• Radiation Oncology Journal
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• v.13 no.3
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• pp.205-214
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• 1995

Purpose : To investigate the effect of Ginkgo biloba extract (GBE) on hypoxic cell fraction and metabolic status in fibrosarcoma (FSa II) of C3H mouse. Materials and Methods : Fibrosarcoma (FSa II) 6 mm in diameter, growing in the right hindleg muscle of C3H mouse was used for estimation of hypoxic cell fraction using comparison of $TCD_{50}$. Radiation was given one hour after administration of GBE (100 mg/kg. i.p.) with or without priming dose of GBE (100 mg/kg, i.p.) given 24 hours earlier. Radiation was also given under air breathing condition or clamp hypoxia without GBE as controls. $^{31}p$ NMR spectroscopy was performed before and one hour after administration of GBE with or without priming dose of GBE. Results : $TCD_{50/120's}$ were 81.7 (77.7-86.0) Gy when irradiated under clamped hypoxia 69.6 (66.8-72.5) Gy under air breathing condition. 67.5 (64.1-71.1) Gy with a single dose of GBE (100 mg/kg) given one hour before irradiation, and 62.2 (59.1-65.5) Gy with two doses of GBE given at 25 hours and one hour before irradiation. The hypoxic cell fractions, estimated from $TCD_{50/120's}$, were $10.6{\%}$ under air breathing condition, $7.2{\%}$ after a single dose of GBE, and $2.7{\%}$ after two doses of GBE. The results of $^{31}P$ NMR spectroscopy were as follow. PCr/Pi ratio was $0.27{\pm}0.04$ and $0.40{\pm}0.04$ before and one hour after a single dose of GBE (p<0.05), respectively, without priming dose and $0.30{\pm}0.02$ and $0.71{\pm}0.04$, respectively, with priming dose (p<0.01). These findings indicate that the metabolic status is slightly improved after a single dose and markedly after repeated administrations. Conclusion : GBE decreases the hypoxic cell fraction and imprvoes the meta bolic status of tumor, probably by increasing the blood flow and delivery of oxygen and nutrients, resulting in increased radiosensitivity of tumor.

• Clinical and Experimental Pediatrics
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• v.46 no.2
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• pp.167-172
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• 2003

Purpose : Pulmonary vascular hypertension is a common problem in congenital heart disease, the most common cardiac condition in childhood. However, the mechanisms responsible for this pathologic change, treatment, and prevention are poorly understood. Therefore, we studied the gene expression of vascular endothelial growth factor(VEGF) by using a hypoxic model of the pulmonary artery smooth muscle cells. Methods : The main pulmonary artery and its proximal branches of a 6 wk old Fischer rat were excised. They were cut into multiple small pieces and suspended in DMEM medium supplemented with 20% fetal bovine serum and incubated in 5% $CO_2$-95% air atmosphere. The smooth muscle cells were confirmed by immunostaining with smooth muscle myosin and ${\alpha}$-smooth muscle actin antibodies. The VEGF gene expression in the hypoxic group was compared with the one in control the group as well as the one in the starved group by RT-PCR and Northern blot hybridization. Results : There was no statistically significant difference among the control, hypoxic and starved groups. Conclusion : There are few studies of pulmonary vascular hypertension at the molecular level in Korea. Therefore, we studied the expression of VEGF gene in hypoxic pulmonary vascular smooth muscle cells. Further studies will be needed to find the difference between newly born and adult rats, or human and rat pulmonary vascular smooth muscle cells in gene expression. We hope that the study will lead to a better understanding of pulmonary vascular hypertension.

