Issues

Interrelation between vasculature, blood flow, proliferation, and hypoxia is shown in an HCT116 tumor xenograft 24 hours following irinotecan treatment. Irinotecan initially halts proliferation throughout the tissue but by 24 hours the S-phase fraction returns to near-control levels. The image was produced using multiplexed immunohistochemistry to illustrate the effects of drugs in the context of the tumor microenvironment. Greyscale images of the individual staining patterns were coregistered to produce the composite image shown here. HCT116 xenografts exhibit a corded architecture, where sheaths of tumor cells can be seen to surround individual vessels. Cells can survive to ∼150 m away from the blood vessels but become increasingly oxygen-deprived and eventually necrose. For details, see the article by Kyle and colleagues on page 2727.