Quantitation and investigation of malignancy of brain tumors

脑肿瘤恶性程度的定量和研究

• 批准号: 02404058
• 负责人: TAKEUCHI Kazuo
• 金额: $ 20.8万
• 依托单位: Kyorin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02404058/
• 关键词: cell kinetics; brain tumor; suppressor gene P-53; glucose transporter; Histone; nucleolin; cell-cell adhesion molecules; MIB-1; モノクロ-ナル抗体; 細胞細胞接着蛋白質; がん抑制遺伝子; 成長因子; 細胞細胞接着蛋白; ガン抑制遺伝子

Cell kinetics of brain tumors Double-labeling studies with BUdR and iododeoxyuridine, performed to analyze the cell cycle progression in over 50 gliomas, revealed that S-phase duration (Ts) was fairly uniform (mean +- SD : 8.9 +- 2.0 hours) regardless of the differences in the LIs. Nevertheless, the potential doubling time (the time for a tumor cell population to double in the absence of cell lose) varied from 2 days to over a month, begin very short for tumors with a high LI, and correlated withthe BUdR LIs (Tp=17.8/LI^<0.77> ; r=0.95). The cell cycle time calculated for gliomas with LIs of 1-20% was 1-2 days. These paramaters are useful in determining the dose, duration, and interval of chemotherapy and in evaluating the effectiveness of treatment. In addition, novel methods for evaluating proliferating activities of brain tumors were developed.1) In situ hybridization for Histone 3 mRNA2) Probuction of nucleolin antibody and its characterization3) Clinical application of MIB-1 antibody immunohistochemistryA tumor suppressor gene P-53 was analyzed, using a polymerase chain reaction-RFLP method. The loss of heterozygosity (LOH) was demonstrated in 48% of brain tumors.The expression of facilitative glucose transporter (GLUT) isoforms in human astrocytic tumors was examined. GLUT1 was observed in the luminal surface of capillaries in all cases, whereas tumor cells were positive for GLUT1 in only two of 14 cases. these of 14 cases expressed the GLUT4 protein, which was localized in the cytoplasm of tumor cells.C-CAM and K3 protein closely related to the formation of blood brain barrier function in the central nervous system.

脑肿瘤的细胞动力学使用 BUdR 和碘脱氧尿苷进行双标记研究，以分析 50 多个神经胶质瘤的细胞周期进展，结果表明，无论 LI 有何差异，S 期持续时间 (Ts) 相当一致（平均 ± SD：8.9 ± 2.0 小时）。然而，潜在的倍增时间（在没有细胞丢失的情况下肿瘤细胞群倍增的时间）从 2 天到一个月以上不等，对于高 LI 的肿瘤来说，开始时间非常短，并且与 BUdR LI 相关（Tp=17.8/LI^<0.77>；r=0.95）。 LI 为 1-20% 的神经胶质瘤的细胞周期时间计算为 1-2 天。这些参数可用于确定化疗的剂量、持续时间和间隔以及评估治疗的有效性。此外，还开发了评估脑肿瘤增殖活性的新方法。1）组蛋白3 mRNA原位杂交2）核仁素抗体的制备及其表征3）MIB-1抗体免疫组化的临床应用采用聚合酶链式反应-RFLP方法对抑癌基因P-53进行分析。 48% 的脑肿瘤显示杂合性缺失 (LOH)。检查了人星形细胞肿瘤中易化葡萄糖转运蛋白 (GLUT) 亚型的表达。所有病例的毛细血管腔表面均观察到 GLUT1，而 14 例中仅 2 例肿瘤细胞呈 GLUT1 阳性。 14例均表达GLUT4蛋白，定位于肿瘤细胞胞质。C-CAM和K3蛋白与中枢神经系统血脑屏障功能的形成密切相关。

项目成果

McDermott MW,Krouwer HGJ,Asai A,Ito S,Hoshino T,Prados MD: "A comparison of CT contrast enhancement and BUdR labeling indices in moderately and highly anaplastic astrocytomas of the cerebral hemispheres." Canad J Neurol. 19. 34-39 (1992)

McDermott MW、Krouwer HGJ、Asai A、Ito S、Hoshino T、Prados MD：“大脑半球中度和高度间变性星形细胞瘤 CT 对比增强和 BUdR 标记指数的比较。”

Hoshino T: "Cell kinetics of glial tumors" Rev Neurol (Paris). 148. 396-401 (1992)

Hoshino T：“神经胶质瘤的细胞动力学”Rev Neurol（巴黎）。

Sibuya M, Sito F, Miwa T, Davis RL, Wilson CB, Hoshino T: "Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts" Acta Neuropathol. 84. 1

Sibuya M、Sito F、Miwa T、Davis RL、Wilson CB、Hoshino T：“使用 Ki-67 和抗 DNA 聚合酶 α 单克隆抗体、溴脱氧尿苷标记和核仁组织区计数对垂体腺瘤进行组织化学研究” Acta Neuropathol。

永松信哉、中道洋子、佐和弘基: "脳タイプのグルコーストランスポーター。" 生体の科学. (1994)

Shinya Nagamatsu、Yoko Nakamichi、Hiroki Sawa：“脑型葡萄糖转运蛋白”（1994 年）。

Hoshino T,Ito S,Asai A,Prados MD,Davis RL,Wilson CB: "Cell kinetic analysis of brain tumors studied by in situ double labelling with IUdR and BUdR." J Neuro-Oncol. 13. 265 (1992)

Hoshino T、Ito S、Asai A、Prados MD、Davis RL、Wilson CB：“通过 IUdR 和 BUdR 原位双标记研究脑肿瘤的细胞动力学分析。”