• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.294-299
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• 2004

Purpose: Both human NIS and mutant $D_2R$ transgenes are proposed as reporting system in transplanted cell tracking. Using hepatoma cell lines, we constructed a dual reporter system containing human sodium-iodide symporter (hNIS) and dopamine 2 receptor ($D_2R$) and compared its characteristics. Materials and Methods: The recombinant plasmid ($pIRES-hNIS/D_2R$) was constructed with IRES (internal ribosome entry site) under control of the CMV promoter $pIRES-hNIS/D_2R$ was transfected to human hepatoma SK-Hep1 cell line with lipofectamine. HEP-ND ($SK-Hep1-hNIS/D_2R$) cells stably expressing hNIS and $D_2R$ was established by selection with G418 for two weeks. RT-PCR was performed to investigate the expression of both hNIS and $D_2R$ genes. The expressions of hNIS and $D_2R$ were measured by $^{125}I$ uptake assays and receptor binding assays. Specific binding of $D_2R$ to $[^3H]spiperone$ was verified by Scatchard plot with (+) butaclamol as a specific inhibitor. $K_d\;and\;B_{max}$ values were estimated. The correlation between hNIS and $D_2R$ expression was compared by using each clone. Results: Similar quantities of hNIS and $D_2R$ genes were expressed on HEP-ND as RT-PCR assays. HEP-ND cells showed 30 to 40 fold higher radioiodine uptakes than those of parental SK-Hep1 cells. $^{125}I$ uptake in HEP-ND cells was completely inhibited by $KClO_4$, a NIS inhibitor Specific binding to HEP-ND cells was saturable and the $K_d\;and\;B_{max}$ values for HEP-ND cells were 2.92 nM, 745.25 fmol/mg protein and 2.91nM, 1323 fmole/mg protein in two clones, respectively. The radioiodine uptake by hNIS activity and $D_2R$ binding was highly correlated. Conclusion: We developed a dual positron and gamma imaging reporter system of hNIS and $D_2R$ in a stably transfected cell line. We expect that $D_2R$ and hNIS genes can complement mutually as a nuclear reporting system or that $D_2R$ can be used as reporter gene when hNIS gene were used as a treatment gene.

• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.325-329
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• 2004

Purpose: Usefulness of mouse liver S9 fraction was evaluated for the measurement of the metabolites in the in vitro metabolism study of $^{18}F$-labeled radiotracers. Materials and Methods: Mouse liver S9 fraction was isolated at au early step in the course of microsome preparation. The in vitro metabolism studies were tarried out by incubating a mixture containing the radiotracer, S9 fraction and NADPH at $37^{\ciirc}C$, and an aliquot of the mixture was analyzed at the indicated time points by radio-TLC. Metabolic defluorination was further confirmed by the incubation with calcium phosphate, a bone mimic. Results: The radiotracer $[^{18}F]1$ underwent metabolic defluorination within 15 min, which was consistent with the results of the in vivo method and the in vitro method using microsome. Radiotracer $[^{18}F]2$ was metabolized to three metabolites including $4-[^{18}F]fluorobenzoic$ acid within 60 min. It is likely that the one of these metabolites at the origin of radio-TLC was identical with the one that obtained from the in vivo and in vitro (microsome) method. Compared with the in vitro method using microsome, the method using S9 fraction gave a similar pattern of the metabolites but with a different ratio, which can be explained by the presence of cytosol in the S9 fraction. Conclusion: These results suggest that the findings of the in vitro metabolism studies using S9 fraction can reflect the in vivo metabolism of novel radiotracers in the liver. Moreover, this method can be used as a tool to determine metabolic defluorination along with calcium phosphate absorption method.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.393-402
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• 1997

