This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shao, R.-G. Articles by Pommier, Y. Search for Related Content PubMed PubMed Citation Articles by Shao, R.-G. Articles by Pommier, Y.

Abrogation of an S-Phase Checkpoint and Potentiation of Camptothecin Cytotoxicity by 7-Hydroxystaurosporine (UCN-01) in Human Cancer Cell Lines, Possibly Influenced by p53 Function

Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892

7-Hydroxystaurosporine (UCN-01) is a selective protein kinase C inhibitor in clinical trial for cancer treatment. In this study, we found that nanomolar concentrations of camptothecin (CPT), a topoisomerase I inhibitor, arrest or delay cell cycle progression during the S and G₂ phases in p53 mutant human colon carcinoma HT29 cells and that UCN-01 abrogates the S-phase arrest or delay induced by CPT. Under these conditions, CPT increased cyclin A levels and cyclin A/cyclin-dependent kinase 2 activity. UCN-01 prevented the increase of cyclin A/cyclin-dependent kinase 2 activity induced by CPT and enhanced Cdc2 kinase activity. Replication protein A (RPA2) was hyperphosphorylated after CPT treatment, and this effect was also abrogated by UCN-01. UCN-01 potentiated the cytotoxicity of CPT and reduced by 6-fold the concentration of CPT required to kill 50% of the HT-29 cells, as determined by clonogenic assays. This effect was observed at concentrations of UCN-01 that alone were not cytotoxic and had no detectable effect on cell cycle progression. UCN-01 markedly potentiated the cytotoxicity of CPT also in HCT116/E6 and MCF-7/ADR cells defective for p53 function, whereas significantly less potentiation was observed in p53-wild-type HCT116 and MCF-7 cells. These results suggest the existence of an S-phase checkpoint that delays replication and that may extend the time available for DNA repair. Thus, pharmacological abrogation of CPT-induced S- and G₂-phase checkpoints by UCN-01 may provide an effective strategy for enhancing the chemotherapeutic activity of CPT, particularly against p53-defective tumors.

¹ To whom requests for reprints should be addressed, at Laboratory of Molecular Pharmacology, Building 37, Room 5C25, NIH, Bethesda, MD 20892-4255. Fax: (301) 402-0752.

Received 5/ 7/97. Accepted 7/17/97.

This article has been cited by other articles:

				Synergistic antitumor effect between vorinostat and topotecan in small cell lung cancer cells is mediated by generation of reactive oxygen species and DNA damage-induced apoptosis Mol. Cancer Ther., November 1, 2009; 8(11): 3075 - 3087.

				Y.-W. Zhang, T. L. Jones, S. E. Martin, N. J. Caplen, and Y. Pommier Implication of Checkpoint Kinase-dependent Up-regulation of Ribonucleotide Reductase R2 in DNA Damage Response J. Biol. Chem., July 3, 2009; 284(27): 18085 - 18095. [Abstract] [Full Text] [PDF]

				A. R. Demidova, M. Y. Aau, L. Zhuang, and Q. Yu Dual Regulation of Cdc25A by Chk1 and p53-ATF3 in DNA Replication Checkpoint Control J. Biol. Chem., February 13, 2009; 284(7): 4132 - 4139. [Abstract] [Full Text] [PDF]

				M. Huang, Z.-H. Miao, H. Zhu, Y.-J. Cai, W. Lu, and J. Ding Chk1 and Chk2 are differentially involved in homologous recombination repair and cell cycle arrest in response to DNA double-strand breaks induced by camptothecins Mol. Cancer Ther., June 1, 2008; 7(6): 1440 - 1449. [Abstract] [Full Text] [PDF]

				H. Hamed, W. Hawkins, C. Mitchell, D. Gilfor, G. Zhang, X.-Y. Pei, Y. Dai, M. P. Hagan, J. D. Roberts, A. Yacoub, et al. Transient exposure of carcinoma cells to RAS/MEK inhibitors and UCN-01 causes cell death in vitro and in vivo Mol. Cancer Ther., March 1, 2008; 7(3): 616 - 629. [Abstract] [Full Text] [PDF]

				S. Antony, K. K. Agama, Z.-H. Miao, K. Takagi, M. H. Wright, A. I. Robles, L. Varticovski, M. Nagarajan, A. Morrell, M. Cushman, et al. Novel Indenoisoquinolines NSC 725776 and NSC 724998 Produce Persistent Topoisomerase I Cleavage Complexes and Overcome Multidrug Resistance Cancer Res., November 1, 2007; 67(21): 10397 - 10405. [Abstract] [Full Text] [PDF]

