NERVE GROWTH-FACTOR PREVENTS EXPERIMENTAL CISPLATIN NEUROPATHY
NERVE GROWTH-FACTOR PREVENTS EXPERIMENTAL CISPLATIN NEUROPATHY
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DOI：
10.1002/ana.410310114
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发表时间：
1992-01-01
影响因子：
11.2
通讯作者：
KESSLER, JA
中科院分区：
文献类型：
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作者：
APFEL, SC;AREZZO, JC;KESSLER, JA
顺铂是一种广泛使用的抗肿瘤药物，其剂量限制性毒性主要是大纤维感觉神经病变。预防这种神经病变将延长这种药物的有效性，允许更高的剂量和更长时间的治疗。我们在此报告，我们已经成功地建立了通过行为、生化和电生理技术测量的小鼠顺铂神经病变，并且皮下给药人重组神经生长因子（NGF）可以预防或延缓神经病变。顺铂降低了感觉神经节中肽递质（降钙素基因相关肽）的水平，减缓了尾部的神经传导，通过在旋转销子上保持平衡的能力来测量本体感觉受损。NGF联合给药似乎可以预防所有这些异常。人类中毒性神经病的发病时间明确，临床病程简单，神经对神经生长因子的可及性系统给予治疗，可能为神经生长因子的首次人体试验提供最佳的临床环境。
Cisplatin is a widely used antitumor agent, the dose-limiting toxicity of which is predominantly large-fiber sensory neuropathy. Prevention of such a neuropathy would extend the usefulness of this agent, allowing higher doses and longer periods of treatment. We report here that we have successfully established cisplatin neuropathy in mice measured by using behavioral, biochemical, and electrophysiological techniques, and that subcutaneous administration of human recombinant nerve growth factor (NGF) prevents or delays the neuropathy. Cisplatin administration reduced sensory ganglion levels of the peptide transmitter, calcitonin gene-related peptide, slowed nerve conduction in the tail and impaired proprioception as measured by the ability to balance on a rotating dowel. NGF coadministration appeared to prevent all these abnormalities. Treatment of the human toxic neuropathy with its well-established time of onset, simple clinical course, and the accessibility of nerve to NGF administered systemically may provide the best clinical setting for the first human trials of NGF.