부산대학교 도서관

Dichloro (5, 7, 8, 10, 11, 13, 14, 16-octahydro [1, 4, 7, 10] tetraoxacyclohexadecino-[13, 12-b: 14, 15-b′] dipyridine-Nl, N20) platinum (II), (KP 1220) is a platinum analog reacting with nucleophilic sites on DNA, causing intra- and interstrand crosslinks as well as DNA-protein crosslinks. This agent has shown antitumor activity in established tumor cell lines. We have studied the effect of KP1220 on in vitrosoft agar colony formation of 77 freshly obtained human tumors using a capillary cloning system. Major tumor subgroups were: 13 melanoma, 10 mesothelioma, 9 renal, 7 breast, 6 non-small cell lung, 6 ovary, and 6 carcinoma of unknown primary. Final concentrations were 0.1, 1.0, 10.0μg/ml fur continuous exposure (21–28 days) and 0.1, 0.4 (equirnolarto cisplatin), 0.48 (equimolar to carboplatin), 1.0, 10.0μg/ml fur short-term (1hour) exposure. Using a continuous exposure, 52/77 specimens (68%) showed evaluable colony formation in controls. KP 1220 inhibited tumor colony formation in a concentration-dependent manner with 2/52 specimens (4%) inhibited at 0.1μg/ml, 12/52 (23%) at 1.0.μg/ml and 36/52 (69%) at 10.0μg/ml. Using a short-term exposure, 49/77 specimens (64%) were evaluable. Again, concentration-dependent inhibition of tumor colony formation was observed with 1/47 specimens (2%) inhibited at 0.1μg/ml, 9/49 (18%) at 0.4μg/ml, 16/48 (33%) at 1.0μg/ml and 35/49 (71%) at 10μg/ml. At concentrations≥1μg/ml, KP 1220 was as active as other clinically used antineoplastic agents. We conclude that KP 1220 has antitumor activity. Further clinical development of these agents should be considered.