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Gan To Kagaku Ryoho. 2000 Mar;27(3):451-8.

[Antitumor effects of TZT-1027, a novel dolastatin 10 derivative, on human tumor xenografts in nude mice].

[Article in Japanese]

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Dept. of Surgery, Ueda Hospital.


TZT-1027 was evaluated for its antitumor effects in sixteen human tumors xenografted in nude mice from gastric (H-81, H-106, H-30, H-154), breast (H-31, H-62), colon (H-110, H-143), lung (LC-376, H-74, Mqnu-1, LC-351), liver (H-181), renal cell (H-12) and ovarian (H-OC-3, SOC-4) cancer lines. In the latter three and lung (Mqnu-1, LC-351) cancers the results were compared with those obtained with CPT-11, VCR, CDDP, ADM. TZT-1027 showed effective antitumor activity (IR > or = 58%) against fifteen of the tumor lines, all but LC-351, and showed markedly effective activity (IR > or = 80%) against twelve tumor lines, including drug-resistant colon (H-110), lung (H-74) and ovarian (SOC-4) cancer lines. The complete regression was shown in five H-OC-3 tumor-bearing mice out of seven. Moreover, TZT-1027 was shown to be more potent in three cancer models (Mqnu-1, H-81, SOC-4) than CPT-11, and to have markedly effective antitumor activity in two cancers (H-12, H-OC-3) in which VCR was ineffective and in ovarian cancer (SOC-4) in which CPT-11, CDDP and ADM were ineffective. The administration of TZT-1027 induced fewer side effects; transient reduction of body weight was observed in four lines out of sixteen tested. These results suggest that TZT-1027 is an excellent candidate for clinical trials for the treatment of cancer.

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