In vivo study of ADH-1 in combination with melphalan for treatment of melanoma. Homo sapiens

To identify patterns of change in gene expression that correlated with drug treatment (saline control, ADH-1 alone, melphalan alone and ADH-1 plus melphalan) in our animal model of regional therapy for extremity melanoma we evaluated gene expression using microarray genechips and a Pearson correlation analysis. Genes were ranked according to the degree to which expression correlated with systemic ADH-1 treatment alone or in combination with regional melphalan. Tissue samples were harvested at 4, 24 and 48 hours after treatment with melphalan. Specific cellular pathways associated with drug treatment were identified using gene set enrichment analysis (GSEA). Keywords: time course; chemotherapy; melanoma; melphalan; N-cadherin; ADH-1 Overall design: Sample size was 2 rats for each drug treatment group at both the 4 and 24 hour time points. At the 48 hour time point sample size was 1 rat for each drug treatment group. ADH-1 treatment preceded melphalan by 1 hour. ADH-1 treatment was repeated at 24 and 48 hrs. Tissue was harvested for RNA analysis at 4, 24 and 48 hours after completion of isolated limb infusion with melphalan (and 1 hour after an ADH-1 dose).

为明确我们构建的肢体黑色素瘤区域治疗动物模型中，与不同药物治疗方案（生理盐水对照组、单独ADH-1给药组、单独美法仑（melphalan）给药组以及ADH-1联合美法仑给药组）相关的基因表达变化模式，我们采用基因芯片（microarray genechips）开展基因表达检测，并进行皮尔逊相关分析。我们依据基因表达与单独系统性ADH-1治疗，或ADH-1联合区域性美法仑治疗的相关性强弱对基因进行排序。分别于美法仑给药后的4、24及48小时采集组织样本。借助基因集富集分析（gene set enrichment analysis, GSEA），我们识别出与药物治疗相关的特定细胞通路。关键词：时间进程；化疗；黑色素瘤；美法仑；N-钙粘蛋白（N-cadherin）；ADH-1 整体实验设计：在4小时与24小时时间点，各药物治疗组的样本量均为2只大鼠；在48小时时间点，各药物治疗组样本量为1只大鼠。ADH-1给药较美法仑提前1小时进行，并于24小时和48小时重复给予ADH-1治疗。组织样本采集于美法仑孤立肢体灌注完成后的4、24及48小时（即末次ADH-1给药后1小时），用于RNA分子分析。