Glucose-capped gold nanoparticles (Glu-GNPs) have been used to improve cellular targeting and radio-sensitization. In this study, we explored the mechanism of Glu-GNP enhanced radiation sensitivity in radiation-resistant human prostate cancer cells. Cell survival and proliferation were measured using MTT and clonogenic assay. Flow cytometry with staining by propidium iodide (PI) was performed to study the cell cycle changes induced by Glu-GNPs, and western blotting was used to determine the expression of p53 and cyclin proteins that correlated to cell cycle regulation. With 2 Gy of ortho-voltage irradiation, Glu-GNP showed a 1.5-2.0 fold enhancement in growth inhibition when compared to x-rays alone. Comparing the cell cycle change, Glu-GNPs induced acceleration in the G0/G1 phase and accumulation of cells in the G2/M phase at 29.8% versus 18.4% for controls at 24 h. G2/M arrest was accompanied by decreased expression of p53 and cyclin A, and increased expression of cyclin B1 and cyclin E. In conclusion, Glu-GNPs trigger activation of the CDK kinases leading to cell cycle acceleration in the G0/G1 phase and accumulation in the G2/M phase. This activation is accompanied by a striking sensitization to ionizing radiation, which may have clinical implications.

: The histology and function of the kidney deteriorates with age and age-related diseases, but the mechanisms involved in renal aging are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stresses that increase replication. This study explored the relationship between age and telomere length in surgical samples from 24 human kidneys, which were either histologically normal (17) or displayed histologic abnormalities (7). Telomere loss was assessed by two independent methods: Southern blotting of terminal restriction fragments (TRF) and slot blotting using telomere-specific probes. The results of these methods correlated with each other. The mean TRF length determined by Southern blotting in cortex was about 12 kb pairs (kbp) in infancy and was shorter in older kidneys. The slope of the regression line was about 0.029 kbp (0.24%, P = 0.023) per year. Telomere DNA loss in cortex by the slot blot method was 0.25% per year (P = 0.011). By both methods, the telomere loss in medulla was not significant and was less than in cortex. Comparisons of TRF length from 20 paired samples from cortex and medulla showed that TRF was greater in cortex than medulla, with the differences being greater in young kidneys and lessening with age due to telomere loss in cortex. These findings indicate that telomeres shorten in an age-dependent manner in the kidney, either due to developmental factors or aging, particularly in renal cortex.

Purpose: Nanotechnology is an emerging field with significant translational potential in medicine. In this study, we applied gold nanoparticles (GNP) to enhance radiation sensitivity and growth inhibition in radiation-resistant human prostate cancer cells. Methods: Gold nanoparticles (GNPs) were synthesized using HAuCl4 as the gold particle source and NaBH4 as the reductant. Either thio-glucose or sodium citrate was then added to the solution separately to bind the GNPs to form thio-glucose-capped gold nanoparticles (Glu-GNP) and neutral gold nanoparticles (TGS-GNPs). Human prostate carcinoma DU-145 cells were exposed to vehicle, irradiation, 15nM TGS-GNPs, or 15nM Glu-GNPs, or GNPs plus irradiation. The uptake assays of GNP were performed using hemocytometer to count cells and the mass spectrometry was applied to calculate gold mass. The cytotoxicity induced by GNPs, irradiation, or GNPs plus irradiation was measured using a standard colorimetric MTT assay. Results: Exposure to Glu-GNPs resulted in a three times increase of nanoparticle uptake compared to that of TGS-GNPs in each target cell (p < 0.005). Cytoplasmic intracellular uptake of both TGS-GNPs and Glu-GNPs resulted in a growth inhibition by 30.57% and 45.97% respectively, comparing to 15.88% induced by irradiation alone, in prostate cancer cells after exposure to the irradiation. Glu-GNPs showed a greater enhancement, 1.5 to 2 fold increases within 72 hours, on irradiation cytotoxicity compared to TGS-GNPs. Tumour killing, however, did not appear to correlate linearly with nanoparticle uptake concentrations. Conclusion: These results showed that functional glucose-bound gold nanoparticles enhanced radiation sensitivity and toxicity in prostate cancer cells. In vivo studies will be followed to verify our research findings.

Improved assessment of donor organ quality at time of transplantation would help in management of potentially usable organs. The transcriptome might correlate with risk of delayed graft function (DGF) better than conventional risk factors. Microarray results of 87 consecutive implantation biopsies taken postreperfusion in 42 deceased (DD) and 45 living (LD) donor kidneys were compared to clinical and histopathology‐based scores. Unsupervised analysis separated the 87 kidneys into three groups: LD, DD1 and DD2. Kidneys in DD2 had a greater incidence of DGF (38.1 vs. 9.5%, p < 0.05) than those in DD1. Clinical and histopathological risk scores did not discriminate DD1 from DD2. A total of 1051 transcripts were differentially expressed between DD1 and DD2, but no transcripts separated DGF from immediate graft function (adjusted p < 0.01). Principal components analysis revealed a continuum from LD to DD1 to DD2, i.e. from best to poorest functioning kidneys. Within DD kidneys, the odds ratio for DGF was significantly increased with a transcriptome‐based score and recipient age (p < 0.03) but not with clinical or histopathologic scores. The transcriptome reflects kidney quality and susceptibility to DGF better than available clinical and histopathological scoring systems.