장암의 치료에 있어서 방사선과 FAM regimen의 병용은 통증완화 및 생존기간의 연장에 기여할 수 있는 바 이에 대한 보다 많은 연구와 고찰이 없어야 차겠다.

• 분석과학
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• 제28권5호
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• pp.331-340
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• 2015

DNA/RNA결합 단백질로 다양한 기능을 한다고 알려진Fused in Sarcoma (FUS)의 유전자 돌연변이가 루게릭병 및 전측두엽성 치매 환자에서 발견되었다. 정상적인 FUS는 핵에 위치하지만 병리상황에서 FUS는 세포질로 잘못 타기팅 되어 스트레스 응집체와 결합된 단백질 응집체를 형성하는 것으로 알려졌다. 그러나 이들에 의한 스트레스 응집체 형성 기전 및 응집체 형성에 관여하는 FUS의 도메인은 정확히 알려지지 않았다. 따라서, 본 연구에서는 루게릭병 연관 FUS 미스센스 돌연변이(P525L, R521C, R521H, R521G)의 세포내 위치 및 세포질 FUS의 응집체 형성에 관여하는 FUS내 도메인을 분석하고 동정하고자 하였다. 이를 위해 먼저, FUS 미스센스 돌연변이의 세포내 위치를 분석한 결과, P525L대부분은 세포질로 위치하여 스트레스 응집체를 형성하는 반면, R521C, R521H, R521G는 핵과 세포질에 위치하였다. 이를 통해 FUS의 핵으로의 이동에는 FUS의 마지막 2개의 아미노산이 매우 중요함을 확인할 수 있었다. 세포질로 빠져 나온 FUS의 응집체 형성에 관여하는 FUS도메인 분석을 위해서 핵 위치서열이 결손되어 대부분 세포질 응집체를 형성하는 FUS-∆17를 이용하여, 다양한 도메인 결손 돌연변이를 제작하고, 이들의 응집체 형성여부를 분석하였다. 그 결과, SYGQ-RGG1나 RGG2-ZnF-RGG3없는 세포질 FUS (FUS-∆SYGQ-RGG1-∆17, FUS-∆RGG2-ZnF-RGG3-∆17)는 스트레스 응집체를 형성하지 않은 반면, RRM이 없는 FUS-∆RRM-∆17은 FUS-∆17에 비해 많은 스트레스 응집체를 형성함을 알 수 있었다. 따라서, 도메인 분석결과 세포질의 FUS는 SYGQ-RGG1나 RGG2-ZnF-RGG3 도메인을 통해 FUS 스트레스 응집체 형성이 촉진되고, RRM도메인은 FUS 응집체 형성을 저해하고 있는 것으로 생각된다. 이러한 연구 결과는 FUS의 스트레스 응집체 형성과 연관된 다양한 퇴행성 뇌질환의 발병기전에 대한 이해뿐만이 아니라 이들 질환 치료를 위한 치료 후보 타겟 물질 발굴에 중요한 단서를 제공할 수 있을 것이다.

• Biomolecules & Therapeutics
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• 제13권3호
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• pp.143-149
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• 2005

We have demonstrated previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase (CD) gene is driven by the tumor-specific L-plastin promoter. The object of this study was to evaluate the efficacy of AdLPCD together with 5-fluorocytosine (5-FC) in suppression of the growth of established human tumor cells of ovary, Consistent with the knowledge that infection of OVCAR-3 cells with AdLPCD resulted in expression of a functional intracellular CD enzyme capable of converting 5-FC to 5-fluorouracil (5-FU) (Chung and Deisseroth, 2004), statistically significant differences in cytotoxicity were observed when AdLPCD infected cells were also exposed to 5-FC for 6 days (p=0.05), 9 days (p<0.0005) and 12 days (p<0.005), compared to 5-FC exposure alone, These results indicate that the CD gene delivered by adenoviral vector could efficiently sensitize OVCAR-3, otherwise non-toxic 5-FC. On the other hand, SKOV-3 cells, an ovarian carcinoma cell line, were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The results of present study suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.

