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Rationale Accumulating evidence has linked prolonged exposure to heavy metals to cancer occurrence in the urinary system. However, the specific biological mechanisms responsible for the association of heavy metals with the unusually high incidence of upper tract urothelial carcinoma in Taiwan are complex and incompletely understood. Methods To elucidate the specific biological mechanism and identify molecular indicators of the unusually high association of upper tract urothelial carcinoma with heavy metal exposure, protein expression following the treatment of T24 human bladder carcinoma and RT4 human bladder papilloma cell line models with arsenic (As) and cadmium (Cd) was studied. Proteomic changes in these cell models were integrated with data from a human bladder cancer (BLCA) tissue proteome to identify possible protein indicators of heavy metal exposure. Results After mass spectrometry based proteomic analysis and verification by Western blotting procedures, we identified 66 proteins that were up-regulated and 92 proteins that were down-regulated in RT4 cell extracts after treatment with As or Cd. Some 52 proteins were up-regulated and 136 proteins were down-regulated in T24 cell extracts after treatment with Cd. We further confirmed that down-expression of the PML (promyelocytic leukemia) protein was sustained for at least 75 days after exposure of bladder cells to As. Dysregulation of these cellular proteins by As was associated with three biological pathways. Immunohistochemical analyses of paraffin-embedded BLCA tissue slides confirmed that PML protein expression was decreased in BLCA tumor cells compared with adjacent noncancerous epithelial cells. Conclusions These data suggest that PML may play an important role in the pathogenesis of BLCA and may be an indicator of heavy metal exposure in bladder cells.

Rationale Typically, a batch metabolomics analysis using liquid chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI-TOF MS) takes 2 to 3 days. However, the mass accuracy - which has an important influence on metabolite identification - can drift by as much as about 17 ppm in such a time period. In an untargeted urinary metabolomics analysis by reversed-phase liquid chromatography (RPLC)/ESI-MS, the signals of sodium formate cluster ions were detected at the column-washing step. The cluster ions were used to calibrate the mass spectrometer for more accurate detection. Methods The spectra were calibrated post-run by the sodium formate cluster ions, which were used as the internal standard, in order to improve the mass accuracy. Results In the analysis of urine samples, we calibrated the spectra acquired by the micrOTOF with the sodium cluster ions. In positive mode ESI, the average errors of these cluster ions were improved to ±0.48 ppm and in negative mode ESI, to ±0.94 ppm after calibration. The mass accuracy remained within ±0.01 ppm over the duration of 6.25 days. An error window of 4 ppm appears to be suitable for metabolite identification when using post-calibration. Conclusions The results showed that sodium formate cluster ions could be utilized for the calibration of LC/ESI-TOF MS and the average instrumental errors could be maintained at low levels for long-term analyses. This method could be applied not only to urine sample, but also to low sodium samples, such as saliva, by dissolving the sample in 1 μM sodium formate solution. This method provides a good solution for accurate mass detection of metabolomic analysis.

Objectives: We present here our early results and learning curve for photoselective vaporization of the prostate (PVP) performed by an experienced urologist and we provide an analysis of the morbidity and early functional outcomes. Methods: Forty-four patients were selected, from May 2006 to January 2009, who had benign prostate hyperplasia (BPH) accompanied by lower urinary tract symptoms (LUTS). After undergoing PVP for BPH at our hospital, the patients were followed up for approximately 2 years. PVP was performed by the same experienced urologist using potassium-titanyl-phosphate (KTP) laser. Baseline characteristics, preoperative and perioperative data, and postoperative complications were evaluated. Regular outpatient department follow-up was conducted after patients were discharged from the hospital at 1, 4 and 12 weeks. Results: The mean age of the 44 patients was 71.6 years. The mean prostate volume was 47.52 mL. The mean PVP surgery time was 79.11 min. The mean urinary catheterization time was 23.41 h. Few complications arose after PVP, except that 47.7% of the patients developed pyuria after being discharged from hospital. The average hospital stay was 2.45 days. There were no significant differences in the efficiency of tissue vaporization among the patients. Conclusion: PVP for BPH has various advantages, including reducing postoperative complications. An experienced urologist can easily perform PVP. However, early results show no significant differences in the efficiency for the PVP technique.