Purpose : When an x-ray beam of small field size is irradiated to target area containing an air cavity, such as larynx, the underdosing effect is observed in the region near the interfaces of air and soft tissue. With a larynx model, air cavity embedded in tissue-equivalent material, this study is intonded for examining Parameters, such as beam quality, field size, and cavity size, to affect the dose distribution near the air cavity. Materials and Methods : Three x-rar beams, 4-, 6- and 10-MV, were employed to Perform a measurement using a 2cm $(width){\times}L$ (length in cm, one side of x-ray field used 2cm (height) air cavity in the simulated larynx. A thin window parallel-plate chamber connected to an electrometer was used for a dosimetry system. A ratio of the dose at various distances from the cavity-tissue interface to the dose at the same points in a homogeneous Phantom (ebservedlexpected ratio, O/E) normalized buildup curves, and ratio of distal surface dose to dose at the maximum buildup depth were examined for various field sizes. Measurement for cavity size effect was performed by varying the height (Z) of the air cavity with the width kept constant for several field sizes. Results : No underdosing effect for 4-MV beam for fields larger than $5cm\times5cm$ was found For both 6- and 10-MV beams, the underdosing portion of the larynx at the distal surface was seen to occur for small fields, $4cm\times4cm\;and\;5cm\times5cm$. The underdosed tissue was increased in its volume with beam energy even for similar surface doses. The relative distal surface dose to maximum dose was changed to 0.99 from 0.95, 0.92, and 0.91 for 4-, 6-, and 10-MV, respectively, with increasing field size, $4cm\times4cm\;to\;8cm\times8cm$, For 6- and 10-MV beams, the dose at the surface of the cavity is measured less than the predicted by about two and three percent. respectively. but decrease was found for 4-MV beam for $5cm\times5cm$ field. For the $4cm\timesL\timesZ$ (height in cm). varying depth from 0.0 to 4.8cm, cavity, O/E> 1.0 was observed regardless of the cavity size for any field larger than about $8cm\times8cm$. Conclusion : The magnitude of underdosing depends on beam energy, field size. and cavity size for the larynx model. Based on the result of the study. caution must be used when a small field of a high quality x-ray beam is irradiated to regions including air cavities. and especially the region where the tumor extends to the surface. Low quality beam. such as. 4-MV x-ray, and larger fields can be used preferably to reduce the risk of underdosing, local failure. In the case of high quality beams such as 6- and 10-MV x-rays, however. an additional boost field is recommended to add for the compensation of the underdosing region when a typically used treatment field. $8cm\times8cm$, is employed.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.147-157
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• 1998

Purpose : The aim of this retrospective study is to assess the necessity of s1aging laparotomy in the management of supradiaphragmatic CS I-II Hodgkin's disease. Prognostic factors and the usefulness of prognostic factor groups were also analyzed. Materials and Methods : From 1985 to 1995, fifty one Patients who were diagnosed as supradiaphragmatic CS I-II Hodgkin's disease at Yonsei Cancer Center in Seoul, Korea were enrolled in this study Age range was 4 to 67 with median age of 30. The number of patients with each CS IA, II A, and IIB were 16, 25, and 10, respectively. Radiotherapy(RT) was delivered using 4 or 6 MV photon beam to a total dose of 19.5 to 55.6Gy (median dose : 45Gy) with a 1.5 to 1.BGy per fraction. Chemotherapy(CT) was given in 2-12 cycles(median : 6 cycles). Thirty one Patients were treated with RT alone, 4 patients with CT alone and 16 patients with combined chemoradiotherapy. RT volumes varied from involved fields(3), subtotal nodal fields(18) or mantle fields(26). Results : Five-year disease-free survival rate(DFS) was $78.0\%$ and overall survival rate(05) was $87.6\%$. Fifty Patients achieved a complete remission after initial treatment and 8 patients were relapsed. Salvage therapy was given to 7 patients, 1 with RT alone, 4 with CT alone, 2 with RT+CT. Only two patients were successfully salvaged. Feminine gender and large media-stinal adenopathy were significant adverse prognostic factors in the univariate analysis for DFS. The significant adverse prognostic factors of OS were B symptom and clinical stage. When patients were analyzed according to European Organization for Research and Treatment of Cancer(EORTC) prognostic factor groups, the DFS in Patients with very favorable, favorable and unfavorable group was 100, 100 and $55.8\%$(p<0.05), and the 05 in each patients' group was 100, 100 and $75.1\%$(p<0.05), respectively. In very favorable and favorable groups, the DFS and 05 were all $100\%$ by RT alone, but in unfavorable group, RT with CT had a lesser relapse rate than RT alone. The subtotal nodal irradiation had better OFS than mantle RT in patients treated with RT. Conclusion : In present study, the DFS and OS in patients who did not undergo s1aging laparotomy were similar with the results in the literatures of which patients were surgically staged. Therefore, we may suggest that staging laparotomy would not influence the outcome of treatments. In univariate analysis, gender, large mediastinal adenopathy. B symptoms and clinical stage were significant prognostic factors for the survival rate. We confirm the usefulness of EORTC prognostic factor groups which may be a good.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.115-123
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• 2004

