No abstract

Background: Computer image analysis techniques have decreased effects of observer biases, and increased the sensitivity and the throughput of immunohistochemistry (IHC) as a tissue-based procedure for the evaluation of diseases.

The redox-active protein thioredoxin plays a critical role in cellular antioxidant systems. 1 This action is partially mediated via a family of enzymes called peroxiredoxins that are able to reduce hydrogen peroxide. 2,3 During this process thioredoxin is oxidized, and the reduced protein is replenished under the action of the selenium-dependent thioredoxin reductase, using the pentose-phosphate pathway as the source of metabolic energy. 4 Thioredoxin also efficiently reduces disulfides that can be formed as a result of oxidative stress. 1,5 It is responsible for the maintenance of many important cellular processes that are dependent on protein thiol redox states, including ribonucleotide reduction and the suppression of apoptosis. One of these processes involves the regulation of gene transcription under the action of redox-sensitive transcription factors including nuclear factor-B, AP1, hypoxia-inducible factor-1, and p53. 6 -9 This is via an interaction with the redox effector factor 1 (ref-1) that maintains cysteine residues in the appropriate redox state needed for the transcription factors to bind to DNA. Thioredoxin provides the reducing potential needed for ref-1 activity. Transcription factors that are dependent on the thioredoxin/ref-1 interaction are responsible for the activation of many genes that have the overall effect of promoting cell viability in response to adverse conditions including hypoxia and oxidative stress. These effects