• Bulletin of the Korean Chemical Society
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• 제33권5호
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• pp.1571-1576
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• 2012

A diarylurea compound 1 possessing pyrrolo[3,2-$c$]pyridine nucleus was designed and synthesized with structure similarity to Sorafenib. Compound 1 was tested over 60-cancer cell line panel at a single dose concentration of 10 ${\mu}M$ and showed high activity. It was further tested in a five-dose mode to determine its $IC_{50}$, TGI, and $LC_{50}$ values over the 60 cell lines. Compound 1 showed high potency and good efficacy, and was accordingly tested at a single dose concentration of 10 ${\mu}M$ over a panel of 40 kinases. At this concentration, it completely inhibited the enzymatic activities of a number of oncogenic kinases, including ABL, ALK, c-RAF, FLT3, KDR, and TrkB. The target compound was subsequently tested over these 6 kinases in 10-dose testing mode in order to determine its $IC_{50}$ values.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3163-3166
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• 2015

Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve this setting. Pomalidomide is a new immunomodulatory drug with high in vitro potency. Immunomodulatory drugs are hypothesized to act through multiple mechanisms. Here we performed a systemic analysis to evaluate pomalidomide-based chemotherapy (pomalidomide in combination with low-dose dexamethasone) as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the efffectiveness of pomalidomide based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: For pomalidomide based regimens, 4 clinical studies which including 291 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 41.2% (120/291). Major adverse effects were hematologic toxicity, including grade 1 or 2 anemia, leucopenia and thrombocytopenia with pomalidomide based treatment. No treatment related death occurred. Conclusion: This pooled analysis suggests that pomalidomide in combination with low-dose dexamethasone is active with good tolerability in treating patients with refractory or relapsed multiple myeloma.

• Clinical and Experimental Reproductive Medicine
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• 제40권2호
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• pp.83-89
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• 2013

Objective: To investigate outcomes of stimulated IVF cycles in which GnRH antagonist was omitted on the ovulation triggering day. Methods: A total of 86 women who underwent controlled ovarian hyperstimulation with recombinant FSH and GnRH antagonist flexible multiple-dose protocols were recruited and prospectively randomized into the conventional group (group A) or cessation group (group B). The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading follicle reached 14 mm in diameter and was continuously administered until the hCG triggering day (group A, 43 cycles) or until the day before hCG administration (group B, 43 cycles). The maturity of oocytes, fertilization rate, embryo quality, and implantation and clinical pregnancy rates were evaluated. Results: The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in group B than group A ($2.5{\pm}0.9$ vs. $3.2{\pm}0.8$ ampoules, p<0.05). There was no premature luteinization in any of the subjects. The proportion of mature oocytes and fertilization rate were not significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs. 66.4%, respectively). There were no significant differences in the implantation or clinical pregnancy rates. Conclusion: Our prospective randomized study suggested that cessation of GnRH antagonist on the hCG administration day during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising its effects on pregnancy rates.

• Archives of Pharmacal Research
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• 제27권2호
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• pp.259-264
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• 2004

The purpose of the present study was to investigate the pharmacokinetics of PEG-hemoglobin SB 1, a modified bovine hemoglobin with polyethylene glycol, after its single and multiple administration in beagle dogs. For this purpose, the analytical method of free hemoglobin in the plasma was developed and validated. Excellent linearity ($r^2$=0.999) was observed in the calibration curve data, with the limit of quantification of 0.005 g/dL. The precision and the deviation of the theoretical values for accuracy were always within $\pm$15％ in both the between-and the within-day results. The method was tested by measuring the plasma concentrations following intravenous administration to beagle dogs and was shown to be suitable for pharmacokinetic studies. In a single dose study, the plasma half-life (t$_{1}$2/) increased and the total body clearance (Cl$_{t}$) decreased with the dose (i.e., 0.017 to 0.75 gHb/kg as PEG-hemoglobin SB1) in both sexes. The volume of distribution at steady-state (Vd$_{ss}$ ) showed no difference with the dose. In contrast, the values of t$_{1}$2/, CL$_{t}$ and the area under the plasma concentration-time curve (AUC) after the multiple dose were significantly different from those of the single dose administration. The values of t$_{1}$2/ in the multiple administration were about two times higher-than that of the single dose. As a result, t$_{1}$2/ of hemoglobin after the administration of PEG-hemoglobin SB1 was about 15-30 h, indicating the PEG modification of the hemoglobin lead to a prolongation of plasma concentration of the protein. Therefore, these observations suggested that the PEG modification of hemoglobin is potentially applicable in the hemoglobin-based therapeutics.tics.