Purpose : This retrospective study was conducted to compare early preliminary results of breast conservation therapy (BCT) with mastectomy In early breast cancer. Materials and Methods : We evaluated 171 women with AJCC stage I and II breast cancer who had been treated at Kangnam St. Mary's Hospital from March 1989 to August 1996. Eighty-eight patients underwent mastectomy and 85 patients did conservative surgery with breast irradiation. in the BCT group, all patients received whole breast irradiation to a total dose of 45$\~$50 Gy/5$\~$6 wks, followed by a boost to the original tumor site at least 60 Gy. Chemotherapy was administered to 29 (34.1$\%$) patients in BCT and 40 (45.5$\%$) in mastectomy, with various sequencing of surgery and/or radiation. We compared survival rate, patterns of failure in each treatment group and the prognostic factors that had a significant effect on treatment failure. The median follow-up time was 63 months (19$\~$111 months). Log rank test was used to estimate the prognostic factors for treatment failure. Results : Overall survival, disease free survival, locoregional recurrence and distant metastasis rates were not significantly different between the two treatment groups. During the follow-up period, 11 patients (12.5$\%$)in the mastectomy group and 10 patients (11.8%$\%$ in the BCT group were failed. Six local recurrences occurred after mastectomy and 5 after BCT Five patients fatted at distant site in mastectomy and 4 in BCT. Of the local recurrence cases, five of 6 mastectomy patients and 3 of S BCT patients were alive with no evidence of disease after salvage surgery and/or chemoirradiation. Our results indicated that the major influence on survival was distant metastasis. Unfortunately, control of distant metastasisis was not frequently achieved. Even with salvage systemic therapy or radiotherapy, most of distant metastasis patients died or had uncontrolled disease in both treatment groups: only one of 4 BCT patients and none of mastectomy patients were alive without disease. There was no apparent difference in the incidence rate of contralateral breast cancer and non-breast 2$^{nd}$ primary tumor between the two treatment groups. Univariate Log-rank test identified the N stage and the involved axillary LN number as distinct prognostic factors that were highly predictive of treatment failure in both treatment groups. Additionally, marginal status in BCT and histologic nuclear grade In the mastectomy group were risk factors for treatment fallure (p < 0.05). Concousion : Although further careful follow-up is necessary to confirm the trends evident In this serles, it would appear that patterns of failure and survival rate following conservative surgery and radiotherapy in early breast cancer are similar to those following mastectomy. The great majority of patients with local recurrence had an exellent salvage rate in both treatment groups. Therefore, these preliminary short term results support BCT as an equally effective management for early breast cancer as an alternative to mastectomy.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.22-31
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• 2005

