International Journal of Colorectal Disease

, Volume 22, Issue 7, pp 739–748 | Cite as

The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer

Review

Abstract

Introduction

High-frequency microsatellite instability (MSI-H) is an alternate pathway of colorectal carcinogenesis, which accounts for 15% of all sporadic colorectal cancers. These tumours arise from mutations in the DNA mismatch repair system and thus have different responses to chemotherapeutic agents compared to microsatellite stable (MSS) cancers.

Objective

This review aims to summarise the available literature on the responses to chemotherapy in MSI-H colorectal cancer (CRC).

Results and discussion

5 Fluorouracil (5FU) is commonly used as a chemotherapeutic agent in colon cancer and in vitro evidence shows reduced response to 5FU in MSI-H CRC. The clinical evidence is conflicting but favours a reduced response to 5FU in MSI-H CRC. Several newer agents such as COX-2 inhibitors and irinotecan are also reviewed.

Conclusion

Available evidence suggests that MSI-H CRC have different behaviour patterns and response to chemotherapy compared with MSS CRC.

Keywords

Colorectal cancer Microsatellite instability (MSI-H) Chemotherapy 5 Fluorouracil (5FU) Cyclo-oxygenase 2 (COX-2) Irinotecan 

References

  1. 1.
    Aaltonen LA, Peltomaki P, Leach FS et al (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260(5109):812–816PubMedGoogle Scholar
  2. 2.
    Gryfe R, Kim H, Hsieh ETK et al (2000) Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342(2):69–77PubMedGoogle Scholar
  3. 3.
    Hemminki A, Mecklin JP, Jarvinen H et al (2000) Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy. Gastroenterology 119(4):921–928PubMedGoogle Scholar
  4. 4.
    Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260(5109):816–819PubMedGoogle Scholar
  5. 5.
    Fearon ER, Cho KR, Nigro JM et al (1990) Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247(4938):49–56PubMedGoogle Scholar
  6. 6.
    Lindblom A, Tannergard P, Werelius B et al (1993) Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer. Nat Genet 5(3):279–282PubMedGoogle Scholar
  7. 7.
    Peltomaki P, Aaltonen LA, Sistonen P et al (1993) Genetic mapping of a locus predisposing to human colorectal cancer (comment). Science 260(5109):810–812PubMedGoogle Scholar
  8. 8.
    Bronner CE, Baker SM, Morrison PT et al (1994) Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368(6468):258–261PubMedGoogle Scholar
  9. 9.
    Liu B, Nicolaides NC, Markowitz S et al (1995) Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nat Genet 9(1):48–55PubMedGoogle Scholar
  10. 10.
    Moslein G, Tester DJ, Lindor NM et al (1996) Microsatellite instability and mutation analysis of hmsh2 and hmlh1 in patients with sporadic, familial and hereditary colorectal cancer. Hum Mol Genet 5(9):1245–1252PubMedGoogle Scholar
  11. 11.
    Thibodeau SN, French AJ, Cunningham JM et al (1998) Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res 58(8):1713–1718PubMedGoogle Scholar
  12. 12.
    Herman JG, Umar A, Polyak K et al (1998) Incidence and functional consequences of hmlh1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA 95(12):6870–6875PubMedGoogle Scholar
  13. 13.
    Cunningham JM, Christensen ER, Tester DJ et al (1998) Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58(15):3455–3460PubMedGoogle Scholar
  14. 14.
    Markowitz S, Wang J, Myeroff L et al (1995) Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 268(5215):1336–1338PubMedGoogle Scholar
  15. 15.
    Souza RF, Appel R, Yin J et al (1996) Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours (published erratum in Nat Genet 14:488). Nat Genet 14(3):255–257PubMedGoogle Scholar
