Foultier M T, Vonarx-Coinsman V, de Brito L X, Morlet L, Robillard N, Patrice T
Faculté de Pharmacie, Nantes, France.
Cancer. 1994 Mar 15;73(6):1595-607. doi: 10.1002/1097-0142(19940315)73:6<1595::aid-cncr2820730610>3.0.co;2-7.
Photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) is a new treatment for cancers of small volume undergoing Phase II or III clinical trials in various medical fields. However, there is a lack of prognostic criteria of efficacy as in other cancer treatment.
Cell DNA content or cell kinetics throughout the cell cycle were analyzed by flow cytometry and propidium iodide staining before and after HPD-PDT in 33 patients with Tis or T1 cancers of the gastrointestinal tract. The authors compared results in near-diploid cancers with those obtained in normal corresponding tissue.
Complete local tumor destruction and negative histologic findings (complete response [CR]) were observed in 17 of 33 patients during a period averaging 15.7 months. Flow cytometry DNA analysis was feasible in 32 patients. Aneuploidy, found in 15 of the 32 indicated a poor prognosis because 5 of 15 patients with aneuploid tumors were classified as having CR, compared with 12 of 17 patients with near-diploid tumors (P < 0.05). Changes in ploidy after PDT in 11 patients consisted of a reduction in the number of aneuploid peaks in 8 patients and the appearance of one aneuploid peak in 3 patients. Percentages of cells in SG2M phase in near-diploid tumors differed from those observed in control subjects for adenocarcinomas, and there was no significant decrease after HPD-PDT. There was no correlation between the decrease of SG2M cells and the response to HPD-PDT.
Results obtained with PDT in this series of patients confirm previously published findings. Changes occurring in the ploidy of PDT-treated patients demonstrate that PDT acts directly on cancer cells in humans and not only on tumor vasculature. However, response to PDT varies from one cell population to another. The appearance of aneuploid populations after PDT suggests that destruction of sensitive cell populations allows the growth of aneuploid clones that initially are not detectable by flow cytometry.
由血卟啉衍生物(HPD)介导的光动力疗法(PDT)是一种针对小体积癌症的新型治疗方法,正在各个医学领域进行II期或III期临床试验。然而,与其他癌症治疗一样,缺乏疗效的预后标准。
采用流式细胞术和碘化丙啶染色法,对33例Tis或T1期胃肠道癌患者在HPD-PDT治疗前后的细胞DNA含量或整个细胞周期的细胞动力学进行分析。作者将近二倍体癌症的结果与相应正常组织的结果进行了比较。
在平均15.7个月的时间里,33例患者中有17例观察到局部肿瘤完全破坏且组织学检查结果为阴性(完全缓解[CR])。流式细胞术DNA分析在32例患者中可行。32例中有15例发现非整倍体,提示预后不良,因为15例非整倍体肿瘤患者中有5例被归类为CR,而17例近二倍体肿瘤患者中有12例(P<0.05)。11例患者PDT后倍体变化包括8例非整倍体峰数量减少,3例出现1个非整倍体峰。腺癌近二倍体肿瘤中SG2M期细胞百分比与对照组不同,HPD-PDT后无明显下降。SG2M细胞减少与对HPD-PDT的反应之间无相关性。
本系列患者PDT的结果证实了先前发表的发现。PDT治疗患者倍体的变化表明,PDT直接作用于人体癌细胞,而不仅仅作用于肿瘤血管。然而,对PDT的反应因细胞群体而异。PDT后非整倍体群体的出现表明,敏感细胞群体的破坏使非整倍体克隆得以生长,这些克隆最初无法通过流式细胞术检测到。