ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.
ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.
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DOI：
10.1371/journal.pone.0027616
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kihara K
中科院分区：
文献类型：
--
作者：
Koga F;Yoshida S;Tatokoro M;Kawakami S;Fujii Y;Kumagai J;Neckers L;Kihara K
肌肉浸润性膀胱癌(MIBC)患者的根治性膀胱切除术常因尿流改道而影响其生活质量。为了改善他们的生活质量，已经开发了一种使用化疗和放射治疗的节省膀胱的替代策略。在保留膀胱的治疗方案中，对诱导放化疗的完全反应(CR)是保存膀胱和良好生存的先决条件。因此，预测和克服放化疗抵抗将增加个体MIBC患者保留膀胱的机会。这项研究的目的是研究用于改善化疗放射反应的假定的分子靶点。应用免疫组织化学方法检测35例膀胱癌患者手术前活检标本中erbB2、NFκB、P53和Survivin的表达水平，并探讨其与放化疗敏感性和肿瘤特异性生存期的关系。在35例患者中，11例(31%)实现了病理CR，其余24例(69%)肿瘤对放化疗耐药。多因素分析显示，erb B2、NFκB过度表达和肾积水是放化疗抵抗的独立危险因素，其相对危险度分别为11.8(P = 0.014)、15.4(P = 0.024)和14.3(P = 0.038)。高表达κB和/或高表达的肿瘤放化疗耐受率为88.5%，而两者均为阴性的肿瘤放化疗耐药率仅为11.1%(P<；0.0001)。总的5年期社区卫生服务率为74%。经多因素分析，κB和/或NF = B的过度表达是膀胱癌死亡的独立危险因素，与放化疗抵抗(P = 0.003)和肾积水(P = 0.018)相比差异无统计学意义(P>0.05)。病理CR的11例患者的5年CSS率为100%，而化疗耐药的24例患者的5年CSS率为61%(P = 0.018)。因此，κB和NF-erb B的过表达与小细胞肺癌的放化疗耐药有关，是克服放化疗耐药的靶点。
Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014), 15.4 (P = 0.024) and 14.3 (P = 0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056) along with chemoradiation resistance (P = 0.003) and hydronephrosis (P = 0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018). Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC.
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DOI：
10.1016/s0360-3016(99)00544-1
发表时间：
2000-03-15
影响因子：
7
作者：
Rödel, C;Grabenbauer, GG;Sauer, R
通讯作者：
Sauer, R
影响因子：
45.3
作者：
Izzo, JG;Malhotra, U;Ajani, JA
通讯作者：
Ajani, JA
DOI：
10.1016/s0360-3016(98)00472-6
发表时间：
1999-03-15
影响因子：
7
作者：
Lara, PC;Pérez, S;Santana, C
通讯作者：
Santana, C
影响因子：
2.4
作者：
Matsumoto, H;Wada, T;Naito, K
通讯作者：
Naito, K
影响因子：
5.7
作者：
Izzo, Julie G.;Correa, Arlene M.;Ajani, Jaffer A.
通讯作者：
Ajani, Jaffer A.