Tulley P N, Neale M, Jackson D, Chana J S, Grover R, Cree I, Grobbelaar A O, Wilson G D
RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, UK.
Br J Ophthalmol. 2004 Dec;88(12):1563-7. doi: 10.1136/bjo.2003.033498.
BACKGROUND/AIM: Interferons (IFN) are currently being used to treat melanoma, including some patients with uveal melanoma. IFN is thought to inhibit tumour growth through downregulation of the c-myc oncogene; the overexpression of which has been shown to be associated with resistance in cell lines. The aim of this study was to investigate the relation between c-myc gene expression and IFN sensitivity in a series of uveal melanomas in a short term chemosensitivity assay.
Tumours from 45 patients with uveal melanoma who had undergone enucleation were studied. The ATP chemosensitivity assay was used to study sensitivity to IFN-alpha-2b in freshly isolated cells from each tumour. Flow cytometry was used to assess c-myc expression in formalin fixed material from the primary specimens.
There was a wide range of IFN sensitivity between the specimens whereas c-myc expression was universal and present in 80% of the tumour cells in 80% of the specimens. Higher c-myc expression was associated with IFN-alpha resistance as measured by the maximum percentage of inhibition (p = 0.05) and there was a trend with the IFN sensitivity index (p = 0.07).
These results demonstrate that tumours with high c-myc expression are also associated with IFN resistance. Future research is required to explore the potential of c-myc gene manipulation combined with IFN therapy.
背景/目的：干扰素（IFN）目前被用于治疗黑色素瘤，包括一些葡萄膜黑色素瘤患者。IFN被认为通过下调c-myc癌基因来抑制肿瘤生长；c-myc癌基因的过表达已被证明与细胞系中的耐药性有关。本研究的目的是在短期化学敏感性试验中，研究一系列葡萄膜黑色素瘤中c-myc基因表达与IFN敏感性之间的关系。
研究了45例接受眼球摘除术的葡萄膜黑色素瘤患者的肿瘤。ATP化学敏感性试验用于研究每个肿瘤新鲜分离细胞对IFN-α-2b的敏感性。流式细胞术用于评估原发标本福尔马林固定材料中的c-myc表达。
各标本之间的IFN敏感性差异很大，而c-myc表达普遍存在，80%的标本中80%的肿瘤细胞有该表达。通过最大抑制百分比测量，较高的c-myc表达与IFN-α耐药性相关（p = 0.05），并且与IFN敏感性指数存在一定趋势（p = 0.07）。
这些结果表明，c-myc高表达的肿瘤也与IFN耐药性有关。未来需要进一步研究探索c-myc基因操作联合IFN治疗的潜力。