				J. A. Seiler, C. Conti, A. Syed, M. I. Aladjem, and Y. Pommier The Intra-S-Phase Checkpoint Affects both DNA Replication Initiation and Elongation: Single-Cell and -DNA Fiber Analyses Mol. Cell. Biol., August 15, 2007; 27(16): 5806 - 5818. [Abstract] [Full Text] [PDF]

				S. Ray, S. Shyam, G. C. Fraizer, and A. Almasan S-phase checkpoints regulate Apo2 ligand/TRAIL and CPT-11-induced apoptosis of prostate cancer cells Mol. Cancer Ther., April 1, 2007; 6(4): 1368 - 1378. [Abstract] [Full Text] [PDF]

				D. Wilsker and F. Bunz Loss of ataxia telangiectasia mutated- and Rad3-related function potentiates the effects of chemotherapeutic drugs on cancer cell survival Mol. Cancer Ther., April 1, 2007; 6(4): 1406 - 1413. [Abstract] [Full Text] [PDF]

				A. N. Tse, R. Carvajal, and G. K. Schwartz Targeting Checkpoint Kinase 1 in Cancer Therapeutics Clin. Cancer Res., April 1, 2007; 13(7): 1955 - 1960. [Abstract] [Full Text] [PDF]

				A. N. Tse, K. G. Rendahl, T. Sheikh, H. Cheema, K. Aardalen, M. Embry, S. Ma, E. J. Moler, Z. J. Ni, D. E. Lopes de Menezes, et al. CHIR-124, a Novel Potent Inhibitor of Chk1, Potentiates the Cytotoxicity of Topoisomerase I Poisons In vitro and In vivo Clin. Cancer Res., January 15, 2007; 13(2): 591 - 602. [Abstract] [Full Text] [PDF]

				R. P. Perez, L. D. Lewis, A. P. Beelen, A. J. Olszanski, N. Johnston, C. H. Rhodes, B. Beaulieu, M. S. Ernstoff, and A. Eastman Modulation of Cell Cycle Progression in Human Tumors: A Pharmacokinetic and Tumor Molecular Pharmacodynamic Study of Cisplatin Plus the Chk1 Inhibitor UCN-01 (NSC 638850) Clin. Cancer Res., December 1, 2006; 12(23): 7079 - 7085. [Abstract] [Full Text] [PDF]

				Y. Liu, A. Rusinol, M. Sinensky, Y. Wang, and Y. Zou DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A J. Cell Sci., November 15, 2006; 119(22): 4644 - 4649. [Abstract] [Full Text] [PDF]

				H. Takemura, V. A. Rao, O. Sordet, T. Furuta, Z.-H. Miao, L. Meng, H. Zhang, and Y. Pommier Defective Mre11-dependent Activation of Chk2 by Ataxia Telangiectasia Mutated in Colorectal Carcinoma Cells in Response to Replication-dependent DNA Double Strand Breaks J. Biol. Chem., October 13, 2006; 281(41): 30814 - 30823. [Abstract] [Full Text] [PDF]

				M. McGahren-Murray, N. H.A. Terry, and K. Keyomarsi The Differential Staurosporine-Mediated G1 Arrest in Normal versus Tumor Cells Is Dependent on the Retinoblastoma Protein Cancer Res., October 1, 2006; 66(19): 9744 - 9753. [Abstract] [Full Text] [PDF]

				S. Antony, K. K. Agama, Z.-H. Miao, M. Hollingshead, S. L. Holbeck, M. H. Wright, L. Varticovski, M. Nagarajan, A. Morrell, M. Cushman, et al. Bisindenoisoquinoline Bis-1,3-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propylamino}propane bis(trifluoroacetate) (NSC 727357), a DNA Intercalator and Topoisomerase Inhibitor with Antitumor Activity Mol. Pharmacol., September 1, 2006; 70(3): 1109 - 1120. [Abstract] [Full Text] [PDF]

				S. J. Hotte, A. Oza, E. W. Winquist, M. Moore, E. X. Chen, S. Brown, G. R. Pond, J. E. Dancey, and H. W. Hirte Phase I trial of UCN-01 in combination with topotecan in patients with advanced solid cancers: a Princess Margaret Hospital Phase II Consortium study Ann. Onc., February 1, 2006; 17(2): 334 - 340. [Abstract] [Full Text] [PDF]

