Clinically Accurate Orthotopic Mouse Models of Cancer

  • Robert M. Hoffman
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 58)


In the past 10 years, we have developed a new approach to the development of a clinically accurate rodent model for human cancer based on our invention of surgical orthotopic implantation (SOI). The SOI models have been described in approx 70 publications (2-72) and in four patents.* SOI allows human tumors of all the major types of human cancer to reproduce clinical-like tumor growth and metastasis in the transplanted rodents (2-72). The major features of the SOI models are reviewed here and also compared to transgenic mouse models of cancer.


Nude Mouse Bone Metastasis Human Prostate Cancer Surgical Suture Tumor Fragment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Fidler, I. J. (1990) Critical factors in the biology of human cancer metastases: twenty eighth G.H.A. Clowes Memorial Lecture. Cancer Res. 50, 6130–6138.PubMedGoogle Scholar
  2. 2.
    Fu, X., Besterman, J. M., Monosov, A., and Hoffman, R. M. (1991) Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically-intact patient specimens. Proc. Natl. Acad. Sci. USA 88, 9345–9349.PubMedCrossRefGoogle Scholar
  3. 3.
    Fu, X., Theodorescu, D., Kerbel, R. S., and Hoffman, R. M. (1991) Extensive multi-organ metastasis following orthotopic onplantation of histologically-in-tact human bladder carcinoma tissue in nude mice. Int. J. Cancer 49, 938–939.PubMedCrossRefGoogle Scholar
  4. 4.
    Fu, X. and Hoffman, R. M. (1992) Human RT-4 bladder carcinoma is highly metastatic in nude mice and comparable to ras-H-transformed RT-4 when orthotopically onplanted as histologically-intact tissue. Int. J. Cancer 51, 989–991.PubMedCrossRefGoogle Scholar
  5. 5.
    Wang, X., Fu, X., and Hoffman, R. M. (1992) A new patient-like metastatic model of human lung cancer constructed orthotopically with intact tissue via thoracotomy in immunodeficient mice. Int. J. Cancer 51, 992–995.PubMedCrossRefGoogle Scholar
  6. 6.
    Fu, X., Guadagni, F., and Hoffman, R. M. (1992) A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically from histologically-intact patient specimens. Proc. Natl. Acad. Sci. USA 89, 5645–5649.PubMedCrossRefGoogle Scholar
  7. 7.
    Hoffman, R.M. (1992) Patient-like models of human cancer in mice. Curr. Perspect. Mol. Cell. Oncol. 1(B), 311–326.Google Scholar
  8. 8.
    Kuo, T-H, Kubota, T., Watanabe, M., Furukawa, T., Kase, S., Tanino, H., et al. (1992) Orthotopic reconstitution of human small-cell lung carcinoma after intravenous transplantation in SCID mice. Anticancer Res. 12, 1407–1410.PubMedGoogle Scholar
  9. 9.
    Fu, X., Herrera, H., Kubota, T. and Hoffman, R. M. (1992) Extensive liver metastasis from human colon cancer in nude and scid mice after orthotopic onplantation of histologically-intact human colon carcinoma tissue. AnticancerRes. 12, 1395–1398.Google Scholar
  10. 10.
    Wang, X., Fu, X., and Hoffman, R. M. (1992) A patient-like metastasizing model of human lung adenocarcinoma constructed via thoracotomy in nude mice. Anti-cancer Res. 12, 1399–1402.Google Scholar
  11. 11.
    Wang, X., Fu, X., Kubota, T., and Hoffman, R. M. (1992) A new patient-like metastatic model of human small-cell lung cancer constructed orthotopic ally with intact tissue via thoracotomy in nude mice. Anticancer Res. 12, 1403–1406.PubMedGoogle Scholar
  12. 12.
    Fu, X., Herrera, H., and Hoffman, R. M. (1992) Orthotopic growth and metastasis of human prostate carcinoma in nude mice after transplantation of histologi-cally intact tissue. Int. J. Cancer 52, 987–990.PubMedCrossRefGoogle Scholar
  13. 13.
    Hoffman, R. M. (1992) Histoculture and the immunodeficient mouse come to the cancer clinic: rational approaches to individualizing cancer therapy and new drug evaluation (Review). Int. J. Oncol. 1, 467–474.PubMedGoogle Scholar
  14. 14.
    Furukawa, T., Fu, X., Kubota, T., Watanabe, M., Kitajima, M., and Hoffman, R. M. (1993) Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically-intact tissue. Cancer Res. 53, 1204–1208.PubMedGoogle Scholar
  15. 15.
    Furukawa, T., Kubota, T., Watanabe, M., Kitajima, M., and Hoffman, R. M. (1993) Orthotopic transplantation of histologically-intact clinical specimens of stomach cancer to nude mice: correlation of metastatic sites in mouse and individual patient donors. Int. J. Cancer 53, 608–612.PubMedCrossRefGoogle Scholar
  16. 16.
