1. NCI60细胞系列及一些常用数据库介绍 谢丽

2. NCI-60细胞系列简介 自1990年已用于筛选超过100，000个化合物
Developmental Therapeutics Program of the National Cancer Institute
NCI60 screening and secondary testing Nat Rev Cancer 2006

3. NCI60细胞系列组织来源 Leukemias Melanomas Cancers of ovarian Cancers of renal
Cancers of breast
Cancers of prostate
Cancers of colon
Cancers of lung
Cancers of CNS origin

5. NCI60 screening and secondary testing
Compound suppliers provide information about the biological rationale and chemical structures of
compounds to be submitted for screening (see figure). Structures are examined and duplicates of
previously screened compounds or representatives of well-studied chemical classes are rejected.
The accepted samples are sent to a central repository and then to testing, either in a pre-screen
model or directly to the US National Cancer Institute (NCI) 60 anticancer drug screen (NCI60). The
results are then examined by a committee of scientists, and compounds that show a pattern of
interest are retested. The Biological Evaluation Committee then considers the activity in the context
of chemical and other available information. Compounds that have reproducible patterns of
interest, usually those with a relatively unique, COMPARE-negative, profile of activity are initially
tested in an in vivo hollow-fibre assay. Compounds that show significant activity in this model are
then tested further in xenograft assays. Compounds with significant activity, and usually a lead as to
their mechanism of action, can be presented to the Drug Development Group as candidates for NCI
clinical development. Data returned to the compound supplier can be used for extramural
development or licensing. DTP, Developmental Therapeutics Program

7. sulforhodamine B assay 测GI50
原理：A means of measuring total biomass by staining cellular proteins with the Sulforhodamine B.
检测流程：
清洗细胞 染色 溶解
吸光值测定

8. 基因各个水平的profile已经非常完备
DNA
RNA
Protein
Chromosome
MiRNA
FREE

10. 相关文献
A gene expression database for the molecular pharmacology of cancer. Nat Genet 2000;24:236– 44.
Chemosensitivity prediction by transcriptional profiling. Proc Natl Acad Sci U S A 2001; 98:10787–92.
Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Res 2004;64:4294–301.
Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet 2000;24: 227–35.
Transcript and protein expression profiles of the NCI-60 cancer cell panel: an integromic microarray study. Mol Cancer Ther 2007;6:820–32.
A protein expression database for the molecular pharmacology of cancer. Electrophoresis 1997; 18:647–53.
Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays. Proc Natl Acad Sci U S A 2003;100:14229–34.
Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling. Cancer Res 2003;63:5243–50.
Transcriptomic analysis of the NCI-60 cancer cell lines. C R Biol 2003;326:909–20.
Mutation analysis of 24 known cancer genes in the NCI-60 cell line set. Mol Cancer Ther 2006;5:2606–12.
Integrating data on DNA copy number with gene expression levels and drug sensitivities in the NCI-60 cell line panel. Mol Cancer Ther 2006;5:853–67.
Karyotypic ‘‘state’’ as a potential determinant for anticancer drug discovery. Proc Natl Acad Sci U S A 2005;102:2964–9.
Karyotypic complexity of the NCI-60 drug-screening panel. Cancer Res 2003;63:8634–47.
Drugs aimed at targeting characteristic karyotypic phenotypes of cancer cells. Mol Cancer Ther 2005;4:1559–68.
Spotlight on molecular profiling: ‘‘integromic’’ analysis of the NCI-60 cancer cell lines. Mol Cancer Ther 2006;5:2601–5.
Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells. Mol Cancer Ther 2006;5:2613–23.
Predicting Cancer Drug Response by Proteomic Profiling. Clin Cancer Res Aug 1;12(15):
Prediction of Broad Spectrum Resistance of Tumors towards Anticancer Drugs. Clin Cancer Res Apr 15;14(8):
Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells. Mol Cancer Ther Feb;6(2):
Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res Mar 15;67(6):

11. 重要的结论 mRNA表达和蛋白表达水平具有40-70％左右的相关性 细胞对于药物的敏感性与细胞的组织学来源关系不大，与细胞的增殖水平有关
一些TCM来源的化合物能够对广谱多药耐药细胞仍然有效，提示作用机制的多靶点
mRNA profiling比miRNA profiling更好的鉴别组织来源

12. DNA copy number

13. 基于NCI-60的基因组合用于预测药物疗效

14. 基于NCI-60的药物靶点预测

15. 从信号通路角度分析DOC敏感性 相关基因

16. 用NCI-60筛选与药物疗效最相关的miRNA

17. CDH1甲基化

18. Mutaion

19. 谢谢:)