tranilast and Urinary-Bladder-Neoplasms

Romidepsin (FK228, depsipeptide, FR901228), a unique cyclic depsipeptide with a histone deacetylase inhibitor (HDACI) activity, is a potential cancer therapeutic agent and currently under clinical trials for several types of cancer. For bladder cancer, romidepsin seems to be a potent antitumor agent from our recent study. In this study, we further delineate a new agent that can enhance both HDACI and antitumor activity of romidepsin.. We screened a chemical library to identify candidate(s) that could enhance romidepsin activity. Chemical synthesis and purification were carried out to produce pure compound to examine its biochemical and antitumor effect on bladder cancer cell lines both in vitro and in vivo.. Tranilast, N-(acetoacetyl) anthranilic acid, was first identified as a lead compound from screening, and then, one of the analogues, 2,3-dimethoxycinnamoyl azide (DMCA), seems to be more potent than tranilast. Our data indicate that DMCA can potentiate the HDACI activity of romidepsin and other biological activities, such as cell cycle arrest and apoptosis; these effects were accompanied with the expression of various key cell cycle regulators in different bladder cancer cells. Consistently, DMCA can enhance the in vivo antitumor effect of romidepsin without causing any more weight loss than romidepsin alone.. DMCA is able to enhance the antitumor effect of romidepsin on bladder cancer from in vitro and in vivo.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Azides; Blotting, Western; Cell Cycle; Cell Proliferation; Cinnamates; Depsipeptides; Enzyme Inhibitors; Histone Deacetylases; Humans; Mice; Mice, Nude; ortho-Aminobenzoates; Reverse Transcriptase Polymerase Chain Reaction; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays

The cytomorphologic features of voided urine specimens from two patients with antiallergic drug (Tranilast)-induced eosinophilic cystitis are described. The urothelial cells tend to occur in clusters and are of variable size. The remarkable vacuolization is observed in the cytoplasm. The markedly vacuolated cytoplasm which may be infiltrated by polymorpho-nuclear leucocytes is unremarkable. Some nuclei usually show transparent center surrounded by a rim of chromatin. The nucleoli are prominent. Marked vacuoles in the nucleus is observed. These findings are very important cytomorphologic characteristics for differential diagnosis between eosinophilic cystitis and malignant bladder tumor and cystitis due to bacterial infection.

Topics: Aged; Asthma; Cystitis; Diagnosis, Differential; Eosinophils; Female; Humans; Male; Middle Aged; ortho-Aminobenzoates; Urinary Bladder Neoplasms; Urine