In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival.
In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival.
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DOI：
10.1038/bjc.2012.207
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发表时间：
2012-06-05
影响因子：
8.8
通讯作者：
Lancaster JM
中科院分区：
文献类型：
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作者：
Bicaku E;Xiong Y;Marchion DC;Chon HS;Stickles XB;Chen N;Judson PL;Hakam A;Gonzalez-Bosquet J;Wenham RM;Apte SM;Fulp W;Cubitt CL;Chen DT;Lancaster JM
卡铂和顺铂，单独或与紫杉醇联合，对卵巢癌（OVCA）具有相似的疗效，但表现出不同的毒性特征。我们描述了OVCA对这些药物反应的共同和独特的细胞途径，并分析了它们是否在OVCA生存中发挥作用。卵巢癌细胞系（n=36）用卡铂、顺铂、紫杉醇或卡铂-紫杉醇（CPTX）处理。对于每种细胞系，定量IC 50水平并进行处理前基因表达分析。对表现出表达/IC 50相关性（通过Pearson测量; P<0.01）的基因进行生物途径分析。一个独立的OVCA临床基因组数据集（n=142）进行了评价与代表的途径相关的临床特征。细胞系对卡铂、顺铂、紫杉醇和CPTX的敏感性分别与77、68、64和25条生物学通路的表达相关（P<0.01）。当比较药物组合时，我们发现了三个共同的途径。其中一条通路（“转录/CREB通路”）的表达与OVCA总生存率相关。转录/CREB通路（与OVCA细胞系铂敏感性和总生存期相关）的鉴定可以改善患者分层，以便使用当前疗法进行治疗，并合理选择靶向这些通路的未来OVCA治疗药物。
Carboplatin and cisplatin, alone or in combination with paclitaxel, have similar efficacies against ovarian cancer (OVCA) yet exhibit different toxicity profiles. We characterised the common and unique cellular pathways that underlie OVCA response to these drugs and analyse whether they have a role in OVCA survival. Ovarian cancer cell lines (n=36) were treated with carboplatin, cisplatin, paclitaxel, or carboplatin–paclitaxel (CPTX). For each cell line, IC50 levels were quantified and pre-treatment gene expression analyses were performed. Genes demonstrating expression/IC50 correlations (measured by Pearson; P<0.01) were subjected to biological pathway analysis. An independent OVCA clinico-genomic data set (n=142) was evaluated for clinical features associated with represented pathways. Cell line sensitivity to carboplatin, cisplatin, paclitaxel, and CPTX was associated with the expression of 77, 68, 64, and 25 biological pathways (P<0.01), respectively. We found three common pathways when drug combinations were compared. Expression of one pathway (‘Transcription/CREB pathway’) was associated with OVCA overall survival. The identification of the Transcription/CREB pathway (associated with OVCA cell line platinum sensitivity and overall survival) could improve patient stratification for treatment with current therapies and the rational selection of future OVCA therapy agents targeted to these pathways.
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影响因子：
4.1
作者：
Lizcano, JM;Morrice, N;Cohen, P
通讯作者：
Cohen, P
影响因子：
10.3
作者：
du Bois, A;Lück, HJ;Pfisterer, J
通讯作者：
Pfisterer, J
DOI：
10.1007/978-0-387-68969-2_16
发表时间：
2008-01-01
期刊：
OVARIAN CANCER: STATE OF THE ART AND FUTURE DIRECTIONS IN TRANSLATIONAL RESEARCH
影响因子：
--
作者：
Hajra, Karen M.;Tan, Lijun;Liu, J. Rebecca
通讯作者：
Liu, J. Rebecca
影响因子：
64.8
作者：
Bannister, AJ;Kouzarides, T
通讯作者：
Kouzarides, T
影响因子：
56.9
作者：
Bonni, A;Brunet, A;Greenberg, ME
通讯作者：
Greenberg, ME