Genetic alteration associated with response to radiotherapy in advanced cervical cancer

与晚期宫颈癌放疗反应相关的基因改变

• 批准号: 09670965
• 负责人: HARIMA Yoko
• 金额: $ 1.66万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-09670965/
• 关键词: Loss of heterozygosity; Microsatellite instability; Radiotherapy; Cervical carcinoma; テロメア活性; PCNA

Chromosome 17 alterations are found in more cancers than those of any other chromosome, and frequently involve the p53 gene on 17p13. The aim of this study was to identify the correlations between the presence of loss of heterozygosity (LOH) and microsatellite instability (MI) on chromosome 17p13 in patients with cervical cancer and the patients' response to radiotherapy. A total of 50 patients were treated with definitive radiotherapy. We performed biopsies and took specimens from the tumour and venous blood of all patients. Tumour and normal DNAs were analyzed by polyrnerase chain reaction for genetic losses and instability at three polymorphic microsatellite locimapped to 17p13. Nineteen of theSO tumours (38%) displayed a genetic alteration (GA) on 17p13, sixteen (32%) were found to have LOH, and 3(6%) showed MI.The sizes of the tumours of the GA-positive patients were significantly greater than those of the GA-negative patients (P=0.009). The mean tumour diameter of all patients wa … More s 6 * 2.4 cm. We divided the patients into those with tumours smaller than 6cm in diameter (n=26) and those with tumours equal to or greater than 6 cm in diameter (n=24). The former group survived significantly longer compared to the latter group(P=0.0002). Among the patients with < 6cm tumours, all 6 GA-positive patients are alive with no evidence of disease (NED), whereas of the 20 GA-negative patients, 18 have NED, and 2 are alive with disease (AWD) or suffered cancer-caused death (CD). Thus, there was no correlation between GA and radiotherapy response in the tumours smaller than 6 cm. However, among the patients with *6 cm turnours, 2 of the GA-positive patients have NED, and 11 are AWD/CD, whereas 7 of the GA-negative patients have NED, and 4 are AWD/CD.Among the patients with * 6 cm tumours, the response to radiotherapy of the GA-positive patients were significantly poorer than those of the GA-negative patients (P=0.02). In addition, the GA-negative patients survived significantly longer compared to the GA-positive patients (P=0.026). The results of this study suggest that GA increases with tumour growth. Improved success in the management of bulky cervical cancer requires a better understanding of its biological behavior. Less

17号染色体的改变在癌症中比任何其他染色体的改变都多，并且经常涉及17 p13上的p53基因。本研究旨在探讨宫颈癌患者染色体17 p13上的杂合性缺失（洛）和微卫星不稳定性（MI）与放疗疗效的关系。共50例患者接受了确定性放疗。我们进行了活检，并采取标本从肿瘤和静脉血的所有患者。通过聚合酶链反应分析肿瘤和正常DNA在定位于17 p13的三个多态性微卫星位点上的遗传丢失和不稳定性。19例（38%）SO肿瘤在17 p13上显示遗传改变（GA），16例（32%）发现有洛缺失，3例（6%）显示MI。GA阳性患者的肿瘤大小显著大于GA阴性患者（P=0.009）。所有患者的平均肿瘤直径为 ...更多信息 s 6 * 2.4 cm。我们将患者分为肿瘤直径小于6cm的患者（n=26）和肿瘤直径等于或大于6cm的患者（n=24）。前一组的存活时间明显长于后一组（P=0.0002）。在肿瘤< 6cm的患者中，所有6名GA阳性患者都活着，没有疾病证据（NED），而在20名GA阴性患者中，18名患有NED，2名患有疾病（AWD）或患有癌症导致的死亡（CD）。因此，在小于6 cm的肿瘤中，GA和放疗反应之间没有相关性。在肿瘤直径为6cm的患者中，GA阳性患者中NED 2例，AWD/CD 11例，GA阴性患者中NED 7例，AWD/CD 4例。此外，GA阴性患者的生存时间明显长于GA阳性患者（P=0.026）。这项研究的结果表明，GA随着肿瘤的生长而增加。提高巨大宫颈癌管理的成功率需要更好地了解其生物学行为。少

项目成果

Y Harima: "Bax and Bcl-2 expression predict response to radiotherapy in human cervical cancer." J.Cancer Res.Clin.Oncol.124. 503-510 (1998)

Y Harima：“Bax 和 Bcl-2 表达可预测人类宫颈癌对放射治疗的反应。”

Y Harima: "WAF1 induction and infection by HPV E6 as a determinants of radiosensitivity in human cervical cancer" Jpn, J, Cancer Clin.44. 185-186 (1998)

Y Harima：“HPV E6 诱导和感染 WAF1 作为人类宫颈癌放射敏感性的决定因素”Jpn，J，Cancer Clin.44。

Y Harima: "Bax and Bcl-2 expression predict response to radiotherapy in human cervical cancer." Jpn.J.Cancer Chemother.25. 1273-1277 (1998)

Y Harima：“Bax 和 Bcl-2 表达可预测人类宫颈癌对放射治疗的反应。”

M Imamura: "Relationship between LET and RBE values for Escherichia coli determined using carbon ion beams from the TIARA cyclotron and HIMAC synchrotron" J.Gen.Appl.Microbiol.43. 175-177 (1997)

M Imamura：“使用 TIARA 回旋加速器和 HIMAC 同步加速器的碳离子束确定大肠杆菌的 LET 和 RBE 值之间的关系”J.Gen.Appl.Microbiol.43。

M Imamura: "Potential applicability of clinical hyperthermia using a Thermotron-RF8 as assessedfrom thermal distribution in an agar phantom containing hydroxyapatite." Oncology Reports. 3. 1017-1019 (1997)

M Imamura：“根据含有羟基磷灰石的琼脂模型的热分布评估，使用 Thermotron-RF8 进行临床热疗的潜在适用性。”