MODULATION OF MYELOID TUMOR CELL GROWTH IN VITRO BY ESTROGEN AND PROGESTERONE

髓系白血病已被证明对 糖皮质激素疗法，一种被证明在 T细胞和B细胞白血病的治疗。我们已经在体外研究了 HL60、U937等几种髓系肿瘤细胞系的敏感性 对各种性激素，包括雌二醇，己烯雌酚(DES)， 黄体酮和睾丸素。所有被测试的细胞系都被证明是被杀死的 雌二醇、DES和黄体酮的含量从10-100微米不等。DES 事实证明这是最有效的。细胞死亡的方法似乎涉及到 胞质肿胀和胞核挤出，伴随DNA 退化。对氢化可的松和地塞米松敏感的白血病 作为T和B细胞白血病，也对DES，雌二醇和 孕激素。所有被测试的细胞系都被发现具有受体 雌二醇(由DES共享)，但不是孕酮受体 可能会被检测到。抗髓系药物有效性的体内研究 裸鼠体内的肿瘤异种移植生长正在进行中。 该项目已停止，但已导致CPB第一阶段高剂量试验 抗癌药物他莫昔芬(P.I.：Ray Bergan)

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 HL60 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 10-100uM. 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 not receptors for progesterone could be detected. In vivo studies of drug effectiveness against myeloid tumor xenograft growth in athymic mice are underway. This project has ceased but has led to a CPB Phase I trial of high dose tamoxifen as an anti-cancer agent (P.I.: Ray Bergan)