© 1991 by Oxford University Press
Journal of the National Cancer Institute, Vol. 83, No. 11, 757-766,
June 5, 1991
© 1991 Oxford University Press
Feasibility of a High-Flux Anticancer Drug Screen Using a Diverse Panel of Cultured Human Tumor Cell Lines
Sponsored in pan by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, under conuact NOICO-23910 with Program Resources. Inc.
Program Resources, Inc., NCI-Frederick Cancer Research and Development Center Frederick, Md.
Developmental Therapeutics Program, Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center Frederick, Md.
*Correspondence to: Anne Monks, PhD, NCl-Frederick Cancer Research and Development Center, Bldg 432, Rm 232, Frederick, MD 21701-1013
We describe here the development and implementation of a pilot-scale, in vitro, anticancer drug screen utilizing a panel of 60 human tumor cell lines organized into subpanels representing leukemia, melanoma, and cancers of the lung, colon, kidney, ovary, and central nervous system. The ultimate goal of this disease-oriented screen is to facilitate the discovery of new compounds with potential cell line-specific and/or subpanel-specific antitumor activity. In the current screening protocol, each cell line is inoculated onto microtiter plates, then preincubated for 2428 hours. Subsequently, test agents are added in five 10-fold dilutions and the culture is incubated for an additional 48 hours. For each test agent, a dose-response profile is generated. End-point determinations of the cell viability or cell growth are performed by in situ fixation of cells, followed by staining with a protein-binding dye, sulforhodamine B (SRB). The SRB binds to the basic amino acids of cellular macromolecules; the solubilized stain is measured spectrophotometrically to determine relative cell growth or viability in treated and untreated cells. Following the pilot screening studies, a screening rate of 400 compounds per week has been consistently achieved.
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J. L. Grem, K. D. Danenberg, K. Behan, A. Parr, L. Young, P. V. Danenberg, D. Nguyen, J. Drake, A. Monks, and C. J. Allegra Thymidine Kinase, Thymidylate Synthase, and Dihydropyrimidine Dehydrogenase Profiles of Cell Lines of the National Cancer Institute's Anticancer Drug Screen Clin. Cancer Res., April 1, 2001; 7(4): 999 - 1009. [Abstract] [Full Text] |
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I. Meinhold-Heerlein, F. Stenner-Liewen, H. Liewen, S. Kitada, M. Krajewska, S. Krajewski, J. M. Zapata, A. Monks, D. A. Scudiero, T. Bauknecht, et al. Expression and Potential Role of Fas-Associated Phosphatase-1 in Ovarian Cancer Am. J. Pathol., April 1, 2001; 158(4): 1335 - 1344. [Abstract] [Full Text] [PDF] |
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S. D. Mertins, T. G. Myers, M. Hollingshead, D. Dykes, E. Bodde, P. Tsai, C. A. Jefferis, R. Gupta, W. M. Linehan, M. Alley, et al. Screening for and Identification of Novel Agents Directed at Renal Cell Carcinoma Clin. Cancer Res., March 1, 2001; 7(3): 620 - 633. [Abstract] [Full Text] |
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A. R. Salomon, D. W. Voehringer, L. A. Herzenberg, and C. Khosla Understanding and exploiting the mechanistic basis for selectivity of polyketide inhibitors of F0F1-ATPase PNAS, December 19, 2000; 97(26): 14766 - 14771. [Abstract] [Full Text] [PDF] |
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R. Perez-Soler, B. Kemp, Q. P. Wu, L. Mao, J. Gomez, A. Zeleniuch-Jacquotte, H. Yee, J. S. Lee, J. Jagirdar, and Y. H. Ling Response and Determinants of Sensitivity to Paclitaxel in Human Non-Small Cell Lung Cancer Tumors Heterotransplanted in Nude Mice Clin. Cancer Res., December 1, 2000; 6(12): 4932 - 4938. [Abstract] [Full Text] |
