• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.9 no.1
• /
• pp.9-16
• /
• 2023

Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of ⁶⁴Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that ⁶⁴Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.35 no.2
• /
• pp.91-101
• /
• 2009

in the cosmetics and medical supply field as a antioxidant material. The stable nano particle emulsion of skin toner type containing VEA was prepared. To evaluate the skin permeation, experiments on VEA permeation to the skin of the ICR outbred albino mice (12 weeks, about 50 g, female) and on differences of solubility as a function of receptor formulations was performed. The analysis of nano-emulsions containing VEA 0.07 % showed that the higher ethanol contents the larger emulsions were formed, while the higher surfactant contents the size became smaller.In this study, vitamin E acetate (VEA, tocopheryl acetate), a lipid-soluble vitamin which is widely used A certain contents of ethanol in receptor phase increased VEA solubility on the nano-emulsion. When the ethanol contents were 10.0 % and 20.0 %, the VEA solubility was higher than 5.0 % and 40.0 %, respectively. The type of surfactant in receptor solution influenced to VEA solubility. The comparison between three kind surfactants whose chemical structures and HLB values are different, showed that solubility of VEA was increased as order of sorbitan sesquioleate (Arlacel 83; HLB 3.7) > POE (10) hydrogenated castor oil (HCO-10; HLB 6.5) > sorbitan monostearate (Arlacel 60; HLB 4.7). VEA solubility was also shown to be different according to the type of antioxidant. In early time, the solubility of the sample including ascorbic acid was similar to those of other samples including other types of antioxidants. However, the solubility of the sample including ascorbic acid was 2 times higher than others after 24 h. Franz diffusion cell experiment using mouse skin was performed with four nano-emulsion samples which have different VEA contents. The emulsion of 10 wt% ethanol was shown to be the most permeable at the amount of 128.8 ${\mu}g/cm^2$. When the result of 10 % ethanol content was compared with initial input of 220.057 ${\mu}g/cm^2$, the permeated amount was 58.53 % and the permeated amount at 10 % ethanol was higher 45.0 % and 15.0 % than the other results which ethanol contents were 1.0 and 20.0 wt%, respectively. Emulsion particle size used 0.5 % surfactant (HCO-60) was 26.0 nm that is one twentieth time smaller than the size of 0.007 % surfactant (HCO-60) at the same ethanol content. Transepidermal permeation of VEA was 54.848 ${\mu}g/cm^2$ which is smaller than that of particlesize 590.7 nm. Skin permeation of nano-emulsion containing VEA and difference of VEA solubility as a function of receptor phase formulation were determined from the results. Using these results, optimal conditions of transepidermal permeation with VEA were considered to be set up.

