LOW DOSE 6-THIOGUANINE FOR OSTEOLYTIC BONE DISEASE

低剂量 6-硫鸟嘌呤治疗溶骨性骨病

• 批准号: 6074553
• 负责人: I ROSS GARRETT
• 金额: $ 10万
• 依托单位: OSTEOSCREEN, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6074553
• 关键词: 6 thioguanine; antineoplastics; bone disorder; bone neoplasms; breast neoplasms; cytotoxicity; dosage; drug screening /evaluation; histology; hypercalcemia; laboratory mouse; metastasis; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; parathyroid hormones; skeletal disorder chemotherapy

Osteolytic bone disease is a serious complication of common tumors such as breast and lung cancer, causing considerable morbidity such as pain, pathological fracture and hypercalcemia. In some patients with advanced disease, a large component of the tumor burden may be present in the skeleton. Since recent data has shown that the tumor-related peptide PTH-rP is not only responsible for hypercalcemia, but also for osteolytic bone disease in the absence of hypercalcemia, the investigators have identified small molecular weight compounds that inhibit bone metastasis by reducing PTH-rP transcription and expression by tumor cells. Such compounds are candidate drugs for the treatment of osteolytic bone lesions and hypercalcemia occurring in patients with common malignancies. PROPOSED COMMERCIAL APPLICATION: Osteolytic bone disease is a major problem in the cancer population. It causes considerable morbidity and mortality, and once tumor cells become housed in the skeleton, the tumor is non-curable. Our goal is to develop effective drugs which inhibit the major molecular mechanisms responsible for this process, and in particular to evaluate the drug 6-thioguanine used in low doses for this effect.

溶骨性骨病是乳腺等常见肿瘤的严重并发症 和肺癌，造成相当大的发病率，如疼痛，病理性骨折， 和高钙血症。 在一些晚期疾病患者中， 肿瘤负荷可能存在于骨骼中。因为最近的数据显示， 肿瘤相关肽PTH-rP不仅导致高钙血症， 同样对于没有高钙血症的溶骨性骨病， 研究者已经鉴定出小分子量化合物， 骨转移通过减少肿瘤细胞PTH-rP的转录和表达。 这类化合物是治疗溶骨性骨病变的候选药物 和常见恶性肿瘤患者的高钙血症。 拟定商业应用： 溶骨性骨病是癌症人群中的主要问题。它会导致 相当大的发病率和死亡率，一旦肿瘤细胞被安置在 骨骼，肿瘤是不可治愈的。 我们的目标是开发有效的药物， 抑制负责这一过程的主要分子机制， 特别是评估药物6-硫鸟嘌呤用于低剂量的这种效果。