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端粒酶激活和端粒长度在头颈癌中的临床应用价值

Clinical usefulness of telomerase activation and telomere length in head and neck cancer.

作者信息

Patel Mintoo M, Parekh Lalit J, Jha Franky P, Sainger Rachana N, Patel Jayendra B, Patel Devendra D, Shah Pankaj M, Patel Prabhudas S

机构信息

Biochemistry Research Section, Division of Research, The Gujarat Cancer Society, Asarwa, Ahmedabad 380016, India.

出版信息

Head Neck. 2002 Dec;24(12):1060-7. doi: 10.1002/hed.10169.

Abstract

BACKGROUND

Telomere shortening at every replication cycle is postulated to limit the life span of human somatic cells. In contrast, activation of telomerase is proposed to be an essential step for cancer cell immortalization. Head and neck cancer is the most common malignancy in the Indian population compared with Western countries. However, there are very few reports on telomerase activity and telomere length in head and neck cancer.

METHODS

Telomerase activation and telomere length alterations were studied in tumor and adjacent normal tissues in 110 patients with head and neck cancer and 40 patients with precancerous/benign conditions. Telomerase activity and telomere lengths were determined by Telomeric Repeat Amplification Protocol (TRAP assay) and Southern blot analysis, respectively.

RESULTS

Telomerase activation was observed in 78.2% of the malignant tissues, 85% of the precancerous tissues, and 53.1% of the adjacent normal tissues. Peak terminal restriction fragment length (TRF) was observed to be significantly lower in malignant tissues compared with the adjacent normal tissues. No significant correlation could be observed between telomerase activation and clinicopathologic characteristics of the patients. Two-year disease-free survival analysis showed that patients showing telomerase activation in the adjacent normal tissues and patients showing higher telomere length in malignant tissues had poor disease-free survival.

CONCLUSIONS

Our results demonstrate the significant clinical usefulness of telomerase activation and telomere length for head and neck cancer patients. These markers may be helpful in predicting the clinical course of the disease and thus in identifying the patients in need of a close follow-up and vigorous adjuvant treatment.

摘要

背景

假定每个复制周期中端粒缩短会限制人类体细胞的寿命。相反,端粒酶激活被认为是癌细胞永生化的关键步骤。与西方国家相比,头颈癌是印度人群中最常见的恶性肿瘤。然而,关于头颈癌中端粒酶活性和端粒长度的报道非常少。

方法

对110例头颈癌患者和40例癌前/良性疾病患者的肿瘤组织及相邻正常组织进行端粒酶激活和端粒长度改变的研究。分别通过端粒重复序列扩增法(TRAP检测)和Southern印迹分析来测定端粒酶活性和端粒长度。

结果

在78.2%的恶性组织、85%的癌前组织和53.1%的相邻正常组织中观察到端粒酶激活。与相邻正常组织相比,恶性组织中的末端限制片段长度峰值(TRF)显著更低。端粒酶激活与患者的临床病理特征之间未观察到显著相关性。两年无病生存分析表明,在相邻正常组织中显示端粒酶激活的患者以及在恶性组织中端粒长度更高的患者无病生存率较差。

结论

我们的结果表明端粒酶激活和端粒长度对头颈癌患者具有显著的临床实用性。这些标志物可能有助于预测疾病的临床进程,从而识别出需要密切随访和积极辅助治疗的患者。

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