Lindner D, Raghavan D
Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH 44195, USA.
Br J Cancer. 2009 Apr 21;100(8):1287-91. doi: 10.1038/sj.bjc.6605022.
Reliable surrogate markers of response to anticancer therapy remain a desirable tool for preclinical modelling and clinical practice in oncology. Clinical evaluation is relatively unreliable when attempting to assess rapidly and prospectively the outcome of treatment. Fluxes in released or circulating tumour marker levels are a useful but inconsistent marker of cytotoxic response. Serial measurement of circulating tumour cells appears to have some utility as a surrogate marker, but assay systems are expensive, and many cancers are not associated with the presence of circulating tumour cells. Because tissue breakdown is associated with release of nucleic acids and other cellular products, we reasoned that serial measurement of intra-tumoural pH may correlate with the extent of tumour lysis, and thus with outcomes of cytotoxic chemotherapy. Doxorubicin-sensitive and doxorubicin-resistant sublines of P388 murine monocytic leukaemia in C57BL/6 mice were treated with increasing concentrations of doxorubicin. Tumours were serially measured by conventional bi-dimensional methods and pH was sampled using a bevelled tip electrode. Mean and median pH changes were statistically different in responsive and resistant tumours, and amplitude of change correlated with long-term responses to doxorubicin. Serial sampling of pH in tumour masses may provide a useful surrogate of long-term response to chemotherapy.
可靠的抗癌治疗反应替代标志物仍然是肿瘤学临床前建模和临床实践中所期望的工具。在试图快速且前瞻性地评估治疗结果时，临床评估相对不可靠。释放或循环肿瘤标志物水平的变化是细胞毒性反应的一个有用但并不一致的标志物。循环肿瘤细胞的连续测量似乎作为替代标志物有一定作用，但检测系统昂贵，而且许多癌症与循环肿瘤细胞的存在并无关联。由于组织分解与核酸及其他细胞产物的释放有关，我们推断肿瘤内pH值的连续测量可能与肿瘤溶解程度相关，进而与细胞毒性化疗的结果相关。用递增浓度的阿霉素处理C57BL/6小鼠中的P388鼠单核细胞白血病的阿霉素敏感和阿霉素耐药亚系。通过传统的二维方法对肿瘤进行连续测量，并使用斜角尖端电极对pH值进行采样。反应性和耐药性肿瘤的平均和中位数pH变化在统计学上有差异，且变化幅度与对阿霉素的长期反应相关。肿瘤块中pH值的连续采样可能为化疗的长期反应提供一个有用的替代指标。
