• 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.

• 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.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.259-265
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• 1993

Between January 1985 and July 1992, 52 patients with locally advanced nasopharyngeal carcinoma were studied retrospectively for the effectiveness of sequential chemotherapy and radiation therapy. The male to female ratio was 3.3:1 with a median age of 41 years. Forty patients had squamous cell carcinoma and the remaining 12 had undifferentiated carcinoma. Seven patients had stage III disease and the remainder had stage IV disease at time of presentation. All patients were treated two courses of chemotherapy followed by radiation therapy. Chemotherapy consisted of either CVB (cisplatin, vincristine and bleomycin) or CF (cisplatin and 5-FU). Total radiation dose to the primary site ranged from 6000 cGy to 7500 cGy. Neck nodes were given booster treatment to maximum of 7000 cGy, depending on the extent of disease. Local control, overall survival and disease-free survival rates were analyzed. The complete response (CR) rate to chemotherapy was $15\%$ and the partial response (PR) rate was $46\%,$ for overall major response rate of $61\%.$ The CR rate was $87\%$ after radiation therapy. Median follow-up time was 51 months. The overall survival and disease-free survival rates at 36 months were $54\%\;and\;49\%,$ respectively. Median time to relapse was 15 months. The patterns of initial relapse in CR patients was as follows: locoregional failure only, 12 patients; distant metastasis only,11: both,2. Cox's multivariate regression model revealed that nodal status was the single most important independant prognostic factor influencing disease-free survival (p=0.001). Comparision of these results with other published reports with radiation therapy alone showed that a high rate of initial response to chemotherapy did not translate into local control or survival. At present time radiation therapy alone remains the standard treatment for locoregional cancer of the nasopharyngeal cancer. More controlled clinical trials must be completed before acceptance of chemotherapy as a part of treatment of advanced nasopharyngeal carcinoma.

• 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.

• 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.

• The Journal of Korean Society for Radiation Therapy
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• v.22 no.2
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• pp.97-103
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• 2010

Purpose: Treating same region with different modalities there is a limit to evaluate the total absorbed dose of normal tissues. The reason is that it does not support to communication each modalities yet. In this article, it evaluates absorbed dose of the patients who had been treated same region by a tomotherapy and a linear accelerator. Materials and Methods: After reconstructing anatomic structure with a anthropomorphic phantom, administrate 45 Gy to a tumor in linac plan system as well as prescribe 15 Gy in tomotherapy plan system for make an ideal treatment plan. After the plan which made by tomoplan system transfers to the oncentra plan system for reproduce plan under the same condition and realize total treatment plan with summation 45 Gy linac treatment plan. To evaluate the absorbed dose of two different modalities, do a comparative study both a simple summation dose values and integration dose values. Then compare and analyze absorbed dose of normal tissues and a tumor with the patients who had been exposured radiation by above two differents modalities. Results: The result of compared data, in case of minimum dose, there are big different dose values in spleen (12.4%). On the other hand, in case of the maximum dose, it reports big different in a small bowel (10.2%) and a cord (5.8%) in head & neck cancer patients, there presents that oral (20.3%), right lens (7.7%) in minimum dose value. About maximum dose, it represents that spinal (22.5), brain stem (12%), optic chiasm (8.9%), Rt lens (11.5%), mandible (8.1%), pituitary gland (6.2%). In case of Rt abdominal cancer patients, there represents big different minimum dose as Lt kidney (20.3%), stomach (8.1%) about pelvic cancer patients, it reports there are big different in minimum dose as a bladder (15.2%) as well as big different value in maximum dose as a small bowel (5.6%), a bladder (5.5%) in addition, making treatment plan it is able us to get. Conclusion: In case of comparing both simple summation absorbed dose and integration absorbed dose, the minimum dose are represented higher as well as the maximum dose come out lower and the average dose are revealed similar with our expected values data. It is able to evaluate tumor & normal tissue absorbed dose which could had been not realized by treatment plan system. The DVH of interesting region are prescribed lower dose than expected. From now on, it needs to develop the new modality which are able to realize exact dose distribution as well as integration absorbed dose evaluation in same treatment region with different modalities.

