Expression of lung resistance-related protein gene in transitional cell carcinoma of the bladder / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of lung resistance-related protein (LRP) in intrinsic multidrug resistance (MDR) of bladder cancer and detect the relationship of LRP expression with the clinical pathologic parameters.</p><p><b>METHODS</b>66 patients were studied with newly diagnosed primary bladder cancer (T(a) = 12, T(1) = 26, T(2) = 11, T(3) = 10, T(4) = 7; G(1) = 35, G(2) = 19, G(3) = 12). No patient was treated preoperatively with either radiation or chemotherapy. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for measure of mRNA expression for LRP, multidrug-resistance gene 1 (MDR1), and multidrug resist nce-associated protein 1 (MRP1). Expressions of LRP, P53 and P63 proteins were examined by immunohistochemistry staining.</p><p><b>RESULTS</b>LRP mRNA had the highest expression rate (64%, 42/66) among three MDR markers in primary bladder cancers without chemotherapy and its level was significantly higher in normal bladder tissue than in TCC of bladder (t = 2.82, P < 0.01), in low grade than in high grade cancers (t = 4.14, P < 0.01), and in superficial than in invasive cancers (t = 3.58, P < 0.05). LRP mRNA expression showed no correlation with either MDR1 or MRP1, but close correlation with LRP protein level (r = 0.89, P < 0.01). LRP was associated with low-grade (r = 0.81, P < 0.01) and low-stage (r = 0.78, P < 0.05) cancers, but not with tumor suppressor P53 or P63 (P > 0.05).</p><p><b>CONCLUSIONS</b>The grade and stage-related expression pattern of LRP indicates that it may be a predictive index for intrinsic MDR in bladder cancer. Anti-cancer drugs out of the MDR spectrum of LRP may be more effective for patients with early bladder cancer.</p>

The role of protein kinase C alpha in recurrence of superficial bladder carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship of protein kinase C-alpha (PKCalpha) expression/activation with tumor differentiation and resistance to chemotherapy drugs in superficial bladder carcinoma.</p><p><b>METHODS</b>Expression of PKCalpha was measured by Western-blot analysis in 76 samples including tumor and normal tissues, respectively. A human RT4 bladder cancer cell line stably expressing green fluorescent protein (GFP)-PKCalpha (RT4/PKCalpha) was established. The sensitivity of the RT4/PKCalpha and parental cells to adriamycin (ADM) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The change of sensitivity of the RT4/PKCalpha to ADM were observed under the conditions of PKC activation and inhibition, respectively.</p><p><b>RESULTS</b>Total level of PKCalpha expression and the ratio of the amount of PKCalpha expression or PKC activity in membrane to that in cytosol (M/C) were all more higher in cancerous tissues than in normal tissues (P < 0.01); With the increase of tumor grade, the relative level of PKCalpha expression significantly increased in membrane (P < 0.01) and decreased in cytosol (P < 0.01), M/C of PKCalpha was significantly elevated (P < 0.01), and total relative level of PKCalpha expression significantly increased (P < 0.01). Thirty-eight cases recurred during the follow-up period in total seventy cases. Multivariate analysis showed that high M/C of PKCalpha was independent prognostic factor for tumor recurrence after standard ADM treatment in the 2-year follow-up (RR = 3.98, 95% CI 1.22-5.68, P = 0.03). Transfection of PKCalpha increased resistance of RT4 cells to ADM [resistance index (RI): 6.97, t = 3.24, P < 0.01]. PKCalpha activation further greatly promoted the resistance (RI: 148.11, t = 5.18, P < 0.001) while inhibition of PKCalpha did conversely (RI: 1.6, t = 1.29, P > 0.05).</p><p><b>CONCLUSION</b>The abnormal activation and expression level of PKCalpha closely correlate with both tumor grade and intrinsic resistance to ADM in patients with superficial bladder carcinoma.</p>

The role of cell adhesion, multidrug resistance and cell proliferation in short-term recurrent cases with T1G3 superficial bladder cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the roles of cell adhesion, multidrug resistance and cell proliferation in short-term recurrent cases with superficial bladder cancer, and the prognostic value of the three indexes.</p><p><b>METHODS</b>Immunohistochemical staining for E-cad, P-gp and Ki-67 was performed on the tumors of 100 patients with stage T0-T1 transitional cell carcinoma of the bladder who had been included in a retrospective research by follow-up.</p><p><b>RESULTS</b>E-cad and P-gp expression was positive in 51 (43.2%)and 17 (14.4%) of the tumors, respectively and mean proliferation index (PI) was 22.1%. The decrease in E-cad expression was accompanied with the increasing recurrent episodes (P < 0.05), while increase of P-gp expression and PI were accompanied with the increasing recurrence episodes (P < 0.05). There was significant difference according to E-cad, P-gp positivity and between T(1)G(3) patients and no-T(1)G(3) patients (P < 0.05). There was negative correlation of E-cad expression with P-gp expression and PI.</p><p><b>CONCLUSIONS</b>Minimum adhesion, strong drug resistance and maximum proliferation are the main factors that promote short-term recurrence of superficial bladder cancer and also the inherent reasons for easy recurrence and high malignancy of T(1)G(3) tumors. During this course, the three aspects may interact.</p>