To clarify the mechanism of the reduction of metastatic @entity96 in @entity35 treated with angiogenesis inhibitor @entity10822 , the death of @entity5 cells was examined pathologically and ultrastructurally. @entity409 were developed by intravenous injection of AH-130 cells. @entity10822 was given subcutaneously after @entity5 cell injection. Alterations in the size and number of @entity3 were examined at various time points, in association with the analysis of cell death pattern. The metastatic nodules were divided into 4 groups according to the morphological patterns of cell death; no cell death, scattered apoptosis, central @entity39 , and @entity39 . The number and size of the @entity3 at 2 weeks in untreated @entity35 were larger than those in treated @entity35 . The number of @entity5 in untreated @entity35 decreased, but the @entity5 size increased. All @entity35 treated with @entity10822 were alive and free from @entity5 after 4 weeks, whereas all the untreated @entity35 died of liver metastases. The percentages of the @entity5 with @entity39 in untreated @entity35 (61.2% at 2 weeks and 100% at 4 weeks) were significantly higher than that (31.8% at 2 weeks) in treated @entity35 (P < 0.01). The percentage of the @entity5 containing apoptotic cells in treated @entity35 was significantly higher than that in untreated @entity35 (54.5% vs. 30.6%; P < 0.05). The growth of @entity3 without treatment might be faster than the growth of vessels in @entity5 , resulting in central @entity39 due to @entity63 . On the other hand, the reduction of metastatic @entity96 treated with @entity10822 might be caused by inhibition of angiogenesis, providing a weak @entity63 stimulus which triggers apoptosis, rather than by a direct cytotoxic effect on @entity5 cells, because previous in vivo experiments demonstrated that @entity10822 affected endothelial cells but not @entity5 cells.

Regression of metastatic @entity96 in @entity35 treated with angiogenesis inhibitor XXXX : occurrence of apoptosis and @entity39 .

@entity96 :: ('MESH:D008113', 'Disease') :: ['liver tumors'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'untreated tumors', 'tumors'] @entity10822 :: ('MESH:C066515', 'Chemical') :: ['TNP-470'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis', 'diffuse necrosis'] @entity409 :: ('MESH:D008107', 'Disease') :: ['Liver metastases'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemic', 'ischemia'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastatic tumors'] @entity35 :: ('10116', 'Species') :: ['rats']
@entity10822 :: (MESH:C066515,Chemical) :: ['TNP-470']