    Fu, X. and Hoffman, R. M. (1993) Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens. Anticancer Res. 13, 283–286.PubMedGoogle Scholar
  17. 17.
    Furukawa, T., Kubota, T., Watanabe, M., Kuo, P. H., Kase, S., Saikawa, Y., et al. (1993) Immunochemotherapy prevents human colon cancer metastasis after orthotopic onplantation of histologically-intact tumor tissue in nude mice. Anticancer Res. 13, 287–291.PubMedGoogle Scholar
  18. 18.
    Kuo, T.-H., Kubota, T., Watanabe, M., Fujita, S., Furukawa, T., Teramoto, T., et al. (1993) Early resection of primary orthotopically-growing human colon tumor in nude mouse prevents liver metastasis: further evidence for patient-like hematogenous metastatic route. Anticancer Res. 13, 293–298.PubMedGoogle Scholar
  19. 19.
    Furukawa, T., Kubota, T., Watanabe, M., Kitajima, M., and Hoffman, R. M. (1993) Differential chemosensitivity of local and metastatic human stomach cancer after orthotopic transplantation of histologically-intact tumor tissue in nude mice. Int. J. Cancer 54, 397–401.PubMedCrossRefGoogle Scholar
  20. 20.
    Furukawa, T., Kubota, T., Watanabe, M., Kitajima, M., and Hoffman, R. M. (1993) A novel &“patient-like&” treatment model of human pancreatic cancer constructed using orthotopic transplantation of histologically-intact human tumor-tissue in nude mice. Cancer Res. 53, 3070–3072.PubMedGoogle Scholar
  21. 21.
    Kuo, T.-H., Kubota, T., Watanabe, M., Furukawa, T., Kase, S., Tanino, H., et al. (1993) Site-specific chemosensitivity of human small-cell lung carcinoma growing orthotopically compared to subcutaneously in SCID mice: The importance of ortho-topic models to obtain relevant drug evaluation data. Anticancer Res. 13, 627–630.PubMedGoogle Scholar
  22. 22.
    Furukawa, T., Kubota, T., Watanabe, M., Kuo, T.-H, Nishibori, H., Kase, S., et al. (1993) A metastatic model of human colon cancer constructed using cecal implantation of cancer tissue in nude mice. Jpn. J. Surg. 23, 420–423.Google Scholar
  23. 23.
    Fu, X., Le, P., and Hoffman, R. M. (1993) A metastatic orthotopic transplant nude-mouse model of human patient breast cancer. Anticancer Res. 13, 901–904.PubMedGoogle Scholar
  24. 24.
    Astoul, P. Colt, H. G., Wang, X., and Hoffman, R. M. (1993) Metastatic human pleural ovarian cancer model constructed by orthotopic implantation of fresh histologically-intact patient carcinoma in nude and SCID-mice. Anticancer Res. 13, 1999–2002.PubMedGoogle Scholar
  25. 25.
    Astoul, P., Wang, X., and Hoffman, R. M. (1993) &“Patient-Like&” nude and SCID mouse models of human lung and pleural cancer (Review). Int. J. Oncol. 3, 713–718.PubMedGoogle Scholar
  26. 26.
    Kubota, T., Inoue, S., Furukawa, T., Ishibiki, K., Kitajima, M., Kawamura, E., and Hoffman, R. M. (1993) Similarity of serum-tumor pharmacokinetics of antitumor agents in man and nude mice. Anticancer Res. 13, 1481–1484.PubMedGoogle Scholar
  27. 27.
    Astoul, P., Colt, H. G., Wang, X., and Hoffman, R. M. (1994) A &“patient-like&” nude mouse model of parietal pleural human lung adenocarcinoma. Anticancer Res. 14, 85–92.PubMedGoogle Scholar
  28. 28.
    Astoul, P., Colt, H. G., Wang, X., Boutin, C., and Hoffman, R. M. (1994) &“ A &“patient-like&” nude mouse metastatic model of advanced human pleural cancer. &” J. Cell Biochem. 56, 9–15.PubMedCrossRefGoogle Scholar
  29. 29.
    Wang, X., Fu, X., Brown, P. D., Crimmin, M. J., and Hoffman, R. M. (1994) Matrix metalloproteinase inhibitor BB-95 (Batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res 54, 4726–4728.PubMedGoogle Scholar
  30. 30.
    Hoffman, R. M. (1994) Orthotopic is orthodox: why are orthotopic-transplant metastatic models different from all other models? J. Cell Biochem. 56, 1–3.PubMedCrossRefGoogle Scholar
  31. 31.
    Togo, S., Shimada, H., Kubota, T., Moossa, A. R., and Hoffman, R.M. (1995) Seed to soil is a return trip in metastasis. Anticancer Res. 15, 791–794.PubMedGoogle Scholar
  32. 32.
