Cancer and Metastasis Reviews

, Volume 28, Issue 1–2, pp 247–263

Osteosarcoma treatment: state of the art

  • Hang T. Ta
  • Crispin R. Dass
  • Peter F. M. Choong
  • Dave E. Dunstan
NON-THEMATIC REVIEW

Abstract

Osteosarcoma (OS) is a class of cancer originating from bone, mainly afflicting children or young adults. It is the second highest cause of cancer-related death in these age groups, mainly due to development of often fatal metastasis, usually in the lungs. Survival for these patients is poor despite the aggressive use of surgery, chemotherapy, and/or radiotherapy. Thus, new effective drugs and other forms of therapy are needed. This article reviews the biology and the state of the art management of OS. New experimental drugs and potential therapies targeting molecular pathways of OS are also discussed.

Keywords

Osteosarcoma Tumor Cancer Bone Chemotherapy Radiotherapy 

References

  1. 1.
    Unni, K. K. (1996). Dahlin’s bone tumors: General aspects and data on 11,087 cases. Philadelphia: Lippincott-Raven.Google Scholar
  2. 2.
    Buecker, P. J., Gebhardt, M. C., Weber, K. (2005). Osteosarcoma. Liddy Shriver Sarcoma Initiative. http://sarcomahelp.org/Newsletters/V02N01/Osteosarcoma/osteosarcoma.htm. Accessed 30 September 2008.
  3. 3.
    The-Cancer-Council-Victoria. (2006). Osteosarcoma and flouride. http://www.ada.org.au/app_cmslib/media/lib/0703/m50781_v1_osteosarcomaandfluoride.pdf. Accessed 20 June 2008.
  4. 4.
    Longhi, A., Errani, C., De Paolis, M., Mercuri, M., & Bacci, G. (2006). Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treatment Reviews, 32, 423–436.PubMedCrossRefGoogle Scholar
  5. 5.
    Quan, G. M. Y., Ojaimi, J., Nadesapillai, W. A. P., Zhou, H., & Choong, P. F. M. (2002). Resistance of epiphyseal cartilage to invasion by osteosarcoma of antiangiogenic factors. Pathobiology, 70, 361–367.PubMedCrossRefGoogle Scholar
  6. 6.
    Whelan, J. (2005). Advances in osteosarcoma. In T. O. B. Eden, et al. (Eds.), Cancer and the adolescent (pp. 113–120). Malden: Blackwell.CrossRefGoogle Scholar
  7. 7.
    Dass, C. R., Ek, E. T., Contreras, K. G., & Choong, P. F. (2006). A novel orthotopic murine model provides insights into cellular and molecular characteristics contributing to human osteosarcoma. Clinical and Experimental Metastasis, 23, 367–380.PubMedGoogle Scholar
  8. 8.
    Marina, N., Gebhardt, M., Teot, L., & Gorlick, R. (2004). Biology and therapeutic advances for pediatric osteosarcoma. The Oncologist, 9, 422–441.PubMedCrossRefGoogle Scholar
  9. 9.
    Clark, J. C. M., Dass, C. R., & Choong, P. F. M. (2007). A review of clinical and molecular prognostic factors in osteosarcoma. Journal of Cancer Research Clinical Oncology, 134, 281–297.CrossRefGoogle Scholar
  10. 10.
    Rytting, M., Pearson, P., & Raymond, A. K. (2000). Osteosarcoma in preadolescent patients. Clinical Orthopaedics, 373, 39–50.CrossRefGoogle Scholar
  11. 11.
    Fraumeni, J. F. (1967). Stature and malignant tumors of bones in childhood and adolescence. Cancer, 20, 967–973.PubMedCrossRefGoogle Scholar
  12. 12.
    Grimer, R. J. (2005). Osteosarcoma and surgery. In T. O. B. Eden, et al. (Eds.), Cancer and the adolescent (pp. 121–132). Malden: Blackwell.CrossRefGoogle Scholar
  13. 13.
    Withrow, S. J., Powers, B. E., Straw, R. C., & Wilkins, R. M. (1991). Comparative aspects of osteosarcoma. Dog versus man. Clinical Orthopaedics and Related Research, 270, 159–168.PubMedGoogle Scholar
  14. 14.
