title: Antitumoral effects of R 75251 on the growth of transplantable R3327 prostatic adenocarcinoma in rats.
abstract: The antitumoral activity of a novel imidazole derivative, R 75,251, has been studied in the androgen-dependent R3327G Dunning prostate adenocarcinoma grafted subcutaneously in syngeneic rats. Dietary application resulting approximately in dose levels of 80, 120, and 160 mg/kg reduced tumor weight by 66, 81, and 79%, respectively. This effect was not significantly different from that measured after castration (-82%). In intact animals, however, serum testosterone levels were almost not affected by R 75,251 treatment while LH levels rose two- to threefold. In castrated rats a tenfold increase in LH was observed. Moreover, prostate and seminal vesicles weights decreased much less after R 75,251 treatment than after castration. In castrated animals, treatment with R 75,251 induced a slight, non-significant reduction in tumor weight (-36%) compared with castration alone. In castrated animals, tumor growth was restored by exogenous administration of testosterone. In such animals R 75,251 also significantly reduced tumor weight by 57%. Similar results were obtained with Dunning R3327G prostate adenocarcinoma grafted beneath the renal capsule in male syngeneic rats receiving twice daily orally by gavage a dose of 80 mg/kg of R 75,251. These data suggest that R 75,251 exerts an antitumoral effect independent of its inhibition of androgen biosynthesis.
authors.affiliation: Janssen Research Foundation, Beerse, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Van Ginckel
authors.forename: R
authors.initials: R
authors.lastname: De Coster
authors.forename: W
authors.initials: W
authors.lastname: Wouters
authors.forename: W
authors.initials: W
authors.lastname: Vanherck
authors.forename: R
authors.initials: R
authors.lastname: van der Veer
authors.forename: N
authors.initials: N
authors.lastname: Goeminne
authors.forename: E
authors.initials: E
authors.lastname: Jagers
authors.forename: H
authors.initials: H
authors.lastname: Van Cauteren
authors.forename: L
authors.initials: L
authors.lastname: Wouters
authors.forename: W
authors.initials: W
authors.lastname: Distelmans
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D013739:Testosterone; C061121:liarozole