Intrinsic resistance to agents targeting phosphoinositide 3-kinase (PI3K)/AKT pathway is one of the major challenges in cancer treatment with such agents. The objective of this study is to identify the genes or pathways that can be targeted to overcome the resistance of non-small cell lung carcinoma (NSCLC) to the AKT inhibitor MK2206, which is currently being evaluated in phase I and II clinic...

Radiation treatment remains one of the major modalities in the treatment of lung cancer. Although the majority of patients initially respond to treatment with radiation, resistance inevitably develops and leads to treatment failure. Therefore, the identification of the underlying molecular mechanisms of radiation resistance may facilitate the development of novel approaches for overcoming resis...

Background: Mesenchymal stem cells (MSCs) are ideal cells for cell and gene therapy. However, the low survival of MSCs after transplantation has limited their applications. We aimed to evaluate the expression of cytoprotective genes including NQO1, TXNRD1, HO-1, GCLC following the over expression of Nrf2 in umbilical cord-derived MSCs (UC-MSCs). Methods: 3-5 passages of UC-MSCs were cultured. ...

The thioredoxin-dependent system is an essential regulator of cellular redox balance. Since oxidative stress has been linked with neurodegenerative disease, we studied the roles of thioredoxin reductases in brain using mice with nervous system (NS)-specific deletion of cytosolic (Txnrd1) and mitochondrial (Txnrd2) thioredoxin reductase. While NS-specific Txnrd2 null mice develop normally, mice ...

Murine (Hepa1c1c7) hepatoma cells are a suitable in vitro system for investigating the regulation of chemoprotective enzymes by selenazolidines, novel l-selenocysteine prodrugs developed as potential chemopreventive agents. They are less sensitive to the cytotoxic effects of both selenite and the less toxic selenazolidines than rat hepatoma (H4IIE) cells. All four selenazolidine 4-carboxylic ac...

PURPOSE Drug-induced liver injury (DILI) is the most common adverse drug reaction; however, it is not easily predicted. We hypothesize that DILI has a common genetic basis. Based on the findings of previous animal studies on toxic hepatitis, we selected the thioredoxin reductase 1 gene (TXNRD1) as a candidate marker of DILI for this genetic association study. METHODS Records from 118 patients...

Oxidative stress is a major determinant of human aging and common hallmark of age-related diseases. A protective role against free radicals accumulation was shown for thioredoxin reductase TrxR1, a key antioxidant selenoprotein. The variability of encoding gene (TXNRD1) was previously found associated with physical status at old age and extreme survival in a Danish cohort. To further investigat...

background: mesenchymal stem cells (mscs) are ideal cells for cell and gene therapy. however, the low survival of mscs after transplantation has limited their applications. we aimed to evaluate the expression of cytoprotective genes including nqo1, txnrd1, ho-1, gclc following the over expression of nrf2 in umbilical cord-derived mscs (uc-mscs). methods: 3-5 passages of uc-mscs were cultured. r...