APPLICATION OF TELOMERE LENGTH AND TELOMERASE ACTIVITY IN SURGERY : EARLY DETECTION OF PREVENTION OF POSTOPERATIVE RECURRENCE AND METASTASIS

端粒长度和端粒酶活性在手术中的应用：早期检测预防术后复发和转移

• 批准号: 09470250
• 负责人: HIYAMA Eiso
• 金额: $ 8.38万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470250/
• 关键词: telomere; telomerase; cancer; surgery; recurrence; metastasis; prognostic indicator; prevention

Postoperative reoccurrence and metastasis is difficult to be predicted at surgery. To evaluate alterations of telomere length and telomerase activity as biomarkers for postoperative reoccurrence/metastasis, we analyzed the correlation between those parameters and clinical status (stages, prognosis, recurrence, etc) in 653 adult and 164 childhood cancer specimens.Shortened telomere (length of terminal restriction fragments <less than or equal>8 kb) was detected in 1 9-50% and elongated telomere (<greater than or equal> 15 kb) was in 0-19%. Telomerase activation was detectable in 48-1 00% of these tumors. High telomerase activity was detected in various percentages (17-88%) of each type of these tumors. In pancreatic cancer and rhabdomyosarcoma specimens, high telomerase activity was detected in more than 80%. Significantly high percentages of postoperative reoccurrence/metastasis occurred in the cases with high telomerase activity and shortened telomere, which were considered to be usef … More ul markers to predict of postoperative reoccurreAmong these cases, we examined the expression of human telomerase RNA component (hTR) and human telomerase reverse transcriptase (hTERT) mRNA using in situ hybridization or in situ PCR.In the cancers with high telomerase activity, almost all cancer cells showed hTERT and hTR expressions, whereas cancer tissues with low telomerase activity showed heterogeneity of their expressions among composing cells. In the tissue specimens, expression levels of telomerase activity using in situ TRAP were equivalent with the hTERT expression levels. Thus, hTERT expression levels in frozen tissues is considered to be a useful recurrence/metastasis-predicting indicator. Then, we established the method for detecting hTERT expression by RT-PCR.Among these cases, we obtained liver biopsy and intraperitoneal lavage samples under informed consents. Telomerase activity, telomere length, hTR, and hTERT mRNA expression in these samples was not significantly correlated with postoperative reoccurrence/metastasis. Less

术后复发和转移在手术中很难预测。为探讨端粒长度和端粒酶活性的变化与肿瘤术后复发转移的关系，我们对653例成人和164例儿童肿瘤标本进行了端粒长度和端粒酶活性与临床分期、预后、复发等的相关性分析，发现端粒长度缩短（末端限制性片段长度<less than or equal>8 kb）占19 ~ 50%，端粒长度延长（<greater than or equal>15 kb）占0- 19%。端粒酶活性在48- 100%的这些肿瘤中可检测到。高端粒酶活性检测在不同百分比（17-88%）的每种类型的这些肿瘤。在胰腺癌和横纹肌肉瘤标本中，端粒酶活性高于80%。端粒酶活性增高和端粒缩短的病例术后复发/转移率明显增高，认为这是治疗恶性肿瘤的有效方法。 ...更多信息 应用原位杂交和原位PCR方法检测了端粒酶RNA组分（hTR）和端粒酶逆转录酶（hTERT）mRNA的表达，结果发现，在端粒酶活性高的癌组织中，几乎所有癌细胞都有hTERT和hTR表达，而端粒酶活性低的癌组织中，hTR和hTERT的表达在组成细胞中存在异质性。在组织标本中，使用原位TRAP的端粒酶活性表达水平与hTERT表达水平相当。因此，冷冻组织中的hTERT表达水平被认为是一个有用的复发/转移预测指标。在此基础上，建立了RT-PCR检测hTERT表达的方法，并在知情同意的情况下，取肝活检和腹腔灌洗标本。端粒酶活性、端粒长度、hTR和hTERTmRNA表达与术后复发/转移无显著相关性。少

项目成果

檜山英三: "消化器癌とテロメラーゼ" 内科. 79・1. 358-359 (1997)

桧山英三：《胃肠癌与端粒酶》内科79・1（1997）。

Yamanishi Y: "Telomerase activity in rheumatoid synovium correlates with the mononuclear cell infiltration level and disease aggressiveness of rheumatoid arthritis." J.Rheumatol.25・2. 214-220 (1998)

Yamanishi Y：“类风湿性滑膜中的端粒酶活性与类风湿性关节炎的单核细胞浸润水平和疾病侵袭性相关。”J.Rheumatol.25·2（1998）。

Keiko Hiyama: "Telomerase activity as a novel marker of lung cancer and immune-associated lung diseases" International Journal of Molecular Meddicine. 1・3. 545-549 (1998)

Keiko Hiyama：“端粒酶活性作为肺癌和免疫相关肺部疾病的新标志物”，《国际分子医学杂志》1·3（1998）。

檜山桂子: "ヒトの悪性腫瘍におけるテロメラーゼ." 炎症と免疫. 6・6. 53-58 (1998)

Keiko Hiyama：“人类恶性肿瘤中的端粒酶”，53-58（1998）。

檜山桂子: "肺癌とテロメア・テロメラーゼ." 分子呼吸器病学. 2・3. 233-235 (1998)

桧山惠子：“肺癌与端粒和端粒酶。”2・3（1998）。