    Togo, S., Shimada, H., Kubota, T., Moossa, A. R., and Hoffman, R. M. (1995) Host organ specifically determines cancer progression. Cancer Res. 55, 681–684.PubMedGoogle Scholar
  33. 33.
    Kuo, T.-H., Kubota, T., Watanbe, M., Furukawa, T., Teramoto, T., Ishibiki, K., et al. (1995) Liver colonization competence governs colon cancer metastasis. Proc. Natl. Acad. Sci. USA 92, 12085–12089.PubMedCrossRefGoogle Scholar
  34. 34.
    Togo, S., Wang, X., Shimada, H., Moossa, A. R., and Hoffman, R. M. (1995) Cancer seed and soil can be highly selective: human-patient colon tumor lung metastasis grows in nude mouse lung but not colon or subcutis. Anticancer Res. 15, 795–798.PubMedGoogle Scholar
  35. 35.
    Dutton, G. (1996) AntiCancer Inc. scientists identify a key governing step in the metastasis of cancer. Genet. Engng. News 16, January 15.Google Scholar
  36. 36.
    Holzman, D. (1996) Of mice and metastasis: a new for-profit model emerges. J. Natl. Cancer Inst. 88, 396–397.CrossRefGoogle Scholar
  37. 37.
    Leff, D. N. (1996) MetaMouse models colon cancer metastasis with clinical potential. BioWorld Today 7, January 8.Google Scholar
  38. 38.
    Sun, F. X., Tang, Z. Y., Liu, K. D., Ye, S. L., Xue, Q., Gao, D. M., and Ma, Z. C. (1996) Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int. J. Cancer 66, 239–243.PubMedCrossRefGoogle Scholar
  39. 39.
    An, Z., Wang, X., Kubota, T., Moossa, A. R., and Hoffman, R. M. (1996) A clinical nude mouse metastatic model for highly malignant human pancreatic cancer. Anticancer Res. 16, 627–632.PubMedGoogle Scholar
  40. 40.
    Riordan, T. (1996) A technique is said to ease attachment of tumors to mice, making them &“little cancer patients.&” New York Times, &“Patents&” Column, March 4.Google Scholar
  41. 41.
    Murray, G., Duncan, M., O’Neil, P., Melvin, W., and Fothergill, J. (1996) Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat. Med. 2, 461–462.PubMedCrossRefGoogle Scholar
  42. 42.
    Hoffman, R. M. (1996) Fertile seed and rich soil: development of patient-like models of human cancer by surgical orthotopic implantation of intact tissue, in Update Series: Comprehensive Textbook of Oncology, Vol. 3, Schimpff, S. C. et al. (eds.), Williams & Wilkins, Baltimore, pp. 1–10.Google Scholar
  43. 43.
    Sun, F-X., Tang, Z-Y., Liu, K-D., Xue, Q., Gao, D-M., Yu, Y-Q., et al. (1996) Metastatic models of human liver cancer in nude mice orthotopically constructed by using histologically intact patient specimens. J. Cancer Res. Clin. Oncol. 122, 397–402.PubMedCrossRefGoogle Scholar
  44. 44.
    Astoul, P., Wang, X., Colt, H. G., Boutin, C., and Hoffman, R. M. (1996) A patient-like human malignant pleural mesothelioma nude-mouse model. Oncol. Rep. 3, 483–487.PubMedGoogle Scholar
  45. 45.
    Colt, H. G., Astoul, P., Wang, X., Yi, E. S., Boutin, C., and Hoffman, R. M. (1996) Clinical course of human epithelial-type malignant pleural mesothelioma replicated in an orthotopic-transplant nude mouse model. Anticancer Res. 16, 633–640.PubMedGoogle Scholar
  46. 46.
    An, Z., Wang, X., Astoul, P., Danays, T., and Hoffman, R. M. (1996) Interferon gamma is higly effective against orthotopically-implanted human pleural adenocarcinoma in nude mice. Anticancer Res. 16, 2545–2551.PubMedGoogle Scholar
  47. 47.
    Olbina, G., Cieslak, D., Ruzdijic, S., Esler, C., An, Z., Wang, X., et al. (1996) Reversible inhibition of IL-8 receptor B mRNA expression and proliferation in non-small cell lung cancer by antisense oligonucleotides. Anticancer Res. 16, 3525–3530.PubMedGoogle Scholar
  48. 48.
    An, Z., Wang, X., Willmott, N., Chander, S. K., Tickle, S., Docherty, A. J. P., et al. (1997) Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor. Clin. Exp. Metast. 15, 184–195.CrossRefGoogle Scholar
  49. 49.