• 한국의학물리학회지:의학물리
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• 제8권1호
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• pp.37-45
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• 1997

차폐된 질 원주기구를 이용한 강내치료시 Co-60 선원에 대한 정확한 흡수선량을 결정 하고자 선원을 교정하고, 질 원주기구에 의한 선량분포변화를 조사하였다. 선량분포의 변화량은 직경 2.5 cm 차폐된 질 원주기구를 폴리스틸렌 팬톰에 설치하여 전리함으로 측정하였으며, 부채꼴 모양인 0.55cm 두께의 9$0^{\circ}C$ 연으로 차폐된 면과 차폐되지 않은 면의 선량분포에 대한 영향을 상대선량 감소율로 측정하였다. 측정된 선량분포의 변화량을 제작사의 선량분포도 및 다점 분할방식으로 구한 선량율표와 비교하였다. 질 원주기구를 이용한 선량 감소율은 차폐되지 않은 변의 경우 원주기구 표면 1cm 거리에서 4.4%를 보였고, 차폐된 면에서는 원주기구 표면에서 20.4% 를 나타냈다. 9$0^{\circ}C$연 차폐된 질 원주기구의 선량감쇄효율은 Co-60 선원에서 평균 0.2가 되었다. Co-60 이동형 선원의 선량분포는 다 점분할방식의 선량율표와 4.1% 이내로 일치하였다.

• 약학회지
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• 제47권1호
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• pp.52-55
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• 2003

Antidiabetic activities of white ginseng 50％ ethanol extract (WGE) and IH901, an intestinal metabolite of ginsenoside R $b_1$, were compared in multiple low dose streptozotocin (STZ)-induced diabetic rats. WGE or IH901 were coadministered with STZ on Day 1 at dose of 100 and 300 mg or 10 and 30 mg, respectively, and continually administered for 16 days. STZ dissolved in citrate boner was injected intraperitoneally at dose of 20 mg/kg for 5 consecutive days. During the experiment, plasma glucose level and body weight were measured every 4$^{th}$ day. Amount of food and water intake were evaluated once a week and compared between groups. WGE and IH901 both significantly reduced the plasma glucose levels on Day 16 as compared with those of the diabetic control group. In the meantime, amount of food and water intake in WGE-and IH901-treated groups were significantly improved in a dose dependent fashion as compared with those of the diabetic control group. Taken together WGE and IH901 showed the comparable antidiabetic activities at the corresponding doses used in this experiment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1597-1602
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• 2014

The purpose of this study was to investigate whether whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases. From January 2007 to December 2012, 19 patients who exhibited massive (with a longest diameter > 5 cm) and invasive liver metastases and multiple metastases were treated with radiotherapy and concurrent chemotherapy. The total radiation dose was 53.4 Gy (range 38.8 Gy-66.3 Gy). All of the patients received a continuous intravenous dose of 5 fluorouracil (5-FU) 225 mg/m2 concurrently with radiation. The median survival time was 19 months. The 1- and 2- year overall survival rates were 78.3% and 14.3%, respectively. Of all of the patients who presented with abdominal pain, 100% experienced a decrease in pain. Decreases in the rates of ascites and jaundice were confirmed by ultrasound and bilirubin levels. No cases of Grade 4 or 5 acute or late toxicity were recorded. There were only two cases of Grade 3 toxicity (elevated bilirubin). These data provide evidence that whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases.

