Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988-1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.

Evaluation of the combined toxicity of multi-walled carbon nanotubes and cadmium on earthworms in soil using multi-level biomarkers.

The coexistence of multi-walled carbon nanotubes (MWCNTs) with cadmium (Cd) in soil may cause the combined biological effects, but few study reported about their joint toxic effects on earthworms. Therefore, this study investigated the effects of sub-lethal levels of MWCNTs (10, 50, 100 mg/kg) and Cd (2.0, 10 mg/kg) on earthworms Eisenia fetida for 14 days. The changes in multi-level biomarkers of growth inhibition rate, cytochrome P450 isoenzymes (CYP1A2, 2C9 and 3A4), and small molecular metabolites (metabolomics) were determined. The toxic interaction between MWCNTs and Cd was characterized by the combination of the biomarker integration index (BRI), joint effect index concentration addition index (CAI), and the effect concentration addition index (EAI). The results showed that the single MWCNTs exposure caused insignificant change in most biomarkers, while the combined exposure of MWCNTs (50-100 mg/kg) and 10 mg/kg Cd led to significant changes in ten most important metabolites identified by metabolomics and activities of CYP1A2, 2C9, and 3A4. Compared with the toxicity of Cd alone, the combined toxicity of the mixture was significantly reduced. According to the integration of BRI and CAI/EAI, a clearly antagonistic interaction at relatively low effects was observed between MWCNTs and Cd. The responses of multiple biomarkers suggest the toxic action mode of the mixture on earthworms was related to the oxidative injury, and the disruption of amino acid, purine, and pyrimidine metabolism, and the urea cycle.