• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.383-393
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• 2008

Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.334-342
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• 2002

Purpose : The aim of this study was to determine if postoperative adjuvant chemotherapy (CT) alone and concurrent chemoradiation (CCRT), following radical surgery, improved the disease free survival (DFS) and overall survival (OS) in rectal cancer AJCC stage II and III patients. Materials and Methods : A total of 144 patients with AJCC stage II and III rectal cancer who had had radical surgery between 1989 and 1999 were included in the study. Of these patients, 72 had been treated with postoperative CT, and the other 72 with postoperative CCRT. The chemotherapy regimen consisted of oral UFT on a daily basis for $1\~12$ months (median 12 months) or 5-FU ($500\;mg/m^2$ for 5 days) intravenous (IV) chemotherapy with 4 week intervals for $1\~18$ cycles (median 6 cycles). Radiation of 4,500 cGy was delivered to the surgical bed and regional pelvic lymph nodes area, followed by $540\~1,440\;cGy$ (median 540 cGy) boost to the surgical bed. The follow-up period ranged from 20 to 150 months, with a median of 44 months. Results : The 5-year OS was $60.9\%\;and\;68.9\%$ (p=0.0915), and the 5-year DFS was $56.1\%\;and\;63.8\%$ (p=0.3510) for postoperative CT and postoperative CCRT, respectively. In the stage nm patients, the 5-year OS was $71.1\%\;and\;92.2\%$, and the 5-year DFS was $57.3\%\;and\;85.4\%$ for postoperative CT and CCRT, respectively. The OS was significantly improved (p=0.0379) but the DFS was not with postoperative CCRT compared to the postoperative CT (p=0.1482). In the stage III patients, the 5-year OS was $52.0\%\;and\;55.0\%$, and the 5-year DFS was $47.8\%\;and\;49.8\%$ for postoperative CT and postoperative CCRT. There were no statistically significant differences between postoperative CT and CCRT (p=0.4280 and p=0.7891) in OS and DFS. The locoregional relapses were $16.7\%\;and\;12.5\%$ for postoperative CT and CCRT, respectively. The distant relapses were $25.0\%\;and\;26.4\%$ for postoperative CT and CCRT, respectively. Conclusion : These results showed that postoperative CCRT compared with CT alone improved OS in stage II patients. Although there was no statistical significance, the addition of postoperative RT to CT reduced locoregional relapses compared to CT alone.