• Journal of the Korean Society of Radiology
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• v.10 no.3
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• pp.195-200
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• 2016

Acute promyelocytic leukemia(APL) is not just the poor grades of treating a type of blood cancer hayeoteul combination with chemotherapy despite concurrent radiation therapy are known to exhibit a greater effect and also works on normal cells to result in side effects. In this study, when after treatment with gamma rays, such as $TNF-{\alpha}$ in order to reduce these side effects was confirmed how affected the cell death of normal cells and cancer cells. HL-60 cells were used as the APL cell line HL-60 cells were differentiated with DMSO for treatment are shown the properties of normal granulocytes was used as a control group. As a result, HL-60 cells treated with $TNF-{\alpha}$ and gamma rays with only showed a cytotoxic effect by inducing the apoptosis cells were put to death. Consequently, $TNF-{\alpha}$ is thought to active substances that can increase the efficiency of cancer treatment to increase the removal of cancer cells when used with low-density gamma-ray treatment in order to eliminate the side effects of chemotherapy.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2004.11a
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• pp.85-87
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• 2004

We fabricated flexible thermoradiotherapy probes to alternated combination with Interstitial hyperthermia and Brachyradiotherapy thermoradiotherapy probe was coated by gold plate on polyethylene brachytherapy probe. When Agar phantom was heated 15 minute with 30 W radiofrequency power, temperature increased as 5oC for polyethylene probe and 20oC for gold coated polyethylene probe. We observed that the 1 cm square array would heat a volume with a 1.25 cm radius circular field cross section to therapeutic temperatures (90% relative SAR using Tm) and the 2 cm square array with a 1.75 cm radius rectangular field with central inhomogeneity. With 2 cm long electrode implants, we observed that the 1 cm square array would heat a 3 cm long sagittal section to therapeutic temperature (90% relative SAR using Tm). The histopathological changes associated with RF heating of normal canine brains have been correlated with thermal distributions. RF needle electrode heating was applied for 50 min to generate tissue temperatures of 43${\circ}$C. We obtained a quarter of the heated tissue material immediately after heating and sacrificed at intervals from 7${\sim}$30 days. The acute stage was demonstrated by liquefactive necrosis, pyknosis of neuronal element in the gray matter. Mild gliosis occurring around the necrosis was demonstrated in the last sacrificed (days30)canine brain.

• Korean Journal of Head & Neck Oncology
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• v.15 no.1
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• pp.35-39
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• 1999

Objectives: The treatment for squamous cell carcinoma of the tonsil remains controversial. Surgery or radiation therapy alone is effective in treating early tonsil cancer, but results with single treatment modality in advanced disease have been disappointing. We retrospectively analyzed 37 patients with advanced squamous cell carcinoma of the tonsil for two treatment modalities in an effort to identify more efficacious therapeutic options. Materials and Methods: From 1990 through 1997, 37 patients who were treated primarily with surgery, were retrospectively sudied. The patients were grouped into two groups according to the method of treatment, extended tonsillectomy followed by irradiation and/or postradiation neck dissection(Group I) and a combination of composite resection and postoperative radiation(Group II). Results: The three year disease-tree survival in patients with stage IV lesions was 59.09% for the Group I patients, and 56.25% for the Group II patients. This difference was not statistically significant(p=0.775). The primary tumor recurrence rate in Group I was 16.7% in contrast to 23.1% for Group II. The local recurrence rate in the neck was 16.7% for the Group I patients and 23.1% for the Group II patients. There was no significant difference in the frequency of recurrences in the primary or neck in the patients treated with extended tonsillectomy or composite resection(p=0.639). Fistula formation and aspiration occurred in four patients after composite resection. Additionally, there were three trismus, one soft tissue necrosis, and one velopharyngeal insufficiency. Major complications were not observed in the patients treated with extended tonsillectomy and irradiation: velopharyngeal insufficiency was observed in eight patients and soft tissue necrosis in two patients. Conclusion: Extended tonsillectomy followed by irradiation may be an effective therapy with low morbidity in selected patients with tonsil cancer.

• Korean Journal of Radiology
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• v.24 no.3
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• pp.235-246
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• 2023

