ABSTRACT
To investigate the antitumor activities of the immunoconjugates composed of anti-type IV collagenase monoclonal antibody Fab' fragment and lidamycin (LDM) prepared with different linkers. The immunoconjugates were prepared by linking Fab' to lysine-69 of LDM apoprotein by SPDP, LCSPDP, SMBS or SSMPB as the intermediate drug linkers. Immunoreactivities of the conjugates were determined by ELISA. The cytotoxicities of the conjugates were examined by clonogenic assay. In vivo antitumor effects of the conjugates were evaluated in nude mice bearing subcutaneously implanted HT-1080 tumor. ELISA assay showed that the conjugates retained part of the immunoreactivity of 3G11 against the antigen. The cytotoxicities of the Fab'-SMBS-LDM and Fab'-SSMPB-LDM to HT-1080 cells were significantly potent, compared with Fab'-SPDP-LDM, Fab'-LCSPDP-LDM and free LDM. In animal models at the same condition, free LDM, Fab'-SPDP-LDM and Fab'-LCSPDP-LDM inhibited the growth of HT-1080 tumor by 70.9%, 74.8% and 72.3%, while Fab'-SMBS-LDM and Fab'-SSMPB-LDM reached 78.0% and 87.7%, respectively. The median survival time of the mice treated with free LDM, Fab'-SPDP-LDM and Fab'-LCSPDP-LDM were prolonged by 71.9%, 82.2% and 107.5%, respectively, compared with that of untreated group. Whereas, the median survival time of Fab'-SMBS-LDM and Fab'-SSMPB-LDM were prolonged by 145.2% and 165.8%, respectively, indicating that Fab'-SSMPB-LDM was more effective than Fab'-SMBS-LDM in tumor suppression and life span prolongation. Fab'-SSMPB-LDM has more marked selective antitumor efficacy and lower toxicity, and might be a novel candidate for cancer therapy.
ABSTRACT
OBJECTIVE:To investigate the neuropotective effect and anticoagulation effect of total Saponins of Radix Liriopes on focal cerebral ischemia in rats.METHODS:Chemical reagent Fecl3 was locally applied on the injured vessels to establish middle cerebral artery thrombosis model,and the effects of total Saponins of Radix Liriopes on rats' behavioral disturbance,brain infarct size,the histopathological changes in brain and the expression rate of nNOS immunoreactive positive neurons were measured,and the bleeding time and coagulation time were also detected with glass tube method and tail transection method.RESULTS:Due to the use of total Saponin of Radix Liriopes(10 and 40mg? kg-1),the brain infarct size was significantly decreased,the behavioral disturbance were improved and the expression rate of the nNOS immunoreactive positive neurons in rats were decreased.At doses of 20 and 60mg? kg-1,total Saponin of Radix Liriopes significantly prolonged the coagulation time and bleeding time.CONCLUSION:Total Saponin of Radix Liriopes has nuroprotective effect on focal cerebral ischemia induced by middle cerebral artery thrombosis and significant anticoagulation effect.