    Tjalma, R. A. (1966). Canine bone sarcoma: estimation of relative risk as a function of body size. Journal of the National Cancer Institute, 36, 1137–1150.PubMedGoogle Scholar
  15. 15.
    Cotterill, S. J., Wright, C. M., Pearce, M. S., & Craft, A. W. (2004). Stature of young people with malignant bone tumors. Pediatric Blood and Cancer, 42, 59–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Gelberg, K. H., Fitzgerald, E. F., Hwang, S., & Dubrow, R. (1997). Growth and development and other risk for osteosarcoma in children and young adults. International Journal of Epidemiology, 26, 272–278.PubMedCrossRefGoogle Scholar
  17. 17.
    Longhi, A., Pasini, A., Cicognani, A., Baronio, F., Pellacani, A., & Baldini, N. (2005). Height as a risk factor for osteosarcoma. Journal of pediatric hematology/oncology, 27, 314–318.PubMedCrossRefGoogle Scholar
  18. 18.
    Longhi, A., Barbieri, E., & FAbbri, N. (2003). Radiation-induced osteosarcoma arising 20 years after the treatment of Ewing’s sarcoma. Tumorigenesis, 89, 569–572.Google Scholar
  19. 19.
    Picci, P. (2007). Osteosarcoma (Osteogenic sarcoma). Orphanet Journal of Rare Diseases, 2, 1–4.CrossRefGoogle Scholar
  20. 20.
    Fuschs, B., & Pritchard, D. J. (2002). Etiology of osteosarcoma. Clinical orthopaedics, 397, 40–52.CrossRefGoogle Scholar
  21. 21.
    Wang, L. L., Gannavaparu, A., & Kozinets, C. A. (2003). Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. Journal of the National Cancer Institute, 95, 669–674.PubMedGoogle Scholar
  22. 22.
    Finkel, M. P., Biskis, B. O., & Jinkins, P. B. (1966). Virus induction of osteosarcomas in mice. Science, 151, 698–701.PubMedCrossRefGoogle Scholar
  23. 23.
    Fuchs, B., & Pritchard, D. J. (2002). Etiology of osteosarcoma. Clinical Orthopaedics, 397, 40–52.CrossRefGoogle Scholar
  24. 24.
    Kakar, S., Mihalov, M., Chachlani, N. A., Ghosh, L., & Johnstone, H. (2000). Correlation of c-fos, p53, and PCNA expression with treatment outcome in osteosarcoma. Journal of surgical oncology, 73, 125–126.PubMedCrossRefGoogle Scholar
  25. 25.
    Mendoza, S. M., Konishi, T., & Miller, C. W. (1998). Integration of SV40 in human osteosarcoma DNA. Oncogene, 17, 2457–2462.PubMedCrossRefGoogle Scholar
  26. 26.
    Engels, E. A. (2005). Cancer risk associated with receipt of vaccines contaminated with simian virus 40: epidemiologic research. Expert Review of Vaccines, 4, 197–206.PubMedCrossRefGoogle Scholar
  27. 27.
    Franchi, A., Arganini, L., & Baroni, G. (1998). Expression of transforming growth factor beta isoforms in osteosarcoma variants: association of TGF beta 1 with high grade osteosarcomas. Journal of pathology, 185, 284–289.PubMedCrossRefGoogle Scholar
  28. 28.
    Huvos, A. (1991). Bone tumors: Diagnosis, treatment and prognosis. Philadelphia: Saunders.Google Scholar
  29. 29.
    Skubitz, K. M., & D’Adamo, D. R. (2007). Sarcoma. Mayo Clinic Proceedings, 82, 1409–1432.PubMedCrossRefGoogle Scholar
  30. 30.
    Wittig, J. C., Bickels, J., Priebat, D., Jelinek, J., Kellar-Graney, K., Shmookler, B., et al. (2002). Osteosarcoma: a multidisciplinary approach to diagnosis and treatment. American Family Physician, 65, 1123–1132.PubMedGoogle Scholar
  31. 31.
