摘要
AIM To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate(CA4 P), among hepatocellular carcinomas(HCCs) and implanted rhabdomyosarcoma(R1) in the same rats by magneticresonance-imaging(MRI), microangiography and histopathology.METHODS Thirty-six HCCs were created by diethylnitrosamine gavage in 14 rats that were also intrahepatically implanted with one R1 per rat as monitored by T2-/T1-weighted images(T2wI/T1wI) on a 3.0 T clinical MRIscanner. Vascular response and tumoral necrosis were detected by dynamic contrast-enhanced(DCE-) and CE-MRI before, 1 h after and 12 h after CA4P iv at 10 mg/kg(treatment group n = 7) or phosphate-buffered saline at 1.0 mL/kg(control group n = 7). Tumor blood supply was calculated by a semiquantitative DCE parameter of area under the time signal intensity curve(AUC30). In vivo MRI findings were verified by postmortem techniques.RESULTS On CE-T1wIs, unlike the negative response in all tumors of control animals, in treatment group CA4P caused rapid extensive vascular shutdown in all R1-tumors, but mildly or spottily in HCCs at 1 h. Consequently, tumor necrosis occurred massively in R1-tumors but patchily in HCCs at 12 h. AUC30 revealed vascular closure(66%) in R1-tumors at 1 h(P < 0.05), followed by further perfusion decrease at 12 h(P < 0.01), while less significant vascular clogging occurred in HCCs. Histomorphologically, CA4P induced more extensive necrosis in R1-tumors(92.6%) than in HCCs(50.2%)(P < 0.01); tumor vascularity heterogeneously scored +^+++ in HCCs but homogeneously scored ++ in R1-tumors.CONCLUSION This study suggests superior performance of CA4P in metastatic over primary liver cancers, which could guide future clinical applications of vascular-disruptingagents.
AIM To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate(CA4 P), among hepatocellular carcinomas(HCCs) and implanted rhabdomyosarcoma(R1) in the same rats by magneticresonance-imaging(MRI), microangiography and histopathology.METHODS Thirty-six HCCs were created by diethylnitrosamine gavage in 14 rats that were also intrahepatically implanted with one R1 per rat as monitored by T2-/T1-weighted images(T2wI/T1wI) on a 3.0 T clinical MRIscanner. Vascular response and tumoral necrosis were detected by dynamic contrast-enhanced(DCE-) and CE-MRI before, 1 h after and 12 h after CA4P iv at 10 mg/kg(treatment group n = 7) or phosphate-buffered saline at 1.0 mL/kg(control group n = 7). Tumor blood supply was calculated by a semiquantitative DCE parameter of area under the time signal intensity curve(AUC30). In vivo MRI findings were verified by postmortem techniques.RESULTS On CE-T1wIs, unlike the negative response in all tumors of control animals, in treatment group CA4P caused rapid extensive vascular shutdown in all R1-tumors, but mildly or spottily in HCCs at 1 h. Consequently, tumor necrosis occurred massively in R1-tumors but patchily in HCCs at 12 h. AUC30 revealed vascular closure(66%) in R1-tumors at 1 h(P < 0.05), followed by further perfusion decrease at 12 h(P < 0.01), while less significant vascular clogging occurred in HCCs. Histomorphologically, CA4P induced more extensive necrosis in R1-tumors(92.6%) than in HCCs(50.2%)(P < 0.01); tumor vascularity heterogeneously scored +^+++ in HCCs but homogeneously scored ++ in R1-tumors.CONCLUSION This study suggests superior performance of CA4P in metastatic over primary liver cancers, which could guide future clinical applications of vascular-disruptingagents.