  16. 16.
    Parsons R, Myeroff LL, Liu B et al (1995) Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. Cancer Res 55(23):5548–5550PubMedGoogle Scholar
  17. 17.
    Biswas S, Chytil A, Washington K et al (2004) Transforming growth factor beta receptor type II inactivation promotes the establishment and progression of colon cancer. Cancer Res 64(14):4687–4692PubMedGoogle Scholar
  18. 18.
    Hahm KB, Lee KM, Kim YB et al (2002) Conditional loss of TGF-beta signalling leads to increased susceptibility to gastrointestinal carcinogenesis in mice. Aliment Pharmacol Ther 16(Suppl 2):115–127PubMedGoogle Scholar
  19. 19.
    Grady WM, Rajput A, Myeroff L et al (1998) Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas. Cancer Res 58(14):3101–3104PubMedGoogle Scholar
  20. 20.
    Ionov Y, Peinado MA, Malkhosyan S et al (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363(6429):558–561PubMedGoogle Scholar
  21. 21.
    Kim HG, Jen J, Vogelstein B et al (1994) Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol 145(1):148–156PubMedGoogle Scholar
  22. 22.
    Lothe RA, Peltomaki P, Meling GI et al (1993) Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res 53(24):5849–5852PubMedGoogle Scholar
  23. 23.
    Jass JR, Do KA, Simms LA et al (1998) Morphology of sporadic colorectal cancer with DNA replication errors. Gut 42(5):673–679PubMedCrossRefGoogle Scholar
  24. 24.
    Aaltonen LA, Salovaara R, Kristo P et al (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338(21):1481–1487PubMedGoogle Scholar
  25. 25.
    Bocker T, Schlegel J, Kullmann F et al (1996) Genomic instability in colorectal carcinomas—comparison of different evaluation methods and their biological significance. J Pathol 179(1):15–19PubMedGoogle Scholar
  26. 26.
    Halling KC, French AJ, McDonnell SK et al (1999) Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers (see comment). J Natl Cancer Inst 91(15):1295–1303PubMedGoogle Scholar
  27. 27.
    Powell SM, Zilz N, Beazer-Barclay Y et al (1992) APC mutations occur early during colorectal tumorigenesis. Nature 359(6392):235–237PubMedGoogle Scholar
  28. 28.
    Aaltonen LA, Peltomaki P, Mecklin JP et al (1994) Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res 54(7):1645–1648PubMedGoogle Scholar
  29. 29.
    Konishi M, Kikuchi-Yanoshita R, Tanaka K et al (1996) Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer. Gastroenterology 111(2):307–317PubMedGoogle Scholar
  30. 30.
    Jacoby RF, Marshall DJ, Kailas S et al (1995) Genetic instability associated with adenoma to carcinoma progression in hereditary nonpolyposis colon cancer. Gastroenterology 109(1):73–82PubMedGoogle Scholar
  31. 31.
    Iino H, Simms L, Young J et al (2000) DNA microsatellite instability and mismatch repair protein loss in adenomas presenting in hereditary non-polyposis colorectal cancer. Gut 47(1):37–42PubMedGoogle Scholar
  32. 32.
    Samowitz WS, Slattery ML (1997) Microsatellite instability in colorectal adenomas. Gastroenterology 112(5):1515–1519PubMedGoogle Scholar
  33. 33.
    Jen J, Powell SM, Papadopoulos N et al (1994) Molecular determinants of dysplasia in colorectal lesions. Cancer Res 54(21):5523–5526PubMedGoogle Scholar
  34. 34.
    Otori K, Oda Y, Sugiyama K et al (1997) High frequency of K-ras mutations in human colorectal hyperplastic polyps. Gut 40(5):660–663PubMedGoogle Scholar
  35. 35.
    Longacre TA, Fenoglio-Preiser CM (1990) Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia. Am J Surg Pathol 14(6):524–537PubMedCrossRefGoogle Scholar
  36. 36.
