[Urothelial carcinoma. Role of G-protein coupled receptors in cell movement and proliferation].
To develop new therapeutic strategies we examined the expression and signaltransduction of G protein-coupled receptors in a human transitional cell carcinoma cell line. The receptors for lysophosphatidic acid (LPA) and thrombin potently stimulate cell migration. Pretreatment with PTX completely inhibited cell motility induced by LPA. In the model of chemically induced bladder carcinoma in rats the effects of intravesical instillation of PTX or phosphate buffered saline was examined. The incidence of G2-G3 cells in cytology was significantly reduced in rats treated with PTX. To ascertain the side effects of intravesical instillation of PTX a Phase I study was initiated. 15 patients were instilled with PTX at 5 dose levels (14-72 micrograms/100 ml) 3 times a week. Instillation of PTX up to 72 micrograms was without local or systemic side effects. PTX is a substance which potently inhibits tumor cell motility and progression. Intravesical treatment was well tolerated and therefore, the influence of PTX on local tumor should be evaluated in a Phase II study.
Lümmen
G
G
Urologische Klinik und Poliklinik, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen. gerd.luemmen@uni-essen.de
Sperling
H
H
Schneider
T
T
Otto
T
T
Rübben
H
H
D000283:Administration, Intravesical; D000368:Aged; D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D020555:GTP-Binding Protein Regulators / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D018179:Receptors, Thrombin / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology*
D020555:GTP-Binding Protein Regulators; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D018179:Receptors, Thrombin; D037342:Pertussis Toxin