MODULATION OF MYELOID TUMOR CELL GROWTH IN VITRO BY ESTROGEN/PROGESTERONE ANALOGS

雌激素/孕激素类似物对骨髓肿瘤细胞生长的体外调节

• 批准号: 3752351
• 负责人: L M NECKERS
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3752351
• 关键词: athymic mouse; cell growth regulation; clone cells; diethylstilbestrol; estradiol; estrogen receptors; hormone regulation /control mechanism; hormone related neoplasm /cancer; hormone therapy; human tissue; myelogenous leukemia; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neoplasm /cancer transplantation; neoplastic growth; nonhuman therapy evaluation; progesterone; sex hormone analog; testosterone; tissue /cell culture; xenotransplantation

Myeloid leukemias have proven to be particularly unresponsive to glucocorticoid therapy, a regimen shown to be quite useful in the treatment of T and B cell leukemias. We have investigated the in vitro sensitivity of several myeloid tumor cell lines, including HL6O and U937, to various sex steroids, including estradiol, diethylstilbestrol (DES), progesterone and testosterone. All cell lines tested proved to be killed by amounts of estradiol, DES and progesterone ranging from l0-l00uM. DES proved the most effective. The method of cell death appears to involve cytoplasmic swelling and extrusion of nuclei, accompanied by DNA degradation. Leukemias sensitive to hydrocortisone and dexamethasone, such as T and B cell leukemias, were also quite sensitive to DES, estradiol and progesterone. All cell lines tested were found to possess receptors for estradiol (which are shared by DES), but no receptors for progesterone could be detected. In vivo studies of drug effectiveness against myeloid tumor xenograft growth in athymic mice are underway.

髓系白血病已被证明对以下药物特别无反应： 糖皮质激素治疗，一种被证明对以下疾病非常有用的治疗方案 T和B细胞白血病的治疗。 我们在体外研究了 几种骨髓肿瘤细胞系的敏感性，包括 HL6O 和 U937， 各种性类固醇，包括雌二醇、己烯雌酚 (DES)、 黄体酮和睾酮。 所有测试的细胞系均被证明被杀死 雌二醇、DES和黄体酮的量范围为10-100μM。 DES 事实证明是最有效的。 细胞死亡的方法似乎涉及 细胞质膨胀和细胞核挤出，伴有 DNA 降解。 对氢化可的松和地塞米松敏感的白血病， 例如 T 细胞白血病和 B 细胞白血病，也对 DES 相当敏感， 雌二醇和黄体酮。 发现所有测试的细胞系都具有 雌二醇受体（DES 共享），但没有 可以检测到孕酮。 药物有效性的体内研究 对抗无胸腺小鼠骨髓肿瘤异种移植物生长的研究正在进行中。