Male Sprague Dawley (SD) rats received RFA or sham puncture with concomitant sorafenib (5 mg/kg qd from day 2) or vehicle. Necrosis volume was calculated from resected specimens. Proliferation and micro vessel density were determined by Ki67 and CD31 immunofluorescence, respectively. mRNA expression of hepatocyte growth factor (HGF), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) was quantified.
While ablation size was identical in all treatment groups at day 1, sorafenib treated animals showed sustained necroses (219 卤 24 vs. 88 卤 52 mm3 in controls; P = 0.03), elevated alanine aminotransferase (ALT) and elevated glutamate dehydrogenase (GLDH) (76 卤 37 vs. 47 卤 58 mm3; P = 0.50) at day 3. By day 7 necrosis volumes equalized for the treatment groups. Ki67 and CD31 staining showed reduced proliferation and micro vessel density at days 1 and 3 following sorafenib. Growth factors HGF and EGF were significantly overexpressed in liver tissue after sorafenib.
Sorafenib initially promotes necrosis after RFA in liver tissue. The delay in tissue repair is overcome at day 7 presumably by transient compensatory overexpression of growth signals. Based on these data from animal studies further investigation of adjuvant sorafenib in humans is warranted.
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