Research in Dr. Messing's laboratory investigates the role of polyamine synthesis and inhibition in the prevention of bladder cancer. Induction of ornithine decarboxylase (ODC), which catalyzes the rate limiting step of polyamine synthesis is characteristic of the malignant transformation of human urothelial cells and indeed many other cell types as well. Tumor promoters obligatorily require enhanced polyamine synthesis primarily through induction of ODC activity. Difluoromethylornithine (DFMO) a non-competitor inhibitor of ODC has been used successfully in vitro and in animal models to prevent the development of urothelial and many other cancers. Dr. Messing's lab has demonstrated both in vitro and in vivo malignant human urothelial cells and have increased ODC activities and putrescine levels and that DFMO can return these levels to normal. He is now studying this drug's effects on a variety of molecular and genetic alterations that characterize malignant urothelial transformation such as alteration in expression of the receptor for epidermal growth factor which seems to precede malignant growth. Utilizing immunohistochemical and in situ hybridization methods, Dr. Messing's lab is assessing the effects of exposure to DFMO on the normal and malignant urothelial tissues. In addition, this agent is now being tested in patients.

With the joint funding through the National Cancer Institute and industry a prospective randomized study of DFMO vs. placebo in the prevention of superficial bladder cancer began in March 1999 in over 40 institutions throughout our country. Dr. Messing serves as study director and utilizes specimens from participants in this study for his continued research in this area providing critical clinical correlation with laboratory observations.

Reeder JE, Morreale JF, O'Connell MJ Stadler WM, Messing EM, Wheeless LL. Loss of the CDKN2A/p16 locu detected in bladder irrigation specimens by flourescece in situ hybridization. Journal of Urology. 158:1721, 1997.

Joseph JV., Messing EM. Chemoprevintion of bladder and prostate carcinoma. Cancer Control. 4:2, 1997.

Stewart J, Kozlowski P, Sowden M, Messing EM, Smith HC,. A quantitative assay for asessing allelic proportions iterative gap ligation. Nucleic Acids Research. 26:4, 961-966, 1998.

Jung I, Reeder JE, Cox C, Siddiqui JFM, O'Connell MJ, Collins L, Yang Z, Messing EM, Wheeless LL. Chromosome 9 Monosomy by Fluorescence in Situ Hybridization of Bladder Irrigation Specimens is Predictive of Tumor Recurrence. Journal of Urology, 162(6):1900-3, 1999.

Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 341(24):1781-8, 1999.

Ochal LK, Sowden MP, Messing EM, Wheeless LL, Reeder JE. Mus musculus DBCCR1 mRNA, complete sequence GenBank Accession AF202896, 1999.

deVereWhite RW, Deitch AD, Daneshmand S, Blumenstein B, Lowe BA, Sagalowsky AI, Smith JA, Schellhammer PF, Stanisic TH, Grossman HB, Messing EM, Crissman JD, Crawford ED. The Prognostic significance of S-phase analysis in stage Ta/T1 bladder cancer: A Southwest Oncology Group Study. Accepted for publication, European Urology, 37(5):595-600, 2000.

Jung I, Messing EM. Molecular Mechanisms, and pathways in bladder cancer development and progression. Cancer Control 7:4;325-334, 2000.