UNASSIGNED: A number of anti-angiogenic drugs targeting @entity319 ( @entity319 ) have developed and enabled significant advances in @entity5 therapy including @entity14 . However, acquired resistance to the drugs occurs, leading to disease progression, such as invasion and @entity3 . How @entity5 become the resistance and promote their malignancy remains fully uncertain. One of possible mechanisms for the resistance and the progression may be the direct effect of @entity319 inhibitors on @entity5 cells expressing @entity319 . We investigated here the direct effect of a @entity319 -targeting agent, @entity8486 , which is the first small molecule inhibitor of @entity7 -Rs for the treatment of @entity1 with @entity14 , on phenotype changes in @entity694 HCT116 cells. Treatment of cells with @entity8486 for only 2 days activated cell migration and invasion, while vehicle-treated control cells showed less activity. Intriguingly, chronic exposure to @entity8486 for 90 days dramatically increased migration and invasion activities and induced a resistance to @entity519 -induced apoptosis. These results suggest that loss of @entity7 signaling in @entity5 cells may induce the acquired resistance to @entity7 / @entity319 targeting therapy by gaining two major malignant phenotypes, apoptosis resistance and activation of migration/invasion. J. Med. Invest. 62: 195-198, August, 2015.

The malignant progression effects of XXXX in @entity1 @entity694 cells.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity7 :: ('7422', 'Gene') :: ['VEGF'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'tumors'] @entity8486 :: ('MESH:C559147', 'Chemical') :: ['regorafenib'] @entity319 :: ('3791', 'Gene') :: ['vascular endothelial growth factor receptors', 'VEGF-R'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxia'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colon cancer']
@entity8486 :: (MESH:C559147,Chemical) :: ['regorafenib']
