Adaptive Response to ionizing Radiation Induced by Low Doses of Gamma Rays in Human Lymphoblastoid Cell Lines

성진실,서창옥,김귀언,Seong, Jin-Sil,Suh, Chang-Ok,Kim, Gwi-Eon The Korean Society for Radiation Oncology 1994 대한방사선종양학회지 Vol.12 No.1

When cells are exposed to low doses of a mutagenic or clastogenic agents. they often become less sensitive to the effects of a higher dose administered subsequently. Such adaptive responses were first described in Escherichia coli and mammalian cells to low doses of an alkylating agent. Since most of the studies have been carried out with human lymphocytes, it is urgently necessary to study this effect in different cellular systems. Its relation with inherent cellular radiosensitivity and underlying mechanism also remain to be answered. In this study, adaptive response by 1 cGy of gamma rays was investigated in three human lymphoblastoid cell lines which were derived from ataxia telangiectasia homozygote, ataxia telangiectasia heterozygote, and normal individual. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher dose (50 cGy), The expression of this adaptive response was similar among three cell lines despite of their different radiosensitivity. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the tested cell lines. Therefore it is suggested that the adaptive response can be observed in human lymphoblastoid cell lines, which was first documented through this study. The expression of adaptive response was similar among the cell lines regardless of their radiosensitivity. The elimination of the adaptive response by 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanism.

유전 가열장치에서 전극의 각도 배열 -온도 분포의 특성 및 임상 적용-

성진실,추성실,김귀언,노준규,양성화,Seong, Jin-Sil,Chu, Sung-Sil,Kim, Gwi-Eon,John, Juhn-Kyu,Yang, Sung-Wha The Korean Society for Radiation Oncology 1989 Radiation Oncology Journal Vol.7 No.2

고주파유전가열 장치는 심부까지도 효과적인 가온이 가능하여 각족 심부암의 치료에 응용되고 있다. 그러나 한쌍의 전극을 평행으로 대칭 배열하는 현재의 방법은 신체의 일측으로 편재되어 있는 병소에는 배열 자체가 불안정할 뿐만 아니라, 노출된 동측 피부표면이 과열되며 종양의 가온 양상도 만족스럽지 못한 경우가 많아서 임상 적응에 난점으로 지적되고 있는 실정이다. 저자들은 상기와 같은 병소를 보다 안전하고_도 효과적으로 가온하기 위하여 두 전극간에 일정한 각도를 이루는 새로운 전극 배열을 시도하였다. 즉, 임상 적용 가능성을 고려한 $60^[\circ},\;90^{\circ}\;및\;120^{\circ}$로 전극을 배열하고 모형 (phantom)에서 가온 실험을 행하여 이같은 각도 배열에서의 온도 분포의 특성을 평가할 수 있었고, 일측에 편재된 병소를 가진 3예의 환자에게 각도 배열로 온열치료를 시행한 결과 환자의 수용성, 부작용 및 온도분포에 있어서 만족할 만한 결과를 얻을 수 있었다. 따라서 저자들이 시도한 전극의 각도배열은 일측에 편재된 병소를 유전 가열 장치로 가온 할 때 평행 배열이라는 한계점을 극복할 수 있는 새로운 방법으로서 매우 고무적으로 생각된다. In capacitive heating device, which considered efficient for deep heating, parallel arrangement of the electrodes is a serious limiting factor in heating for eccentrically located lesions because it causes overheating of the exposed ipsilateral skin surface, the heating pattern is also frequently inappropriate, and the arrangement tends to be unstable due to the patient's gravity. Therefore we attempted an angular arrangement of the electordes to achieve more homogenous and efficient heating for such lesions. In phantom study, both the thermal profile and thermogram established the heating pattern in this unusual angular arrangement of the electrodes at $60^{\circ},\;90^{\circ}\; and\;120^{\circ}$ angles, respectively. An angular arrangement was also clinically applied to 3 patients. The patients' tolerance was good without significant complication and the thermal distribution was satisfactory. In conclusion, this unusual arrangement of electrodes appears to be promising in the clinical application to the eccentrically located lesions.