Purpose : To conduct a nationwide survey on the principals in radiotherapy for rectal cancer, and produce a database of Korean Patterns of Care Study. Materials and Methods : We developed web-based Patterns of Care Study system and a national survey was conducted using random sampling based on power allocation methods. Eligible patients were who had postoperative radiotherapy for rectal cancer without gross residual tumor after surgical resection and without previous history of other cancer and radiotherapy to pelvis. Data of patients were Inputted to the web based PCS system by each investigators in 19 institutions. Results : Informations on 309 patients with rectal cancer who received radiotherapy between 1998 and 1999 were collected. Male to female ratio was 59 : 41, and the most common location of tumor was lower rectum ($46\%$). Preoperative CEA was checked in $79\%$ of cases and its value was higher than 6 ng/ml in $32\%$. Pathologic stage were I in $1.5\%$, II in $32\%$, III in $53\%$, and IV in $1.6\%$. Low anterior resection was the most common type of surgery and complete resection was peformed in $95\%$ of cases. Distal resection margin was less than 2 cm in $30\%$, and number of lymph node dissected was less than 12 in $31\%$. Chemotherapy was peformed in $91\%$ and most common regimen was 5-FU and leucovorine ($59\%$). The most common type of field arrangement used for the initial pelvic field was the four field box (Posterior-Right-Left) technique ($65.0\%$), and there was no AP-PA parallel opposing field used. Patient position was prone in $81.2\%$, and the boost field was used in $61.8\%$. To displace bowel outward, pressure modulating devices or bladder filling was used in $40.1\%$. Radiation dose was prescribed to isocenter in $45.3\%$ and to isodose line in 123 cases ($39.8\%$). Percent delivered dose over $90\%$ was achieved in $92.9\%$. Conclusion : We could find the Patterns of Care for the radiotherapy in Korean rectal cancer patients was similar to that of US national survey. The type of surgery and the regimen of chemotherapy were variable according to institutions and the variations of radiation dose and field arrangement were within acceptable range.

• Journal of Sasang Constitutional Medicine
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• v.8 no.1
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• pp.247-294
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• 1996

By means of the statistical data which has been collected with newly revised QSCC made use of the outpatient group examined at Kyung-Hee Medical Center and an open ordinary person group, the author proceeded statistical analysis for the validation study of the revised questionnaire itself. First, check the accurate discrimination rate by performing discriminant analysis on the statistical data of the patient group. And next, sought T-score by applying the norms gained in process of standadization of the open ordinary person group to the Sasang scale score of the outpatient group and investigated the distinctive feature between the subpopulations which was devided in the process of multivarite cluster analysis. The result was summarized as follows ; 1. The validity of the questionnaire was established through the fact that the accurate discrimination rate the ratio between predicted group and actual group was figured out 70.08%. 2. At the profile analysis the response to the relevant scale showed notable upward tendency in each constitutional group and therefore it seems to be pertinent in the field of constitutional discrimination. 3. In the observation of the power of expression through the profile analysis of each constitutional group the Soyang group demonstrated the most remarkable outcome, the Soeum group was the most inferior and the Taieum group revealed a sort of dual property. 4. What is called the group of seceder out of three subpopulation of each constitutional group distinguished definitely from the contrasted groups at the point of the distinctive profile feature and the content is like following description. (1) The seceder group of Soyang-in showed considerably passive disposition differently from general character of ordinary Soyang group and an appearance attracting the attention is that they demonstrated comparatively higher response at Soeum scale (2) The seceder group of Taieum-in gained low scores in general that informed the passive disposition of the group and the other way of the general property of Taieum group which showed accompanied ascension in Taiyang-Taieum scales they demonstrated sharply declined score at Taiyang scale (3) The seceder group of Soeum-in demonstrated distinctive property similar to the profile feature of Soyang group and it notifies that the passive property of Soeum group was diluted for the most part. According to the above result, the validity of newly revised questionnaire has been proven successfully and the property of seceder groups could be noticed to some degree through the profile analysis on the course of this study. The result of this study is expected to use as a research materials to produce next edition of the questionnaire and it is regarded that further inquisition about the difference between the seceder group and the contrasted group is required for the promotion of the questionnaire as it refered several times in the contents of the main discourse.

