Results of transarterial chemoembolization on rats with grafted hepatocellular cancer of liver

Abstract

Modeling of a transarterial chemoembolization (TACE) is carried out on rats (n = 6) with hepatocellular cancer of liver RS1 (Vcp = 4.5 cm3) which has developed in muscles of the leg (i.m.). Sensitivity of a tumor to the single introduction of substance of doxorubicine (sDOX) in maximum tolerated doses (MTD) of 5-12 mg/kg with the achievement of significantly tumor growth inhibition on 55-77% (p = 0.001) is previously shown. TACE is executed with the elastic polyvinyl alcohol microspheres in size of 0.2 mm in diameter loaded with doxorubicine (MS/sDOX) with the release within 7 days. MS/sDOX in the volume of 0.034-0.1 ml (a cumulative dose of sDOX of 3.3-10.5 mg/kg) was introduced into a femoral artery (i/a) with a diameter of 0.16 mm under control of an embolization (MS or arterial ligature) and chemotherapy (sDOX). TACE gave rise in the cytoreductive effect of the tumor nodule by 67% (T/C = 33%, p = 0.0004) with the single regression and the development of the grade 1 therapeutical pathomorphosis (TP). The therapeutic gain of MC/sDOX manifested in coupled with the cytoreduction the decline of the tumor growth rate («т» = 11-16 against 1.9-2.0 days in the control group) and at the equal inhibiting action with sDOX dose reduced by 20% against MTD. Side effects of TACE (a necrosis of soft tissues, 7th-16th days) were not associated with the full stagnation of a regional blood flow due to the discrepancy of MS to diameter of the artery. The whole of the revealed effects has allowed to consider the modeling of i/m tumor on rats to be suitable for the screening of the specific activity of agents clients for TACE. The preclinical study of the method is rational to execute on the corresponding model on large animals with regional artery of the sufficient cross section of the vessel permitting to perform TACE satisfactory.