    Hoffman, R. M. (1997) Fertile seed and rich soil: the development of clinically relevant models of human cancer by surgical orthotopic implantation of intact tissue, in Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval, Teicher, B. (ed.), Humana Press, Totowa, NJ, pp. 127–144.Google Scholar
  50. 50.
    hishima, T., Miyagi, Y., Wang, X., Yamaoka, H., Shimada, H., Moossa, A. R., and Hoffman, R. M. (1997) Cancer invasion and micrometastasis visualized in live tissue by green fluorescent protein expression. Cancer Res. 57, 2042–2047.Google Scholar
  51. 51.
    Inada, T., Ichikawa, A., Kubota, T., Ogata, Y., Moossa, A. R., and Hoffman, R. M. (1997) 5-FU-induced apoptosis correlates with efficacy against human gastric and colon cancer xenografts in nude mice. Anticancer Res. 17, 1965–1972.PubMedGoogle Scholar
  52. 52.
    Chishima, T., Miyagi, Y., Wang, X., Baranov, E., Tan, Y., Shimada, H., et al. (1997) Metastatic patterns of lung cancer visualized live and in process by green fluorescent protein expression. Clin. Exp. Metast. 15, 547–552.CrossRefGoogle Scholar
  53. 53.
    Chishima, T., Miyagi, Y., Wang, X., Tan, Y., Shimada, H., Moossa, A. R., and Hoffman, R. M. (1997) Visualization of the metastatic process by green fluorescent protein expression. Anticancer Res. 17, 2377–2384.PubMedGoogle Scholar
  54. 54.
    Chishima, T., Yang, M., Miyagi, Y., Li, L., Tan, Y., Baranov, E., et al. (1997) Governing step of metastasis visualized in vitro. Proc. Natl. Acad. Sci. USA 94, 11,573–11,576.CrossRefGoogle Scholar
  55. 55.
    Tomikawa, M., Kubota, T., Matsuzaki, S.W., Takahasi, S., Kitajima, M., Moossa, A. R., and Hoffman, R. M. (1997) Mitomycin C and cisplatin increase survival in a human pancreatic cancer metastatic model. Anticancer Res. 17, 3623–3626.PubMedGoogle Scholar
  56. 56.
    Chishima, T., Miyagi, Y., Li, L., Tan, Y., Baranov, E., Yang, M., et al. (1997) The use of histoculture and green fluorescent protein to visualize tumor cell host interaction. In Vitro Cell. Dev. Biol. 33, 745–747.CrossRefGoogle Scholar
  57. 57.
    Chang, S-G., Kim, J.I., Jung, J-C., Rho, Y-S., Lee, K-T., An, Z., Wang, X., and Hoffman, R. M. (1997) Antimetastatic activity of the new platinum analog (cis-dach)(DPPE)·2NO3 in a metastatic model of human bladder cancer. Anticancer Res. 17, 3239–3242.PubMedGoogle Scholar
  58. 58.
    Dev, S. B., Nanda, G. S., An, Z., Wang, X., Hoffman, R. M., and Hofmann, G. A. (1997) Effective electroporation therapy of human pancreatic tumors implanted in nude mice. Drug Delivery 4, 293–299.CrossRefGoogle Scholar
  59. 59.
    An, Z., Wang, X., Geller, J., Moossa, A. R., and Hoffman, R. M. (1998) Surgical orthotopic implantation allows high lung and lymph node metastatic expression of human prostate carcinoma cell line PC-3 in nude mice. Prostate 34, 169–174.PubMedCrossRefGoogle Scholar
  60. 60.
    Nanda, G. S., Sun, F. X., Hofmann, G. A., Hoffman, R. M., and Dev, S. B. (1998) Electroporation therapy of human larynx tumors HEp-2 implanted in nude mice. Anticancer Res. 18, 999–1004.PubMedGoogle Scholar
  61. 61.
    Nanda, G. S., Sun, F. X., Hofmann, G. A., Hoffman, R. M., and Dev, S. B. (1998) Electroporation enhances therapeutic efficacy of anticancer drugs: Treatment of human pancreatic tumor in animal model. Anticancer Res. 18, 1361–1366.PubMedGoogle Scholar
  62. 62.
    Yang, M., Hasegawa, S., Jiang, P., Wang, X., Tan, Y., Chishima, T., et al. (1998) Widespread skeletal metastatic potential of human lung cancer revealed by green fluorescent protein expression. Cancer Res. 58, 4217–4221.PubMedGoogle Scholar
  63. 63.
    Sun, F-X., Sasson, A. R., Jiang, R., An, Z., Gamagami, R., Li, L., Moossa, A. R., and Hoffman, R. H. (1999) An ultra-metastatic model of human colon cancer in nude mice. Clin. Exp. Metast. 17, 41–48.CrossRefGoogle Scholar
  64. 64.
    Kiguchi, K., Kubota, T., Aoki, D., Udagawa, Y., Tamanouchi, S., Saga, M., et al. (1998) A patient-like orthotopic implantation nude mouse model of highly metastatic human ovarian cancer. Clin. Exp. Metast. 16, 751–756.CrossRefGoogle Scholar
  65. 65.