    Hawkins NJ, Ward RL (2001) Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas (see comment). J Natl Cancer Inst 93(17):1307–1313PubMedGoogle Scholar
  37. 37.
    Goldstein NS, Bhanot P, Odish E et al (2003) Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas. Am J Clin Pathol 119(6):778–796PubMedGoogle Scholar
  38. 38.
    Kochhar R, Halling KC, McDonnell S et al (1997) Allelic imbalance and microsatellite instability in resected Duke’s D colorectal cancer. Diagn Mol Pathol 6(2):78–84PubMedGoogle Scholar
  39. 39.
    Fishel R, Wilson T (1997) MutS homologs in mammalian cells. Curr Opin Genet Dev 7(1):105–113PubMedGoogle Scholar
  40. 40.
    Fishel R, Lescoe MK, Rao MR et al (1993) The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer [published erratum appears in Cell 1994 Apr 8;77(1):167]. Cell 75(5):1027–1038PubMedGoogle Scholar
  41. 41.
    Wilson TM, Ewel A, Duguid JR et al (1995) Differential cellular expression of the human MSH2 repair enzyme in small and large intestine. Cancer Res 55(22):5146–5150PubMedGoogle Scholar
  42. 42.
    Kolodner RD, Marsischky GT (1999) Eukaryotic DNA mismatch repair. Curr Opin Genet Dev 9(1):89–96PubMedGoogle Scholar
  43. 43.
    Fink D, Aebi S, Howell SB (1998) The role of DNA mismatch repair in drug resistance. Clin Cancer Res 4(1):1–6PubMedGoogle Scholar
  44. 44.
    Fink D, Nebel S, Norris PS et al (1998) The effect of different chemotherapeutic agents on the enrichment of DNA mismatch repair-deficient tumour cells. Br J Cancer 77(5):703–708PubMedGoogle Scholar
  45. 45.
    Andreotti P, Cree I, Kurbacher C et al (1995) Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma. Cancer Res 55(22):5276–5282PubMedGoogle Scholar
  46. 46.
    Griffin S, Branch P, Xu YZ et al (1994) DNA mismatch binding and incision at modified guanine bases by extracts of mammalian cells: implications for tolerance to DNA methylation damage. Biochemistry 33(16):4787–4793PubMedGoogle Scholar
  47. 47.
    Boyer JC, Umar A, Risinger JI et al (1995) Microsatellite instability, mismatch repair deficiency, and genetic defects in human cancer cell lines. Cancer Res 55(24):6063–6070PubMedGoogle Scholar
  48. 48.
    Koi M, Umar A, Chauhan DP et al (1994) Human chromosome 3 corrects mismatch repair deficiency and microsatellite instability and reduces N-methyl-N′-nitro-N-nitrosoguanidine tolerance in colon tumor cells with homozygous hMLH1 mutation [erratum appears in Cancer Res 1995 Jan 1;55(1):201]. Cancer Res 54(16):4308–4312PubMedGoogle Scholar
  49. 49.
    Watanabe Y, Haugen-Strano A, Umar A et al (2000) Complementation of an hMSH2 defect in human colorectal carcinoma cells by human chromosome 2 transfer. Mol Carcinog 29(1):37–49PubMedGoogle Scholar
  50. 50.
    Umar A, Koi M, Risinger JI et al (1997) Correction of hypermutability, N-methyl-N′-nitro-N-nitrosoguanidine resistance, and defective DNA mismatch repair by introducing chromosome 2 into human tumor cells with mutations in MSH2 and MSH6. Cancer Res 57(18):3949–3955PubMedGoogle Scholar
  51. 51.
    Hickman MJ, Samson LD (1999) Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents. Proc Natl Acad Sci USA 96(19):10764–10769PubMedGoogle Scholar
  52. 52.
    Carethers JM, Hawn MT, Chauhan DP et al (1996) Competency in mismatch repair prohibits clonal expansion of cancer cells treated with N-methyl-N′-nitro-N-nitrosoguanidine. J Clin Invest 98(1):199–206PubMedCrossRefGoogle Scholar
  53. 53.
    Hawn MT, Umar A, Carethers JM et al (1995) Evidence for a connection between the mismatch repair system and the G2 cell cycle checkpoint. Cancer Res 55(17):3721–3725PubMedGoogle Scholar
  54. 54.
    Elion GB (1989) The purine path to chemotherapy. Science 244(4900):41–47PubMedGoogle Scholar
