GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON.
GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON.
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DOI：
10.1038/sj.bjc.6601260
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发表时间：
2003-10-06
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
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葡萄糖转运蛋白-1（GLUT 1）和碳酸酐酶IX（CAIX）受缺氧诱导因子-1（HIF-1）调节，并已被研究为缺氧的假定内在细胞标志物。本研究直接比较了CAIX和GLUT 1与pimonidazole结合在一系列前瞻性膀胱癌患者中的作用，并研究了这些标志物与血管分布和增殖结合在一系列回顾性膀胱癌患者中的预后意义，这些患者在一项II期试验中接受了carbogen和nicotinamide（ARCON）的根治性放疗。共有21名诊断为膀胱移行细胞癌的患者接受了0.5 g m−2 pimonidazole。对连续肿瘤切片进行pimonidazole、GLUT 1和CAIX染色并进行比较。从先前使用ARCON治疗浸润性膀胱癌的一系列64名患者获得的组织切片针对GLUT 1和CAIX以及Ki-67和CD 31/34进行染色。两种内在标志物与匹莫硝唑有良好的地理共定位，并且在个体患者中具有高度显著的一致性; GLUT 1的相关系数为0.82（P=0.0001），CAIX的相关系数为0.74（P<0.0001）。在这两个系列的患者中，内源性缺氧标志物彼此高度相关，并且在回顾性研究中与增殖的相关性也很明显。在单变量和多变量分析中，GLUT 1和CAIX是总体和病因特异性生存的独立预测因子。缺氧标志物不能预测局部控制或无瘤生存，尽管较高的Ki-67指数显示局部失败的趋势。这些数据表明，低氧修饰和加速治疗可能是膀胱癌的有效治疗选择。
Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5 g m−2 pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P=0.0001) for GLUT1 and 0.74 (P<0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.
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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：
5.7
作者：
Nordsmark, M;Overgaard, M;Overgaard, J
通讯作者：
Overgaard, J
DOI：
10.1016/s0360-3016(00)01505-4
发表时间：
2001-02-01
影响因子：
7
作者：
Raleigh, JA;Chou, SC;Varia, MA
通讯作者：
Varia, MA
影响因子：
2.1
作者：
Chang, SG;Lee, SJ;Kim, YW
通讯作者：
Kim, YW
影响因子：
5.7
作者：
MACIEJEWSKI, B;MAJEWSKI, S
通讯作者：
MAJEWSKI, S