    Yang, M., Jiang, P., Sun, F. X., Hasegawa, S., Baranov, E., Chishima, T., et al. (1999) A fluorescent orthotopic bone metastasis model of human prostate cancer. Cancer Res. 59, 781–786.PubMedGoogle Scholar
  66. 66.
    Wang, X., An, Z., Geller, J., and Hoffman, R. M. (1999) A high malignancy orthotopic nude mouse model of the human prostate cancer LNCaP. Prostate 39, 182–186.PubMedCrossRefGoogle Scholar
  67. 67.
    Kanai, T., Konno, H., Tanaka, T., Matsumoto, K., Baba, M., Nakamura, S., and Baba, S.(1997) Effect of angiogenesis inhibitor TNP-470 on the progression of human gastric cancer xenotransplanted into nude mice. Int. J. Cancer 71, 838–841.PubMedCrossRefGoogle Scholar
  68. 68.
    Konno, H., Tanaka, T., Kanai, T., Maruyama, K., Nakamura, S., and Baba S. (1996) Efficacy of an angiogenesis inhibitor, TNP-470, in xenotransplanted colorectal cancer with high metastatic potential. Cancer 77, 1736–1740.PubMedGoogle Scholar
  69. 69.
    Konno, H., Tanaka, T., Matsuda, I., Kanai, T., Maruo, Y., Nishino, N., et al. (1995) Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP-470 and mitomycin C on the growth and liver metastasis of human colon cancer. Int. J. Cancer 61, 268–271.PubMedCrossRefGoogle Scholar
  70. 70.
    Konno, H., Tanaka, T., Baba, M., Matsumoto, K., Kamiya, K., Nakamura, S., et al. (1997) Antitumor effect of angiogenesis inhibitors on colon cancer. Biotherapy 11, 993–996.Google Scholar
  71. 71.
    Tanaka, T., Konno, H., Matsuda, I., Nakamura, S., and Baba, S. (1995) Prevention of hepatic metastasis of human colon cancer by angiogenesis inhibitor TNP-470. Cancer Res. 55, 836–839.PubMedGoogle Scholar
  72. 72.
    Konno, H., Arai, T., Tanaka, T., Baba, M., Matsumoto, K., Kanai, T., et al. (1998) Antitumor effect of neutralizing antibody to vascular endothelial growth factor on liver metastasis of endocrine neoplasm. Jpn. J. Cancer Res. 89, 933–939.PubMedCrossRefGoogle Scholar
  73. 73.
    Tanizawa, A., Fujimori, A., Fujimori, Y., and Pommier, Y. (1994) Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. J. Natl. Cancer Inst. 86, 836–842.PubMedCrossRefGoogle Scholar
  74. 74.
    Schabel, F. M. (1975) animal models as predictive systems. In Cancer Chemotherapy Fundamental Concepts and Recent Advances, Year Book Publishers, pp. 323–355.Google Scholar
  75. 75.
    Goldin, A., Serpick, A. A., and Mantel, N. (1966) A commentary. Experimental procedures and clinical predictability value. Cancer Chemother. Rep. 50, 173–218.PubMedGoogle Scholar
  76. 76.
    Rygaard, J. and Poulsen, C. O. (1969) Heterotransplantation of a human malignant tumor to nude mice. Acta Pathol. Microbiol. Scand. 77, 758–760.PubMedCrossRefGoogle Scholar
  77. 77.
    Ovejera, A. (1987) The use of human tumor xenografts in large-scale drug screening, in Rodent Tumor Model in Experimental Cancer Therapy, Kalimann, R. F. (ed.),Pergamon Press, New York, pp. 218–220.Google Scholar
  78. 78.
    Wilmanns, C., Fan, D., O’Brian, C. A., Bucana, C. D., and Fidler, I. J. (1992) Orthotopic and ectopic organ environments differentially influence the sensitivity of murine colon carcinoma cells to doxorubicin and 5-fluorouracil. Int. J. Cancer 52, 98–104.PubMedCrossRefGoogle Scholar
  79. 79.
    Maeda, H., Segawa, T., Kamoto, T., Yoshida, H., Kakizuka, A., Ogawa, O., and Kakehi, Y. (2000) Rapid detection of candidate metastatic foci in the orthotopic inoculation model of androgen-sensitive prostate cancer cells introduced with green fluorescent protein. Prostate 45, 335–340.PubMedCrossRefGoogle Scholar
  80. 80.
    Rougier, R., Bugat, R., Douillard, J. Y., Culine, S., Suc, E., Brunet, P., et al. (1997) Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naïve patients and patients pretreated with fluorouracil-based chemotherapy. J. Clin. Oncol., 15, 251–260.PubMedGoogle Scholar
  81. 81.
