Ogawa Y, Nishioka A, Hamada N, Terashima M, Inomata T, Yoshida S, Seguchi H, Kishimoto S
Department of Radiology, Kochi Medical School, Okoh-cho, Nankoku-shi, Kochi-Prefecture 783-8505, Japan.
Int J Mol Med. 1998 Sep;2(3):301-7. doi: 10.3892/ijmm.2.3.301.
Telomerase activity has been evaluated for many kinds of malignancies, and it has been clarified that the activity reflected the malignant potential of the tumor. With regard to radiation therapy for cancer, simple and reliable assays for the prediction of therapeutic effect have not been fully developed yet. Therefore, we aimed to determine whether telomerase activity is changed by radiotherapy for advanced head and neck malignancies, and to clarify the possible correlation of telomerase activity with the therapeutic effect of radiation therapy and patients' clinical outcomes. Twenty-five patients with advanced cancers of the oral cavity and oropharynx were examined. All the cancers were confirmed histopathologically as squamous cell carcinomas. Biopsies were performed before treatment and at doses of 4 and/or 10 Gy, and 20 Gy of radiotherapy. To semi-quantitate telomerase activity, a highly sensitive PCR-based telomeric repeat amplification protocol assay was performed. Nineteen of the 21 cancers (90.1%) showed telomerase activity of varied extents prior to radiation therapy. Nine of the 25 patients showed continuous elevations of telomerase activity (> 10 TPG units/microg protein) in their tumors during radiation therapy, and these nine showed 13.8-216.9 TPG units/microg protein at 20 Gy of radiotherapy. In eight of the nine patients, tumors did not respond well to radiotherapy and relapsed locally in a short period after the treatment. On the other hand, in another group of 11 patients, who showed low (< 10) and/or no activity of telomerase in their tumors at 20 Gy of radiotherapy, there were nine patients whose tumors responded well to radiotherapy (p < 0.025 by the chi2 test). None of them relapsed locally in the follow-up period of approximately 21 months, and the difference was statistically significant (p < 0.025 by the chi2 test). It is concluded that the high activity of telomerase in tumor tissue at 20 Gy of radiotherapy can predict a poor therapeutic effect of radiation therapy and unfavorable patients' outcomes for advanced cancers of oral cavity and oropharynx.
端粒酶活性已在多种恶性肿瘤中进行了评估，并且已经明确该活性反映了肿瘤的恶性潜能。关于癌症的放射治疗，用于预测治疗效果的简单可靠检测方法尚未完全开发出来。因此，我们旨在确定晚期头颈部恶性肿瘤放疗后端粒酶活性是否发生变化，并阐明端粒酶活性与放射治疗效果及患者临床结局之间可能存在的相关性。对25例口腔和口咽晚期癌症患者进行了检查。所有癌症经组织病理学确诊为鳞状细胞癌。在治疗前以及放疗剂量达到4和/或10 Gy以及20 Gy时进行活检。为了半定量端粒酶活性，进行了基于聚合酶链反应的高灵敏度端粒重复序列扩增协议检测。21例癌症中的19例（90.1%）在放疗前显示出不同程度的端粒酶活性。25例患者中有9例在放疗期间肿瘤中端粒酶活性持续升高（>10 TPG单位/微克蛋白质），这9例患者在放疗20 Gy时端粒酶活性为13.8 - 216.9 TPG单位/微克蛋白质。在这9例患者中的8例中，肿瘤对放疗反应不佳，治疗后短期内局部复发。另一方面，在另一组11例患者中，其肿瘤在放疗20 Gy时端粒酶活性低（<10）和/或无活性，其中9例患者的肿瘤对放疗反应良好（卡方检验p<0.025）。在大约21个月的随访期内，他们均无局部复发，差异具有统计学意义（卡方检验p<0.025）。结论是，放疗20 Gy时肿瘤组织中端粒酶的高活性可预测口腔和口咽晚期癌症放射治疗效果不佳及患者预后不良。
