• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.77-83
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• 2024

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ_25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ_25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ_25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ_25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ_25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ_25-35-induced neurotoxicity and might be used to treat and/or prevent AD.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.185-194
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• 1998

Purpose : With the development of stereotactic immobilization systems capable of reliable serial repositioning, fractionated stereotactic radiation therapy (FSRT) offers the Potential for an improved treatment outcome by excellent dose delivery, and dose distribution characteristics with the favorable radiobiological properties of fractionated irradiation. We describe our initial experience using FSRT for the treatment of intracranial benign tumor. Materials and Methods : Between August 1995 and December 1996. 15 patients(7 males and 8 females aged 6-70 years) were treated with FSRT. The patients had the following diagnosis pituitary adenoma(10) including one patient who previously had received radiotherapy, craniopharyngioma (2), acoustic neurinoma (1), meningioma (2). Using the Gill-Thomas-Cosman relocatable head frame and multiple non-coplanar therapy, the daily dose of 2Gy was irradiated at 90% to 100% isodose surface of the isocenter The collimator sizes ranged from 26mm to 70mm. Results : In all patients except one follow-up lost, disease was well-controlled. Acute complication was negligible and no patient experienced cranial nerve neuropathies and radiation necrosis. In overall patient setup with scalp measurements, reproducibility was found to have mean of $1.1{\pm}0.6mm$ from the baseline reading. Conclusion : Relocatable stereotactic system for FSRT is highly reproducible and comfortable. Although the follow-up period was relatively short. FSRT is considered to be a safe and effective radiation technique as the treatment of intracranial tumor. But the fractionation schedule(fraction size, overall treatment time and total dose) still remains to be solved by further clinical trials.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.325-335
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• 1998

Purpose : Since the mid cranial fossa is composed of various thickness of bone, the tissue inhomogeneity caused by bone would produce dose attenuation in cobalt-60 gamma knife irradiation. The correction factor for bone attenuation of cobalt-60 which is used for gamma knife source is -3.5$\%$. More importantly, nearly all the radiosurgery treatment planning systems assume a treatment volume of unit density: any perturbation due to tissue inhomogeneity is neglected, This study was performed to confirm the bone attenuation in mid cranial fossa using gamma knife. Materials and Methods : Computed tomography was performed after Leksell stereotactic frame had been liked to the Alderson Rando Phantom (human phantom) skull area. Kodak X-omat V film was inserted into two sites of pituitary adenoma point and acoustic neurinoma point, and irradiated by gamma knife with 14mm and 18mm collimator. An automatic scanning densitometer with a 1mm aperture is used to measure the dose profile along the x and y axis. Results : Isodose curve constriction in mid cranial fossa is observed with various ranges. Pituitary tumor point is greater than acoustic neurinoma point (0.2-3.0 mm vs 0.1-1.3 mm) and generally 14 mm collimator is greater than 18mm collimator (0.4-3.0 mm vs. 0.2-2.2 mm) Even though the isodose constriction is found, constriction of 50$\%$ isodose curve which is used for treatment reference line does not exceed 1 mm. This range is too small to influence the treatment planning and treatment results. Conclusion : Radiosurgery planning system of gamma knife does not show significant error to be corrected without consideration of bone attenuation.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.439-448
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• 1993

The B-type gamma knife unit was installed at Kyung-Hee University Hospital in March 1992. The selective beam plugging method can be used to reduce the low percentage isodose profiles of normal sensitive organ and to modify the isodose curves of treatment volume for better shaping of the target volume. For representing the changes of the low percentage isodose profiles, the variations of dose distribution for several cases were discussed in this paper. The film dosimetry was peformed for the evaluation of calculated isodose profiles predicted by KULA dose planning system. The results were verified by RFA-3 automatic densitometry. The clinical application of selective beam shielding method was peformed in 17 patients in 100 patients who have undergone gamma knife radiosurgery for a year. The calculated and the measured isodose profiles for the high percentage regions were well consistent with each other. When the target of pituitary tumor is macro-size, the selective beam shielding method is the most applicable method. When the target size, however, is small, the correct selection of the proper helmet size is very important. All patients were exposed almost about 3~12 Gy for brain stem, and 3~11.2 Gy for optic apparatus. It is recommended that the same or other plugging patterns with multiple isocenters should be used for protection of the radiosensitive normal structures with precise treatment of CNS lesions.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.53-65
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• 2001

Purpose : To improve the local control of patients with nasopharyngeal cancer, we have implemented 3-D conformal radiotherapy and forward intensity modulated radiation therapy (IMRT) to used of compensating filters. Three dimension conformal radiotherapy with intensity modulation is a new modality for cancer treatments. We designed 3-D treatment planning with 3-D RTP (radiation treatment planning system) and evaluation dose distribution with tumor control probability (TCP) and normal tissue complication probability (NTCP). Material and Methods : We have developed a treatment plan consisting four intensity modulated photon fields that are delivered through the compensating tilters and block transmission for critical organs. We get a full size CT imaging including head and neck as 3 mm slices, and delineating PTV (planning target volume) and surrounding critical organs, and reconstructed 3D imaging on the computer windows. In the planning stage, the planner specifies the number of beams and their directions including non-coplanar, and the prescribed doses for the target volume and the permissible dose of normal organs and the overlap regions. We designed compensating filter according to tissue deficit and PTV volume shape also dose weighting for each field to obtain adequate dose distribution, and shielding blocks weighting for transmission. Therapeutic gains were evaluated by numerical equation of tumor control probability and normal tissue complication probability. The TCP and NTCP by DVH (dose volume histogram) were compared with the 3-D conformal radiotherapy and forward intensity modulated conformal radiotherapy by compensator and blocks weighting. Optimization for the weight distribution was peformed iteration with initial guess weight or the even weight distribution. The TCP and NTCP by DVH were compared with the 3-D conformal radiotherapy and intensitiy modulated conformal radiotherapy by compensator and blocks weighting. Results : Using a four field IMRT plan, we have customized dose distribution to conform and deliver sufficient dose to the PTV. In addition, in the overlap regions between the PTV and the normal organs (spinal cord, salivary grand, pituitary, optic nerves), the dose is kept within the tolerance of the respective organs. We evaluated to obtain sufficient TCP value and acceptable NTCP using compensating filters. Quality assurance checks show acceptable agreement between the planned and the implemented MLC(multi-leaf collimator). Conclusion : IMRT provides a powerful and efficient solution for complex planning problems where the surrounding normal tissues place severe constraints on the prescription dose. The intensity modulated fields can be efficaciously and accurately delivered using compensating filters.