M. Kragh et al., Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice, ONCOL REP, 6(4), 1999, pp. 759-762
We examined the effect of the anti-angiogenic compound TNP-470 on early tum
or growth characteristics following subcutaneous implantation of 1 mm(3) ti
ssue blocks of human glioblastoma U87, in nude mice. The mice received dail
y injections with TNP-470, 7 mg/kg, from one day before until either 3, 7,
11, or 15 days after inoculation. The time from inoculation until initiatio
n of exponential tumor growth was determined along with the post-therapeuti
c growth delay and the initial tumor doubling time (TD) for each individual
tumor (n=103) on the basis of tumor volume growth curves. We found that: i
) the onset of growth of U87 xenografts was effectively inhibited by concur
rent treatment with TNP-470 beyond the first three days after inoculation,
ii) this effect was fully reversible upon termination of therapy, and iii)
the posttherapeutic growth delay was independent of the accumulated dose. T
hese findings demonstrate that the in vivo effect of TNP-470 on tumor growt
h is tumor inhibitory rather than cytotoxic. The lack of effect of the anti
-angiogenic compound, TNP-470, in the early 3-day schedule is consistent wi
th the existence of an early avascular phase which precede the angiogenesis
-dependent tumor growth.