Thioredoxin system protein expression in carcinomas of the pancreas, bile duct and ampulla

Background: Pancreatic cancer (PC), including the ampulla and bile duct, is very aggressive, and thus difficult to treat with effective therapies. The current treatment options have failed to improve PC five-year survival rates over the last 30 to 40 years, which remain very low, at ~3%; there is, therefore, an urgent need to identify new targets and treatment modalities (1). Methods: The protein expression of thioredoxin (Trx), thioredoxin reductase (TrxR) and thioredoxin interacting protein (TxNIP) was assessed in two cancer patient cohorts by standard immunohistochemistry using tissue microarrays. The first cohort was composed of 85 pancreatic adenocarcinomas (PAD) and the second of 145 cancers of the bile duct and ampulla. Results: In the PAD cohort, high cytoplasmic TrxR expression significantly associated with lymph node metastasis (P = 0.033). High expression of cytoplasmic (P = 0.018) and nuclear (P = 0.006) Trx were significantly associated with better overall survival, with nuclear Trx expression remaining significantly associated with survival in multivariate Cox-regression (Hazard Ratio (HR) 0.316; 95% Confidence Interval (95% CI) 0.174-0.573; P < 0.0001) when potentially confounding factors were included (gender, age, tumour size, tumour grade, tumour stage, lymph node status, perineural and venous invasion). In cancers of the bile duct and ampulla, high expression of nuclear TrxR and high cytoplasmic TxNIP were associated with patients aged above 60 years (P = 0.024 and P = 0.049 respectively). Associations were also observed between high nuclear TrxR expression and the presence of venous (P = 0.001) and perineural (P = 0.021) invasion. Low cytoplasmic TxNIP expression was also associated with the presence of perineural invasion (P = 0.025). High expression of cytoplasmic TxNIP was significantly associated with better overall survival (P = 0.0002), which remained significant in multivariate Cox-regression analysis (HR 0.548; 95% CI 0.340-0.882; P = 0.013) when potentially confounding factors were included (tumour grade, stage, lymph node status, perineural and venous invasion). Conclusion: Current findings demonstrate the prognostic importance of Trx system protein expression in pancreatic, bile duct and ampullary cancers, with expression of certain members potentially being involved in disease progression. Current findings warrant a larger follow-up study

Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas

The thioredoxin (Trx) system is an important enzyme family that regulates cellular redox homeostasis. Protein expression of Trx system family members has been assessed in various cancers and linked to various clinicopathological variables, disease progression, treatment response and survival outcomes but information is lacking in brain tumours. Expression of the system was therefore examined, by immunohistochemistry in different brain tumour types, adult and paediatric cases, to determine if expression was of importance to clinical outcome. Trx system proteins were expressed, to variable levels, across all brain tumour types with significant variations in expression between different tumour types/grades/regions. High Trx reductase (TrxR) expression was linked to worse prognosis across all cohorts. High cytoplasmic TrxR expression was significantly associated with adverse overall survival (OS) in adult glioblastoma (P=0.027) and paediatric low-grade glioma (LGG) patients (P=0.012). High expression of nuclear TrxR, cytoplasmic and nuclear Trx, and Trxinteracting protein (TxNIP) was associated with improved OS in paediatric LGGs (P=0.031,

Retraction Note: SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

The authors are retracting this article [1] because the data have already been published in [2] making this a redundant publication. Ghazi Alsbeih, Najla Al-Harbi, Khaled Al-Hadyan, Mohamed Shoukri and Nasser Al-Rajhi agree with this retraction. Medhat El-Sebaie did not respond to our correspondence