Objective: It is difficult to predict the treatment response of tissue after stereotactic radiosurgery (SRS) because radiation necrosis (RN) and tumor recurrence can coexist. Our study aimed to predict tumor recurrence, including the recurrence site, after SRS of brain metastasis by performing a longitudinal tumor habitat analysis. Materials and Methods: Two consecutive multiparametric MRI examinations were performed for 83 adults (mean age, 59.0 years; range, 27-82 years; 44 male and 39 female) with 103 SRS-treated brain metastases. Tumor habitats based on contrast-enhanced T1- and T2-weighted images (structural habitats) and those based on the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) images (physiological habitats) were defined using k-means voxel-wise clustering. The reference standard was based on the pathology or Response Assessment in Neuro-Oncologycriteria for brain metastases (RANO-BM). The association between parameters of single-time or longitudinal tumor habitat and the time to recurrence and the site of recurrence were evaluated using the Cox proportional hazards regression analysis and Dice similarity coefficient, respectively. Results: The mean interval between the two MRI examinations was 99 days. The longitudinal analysis showed that an increase in the hypovascular cellular habitat (low ADC and low CBV) was associated with the risk of recurrence (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.46-4.91; P = 0.001). During the single-time analysis, a solid low-enhancing habitat (low T2 and low contrast-enhanced T1 signal) was associated with the risk of recurrence (HR, 1.54; 95% CI, 1.01-2.35; P = 0.045). A hypovascular cellular habitat was indicative of the future recurrence site (Dice similarity coefficient = 0.423). Conclusion: After SRS of brain metastases, an increased hypovascular cellular habitat observed using a longitudinal MRI analysis was associated with the risk of recurrence (i.e., treatment resistance) and was indicative of recurrence site. A tumor habitat analysis may help guide future treatments for patients with brain metastases.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.1-9
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• 2001

Purpose : To establish the role of stereotactic radiosurgery (SRS) for the treatment of patients with angiographically occult vascular malformation (AOVM). Materials and Methods : Eleven patients (12 lesions) with AOVM were treated with linear accelerator-based SRS between February 1995 and December 1999. A magnetic resonance imaging of each patients showed well-circumscribed vascular lesion with reticulated core of heterogeneous signal intensity and peripheral rim of low signal intensity. SRS were peformed with the median peripheral dose of 16 Gy (range 13~25). A single isocenter was used with median collimator size of 14 mm (range 8~20) diameter. Results : With a median follow-up period of 42 months (range 12~56), rebleeding occurred in 3 AOVMS at 5, 6 and 12 months after SRS but no further bleeding did. Two patients experienced radiation-induced necrosis associated with permanent neurologic deficit and one patient showed transient edema of increased 72 signal intensity. Conclusion : SRS may be effective for the prevention of rebleeding in AOVM located in surgically inaccessible region of the brain. Careful consideration should be needed in the decision of case selection and dose prescription because the incidence of radiation-induced complications is too high to be accepted.

• 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.18 no.4
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• pp.314-320
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• 2000

Purpose :To investigate whether changes in plasma concentrations of transforming growth factor-$\beta$1(TGF-$\beta$1), tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin-6 (IL-6) could be used to identify the development of radiation-induced pneumonitis in the lung cancer patients. Methods and Materials :Seventeen patients with lung cancer (11 NSCLC, 6 SCLC) were enrolled in a prospective study designed to evaluate clinical and molecular biologic correlation of radiation-induced pneumonitis. The study began in May 1998 and completed in July 1999. All patients were treated with radiotherapy with curative intent : 1.8 Gy per day, 5 fractions per week. Serial measurements of plasma TGF-$\beta$1, TNF-$\alpha$ and IL-6 were obtained in all patients before, weekly during radiotherapy and at each follow-up visits after completion of treatment. These measurements were quantified using enzyme linked immunosorbent assay (ELISA). All patients were evaluated for signs and symptoms of pneumonitis at each follow-up visit after completion of radiotherapy. High resolution CT (HRCT) scans were obtained when signs and symptoms of pneumonitis were developed after completion of radiotherapy. Results : Thirteen patients eventually developed signs and symptoms of clinical pneumonitis 씬file four patients did not. TGF-$\beta$ 1 levels were elevated in all 13 patients with pneumonitis, which showed characteristic pattern of elevation (38.45 ng/ml at pretreatment, 13.66 ng/ml during radiotherapy, then 60.63 ng/ml at 2-4 weeks after completion of radiotherapy). The levels of TNF- $\alpha$ and IL-6 were also elevated In the group of patients who developed pneumonitis but the pattern was not characteristic. Conclusions : Changes in plasma TGF$\beta$-1 levels before, during and after radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic pneumonitis. Other cytokines like TNF- $\alpha$ and IL-6 shows no meaningful changes in association with radiation pneumonitis.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.29-34
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• 2013

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.40-54
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• 2004

Purpose : Captopril (angiotension converting enzyme inhibitor) is known to have a radioproptective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotectlve efiect and mechanism of captopril on the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. Materials and Methods : The histopathological changes and immunohistochemical stains ($TNF{\alpha}$, $TGF{\beta}1$, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. Results : In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial $TNF-{\alpha}$ and $TGF-{\beta}1$ in the radiation alone group continuously increased. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of $TNF-{\alpha}$ in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). Conclusion : This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

• Journal of Korean Neurosurgical Society
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• v.66 no.5
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• pp.511-524
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• 2023

Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.