• Korean Journal of Environmental Biology
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• v.31 no.3
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• pp.204-212
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• 2013

This study analyzed the occurrence of tunic softness, survival rate, metabolic rate and histopathologic changes arising from the effect of hypoxic environment in order to find the causes of occurrences of tunic softness, which manifests as the key phenomenon of mass mortality of Halocynthia roretzi. Regarding the survival of H. roretzi with reduction in dissolved oxygen, all the entities died on the 4th day of exposure to the dissolved oxygen concentration of $2mg\;L^{-1}$ while 50% mortality was observed on the 5th day of exposure to the dissolved oxygen concentration of $3mg\;L^{-1}$. Therefore the 5 days-$LC_{50}$ was found to be $3.55mg\;L^{-1}$ (1.86~$4.96mg\;L^{-1}$). However, occurrence of tunic softness was not observed during the period of exposure to low oxygen concentration. The oxygen consumption rate significantly decreases at the dissolved oxygen concentration of less than $5mg\;L^{-1}$ in comparison to the control group. Therefore, it is presumed that H. roretzi controls the respiration rate for prescribed period of time when exposed to hypoxic environment. Regarding the histopathologic changes in the gill, digestive gland and cyst of H. roretzi due to hypoxic environment, necrosis of epithelial layer, in filtration of blood cells, and condensation of nucleus that compose each of the organs were observed. Regarding morphological changes, the decrease in volume with shrinking of the tunic, discoloration of the internal organs and necrosis of gill and hepatopancreas were observed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2353-2358
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• 2014

Purpose: We aimed to detect the expression of HIF-1${\alpha}$, VEGF, HPSE-1 and CD31 in SKOV3 xenografts in nude mice treated with different doses of ionizing radiation, trying to explore the possible mechanism of hypoxia and radioresistance. Methods: Nude mice bearing SKOV3 xenografts were randomly divided into 4 groups: Group A (control group, no ionizing radiation), Group B (treated with low dose of ionizing radiation: 50cGy), Group C (treated with high dose of ionizing radiation: 300cGy), Group D ( combined ionizing radiation, treated with ionizing radiation from low dose to high dose : 50cGy first and 300cGy after 6h interval). The mRNA levels of HIF-1 and VEGF in each group were detected by real time polymerase chain reaction, while HPSE-1 expression was measured by ELISA. The microvessel density (MVD) and hypoxic cells were determined through immunohistochemical (IHC) staining of CD31 and HIF-1a. Results: Significant differences of HIF-1${\alpha}$ mRNA level could be found among the 4 groups (F=74.164, P<0.001): Group C>Group A>Group D> Group B. The mRNA level of VEGF in Group C was significantly higher than in the other three groups (t=-5.267, P=0.000), while no significant difference was observed among Group A, B and D (t=1.528, 1.588; P=0.205, 0.222). In addition, the MVD was shown to be the highest in Group C (t=6.253, P=0.000), whereas the HPSE-1 level in Group A was lower than in Group B (t=14.066, P=0.000) and higher than in Group C (t=-21.919, P=0.000), and similar with Group D (t=-2.066, P=0.058). Through IHC staining of HIF-1a, the expression of hypoxic cells in Group A was (++), Group B was (+), Group C was (+++) and Group D was (+). Conclusion: Ionizing radiation with lowerdoses might improve tumor hypoxia through inhibiting the expression of HIF-1 and HPSE-1, whereas higherdoses worsen tumor hypoxic conditions by up-regulating HIF-1${\alpha}$, HPSE-1, VEGF and CD31 levels. A protocol of low-dose ionizing radiation followed by a high-dose irradiation might at least partly improve tumor hypoxia and enhance radiosensitivity.

• Radiation Oncology Journal
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• v.8 no.1
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• pp.1-6
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• 1990

In the present study, a perfluorchemical emulsion (Fluosol-DA $20\%$) did not alter $D_o\;and\;D_q$ values on cell survival curve, indicating that the lack of a direct effect of Fluosol-DA $20\%$ on cellular radiosensitivity in vitro. The effect of Fluosol-DA $20\%$ injection in combination with carbogen breathing was determined on the hypoxic cell fraction in SCK tumors. The hypoxic cell fraction in control SCK tumors was 0.39. This value decreased to 0.05 when the mice were i.v. injected with 12 ml/kg of Fluosol-DA $20\%$ in a carbogen atomosphere. The measured mean and median $PO_2$ values with a microelectrode in the control tumors was 9 mmHg and 4 mmHg, respectively. The treatment of the SCK tumors in the host mice with injected Fluosol-DA $20\%$ in combination with carbogen breathing increased the mean and median $PO_2$ values to 67 mmHg and 62 mmHg, respectively. Using carbogen breathing alone caused a moderate increase of tumor $PO_2$. But Fluosol-DA $20\%$ injection alone caused little change $PO_2$ in the tumor. It was concluded that the combination of Fluosol-DA injection and carbogen breathing is an effective means to improve oxygenation of tumors.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.24 no.5
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• pp.303-314
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• 1991

