Assessment of all-trans retinoic acid (ATRA) efficacy as a single agent in primary lymphoid neoplasia.
Assessment of all-trans retinoic acid (ATRA) efficacy as a single agent in primary lymphoid neoplasia.
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全反式视黄酸（ATRA）作为单药治疗原发性淋巴肿瘤的疗效评估。
DOI：
10.1007/bf02785845
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Rudikoff,S
中科院分区：
文献类型：
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作者：
Swaminathan,N;Lopez-Berestein,G;Rudikoff,S
全反式维甲酸（ATRA）目前被广泛用于治疗急性早幼粒细胞白血病，并正在对其他几种恶性肿瘤进行体外和体内试验。以前，ATRA已被证明可以抑制体外建立的人骨髓瘤细胞系以及培养的患者原代骨髓瘤细胞的生长。ATRA通过下调骨髓瘤细胞表面的IL-6受体-α或gp 130发挥作用。然而，尽管它对骨髓瘤细胞的体外效应，ATRA治疗晚期多发性骨髓瘤（MM）患者迄今为止在很大程度上是无效的。在目前的研究中，我们已经评估了ATRA治疗对原发性小鼠浆细胞瘤的疗效，这是一种人类MM的动物模型。这些肿瘤在降植烷致敏的BALB/c小鼠中通过注射含有v-raf/v-myc的逆转录病毒诱导约50%的发病率，并且是IL-6依赖的。使用这种动物模型，我们评估了ATRA作为治疗剂在疾病发展的两个早期时间点对原发性肿瘤的影响。ATRA在脂质体囊泡（ATRAGEN®）中给药，因为脂质体-ATRA已被证明可以绕过肝微粒体的清除机制，而肝微粒体的清除机制通常与游离ATRA一起发生。此外，先前显示ATRAGEN®在小鼠中的毒性低于游离ATRA。在病毒注射后第25天或第45天开始施用ATRAGEN®，并且每周两次持续8-11周。与对照动物相比，在任一时间点开始的ATRAGEN®给药均未改变浆细胞肿瘤的发生率或潜伏期。这些结果表明，ATRA可能不是治疗早期MM的唯一有效疗法。
All-transretinoic acid (ATRA) is currently widely used in the therapy of acute promyelocytic leukimia and is being testedin vitroandin vivoon several other malignancies. Previously ATRA has been shown to inhibit the growthin vitro, of established human myeloma cell lines as well as cultured primary myeloma cells from patients. ATRA acts by down-regulating IL-6-receptor-alpha or gp130 on the surface of the myeloma cells. However, despite itsin vitroeffects on myeloma cells, ATRA therapy on advanced stage multiple myeloma (MM) patients has so far largely been ineffective. In current studies, we have assessed the efficacy of ATRA therapy against primary murine plasma cell tumors, which are an animal model for human MM. These tumors are induced at about 50% incidence in pristane-primed BALB/c mice by injection ofv-raf/v-myc-containing retroviruses and are IL-6 dependent. Using this animal model, we assessed the effect of ATRA as a therapeutic agent against primary tumors at two early time points in disease development. ATRA was administered in liposomal vesicles (ATRAGEN®), since liposomal-ATRA has been shown to circumvent clearance mechanisms by hepatic microsomes, which normally occur with free ATRA. In addition, ATRAGEN® was previously shown to be less toxic in mice than free ATRA. ATRAGEN® was administered beginning on day 25 or day 45 after virus injection and continued twice weekly for 8–11 weeks. ATRAGEN® administration begun at either time point did not alter the incidence or the latency of plasma cell tumors compared with control animals. These results suggest that ATRA may not be an effective sole therapy against early MM.