| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Research Abstract |
The growth of cancer metastatic foci will be suppressed completely, when attained anti-angiogenesis and cancer cell killing simultaneously. The anti-vascular endofeefial growth factor (VEGF) antibody may accumulate in cancer tissue where VEGF concentration is high, and inhibit the development of tumor vessels. The anti-cancer drug, Mtomycin C (MMC), has direct cytoridal effects on cancer cells. The conjugate of anti-VEGF antibody and MMC has both effects above mentioned, and finally suppress tumor growth. Thus, new and sophisticated drug for cancer therapy was produced by BrCN method The conjugate consisted of 1 mol of anti-VEGF antibody and 6 mol of MMC. The cytoddal effect of fee conjugate was 4 times stronger than that of MMC, and 63 times stronger than that of anti-VEGF antibody in vitro. In vivo effects of the conjugate was investigated using the model of fiver metastasis in mice initially. However, the effects were not evaluated because the uniformity of the metastatic nodule in the fiver was not obtained between treatment groups. Then, in vivo experimental model was changed from liver metastasis to peritoneal dissemination The uniform peritoneal dissemination was obtained by injection of PD7 cells to the abdominal cavity of SCID mice. After creation of peritoneal dissemination model, conjugate, MMC, or anti-VEGF antibody was administered intraperitoneally in day 1 and day 2. Mice were sacrificed in day 15 and abdominal dissemination nodules were observed. The weight of dissemination nodules was significantly smaller in the conjugate-treatment group, when compared wife the MMC- or antibody-treatment group. The usefulness of anti-VEGF antibody-MMC conjugate was demonstated for treatment of cancer metastasis.
|
