Abstract 1549: Oral inhibitors of macrophage migratory inhibitory factor (MIF) lead to reduced tumor burden in a murine model of invasive bladder cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 8_Supplement; p. 1549
• Main Authors: Taylor, John A., Choudhary, Shilpa, Hegde, Poornima, Voznesensky, Olga, de la Cruz, Vidal F., Pruitt, James R., Sielecki, Thais M., Pilbeam, Carol
• Format: Journal Article
• Language: English
• Published: 15.04.2010
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-1549

Abstract INTRODUCTION AND OBJECTIVES: MIF is a proinflammatory cytokine with regulatory properties over tumor suppressor proteins involved in bladder cancer. We have reported that absence of MIF in transgenic mice leads to decreased angiogenesis and invasion in the BBN model of bladder cancer. We evaluated the impact of 2 oral inhibitors of MIF (Cytokine PharmaSciences, King of Prussia, PA; CPSI) in the BBN model. METHODS: 30, 3 mnth old male C57Bl/6 mice were treated with BBN 0.05% in drinking water for 22 wks. Mice (n=10/grp) received vehicle (PEG 300, methylcelluose), oral inhibitor CPSI-2705 or CPSI-1306 daily (25 mg/kg) by gavage from wks 16-22, corresponding to time of progression from CIS to invasive disease as determined in previous experiments. Animals were inspected daily for general health with weights recorded weekly. Bladders were weighed, fixed and assessed for tumor stage, grade, burden and associated angiogenesis. RESULTS: In general, the group receiving CPSI-1306 appeared healthier during drug treatment. There was a 16% weight loss from the start of gavage in the control group vs 10-11% in the drug groups. Two animals each from the control and CPSI-2705 group died prior to study completion. The majority of control animals had evidence of upper tract obstruction with less noted in CPSI 2705 and none in the 1306 group. Average bladder weights were 0.5 ± 0.5 gm, 0.3 ± 0.3 gm and 0.2 ± 0.2 gm for control, 2705 and 1306 respectively which approached statistical significance for control vs 1306 (log transf p=0.06). There was a higher proportion of pT3 disease in the control (80%) vs inhibitor groups (60%). Tumor burden was markedly diminished in the drug groups (81% cntrl vs 62% 2705 vs 59% 1306, involvement invasive disease) with some bladders in these arms having only focal areas of invasion. Tumor grade trended lower in the drug groups as well. CONCLUSIONS: The use of MIF oral inhibitors CPSI 2705 and CPSI 1306 in the BBN bladder cancer model resulted in less weight loss, improved general health, decreased tumor burden with a trend toward lower stage, grade and tumor associated angiogenesis. The results of this experiment warrant larger studies to validate and expand these findings with a goal of development for clinical use. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1549.