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Nicotinamide for skin cancer chemoprevention: effects of nicotinamide on melanoma in vitro and in vivo.
Photochemical & Photobiological Sciences ( IF 3.1 ) Pub Date : 2020-01-16 , DOI: 10.1039/c9pp00388f
Rashi Malesu 1 , Andrew J Martin , J Guy Lyons , Richard A Scolyer , Andrew C Chen , Catriona A McKenzie , Jason Madore , Gary M Halliday , Diona L Damian
Affiliation  

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.

中文翻译:

烟酰胺用于皮肤癌的化学预防:烟酰胺在体内外对黑色素瘤的作用。

烟酰胺(NAM)是维生素B3的酰胺形式,在暴露于紫外线(UVR)后会补充细胞能量,从而增强DNA修复并降低UVR的免疫抑制作用。NAM可以降低高危人群的光化性角化病和新的角质形成细胞癌,但对黑素瘤的作用尚不清楚。通过免疫组织化学检查了ONTRAC皮肤癌化学预防试验(口服烟酰胺减少光化性癌症)中NAM或安慰剂引起的黑素瘤。还研究了NAM(50μM,5 mM和20 mM)对四种人类黑素瘤细胞系的生存能力,增殖和侵袭性以及在有和无紫外线照射下对两种人类黑素细胞系的生存能力和增殖的影响。50μMNAM不会影响黑色素瘤或黑色素细胞细胞系的活力,增殖或侵袭,而浓度太高而无法在体内达到,则降低了活力和增殖。烟酰胺在体外并未增强黑色素瘤的生存力,增殖或侵袭性,从而为其在高危患者的临床试验中使用的安全性提供了更多的信心。与安慰剂相比,NAM产生的黑色素瘤的周膜和肿瘤浸润性CD4 +和CD8 +淋巴细胞显着增加。鉴于烟酰胺对角质形成细胞癌的化学预防活性,其对黑素细胞的DNA修复增强作用以及现在对肿瘤浸润淋巴细胞的潜在增强作用以及对黑素瘤细胞生长和增殖的不利影响,现在表明了烟酰胺可用于黑素瘤化学预防的临床试验。
更新日期:2020-02-19
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