The thioredoxin-thioredoxin reductase system: over-expression in human cancer. Lincoln David T,Ali Emadi Eman M,Tonissen Kathryn F,Clarke Frank M Anticancer research Redox control has emerged as a fundamental biological control mechanism. One of the major redox control systems is the thioredoxin system comprised of thioredoxin (TRX) and thioredoxin reductase (TR). Together they form a powerful system involved in many central intracellular and extracellular processes including cell proliferation, the redox regulation of gene expression and signal transduction, protection against oxidative stress, anti-apoptotic functions, growth factor and co-cytokine effects, and regulation of the redox state of the extracellular environment. Over recent years this system has increasingly been linked to the development and expression of cancer phenotypes. In this report immunocytochemical approaches have been used to simultaneously determine the expression and localisation of both TRX and TR in primary human cancers, including breast cancer, thyroid, prostate and colorectal carcinoma, and malignant melanoma. In aggressive invasive mammary carcinomas and advanced malignant melanomas, thioredoxin was highly over-expressed compared to tumours of lesser aggressive nature. TRX expression was found in both nuclear and cytoplasmic location in the neoplastic cells. Furthermore, increased levels of TRX positively correlate with thioredoxin reductase (TR) expression and localisation. These results, which are the first immunocytochemical studies on the in vivo expression and localisation of TRX and TR in melanomas, thyroid, prostate and colorectal carcinomas and the first reports of TR expression in breast carcinomas, significantly extend the range of human cancers for which such data is available. Overall the results support the conclusion that aggressive tumours greatly over-express both TRX and TR. Such tumours have a high proliferation capacity, a low apoptosis rate and an elevated metastatic potential strongly implicating the involvement of the TRX system in the processes of oncogenesis and tumourogenesis and confirming its potential as a target for anticancer therapy for a wide range of human tumours.

Oxidative stress in patients with differentiated thyroid cancer: early effects of radioiodine therapy. Vrndic Olgica B,Radivojevic Snezana D,Jovanovic Marina D,Djukic Svetlana M,Teodorovic Ljiljana C Mijatovic,Simonovic Snezana T Zivancevic Indian journal of biochemistry & biophysics Ionizing radiation in differentiated thyroid cancer (DTC) patients treated with radioiodine (131-I) produces reactive oxygen species (ROS), which could induce oxidative stress with disturbance of redox balance. The aim of this study was to evaluate oxidative stress in DTC patients treated with 3.7 or 5.5 GBq of 131-I using values for serum malondialdehyde (MDA, a marker of oxidative stress), uric acid (to determine antioxidant status) and total antioxidative status (TAS). The study population included 20 DTC patients and 20 healthy controls. Significant differences in MDA concentrations were found between DTC patients before 131-I therapy and control subjects (p = 0.001), while TAS values were similar in both populations (p > 0.05). There was a negative correlation between MDA concentrations and TAS in the DTC group before therapy (R2 = 0.2973, p = 0.013). Three days after 131-I therapy, MDA concentrations were higher than the pretreatment values (3.36 +/- 1.69 nmol/mL vs. 2.93 +/- 1.31 nmol/mL; p = 0.006), while serum uric acid concentrations declined progressively from 341.0 +/- 80.39 micromol/L to 304.25 +/- 77.25 micromol/L (p = 0.026) in 3 days and 291.2 +/- 88.86 micromol/L (p = 0.009) in 7 days after 131-I therapy. There was no dose-dependent effect on MDA, or uric acid concentrations and TAS. Thus, 131-I therapy in DTC patients induced oxidative stress, which was accompanied by a simultaneous and extended reduction in uric acid concentration, but without significant disturbances in TAS. This is the first study that evaluated TAS capacity in DTC patients before and 7 days after 131-I therapy. The relatively stabile TAS values in these patients indicated a good protection from oxidative stress induced by high doses of ionizing radiation.

Total oxidant/antioxidant status in sera of patients with thyroid cancers. Wang Dong,Feng Jia-Fu,Zeng Ping,Yang Yun-Hong,Luo Jun,Yang Yu-Wei Endocrine-related cancer Oxidative stress is considered to be involved in the pathophysiology of all cancers. In order to evaluate the total oxidant/antioxidant status in patients with thyroid cancer and to investigate the relationship between oxidative stress parameters and serum thyroid profiles among thyroid cancer patients and various controls, we determined oxidative status including total antioxidant status (TAS) and total oxidant status (TOS) and calculation of oxidative stress index (OSI) in sera in 82 thyroid cancer patients, 56 benign thyroid disease patients, and 50 healthy controls. It was found that serum TAS levels were significantly lower in patients with thyroid cancer than in controls (P<0.001), while serum TOS levels and OSI values were significantly higher (both P<0.001) in the cancer patients. No significant correlations were observed between various oxidative stress markers and thyroid profiles in either the thyroid cancer patients or the controls. Receiver operating characteristic curve analysis demonstrated that OSI was the best indicator for distinguishing cancer patients from benign thyroid diseased or healthy controls, followed by TOS and TAS. Risk estimate statistics also indicated that TOS and/or OSI were good risk factors to discriminate patients with thyroid cancer from two controls. These findings suggested that oxidants are increased and antioxidants are decreased in patients with thyroid cancer. OSI may be a more useful oxidative stress biomarker than TAS and TOS for monitoring the clinical status of thyroid cancer patients. 10.1530/ERC-11-0230