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.
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 humantumor 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 (humancolon cancer), St-4 (humangastric cancer), and CRL1420 (humanpancreatic cancer) were evaluated as sensitive to MKT-077 in tested 5 strains. CONCLUSION: The antitumor activity of MKT-077 was confirmed using humantumor xenografts in nude mice.
Authors: Xiaokai Li; Sharan R Srinivasan; Jamie Connarn; Atta Ahmad; Zapporah T Young; Adam M Kabza; Erik R P Zuiderweg; Duxin Sun; Jason E Gestwicki Journal: ACS Med Chem Lett Date: 2013-11-14 Impact factor: 4.345
Authors: Anna Budina-Kolomets; Gregor M Balaburski; Anastasia Bondar; Neil Beeharry; Tim Yen; Maureen E Murphy Journal: Cancer Biol Ther Date: 2013-11-01 Impact factor: 4.742