Analysis of characterization of a GC factor in malignant brain tumor and its application to the gene therapy

恶性脑肿瘤GC因子特征分析及其在基因治疗中的应用

• 批准号: 09470296
• 负责人: KURISU Kaoru
• 金额: $ 4.29万
• 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 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470296/
• 关键词: GC factor; malignant glioma; EGFR; adenovirus; cell cycle; NBS1; telomerase; GC-Factor; 抗癌剤; *剤感受性; アデノウィルス; GC factor; アデノウイルスベクター; 細胞増殖抑制; GCfactor; 遺伝子導入

GC factor (GCF) is a human transcriptional regulator that binds to specific GC-rich sequences in the certain genes promoter and represses its transcription. Malignant glioma express multiautocrine loops of growth factor/receptor, especially overexpress the epidermal growth factor receptor (EGFR). We investigated the expression of the EGFR in glioma cell lines. By the use of GCF transfection, we examined whether GCF represses the expression of growth factors and receptors and cause growth inhibition of glioma cells. The transfection of GCF expression vector into glioma cell line (U251-MG) decreased the protein level of EGFR and insulin-like growth factor-II (IGF-II). We also examined the effect of GCF gene transfer on the chemosenstivity to ACNU, CDDP and VCR. The slight increase of sensitivity to ACNU. CDDP and VCR was found. We developed a recomblnant adenovirus expressing GCF gene (AxCA-GCF) by COS-TPC method. We are investigating the growth inhibition of glioma by infection of AxCA-GCF and in vitro and in vivo.Also, we investigated the molecular changes of p16 gene, NBS1, telomerase activity in human gliomas and malignant lymphoma. And we studied p16 gene transfection effects on growth of glioma cells and senstivity of cells to ACNU, CDDP and AZC.

GC因子（GCF）是一种人类转录调节剂，它与某些基因启动子中特定的富含GC序列结合并抑制其转录。恶性神经胶质瘤表达生长因子/受体的多分裂环，尤其是表皮生长因子受体（EGFR）。我们研究了胶质瘤细胞系中EGFR的表达。通过使用GCF转染，我们检查了GCF是否抑制生长因子和受体的表达并引起胶质瘤细胞的生长抑制。将GCF表达载体转染到神经胶质瘤细胞系（U251-mg）降低了EGFR和胰岛素样生长因子-II（IGF-II）的蛋白质水平。我们还检查了GCF基因转移对ACNU，CDDP和VCR的化学效果的影响。对ACNU的敏感性略有提高。发现CDDP和VCR。我们开发了一种通过COS-TPC方法表达GCF基因（AXCA-GCF）的腺病毒。我们正在研究通过感染AXCA-GCF和体外和体内的神经胶质瘤的生长抑制。此外，我们研究了p16基因，NBS1，人神经胶质瘤和恶性淋巴瘤中端粒酶活性的分子变化。我们研究了P16基因转染对神经胶质瘤细胞生长以及细胞对ACNU，CDDP和AZC的剂量的影响。

项目成果

Kaoru Kurisu: "Induction and maintenance therapy for high grade glioma of cerepral hemisphere using ACNC.platium,CSF"Proceedings of 11th ICNS. 411-415 (1997)

Kaoru Kurisu：“使用 ACNC.platium、CSF 对大脑半球高级神经胶质瘤进行诱导和维持治疗”第 11 届 ICNS 会议记录。

Harada Kunyu: "Telomerase acitivity in central nervous cystem malignant lymphoma"Cancer. 86. 1050-1055 (1999)

Harada Kunyu：“中枢神经囊肿恶性淋巴瘤中的端粒酶活性”癌症。

Seiji Hama: "Absence of mutations in the NBSI gene in B-cell malignant lymphoma patients"Anticancer research. (2000)

Seiji Hama：“B细胞恶性淋巴瘤患者的NBSI基因不存在突变”抗癌研究。

Hiroyuki Yoshioka: "Peritumoval Brain Edema Associated with Mewingioima." CANCER. 85(4). 936-944 (1999)

Hiroyuki Yoshioka：“与 Mewingioima 相关的瘤周脑水肿。”

Seiji Hama, Shinya Matsuura, Hiroshi Tauchi, Jyunko Sawada, Chikage Kato, Fumiyuki Yamasaki, Hiroyuki Yoshioka, Kazuhiko Sugiyama, Kazunori Arita, Kaoru Kurisu, Nakano Kamada, Yuji Heike, Keishi Komatsu: "Absence of mutations in the NBS1"Anticancer resear

Seiji Hama、Shinya Matsuura、Hiroshi Tauchi、Jyunko Sawada、Chikage Kato、Fumiyuki Yamasaki、Hiroyuki Yoshioka、Kazuhiko Sugiyama、Kazunori Arita、Kaoru Kurisu、Nakano Kamada、Yuji Heike、Keishi Komatsu：“NBS1 中不存在突变”抗癌研究