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S. A. Amundson, T. G. Myers, D. Scudiero, S. Kitada, J. C. Reed, and A. J. Fornace Jr. An Informatics Approach Identifying Markers of Chemosensitivity in Human Cancer Cell Lines Cancer Res., November 1, 2000; 60(21): 6101 - 6110. [Abstract] [Full Text] |
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S. S. Palakurthi, R. Fluckiger, H. Aktas, A. K. Changolkar, A. Shahsafaei, S. Harneit, E. Kilic, and J. A. Halperin Inhibition of Translation Initiation Mediates the Anticancer Effect of the n-3 Polyunsaturated Fatty Acid Eicosapentaenoic Acid Cancer Res., June 1, 2000; 60(11): 2919 - 2925. [Abstract] [Full Text] [PDF] |
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M. J. Newman, J. C. Rodarte, K. D. Benbatoul, S. J. Romano, C. Zhang, S. Krane, E. J. Moran, R. T. Uyeda, R. Dixon, E. S. Guns, et al. Discovery and Characterization of OC144-093, a Novel Inhibitor of P-Glycoprotein-mediated Multidrug Resistance Cancer Res., June 1, 2000; 60(11): 2964 - 2972. [Abstract] [Full Text] [PDF] |
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D. R.A. Mans, A. B. da Rocha, and G. Schwartsmann Anti-Cancer Drug Discovery and Development in Brazil: Targeted Plant Collection as a Rational Strategy to Acquire Candidate Anti-Cancer Compounds Oncologist, June 1, 2000; 5(3): 185 - 198. [Abstract] [Full Text] |
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C. P. Webb, C. D. Hose, S. Koochekpour, M. Jeffers, M. Oskarsson, E. Sausville, A. Monks, and G. F. Vande Woude The Geldanamycins Are Potent Inhibitors of the Hepatocyte Growth Factor/Scatter Factor-Met-Urokinase Plasminogen Activator-Plasmin Proteolytic Network Cancer Res., January 1, 2000; 60(2): 342 - 349. [Abstract] [Full Text] |
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H.-M. Koo, M. J. McWilliams, W. G. Alvord, and G. F. Vande Woude Ras Oncogene-Induced Sensitization to 1-{{beta}}-D-Arabinofuranosylcytosine Cancer Res., December 1, 1999; 59(24): 6057 - 6062. [Abstract] [Full Text] [PDF] |
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A. Kubo, K. Nakagawa, R. K. Varma, N. K. Conrad, J. Q. Cheng, W.-C. Lee, J. R. Testa, B. E. Johnson, F. J. Kaye, and M. J. Kelley The p16 Status of Tumor Cell Lines Identifies Small Molecule Inhibitors Specific for Cyclin-dependent Kinase 4 Clin. Cancer Res., December 1, 1999; 5(12): 4279 - 4286. [Abstract] [Full Text] [PDF] |
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W. Nieves-Neira, M. I. Rivera, G. Kohlhagen, M. L. Hursey, P. Pourquier, E. A. Sausville, and Y. Pommier DNA Protein Cross-Links Produced by NSC 652287, a Novel Thiophene Derivative Active Against Human Renal Cancer Cells Mol. Pharmacol., September 1, 1999; 56(3): 478 - 484. [Abstract] [Full Text] |
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S. Jariyawat, T. Sekine, M. Takeda, N. Apiwattanakul, Y. Kanai, S. Sophasan, and H. Endou The Interaction and Transport of beta -Lactam Antibiotics with the Cloned Rat Renal Organic Anion Transporter 1 J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 672 - 677. [Abstract] [Full Text] |
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I. Naasani, H. Seimiya, T. Yamori, and T. Tsuruo FJ5002: A Potent Telomerase Inhibitor Identified by Exploiting the Disease-oriented Screening Program with COMPARE Analysis Cancer Res., August 1, 1999; 59(16): 4004 - 4011. [Abstract] [Full Text] [PDF] |
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T. Yamori, A. Matsunaga, S. Sato, K. Yamazaki, A. Komi, K. Ishizu, I. Mita, H. Edatsugi, Y. Matsuba, K. Takezawa, et al. Potent Antitumor Activity of MS-247, a Novel DNA Minor Groove Binder, Evaluated by an in Vitro and in Vivo Human Cancer Cell Line Panel Cancer Res., August 1, 1999; 59(16): 4042 - 4049. [Abstract] [Full Text] [PDF] |