• Radiation Oncology Journal
• /
• v.20 no.2
• /
• pp.155-164
• /
• 2002

Purpose : A ginkgo biloba extract (GBE) has been known as a hypoxic cell radiosensitizer. Its mechanisms of action are increase of the red blood cell deformability, decrease the blood viscosity, and decrease the hypoxic cell fraction in the tumor. The aims of this study were to estimate the effect of GBE on fractionated radiotherapy and to clarify the mechanism of action of the GBE by estimating the blood flow in tumor and normal muscle. Materials and Methods : Fibrosarcoma (FSall) growing in a C3H mouse leg muscle was used as the tumor model. When the tumor size reached 7 mm in diameter, the GBE was given intraperitoneally at 1 and 25 hours prior to irradiation. The tumor growth delay was measured according to the various doses of radiation (3, 6, 9, 12 Gy and 15 Gy) and to the fractionation (single and fractionated irradiation) with and without the GBE injection. The radiation dose to the tumor the response relationships and the enhancement ratio of the GBE were measured. In addition, the blood flow of a normal muscle and a tumor was compared by laser Doppler flowmetry according to the GBE treatment. Results : When the GBE was used with single fraction irradiation with doses ranging from 3 to 12 Gy, GBE increased the tumor growth delay significantly (p<0.05) and the enhancement ratio of the GBE was 1.16. In fractionated irradiation with 3 Gy per day, the relationships between the radiation dose (D) and the tumor growth delay (TGD) were TGD $(days)=0.26{\times}D$ (Gy)+0.13 in the radiation alone group, and the TGD $(days)=0.30{\times}D$ (Gy)+0.13 in the radiation with GBE group. As a result, the enhancement ratio was 1.19 ($95\%$ confidence interval; $1.13\~1.27$). Laser Doppler flowmetry was used to measure the blood flow. The mean blood flow was higher in the muscle (7.78 mL/100 g/min in tumor and the 10.15 mL/100 g/min in muscle, p=0.005) and the low blood flow fraction (less than 2 mL/100 g/min) was higher in the tumor $(0.5\%\;vs.\;5.2\%,\;p=0.005)$. The blood flow was not changed with the GBE in normal muscle, but was increased by $23.5\%$ ( p=0.0004) in the tumor. Conclusion : Based on these results, it can be concluded that the GBE enhanced the radiation effect significantly when used with fractionated radiotherapy as well as with single fraction irradiation. Furthermore, the GBE increased the blood flow of the tumor selectively.

• KIPS Transactions on Computer and Communication Systems
• /
• v.9 no.11
• /
• pp.281-290
• /
• 2020

With the spread of smartphones, services that want to use personalized data are increasing. In particular, healthcare-related services deal with a variety of data, and data visualization techniques are used to effectively show this. As data visualization techniques are used, interactions in visualization are also naturally emphasized. In the PC environment, since the interaction for data visualization is performed with a mouse, various filtering for data is provided. On the other hand, in the case of interaction in a mobile environment, the screen size is small and it is difficult to recognize whether or not the interaction is possible, so that only limited visualization provided by the app can be provided through a button touch method. In order to overcome the limitation of interaction in such a mobile environment, we intend to enable data visualization interactions through conversations with chatbots so that users can check individual data through various visualizations. To do this, it is necessary to convert the user's query into a query and retrieve the result data through the converted query in the database that is storing data periodically. There are many studies currently being done to convert natural language into queries, but research on converting user queries into queries based on visualization has not been done yet. Therefore, in this paper, we will focus on query generation in a situation where a data visualization technique has been determined in advance. Supported interactions are filtering on task x-axis values and comparison between two groups. The test scenario utilized data on the number of steps, and filtering for the x-axis period was shown as a bar graph, and a comparison between the two groups was shown as a line graph. In order to develop a natural language processing model that can receive requested information through visualization, about 15,800 training data were collected through a survey of 1,000 people. As a result of algorithm development and performance evaluation, about 89% accuracy in classification model and 99% accuracy in query generation model was obtained.

• The Korean Journal of Mycology
• /
• v.29 no.1
• /
• pp.15-21
• /
• 2001

This study was conducted to investigate the immunomodulatory activities of proteoglycan extracted from cultured mycelia of Ganoderma lucidum IY009. The proteoglycan contained two polymer peaks, one was the higher MW peak of 2,000 kD and the other was low peaks of 12kD. To understand the part of strong pharmaceutical activity between two peak, the proteoglycan was separated by ultrafiltration and column chromatography and then examined the various pharmaceutical effects. High molecular weight fraction possesing high content of ${\beta}-linked$ glucan was exhibited high antitumor activity, against sarcoma 180 bearing ICR mouse. And also, anticomplementary activity was highly observed in high molecule fraction than low it fraction. When the raw 264.7 and murine peritoneal macrophage treated with low fraction, high fraction and other stimuli. The activities inducing tumor necrosis factor of the high factions were $2.2{\sim}2.5$ times stronger than that of low fraction.