Hypoxic bottom $(\leq2.0ml/l),\;40\%\;oxygen\;saturation)$ is formed in the semi-closed Wonmun bay during summer and autumn early. This study was carried out to know seasonal distribution of marine bacteria and the role of marine bacteria for forming the hypoxic bottom at Wonmun bay during summer and autumn early, 1990. During the study periods, 170 bacterial strains were isolated from sea water and sediment. Viable cell counts were ranged between $10^5-10^7\;cells/ml$. The dominant species were Acinetobacter spp. in spring, Flavobacerium spp. in summer, Pseudomonas spp. in autumn, Serratia spp. in winter. Because ETSA(Electron Transport System Activity) reveals potential consumption of oxygen in the aquatic microorganisms, the ETSA was used as potential consumption of oxygen in this study. The potential consumption of oxygen was in the range of $232.4-637.5{\mu}l/O_2/l/day$ by marine organism and $142.6-432.4{\mu}l/O_2/l/day$ by marine bacteria during the study periods. The ratio of potential oxygen consumption of marine bacteria to total marine microorganism was 0.54. The potential consumption of oxygen by marine bacteria closely related with the number of viable cells. Consequently, bacteria play an important role to form Hypoxic bottom at marine environment.

• Molecules and Cells
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• v.37 no.11
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• pp.785-794
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• 2014

Mitophagy, a cellular process that selectively targets dysfunctional mitochondria for degradation, is currently a hot topic in research into the pathogenesis and treatment of many human diseases. Considering that hypoxia causes mitochondrial dysfunction, which results in cell death, we speculated that selective activation of mitophagy might promote cell survival under hypoxic conditions. In the present study, we introduced the Regulator of calcineurin 1-1L (Rcan1-1L) to initiate the mitophagy pathway and aimed to evaluate the effect of Rcan1-1L-induced mitophagy on cell survival under hypoxic conditions. Recombinant adenovirus vectors carrying Rcan1-1L were transfected into human umbilical vein endothelial cells and human adult cardiac myocytes. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and Trypan blue exclusion assay, Rcan1-1L overexpression was found to markedly reverse cell growth inhibition induced by hypoxia. Additionally, Rcan1-1L overexpression inhibited cell apoptosis under hypoxic conditions, as detected by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis assay. Meanwhile, the mitochondria-mediated cell apoptotic pathway was inhibited by Rcan1-1L. In contrast, knockdown of Rcan1-1L accelerated hypoxia-induced cell apoptosis. Moreover, Rcan1-1L overexpression significantly reduced mitochondrial mass, decreased depolarized mitochondria, and downregulated ATP and reactive oxygen species production. We further delineated that the loss of mitochondrial mass was due to the activation of mitophagy induced by Rcan1-1L. Rcan1-1L overexpression activated autophagy flux and promoted translocation of the specific mitophagy receptor Parkin into mitochondria from the cytosol, whereas inhibition of autophagy flux resulted in the accumulation of Parkin-loaded mitochondria. Finally, we demonstrated that mitochondrial 1permeability transition pore opening was significantly increased by Rcan1-1L overexpression, which suggested that Rcan1-1L might evoke mitophagy through regulating mitochondrial permeability transition pores. Taken together, we provide evidence that Rcan1-1L overexpression induces mitophagy, which in turn contributes to cell survival under hypoxic conditions, revealing for the first time that Rcan1-1L-induced mitophagy may be used for cardioprotection.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2013.05a
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• pp.665-666
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• 2013

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.187-187
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• 2001

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.173.1-173.1
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• 2000