담도계를 침범한 간세포암의 방사선 치료

성진실 ( Jin Sil Seong ) 대한간암학회 2001 대한간암학회지 Vol.1 No.-

토모테라피(추계학술대회 초록집)

성진실 ( Jin Sil Seong ) 대한간학회 2006 Clinical and Molecular Hepatology(대한간학회지) Vol.12 No.5(S)

간세포암종의 정밀 방사선치료

성진실 ( Jin Sil Seong ) 대한간암학회 2005 대한간암학회지 Vol.5 No.-

Combined Radiotherapy and Hyperthermia for Nonresectable Hepatocellular Carcinoma

성진실(Jin Sil Seong),노준규(John Juhn Kyu Loh),서창옥(Chong Ok Suh)김귀언(Gwi Eon Kim),한광협(Kwong Hyub Han),이상인(Song In Lee),노재경(Joe Kyung Roh),김병수( Byung Soo Kim),최흥재(Heung Jai Choi) 대한방사선종양학회 1989 Radiation Oncology Journal Vol.7 No.2

절제 불가능한 원발성 간암은 여러 가지 다양한 치료법의 시도에도 불구하고 그 예후는 극히 불량하다. 이에 본 저자들은 온열요법에 대한 축적된 경험을 바탕으로 1988년 4월부터 7월까지 본과에 내원한 30명의 절제 불가능한 원발성간암 환자들에 대하여 온열 및 방사선 병용요법을 시행하였다. 방사선치료는 일일 조사량 180 cGy 씩 3.5주에 3060 cGy를 조사하였고 온열요법은 8MHz 유전형온열치료기(Thermotron RF-8, Cancermia)를 사용하여 주 2회씩 총 6회 시행하되 순서는 방사선 치료를 먼저 한 후 30분 이내에 온열요법이 30~60분간 시행되었다. 그 결과 부분반응이 12예에서 관찰되었고(40%), 증상의 호전이 28예중 22예에서 관찰되었다(78.6%). 종양의 반응을 예측할 수 있는 인자로서는 형태학적 유형이 가장 유의하게 나타났다(single massive: 10/14, 71.4%; diffuse infiltrative: 2/10, 20%; multinodular: 0/6, 0%; p<0.005). 치료로 인한 심각한 부작용은 관찰되지 않았다. 1년 생존율은 34%였고 정중앙 생존기간은 6.5개월이었다. 부분반응을 보인 환자군의 생존율 및 정중앙 생존 기간은 각각 50%, 11개월로서 반응을 보이지 않은 환자군의 22%, 5개월과 비교해 볼 때 정중앙 생존기간의 차이가 통계족으로 유의하였다(p<0.05). 결론적으로 온열 및 방사선 병용요법은 절제 불가능한 원발성 간암의 증상호전 및 국소적 치료에 효과가 있는 것으로 생각되며 생존율 및 부작용등에 관해서는 앞으로 연구가 더 진행되어야 할 것으로 생각된다. Thirty patients with nonresectable hepatocellular carcinoma (HOC) due to either locally advanced lesion of association with liver cirrhosis, treated with combined radiotherapy and hyperthermia between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei university College of medicine, were analysed. External radiotherapy of a total dose of 3060 cGy/3.5 wks was given, Hyperthermia was given twice a week with a total of 6 treatment sessions using 8 MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. ln all cases hyperthermia was given within 30 minutes after radiotherapy for 30~60 min. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance only for those who had not bleeding tendency. As a result, partial response (PR) was achieved in 12 patients (40%), and symptomatic improvement was observed in 22 patients (78.6%) among 28 patients who had suffered from abdominal pain. The most significant factor affecting the tumor response rate was the type or tumor (single massive: 10/14, 71.4%; diffuse infiltrative: 2/10, 20%: multinodular: 0/6, 0%; p<0.005). There were not any significant side effects relating to combined treatment. The overall 1 year survival rate was 34%, with 50% in the PR group and 22% in the no response group (NR), respectively. Median survival was 6.5 months and longer for those of PR than of NA (11 mos. vs 5, p<0.05). In conclusion, combined radiotherapy and hyperthermia appeared to be effective in local control and symptomatic palliation of HCC. Further study including a larger number of the patients to confirm its effect in survival and detrimental side effect should be urged.

