GLIAL ANTIPROLIFERATIVE FACTOR AS A TUMOROSTATIC AGENT

胶质细胞抗增殖因子作为肿瘤抑制剂

• 批准号: 3492905
• 负责人: DIANNE LORTON
• 金额: $ 5万
• 依托单位: GLIATECH, INC.
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3492905
• 关键词: Schwann cells; antineoplastics; cell growth regulation; drug design /synthesis /production; drug screening /evaluation; endopeptidases; enzyme linked immunosorbent assay; glia; glioma; growth media; laboratory rat; metalloproteins; neoplasm /cancer chemotherapy; neoplastic growth; nonhuman therapy evaluation; tissue /cell culture

Malignant gliomas are the most commonly occurring cerebral neoplasms in humans. The incidence of primary brain tumors is 16,000 cases annually, with malignant gliomas (glioblastoma multiforme) comprising 20-40% of these cases. Despite concentrated research efforts, the outlook for glioma patients remains grim. Approximately 90% of all glioma patients die within two years of diagnosis. This proposal examines the use of glial antiproliferative factors derived from Schwann cells (SC) or synthesized by SC proteases for treatment of malignant gliomas. Studies to determine the mechanisms underlying the cessation of SC proliferation in vitro have demonstrated that SC conditioned medium (CM) inhibits glia cell proliferation in vitro. This antiproliferative activity results following production of a 55 kD protein by SCs. This protein is a Zn++ metalloprotease which acts on fibronectin to produce 29 kD heparin-binding fibronectin fragments, which also inhibit in vitro primary glial cell and glioma proliferation. The experiments in the present proposal will evaluate the ability of the 29 kD protein, termed glial antiproliferative protein (GAP), to inhibit glial tumor cell proliferation and growth in vitro and in vivo . In Phase 11, drug formulation and the use of GAP in combination with resection, radiation, and chemotherapy for treating glioblastomas will be examined.

恶性神经胶质瘤是最常见的脑肿瘤 人类。 原发性脑肿瘤的发生率每年为16,000例， 其中包括20-40％的恶性神经胶质瘤（胶质母细胞瘤） 案例。 尽管集中了研究工作，但神经胶质瘤的前景 患者仍然严峻。 大约90％的所有神经胶质瘤患者死亡 两年的诊断。 该建议检查了神经胶质的使用 源自Schwann细胞（SC）的抗增殖因子或由 SC蛋白酶用于治疗恶性神经胶质瘤。 确定的研究 体外SC增殖的停止的基础机制 证明SC条件培养基（CM）抑制了神经胶质细胞 体外增殖。 这种抗增生活性在 SCS生产55 kD蛋白。 该蛋白是Zn ++ 金属蛋白酶作用于纤连蛋白，产生29 kD肝素结合 纤连蛋白片段，也抑制体外原发性神经胶质细胞和 神经胶质瘤增殖。 本提案中的实验将 评估29 kD蛋白的能力，称为神经胶质抗增殖 蛋白质（GAP），以抑制神经胶质肿瘤细胞的增殖和生长 体内和体内。在第11阶段，药物制剂和间隙在 结合切除，放射和化学疗法 将检查胶质母细胞瘤。