  55. 55.
    Aebi S, Fink D, Gordon R et al (1997) Resistance to cytotoxic drugs in DNA mismatch repair-deficient cells. Clin Cancer Res 3(10):1763–1767PubMedGoogle Scholar
  56. 56.
    Claij N, te Riele H (1999) Microsatellite instability in human cancer: a prognostic marker for chemotherapy? Exp Cell Res 246(1):1–10PubMedGoogle Scholar
  57. 57.
    Aebi S, Kurdihaidar B, Gordon R et al (1996) Loss of DNA mismatch repair in acquired resistance to cisplatin. Cancer Res 56(13):3087–3090PubMedGoogle Scholar
  58. 58.
    Anthoney DA, McIlwrath AJ, Gallagher WM et al (1996) Microsatellite instability, apoptosis, and loss of p53 function in drug-resistant tumor cells. Cancer Res 56(6):1374–1381PubMedGoogle Scholar
  59. 59.
    Cascinu S, Georgoulias V, Kerr D et al (2003) Colorectal cancer in the adjuvant setting: perspectives on treatment and the role of prognostic factors. Ann Oncol 14(Suppl 2):ii25–ii29PubMedGoogle Scholar
  60. 60.
    Longley DB, Harkin DP, Johnston PG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3(5):330–338PubMedGoogle Scholar
  61. 61.
    van Laar JA, Rustum YM, Ackland SP et al (1998) Comparison of 5-fluoro-2′-deoxyuridine with 5-fluorouracil and their role in the treatment of colorectal cancer. Eur J Cancer 34(3):296–306PubMedGoogle Scholar
  62. 62.
    Elsaleh H, Powell B, Soontrapornchai P et al (2000) p53 gene mutation, microsatellite instability and adjuvant chemotherapy: impact on survival of 388 patients with Dukes’ C colon carcinoma. Oncology 58(1):52–59PubMedGoogle Scholar
  63. 63.
    Elsaleh H, Joseph D, Grieu F et al (2000) Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer (comment). Lancet 355(9217):1745–1750PubMedGoogle Scholar
  64. 64.
    Barratt PL, Seymour MT, Stenning SP et al (2002) DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study. Lancet 360(9343):1381–1391PubMedGoogle Scholar
  65. 65.
    Hemminki A, Mecklin JP, Jarvinen H et al (2000) Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy (comment). Gastroenterology 119(4):921–928PubMedGoogle Scholar
  66. 66.
    Ribic CM, Sargent DJ, Moore MJ et al (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349(3):247–257PubMedGoogle Scholar
  67. 67.
    Carethers JM, Chauhan DP, Fink D et al (1999) Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 117(1):123–131PubMedGoogle Scholar
  68. 68.
    Yang JL, Friedlander ML (2001) Effect of nifedipine in metastatic colon cancer with DNA mismatch repair gene defect. Lancet 357(9270):1767–1768PubMedGoogle Scholar
  69. 69.
    Chen XX, Lai MD, Zhang YL et al (2002) Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5-fluorouracil alone in human colon cancer cell lines. World Journal of Gastroenterology 8(5):841–846PubMedGoogle Scholar
  70. 70.
    Bras-Goncalves RA, Pocard M, Formento JL et al (2001) Synergistic efficacy of 3n-butyrate and 5-fluorouracil in human colorectal cancer xenografts via modulation of DNA synthesis. Gastroenterology 120(4):874–888PubMedGoogle Scholar
  71. 71.
    Meyers M, Wagner MW, Hwang HS et al (2001) Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. Cancer Res 61(13):5193–5201PubMedGoogle Scholar
  72. 72.
    Bunz F, Hwang PM, Torrance C et al (1999) Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J Clin Invest 104(3):263–269PubMedGoogle Scholar
  73. 73.
    Longley DB, Boyer J, Allen WL et al (2002) The role of thymidylate synthase induction in modulating p53-regulated gene expression in response to 5-fluorouracil and antifolates. Cancer Res 62(9):2644–2649PubMedGoogle Scholar
  74. 74.
