Objectives. To evaluate the normal distribution of serum prostate-specific antigen (PSA) levels in healthy Chinese men, because, until recently, studies conducted to establish normal serum PSA values have not involved a Chinese population. Methods. Between September 1999 and December 2001, 1096 healthy Chinese men aged 23 to 85 years, who had undergone a routine health examination, were recruited to this study. All underwent detailed clinical examinations, including serum PSA determination and digital rectal examination. All men with abnormal digital rectal examination findings and/or an abnormal serum PSA level (greater than 4.0ng/mL) underwent transrectal ultrasound-guided sextant biopsy. Results. The median serum PSA concentration was 0.50 ng/mL (95th percentile 1.20) for men 23 to 29 years old (n=77); 0.55ng/mL (95th percentile 1.21) for men 30 to 39 years old (n=189); 0.54ng/mL (95th percentile 1.23) for men 40 to 49 years old (n=233); 0.82ng/mL (95th percentile 2.35) for men 50 to 59 years old (n=177); 0.93ng/mL (95th percentile 3.20) for men 60 to 69 years old (n=265); and 1.17ng/mL (95th percentile 3.39) for men 70 years old or older (n=155). The serum PSA concentration correlated with age (P=0.001), with an increase of approximately 1.1% annually. No change occurred in the median serum PSA value and 95th percentile in men younger than 50 years old; a gradual increase was observed in men older than 50 years. In those 50 years old or older, the median and 95th percentile serum PSA values for Chinese men were significantly lower than those for other races and even for other Asian men. Conclusions. These findings further confirm that the serum PSA level correlates with age. Moreover, the distribution and cutoff value of the serum PSA level differs along ethnic lines. In addition, our findings raise the question of whether lowering the PSA cutoff may enhance the detection of cancer in Chinese men who have the lowest prostate cancer rate.

Objectives To examine the anti-oncogenic effects of promyelocytic leukemia (PML) on bladder cancer and to explore its molecular mechanisms of growth suppression. Methods Wild-type PML was transfected into bladder cancer cells (5637 cell) and expressed in a replication-deficient adenovirus-mediated gene delivery system and introduced into human bladder cancer cells (5637 cell) in vitro and in vivo. The effect and mechanisms of the PML gene in cell growth, clonogenicity, and tumorigenicity of bladder cancer cells were studied using in vitro and in vivo growth assays, soft agar colony-forming assay, cell cycle analysis, apoptosis assay and in vivo tumorigenicity assay. Results Overexpression of PML in 5637 cells significantly reduced their growth rate and clonogenicity on soft agar. PML suppressed bladder cancer cell growth by inducing G1 cell cycle arrest and apoptosis. Adenovirus-mediated PML (Ad-PML) significantly suppressed the tumorigenicity and growth of bladder cancer cells. Intratumoral injection of Ad-PML into tumors induced by 5637 cells dramatically suppressed their growth. Conclusions The results indicated that overexpression of PML protein may promote efficient growth inhibition of human bladder cancer cells by inducing G1 cell cycle arrest and apoptosis, and adenovirus- mediated PML (Ad-PML) expression efficientlv suppresses human bladder cancer qrowth.

Our previous studies demonstrated that the promyelocytic leukemia gene, PML,encodes a growth and transformation suppressor. Overexpres sion of PML inhibits cancer cell growth in vitroand in vivo. In this study, we further explored the possibility of applying PML as a potential agent for developing prostate cancer gene therapy using an adenovirus delivery system. We have constructed and produced the recombinant PML-ade novirus, Ad-PML, in which the full-length PML eDNA is driven by the strong cytomegalovirus promoter. In LNCaP, DU145, and PC-3 prostate cancer cell lines, an infection efficiency of 90% can be achieved at a concentration of 2, 10, and 100 multiplicity of infection (MOl), respec tively. Western blotting and immunofluorescence staining demonstrated that the AD-PML-infected cells expressed a high level of PML protein. The protein expression peaked at days 3—4postinfection, and a detectable level of PML was found at day 18 after viral infection. To test the effect of Ad-PML on the growth of prostate cancer cells, the DU145 and LNCaP cells were infected with 10 and 2 MOl of Ad-PML. We found that the growth rate of the Ad-PML-infected DU145 and LNCaP cells were sig nificantly inhibited. A tumorigenicity test in nude mice showed that the Ad-PML-treated DU145 cells failed to form tumors. Most importantly, direct injection of Ad-PML into DU145-induced tumors was able to repress tumor growth in nude mice by 64%. Taken together, these data indicate that PML is a tumor growth suppressor in prostate cancer and that Ad-PML may be a potential candidate for human prostate cancer therapy.

