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J Korean Soc Ther Radiol Oncol > Volume 16(3); 1998 > Article
The Journal of the Korean Society for Therapeutic Radiology and Oncology 1998;16(3): 225-231.
Potentiation of Antitumor Effect of Radiotherapy by Recombinant Tumor Necrosis Factor-alpha
Jinsil Seong, Hang Chul Shin, Gwi Eon Kim, Chang Ok Suh
1Department of Radiation Oncology, Yonsei University Medical College, Seoul Korea.
2Hanhyo Institute of Technology, Taejon, Korea.
To determine whether TNF-alpha increases the antitumor effect of radiotherapy in murine syngeneic tumor system.
Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I (hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter, mice were treated with TNF-alpha, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-alpha mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 microgram per mouse for 7 days. In combination of radiation and TNF-alpha, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment.
Among 4 tested tumors, TNF-alpha alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-alpha showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-alpha alone and radiation, i.e., 6.5 days and 26.9 days, respectively (p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-alpha did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-alpha alone and radiation.
TNF-alpha alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-alpha acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-alpha and radiation has different therapeutic potential depending on tumor model and further study is advocated.
Key Words: TNF-alpha, Radiotherapy, Murine tumor
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