• Journal of Oral Medicine and Pain
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• v.35 no.3
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• pp.165-175
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• 2010

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of Oral Medicine and Pain
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• v.38 no.3
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• pp.221-233
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• 2013

Bile acids are polar derivatives of cholesterol essential for the absorption of dietary lipids and regulate the transcription of genes that control cholesterol homeostasis. Recently it have been identified the synthetic chenodeoxycholic acid (CDCA) derivatives HS-1200 and cisplatin showed apoptisis-inducing activity on various cancer cells in vivo and in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with HS-1200 and cisplatin on human tongue squamous cell carcinoma cells (SCC25 cells). To investigate whether the co-treatment with HS-1200 and cisplatin compared to each single treatment efficiently reduces the viability of SCC25 cells, MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis DNA hypoploidy. Westen blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, co-treatment with HS-1200 and cisplatin on SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, reduction of MMP and proteasome activity, the increase of Bax and the decrease of Bcl-2, decrease of DNA content, the release of cytochrome c into cytosol, translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated SCC25 cells did not show these patterns. Although the single treatment of $25{\mu}M$ HS-1200 and $4{\mu}g/ml$ cisplatin for 24 h did not induce apoptosis, the co-treatment of these reagents prominently induced apoptosis. Therefore our data provide the possibility that the combination therapy with HS-1200 and cisplatin could be considered as a novel therapeutic strategy for human squamous cell carcinoma.

• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of the Korean Geographical Society
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• v.30 no.3
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• pp.242-254
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• 1995

The Hadano Basin is located at a distance of about 70kms and 60kms from Tokyo and Yokohama and lies in the south-west part of the Kanto region in Japan. The basin area, which correspoends to the catchment of the Kaname River, is about areal size of 60.7$\textrm{km}^2$ and extends about length of 8kms in E-W direction and about width of 5kms in N-S direction (Fig.1). The Hadano basin is filled with thick pile of the alluvum from deposits composed of volcanic materials, mostly came from the Hakone Volcano and overlain by Fuji Volcanic ashes. Fluvial deposits form the good aquifer, therefore water resources of Handano City has been largely depending upon the eroundwater. Urbanization and industrialization of the basin has been rapid in the last thirty years, after activation of "Factory Attraction Policy of Hadano City" in 1956. Growth in population and number of factory due to urbanization changed the land-use pattern of the basin rapidly and increased the water demands. Therefore, Hadano City exploited a new source of water supply, and have introduced the prefectureal waterworks since 1976. On the other hand, the rapid urbanization has brought about the pollution of streams in the basin by domestic sewage and industrial waste water. Diffusion rate of sewerage systems in Hadano City is 38% in 1993. In ordcr to examine the impact of anthropogenic factors on river environments, the author took up the change of land-use and diffusion area of sewerage as parameters, and performed field surveys on water discharge and quality. The survey has been made at upstream and downstream of the main stream regularly per month, to get informati ons about the variation of discharge and water quality aiong the stream and its diurnal fluctuation. Annual variation has been analyzed based the data from Hadano City Office. The results are summarized as follows. 1. Stream discharge has been increasing by urbanization (Fig.3). Water quality (C $l^{-10}$ , N $H^{+}$$_{ 4}$-N, BOD) has been improving gradually after the application of sewerage service, yet water pollution load at the lower station has increased than that at the upper one because of the larger anthropogenic discharge volumes (Fig.4). 2. Corrclation coefficient of discharges between upper and lower was 0.81-0.92. Pollutant loads of the R. Kamame after the confluence with R. Kuzuha grew up by 2.4-3.7 times as compared with its upper reaches, and it increased to 3.7-6.9 times after the confluence with the R. Muro (Fig.5). 3. The changes of water quality along the stream can be divided into two groups (Fig.6a). First: water quality of the R. Kaname and R. Shijuhachisse is becoming worse towards the lower reaches because the water from branches are polluted. Second: water quality are improved in the lower where spring and small branch streams supply clear water, for example R. Mizunashi, R. Muro and R. Kuzuha. 4. Measured discharge at the upper station in the R. Shijuhachisse is 0.153㎥/sec, and about 55% of this is recharged until it reaches to the lower point. The R. Mizunashi has a discharge of 1.155㎥/sec at the upper point, is recharged 0.24㎥/sec until the midstream and groundwater spring 0.2㎥/sec at the lower reaches. R. Kuzuha recharged all the mountain runoff (0.2㎥/sec) at the upper reaches. The R. Muro is supplied by many springs and the estimated discharge of spring was 0.47㎥/sec (Fig.6b). 5. Diurmal variations in discharge and water quality are influenced clearly by domestic and industrial waste waters (Fig.7, 8).ed clearly by domestic and industrial waste waters (Fig.7, 8).

• Progress in Medical Physics
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• v.20 no.1
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• pp.37-42
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• 2009

Proton therapy facility, which is recently installed at National Cancer Center in Korea, generally produces a large amount of radiation near cyclotron due to the secondary particles and radioisotopes caused by collision between proton and nearby materials during the acceleration. Although the level of radiation by radioisotope decreases in length of time, radiation exposure problem still exists since workers are easily exposed by a low level of radiation for a long time due to their job assignment for maintenance or repair of the proton facility. In this paper, the working environment near cyclotron, where the highest radiation exposure is expected, was studied by measuring the degree of radiation and its duration for an appropriate level of protective action guide. To do this, we measured the radiation change in the graphite based energy degrader, the efficiency of transmitted beam and relative activation degree of the transmission beam line. The results showed that while the level of radiation exposure around cyclotron and beam line during the operation is much higher than the other radiation therapy facilities, the radiation exposure rate per year is under the limit recommended by the law showing 1~3 mSv/year.