    Bissery, M-C., Vrignaud, P., and Lavelle, F. (1995) Preclinical Profile of Docetaxel (Taxotere): efficacy as a single agent and in combination. Semin. Oncol. 22, Suppl. 13, 3–16.Google Scholar
  82. 82.
    Bissery, M-C., Guénard, D., Guéritte-Voegelein, F., and Lavelle, F. (1991) Experimental antitumor activity of Taxotere (RP 56976, NSC 628503), a taxol analogue. Cancer Res. 51, 4845–4852.PubMedGoogle Scholar
  83. 83.
    Nomura, T., Sakurai, Y., and Inaba, M. (1996) The Nude Mouse andAntican-cer Drug Evaluation. Central Institute for Experimental Animals, Kawasaki, Japan, 1996.Google Scholar
  84. 84.
    Plowman, J., Camalier, R., Alley, M., Sausville, E., and Schepartz, E. (1999) US-NCI testing procedures, in Relevance of Tumor Models for Anticancer Drug Development, Karger, pp. 121–136.Google Scholar
  85. 85.
    Double, J. A. (1999) A pharmacological approach for the selection of potential anticancer agents, in Relevance of Tumor Models for Anticancer Drug Development, Karger, pp. 137–144.Google Scholar
  86. 86.
    Culling, C. F. A., ed. (1963) Handbook of Histopathological Techniques, 2nd edit., Butterworth, London.Google Scholar
  87. 87.
    Hillman, G. G., Maughn, R. L., Grignon, D. J., Yudelev, M., Rubio, J., Tekyi-Mensah, S., et al. (2001) Neutron or photon irradiation for prostate tumors: enhancement of cytokine therapy in a metastatic tumor model. Clin. Cancer Res. 7, 136–144.PubMedGoogle Scholar
  88. 88.
    Cifuentes, N. and Pickren, J. W. (1979) Metastasis from carcinoma of mammary gland: an autopsy study. J. Surg. Oncol. 11, 193–205.PubMedCrossRefGoogle Scholar
  89. 89.
    Mundy, G. R. and Yoneda, T. (1995) Facilitation and suppression of bone metastasis. Clin. Orthop. 312, 34–44.PubMedGoogle Scholar
  90. 90.
    Guise, T. A. (1997) Parathyroid hormone-related protein and bone metastases. Cancer 80, 1572–1580.PubMedCrossRefGoogle Scholar
  91. 91.
    Olden, K. (1990) Human tumor bone metastasis model in athymic nude rats. J. Natl. Cancer Inst. 82, 340–341.PubMedCrossRefGoogle Scholar
  92. 92.
    Price, J. E., Polyzos, A., Zhang, R. D., and Daniels, L. M. (1990) Tumorigenic-ity and metastasis of human breast carcinoma cell lines in nude mice. Cancer Res. 50, 717–721.PubMedGoogle Scholar
  93. 93.
    Jia, T., Liu, Y. E., Liu, J., and Shi, Y. E. (1999) Stimulation of breast cancer invasion and metastasis by synuclein-γ. Cancer Res. 59, 742–747.PubMedGoogle Scholar
  94. 94.
    Bagheri-Yarmand, R., Kourbali, Y., Rath, A. M., Vassy, R., Martin, A., Jozefonvicz, J., et al. (1999) Carboxymethyl benzylamide dextran blocks angio-genesis of MDA-MB435 breast carcinoma xenograft in fat pad and its lung metastases in nude mice. Cancer Res. 59, 507–510.PubMedGoogle Scholar
  95. 95.
    Kurebayashi, J., Nukatsuka, M., Fujioka, A., Saito, H., Takeda, S., Unemi, N., et al. (1997) Postsurgical oral administration of uracil and tegafur inhibits progression of micrometastasis of human breast cancer cells in nude mice. Clin. Cancer Res. 3, 653–659.PubMedGoogle Scholar
  96. 96.
    Thompson, E. W., Brunner, N., Torri, J., Johnson, M. D., Boulay, V., Wright, A., et al. (1993) The invasive and metastatic properties of hormone-independent but hormone-responsive variants of MCF-7 human breast cancer cells. Clin. Exp. Metast. 11, 15–26.CrossRefGoogle Scholar
  97. 97.
    Arguello, F. B., Baggs, R. B., and Frantz, C. N. (1988) A murine model of experimental metastasis to bone and bone marrow. Cancer Res. 48, 6876–6881.PubMedGoogle Scholar
  98. 98.
    Sasaki, A., Boyce, B. F., Story, B., Wright, K. R., Chapman, M., Boyce, R., et al. (1995) Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res. 55, 3551–3557.PubMedGoogle Scholar
  99. 99.
    Morinaga, Y., Fujita, N., Ohishi, K., and Tsuruo, T. (1997) Stimulation of interleukin-11 production from osteoblast-like cells by transforming growth factor-β and tumor cell factors. Int. J. Cancer 71, 422–428.PubMedCrossRefGoogle Scholar
  100. 100.