    Link, M. P., Goorin, A. M., Horowitz, M., Meyer, W. H., Belasco, J., Baker, A., et al. (1991). Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the multi-institutional osteosarcoma study. Clinical Orthopaedics and Related Research, 270, 8–14.PubMedGoogle Scholar
  32. 32.
    Hannisdal, E., Solheim, O. P., Theodorsen, L., & Host, H. (1990). Alterations of blood analyses at relapse of osteosarcoma and Ewing’s sarcoma. Acta oncologica, 29, 585–587.PubMedCrossRefGoogle Scholar
  33. 33.
    Bacci, G., Longhi, A., Ferrari, S., Lari, S., Manfrini, M., Donati, D., et al. (2002). Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: recent experience at Rizzoli Institute. Oncology reports, 9, 171–175.PubMedGoogle Scholar
  34. 34.
    Bacci, G., Longhi, A., Ferrari, S., Briccoli, A., Donati, D., Paolis, M. D., et al. (2004). Prognostic significance of serum lactate dehydrogenase in osteosarcoma of the extremity: Experience at Rizzoli on 1421. Tumorigenesis, 90, 478–484.Google Scholar
  35. 35.
    Aisen, A. M., Martel, W., Braunstein, E. M., McMillin, K. I., Phillips, W. A., & Kling, T. F. (1986). MRI and CT evaluation of primary bone and soft-tissue tumors. AJR. American Journal of Roentgenology, 146, 749–756.PubMedGoogle Scholar
  36. 36.
    Mankin, H. J., Mankin, C. J., & Simon, M. A. (1996). The hazards of the biopsy, revisited: members of the Musculoskeletal Tumor Society. The Journal of bone and joint surgery, 78, 656–663.PubMedGoogle Scholar
  37. 37.
    Dahlin, D. C. (1978). Osteosarcoma of bone and a consideration of prognostic variables. Cancer Treatment Reports, 62, 189–192.PubMedGoogle Scholar
  38. 38.
    Ozaki, T., Flege, S., Kevric, M., Lindner, N., Masas, R., Delling, G. S. R., et al. (2003). Osteosarcoma of the pelvic: experience of the Cooperative Osteosarcoma Study Group. Journal of Clinical Oncology, 21, 334–341.PubMedCrossRefGoogle Scholar
  39. 39.
    Ozaki, T., Flege, S., Liljenqvist, U., Hillmann, A., Delling, G. S. R., Salzer-Kuntschik, M., et al. (2002). Osteosarcoma of the spine: experience of the Cooperative Osteosarcoma Study Group. Cancer, 94, 1069–1077.PubMedCrossRefGoogle Scholar
  40. 40.
    Magishi, K., Yoshida, H., Izumi, Y., Ishikawa, N., & Kubota, H. (2004). Primary osteosarcoma of the lung: report of a case. Surgery Today, 34, 150–152.PubMedCrossRefGoogle Scholar
  41. 41.
    Bieling, P., Rehan, N., Winkler, P., Helmke, K., Maas, R., Fuchs, N., et al. (1996). Tumor size and prgonosis in sggressively treated osteosarcoma. Journal of Clinical Oncology, 14, 848–858.PubMedGoogle Scholar
  42. 42.
    Wolf, R. E., & Enneking, W. F. (1996). The staging and surgery of musculoskeletal neoplasms. The Orthopedic clinics of North America, 27, 473–481.PubMedGoogle Scholar
  43. 43.
    Greene, F. L., Page, D. L., Fleming, I. D., Fritz, A., Balch, C. M., Haller, D. G., et al. (2002). AJCC cancer staging manual (6th). New York: Springer.CrossRefGoogle Scholar
  44. 44.
    Meyers, P. A., & Gorlick, R. (1997). Osteosarcoma. Pediatric clinics of North America, 44, 973–989.PubMedCrossRefGoogle Scholar
  45. 45.
    Bacci, G., Longhi, A., Fagioli, F., Briccoli, A., Versari, M., & Picci, P. (2005). Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 years experience at Rizzoli Institute, Italy. European Journal of Cancer, 41, 2836–2845.PubMedCrossRefGoogle Scholar
  46. 46.