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H.-M. Koo, M. Gray-Goodrich, G. Kohlhagen, M. J. McWilliams, M. Jeffers, A. Vaigro-Wolff, W. G. Alvord, A. Monks, K. D. Paull, Y. Pommier, et al. The ras Oncogene-Mediated Sensitization of Human Cells to Topoisomerase II Inhibitor-Induced Apoptosis J Natl Cancer Inst, February 3, 1999; 91(3): 236 - 244. [Abstract] [Full Text] [PDF] |
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M. Alvarez, R. Robey, V. Sandor, K. Nishiyama, Y. Matsumoto, K. Paull, S. Bates, and T. Fojo Using the National Cancer Institute Anticancer Drug Screen to Assess the Effect of MRP Expression on Drug Sensitivity Profiles Mol. Pharmacol., November 1, 1998; 54(5): 802 - 814. [Abstract] [Full Text] |
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V. Fischer, A. Rodríguez-Gascón, F. Heitz, R. Tynes, C. Hauck, D. Cohen, and A. E. M. Vickers The Multidrug Resistance Modulator Valspodar (PSC 833) Is Metabolized by Human Cytochrome P450 3A. Implications for Drug-Drug Interactions and Pharmacological Activity of the Main Metabolite Drug Metab. Dispos., August 1, 1998; 26(8): 802 - 811. [Abstract] [Full Text] |
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S. Dhar, J. Gullbo, K. Nilsson, P. Nygren, and R. Larsson A Nonclonogenic Cytotoxicity Assay Using Primary Cultures of Patient Tumor Cells for Anticancer Drug Screening J Biomol Screen, April 1, 1998; 3(3): 207 - 216. [Abstract] [PDF] |
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L. A. Mickley, J.-S. Lee, Z. Weng, Z. Zhan, M. Alvarez, W. Wilson, S. E. Bates, and T. Fojo Genetic Polymorphism in MDR-1: A Tool for Examining Allelic Expression in Normal Cells, Unselected and Drug-Selected Cell Lines, and Human Tumors Blood, March 1, 1998; 91(5): 1749 - 1756. [Abstract] [Full Text] [PDF] |
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L. M. Shi, T. G. Myers, Y. Fan, P. M. O'Connor, K. D. Paull, S. H. Friend, and J. N. Weinstein Mining the National Cancer Institute Anticancer Drug Discovery Database: Cluster Analysis of Ellipticine Analogs with p53-Inverse and Central Nervous System-Selective Patterns of Activity Mol. Pharmacol., February 1, 1998; 53(2): 241 - 251. [Abstract] [Full Text] |
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P. Verdier-Pinard, J.-Y. Lai, H.-D. Yoo, J. Yu, B. Marquez, D. G. Nagle, M. Nambu, J. D. White, J. R. Falck, W. H. Gerwick, et al. Structure-Activity Analysis of the Interaction of Curacin A, the Potent Colchicine Site Antimitotic Agent, with Tubulin and Effects of Analogs on the Growth of MCF-7 Breast Cancer Cells Mol. Pharmacol., January 1, 1998; 53(1): 62 - 76. [Abstract] [Full Text] |
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S. E. Bates, W. H. Wilson, A. T. Fojo, M. Alvarez, Z. Zhan, J. Regis, R. Robey, C. Hose, A. Monks, Y. K. Kang, et al. Clinical Reversal of Multidrug Resistance Oncologist, August 1, 1996; 1(4): 269 - 275. [Abstract] [Full Text] [PDF] |
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J. Weinstein, K. Kohn, M. Grever, V. Viswanadhan, L. Rubinstein, A. Monks, D. Scudiero, L Welch, A. Koutsoukos, A. Chiausa, et al. Neural computing in cancer drug development: predicting mechanism of action Science, October 16, 1992; 258(5081): 447 - 451. [Abstract] [PDF] |
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H.-M. Koo, M. VanBrocklin, M. J. McWilliams, S. H. Leppla, N. S. Duesbery, and G. F. V. Woude Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activated protein kinase kinase PNAS, March 5, 2002; 99(5): 3052 - 3057. [Abstract] [Full Text] [PDF] |
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A. J. Butte, P. Tamayo, D. Slonim, T. R. Golub, and I. S. Kohane Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks PNAS, October 24, 2000; 97(22): 12182 - 12186. [Abstract] [Full Text] [PDF] |
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