Antiangiogenic drugs for chemotherapy of bladder tumours.
BACKGROUND
Bladder cancers have different angiogenic pathways distinguishing not only papillary from solid tumours, but even papillary superficial from papillary invasive ones, thus representing selective targets for antiangiogenic drugs.


METHODS
The bacterial wall component tecogalan, inhibiting basic fibroblast growth factor (bFGF), the fumagillin derivative TNP-470, inhibiting vascular endothelial growth factor (VEGF), the distamycin A derivative PNU153429, and the tetracycline minocycline were administered to nude mice injected with the human bladder cancer cell lines 639V, causing bFGF-expressing papillary superficial tumours, or T24, causing VEGF-expressing papillary invasive tumours.


RESULTS
Tecogalan had no effect even on 639V tumour growth, where bFGF was unaffected. TNP-470 only had an effect on T24 tumours, delaying tumour appearance and growth and lowering VEGF; these effects were augmented by adding minocycline. PNU153429 had no effect on 639V tumours, and a slight effect on T24 tumours.


CONCLUSIONS
TNP-470 may represent a selective drug for the treatment of VEGF-expressing invasive papillary bladder tumours.
Rocchetti
Romina
R
Institute of Microbiology and Biomedical Sciences, Polytechnic University of Marche, Ancona, Italy.
Talevi
Simona
S
Margiotta
Chiara
C
Calza
Roberta
R
Corallini
Alfredo
A
Possati
Laura
L
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003510:Cyclohexanes; D004214:Distamycins / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000494:pharmacology / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D004214:Distamycins; C113015:PNU 153429; D047495:PPAR gamma; D011135:Polysaccharides, Bacterial; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C079061:tecogalan; D008911:Minocycline; D000077609:O-(Chloroacetylcarbamoyl)fumagillol