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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.
ABSTRACT
PURPOSE:
To determine whether TNF-alpha increases the antitumor effect of radiotherapy in murine syngeneic tumor system.
MATERIALS AND METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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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