• The Journal of Korean Society for Radiation Therapy
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• v.28 no.1
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• pp.35-46
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• 2016

Purpose : BoS(Base of Skull) Frame, the fixation tool which is used for the proton of brain cancer increases the lateral penumbra by increasing the airgap (the distance between patient and beam jet), due to the collision of the beam of the posterior oblique direction. Thus, we manufactured the fixation tool per se for improving the limits of BoS frame, and we'd like to evaluate the utility of the manufactured fixation tool throughout this study. Materials and Methods : We've selected the 3 patients of brain cancer who have received the proton therapy from our hospital, and also selected the 6 beam angles; for this, we've selected the beam angle of the posterior oblique direction. We' ve measured the planned BoS frame and the distance of Snout for each beam which are planned for the treatment of the patient using the BoS frame. After this, we've proceeded with the set-up that is above the location which was recommended by the manufacturer of the BoS frame, at the same beam angle of the same patient, by using our in-house Bos frame fixation tool. The set-up was above 21 cm toward the superior direction, compared to the situation when the BoS frame was only used with the basic couch. After that, we've stacked the snout to the BoS frame as much as possible, and measured the distance of snout. We've also measured the airgap, based on the gap of that snout distance; and we've proceeded the normalization based on each dose (100% of each dose), after that, we've conducted the comparative analysis of lateral penumbra. Moreover, we've established the treatment plan according to the changed airgap which has been transformed to the Raystation 5.0 proton therapy planning system, and we've conducted the comparative analysis of DVH(Dose Volume Histogram). Results : When comparing the result before using the in-house Bos frame fixation tool which was manufactured for each beam angle with the result after using the fixation tool, we could figure out that airgap than when not used in accordance with the use of the in-house Bos frame fixation tool was reduced by 5.4 cm ~ 15.4 cm, respectively angle. The reduced snout distance means the airgap. Lateral Penumbra could reduce left, right, 0.1 cm ~ 0.4 cm by an angle in accordance with decreasing the airgap while using each beam angle in-house Bos frame fixation tool. Due to the reduced lateral penumbra, Lt.eyeball, Lt.lens, Lt. hippocampus, Lt. cochlea, Rt. eyeball, Rt. lens, Rt. cochlea, Rt. hippocampus, stem that can be seen that the dose is decreased by 0 CGE ~ 4.4 CGE. Conclusion : It was possible to reduced the airgap by using our in-house Bos frame fixation tool for the proton therapy; as a result, it was possible to figure out that the lateral penumbra reduced. Moreover, it was also possible to check through the comparative analysis of the treatment plan that when we reduce the lateral penumbra, the reduction of the unnecessary irradiation for the normal tissues. Therefore, Using the posterior oblique the Brain cancer proton therapy should be preceded by decreasing the airgap, by using our in-house Bos frame fixation tool; also, the continuous efforts for reducing the airgap as much as possible for the proton therapy of other area will be necessary as well.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.67-76
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• 2006

Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.

• The Journal of Korean Society for Radiation Therapy
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• v.30 no.1_2
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• pp.117-128
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• 2018

Purpose : To evaluate the usability of plan transfer between TOMO HD and Radixact, we compared the differences of dose in transferred plans by evaluating the dose of normal organ and target. TOMO HDA and Radixact. The completed plans were transferred each other and we compared the differences of dose by evaluating the DVH of each plans. Materials and Methods : We planned 4 different plans assuming the treatment of 2 cases in Head and Neck Cancer and 2 cases Prostate cancer. Each plan was designed so that 95 % of the prescription dose was irradiated over 99 % of the target volume, and the normal organ constraints dose was based on the SMC tolerance dose protocol. Each plan was transferred to each equipment and DVH(dose volume histogram) analysis of the transferred plans was compared and evaluated. Results : The Mean dose of CTV and GTV was increased and decreased in the transferred plans, but there was no significant differences. The target coverage of CTV and GTV was decreased in all cases of transferred plans from TOMO HAD to Radixact, and the change of CI and HI in CTV was within 0.1. Normal organ dose was increased in most cases when transferring from HAD to Radixact in both treatment plans. Conclusion : According to the results of this experiment, the target coverage was above the standard and the normal organ dose was almost same or decreased when transferring the plans from Radixact to HDA equipment. However the target coverage was reduced when transferring the plans from HDA to Radixact and there was an increase in dose in normal organs that could cause sever side effects such as Optic Chiasm ($D_{max}$1.38 Gy), Bladder ($D_{max}$3.07 Gy), Penile Bulb ($D_{max}$1.14 Gy). Therefore, it is necessary to pay attention to the dose change when transferring the plan and one-time transfer due to equipment inspection will be useful for efficient radiation therapy, but if the transferred treatment plans continue for several consecutive days, the treatment plan should be resumed.

• The Journal of Korean Society for Radiation Therapy
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• v.32
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• pp.31-39
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• 2020

