Weber and co workers observed that xan thine oxidase, the key rate limiting enzyme of purine catabolism, was decreased 2 to 10 fold in all hepatomas studied, regardless of the degree of malignancy, growth sellectchem rates and degrees of the histological differentiation of the neoplasms. A wide range of enzyme assays and other experimental methods have been employed to study oxidoreductase enzymes Inhibitors,Modulators,Libraries in Hepatocellular carcinoma. They include reverse transcriptase polymerase chain reaction amplifica tion, immunohistochemical staining, in situ hybridization, and Western blotting. Many oxidoreductase enzyme assays incorporate spectro scopic absorbance and polarography. Other utilize RNA blot hybridization, run on assays and Lowry protein assays.

Although the above experimental methods have contrib uted immensely to better understanding Inhibitors,Modulators,Libraries of the pathobiol ogy of oxidoreductase enzymes in hepatic neoplasia, they all suffer from lack of specificity in the structural informa tion they provide, ability to analyze sample mol ecules in the presence of interfering contaminants and ability to map the broad cellular biology and biophysical profiles of the tumor vs. matched benign cohorts. To date, no proteomics method for oxidoreductase enzymes in Hepatocellular carcinoma has been attempted or documented. The mass spectrometry based proteomic approach presented in this work holds the potential to overcome all of the above limitations, in addition to pro viding improved ease of automation, speed and sensitiv ity. HepG2 cell line, rather than hepatoma, is chosen for pro teomic comparison with normal human liver in this work.

The reason for choosing a cell line is because heterogene ity Inhibitors,Modulators,Libraries inherently associated with complex liver tumor matrix, which could be further compounded by cirrhosis, hepati tis B virus, Hepatitis C virus, inflammation, regenerative liver fibrosis and other lesions, may introduce inordinate errors. Unique challenges posed by the heterogeneity of complex liver Inhibitors,Modulators,Libraries tumor matrix is attested by the work of Fernandez and co workers, who clearly showed that the varia tion within adenocarcinoma tissue samples is considera bly greater than that within the matched benign cohorts. Therefore, HepG2 cell line is chosen for this study prima rily because it Inhibitors,Modulators,Libraries is more homogenous. However, tumor cell lines do not always accurately represent the in vivo biolog ical profiles of the tumor tissues from selleck products which they are derived. For example, Sandberg and co workers found that only 34 of the 60 cell lines used in a quantita tive tissue similarity index analysis were most similar to the tumor types from which they were derived.