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pdf (15 mb) - 埼玉医科大学
32 2 17 4
Anti Tumor Effects of Thalidomide Against Liver Metastasis in a
Murine Model of Colon Cancer
Shutaro Ozawa1), Hideyuki Tawara, Isamu Koyama
First Department of Surgery, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350 - 0495, Japan
Background: Thalidomide was introduced in the 1950s as a nontoxic sedative, but was removed from the market
because of its teratogenicity. Recent studies have demonstrated that the most likely etiology of limb defects produced
by fetal exposure to thalidomide is the inhibition of angiogenesis in the developing limb bud. Also many studies
have shown that thalidomide inhibits tumor growth in several malignancies by the inhibition of VEGF. Methods:
We determined whether the systemic administration of thalidomide inhibits colon cancer liver metastasis in mice.
We also evaluated the optimal schedule of this treatment against murine colon cancer liver metastasis. Murine
colon cancer CT-26 cells were implanted into the spleens of BALB/c mice. 7 days after tumor implantation, the mice
received an intra-peritoneal injection of thalidomide (0, 30 mg/kg) daily or every other day (3 times per week).
After the treatments, all mice were sacrificed. The numbers of liver metastases were counted and the expression of
VEGF and the micro vessel density were analyzed by immunohistochemistry against liver metastases. Results: 4
out of 10 mice which received a daily administration of thalidomide (30 mg/kg) died. But in this group, we found a
significant reduction in the number of liver metastases compared with the control group (0 mg/kg). All mice which
received thalidomide every other day survived. In this group, there was also a signific
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