				C. J. Strock, J.-I. Park, D. M. Rosen, B. Ruggeri, S. R. Denmeade, D. W. Ball, and B. D. Nelkin Activity of Irinotecan and the Tyrosine Kinase Inhibitor CEP-751 in Medullary Thyroid Cancer J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 79 - 84. [Abstract] [Full Text] [PDF]

				D. L. Morse, H. Gray, C. M. Payne, and R. J. Gillies Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells Mol. Cancer Ther., October 1, 2005; 4(10): 1495 - 1504. [Abstract] [Full Text] [PDF]

				H.-V. Le, A. J. Minn, and J. Massague Cyclin-dependent Kinase Inhibitors Uncouple Cell Cycle Progression from Mitochondrial Apoptotic Functions in DNA-damaged Cancer Cells J. Biol. Chem., September 9, 2005; 280(36): 32018 - 32025. [Abstract] [Full Text] [PDF]

				M. R. v. Z. K. Fagundes, C. P. Semighini, I. Malavazi, M. Savoldi, J. F. de Lima, M. H. de Souza Goldman, S. D. Harris, and G. H. Goldman Aspergillus nidulans uvsBATR and scaANBS1 Genes Show Genetic Interactions during Recovery from Replication Stress and DNA Damage Eukaryot. Cell, July 1, 2005; 4(7): 1239 - 1252. [Abstract] [Full Text] [PDF]

				K. Flatten, N. T. Dai, B. T. Vroman, D. Loegering, C. Erlichman, L. M. Karnitz, and S. H. Kaufmann The Role of Checkpoint Kinase 1 in Sensitivity to Topoisomerase I Poisons J. Biol. Chem., April 8, 2005; 280(14): 14349 - 14355. [Abstract] [Full Text] [PDF]

				E. Fuse, T. Kuwabara, A. Sparreboom, E. A. Sausville, and W. D. Figg Review of UCN-01 Development: A Lesson in the Importance of Clinical Pharmacology J. Clin. Pharmacol., April 1, 2005; 45(4): 394 - 403. [Abstract] [Full Text] [PDF]

				M. Hahn, W. Li, C. Yu, M. Rahmani, P. Dent, and S. Grant Rapamycin and UCN-01 synergistically induce apoptosis in human leukemia cells through a process that is regulated by the Raf-1/MEK/ERK, Akt, and JNK signal transduction pathways Mol. Cancer Ther., March 1, 2005; 4(3): 457 - 470. [Abstract] [Full Text] [PDF]

				Y. Dai, M. Rahmani, X.-Y. Pei, P. Khanna, S. I. Han, C. Mitchell, P. Dent, and S. Grant Farnesyltransferase inhibitors interact synergistically with the Chk1 inhibitor UCN-01 to induce apoptosis in human leukemia cells through interruption of both Akt and MEK/ERK pathways and activation of SEK1/JNK Blood, February 15, 2005; 105(4): 1706 - 1716. [Abstract] [Full Text] [PDF]

				C. Vogel, A. Kienitz, R. Muller, and H. Bastians The Mitotic Spindle Checkpoint Is a Critical Determinant for Topoisomerase-based Chemotherapy J. Biol. Chem., February 11, 2005; 280(6): 4025 - 4028. [Abstract] [Full Text] [PDF]

				E. C. Dees, S. D. Baker, S. O'Reilly, M. A. Rudek, S. B. Davidson, C. Aylesworth, K. Elza-Brown, M. A. Carducci, and R. C. Donehower A Phase I and Pharmacokinetic Study of Short Infusions of UCN-01 in Patients with Refractory Solid Tumors Clin. Cancer Res., January 15, 2005; 11(2): 664 - 671. [Abstract] [Full Text] [PDF]

				A. N. Tse and G. K. Schwartz Potentiation of Cytotoxicity of Topoisomerase I Poison by Concurrent and Sequential Treatment with the Checkpoint Inhibitor UCN-01 Involves Disparate Mechanisms Resulting in Either p53-Independent Clonogenic Suppression or p53-Dependent Mitotic Catastrophe Cancer Res., September 15, 2004; 64(18): 6635 - 6644. [Abstract] [Full Text] [PDF]

