Eberle Jürgen, Fecker Lothar F, Hossini Amir M, Kurbanov Bahtier M, Fechner Henry
Department of Dermatology and Allergy, Skin Cancer Center, Charité- Universitätsmedizin Berlin, Berlin, Germany.
Exp Dermatol. 2008 Jan;17(1):1-11. doi: 10.1111/j.1600-0625.2007.00655.x.
In the last decades melanoma incidence has been increasing worldwide, while mortality remained on a high level. Until now, there is no suitable therapy for metastasized melanoma, which could lead to a significant increase in overall survival. Apoptosis deficiency is supposed to be a critical factor for therapy resistance, and previous work has characterized the basic mechanisms of apoptosis regulation in melanoma. Genes and strategies suitable for efficient induction of apoptosis in melanoma cells were identified, which are based on proapoptotic Bcl-2 proteins (Bcl-x(S), Bcl-x(AK), Bik/Nbk and Bax) as well as on tumor necrosis factor (TNF)-related death ligands (CD95L/Fas ligand and TNF-related apoptosis-inducing ligand, TRAIL). Proapoptotic genes may be employed in improved gene therapeutic strategies, based on conditional oncolytic adenoviral vectors.
在过去几十年中，黑色素瘤的发病率在全球范围内一直在上升，而死亡率仍处于较高水平。到目前为止，对于转移性黑色素瘤尚无合适的治疗方法，这可能导致总体生存率显著提高。细胞凋亡缺陷被认为是治疗耐药的关键因素，先前的研究已经阐明了黑色素瘤中细胞凋亡调控的基本机制。已鉴定出适用于有效诱导黑色素瘤细胞凋亡的基因和策略，这些基因和策略基于促凋亡Bcl-2蛋白（Bcl-x(S)、Bcl-x(AK)、Bik/Nbk和Bax）以及肿瘤坏死因子（TNF）相关死亡配体（CD95L/Fas配体和TNF相关凋亡诱导配体TRAIL）。基于条件性溶瘤腺病毒载体，促凋亡基因可用于改进的基因治疗策略。