• KSBB Journal
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• 제13권6호
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• pp.669-674
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• 1998

This study was carried out particularly focusing on he antitumor effect in combination with 5-fluorocytosine(5-FC), antifungal agent, and extracellular cytosine deaminase from Chromobacterium violaceum YK 391 against U-937, K-562 and SNU-C4 cells. While the addition of 10$\mu\textrm{g}$/100 ${\mu}\ell$ of anticancer agent, 5-fluorouracil(5-FU), to U-937, K-562 and SNU-C4 caused the decrease of proliferation 90%, 75% and 93% respectively, the addition of 20 $\mu\textrm{g}$/100 ${\mu}\ell$ of the extracellular cytosine deaminase and 10 $\mu\textrm{g}$/100 ${\mu}\ell$ of antifungal agent 5-FC caused the decrease of proliferation 80%, 70% and 90%, respectively. These results, therefore, reveal that this enzyme has the similar clinical effect for considering of adjuvant antitumor effect. From the above results, the treatment of 5-FC and the cytosine deaminase was very effective and showed the possibility to remove side effects which easily occur by the treatment of 5-FU only. An extracellular cytosine deaminase.

• Radiation Oncology Journal
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• 제20권4호
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• pp.328-333
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• 2002

목적 : 절제 불가능한 췌장암은 예후가 불량하여 효과적인 치료법의 개발이 요망되고 있다. 본 연구에서는 Gemcitabine 또는 Paclitaxel과 5-Fluorouracil (5-FU)을 이용한 동시항암화학방사선요법을 시행하여 치료효과를 분석하고자 하였다. 대상 및 방법: 임상적으로 혹은 개복수술 소견 상 절제 불가능한 췌장암으로 진단받은 환자를 대상으로 Gemcitabine 또는 Paclitaxel과 5-FU을 이용한 동시항암화학방사선요법을 시행하였다. 방사선 치료는 원발병소와 주위 림프절을 포함하여 5주 동안 45 Gy를 조사하였다. 이 기간동안 Gemcitabine $1,000\;mg/m^2$ 또는 Paclitaxel $50\;mg/m^2$의 매주 1회 주사 및 5-FU의 매일 경구 투여를 시행하였다. 추적관찰기간은 6개월에서 36개월이었으며, 생존율은 Kaplan-Meier법을 이용하여 분석하였다. 결과 : 1999년 1월부터 2001년 11월까지 본 치료법이 시행된 경우는 54예였으며, 이중 계획된 치료를 종료한 42예를 분석하였다. 남녀 비는 30 : 12였고 중앙 연령은 60세였다. 총 54예 중 치료 중 원격전이나 암종증(carcinomatosis) 등으로의 진행 6명$(50\%)$, 시작시 불량한 전신수행 상태 4명$(33.3\%)$, 병변과 무관한 병발질환 1명$(8.3\%)$, 치료 거부 1명$(8.3\%)$ 등으로 총 12예에서 치료가 중단되었다. 42명의 환자 중 40예에서 반응 평가가 가능하였으며 완전 관해 1예, 부분 관해 24예로 관해율은 $59\%$로 나타났다. 중앙 생존값은 12개월, 1년 생존율은 $46.7\%$, 2년 생존율은 $17.0\%$였다. Grade III 이상의 치료독성으로는 혈액학적 독성이 8예$(19\%)$, 오심, 구토 등의 비혈액학적 독성이 9예$(20\%)$이었다. 이중 2명은 치료독성에 의한 상부 소화기 출혈로 사망하였다. 결론 : 절제 불가능한 췌장암에서 Gemcitabine 또는 Paclitaxel를 이용한 동시항암화학방사선요법은 관해율과 생존율에 있어서 효과적인 치료로 생각된다. 그러나 독성감소를 위한 연구가 또한 병행되어야 할 것으로 생각된다.