Mishkin S Y, Farber E, Ho R, Mulay S, Mishkin S
Eur J Cancer Clin Oncol. 1985 May;21(5):615-23. doi: 10.1016/0277-5379(85)90090-2.
Hepatic hyperplastic nodules (HHNs) induced by the 'resistant hepatocyte method' of Solt et al. were studied as an experimental prototype of oral contraceptive-related tumors. Cytoplasmic estrogen receptors were present in all HHNs harvested and their concentration was always less than that in normal liver. No specific cytoplasmic progestin receptors could be measured in the above tumor or liver specimens. The long-term administration of estradiol-17 beta (4.8-24.0 micrograms/day) resulted in the death of all but one of 20 animals prior to termination at 10 months. Tamoxifen (0.25-2.5 mg biweekly), which did not lead to excess mortality, decreased HHN grade (proportion of liver slice occupied by HHN) and inhibited malignant transformation. Combination therapy with single-dose estradiol-17 beta (4.8 micrograms/day) and various doses of tamoxifen (0.25-2.5 mg biweekly) in most cases reduced mortality, HHN grade and malignant transformation. Cytoplasmic progestin receptors were absent and estrogen receptors were either undetectable or present in low concentrations in hepatic tumors harvested at the time of termination. Our results indicated that HHNs are hormone-dependent and that malignant transformation can be inhibited by tamoxifen alone or in combination with estradiol-17 beta.
对索尔等人采用“抗性肝细胞法”诱导产生的肝增生结节（HHN）进行了研究，将其作为口服避孕药相关肿瘤的实验原型。在所有采集的HHN中均存在细胞质雌激素受体，其浓度始终低于正常肝脏中的浓度。在上述肿瘤或肝脏标本中未检测到特异性细胞质孕激素受体。长期给予雌二醇-17β（4.8 - 24.0微克/天）导致20只动物中有19只在10个月终止实验前死亡。他莫昔芬（每两周0.25 - 2.5毫克）不会导致额外死亡，可降低HHN分级（肝脏切片中HHN所占比例）并抑制恶性转化。在大多数情况下，单剂量雌二醇-17β（4.8微克/天）与不同剂量他莫昔芬（每两周0.25 - 2.5毫克）联合治疗可降低死亡率、HHN分级和恶性转化。在实验终止时采集的肝肿瘤中不存在细胞质孕激素受体，雌激素受体要么无法检测到，要么浓度很低。我们的结果表明，HHN是激素依赖性的，他莫昔芬单独使用或与雌二醇-17β联合使用可抑制恶性转化。
