metastasized site-specific molecular targeted therapy utilizing redox signaling in urothelial carcinoma

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To improve conventional chemotherapeutic-efficacy for the treatment of metastasized urothelial carcinoma, a combination use of traditional medicines is not completely effective and detailed mechanisms have been rarely elucidated. First, we demonstrated that a comprehensive approach for the detection of p53 mutations may be essential to elucidate their clinical significance. In addition to that, 3-30-Methylene-bis [4-hydroxycoumarin] (dicoumarol), an inhibitor of NADPH: quinone oxidoreductase 1, was assessed for its potential antineoplastic effects and the ability to abrogate p53 protein. It is suggested that dicoumarol could enhance cytotoxicity of CDDP in urogenital cancer cells with wild-type p53 through the p53/p21/JNK pathways.Second, we assessed the possibility of galectin-7 to accelerate CDDP-induced cell killing in vitro and also to predict chemosensitivity against CDDP in urothelial cancer patients. We found that Galectin-7 is a candidate for a predictive marker of chemosensitivity against CDDP, and the targeted expression of galectin-7 might overcome the chemoresistance of urothelial cancer.Finally, we clarified how triptolide (PG490), an oxygenated diterpene derived from a Chinese herb, enhances the cisplatin (CDDP) -induced cytotoxicity in urothelial cancer cells. It is proven that cancer-specific enhancement of CDDP-induced cytotoxicity with triptolide may effectively overcome the resistance to a CDDP-based conventional chemotherapy as a treatment for urothelial cancer.In the near future these facts obtained from our studies can contribute to establish new strategies of chemotherapy for urothelial carcinoma.