				D. Loegering, S. J. H. Arlander, J. Hackbarth, B. T. Vroman, P. Roos-Mattjus, K. M. Hopkins, H. B. Lieberman, L. M. Karnitz, and S. H. Kaufmann Rad9 Protects Cells from Topoisomerase Poison-induced Cell Death J. Biol. Chem., April 30, 2004; 279(18): 18641 - 18647. [Abstract] [Full Text] [PDF]

				W. Jia, C. Yu, M. Rahmani, G. Krystal, E. A. Sausville, P. Dent, and S. Grant Synergistic antileukemic interactions between 17-AAG and UCN-01 involve interruption of RAF/MEK- and AKT-related pathways Blood, September 1, 2003; 102(5): 1824 - 1832. [Abstract] [Full Text] [PDF]

				S. S. Daoud, P. J. Munson, W. Reinhold, L. Young, V. V. Prabhu, Q. Yu, J. LaRose, K. W. Kohn, J. N. Weinstein, and Y. Pommier Impact of p53 Knockout and Topotecan Treatment on Gene Expression Profiles in Human Colon Carcinoma Cells: A Pharmacogenomic Study Cancer Res., June 1, 2003; 63(11): 2782 - 2793. [Abstract] [Full Text] [PDF]

				T. Furuta, H. Takemura, Z.-Y. Liao, G. J. Aune, C. Redon, O. A. Sedelnikova, D. R. Pilch, E. P. Rogakou, A. Celeste, H. T. Chen, et al. Phosphorylation of Histone H2AX and Activation of Mre11, Rad50, and Nbs1 in Response to Replication-dependent DNA Double-strand Breaks Induced by Mammalian DNA Topoisomerase I Cleavage Complexes J. Biol. Chem., May 23, 2003; 278(22): 20303 - 20312. [Abstract] [Full Text] [PDF]

				H. Miao, J. A. Seiler, and W. C. Burhans Regulation of Cellular and SV40 Virus Origins of Replication by Chk1-dependent Intrinsic and UVC Radiation-induced Checkpoints J. Biol. Chem., January 31, 2003; 278(6): 4295 - 4304. [Abstract] [Full Text] [PDF]

				E. A. Kohn, C. J. Yoo, and A. Eastman The Protein Kinase C Inhibitor Go6976 Is a Potent Inhibitor of DNA Damage-induced S and G2 Cell Cycle Checkpoints Cancer Res., January 1, 2003; 63(1): 31 - 35. [Abstract] [Full Text] [PDF]

				B. Zhao, M. J. Bower, P. J. McDevitt, H. Zhao, S. T. Davis, K. O. Johanson, S. M. Green, N. O. Concha, and B.-B. S. Zhou Structural Basis for Chk1 Inhibition by UCN-01 J. Biol. Chem., November 22, 2002; 277(48): 46609 - 46615. [Abstract] [Full Text] [PDF]

				Q. Yu, J. La Rose, H. Zhang, H. Takemura, K. W. Kohn, and Y. Pommier UCN-01 Inhibits p53 Up-Regulation and Abrogates {gamma}-Radiation-induced G2-M Checkpoint Independently of p53 by Targeting Both of the Checkpoint Kinases, Chk2 and Chk1 Cancer Res., October 15, 2002; 62(20): 5743 - 5748. [Abstract] [Full Text] [PDF]

				A. Eastman, E. A. Kohn, M. K. Brown, J. Rathman, M. Livingstone, D. H. Blank, and G. W. Gribble A Novel Indolocarbazole, ICP-1, Abrogates DNA Damage-induced Cell Cycle Arrest and Enhances Cytotoxicity: Similarities and Differences to the Cell Cycle Checkpoint Abrogator UCN-01 Mol. Cancer Ther., October 1, 2002; 1(12): 1067 - 1078. [Abstract] [Full Text] [PDF]

				D. Sampath, Z. Shi, and W. Plunkett Inhibition of Cyclin-Dependent Kinase 2 by the Chk1-Cdc25A Pathway during the S-Phase Checkpoint Activated by Fludarabine: Dysregulation by 7-Hydroxystaurosporine Mol. Pharmacol., September 1, 2002; 62(3): 680 - 688. [Abstract] [Full Text] [PDF]

				A. M. Senderowicz The Cell Cycle as a Target for Cancer Therapy: Basic and Clinical Findings with the Small Molecule Inhibitors Flavopiridol and UCN-01 Oncologist, August 1, 2002; 7(90003): 12 - 19. [Abstract] [Full Text] [PDF]