• The Korean Journal of Nuclear Medicine
• /
• v.37 no.6
• /
• pp.393-401
• /
• 2003

Objective: Pullulan derivatives (PD) can be used to make self-assembled hydrogel nanoparticles which are responsive to ionic strength. The aim of this study is to evaluate the potential of PD as a retaining carrier of radioisotope inside tumors. Materials and Methods: Four types of PD were evaluated which included pullulan acetate (PA), succinylated PA (SPA), PA-DTPA and SPA-DTPA conjugates. They were radiolabeled with Tc-99m. Labelling efficiencies were determined at 30 min, 1, 2, 4 and 12 hours after radiolabeling. CT-25 colon cancer cells were subcutaneously injected into Balb/c mice. After 2 weeks of subcutaneous injection, Tc-99m-labelled PD (Tc-99m-PD) were injected into the tumors. Whole body images of mice were obtained at 30 min, 1, 2, and 12 hr after intratumoral injection. All twenty mice were grouped into four groups by largest diameter; control A (largest diameter = 5 mm, n = 5), control B (largest diameter = 10 mm, n = 5), pullulan A (largest diameter = 5 mm, n = 5), pllulan B (largest diameter = 10 mm, n = 5). Dynamic images were obtained for 1 hour after intratumoral injection. Static images were obtained at 1 hr, 2 hr, 3 hr and 4 hr after intratumoral injection with Tc-99m pertechnetate and Tc-99m-PA. Target-to-background ratios and retention rates were calculated. Results: Labeling efficiencies of PA, SPA, PA-DTPA and SPA-DTPA were $94.5{\pm}5.9%,\;97.8{\pm}3.5%\;94.2{\pm}3.8%,\;and\;92.5{\pm}6.2%$, respectively (p>0.05). Percent retention rates (%RR) of PA and PA-DTPA were significantly higher than those of control, however, those of SP-DTPA and SPA became similar to control at 4 and 12 hr, respectively. %RR of pullulan A and pullulan B at 1, 4 and 8 hr is significantly higher than that of control (p < 0.05). However, %RR between pullulan A and pullulan B were similar. Conclusion: The lonic strength dependent PD-nanoparticles are retained in the tumor. No difference of %RR according to tumor size was noted. Therapeutic application of PD labelled with beta- or alpha- emitting radionuclides can be expected.

• Journal of radiological science and technology
• /
• v.34 no.3
• /
• pp.239-244
• /
• 2011

In this study, we evaluated diffusion weighted imaging (DWI) to investigate whether the DWI parameters can predict characteristic parameters on pathologic specimens of tumor or not. CFPAC-1 was injected subcutaneously on the back flank of athymic nude mice (n=13) then two tumors were initiated on each mouse (2${\times}$13=26 tumors). The mice were sacrificed to make specimen immediately after initial MR imaging then were compared with the MR image. A dedicated high-field (7T) small-animal MR scanner was used for image acquisitions. A T1 and T2 weighted axial image using RARE technique was acquired to measure the T2 values and tumor size. DWI MR was performed for calculating ADC values. To evaluate tumor cellularity and determine the levels of MVD, tumor cells were excised and processed for H-E staining and immunostaining using CD31. T2 values and ADC values were computed and analyzed for each half of the tumors and compared to the correlated specimens slide. Median ADC within each half of mass was compared to the cellularity and MVD in the correlated area of pathologic slide. The mean of ADC value is $0.7327{\times}10^{-3}$ $mm^2/s$ and standard deviation is $0.1075{\times}10^{-3}$ $mm^2/s$. There is a linear relationship between ADC value and tumor necrosis (R2=0.697, p< 0.001). DW image parameters including the ADC values can be utilized as surrogate markers to assess intratumoral neoangiogenesis and change of the internal structure of tumor cells.