    Guise, T. A., Yin, J. J., Taylor, S. D., Kumagai, Y., Dallas, M., Boyce, B. F., et al. (1996) Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. J. Clin. Invest. 98, 1544–1549.PubMedCrossRefGoogle Scholar
  101. 101.
    Sung, V., Gilles, C., Murray, A., Clarke, R., Aaron, A. D., Azumi, N., and Thompson, E. W. (1998) The LCC15-MB human breast cancer cell line expresses osteopontin and exhibits an invasive and metastatic phenotype. Exp. Cell Res. 241, 273–284.PubMedCrossRefGoogle Scholar
  102. 102.
    Wang, C. Y. and Chang, Y. W. (1997) A model for osseous metastasis of human breast cancer established by intrafemur injection of the MDA-MB-435 cells in nude mice. Anticancer Res. 17, 2471–2474.PubMedGoogle Scholar
  103. 103.
    Boring, C. C., Squines, T. S., Tong, T., and Montgomery, S. (1994) Cancer Statistics CA. 44, 7–26.CrossRefGoogle Scholar
  104. 104.
    Lepor, H., Ross, A., and Walsh, P. C. (1982) The influence of hormonal therapy on survival of men with advanced prostatic cancer. J. Urol. 128, 335–340.PubMedGoogle Scholar
  105. 105.
    Kaighn, M. E., Narayan, K. S., Ohnuki, Y., Lechner, J. F., and Jones, L. W. (1979) Establishment and characterization of a human prostate carcinoma cell line (PC-3). Invest. Urol. 17, 16–23.PubMedGoogle Scholar
  106. 106.
    Shevrin, D. H., Kukreja, S. C., Ghosh, L., and Lad, T. E. (1988) Development of skeletal metastasis by human prostate cancer in athymic nude mice. Clin. Exp. Metast. 6, 401–409.CrossRefGoogle Scholar
  107. 107.
    Pettaway, C. A., Pathak, S., Greene, G., Ramirez, E., Wilson, M. R., Killion, J. J., and Fidler, I. J. (1996) Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin. Cancer Res. 2, 1627–1636.PubMedGoogle Scholar
  108. 108.
    Wu, T. T., Sike, R. A., Cui, Q., Thalmann, G. N., Kao, C., Murphy, C. F., et al. (1998) Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. Int. J. Cancer 77, 887–894.PubMedCrossRefGoogle Scholar
  109. 109.
    Stephenson, R. A., Dinney, C. P. N., Gohji, K., Ordonez, N. G., Kilion, J. J., and Fidler, I. J. (1992) Metastasis model for human prostate cancer using orthotopic implantation in nude mice. J. Natl. Cancer Inst. 84, 951–957.PubMedCrossRefGoogle Scholar
  110. 110.
    Sato, N., Gleave, M. E., Bruchovshy, N., Rennie, P. S., Beraldi, E., and Sullivan, L. D. (1997) A metastatic and androgen-sensitive human prostate cancer model using intraprostatic inoculation of LNCaP cells in SCID mice. Cancer Res. 57, 1584–1589.PubMedGoogle Scholar
  111. 111.
    Rembrink, K., Romijn, J. C., van der Kwast, T. H., Rubben, H., and Schroder, F. H. (1997) Orthotopic implantation of human prostate cancer cell lines: a clinically-relevant animal model for metastatic prostate cancer. Prostate 31, 168–174.PubMedCrossRefGoogle Scholar
  112. 112.
    Thalmann, G. N., Anezinis, P. E., Chang, S. M., Zhau, H. E., Kim, E. E., Hopwood, V. L., et al. (1994) Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res. 54, 2577–2581.PubMedGoogle Scholar
  113. 113.
    Fleisch, H. (1991) Biphosphonates. Pharmacology and use in the treatment of tumour-induced hypercalcaemic and metastatic bone disease. Drugs 42, 919–944.PubMedCrossRefGoogle Scholar
  114. 114.
    Diel, I. J., Solomayer, E-F., Costa, S. D., Gollan, C., Goerner, R., Wallwiener, D., et al. (1998) Reduction in new metastasis in breast cancer with adjuvant clodronate treatment. N. Engl. J. Med. 339, 357–363.PubMedCrossRefGoogle Scholar
  115. 115.
    Hortobagyi, G. N., Theriault, R. L., Porter, L., et al. (1996) Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. N. Engl. J. Med. 335, 1785–1791.PubMedCrossRefGoogle Scholar
  116. 116.
    O’Rourke, N., McCloskey, E., Houghton, F., Huss, H., and Kanis, J. A. (1995) Double-blind, placebo-controlled, dose-response trial of oral clodronate in patients with bone metastases. J. Clin. Oncol. 13, 929–934.PubMedGoogle Scholar
  117. 117.
