a. The syngeneic orthotopic murine bladder cancer model MB49 is hampered by unreliable tumor implantation. We optimized this model by a simple modification of the standard implantation technique in three groups of mice. The prolonged dwell time of tumor cells resulted in take rates of 100% in all three groups. Survival and bladder weights were significantly correlated with the number of instilled cells. Even with the highest tumor load, Bacillus Calmette-Guerin therapy improved survival and reduced bladder weights significantly, as compared to PBS. Thus, the modified model is highly reliable and maintains its susceptibility to topical immunotherapy. b. Hematogenous spread of bacillus Calmette-Guerin (BCG) after intravesical instillation for bladder cancer is rare but it may result in systemic infection and hypersensitivity reaction. We investigated fluoroquinolones and steroids in an animal model to improve the therapeutic options in local and systemic BCG infection. Furthermore, the antitumor effectiveness of intravesical BCG with simultaneous application of fluoroquinolones and/or steroids was tested. BCG infections, whereas the hyperergic reaction after repeat BCG infection was susceptible only to steroids. Administering fluoroquinolones during an intravesical treatment course does not affect the antitumor efficacy of BCG. c. A presumed reason for the high recurrence rate of superficial bladder cancer after transurethral tumor resection is the reimplantation of tumor cells. Because tumor cell adhesion to the extracellular matrix is mediated by integrin molecules, we tested specific integrin receptor blocking oligopeptides to prevent this mechanism. Combining oligopeptides with various specificities significantly inhibited tumor cell adhesion and tumor outgrowth. Application of this principle in a clinical setting may be an effective method for reducing the recurrence rate of superficial bladder cancer. d. The development of intra-abdominal tumor spread and portsite metastases in urothelial cancer are still questions regarding the safety of laparoscopic methods for the resection of malignancies. Currently, the actual incidence of intra-abdominal tumor spread and portsite metastasis remains unknown. Herein, we investigated the influence of antiadhesive oligopeptides and cytotoxic agents (administered intraperitoneally) on implantation of a tumor cell suspension after laparoscopic surgery in an experimental model. Conclusions: This study suggests that tumor implantation after laparoscopic surgery and port-site metastases might be prevented by the intraperitoneal administration of specific oligopeptides or cytotoxic agents. Moreover, oligopeptides, in comparison with mitomycin, caused less weight loss of the mice. e. To improve the orthotopic murine bladder cancer model by using bioluminescent (BL) MB49 tumour cells for noninvasive in vivo monitoring of tumour growth and to examine the efficacy of integrin receptor-blocking oligopeptides on preventing tumour cell adhesion in this improved bladder cancer model. Peptides targeting adhesion molecules prevent attachment of bladder cancer cells to the injured bladder wall. BLI is a sensitive method for detecting luminescent bladder cancer cells in an orthotopic mouse model. |