    Patel, S. J., Lynch, J. W. J., Johnson, T., Carroll, R. R., Schumacher, C. R. N., Spanier, S., & Scarborough, M. (2002). Dose-intense ifosfamide/doxorubicin/cisplatin based chemotherapy for osteosarcoma in adults. American Journal of Clinical Oncology, 25, 489–495.PubMedCrossRefGoogle Scholar
  47. 47.
    Halperin, E. C. (2005). Osteosarcoma. In E. C. Halperin, et al. (Eds.), Pediatric Radiation Oncology (pp. 291–318). Philadelphia: Williams & Wilkins.Google Scholar
  48. 48.
    Ferguson, W. S., & Goorin, A. M. (2001). Current treatment of osteosarcoma. Cancer Investigation, 19, 292–315.PubMedCrossRefGoogle Scholar
  49. 49.
    Ozaki, I., Flege, S., Lijenqvist, U., Hillmann, A., Delling, G., Salzer-Kuntschik, M., et al. (2002). Osteosarcoma of the spine: experience of the Cooperative Osteosarcom Study Group. Cancer, 94, 1069–1077.PubMedCrossRefGoogle Scholar
  50. 50.
    Ferrari, S., Smeland, S., Mercuri, M., Bertoni, F., Longhi, A., Ruggieri, P., et al. (2005). Neoadjuvant chemotherapy with high-dose ifosfamide, high-dose methotrexate, cisplatin and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma Groups. Journal of Clinical Oncology, 23, 8845–8852.PubMedCrossRefGoogle Scholar
  51. 51.
    Jaff, N., Carrasco, H., Raymond, K., Ayala, A., & Eftekhari, F. (2003). Cancure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery. Cancer, 95, 2202–2210.CrossRefGoogle Scholar
  52. 52.
    Lee, E. S. (1971). Treatment of bone sarcoma. Proceedings of the Royal Society of Medicine, 64, 1179–1181.PubMedGoogle Scholar
  53. 53.
    Philips, T. L., & Sheline, G. E. (1969). Radiation therapy of malignant bone tumors. Radiology, 92, 1537–1545.Google Scholar
  54. 54.
    Machak, G. N., Tkachev, S. I., Solovyev, Y. N., Sinyukov, P. A., Ivanov, S. M., Kochergina, N. V., et al. (2003). Neoadjuvant chemotherapy and local radiotherapy for high grade osteosarcoma of the extremities. Mayo Clinic Proceedings, 78, 147–155.PubMedCrossRefGoogle Scholar
  55. 55.
    Yamamoto, T., Akisue, T., Marui, T., Nagira, K., & Kurosaka, M. (2002). Osteosarcoma of the distal radius treated by introperative extracorporeal irradiation. Journal of the Hand Surgery, 27, 160–164.Google Scholar
  56. 56.
    Hong, A., Stevens, G., Stalley, P., Pendlebury, S., Ahern, V., Ralston, A., et al. (2001). Extracorporeal irradiation for malignant bone tumors. International Journal of Radiation Oncology, Biology, Physics, 50(2), 441–447.PubMedCrossRefGoogle Scholar
  57. 57.
    Araki, N., Myoui, A., Kuratsu, S., Hashimoto, N., Inoue, T., Kudawara, I., et al. (1999). Intraoperative extracorporeal autogenous irradiated bone graft in tumor surgery. Clinical Orthopaedics, 368, 196–206.CrossRefGoogle Scholar
  58. 58.
    Gilchrist, G. S., Pritchard, D. J., & Dahlin, D. C. (1981). Management of osteogenic sarcoma: a perspective based on the Mayo Clinic experience. National Cancer Institute Monograph, 56, 193–199.PubMedGoogle Scholar
  59. 59.
    Giritsky, A. S., Etucubanas, E., & Mark, J. B. (1978). Pulmonary resection in children with metastaic osteogenic sarcoma: improved survival with surgery, chemotherapy, and irradiation. The Journal of Thoracic and Cardiovascular Surgery, 75, 354–362.PubMedGoogle Scholar
  60. 60.
