Effect of TNP-470 (AGM-1470) on the growth of rat rhabdomyosarcoma tumors of different sizes.
Potential anticancer therapy with the fumagillin analog TNP-470 was investigated in the present project using subcutaneously growing rhabdomyosarcomas in rats. Specifically, influences of different tumor sizes at the start of treatment as well as dose/schedules were evaluated with this angiogenesis inhibitor. The results show a significant (p = < or = 0.01) reduction of the growth rate, even for relatively large-sized (> 7 cm3) tumors, when 50 mg/kg TNP-470 was used every other day for up to 3 or 5 injections. With 30 mg/kg TNP-470 injections, effects were seen only with tumors measuring < 7 cm3. The histologic examinations demonstrate an increase in necrosis, both in the center and in the peripheral part of TNP-470-treated tumors. Overall, both tumor volume and drug dose determine treatment outcome with the rat rhabdomyosarcoma. The results suggest that angiogenesis inhibitors could represent a valid component in the treatment of progressive tumor growth, also of large tumors as often encountered in clinics. The antivasculature therapy might also improve hypoxia/necrosis-related therapeutic approaches.
Landuyt
W
W
University Hospital, K.U. Leuven, Belgium. Willy.Landuyt@rega.kuleuven.ac.be
Theys
J
J
Nuyts
S
S
Drijkoningen
M
M
Fowler
J
J
Reijnders
A
A
Liekens
S
S
Neyts
J
J
de Bruijn
E
E
Anné
J
J
Lambin
P
P
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002470:Cell Survival; D003510:Cyclohexanes; D004334:Drug Administration Schedule; D008297:Male; D009336:Necrosis; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol