Solomon A
J Clin Invest. 1978 Jan;61(1):97-108. doi: 10.1172/JCI108930.
The effect of corticosteroids and cytotoxic chemotherapeutic agents on the excretion of Bence Jones protein was determined for periods of 1 - 62 mo in 29 patients with multiple myeloma and Bence Jones proteinuria. The amount of protein present in 24-h urine specimens collected before treatment and at frequent intervals during monthly treatment cycles was determined. Striking variations occurred in the amount of Bence Jones protein excretion; these changes were especially evident when 75 mg of prednisone were given daily for 7 days as part of a monthly chemotherapeutic regimen. Within the 7-day period seven patients showed essentially no decrease (<25%), whereas 13 and 9 patients had a moderate decrease (25-75%) or a marked decrease (>75%), respectively, in Bence Jones proteinuria as compared to pre-treatment values. The decrease in excretion of Bence Jones protein during this period was attributed mainly to corticosteroid therapy because of the transient nature of the response in most patients and the lack of such response in three patients when the hormone was omitted. Biosynthetic studies were performed to determine in vitro the effect of corticosteroids on Bence Jones protein synthesis. Plasma cells obtained from the bone marrow of 13 patients were incubated in a growth medium containing (14)C-labeled lysine and isoleucine and prednisone in concentrations up to 240 mug/ml, and the amount of Bence Jones protein synthesized was determined immunochemically. No differences in viability were apparent between untreated and prednisone-treated cells. The type of response exhibited by an individual patient in the percent decrease of Bence Jones protein excreted after 7 days of prednisone treatment was comparable to the percent decrease in newly-synthesized Bence Jones protein secreted by tumor cells when cultured in the presence of prednisone at a concentration of 120 mug/ml. The marked differences in the capacity of corticosteroids to affect Bence Jones protein synthesis appear to reflect a biochemical heterogeneity among plasma cell neoplasms.
在29例患有多发性骨髓瘤和本-周蛋白尿的患者中,研究了皮质类固醇和细胞毒性化疗药物对本-周蛋白排泄的影响,观察期为1至62个月。测定了治疗前及每月治疗周期中频繁采集的24小时尿液标本中的蛋白含量。本-周蛋白排泄量出现显著变化;当作为每月化疗方案的一部分,每日给予75毫克泼尼松,持续7天时,这些变化尤为明显。在这7天内,7例患者的本-周蛋白尿基本无下降(<25%),而与治疗前值相比,13例和9例患者的本-周蛋白尿分别有中度下降(25 - 75%)或显著下降(>75%)。在此期间本-周蛋白排泄量的下降主要归因于皮质类固醇治疗,这是因为大多数患者的反应具有短暂性,且在3例患者停用激素时未出现这种反应。进行了生物合成研究,以在体外确定皮质类固醇对本-周蛋白合成的影响。从13例患者的骨髓中获取浆细胞,在含有(14)C标记的赖氨酸和异亮氨酸以及浓度高达240微克/毫升泼尼松的生长培养基中培养,通过免疫化学方法测定合成的本-周蛋白量。未处理细胞和泼尼松处理细胞之间的活力无明显差异。在泼尼松治疗7天后,个体患者本-周蛋白排泄量下降百分比所表现出的反应类型,与在浓度为120微克/毫升泼尼松存在下培养时肿瘤细胞分泌的新合成本-周蛋白下降百分比相当。皮质类固醇影响本-周蛋白合成能力的显著差异似乎反映了浆细胞瘤之间的生化异质性。