    Weichselbaum, R. R., Cassady, J. R., & Jaffe, N. (1977). Preliminary results of aggressive multimodality therapy for metastatic osteosarcoma. Cancer, 40, 78–83.PubMedCrossRefGoogle Scholar
  61. 61.
    Picci, P., Bacci, G., Campanacci, M., Gasparini, M., Pilotti, S., Cerasoli, S., et al. (1985). Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy. Cancer, 56, 1515–1521.PubMedCrossRefGoogle Scholar
  62. 62.
    Eilber, F., Giuliano, A., Eckardt, J., Patterson, K., Moseley, S., & Goodnight, J. (1987). Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. Journal of Cancer and Clinical Oncology, 5, 21–26.Google Scholar
  63. 63.
    Link, M. P., Goorin, A. M., Horowitz, M., Meyer, W. H., Belasco, J., Baker, A., et al. (1991). Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. Clinical orthopaedics, 270, 8–14.Google Scholar
  64. 64.
    Rosen, G., Caparros, B., Huvos, A. G., Kosloff, C., Nirenberg, A., Cacavio, A., et al. (1982). Preoperative chemotherapy of osteosarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to the preoperative therapy. Cancer, 49, 1221–1230.PubMedCrossRefGoogle Scholar
  65. 65.
    Hudson, M., Jaffe, M. R., Jaffe, N., Ayala, A., Raymond, A. K., Carrasco, H., et al. (1990). Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. Journal of Clinical Oncology, 12, 1988–1997.Google Scholar
  66. 66.
    Provisor, A. J., Ettinger, L. J., Nachman, J. B., Krailo, M. D., Makley, J. T., Yunis, E. J., et al. (1997). Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children’s Cancer Group. Journal of Clinical Oncology, 15, 76–84.PubMedGoogle Scholar
  67. 67.
    Man, T.-K., Chintagumpala, M., Visvanathan, J., Shen, J., Perlaky, L., Hicks, J., et al. (2005). Expression Profiles of Osteosarcoma That Can Predict Response to Chemotherapy. Cancer Research, 65, 8142–8150.PubMedCrossRefGoogle Scholar
  68. 68.
    Souhami, R. L., Craft, A. W., Van der Eijken, J. W., Nooij, M., Spooner, D., Bramwell, V. H., et al. (1997). Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup. Lancet, 350, 911–917.PubMedCrossRefGoogle Scholar
  69. 69.
    Ferrari, S., & Palmerini, E. (2007). Adjuvant and neoadjuvant combination chemotherapy for osteogenic sarcoma. Current Opinion in Oncology, 19, 341–346.PubMedCrossRefGoogle Scholar
  70. 70.
    Fuchs, N., Bielack, S. S., Epler, D., Biding, P., Delling, G., Körholz, D., et al. (1998). Long-term results of the co-operative German-Austrian-Swiss Osteosarcoma Study Group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Annals of Oncology, 9, 893–899.PubMedCrossRefGoogle Scholar
  71. 71.
    Petrilli, A. S., de Camargo, B., Filho, V. O., Bruniera, P., Brunetto, A. L., Jesus-Garcia, R., et al. (2006). Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: prognostic factors and impact on survival. Journal of Clinical Oncology, 24, 1161–1168.PubMedCrossRefGoogle Scholar
  72. 72.
    Meyers, P. A., Schwartz, C. L., Krailo, M. D., Kleinerman, E. S., Betcher, D., Bernstein, M. L., et al. (2005). Osteosarcoma: a randomized prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin and high-dose methotrexate. Journal of Clinical Oncology, 23, 2004–2011.PubMedCrossRefGoogle Scholar
  73. 73.
    Eselgrim, M., Grunert, H., Kuhne, T., Zoubek, A., Kevric, M., Bürger, H., et al. (2006). Dose intensity of chemotherapy for osteosarcoma and outcome in the Cooperative Osteosarcoma Study Group (COSS) trial. Pediatric Blood and Cancer, 47, 42–50.PubMedCrossRefGoogle Scholar
  74. 74.