    Maxwell PJ, Longley DB, Latif T et al (2003) Identification of 5-fluorouracil-inducible target genes using cDNA microarray profiling. Cancer Res 63(15):4602–4606PubMedGoogle Scholar
  75. 75.
    Pocard M, Bras-Goncalves R, Hamelin R et al (2000) Response to 5-fluorouracil of orthotopically xenografted human colon cancers with a microsatellite instability: influence of P53 status. Anticancer Res 20(1A):85–90PubMedGoogle Scholar
  76. 76.
    Wong NA, Brett L, Stewart M et al (2001) Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma. Br J Cancer 85(12):1937–1943PubMedGoogle Scholar
  77. 77.
    van Triest B, Pinedo HM, van Hensbergen Y et al (1999) Thymidylate synthase level as the main predictive parameter for sensitivity to 5-fluorouracil, but not for folate-based thymidylate synthase inhibitors, in 13 nonselected colon cancer cell lines. Clin Cancer Res 5(3):643–654PubMedGoogle Scholar
  78. 78.
    van Triest B, Pinedo HM, Blaauwgeers JLG et al (2000) Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer. Clin Cancer Res 6(3):1063–1072PubMedGoogle Scholar
  79. 79.
    Peters GJ, van der Wilt CL, van Groeningen CJ et al (1994) Thymidylate synthase inhibition after administration of fluorouracil with or without leucovorin in colon cancer patients: implications for treatment with fluorouracil. J Clin Oncol 12:2035–2042PubMedGoogle Scholar
  80. 80.
    Boulay JL, Mild G, Lowy A et al (2002) SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer. Br J Cancer 87(6):630–634PubMedGoogle Scholar
  81. 81.
    Tajima A, Hess MT, Cabrera BL et al (2004) The mismatch repair complex hMutS alpha recognizes 5-fluorouracil-modified DNA: implications for chemosensitivity and resistance. Gastroenterology 127(6):1678–1684PubMedGoogle Scholar
  82. 82.
    Rosty C, Chazal M, Etienne MC et al (2001) Determination of microsatellite instability, p53 and K-RAS mutations in hepatic metastases from patients with colorectal cancer: relationship with response to 5-fluorouracil and survival. Int J Cancer 95(3):162–167PubMedGoogle Scholar
  83. 83.
    Carethers JM, Smith EJ, Behling CA et al (2004) Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 126(2):394–401PubMedGoogle Scholar
  84. 84.
    Giardiello FM, Hamilton SR, Krush AJ et al (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328(18):1313–1316PubMedGoogle Scholar
  85. 85.
    Giardiello FM, Yang VW, Hylind LM et al (2002) Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med 346(14):1054–1059PubMedGoogle Scholar
  86. 86.
    Giovannucci E, Egan KM, Hunter DJ et al (1995) Aspirin and the risk of colorectal cancer in women. N Engl J Med 333(10):609–614PubMedGoogle Scholar
  87. 87.
    Suh O, Mettlin C, Petrelli NJ (1993) Aspirin use, cancer, and polyps of the large bowel. Cancer 72(4):1171–1177PubMedGoogle Scholar
  88. 88.
    Thun MJ, Namboodiri MM, Heath CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325(23):1593–1596PubMedCrossRefGoogle Scholar
  89. 89.
    Thun MJ, Namboodiri MM, Calle EE et al (1993) Aspirin use and risk of fatal cancer (see comment). Cancer Res 53(6):1322–1327PubMedGoogle Scholar
  90. 90.
    Peleg, II, Maibach HT, Brown SH et al (1994) Aspirin and nonsteroidal anti-inflammatory drug use and the risk of subsequent colorectal cancer (see comment). Arch Intern Med 154(4):394–399PubMedGoogle Scholar
  91. 91.
    Sheehan KM, Sheahan K, O’Donoghue DP et al (1999) The relationship between cyclooxygenase-2 expression and colorectal cancer [erratum appears in JAMA 2000 Mar 15;283(11):1427]. Jama 282(13):1254–1257PubMedGoogle Scholar
  92. 92.
    Chapple KS, Cartwright EJ, Hawcroft G et al (2000) Localization of cyclooxygenase-2 in human sporadic colorectal adenomas. Am J Pathol 156(2):545–553PubMedGoogle Scholar
