ABSTRACT
The aim of the present study was to evaluate the association between xeroderma pigmentosum group C (XPC) polymorphisms and pancreatic cancer (PC) risk. A total of 7 XPC tagging SNPs (tag-SNPs) were selected from the International HapMap Project Databases (rs2228001A/C, rs2470353G/C, rs2228000C/T, rs3731114C/G, rs3729587G/C, rs2607775C/G and rs3731055G/A) and were genotyped in 205 patients with PC and 230 non-cancer control subjects using a SNaPshot assay. The C allelic gene frequency of rs2470353 was higher in patients with PC compared with that in the control group (P=0.003). Compared with the GG gene type, PC risk was increased in subjects with GC and GC+CC gene types (P=0.012 and P=0.006, respectively). PC risk increased 3.505-fold for the subjects who were heavy smokers (tobacco, ≥25 packets/year) with the GC+CC gene type (P=0.008). The G allelic gene frequency of rs2607775 was higher in PC patients compared with that in the control group (P=0.003). Compared with the CC gene type, PC risk increased in subjects with CG and CG+GG gene types (P=0.013 and P=0.005, respectively). Furthermore, PC risk increased 3.950-fold in subjects who were heavy smokers (tobacco, ≥25 packets/year) with the CG+GG gene type (P=0.001). Haplotype analysis further revealed that the CCC haplotype of rs2228000, rs3731114 and rs3729587 increased PC risk (odds ratio, 1.610; 95% confidence interval, 1.035-2.481; P=0.034). The present study revealed that XPC gene polymorphisms could increase the risk of PC in the study population, particularly among heavy smokers.
ABSTRACT
Marked up-regulation of aldose reductase (AR) is reportedly associated with the development of hepatocellular carcinoma (HCC). We investigated how aberrantly overexpressed AR might promote oncogenic transformation in liver cells and tissues. We found that overexpressed AR interacted with the kinase domain of AKT1 to increase AKT/mTOR signaling. In both cultured liver cancer cells and liver tissues in DEN-induced transgenic HCC model mice, we observed that AR overexpression-induced AKT/mTOR signaling tended to enhance lactate formation and hepatic inflammation to enhance hepatocarcinogenesis. Conversely, AR knockdown suppressed lactate formation and inflammation. Using cultured liver cancer cells, we also demonstrated that AKT1 was essential for AR-induced dysregulation of AKT/mTOR signaling, metabolic reprogramming, antioxidant defense, and inflammatory responses. These findings suggest that aberrantly overexpressed/over-activated hepatic AR promotes HCC development at least in part by interacting with oncogenic AKT1 to augment AKT/mTOR signaling. Inhibition of AR and/or AKT1 might serve as an effective strategy for the prevention and therapy of liver cancer.
ABSTRACT
Circulating tumor cells (CTCs) are used for metastasis surveillance in cancer patients, but low detection rates limit their use in colorectal cancer (CRC). We investigated the distribution of CTCs in peripheral and portal blood of CRC patients, and analyzed the relationship between serum tumor CEA/CA19-9 markers and CTCs blood levels. CTC levels detected in first reflux/portal vein blood were higher than in peripheral blood, and liver reduced CTCs amount. CTCs-positive patients had increased serum CEA and CA 19-9 levels, and the CEA and CA 19-9 levels correlated with the CTCs levels. Even in non-metastatic CRC patients with barely detectable CTCs in peripheral blood, serum CA 19-9 levels correlated with the CTC levels in first reflux/portal vein blood. These results demonstrate that CTC detection in the first reflux vein/portal vein blood is more sensitive than in peripheral blood, suggesting that clinical diagnosis using the CellSearch System should be based on the CTC detection in first reflux vein blood due to the high detection rates. In addition, our results indicate that serum CA 19-9 levels may serve as a diagnostic marker for further evaluation of CTC levels in portal blood.
ABSTRACT
We report two novel types of hierarchically structured iodine-doped ZnO (I-ZnO)-based dye-sensitized solar cells (DSCs) using indoline D205 and the ruthenium complex N719 as sensitizers. It was found that iodine doping boosts the efficiencies of D205 I-ZnO and N719 I-ZnO DSCs with an enhancement of 20.3 and 17.9 %, respectively, compared to the undoped versions. Transient absorption spectra demonstrated that iodine doping impels an increase in the decay time of I-ZnO, favoring enhanced exciton life. Mott-Schottky analysis results indicated a negative shift of the flat-band potential (V(fb)) of ZnO, caused by iodine doping, and this shift correlated with the enhancement of the open circuit voltage (V(oc)). To reveal the effect of iodine doping on the effective separation of e(-)-h(+) pairs which is responsible for cell efficiency, direct visualization of light-induced changes in the surface potential between I-ZnO particles and dye molecules were traced by Kelvin probe force microscopy. We found that potential changes of iodine-doped ZnO films by irradiation were above one hundred millivolts and thus significantly greater. In order to correlate enhanced cell performance with iodine doping, electrochemical impedance spectroscopy, incident-photon-current efficiency, and cyclic voltammetry investigations on I-ZnO cells were carried out. The results revealed several favorable features of I-ZnO cells, that is, longer electron lifetime, lower charge-transfer resistance, stronger peak current, and extended visible light harvest, all of which serve to promote cell performance.
