Investigation for oncogenes relating to chemotherapy resistance of human malignant gliomas

人恶性胶质瘤化疗耐药相关癌基因的研究

• 批准号: 14571295
• 负责人: SAWAMURA Yutaka
• 金额: $ 2.24万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571295/
• 关键词: Anti-OLIG2 antibody; Auxiliary diagnostic tooL; Human gliomas; Immunohistochemistry; Olig1; Olig2; Quantitative RT-PCR; oligodendroglioma; tumor marker; loss of heterozygosity; fluorescence in situ hybridization; microsatellite analysis; chemo

Because a specific group of oligodendrogliomas is susceptible to adjuvant therapy, it is important to elucidate the biological characteristics of these tumors. In situ hybridization analyses have revealed that Olig genes are expressed in oligodendroglial lineage cells and are highly expressed in oligodendrogliomas. To clarify whether OLIG is a tumor-specific marker for oligodendrogliomas, we have investigated the expression of Olig transcripts by semiquantitative RT-PCR assay and OLIG2 protein with a new antibody in a variety of glial tumors. The semiquantitative RT-PCR revealed that high levels of expression of Olig1 and Olig2 mRNAs were present in anaplastic oligodendrogliomas and anaplastic astrocytomas, while expression of these mRNAs in grade IV glioblastomas was lower than in grade II and grade III gliomas (p<0.01). Immunohistochemical analyses demonstrated that the mean immunopositive proportion of OLIG2 was 82% in anaplastic oligodendrogliomas, but only 34% in anaplastic astrocytomas. Therefore, although OLIG2 expression was detected in a range of gliomas not specific for oligodendrogliomas, the expression level in anaplastic oligodendrogliomas was more uniform and intense than that in other glial tumors. In conclusion, combining Olig mRNA expression and immunohistochemistry of OLIG2 enables oligodendrogliomas to be distinguished from glioblastomas and other astrocytic glial tumors.

由于一组特定的少突胶质细胞瘤对辅助治疗敏感，因此阐明这些肿瘤的生物学特征非常重要。原位杂交分析表明，Olig 基因在少突胶质细胞系细胞中表达，并且在少突胶质细胞瘤中高度表达。为了阐明 OLIG 是否是少突胶质细胞瘤的肿瘤特异性标志物，我们通过半定量 RT-PCR 测定和使用新抗体研究了 OLIG2 蛋白在多种胶质瘤中的表达。半定量RT-PCR显示，间变性少突胶质细胞瘤和间变性星形细胞瘤中存在高水平的Olig1和Olig2 mRNA表达，而这些mRNA在IV级胶质母细胞瘤中的表达低于II级和III级胶质瘤（p<0.01）。免疫组织化学分析表明，间变性少突胶质细胞瘤中 OLIG2 的平均免疫阳性比例为 82%，但间变性星形细胞瘤中仅为 34%。因此，尽管在一系列对少突胶质细胞瘤不具有特异性的神经胶质瘤中检测到了 OLIG2 表达，但间变性少突胶质细胞瘤中的表达水平比其他神经胶质瘤中的表达水平更加均匀和强烈。总之，结合 Olig mRNA 表达和 OLIG2 的免疫组织化学，能够将少突胶质细胞瘤与胶质母细胞瘤和其他星形细胞胶质瘤区分开来。

项目成果

Ohnishi A, Sawa H, Tsuda M, Sawamura Y., et al.: "Expression of oligodendroglial linage-associated markers Oligo1 and Oligo2 in different types of human gliomas."J Neuropath Exp Neurol. 62. 1052-1059 (2003)

Ohnishi A、Sawa H、Tsuda M、Sawamura Y. 等人：“少突胶质细胞系相关标记 Oligo1 和 Oligo2 在不同类型的人类神经胶质瘤中的表达。”J Neuropath Exp Neurol。

Aoyama T, Shirato H, Ikeda J, Fujieda K, Miyasaka K, Sawamura Y.: "Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors."J Clin Oncol. 20. 857-865 (2002)

Aoyama T、Shirato H、Ikeda J、Fujieda K、Miyasaka K、Sawamura Y.：“颅内生殖细胞肿瘤的诱导化疗后进行低剂量受累野放疗。”J Clin Oncol。

Ohnisih A, et al.: "Expression of oligodendroglial linage-associated markers Olig1 and Olig2 in different types of human gliomas."J Neuropath Exp Neurol. 62. 1052-1059 (2003)

Ohnisih A 等人：“少突胶质细胞系相关标记 Olig1 和 Olig2 在不同类型的人类神经胶质瘤中的表达。”J Neuropath Exp Neurol。

Ohnishi A, Sawa H, Tsuda M, Sawamura Y, Itoh T, Iwasaki Y, Nagashima K: "Expression of oligodendroglial linage-associated markers Olihg1 and Olig2 in different types of human gliomas."J Neuropath Exp Neurol. 62. 1052-1059 (2003)

Ohnishi A、Sawa H、Tsuda M、Sawamura Y、Itoh T、Iwasaki Y、Nagashima K：“少突胶质细胞系相关标记 Olihg1 和 Olig2 在不同类型的人类神经胶质瘤中的表达。”J Neuropath Exp Neurol。

Aoyama H, et al.: "Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors."J Clin Oncol. 20. 857-865 (2002)

Aoyama H 等人：“颅内生殖细胞肿瘤的诱导化疗后进行低剂量受累野放疗。”J Clin Oncol。