Ye D, Li H, Qian S, Sun Y, Zheng J, Ma Y
Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
J Urol. 1998 Dec;160(6 Pt 1):2025-8; discussion 2029.
Studies have shown that the effects of chemotherapy depend on some biochemical mechanisms to induce apoptosis. Many genes are involved in apoptosis modulation, including p53, bcl-2 and bax. We determined the roles of p53 status and the ratio of bcl-2/bax proteins for predicting the recurrence of bladder superficial transitional cell carcinoma that had been treated with intravesical chemotherapy after resection.
We performed Western blot analysis to express bcl-2 and bax proteins, and PCR-SSCP to determine the alteration in the p53 gene in 43 patients with transitional cell carcinoma of the bladder treated with intravesical chemotherapy after tumor resection.
The expression of bcl-2 or bax did not correlate with histological grade, clinical stage or relapse. In cases of relapse within 1 year after resection bcl-2/bax was greater than and less than 1 in 50 and 11%, respectively (p <0.01). Recurrence within 1 year after the initial operation was also more common in patients with than without p53 gene mutation (64 versus 22%, p <0.05). Furthermore, bcl-2/bax greater than and less than 1 was associated with p53 gene mutation in 38 and 11% of cases, respectively (p <0.05).
A bcl-2/bax ratio greater than 1 and p53 gene mutation were closely associated with early relapse in patients with superficial transitional cell carcinoma of the bladder during intravesical chemotherapy after resection. This finding suggests that the relative levels of bcl-2 and bax, and p53 gene status may contribute to drug sensitivity and progression, and help to predict recurrence. Moreover, bcl-2/bax correlated with p53 status, which implies that cross talk among bcl-2, bax and p53 has a role in influencing drug induced apoptosis and regulating resistance to chemotherapy.
研究表明，化疗效果取决于诱导细胞凋亡的一些生化机制。许多基因参与细胞凋亡调节，包括p53、bcl-2和bax。我们确定了p53状态以及bcl-2/bax蛋白比率在预测膀胱浅表性移行细胞癌经膀胱内化疗切除术后复发中的作用。
我们对43例膀胱移行细胞癌患者进行了蛋白质免疫印迹分析以检测bcl-2和bax蛋白的表达，并采用聚合酶链反应-单链构象多态性分析（PCR-SSCP）来确定p53基因的改变，这些患者均在肿瘤切除后接受了膀胱内化疗。
bcl-2或bax的表达与组织学分级、临床分期或复发无关。在切除术后1年内复发的病例中，bcl-2/bax大于1和小于1的情况分别占50%和11%（p<0.01）。初次手术后1年内复发在有p53基因突变的患者中比无p53基因突变的患者更常见（64%对22%，p<0.05）。此外，bcl-2/bax大于1和小于1分别在38%和11%的病例中与p53基因突变相关（p<0.05）。
bcl-2/bax比率大于1和p53基因突变与膀胱浅表性移行细胞癌患者在切除术后膀胱内化疗期间的早期复发密切相关。这一发现表明，bcl-2和bax的相对水平以及p53基因状态可能影响药物敏感性和疾病进展，并有助于预测复发。此外，bcl-2/bax与p53状态相关，这意味着bcl-2、bax和p53之间的相互作用在影响药物诱导的细胞凋亡和调节化疗耐药性方面发挥作用。
