The relationship of expression of bcl-2, p53, and proliferating cell nuclear antigen (PCNA) to cell proliferation and apoptosis in renal cell carcinoma / 华中科技大学学报（医学）（英德文版）

To investigate the relationship of bcl-2, p53, proliferating cell nuclear antigen (PCNA) to cell proliferation, apoptosis and pathological parameters, the patterns of cell growth and turnover in renal cell carcinoma (RCC), formalin-fixed and paraffin-embedded tissue blocks from 34 patients with RCC were examined. Cell proliferation activity was detected by PCNA immunostaining and the proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy- nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells. Expressions of bcl-2 and p53 were assessed immunohistochemically. Our results showed that the PI ranged from 6.0% to 24.0% (median 12.3%) and the AI from 2.0% to 8.0% (median 5.4%) in RCC. The expression of the bcl-2 protein was demonstrated in 15 cases (44.1%); the expression of the p53 protein, however, was seen in only 3 case. bcl-2 positivity was not associated with PI or AI or any pathological parameters. There were close associations between PI and tumor grade and stage, and a significant relationship between AI and the tumor grade of RCC, Our study suggests that bcl-2 positivity was not associated with PI or AI or any pathological parameters. There are close associations between PI and AI and tumor grade and stage of RCC. Active cell proliferation may be accompanied by frequent apoptosis in RCC.

Bladder cancer therapy using combined proliferating cell nuclear antigen antisense oligonucleotides and recombinant adenovirus p53 / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the antitumor efficacy of proliferating cell nuclear antigen antisense oligonucleotide (PCNA-ASO) in combination with recombinant adenovirus p53 (Ad-p53) against bladder cancer EJ and BIU-87 cells in vitro and in vivo.</p><p><b>METHODS</b>Cells were transfected with Ad-p53 (100 MOI), and PCNA-ASO (1.6 micro mol/L) was then introduced into the cells using a cationic lipid (lipofectamine, 20 micro l/ml). In vitro and in vivo antitumor effects of combining PCNA-ASO with Ad-p53 were measured using the MTT assay, flow cytometry, clone formation, and a nude mice model.</p><p><b>RESULTS</b>The combination of PCNA-ASO and Ad-p53 inhibited cell viability in both the EJ (89.3%) and BIU-87 (78.6%) cell lines. The ability of the cells to form foci was also reduced by 74.8% in EJ cells and by 67.5% in BIU-87 cells (P < 0.01). A significant decrease of cells in the S phase (11.4% in EJ cells, 14.6% in BIU-87 cells) and a significant increase of cells in G1 phase (62.2% in EJ, 56.8% in BIU-87) were noted. The mean tumor volume after 7 days of treatment with PCNA-ASO or Ad-p53 in combination decreased to 47.6% or 36.4% of the initial tumor size in the two cell lines respectively.</p><p><b>CONCLUSION</b>These results indicate that combined PCNA-ASO and Ad-p53 in the treatment of bladder cancer with mutant p53 has important therapeutic potential, significantly suppressing the growth of human bladder cancer both in vitro and in vivo.</p>

Adenovirus-mediated transfer of p53 and p16 inhibiting proliferating activity of human bladder cancer cell EJ in vitro and in vivo / 华中科技大学学报（医学）（英德文版）

To evaluate the effects of adenovirus (Ad)-mediated transfer of p53 and p16 on human bladder cancer cells EJ, EJ were transfected with Ad-p53 and Ad-p16. Cell growth, morphological change, cell cycle, apoptosis were measured using MTT assay, flow cytometry, cloning formation, immunocytochemical assays. Ad-p16 or Ad-p53 alone could inhibit the proliferating activity of EJ cells in vitro. Ad-p53 could induce apoptosis of partial EJ cells. G1 arrest was observed 72 h after infection with Ad-p16, but apoptosis was not obvious. The transfer of Ad-p16 and Ad-p53 could significantly inhibit the growth of EJ cells, decrease the cloning formation rate and induce apoptosis of large number of EJ cells. The occurrence time of subcutaneous tumor was delayed and the tumor volume in 4 weeks was diminished by using Ad-p53 combined with Ad-p16 and the difference was significant compared with using Ad-p53 or Ad-p16 alone. It was suggested that the transfer of wild-type p53 and p16 could significantly inhibit the growth of human bladder cancer in vitro and in vivo.