MKT-077, localized lipophilic cation: antitumor activity against human tumor xenografts serially transplanted into nude mice.

Abstract

BACKGROUND:

In in vitro experiments, the localized lipophilic cation, MKT-077, demonstrated time- and concentration-dependent antitumor activity. In the present experiment, the in vivo antitumor activity of MKT-077 was evaluated using human tumor xenografts serially transplanted into nude mice.

MATERIALS AND METHODS:

The antitumor efficacy of MKT-077 against five xenografts inoculated subcutaneously into nude mice was studied. Treatment with MKT-077 was initiated when the tumors started exponential growth. The antitumor activity of MKT-077 was assessed by a) the lowest value of the relative mean tumor weight of the treated:control tumors (T/CRW), where relative weight (RW) represented the change from baseline weight; and by b) the unadjusted weight of treated tumors at the end of the experiment.

RESULTS:

When MKT-077 was administered continuously using the Osmotic Micropump, antitumor activity was positively correlated with exposure time and drug concentration from 7.5 to 40 mg/kg/day. The maximum tolerated dose was 20 mg/kg/day for 7 days. Co-4 (human colon cancer), St-4 (human gastric cancer), and CRL1420 (human pancreatic cancer) were evaluated as sensitive to MKT-077 in tested 5 strains.

CONCLUSION:

The antitumor activity of MKT-077 was confirmed using human tumor xenografts in nude mice.

• Authors: Y Chiba, T Kubota, M Watanabe, S W Matsuzaki, Y Otani, T Teramoto, Y Matsumoto, K Koya, M Kitajima
• Journal: Anticancer research (Anticancer Res) 1998 Mar-Apr Vol. 18 Issue 2A Pg. 1047-52 ISSN: 0250-7005 [Print] Greece
• PMID: 9615763 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Pyridines
• Thiazoles
• MKT 077

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Humans
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neoplasms, Experimental (drug therapy)
• Pyridines (therapeutic use)
• Thiazoles (therapeutic use)
• Transplantation, Heterologous