The Relation of the Preoperative Estimate to the Pathologic Demonstration of the Extent of Vesical Neoplasms

Objective: To investigate the relationship of oncoproteins with histological grade, tumor stage, cell cycle and multidrug resistance (MDR) in bladder cancer. Methods: The expression of various oncoproteins (p21, EGFR1, erbB-2, c-jun, c-myc, bcl-2, Bax) and suppressor gene products (WT-1, RB gene, p53) was studied in normal urothelium, transitional cell carcinoma (TCC) cell lines and their MDR sublines by using specific antibodies and an indirect immunofluorescence flow-cytometric method. Results: The total increased rate of measured oncoproteins in TCC cell lines was 62.7%. There was no difference in the expression rate of oncoproteins between low-grade/stage TCC cell lines and high-grade/stage TCC cell lines. All of these TCC cell lines have aneuploidy and increased proliferative activity in the cell cycle, but a correlation with oncoprotein expression was not seen. They had a low expression rate of c-myc, Bax and RB gene when compared to normal urothelium. On the contrary, the expressions of p21, EGFR1, erbB-2, bcl-2, WT-1 and p53 oncoproteins were significantly higher than in normal urothelium (p < 0.05). A long-term cultured MDR subline of TCC8702 (TCC8702/ADR1000) demonstrated a generally decreasing expression of oncoproteins in addition to p53. Conclusions: The p21, EGFR1, erbB-2, bcl-2, WT-1 and p53 oncoproteins were increased in TCC cells compared to normal urothelium. Oncoprotein expression is related to tumorigenesis of TCC cells, but no correlation was seen between the incidence and tumor differentiation and cell cycle. These oncoproteins decreased gradually in the process of generation of MDR in addition to p53. It indicates that the p53 oncogene is closely related to the acquired MDR of TCC cells.

Section: Methodsmentioning

confidence: 99%

The Expression of Oncoproteins in Transitional Cell Carcinoma: Its Correlation with Pathological Behavior, Cell Cycle and Drug Resistance

Yü

Chang²

2002

“…The tumors were classified according to their degree of cellular differentiation and stage of parietal infiltration [6][7][8]. After resection, all specimens were fixed in 10% neutral buffered formalin, embedded in paraffin wax and cut up into 5-pm sec tions.…”

Section: Methodsmentioning

confidence: 99%

T-Zone Histiocytes and Recurrence of Papillary Urothelial Bladder Carcinoma

López-Beltrán¹,

Morales²,

Reymundo³

et al. 1989

We have studied the histologic distribution and prognostic significance of T-zone histiocytes (TZH) in 89 papillary urothelial bladder carcinomas (PUC), 3 cases of nonspecific cystitis (NC) and 4 cases of follicular cystitis (FC) by immunohistochemical determination of S-100 protein. Nineteen (21.37%) of the PUC cases have been found to have TZH S-100-positive with a variable density intratumor, along the papillary axis, or in the lymphoid aggregates of the vesical wall. All four FC cases were also TZH-positive, with a distribution and density similar to those of follicular dendritic cells of lymph nodes, although none of the 3 NC cases presented TZH. The recurrence-free period was significantly (p < 0.05) longer in TZH-positive patients.

“…Human TCC cell lines HAT-1376, RT4, T24, J82 and mouse TCC cell lines MBT-2 and 1660 were obtained from the American Type Culture Collection (Rockville, Md., USA). Tumor grading and staging are done according to the WHO classification and Marshall-modified Jewett and Strong system [14,15].…”

Section: Methodsmentioning

confidence: 99%

Synergism of Fas-Mediated Apoptosis and Tumor Necrosis Factor on Adriamycin Cytotoxicity to Transitional Cell Carcinoma

Yü

Hsieh²,

Chen³

et al. 2003

Objective: To explore the accurate Fas antigenic expression in transitional cell carcinoma (TCC) cells and and compare its synergistic modulation on adriamycin cytotoxicity with α-tumor necrosis factor (TNF-α). Methods: The expression of Fas antigen in normal urothelium and TCC cell lines was measured by flow cytometry. The Fas/Fas ligand reaction-induced cytotoxic changes in tumor cells were evaluated by microculture MTT technique. The synergism efficacy of Fas-mediated apoptosis and TNF-α on adriamycin cytotoxicity of TCC cells was analyzed. The Fas/Fas ligand-induced apoptosis in tumor cells was studied by annexin-V apoptotic cell expression and DNA ladder fragmentation analysis. Results: 75% of TCC cell lines showed Fas antigen expression. The Fas expression was not influenced by in vitro growth density of tumor cells. Apoptosis of TCC cells was observed during 48 h of treatment after activation of the Fas/Fas ligand pathway. TNF-α had a higher cytotoxicity activity on TCC cells than Fas ligand (17 vs. 0.7%) while combination of both reagents had 30% increased synergistic cytotoxicity. The increasing rate of apoptotic body after 3 days of treatment was 74% in adriamycin, 32% in Fas ligand, 60% in TNF-α, 69% in Fas and adriamycin combination and Fas and TNF-α combination, 103% in combination of TNF-α and adriamycin, and 136% in combination of these three reagents individually. In the DNA ladder analysis, Fas ligand had a 1.5-fold increase of DNA fragmentation when compared with adriamycin while TNF-α had a 4.4-fold increase and triple combination had a 5.5-fold increase after 3 days of treatment. Conclusions: Although the Fas antigen expression is common in TCC cells and apoptosis can be activated by the Fas/Fas ligand pathway activation, the synergistic cytotoxicity of adriamycin by the Fas/Fas ligand pathway is lower than that of TNF-α.