• 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.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.49-56
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• 1997

Purpose : To evaluate the pathologic effects of preoperative radiotherapy o the resectable distal rectal cancer, we analyzed the results of postoperative pathologic findings for the patients with preoperative radiotherapy ant surgery Materials and Methods: From July 1995 to April 1996, we treated sixteen patients of resectable rectal cancer with preoperative radiation therapy and curative surgery At diagnosis, Thomas Jefferson (TJ) system was used for the clinical stage of the Patients. We treated the patients with conventional radiation therapy of 4500~5000cGy before surgery. The surgery was carried out 4 weeks after completion of radiation therapy. Modified Astler Coller (MAC) system was used for the postoperative pathologic stage. We analyzed the pathologic stages and findings according to preoperative clinical stage and compared with those of the control group in similar clinical stages. Result : All patients were treated with sphincter preservation surgery after Preoperative radiation therapy. Pathoiogic complete response (CR) was shown in 1 case $(6.3\%)$. We compared the results between preoperative radiation therapy group (Preop.RT group) and surgery only group (control group). In TJ stage II, among nine patients of Preop.RT group, 8 patients $(88.9\%)$ were in MAC stage 8 except 1 CR patient, but among 17 patients of control group. 11 patients$(64.7\%)$ were in MAC stage B and 6 Patients $(35.3\%)$ in MAC stage C. In TJ stage III, among 7 patients of Preop.RT group, 4 patients $(57.1\%)$ were in MAC stage B and 3 patients$(42.9\%)$ in MAC stage C. Among 14 Patients of control group, 4 patients $(28.6\%)$ were in MAC stage B and 10 Patients $(71.4\%)$ in MAC stage C. Above results showed that postoperative Pathologic stage was decreased in Preop.RT group with statistical significance (P=0.049). The postoperative Pathologic findings (blood vessel invasion. Iymphatic vessel invasion, perineural invasion) were decreased in the Preop.RT group compared with those of control group. But statistical significance was found only in Iymphatic vessel invasion (p=0.019). Conclusion : The Postoperative pathologic stages and adverse Prognostic pathologic findings were decreased in preoperative radiation therapy group. The Iymphatic vessel invasion and MAC stage C findings were abruptly decreased in Preoperative radiation therapy group. The preoperative radiation therapy was found to be effective in resectable rectal cancer. The patients group in our study was very small and long term follow up was not done. Therefore, further study about this issues is needed.

• The Journal of Korean Academy of Prosthodontics
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• v.46 no.2
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• pp.157-168
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• 2008

Statement of problem: Over the past two decades, implant supported fixed prosthesis have been widely used. However, there are few studies conducted systematically and intensively on the splinting effect of implant systems in mandible. Purpose: The purpose of this study was to investigate the changes in stress distributions in the mandibular implants with splinting or non-splinting crowns by performing finite element analysis. Materials and methods: Cortical and cancellous bone were modeled as homogeneous, transversely isotropic, linearly elastic. Perfect bonding was assumed at all interfaces. Implant models were classified as follows. Group 1: $Br{{\aa}}nemark$ length 8.5mm 13mm splinting type Group 2: $Br{{\aa}}nemark$ length 8.5mm 13mm Non-splinting type Group 3: ITI length 8.5mm 13mm splinting type Group 4: ITI length 8.5mm 13mm Non-splinting type An load of 100N was applied vertically and horizontally. Stress levels were calculated using von Mises stresses values. Results: 1. The stress distribution and maximum von Mises stress of two-length implants (8.5mm, 13mm) was similar. 2. The stress of vertical load concentrated on mesial side of implant while the stress of horizontal load was distributed on both side of implant. 3. Stress of internal connection type was spreading through abutment screw but the stress of external connection type was concentrated on cortical bone level. 4. Degree of stress reduction was higher in the external connection type than in the internal connection type.