    Kanis, J. A., Powles, T., Paterson, A. H. G., McCloskey, E. V., and Ashley S. (1996) Clodronate decreases the frequency of skeletal metastases in women with breast cancer. Bone 19, 663–667.PubMedCrossRefGoogle Scholar
  118. 118.
    Sasaki, A., Yoneda, T., Terakado, N., Alcalde, R. E., Suzuki, A., and Matsumura, T. (1998) Experimental bone metastasis model of the oral maxillofacial region. Anticancer Res. 18, 1579–1584.PubMedGoogle Scholar
  119. 119.
    Stewart, T. A., Pattengale, P. K., and Leder, P. (1984) Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 38, 627–637.PubMedCrossRefGoogle Scholar
  120. 120.
    Sinn, E., Muller, W., Pattengale, P., Tepler, I., Wallace, R., and Leder, P. (1987) Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 49, 465–475.CrossRefGoogle Scholar
  121. 121.
    Guy, C. T., Cardiff, R. D., and Muller, W. J. (1992) Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol. Cell. Biol. 12, 954–961.PubMedGoogle Scholar
  122. 122.
    Guy, C. T., Webster, M. A., Schaller, M., Parsons, T. J., Cardiff, R. D., and Muller, W. J. (1992) Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc. Natl. Acad. Sci. USA 89, 10578–10582.PubMedCrossRefGoogle Scholar
  123. 123.
    Ritland, S. R., Rowse, G. J., Chang, Y., and Gendler, S. J. (1997) Loss of heterozygosity analysis in primary mammary tumors and lung metastases of MMTV-MTAg and MMTV-neu transgenic mice. Cancer Res. 57, 3520–3525.PubMedGoogle Scholar
  124. 124.
    Leder, A., Pattengale, P. K., Kuo, A., Stewart, T. A., and Leder, P. (1986) Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasma and normal development. Cell 45, 485–495.PubMedCrossRefGoogle Scholar
  125. 125.
    Greenberg, N. M., DeMayo, F., Finegold, M. J., Medina, D., Tilley, W. D., Aspinall, J. O., et al. (1995) Prostate cancer in a transgenic mouse. Proc. Natl. Acad., Sci. USA 92, 3439-3443.Google Scholar
  126. 126.
    Gingrich, J. R., Barrios, R. J., Morton, R. A., Boyce, B. F., DeMayo, F. J., Finegold, M. J., et al. (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res. 56, 4096–4102.PubMedGoogle Scholar
  127. 127.
    Gingrich, J. R., Barrios, R. J., Kattan, M. W., Nahm, H. S., Finegold, M. J., and Greenberg, N. M. (1997) Androgen-independent Prostate Cancer Progression in the TRAMP Model. Cancer Res. 57, 4687–4691.PubMedGoogle Scholar
  128. 128.
    Zhu, Y., Richardson, J. A., Parada, L. F., and Graff, J. M. (1998) Smad3 Mutant Mice Develop Metastatic Colorectal Cancer. Cell 94, 703–714.PubMedCrossRefGoogle Scholar
  129. 129.
    Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, Jr., C. A., Butel, J. S., and Bradley, A. (1992) Mice deficient for p53 are develop-mentally normal but susceptible to spontaneous tumors. Nature 356, 215–221.PubMedCrossRefGoogle Scholar
  130. 130.
    Advanced Colorectal Cancer Meta-Analysis Project (1992) Modulation of fluo-rouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. J. Clin. Oncol. 10, 896–903.Google Scholar
  131. 131.
    De Gramont, A., Bosset, J. F., Milan, C., et al. (1995) A prospectively randomized trial comparing 5-FU bolus with low dose folinic acid (FUFOL1d) and 5-FU bolus plus continuous infusion with high dose folinic acid (LV5FU2) for advanced colorectal cancer. Proc. Am. Soc. Clin. Oncol. 14, 455 (Abstr).Google Scholar
  132. 132.
    Creemer, G. J., Lund, B., and Verweij, J. (1994) Topoisomerase I inhibitors: topotecan and irinotecan. Cancer Treat. Rev. 20, 73–96.CrossRefGoogle Scholar
  133. 133.
    Hsiang, Y. H., Lihou, M. G., and Liu, L. F. (1989) Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin. Cancer Res. 49, 5077–5082.PubMedGoogle Scholar
  134. 134.
    An, Z., Jiang, P., Wang, X., Moossa, A. R., and Hoffman, R. M. (1999) Development of a high metastatic orthotopic model of human renal cell carcinoma in nude mice: benefits of fragment implantation compared to cell-suspension injection. Clin. Exp. Metast. 17, 265–270.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2001

Authors and Affiliations

  • Robert M. Hoffman
    • 1
  1. 1.AntiCancer, Inc. and Department of SurgeryUniversity of CaliforniaSan Diego

Personalised recommendations