1145 ORAL INHIBITORS OF MACROPHAGE MIGRATORY INHIBITORY FACTOR (MIF) LEAD TO REDUCED TUMOR STAGE AND BURDEN IN A MURINE MODEL OF INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 20101145 ORAL INHIBITORS OF MACROPHAGE MIGRATORY INHIBITORY FACTOR (MIF) LEAD TO REDUCED TUMOR STAGE AND BURDEN IN A MURINE MODEL OF INVASIVE BLADDER CANCER John Taylor, Shilpa Choudhary, Poornima Hegde, Olga Voznesensky, Vidal de la Cruz, James Pruitt, Thais Sielecki, and Carol Pilbeam John TaylorJohn Taylor Farmington, CT More articles by this author , Shilpa ChoudharyShilpa Choudhary Farmington, CT More articles by this author , Poornima HegdePoornima Hegde Farmington, CT More articles by this author , Olga VoznesenskyOlga Voznesensky Farmington, CT More articles by this author , Vidal de la CruzVidal de la Cruz King of Prussia, PA More articles by this author , James PruittJames Pruitt King of Prussia, PA More articles by this author , Thais SieleckiThais Sielecki King of Prussia, PA More articles by this author , and Carol PilbeamCarol Pilbeam Farmington, CT More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.644AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail 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. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e443 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Taylor Farmington, CT More articles by this author Shilpa Choudhary Farmington, CT More articles by this author Poornima Hegde Farmington, CT More articles by this author Olga Voznesensky Farmington, CT More articles by this author Vidal de la Cruz King of Prussia, PA More articles by this author James Pruitt King of Prussia, PA More articles by this author Thais Sielecki King of Prussia, PA More articles by this author Carol Pilbeam Farmington, CT More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...