This work was partly funded by the National Institutes of Health (T32 CA009672, R01 CA173292), The Univer- sity of Michigan M-TRAC Program, the University of Michigan Comprehensive Cancer Center Support Grant (P30 CA046592), and the University Of Michigan Department Of Surgery.
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DISCUSSION
Dr Bradford K. Mitchell (Morgantown, WV): I have nothing to disclose. Can you tell us a little bit about the uptake of these nanoparticles? You suggest by the discussion on the sphere formation and its impact the possibility that these particles’ uptake is based on receptor expression on the sur- face or something else on the surface that’s going to dramatically change in your cells grown in monolayer. I wonder if that would impact your de- cision making about further testing.
Dr Mark S. Cohen (Ann Arbor, MI): We have actually looked at this in sphere formation, and we have recently completed, actually, some animal data as well. If you look at the SRB1 receptor expres- sion levels, ACCs have about 100-fold greater expression than any other cancer and almost a thou- sand fold greater expression than any other cell type. It makes a very selective target for this partic- ular HDL type of therapy. What we are seeing in the aggregate is an example of what we would expect to see in a tumor. We actually do see targeting and
localization in vivo, which I have not presented in this paper, but that is part of our ongoing studies.
Dr Bradford K. Mitchell: What is the expression in the monolayer?
Dr Mark S. Cohen: We did look at monolayer expression, and we have some data on Western to show that I did not include here, but compared with tissue levels, it is pretty high. I would say it is 10- to 20-fold higher than what you would see in normal cells at least, maybe even 100-fold higher, but it is pretty dense expression.