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


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.


CONCLUSIONS
The antitumor activity of MKT-077 was confirmed using human tumor xenografts in nude mice.
Chiba
Y
Y
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Watanabe
M
M
Matsuzaki
S W
SW
Otani
Y
Y
Teramoto
T
T
Matsumoto
Y
Y
Koya
K
K
Kitajima
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011725:Pyridines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D011725:Pyridines; D013844:Thiazoles; C097880:MKT 077