Aim: To construct a recombinant retrovirus vector carrying human promyelocytic leukemia (PML) cDNA and identify its expression and biology role in bladder cancer UM-UC-2 cells for future gene therapy. Methods: PML full-length cDNA was inserted into the EcoR I and BamH I site of pLXSN vector containing the long terminal repeat (LTR) promoter. The vector was identified by restriction enzyme digestion and then transfected into PA317 packaging cell line by calcium phosphate coprecipitation. PML cDNA was detected by polymerase chain reaction PCR) and the protein was identified by laser confocal microscopy and Western blot in bladder cancer cells, respectively. The morphology was observed by inverted phase contrast microscope, and MTT assay determined growth curve of the bladder cancer cells. Results: Restriction enzyme digestion proved that a 2.1 kb PML cDNA was inserted into the pLXSN vector. PCR assay demonstrated that 304 bp fragments were found in UM-UC-2/pLPMLSN transfects. Laser confocal microscopy showed speck dots fluorescence in the UM-UC-2/pLPMLSN nucleus. A 90 kD specific brand was found by Western blot. MTT assay demonstrated the UM-UC-2/pLPMLSN bladder cancer growth inhibition. Conclusion: The retrovirus pLPMLSN vector was successfully constructed and could generate high effective expression of human PML in bladder cancer cell UM-UC-2, suggesting that PML recombinant retrovirus have potential utility in the gene therapy for bladder cancer.

Bac kgro und Recent studies have revealed the important role of free radicals in renal damage induced by high-energy shock waves (HESW). This study aimed at investigating the effects of Ast ragal us membranaceus, a traditional Chinese medicinal herb, on free radical-mediated HESW-induced damage to renal tubules in a live rabbit model. Met hods Forty-five healthy male New Zealand white rabbits were randomly divided into three groups: cont rol group (n=15), sham group (n=15), and herb-treated group (n=15) 1 Three days prior to HESW application, the controls received verapamil (014mg/kg), the shams received physiological saline (-0ml), and the herb-t reated animals received Ast ragal us membranaceus (-14g/kg) int ravenously. HESW (1500 shocks, 18kV) was applied to the right kidneys of all anesthetized rabbits1 We measured superoxide dismutase (SOD) and malondialdehyde (MDA) levels before and after shock treatment in blood and kidney homogenates1 Histopathological changes were also observed1 Results MDA levels increased and SOD activity decreased significantly in the sham group (P<0105 for both) after shock treatment1 MDA levels showed a much less increase in the cont rols (P<0105) and did not increase to statistically significant levels in the group receiving Ast ragal us membranaceus (P>0105). SOD values were significantly higher in the controls than in the shams (P<0105) 1 By cont rast, SOD levels recovered rapidly in the rabbits receiving Ast ragal us membranaceus, reaching a nadir within -4 hours, and returning to baseline more quickly than in control and sham rabbits (P<0105). Histopathological examinations showed that renal tubular damage in the cont rols was less severe than in the shams, while damage in the Ast ragal us membranaceus group was even more mild, with rapid recovery in comparison with the cont rols1 Conclusion This study provides preliminary evidence indicating that Ast ragal us membranaceus has strong protective effect son free radical-mediated renal tubular damage induced by HESW and that these effects are superior to the effect s of verapamil.