Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures.
Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures.
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DOI：
10.1186/1471-2407-8-313
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发表时间：
2008-10-29
期刊：
影响因子：
3.8
通讯作者：
Marcus, Lehnhardt
中科院分区：
文献类型：
--
作者：
Adrien, Daigeler;Ludger, Klein-Hitpass;Michael, Chromik Ansgar;Oliver, Mueller;Joerg, Hauser;Heinz-Herbert, Homann;Hans-Ulrich, Steinau;Marcus, Lehnhardt
阿霉素被认为是治疗脂肪肉瘤最有效的化疗药物之一；然而，回复率通常低于 30%，仍然令人失望。本研究旨在确定阿霉素治疗后脂肪肉瘤中基因表达的变化。术中收获 19 个原代人脂肪肉瘤细胞并进行细胞培养。将细胞与阿霉素一起孵育24小时，分离RNA并通过微阵列技术分析差异基因表达。不同样本中涉及细胞凋亡的多种基因上调和下调，揭示了 19 种原代肿瘤细胞培养物响应阿霉素治疗的异质表达模式。然而，超过 50% 的样本显示促凋亡基因上调，例如 TRAIL Receptor2、CDKN1A、GADD45A、FAS、CD40、PAWR、NFKBIA、IER3、PSEN1、RIPK2 和 CD44。抗凋亡基因 TNFAIP3、PEA15、Bcl2A1、NGFB 和 BIRC3 也上调。在用多柔比星治疗后，促凋亡 CD14、TIA1 和 ITGB2 在超过 50% 的肿瘤培养物中下调，抗凋亡 YWHAH 也是如此。尽管差异调节基因的数量与肿瘤分级以及较小程度的组织学亚型相关，但表达模式差异很大；然而，特别是在高级别肿瘤中，选定的凋亡基因的反应是相似的。先前描述的低级别脂肪肉瘤对阿霉素的低临床反应率与我们的结果相对应，基因表达水平只有很小的变化，并且关于不同肉瘤样品中单个基因的上调和下调的发现也存在分歧。
Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment. Cells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique. A variety of genes involved in apoptosis were up and down regulated in different samples revealing a heterogeneous expression pattern of the 19 primary tumor cell cultures in response to doxorubicin treatment. However, more than 50% of the samples showed up-regulation of pro-apoptotic genes such as TRAIL Receptor2, CDKN1A, GADD45A, FAS, CD40, PAWR, NFKBIA, IER3, PSEN1, RIPK2, and CD44. The anti-apoptotic genes TNFAIP3, PEA15, Bcl2A1, NGFB, and BIRC3 were also up-regulated. The pro-apoptotic CD14, TIA1, and ITGB2 were down-regulated in more than 50% of the tumor cultures after treatment with doxorubicin, as was the antiapoptotic YWHAH. Despite a correlation of the number of differentially regulated genes to the tumor grading and to a lesser extent histological subtype, the expression patterns varied strongly; however, especially among high grade tumors the responses of selected apoptosis genes were similar. The predescribed low clinical response rates of low grade liposarcoma to doxorubicin correspond to our results with only little changes on gene expression level and also divergent findings concerning the up- and down-regulation of single genes in the different sarcoma samples.
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影响因子：
11.2
作者：
Eliaz, RE;Nir, S;Szoka, FC
通讯作者：
Szoka, FC
影响因子：
6
作者：
Engström, K;Willén, H;Åman, P
通讯作者：
Åman, P
影响因子：
11.2
作者：
Baird, K;Davis, S;Meltzer, PS
通讯作者：
Meltzer, PS
影响因子：
6.2
作者：
Bassett, MD;Schuetze, SM;Rubin, BP
通讯作者：
Rubin, BP
影响因子：
8.4
作者：
Coosemans, A.;Nik, S. Amini;Amant, F.
通讯作者：
Amant, F.