• 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.

• 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.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.

• The Journal of Korean Society for Radiation Therapy
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• v.34
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• pp.7-12
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• 2022

Purpose: When it is difficult to secure the skin dose when treating Irregularly Shaped Skin Surface such as the nose where it is difficult to apply a bolus, increase the skin dose with a treatment plan that combines the IMRT (Intensity Modulated Radiation Therapy) delivery technique and FFF (Flattening Filter Free), It was tried to find out whether or not through the phantom experiment. Materials & Methods: Based on the 6MV-FF (Flattening Filter) and VMAT (Volumetric-Modulated Arc Therapy) treatment plans, which are the most commonly used treatment plans for head and neck cancer, A comparison group was created by combining VMAT and IMRT, FF and FFF, and the presence or absence of 5 mm bolus application. A virtual target was created on the Rando Phantom's nose, and a virtual bolus of 5 mm was applied assuming full contact on the Rando Phantom's nose. Five measurement points were determined based on the phantom's nose, and the absorbed dose was measured by irradiating each treatment plan 3 times per treatment plan according to the treatment technique and whether or not the bolus was applied. Result: The difference in skin dose in FF vs FFF increased in the case of FFF in VMAT bolus off, and there was no difference in case of IMRT bolus off. In VMAT bolus 5 mm and IMRT bolus 5 mm, it was confirmed that the skin dose was rather decreased in FFF. The difference in skin dose between VMAT and IMRT increased only in the case of FFF bolus off, and there was no statistical difference in the rest. For the difference in skin dose between bolus off vs bolus 5 mm, it was confirmed that the skin dose increased at bolus 5 mm, except for the case of using IMRT FFF. The treatment plan combining IMRT and FFF did not find any statistically significant difference as a result of analyzing the measured values of the treatment plan skin dose applied with a 5 mm bolus using the commonly used VMAT and FF. Therefore, it is thought that by using IMRT_FFF, it is possible to deliver a skin dose similar to that of applying a 5 mm bolus to VMAT_FF, which can be useful for patients who need a high skin dose but have difficulty applying a bolus. Conclusion: For patients who find it difficult to apply bolus, an increase in skin dose can be expected with a treatment plan that properly combines IMRT and FFF compared to VMAT and FF.

• Radiation Oncology Journal
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• v.18 no.2
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• pp.150-156
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• 2000

Purpose : Stereotactic radiation therapy (SRT) can deliver highly focused radiation to a small and spherical target lesion with very high degree of mechanical accuracy. For non-spherical and large lesions, however, inclusion of the neighboring normal structures within the high dose radiation volume is inevitable in SRT This is to report the beam shaping using the partial closure of the independent jaw in SRT and the verification of dose calculation and the dose display using a home-made soft ware. Materials and Methods : Authors adopted the idea to partially close one or more independent collimator jaw(5) in addition to the circular collimator cones to shield the neighboring normal structures while keeping the target lesion within the radiation beam field at all angles along the arc trajectory. The output factors (OF's) and the tissue-maximum ratios (TMR's) were measured using the micro ion chamber in the water phantom dosimetry system, and were compared with the theoretical calculations. A film dosimetry procedure was peformed to obtain the depth dose profiles at 5 cm, and they were also compared with the theoretical calculations, where the radiation dose would depend on the actual area of irradiation. Authors incorporated this algorithm into the home-made SRT software for the isodose calculation and display, and was tried on an example case with single brain metastasis. The dose-volume histograms (DVH's) of the planning target volume (PTV) and the normal brain derived by the control plan were reciprocally compared with those derived by the plan using the same arc arrangement plus the independent collimator jaw closure. Results : When using 5.0 cm diameter collimator, the measurements of the OF's and the TMR's with one independent jaw set at 30 mm (unblocked), 15.5 mm, 8.6 mm, and 0 mm from th central beam axis showed good correlation to the theoretical calculation within 0.5% and 0.3% error range. The dose profiles at 5 cm depth obtained by the film dosimetry also showed very good correlation to the theoretical calculations. The isodose profiles obtained on the home-made software demonstrated a slightly more conformal dose distribution around the target lesion by using the independent jaw closure, where the DVH's of the PTV were almost equivalent on the two plans, while the DVH's for the normal brain showed that less volume of the normal brain receiving high radiation dose by using this modification than the control plan employing the circular collimator cone only. Conclusions : With the beam shaping modification using the independent jaw closure, authors have realized wider clinical application of SRT with more conformal dose planning. Authors believe that SRT, with beam shaping ideas and efforts, should no longer be limited to the small spherical lesions, but be more widely applied to rather irregularly shaped tumors in the intracranial and the head and neck regions.

• Journal of Life Science
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• v.19 no.6
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• pp.770-780
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• 2009

A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a), was derived from Spirulina platensis. We conducted a series of experiments, in vitro and in vivo, to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-a and 660 nm diode lasers on a squamous carcinoma cell line. We studied the cytotoxic effects of pheophytin-a, 9-HpbD-a, 9-HpbD-a red and 660 nm diode lasers in a human head and neck cancer cell line (SNU-1041). Cell growth inhibition was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of 9-HpbD was higher than those of 9-HpbD-a red or pheophytin-a in PDT. We then tested the cytotoxic effects of 9-hydroxypheophorbide-a (9-HpbD-a) in vitro. The cultured SNU-I041 cells were treated with serial concentrations of 9-HpbD-a followed by various energy doses (0, 0.1, 0.5, 3.2 J/$cm^{2}$) and by various interval times (0, 3, 6, 9, 12 hr) until laser irradiation, then MTT assay was applied to measure the relative inhibitory effects of photodynamic therapy (PDT). Optimal laser irradiation time was 30 minutes and the cytotoxic effects according to incubation time after 9-HpbD-a treatment increased until 6 hours, after which it then showed no increase. To observe the cell death mechanism after PDT, SUN-I041 cells were stained by Hoechst 33342 and propidium iodide after PDT, and observed under transmission electron microscopy (TEM). The principal mechanism of PDT at a low dose of 9-HpbD-a was apoptosis, and at a high dose of 9-HpbD-a it was necrosis. PDT effects were also observed in a xenografted nude mouse model. Group I (no 9-HpbD-a, no laser irradiation) and Group II (9-HpbD-a injection only) showed no response (4/4, 100%), and Group III (laser irradiation only) showed recurrence (1/4,25%) or no response (3/4, 75 %). Group IV (9-HpbD-a + laser irradiation) showed complete response (10/16, 62.5%), recurrence (4/16, 25%) or no response (2/16, 12.5%). Group IV showed a significant remission rate compared to other groups (p<0.05). These results suggest that 9-HpbD-a is a promising photosensitizer for the future and that further studies on biodistribution, toxicity and mechanism of action would be needed to use 9-HpbD-a as a photosensitizer in the clinical setting.

• 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.