  93. 93.
    Sato T, Yoshinaga K, Okabe S et al (2003) Cyclooxygenase-2 expression in colorectal adenomas. Dis Colon Rectum 46(6):786–792PubMedGoogle Scholar
  94. 94.
    Sheehan KM, O’Connell F, O’Grady A et al (2004) The relationship between cyclooxygenase-2 expression and characteristics of malignant transformation in human colorectal adenomas. Eur J Gastroenterol Hepatol 16(6):619–625PubMedGoogle Scholar
  95. 95.
    Oshima M, Dinchuk JE, Kargman SL et al (1996) Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87(5):803–809PubMedGoogle Scholar
  96. 96.
    Oshima M, Murai N, Kargman S et al (2001) Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. Cancer Res 61(4):1733–1740PubMedGoogle Scholar
  97. 97.
    Yao M, Kargman S, Lam EC et al (2003) Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice. Cancer Res 63(3):586–592PubMedGoogle Scholar
  98. 98.
    Tomozawa S, Nagawa H, Tsuno N et al (1999) Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522. Br J Cancer 81(8):1274–1279PubMedGoogle Scholar
  99. 99.
    Masferrer JL, Leahy KM, Koki AT et al (2000) Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60(5):1306–1311PubMedGoogle Scholar
  100. 100.
    Tsujii M, Kawano S, Tsuji S et al (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93(5):705–716PubMedGoogle Scholar
  101. 101.
    Karnes WE Jr, Shattuck-Brandt R, Burgart LJ et al (1998) Reduced COX-2 protein in colorectal cancer with defective mismatch repair. Cancer Res 58(23):5473–5477PubMedGoogle Scholar
  102. 102.
    Sinicrope FA, Lemoine M, Xi L et al (1999) Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers. Gastroenterology 117(2):350–358PubMedGoogle Scholar
  103. 103.
    Nasir A, Kaiser HE, Boulware D et al (2004) Cyclooxygenase-2 expression in right- and left-sided colon cancer: a rationale for optimization of cyclooxygenase-2 inhibitor therapy. Clinical Colorectal Cancer 3(4):243–247PubMedCrossRefGoogle Scholar
  104. 104.
    Sheng H, Shao J, Kirkland SC et al (1997) Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 99(9):2254–2259PubMedGoogle Scholar
  105. 105.
    Smith ML, Hawcroft G, Hull MA (2000) The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action. Eur J Cancer 36(5):664–674PubMedGoogle Scholar
  106. 106.
    Fink D, Nebel S, Norris PS et al (1998) The effect of different chemotherapeutic agents on the enrichment of DNA mismatch repair-deficient tumour cells. Br J Cancer 77(5):703–708PubMedGoogle Scholar
  107. 107.
    Cassinello J, Lopez-Alvarez P, Martinez-Guisado A et al (2003) Phase II study of weekly irinotecan (CPT-11) as second-line treatment of patients with advanced colorectal cancer. Med Oncol 20(1):37–43PubMedGoogle Scholar
  108. 108.
    Bras-Goncalves RA, Rosty C, Laurent-Puig P et al (2000) Sensitivity to CPT-11 of xenografted human colorectal cancers as a function of microsatellite instability and p53 status. Br J Cancer 82(4):913–923PubMedGoogle Scholar
  109. 109.
    Magrini R, Bhonde MR, Hanski M et al (2002) Cellular effects of CPT-11 on colon carcinoma cells: dependence on p53 and hMLH1 status. Int J Cancer 101:23–31PubMedGoogle Scholar
  110. 110.
    Chamara M, Edmonston TB, Burkholder S et al (2004) Microsatellite statusand cell cycle associated markers in rectal cancer patients undergoing combined regimen of 5-FU and CPT-11 chemotherapy and radiotherapy. Anticancer Res 24(5B):3161–3167Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Cancer Genetics, Kolling Institute of Medical ResearchRoyal North Shore Hospital and University of SydneySt. LeonardsAustralia

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