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Proteomics in Bladder Cancer Research: Protein Profiling of Bladder Squamous Cell Carcinomas, Rev C

Figures 1 and 3), and exhibit distinct squamous features such as pearl formation and keratohyalin bodies. Grading of these tumors is subjective and takes into consideration the degree of nuclear polymorphism, nuclear to cytoplasmic ratio, and chromatin clumping, as well as the number of mitotic cells (Friedell et al. 1983).

To achieve a more reliable and objective classification of bladder SCCs that may eventually pave the way for studies of the molecular mechanisms underlying progression, we are exploring the possibility of using proteome expression profiles of these lesions as fingerprints to identify tumor subtypes and to define their grade of atypia (Celis et al. 1996b, stergaard et al. 1997). Proteins are frequently the functional molecules and, therefore, the most likely to reflect qualitative (expression of new proteins, changes in posttranslational modifications) and quantitative (up and down regulation, coregulated proteins) differences associated with various stages of cancer development. Genes may be present; they may be mutated, but they are not necessarily transcribed. Some messengers are transcribed but not translated, and the number of mRNA copies does not necessarily reflect the number of functional protein molecules (Anderson and Seilhamer 1997). Consequently, because of these uncertainties, focusing on the proteins eliminates many of the problems encountered at the nucleic acid level.

In addition to the above-mentioned studies, we are interested in assaying the urine of patients with SCCs for biomarkers that may be of value for identifying individuals at risk (Celis et al. 1996b, Rasmussen et al. 1996, stergaard et al. 1997). The strategy for searching for such markers is based on a syst
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