Objective To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. Conclusions Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.
Intravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.
Bladder cancer comprises a heterogeneous group of tumors, the majority of which are non-muscle-invasive bladder cancer (NMIBC) at initial presentation. Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome. Although the risk of progression is less than 1% in 5 years, almost 15% will recur after 1 year, and 32% after 5 years. A complete transurethral resection, followed by an immediate single postoperative instillation of chemotherapy will reduce the risk of recurrence for the first 2 years. Follow-up cystoscopy is required to detect recurrence; in the vast majority of cases the recurrent tumor is of the same stage and grade as the primary tumor. The first follow-up visit, 3 months after surgery, is the most important in predicting risk of recurrence for the future. Recent developments in profiling urine and cancer tissue make it possible to better predict risk of progression and recurrence. In the future this profiling will play an important role in the timing and the choice of treatment, as well as guiding follow-up procedures.
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