에스자결장암에서 근치적 절졔술 후 방사선 치료의 역할

박원,성진실,금기창,서창옥,이상욱,임지훈,민진식,노재경,김주항,정현철,이강규,김귀언,Park, Won,Seong, Jin-Sil,Keum, Ki-Chang,Suh, Chang-Ok,Lee, Sang-Wook,Lim, Ji-Hoon,Min, Jin-Sik,Roh, Jae-Kyung,Kim, Joo-Hang,Chung, Hyun-Cheol,Lee, Kang-K 대한방사선종양학회 1997 대한방사선종양학회지 Vol.15 No.4

Purpose : To evaluate the role of postoperative radiation therapy after curative resection of sigmoid colon cancer Materials and Methods : From 1988 to 1993, a total of 93 Patients with curative resectable sigmoid colon cancer of modified Astler-Coiler (MAC) stage B2, B3, C2, C3 was divided into two groups on the basis of those who received radiation treatment and those who did not. Forty-three patients who treated by surgery alone were classified as postop RT (-) group The remaining 50 patients who underwent postoperative radiotherapy were classified as postop RT (+) group. In all patients in Postop RT (+) group. radiation therapy was delivered using 4 or 10 MV linear accelerators to treat the tumor bed with approximately 5cm margin to a total dose 50.4-61Gy(median 54Gy) in 1.8Gy per fraction. Thirty-two patients were treated. with 5-Fluorouracil based adjuvant chemotherapy at least 3 cycles. but these was no significant difference between two groups. Treatment failure Pattern, 5-year local failure-free survival rates (LFFS), and 5-year disease-free survival rates (DFS) were compared between two groups. Result : Five year LFFS and DFS were $85.1\%,\;68.5\%$, respectively, In Postop RT (-) group, LFFS was $76.2\%$ compared with $91.7\%$ in Postop RT (+) group. Improved LFFS and DFS were seen for patients with stage C3 sigmoid colon carcinoma with postoperative radiation therapy compared with postop RT (-) group (P=0.01, p=0.06 respectively), in stage B3, LFFS washigher in postop RT (+) group than that in Postop RT (-) group. although itwas not significant. Especially, local control was higher in stage 74 inpostop RT (+) group than that in postop RT (-) group, Conclusion : This studv showed significantly improved LFFS and DFS in MAC Stage C3 and improved tendency of LFFS and DFS in MAC Stage B3 disease. Large scale prospective study is required to verify the role of adjuvant radiation therapy in resectable sigmoid colon cancer.

국소적으로 진행된 담낭암에서 방사선치료의 역할

신현수,성진실,Shin, Hyun-Soo,Seong, Jin-Sil 대한방사선종양학회 2000 대한방사선종양학회지 Vol.18 No.4

Purpose :A retrospective review of 72 patients with locally advanced gallbladder carcinoma, between January 1990 and December 1996, was peformed. Survival results and prognostic factors are analyzed for the patients treated with a various modalities. Materials and Methods :We patients were classified by treatment modality: group 1 included to 27 patients treated with palliative surgery alone, and group 2 for 11 patient treated with palliative surgery and radiotherapy; group 3 for 18 patients not treated by any treatment modality, and group 4 for 16 patients treated with radiotherapy alone. Age distribution ranged from 35 to 80 years with mean of 63 years. The stage was classified by TNM and Nevin's staging system; all patients had an advanced stage more than III. Palliative surgery was done in .: patients and adiuvant radiation therapy (RT) was followed in 11. For 34 patients, in whom no resection was tried, definitive RT was done in 16. Radiation delivered to tumor site and draining nodes up to 45~61.2 Gy using 10 MV linear accelerator. Chemotherapy was given to 25 patients with 5-FU based regimens. Results :Modian suwival time was 10.3 months and 3-year survival rates (3-YSR) were 13.0$\%$ in all patients. Survival rates according to the treatment modalities were as followed; in palliative surgery alone, 3-YSR was 2.5$\%$; in palliative surgery and adjuvant RT, 3-YSR was 45.5$\%$, in no treatment group, 3-VSR were 8.3$\%$; and definitive RT was 13.1$\%$. It was better survival in additional RT after palliative surgery group than palliative surgery alone (p=0.0009). It was better survival in definitive RT group than no treatment group (p=0.002). Significant prognostic factors by univariate analysis were treatment moonlities, the type of tumor and TNM stage. Significant prognostic factors by multivariate analysis were treatment modalities, the type of tumor and the presence of jaundice. Conclusion : It is suggested that RT could be potentially of effective as adjuvant treatment modalities after palliative surgery or primary treatment for locally advanced and unresectable gallbladder carcinoma.