				E. A. Kohn, N. D. Ruth, M. K. Brown, M. Livingstone, and A. Eastman Abrogation of the S Phase DNA Damage Checkpoint Results in S Phase Progression or Premature Mitosis Depending on the Concentration of 7-Hydroxystaurosporine and the Kinetics of Cdc25C Activation J. Biol. Chem., July 12, 2002; 277(29): 26553 - 26564. [Abstract] [Full Text] [PDF]

				R. Garcia-Carbonero and J. G. Supko Current Perspectives on the Clinical Experience, Pharmacology, and Continued Development of the Camptothecins Clin. Cancer Res., March 1, 2002; 8(3): 641 - 661. [Abstract] [Full Text] [PDF]

				T. Yamauchi, M. J. Keating, and W. Plunkett UCN-01 (7-Hydroxystaurosporine) Inhibits DNA Repair and Increases Cytotoxicity in Normal Lymphocytes and Chronic Lymphocytic Leukemia Lymphocytes Mol. Cancer Ther., February 1, 2002; 1(4): 287 - 294. [Abstract] [Full Text] [PDF]

				T. Ikegami, L. Ha, K. Arimori, P. Latham, K. Kobayashi, S. Ceryak, Y. Matsuzaki, and B. Bouscarel Intestinal Alkalization As a Possible Preventive Mechanism in Irinotecan (CPT-11)-induced Diarrhea Cancer Res., January 1, 2002; 62(1): 179 - 187. [Abstract] [Full Text] [PDF]

				M. Motwani, C. Jung, F. M. Sirotnak, Y. She, M. A. Shah, M. Gonen, and G. K. Schwartz Augmentation of Apoptosis and Tumor Regression by Flavopiridol in the Presence of CPT-11 in Hct116 Colon Cancer Monolayers and Xenografts Clin. Cancer Res., December 1, 2001; 7(12): 4209 - 4219. [Abstract] [Full Text] [PDF]

				P. Pichierri, A. Franchitto, R. Piergentili, C. Colussi, and F. Palitti Hypersensitivity to camptothecin in MSH2 deficient cells is correlated with a role for MSH2 protein in recombinational repair Carcinogenesis, November 1, 2001; 22(11): 1781 - 1787. [Abstract] [Full Text] [PDF]

				Y. Hirose, M. S. Berger, and R. O. Pieper Abrogation of the Chk1-mediated G2 Checkpoint Pathway Potentiates Temozolomide-induced Toxicity in a p53-independent Manner in Human Glioblastoma Cells Cancer Res., August 1, 2001; 61(15): 5843 - 5849. [Abstract] [Full Text] [PDF]

				K. P. L. Bhat and J. M. Pezzuto Resveratrol Exhibits Cytostatic and Antiestrogenic Properties with Human Endometrial Adenocarcinoma (Ishikawa) Cells Cancer Res., August 1, 2001; 61(16): 6137 - 6144. [Abstract] [Full Text] [PDF]

				M. A. Shah and G. K. Schwartz Cell Cycle-mediated Drug Resistance: An Emerging Concept in Cancer Therapy Clin. Cancer Res., August 1, 2001; 7(8): 2168 - 2181. [Abstract] [Full Text] [PDF]

				Y. Dai, C. Yu, V. Singh, L. Tang, Z. Wang, R. McInistry, P. Dent, and S. Grant Pharmacological Inhibitors of the Mitogen-activated Protein Kinase (MAPK) Kinase/MAPK Cascade Interact Synergistically with UCN-01 to Induce Mitochondrial Dysfunction and Apoptosis in Human Leukemia Cells Cancer Res., July 1, 2001; 61(13): 5106 - 5115. [Abstract] [Full Text] [PDF]

				G. G. Oakley, L. I. Loberg, J. Yao, M. A. Risinger, R. L. Yunker, M. Zernik-Kobak, K. K. Khanna, M. F. Lavin, M. P. Carty, and K. Dixon UV-induced Hyperphosphorylation of Replication Protein A Depends on DNA Replication and Expression of ATM Protein Mol. Biol. Cell, May 1, 2001; 12(5): 1199 - 1213. [Abstract] [Full Text]

				Z. Shi, A. Azuma, D. Sampath, Y.-X. Li, P. Huang, and W. Plunkett S-Phase Arrest by Nucleoside Analogues and Abrogation of Survival without Cell Cycle Progression by 7-Hydroxystaurosporine Cancer Res., February 1, 2001; 61(3): 1065 - 1072. [Abstract] [Full Text]

				S. Harvey, R. Decker, Y. Dai, G. Schaefer, L. Tang, L. Kramer, P. Dent, and S. Grant Interactions between 2-Fluoroadenine 9-{beta}-D-Arabinofuranoside and the Kinase Inhibitor UCN-01 in Human Leukemia and Lymphoma Cells Clin. Cancer Res., February 1, 2001; 7(2): 320 - 330. [Abstract] [Full Text]

				A. J. Janss, A. Maity, C.-B. Tang, R. J. Muschel, W. G. McKenna, L. Sutton, and P. C. Phillips Decreased cyclin B1 expression contributes to G2 delay in human brain tumor cells after treatment with camptothecin Neuro-oncol, January 1, 2001; 3(1): 11 - 21. [Abstract] [PDF]

				Y. Urasaki, G. Laco, Y. Takebayashi, C. Bailly, G. Kohlhagen, and Y. Pommier Use of Camptothecin-resistant Mammalian Cell Lines to Evaluate the Role of Topoisomerase I in the Antiproliferative Activity of the Indolocarbazole, NB-506, and Its Topoisomerase I Binding Site Cancer Res., January 1, 2001; 61(2): 504 - 508. [Abstract] [Full Text]

				C. Erlichman, S. A. Boerner, C. G. Hallgren, R. Spieker, X.-Y. Wang, C. D. James, G. L. Scheffer, M. Maliepaard, D. D. Ross, K. C. Bible, et al. The HER Tyrosine Kinase Inhibitor CI1033 Enhances Cytotoxicity of 7-Ethyl-10-hydroxycamptothecin and Topotecan by Inhibiting Breast Cancer Resistance Protein-mediated Drug Efflux Cancer Res., January 1, 2001; 61(2): 739 - 748. [Abstract] [Full Text]

				Y. Takebayashi, F. Goldwasser, Y. Urasaki, G. Kohlhagen, and Y. Pommier Ecteinascidin 743 Induces Protein-linked DNA Breaks in Human Colon Carcinoma HCT116 Cells and Is Cytotoxic Independently of Topoisomerase I Expression Clin. Cancer Res., January 1, 2001; 7(1): 185 - 191. [Abstract] [Full Text]

				I. Petak, D. M. Tillman, and J. A. Houghton p53 Dependence of Fas Induction and Acute Apoptosis in Response to 5-Fluorouracil-Leucovorin in Human Colon Carcinoma Cell Lines Clin. Cancer Res., November 1, 2000; 6(11): 4432 - 4441. [Abstract] [Full Text] [PDF]

				U. Wenzel, S. Kuntz, M. D. Brendel, and H. Daniel Dietary Flavone Is a Potent Apoptosis Inducer in Human Colon Carcinoma Cells Cancer Res., July 1, 2000; 60(14): 3823 - 3831. [Abstract] [Full Text]

				A. M. Senderowicz and E. A. Sausville Preclinical and Clinical Development of Cyclin-Dependent Kinase Modulators J Natl Cancer Inst, March 1, 2000; 92(5): 376 - 387. [Abstract] [Full Text] [PDF]

				P. R. Graves, L. Yu, J. K. Schwarz, J. Gales, E. A. Sausville, P. M. O'Connor, and H. Piwnica-Worms The Chk1 Protein Kinase and the Cdc25C Regulatory Pathways Are Targets of the Anticancer Agent UCN-01 J. Biol. Chem., February 25, 2000; 275(8): 5600 - 5605. [Abstract] [Full Text] [PDF]

				J. R. Jackson, A. Gilmartin, C. Imburgia, J. D. Winkler, L. A. Marshall, and A. Roshak An Indolocarbazole Inhibitor of Human Checkpoint Kinase (Chk1) Abrogates Cell Cycle Arrest Caused by DNA Damage Cancer Res., February 1, 2000; 60(3): 566 - 572. [Abstract] [Full Text]

				W. H. Wilson, L. Sorbara, W. D. Figg, E. K. Mont, E. Sausville, K. E. Warren, F. M. Balis, K. Bauer, M. Raffeld, A. M. Senderowicz, et al. Modulation of Clinical Drug Resistance in a B Cell Lymphoma Patient by the Protein Kinase Inhibitor 7-Hydroxystaurosporine: Presentation of a Novel Therapeutic Paradigm Clin. Cancer Res., February 1, 2000; 6(2): 415 - 421. [Abstract] [Full Text]

				S. J. Chmura, M. E. Dolan, A. Cha, H. J. Mauceri, D. W. Kufe, and R. R. Weichselbaum In Vitro and in Vivo Activity of Protein Kinase C Inhibitor Chelerythrine Chloride Induces Tumor Cell Toxicity and Growth Delay in Vivo Clin. Cancer Res., February 1, 2000; 6(2): 737 - 742. [Abstract] [Full Text]

				H. Shinohara, J. J. Killion, C. D. Bucana, S. Yano, and I. J. Fidler Oral Administration of the Immunomodulator JBT-3002 Induces Endogenous Interleukin 15 in Intestinal Macrophages for Protection against Irinotecan-mediated Destruction of Intestinal Epithelium Clin. Cancer Res., August 1, 1999; 5(8): 2148 - 2156. [Abstract] [Full Text] [PDF]

				H. Yamashita, J. Xu, R. A. Erwin, A. C. Larner, and H. Rui A Lymphoma Growth Inhibitor Blocks Some but Not All Prolactin-stimulated Signaling Pathways J. Biol. Chem., May 21, 1999; 274(21): 14699 - 14705. [Abstract] [Full Text] [PDF]

				C. D. Britten, S. G. Hilsenbeck, S. G. Eckhardt, J. Marty, G. Mangold, J. R. MacDonald, E. K. Rowinsky, D. D. Von Hoff, and S. Weitman Enhanced Antitumor Activity of 6-Hydroxymethylacylfulvene in Combination with Irinotecan and 5-Fluorouracil in the HT29 Human Colon Tumor Xenograft Model Cancer Res., March 1, 1999; 59(5): 1049 - 1053. [Abstract] [Full Text] [PDF]

				C. Bailly, X. Qu, F. Anizon, M. Prudhomme, J.-F. Riou, and J. B. Chaires Enhanced Binding to DNA and Topoisomerase I Inhibition by an Analog of the Antitumor Antibiotic Rebeccamycin Containing an Amino Sugar Residue Mol. Pharmacol., February 1, 1999; 55(2): 377 - 385. [Abstract] [Full Text]

				D. M. Tillman, I. Petak, and J. A. Houghton A Fas-dependent Component in 5-Fluorouracil/Leucovorin-induced Cytotoxicity in Colon Carcinoma Cells Clin. Cancer Res., February 1, 1999; 5(2): 425 - 430. [Abstract] [Full Text] [PDF]

				L. Yu, L. Orlandi, P. Wang, M. S. Orr, A. M. Senderowicz, E. A. Sausville, R. Silvestrini, N. Watanabe, H. Piwnica-Worms, and P. M. O'Connor UCN-01 Abrogates G2 Arrest through a Cdc2-dependent Pathway That Is Associated with Inactivation of the Wee1Hu Kinase and Activation of the Cdc25C Phosphatase J. Biol. Chem., December 11, 1998; 273(50): 33455 - 33464. [Abstract] [Full Text] [PDF]

				J. Lozano, S. Menendez, A. Morales, D. Ehleiter, W.-C. Liao, R. Wagman, A. Haimovitz-Friedman, Z. Fuks, and R. Kolesnick Cell Autonomous Apoptosis Defects in Acid Sphingomyelinase Knockout Fibroblasts J. Biol. Chem., January 5, 2001; 276(1): 442 - 448. [Abstract] [Full Text] [PDF]

				B. Hu, X.-Y. Zhou, X. Wang, Z.-C. Zeng, G. Iliakis, and Y. Wang The Radioresistance to Killing of A1-5 Cells Derives from Activation of the Chk1 Pathway J. Biol. Chem., May 18, 2001; 276(21): 17693 - 17698. [Abstract] [Full Text] [PDF]

				W. A. Cliby, K. A. Lewis, K. K. Lilly, and S. H. Kaufmann S Phase and G2 Arrests Induced by Topoisomerase I Poisons Are Dependent on ATR Kinase Function J. Biol. Chem., January 4, 2002; 277(2): 1599 - 1606. [Abstract] [Full Text] [PDF]