Intravesical administration of plasminogen activator inhibitor type-1 inhibits in vivo XXXX invasion and progression.

@entity137 @entity2630 @entity5 @entity189 @entity150 @entity35 @entity11693
PURPOSE: The potent effects of @entity2630 on tumorigenesis and angiogenesis in various experimental models are complex, complicated and at times contradictory. We determined the therapeutic potential of @entity2630 for inhibiting @entity150 invasion under conditions that closely mimic the clinical setting. MATERIALS AND METHODS: An orthotopic @entity35 @entity150 model was established by implanting AY-27 @entity35 transitional @entity189 cells into the bladder lumen of syngeneic Fischer F344 @entity35 . Three weeks after implantation 1 microM @entity2630 was administrated directly into the bladder lumen twice weekly for 2 weeks. Two days after the final treatment @entity5 size, total bladder weight, @entity5 stage and angiogenesis were assessed. To assess the @entity11693 axis the levels of active and total @entity11693 , and active and total @entity2630 in @entity5 extracts were determined 0, 2, 24 and 48 hours after intravesical @entity2630 administration. RESULTS: Intravesical @entity2630 bound and inactivated its molecular target, @entity5 @entity11693 . There was significant inhibition of @entity150 progression, as manifested by 53%, 37% and 57% reductions in @entity5 size, total bladder weight and angiogenesis, respectively. Only 22% of @entity2630 treated @entity5 invaded muscle vs 79% in controls. No @entity2630 @entity137 was detected. CONCLUSIONS: To our knowledge this study is the first to demonstrate that intravesical treatment with @entity2630 significantly inhibits @entity5 progression in an in vivo model of @entity150 . Further clinical development is warranted for using @entity2630 directly or in combination with current standards, such as bacillus Calmette-Guerin or interferon.