Purpose: The aims of this study were to compare the superficial dose with Optically Stimulated Luminescence Dosimeter(OSLD) measurement and Treatment Planning System(TPS) calculation for 6MV-Flattening Filter Free(FFF) energy using HalcyonTM and TrueBeamTM. Materials and methods: Phantom study was performed using the CT images of human phantom. In the treatment planning system, the Planning Target Volume(PTV) was contoured which is similar to Glottic cancer. Furthermore, Point(M), Point(R), and Point(L) were contoured at the iso-center of head and neck region and 5mm bolus was applied to the body contour. Each treatment plans using 6MV-FFF energy from HalcyonTM and TrueBeamTM with static Intensity Modulated Radiation Therapy(IMRT) and Volumetric Modulated Arc Therapy(VMAT) were established with eclipse. To reproduce the same position as the TPS, OSLDs were placed at the iso-center point and 5mm bolus was applied to compare the error rate after the dose delivery. Result: The results of the study using human phantom are as follows. In case of HalcyonTM, the mean absolute error rates of the point dose using the treatment planning system and the dose measured by OSLD were 1.7%±1.2% for VMAT and 4.0±2.8% for IMRT. Also TrueBeamTM was identified as 2.4±0.4% and 8.6±1.8% respectively for VMAT and IMRT. Conclusion: Through the results of this study, TrueBeamTM confirmed that the average error rate was 2.4 times higher for VMAT and 3.6 times higher for IMRT than HalcyonTM. Therefore, based on the results of this study, If we need a more accurate dose assessment for the superficial dose, It is expected that using HalcyonTM would be better than TrueBeamTM.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.287-300
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• 2005

Squamous cell carcinoma (SCC) in head and neck show a variability in the response to chemotherapy, even when it present with similar histological tumor type, grade, and clinical stage. The purpose of present study it to identify predictive bio-marker for the sensitivity or resistance to conventional chemotherapeutic agents, 5-fluorouracil (5-FU) and Cisplatin Oral cancer cell lines were used in present study. MTT assay was performed to evaluate the sensitivity and/or resistance to 5-FU and Cisplatin. And RT-PCR was carried out for evaluation of the mRNA expressions of various genes associated with mutation, inflammation (COX pathway), cell cycle, senescence and extracellular matrix (ECM). The molecules which are correlated with the sensitivity to 5-FU are XPA, XPC, OGG, APEX, COX-2, PPAR, Cyclin E, Cyclin B1, CDC2, hTERT, hTR, TIMP-3, TIMP-4 and HSP47. And the molecules are correlated with the sensitivity to Cisplatin are COX-1, iNOS, eNOS, PCNA, collagen 1 and MMP-9. Taken together, when choosing the appropriate chemotherpeutic agents for patients, considering the molecules which are correlated or reversely correlated is helpful to choose the resonable agents for cancer patients.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.9-15
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• 2006

Purpose: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. Materials and Methods: Total patients were 119 cases (Men 15, $48{\pm}13$ yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was stored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. Results: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. Conclusion: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

• Applied Microscopy
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• v.30 no.1
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• pp.45-59
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• 2000

Cis-platin is a widely used anticancer drug against certain solid tumors such as malignant ovarian tumor, malignant carcinoma of head and neck, bladder cancer and cervical cancer of uterus, and its major mechanism of action is inhibition of DNA synthesis of the tumor cell. To investigate the inhibitory effects of cis-platin on the ciliogensis of the ciliated cells in the mucosa of oviduct, the author pursued the alterations of $\alpha-tubulin$, which is the main constituent of the microtubles in cilia, after cis-platin treatment. To eliminate the possible variations due to ovarian cycle, female Spargue-Dawley rats ($150\sim200gm$ in B.W.) were pretreated with estradiol benzoate (20 mg/kg, once a day, for 4 consecutive days). Animals were administrated with cis-platin (6 mg/kg, i.p.) and sacrificed at 1day, 3days, 5days and 7days after treatment, respectively. Immunohistochemistry for $\alpha-tubulin$ using mouse anti-rat $\alpha-tubulin$ monoclonal antibody as primary antibody was done. Immunogold electronmicroscopy for intracellular distributions of $\alpha-tubulin$ was also performed with same primary antibody and Goat anti- mouse IgM which is preconjugated with gold particles of 15 nm as secondary antibody. The results obtained were as follows; 1. Strong immunoreactivity of $\alpha-tubulin$ was observed in ciliated cells of oviducts at 1, 3 and 5 days after estradiol pretreatment. 2. Weak immunoreactivity of $\alpha-tubulin$ was observed in ciliated cells of oviducts at 1 and 3 days after cis-platin treatment but it was recovered to strong immunoreactivity in 5 days 3. In immunogold electronmicroscopy, density of gold particles for $\alpha-tubulin$ reactions was decreased in apical cytoplasm, but few changes were observed in basal body or cilia at 1 and 3 days after cis-platin treatment. From these above results, it is indicated that synthesis of $\alpha-tubulin$ in ciliated cells of rat oviduct is inhibited by cis-platin treatment.

• Progress in Medical Physics
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• v.24 no.4
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• pp.271-277
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• 2013

In prostate IMRT planning, the planning target volume (PTV), extended from a clinical target volume (CTV), often contains an overlap air volume from the rectum, which poses a problem inoptimization and prescription. This study was aimed to establish a planning method for such a case. There can be three options in which volume should be considered the target during optimization process; PTV including the air volume of air density ('airOpt'), PTV including the air volume of density value one, mimicking the tissue material ('density1Opt'), and PTV excluding the air volume ('noAirOpt'). Using 10 MV photon beams, seven field IMRT plans for each target were created with the same parameter condition. For these three cases, DVHs for the PTV, bladder and the rectum were compared. Also, the dose coverage for the CTV and the shifted CTV were evaluated in which the shifted CTV was a copied and translated virtual CTV toward the rectum inside the PTV, thus occupying the initial position of the overlap air volume, simulating the worst condition for the dose coverage in the target. Among the three options, only density1Opt plan gave clinically acceptable result in terms of target coverage and maximum dose. The airOpt plan gave exceedingly higher dose and excessive dose coverage for the target volume whereas noAirOpt plan gave underdose for the shifted CTV. Therefore, for prostate IMRT plan, having an air region in the PTV, density modification of the included air to the value of one, is suggested, prior to optimization and prescription for the PTV. This idea can be equally applied to any cases including the head and neck cancer with the PTV having the overlapped air region. Further study is being under process.