• Proceedings of the Technology Innovation Conference
• /
• 1997.07a
• /
• pp.222-223
• /
• 1997

By analyzing the successful innovation case of potato microtuber mass production technology, a representative case of technology-push type creative innovation in an imitation oriented research culture, this paper attempts to figure out conceptual model of creative innovation that is initiated by the public laboratories in catching-up country, Stages of creative innovation can be divided into the internal R&D stage and the external commercialization stage. Success of the internal R&D stage depended on autonomy to secure creative research idea and commitment of individual researchers. Psychological pressure evoked from sportlights of mass media and commitment of sponsor increased the intensity of research efforts of the researcher Recognition of research problem and its significance was intensified by site visits of agricultural fields, and the recognized higher impacts of expected research results and knowledge creation achieved were a fundamental source of self-motivation. In the stage of commercialization stage, various legal, socio-economic, and psychological barriers were confronted. In a catching-up country lacking of experiences of creative innovation, creative innovation process can be regarded as a barrier elimination and cultural revolution process. Among the barriers, psychological refusal of farmers to corn-sized potato seeds was critical, which finally enforced to further researches to enlarge the size of potato seeds. In addition, the researcher has concentrated his research efforts in one specialized research area by getting a series of similar research project funds rather than diversification. It was lucky for him to have a chance to carry out a series of similar researches in one research area during the last 10 years. In getting research funds from government and private companies continuously in one research area, both internal and external promoters played significant roles.

• Journal of Veterinary Clinics
• /
• v.31 no.5
• /
• pp.394-402
• /
• 2014

The objective of this study was to investigate the effect of chronic unpredictable stress on the reproductive function and ovarian luteinizing hormone receptor (LHR) expression. 9-week-old C57BL/6 female mice were randomly divided into two groups: control group and stressed group. Mice have been stressed twice a day for 35 days with 12 different stressors which were randomly selected. The results demonstrate that there is significant increase in the anxiety-related behaviors (P < 0.05), decrease body weight gain rate (P < 0.01) and decrease in the average of litter size in stressed mice compared with control group (P < 0.01). Furthermore, the rate of primary, secondary and early antral follicles in stressed mice significantly decreased (P < 0.05), whereas that of atretic follicles significantly increased compared with control mice (P < 0.01). The immunohistochemical analysis revealed that reduced LHR expression in granulosa cells of follicle and luteal cells of corpus luteum in response to chronic unpredictable stress. The western blot analysis revealed significantly decrease in LHR expression in the stressed mice ovaries compared with the control (P < 0.05). These results suggest that ovarian LHR expression affected by chronic unpredictable stress and the modulated ovarian LHR is responsible for ovarian follicular maldevelopment and reproductive dysfunction.

• Korean Journal of Food Science and Technology
• /
• v.31 no.1
• /
• pp.238-245
• /
• 1999

Antioxidative effects of the water or ethanol extracts from Rhus verniciflua Stokes (RVS) were measured by protection against hydroxyl radicals in mouse brain tissue culture. In the water extracts from RVS, cell viabilities were estimated 60.0, 66.0, 72.0, 84.0 and 90.0% at addition of 1, 2, 4, 7 and $10{\mu}L$, respectively, compared with GO (20 mU/mL) alone. The cell viability in the ethanol extracts was similarly with water extracts. In the antitumor effects, the results showed that percentages of the HeLa cell death were approximately 24% for 12 hrs, 57% for 48 hrs at addition of 10%/well ethanol extracts respectively. To know inhibition of tumor growth, in vivo, mice (BALB/c) were inoculated with 0.25 mL CT-26 $(1{\times}10^6\;cells/mL)$ subcutaneously. After the generation of tumor, the results of RVS extracts (ethanol, water) injection showed generally that the tumor size in BALB/c was reduced. For physicochemical characterization of the RVS extracts, purified substances of water or ethanol extracts were analized with SDS-PAGE and ICP spectrometer. In electrophoresis, gel showed 2 bands (210, 230 KDa). The results of ICP verified that RVS extracts contain $Cu^{2+}$ in both samples. Conclusively, this substance might be a laccase which has a biological effective function, as a natural bioactive substance.