• 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.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.2
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• pp.177-182
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• 2014

Purpose : The goal of this study was to compare and analysis the dose distribution and treatment time between Tomotherapy planning with fixed jaw(FJ) and dynamic jaw(DJ). Materials and Methods : Seven patients were selected in the study including five common clinical cases(brain, head and neck(HN), lung, prostate, spine). 1) Helical Tomotherapy plans with FJ and DJ were generated with the same planning parameters such as Modulation factor, Pitch and Field width. 2) Tomo_edge plans with a larger field width were generated to compare to conventional HT delivery with fixed jaw. Dosimetric evaluation indices for target coverage are Dmin, Conformity index(CI) and for whole body including target are $V_{10%}$, $V_{25%}$, $V_{50%}$, $V_{75%}$ using Dose-volume histogram(DVH). Also, Treatment time and Cumulative MU were used for clinical review on Tomo_edge. Results : In case of using the same field width of Tomotherapy planning with FJ and DJ, the averaged variations were $V_{10%}$: -11.91%, $V_{25%}$: -7.6%, $V_{50%}$ :-4.75%, $V_{75%}$: -1.04%. Tomo_edge with a larger field width provides the averaged variations for target coverage: Dmin: -0.72%, CI: -1.25% and also shows the tendency of a sharp $V_{x%}$ decline in low dose area. The clinical improvements in the larger field width with DJ were observed in the treatment time, ranging from -51.21% to -15.11, and the Cumulative MU decrease, ranging from -57.74% to -15.31%. Conclusion : Target coverage achieved by FJ and DJ with the same field width has little differences. But integral doses on whole body efficiently decreased. Compared to the conventional HT delivery, Tomo_edge with a larger field width presents a little worse target coverage. However, it provides faster treatment delivery and improved cranial-caudal target dose conformity. Therefore, Tomo_edge mode is efficient in improving the treatment time and integral dose while maintaining comparable plan quality in clinic.

• The Journal of Korean Society for Radiation Therapy
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• v.19 no.1
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• pp.27-33
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• 2007

Purpose: We have performed SRS (stereotactic radiosurgery) for avm (arterry vein malformation) and brain cancer. In order to verify dose and localization of SRS, dose distributions from TPS ($X-Knife^{(R)}$ 3.0, Radionics, USA) and GafChromic $EBT^{(R)}$ film in a head phantom were compared. Materials and Methods: In this study, head and neck region of conventional humanoid phantom was modified by substituting one of 2.5 cm slap with five 0.5 cm acrylic plates to stack the GafChromic $EBT^{(R)}$ film slice by slice with 5 mm intervals. Four films and five acrylic plates were cut along the contour of head phantom in axial plane. The head phantom was fixed with SRS head ring and adapted SRS localizer as same as real SRS procedure. CT images of the head phantom were acquired in 5 mm slice intervals as film interval. Five arc 6 MV photon beams using the SRS cone with 2 cm diameter were delivered 300 cGy to the target in the phantom. Ten small pieces of the film were exposed to 0, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900 cGy, respectively to calibrate the GafChromic $EBT^{(R)}$ film. The films in the phantom were digitized after 24 hours and its linearity was calibrated. The pixel values of the film were converted to the dose and compared with the dose distribution from the TPS calculation. Results: Calibration curve for the GafChromic $EBT^{(R)}$ film was linear up to 900 cGy. The R2 value was better than 0.992. Discrepancy between calculated from $X-Knife^{(R)}$ 3.0 and measured dose distributions with the film was less than 5% through all slices. Conclusion: It was possible to evaluate every slice of humanoid phantom by stacking the GafChromic EBT film which is suitable for 2 dimensional dosimetry, It was found that film dosimetry using the GafChromic $EBT^{(R)}$ film is feasible for routine dosimetric QA of stereotactic radiosurgery.