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Nicotinamide for skin cancer chemoprevention: effects of nicotinamide on melanoma in vitro and in vivo.

烟酰胺用于皮肤癌化学预防: 烟酰胺在体内外对黑色素瘤的影响。

  • 影响因子:2.59
  • DOI:10.1039/c9pp00388f
  • 作者列表:"Malesu R","Martin AJ","Lyons JG","Scolyer RA","Chen AC","McKenzie CA","Madore J","Halliday GM","Damian DL
  • 发表时间:2020-02-19
Abstract

:Nicotinamide (NAM), an amide form of vitamin B3, replenishes cellular energy after ultraviolet radiation (UVR) exposure, thereby enhancing DNA repair and reducing UVR's immunosuppressive effects. NAM reduces actinic keratoses and new keratinocyte cancers in high risk individuals, but its effects on melanoma are unknown. Melanomas arising on NAM or placebo within the ONTRAC skin cancer chemoprevention trial (Oral Nicotinamide To Reduce Actinic Cancer) were examined by immunohistochemistry. The effects of NAM (50 μM, 5 mM and 20 mM) on the viability, proliferation and invasiveness of four human melanoma cell lines and on the viability and proliferation of two human melanocyte lines, with and without UV irradiation were also investigated. 50 μM NAM did not affect viability, proliferation or invasion of melanoma or melanocyte cell lines, whereas concentrations too high to be achievable in vivo reduced viability and proliferation. Nicotinamide did not enhance melanoma viability, proliferation or invasiveness in vitro, providing additional confidence in its safety for use in clinical trials in high risk patients. Peritumoral and tumour infiltrating CD4+ and CD8+ lymphocytes were significantly increased in melanomas arising on NAM compared to those arising on placebo. Given the chemopreventive activity of nicotinamide against keratinocyte cancers, its DNA repair enhancing effects in melanocytes and now its potential enhancement of tumour-infiltrating lymphocytes and lack of adverse effects on melanoma cell growth and proliferation, clinical trials of nicotinamide for melanoma chemoprevention are now indicated.

摘要

: 烟酰胺 (NAM) 是维生素B3 的一种酰胺形式,在紫外线辐射 (UVR) 暴露后补充细胞能量,从而增强DNA修复并降低UVR的免疫抑制作用。NAM减少高危个体的光化性角化病和新的角质形成细胞癌,但其对黑色素瘤的影响尚不清楚。通过免疫组化检查ONTRAC皮肤癌化学预防试验 (口服烟酰胺减少光化性癌) 中NAM或安慰剂引起的黑色素瘤。NAM (5 0 μ m、 5 mM和 20 mM) 对四种人黑色素瘤细胞系的活力、增殖和侵袭力的影响以及对两种人黑色素细胞系的活力和增殖的影响,还研究了有无紫外线照射。50 μ m NAM不影响黑色素瘤或黑素细胞系的活力、增殖或侵袭,而浓度过高无法在体内实现,降低了活力和增殖。烟酰胺在体外没有增强黑色素瘤的活力、增殖或侵袭性,为其在高危患者临床试验中的安全性提供了额外的信心。与安慰剂组相比,NAM组黑色素瘤的瘤周和肿瘤浸润CD4 + 和CD8 + 淋巴细胞显著增加。鉴于烟酰胺对角质形成细胞癌的化学预防活性,其在黑素细胞中的DNA修复增强作用,现在其潜在的肿瘤浸润淋巴细胞的增强作用以及对黑素瘤细胞生长和增殖缺乏不良影响,现在指出烟酰胺用于黑色素瘤化学预防的临床试验。

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影响因子:0.96
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皮肤肿瘤方向

皮肤肿瘤是发生在皮肤的细胞增生性疾病,是一种常见病。发生于皮内或皮下组织的新生物,种类很多,临床上分良性肿瘤和恶性肿瘤。恶性肿瘤可以不断增殖,引起转移,威胁生命,称为皮肤癌。

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