Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
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DOI：
10.1371/journal.pone.0005209
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Jones C
中科院分区：
文献类型：
--
作者：
Bax DA;Little SE;Gaspar N;Perryman L;Marshall L;Viana-Pereira M;Jones TA;Williams RD;Grigoriadis A;Vassal G;Workman P;Sheer D;Reis RM;Pearson AD;Hargrave D;Jones C
虽然儿童高级别胶质瘤在许多方面与成人类似，但似乎存在明显的临床和生物学差异。阻碍新靶向疗法开发的一个重要因素是相对缺乏来自儿童胶质瘤患者的细胞系，因为目前尚不清楚常用的成熟成人细胞系是否代表儿童肿瘤的潜在分子遗传学。我们已经进行了详细的分子和表型特征的一系列儿科高级别胶质瘤细胞系相比，常规使用的成人线。所有细胞系均增殖为贴壁单层并表达神经胶质标志物。拷贝数分析揭示了复杂的基因组，包括已知在核心胶质母细胞瘤信号通路中起关键作用的基因的扩增和缺失。表达谱鉴定了93个差异表达基因，这些基因能够区分成人和儿科高级别细胞系，包括许多激酶和与DNA完整性和免疫应答相关的协调基因组。这些数据表明，来自儿科患者的神经胶质瘤细胞系与来自成人的细胞系显示出关键的分子差异，其中一些是众所周知的，而另一些可能为原发性肿瘤的评估提供新的靶点。因此，我们提供了理论依据，并证明了使用儿科胶质瘤细胞系进行临床前和机制研究的实用性。
Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines. All lines proliferate as adherent monolayers and express glial markers. Copy number profiling revealed complex genomes including amplification and deletions of genes known to be pivotal in core glioblastoma signalling pathways. Expression profiling identified 93 differentially expressed genes which were able to distinguish between the adult and paediatric high grade cell lines, including a number of kinases and co-ordinated sets of genes associated with DNA integrity and the immune response. These data demonstrate that glioma cell lines derived from paediatric patients show key molecular differences to those from adults, some of which are well known, whilst others may provide novel targets for evaluation in primary tumours. We thus provide the rationale and demonstrate the practicability of using paediatric glioma cell lines for preclinical and mechanistic studies.
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雷帕霉素在I期试验中针对复发性PTEN缺陷型胶质母细胞瘤患者的抗肿瘤活性。
影响因子：
15.8
作者：
Cloughesy, Tim F.;Yoshimoto, Koji;Nghiemphu, Phioanh;Brown, Kevin;Dang, Julie;Zhu, Shaojun;Hsueh, Teli;Chen, Yinan;Wang, Wei;Youngkin, David;Liau, Linda;Martin, Neil;Becker, Don;Bergsneider, Marvin;Lai, Albert;Green, Richard;Oglesby, Tom;Koleto, Michael;Trent, Jeff;Horvath, Steve;Mischel, Paul S.;Mellinghoff, Ingo K.;Sawyers, Charles L.
通讯作者：
Sawyers, Charles L.
影响因子：
--
作者：
Krupp, W;Geiger, K;Froster, UG
通讯作者：
Froster, UG
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
影响因子：
14.9
作者：
Nygren AO;Ameziane N;Duarte HM;Vijzelaar RN;Waisfisz Q;Hess CJ;Schouten JP;Errami A
通讯作者：
Errami A
影响因子：
158.5
作者：
Hegi, ME;Diserens, A;Stupp, R
通讯作者：
Stupp, R