방사선에 의한 Apoptosis에서 Fas의 역할

김성희,성진실,성제경,Kim, Sung-Hee,Seong, Jin-Sil,Seong, Je-Kyung 대한방사선종양학회 2002 대한방사선종양학회지 Vol.20 No.3

Purpose : It has been recognized that interaction of the Fas : Fas ligand plays an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas mutation in radiation-induced apoptosis in vivo. Materials and Method : Mice with mutations in Fas, $MRL/Mpj-Fas^{Ipr}$, and its normal control, MRL/Mpj, were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed and their spleens were collected at different time intervals. Tissue samples were stained with hematoxylin-eosin and the numbers of apoptotic cells were scored. Regulating molecules of apoptosis including p53, Bcl-2, Bax, $Bcl-X_L,\;and\;Bcl-X_S$ were also analyzed by Western blotting. Results : At 25 Gy irradiation, the level of apoptosis reached the peak value at 8 hr after radiation and recovered to the normal value at 24 hr after radiation in MRL/Mpj mice. In contrast, the peak apoptosis level appeared at 4 hr after radiation in $MRL/Mpj-Fas^{Ipr}$. At 8 hr after radiation, the levels of apoptosis in MRL/Mpj mice and $MRL/Mpj-Fas^{Ipr}$ mice were $52.3{\pm}7.8\%\;and\;8.0{\pm}8.6\%$, respectively (p<0.05). The expression of apoptosis regulating molecules, p53, $Bcl-X_L\;and\;Bcl-X_S$, increased in MRL/Mpj mice in response to radiation; p53 with a peak level of 3-fold at 8 h, $Bcl-X_L$ with a peak level of 3.3-fold at 12 h, and $Bcl-X_S$ with a peak level of 3-fold at 12 h after 25 Gy radiation. Bcl-2 and Bax did not show significant change in MRL/Mpj mice. However in $MRL/Mpj-Fas^{Ipr}$ mice, the expression levels of p53, Bcl-2, Bax, $BCl-X_L\;and\;BCl-X_S$ showed no significant change. Conclusion : The level of radiation-induced apoptosis was lower in Fas mutated mice, Ipr, than in control mice. This seemed to be related to the lack of radiation-induced p53 activation in the Ipr mice. This result suggests that Fas plays an important role in radiation-induced apoptosis in vivo.

절제 불가능한 췌장암의 동시항암화학방사선요법

김용배,성진실,송시영,박승우,서창옥,Kim, Yong-Bae,Seong, Jin-Sil,Song, Si-Young,Park, Seung-Woo,Suh, Chang-Ok 대한방사선종양학회 2002 대한방사선종양학회지 Vol.20 No.4

Purpose : To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. Materials & Methods : The patients, who were diagnosed by imaging modalities or by explo-laparotomy, were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine $1,000\;mg/m^2$ or Paclitaxel $50\;mg/m^2$ weekly and oral 5-FU daily The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months, Survival was analyzed using the Kaplan-Meier method. Results : Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 50 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to: disease progression for 6 $(50\%)$, poor performance status for 4 $(33.3\%)$, intercurrent disease for 1 $(8.3\%)$, and refusal for 1 $(8.3\%)$. Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was $59\%$. The survival rates were $46.7\%\;and\;17.0\%$ at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients $(19\%)$, while grade III or IV non-hematologic toxicity was shown in 5 patients $(12\%)$. Conclusion : Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient selection and the treatment outcome as well as to reduce the toxicity.