• Journal of Pharmaceutical Investigation
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• 제24권3호
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• pp.115-129
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• 1994

In the present study, quantitative and qualitative histology was used to assess the effects of ibuprofen suppositories with various treatments on the rectal mucosa of rats. Two suppositories were prepared with Witepsol W35 and compared with two commercial ibuprofen suppositories Reference I (Showa Pharm.ind., Tokyo, Japan), Reference II (P.Pharm., Seoul, Korea). Single and multiple dose(dosing interval 4 hr, n=4) studies were conducted. All suppositories significantly increased epithelial cell loss, but the extent of rectal irritation was variable. These studies showed that the incorporation of ibuprofen into the suppository bases increases the morphological change in rectal tissue both for the single and multiple administrations of suppositories, but which was significantly recovered within 24 hr although the interanimal variability in scores was very substantial. Multiple administration of ibuprofen suppositories caused significant damage to rectal mucosa, but it must be considered that these were under the severe condition, that is, interval of administration (4 hr) was three times shorter than normal interval of administration and dose was fifteen times larger than usual human dose. Aluminum oxide $(Al_2O_3)$, a dispersing agent, slightly increased the irritation of rectal mucosa in rats at 5 hr and 24 hr after multiple administration, but it was possible to ignore the difference of irritation in the data at 5hr and 24hr after single administration. Finally, it was concluded that Witepsol W35 and ibuprofen had a slight rectal mucosa-irritating effect on the usual human dose, and ibuprofen suppositories prepared with Witepsol W35 or Witepsol W35, $Al_2O_3$ showed almost similar extent of rectal irritation with commercial ibuprofen products.

• 약학회지
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• 제48권4호
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• pp.247-253
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• 2004

We investigated the hypoglycemic effect of formula containing Euonymus alatus (EA) and Mori Folium (MF) in multiple low dose (MLD) streptozotocin (STZ)-induced diabetic rats. In order to iduce hyperglycemic state 25 mg/kg of STZ was injected intraperitoneally for 5 consecutive days. SD rats were randomly divided into diabetic control and treatment groups. Treatment groups were administered with either 250 mg/kg of EA and 250 mg/kg of MF (E1Ml), or 500 mg/kg of EA mixed with same dose of MF (E2M2) for 3 weeks. Blood glucose levels and body weights were measured every 5th or 6th day. E1Ml and E2M2 both significantly reduced food intake, water intake, and fasting blood and urine glucose levels as compared to those in diabetic control group in a dose dependent manner. Body weight in diabetic control group was increased slightly after 3 weeks. Treatment group, however, showed gradual increase in body weights during 3 week-period. While plasma insulin levels of the diabetic control group were decreased to the level of 387$\pm$14 pg/ml from 534$\pm$36 pg/ml, those levels in E1Ml and E2M2-treated groups were both markedly increased by 13% and 26%, respectively. Urine glucose levels in E1Ml and E2M2-treated groups were also remarkably reduced by 17 and 26% compared to the levels of diabetic control group. While expression of membrane-bound glucose transporter-4 (GLUT-4) protein in skeletal muscle was reduced by 45% in diabetic control compared to the normal control, GLUT-4 protein expressions in E1Ml and E2M2-treated groups were augmented by 2 and 3.5 times compared to the diabetic control, respectively. Pancreatic HE staining experiments showed that E2M2-treated group revealed much less infiltrated mononuclear cells, indicating that E2M2 efficiently blocked insulitis induced by multiple low dose streptozotocin. Taken together, we conclude that formula containing EA and MF may prevent or delay the development of hyperglycemia through overexpression of GLUT-4 protein in skeletal muscle and prevention of insulitis.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.97.1-97.1
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• 2003

Antidiabetic activity of formular containing an Euonymus alata (EA) and Mori Foluim (MF) was investigated in oral glucose tolerance test (OGTT) and multiple low dose Streptozotocin (MLDSTZ)-induced rats. Optimum ratio between EA and MF was found to be 1:1 in OGTT, and two strengths (250 and 500 mg/kg for each medicinal plant) were coadministered with 20 mg/kg of STZ in 5 consecutive days. At 3rd week, water and food intakes were compared between groups and polydipsia and polyphagia shown in diabetic control were markedly improved in dose dependent manner. (omitted)