Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice.
We examined the effect of the anti-angiogenic compound TNP-470 on early tumor growth characteristics following subcutaneous implantation of 1 mm3 tissue blocks of human glioblastoma U87, in nude mice. The mice received daily 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 initiation of exponential tumor growth was determined along with the post-therapeutic 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 concurrent treatment with TNP-470 beyond the first three days after inoculation, ii) this effect was fully reversible upon termination of therapy, and iii) the post-therapeutic growth delay was independent of the accumulated dose. These findings demonstrate that the in vivo effect of TNP-470 on tumor growth 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 with the existence of an early avascular phase which precede the angiogenesis-dependent tumor growth.
Kragh
M
M
Institute of Molecular Pathology, University of Copenhagen, DK-2100, Copenhagen, Denmark.
Spang-Thomsen
M
M
Kristjansen
P E
PE
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D003510:Cyclohexanes; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol