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Cycle in cancer: CDK and cell cycle checkpoint kinase inhibitors. Curr Opin Pharmacol 2005, 5:366?73. 9. Hanahan D, Weinberg RA: The hallmarks of cancer. Cell 2000, 100:57?0. 10. Vermeulen K, Van Bockstaele DR, Berneman ZN: The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif 2003, 36:131?49. 11. Schwartz GK, Shah MA: Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol 2005, 23:9408?421. 12. Shapiro GI: Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 2006, 24:1770?783. 13. Joshi KS, Rathos MJ, Joshi RD, et al: In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00. Mol Cancer Ther 2007, 6:918?25. 14. Joshi KS, Rathos MJ, Mahajan P, et al: P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatinresistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther 2007, 6:926?34. 15. Dengler WA, Schulte J, Berger DP, Mertelsmann R, Fiebig HH: Development of a propidium fluorescence assay for proliferation and cytotoxicity assays. Anticancer Drugs 1995, 6:522?32. 16. Chau YJ, Cunningham D: Adjuvant treatment for respectable pancreatic cancer. J Clin Oncol 2005, 23:4532?537. 17. Chou T-C: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006, 58:621?81. 18. Berlin JD, Rothenberg ML: Chemotherapeutic advances in pancreatic cancer. Curr Oncol Rep 2003, 5:219?26.Conclusions The present study describes the molecular mechanisms underlying the synergistic inhibition of pancreatic cancer cell BMS-214662 cancer growth in vitro by P276-00 and gemcitabine. Moreover, the significant in vivo antitumour activity by P27600 and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27597769 gemcitabine together with the absence of toxicity, provide a rationale basis for the development of novel therapies using the gold standard gemcitabine in combination with Cdk inhibitor in patients with advanced pancreatic cancer. Additional fileAdditional file 1: Figure S1. Densitometric analysis of the mRNA bands. Samples were obtained from PANC-1 cells treated with 300 nM of P27600 and/or 70 nM gemcitabine at various time points as indicated in the figure. The figures show the relative densities of BNIP3, p8 and COX-2 mRNA bands shown in Figure 5A.Competing interests The authors declare that they have no competing interests.Rathos et al. Journal of Translational Medicine 2012, 10:161 http://www.translational-medicine.com/content/10/1/Page 11 of19. Diaz-Rubio E: New chemotherapeutic advances in pancreatic, colorectal, and gastric cancers. Oncologist 2004, 9:282?94. 20. Arends JJ, Sleeboom HP, Leys MB, et al: A phase II study of raltitrexed and gemcitabine in patients with advanced pancreatic carcinoma. Br J Cancer 2005, 92:445?48. 21. Bold RJ, Virudachalam S, McConkey DJ: BCL2 expression correlates with metastatic potential in pancreatic cancer cell lines. Cancer 2001, 92(5):1122?129. 22. Nakano Y, Tanno S, Koizumi K, Nishikawa T, Nakamura K, Minoguchi M, Izawa T, Mizukami Y, Okumura T, Kohgo Y: Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells. Br J Cancer 2007, 96:457?63. 23. Yip Schneider MT, Barnard DS, Billings SD, et al: Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis 2000, 21:139?46. 24. Kokawa A, Kondo H, Gotoda T, Ono H, et al: Increased expression o.
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