Preisler H D, Kotelnikov V M, LaFollette S, Taylor S, Mundle S, Wood N, Coon J S, Hutchinson J, Panje W, Caldarelli D D, Griem K
Rush Cancer Institute, Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3833, USA.
Clin Cancer Res. 1996 Sep;2(9):1453-60.
The effect of cytotoxic therapy on the proliferation of squamous cell carcinoma of the head and neck in vivo in patients was evaluated before and 15-35 days after the start of therapy. To accomplish this, iododeoxyuridine was administered at t = 0, and bromodeoxyuridine was administered 15-35 days later during treatment with a tumor biopsy obtained for study immediately after each pyrimidine infusion. Monoclonal antibodies specific for the halogenated pyrimidines were used to identify cells that were in the S-phase at the time of the infusions. Eleven patients were studied prior to treatment. Of those, the intratreatment biopsy of eight patients contained tumor tissue. In the other three patients, tumor tissue was not present in the second biopsy. Continued precursor incorporation into DNA-synthesizing cells during treatment was detected in six of eight tumor specimens. In two tumor specimens, an increase in the percentage of S-phase cells was noted, in two specimens tumor cells synthesizing DNA were not detected, and in four specimens the percentage of S-phase tumor cells was lower than that in the pretherapy specimen. Patients in whom there were no S-phase cells detected during treatment or in whom no tumor was detected in the second biopsy had a favorable treatment outcome in comparison to those patients in whom continued tumor proliferation during treatment was detected. The number of cells in S-phase prior to the initiation of treatment was not predictive of whether or not proliferation would continue during cytotoxic therapy. Evidence for reentry of kinetically quiescent cells into the cycle during treatment was noted. Additionally, cytotoxic therapy altered the proliferation pattern of normal-appearing mucosa as well. The results of this study demonstrate that tumor cell proliferation does continue in some squamous cell carcinoma of the head and neck during intensive cytotoxic therapy.
在患者体内评估了细胞毒性疗法对头颈部鳞状细胞癌增殖的影响，分别在治疗开始前以及开始治疗15 - 35天后进行评估。为此，在t = 0时给予碘脱氧尿苷，并在治疗15 - 35天后给予溴脱氧尿苷，每次嘧啶输注后立即获取肿瘤活检组织用于研究。使用对卤代嘧啶具有特异性的单克隆抗体来识别输注时处于S期的细胞。在治疗前对11名患者进行了研究。其中，8名患者的治疗中活检包含肿瘤组织。另外3名患者的第二次活检中未发现肿瘤组织。在8个肿瘤标本中的6个中检测到治疗期间前体持续掺入DNA合成细胞。在2个肿瘤标本中，观察到S期细胞百分比增加；在2个标本中未检测到合成DNA的肿瘤细胞；在4个标本中，S期肿瘤细胞百分比低于治疗前标本。与那些在治疗期间检测到肿瘤持续增殖的患者相比，在治疗期间未检测到S期细胞或第二次活检未发现肿瘤的患者治疗效果良好。治疗开始前S期细胞的数量并不能预测细胞毒性治疗期间增殖是否会持续。注意到有证据表明静止细胞在治疗期间重新进入细胞周期。此外，细胞毒性疗法也改变了外观正常的黏膜的增殖模式。本研究结果表明，在强化细胞毒性治疗期间，一些头颈部鳞状细胞癌的肿瘤细胞增殖确实会持续。