    Lewis, I. J., Weeden, S., Machin, D., Stark, D., & Craft, A. W. (2000). Received dose and dose intensity of chemotherapy and outcome in nonmetastatic extremity osteosarcoma. European Osteosarcoma Intergroup. Journal of Clinical Oncology, 18, 4028–4037.PubMedGoogle Scholar
  75. 75.
    Daw, N. C., Billups, C. A., Rodriguez-Galindo, C., McCarville, M. B., Rao, B. N., Cain, A. M., et al. (2006). Metastatic osteosarcoma. Cancer, 106, 403–412.PubMedCrossRefGoogle Scholar
  76. 76.
    Bacci, G., Fabbri, N., Balladelli, A., Forni, C., Palmerini, E., & Picci, P. (2006). Treatment and prognosis for synchronous multifocal osteosarcoma in 42 patients. Journal of Bone and Joint Surgery American, 88, 1071–1075.CrossRefGoogle Scholar
  77. 77.
    Kager, L., Zoubek, A., Kastner, U., Kempf-Bielack, B., Potratz, J., Kotz, R., et al. (2006). Skip metastases in osteosarcoma : Experience of The Cooperative Osteosarcoma Study Group. Journal of Clinical Oncology, 24, 1535–1541.PubMedCrossRefGoogle Scholar
  78. 78.
    Ek, E. T. H., Dass, C. R., Contreras, K. G., & Choong, P. F. M. (2007). Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis. Cancer Gene Therapy, 14, 616–626.PubMedCrossRefGoogle Scholar
  79. 79.
    Okuno, S. (2006). Mammalian target of rapamycin inhibitors in sarcomas. Current Opinion in Oncology, 18, 360–362.PubMedCrossRefGoogle Scholar
  80. 80.
    Kubo, T., Shimose, S., Matsuo, T., Tanaka, K., Yasunaga, Y., Sakai, A., et al. (2006). Inhibitory effects of a new bisphosphonate, minodronate, on proliferation and invasion of a variety of malignant bone tumor cells. Journal of Orthopaedic Research, 24, 1138–1144.PubMedCrossRefGoogle Scholar
  81. 81.
    Murayama, T., Kawasoe, Y., Yamashita, Y., Ueno, Y., Minami, S., Yokouchi, M., et al. (2008). Efficacy of the third-generation bisphosphonate risedronate alone and in combination with anticancer drugs against osteosarcoma cell lines. Anticancer Reseach, 28, 2147–2154.Google Scholar
  82. 82.
    Kubista, B., Trieb, K., Sevelda, F., Toma, C., Arrich, F., Heffeter, P., et al. (2006). Anticancer effects of zoledronic acid against human osteosarcoma cells. Journal of Orthopaedic Research, 24, 1145–1152.PubMedCrossRefGoogle Scholar
  83. 83.
    Horie, N., Murata, H., Kimura, S., Takeshita, H., Sakabe, T., Matsui, T., et al. (2007). Combined effects of a third-generation bisphosphonate, zoledronic acid with other anticancer agents against murine osteosarcoma. British Journal of Cancer, 96, 255–261.PubMedCrossRefGoogle Scholar
  84. 84.
    Benassi, M., Chiechi, A., Ponticelli, F., Pazzaglia, L., Gamberi, G., Zanella, L., et al. (2006). Growth inhibition and sensitization to cisplatin by zoledronic acid in osteosarcoma cells. Cancer Letters, 250, 194–205.PubMedCrossRefGoogle Scholar
  85. 85.
    Tomlin, J. L., Pead, M. J., & Muir, P. (2000). Use of the bisphosphonate drug alendronate for palliative management of osteosarcoma in two dogs. The Veterinary Record, 147, 129–132.PubMedGoogle Scholar
  86. 86.
    Kotz, R., Plattner, E., Ramach, W., Flener, R., & Bodo, G. (1982). Interferon/controlled study in 3-year survival of patients with recurrent osteosarcoma. Arzneimittelforschung, 32, 446–448.PubMedGoogle Scholar
  87. 87.
    Müller, C. R., Smeland, S., Bauer, H. C., Saeter, G., & Strander, H. (2005). Interferon-alpha as the only adjuvant treatment in high-grade osteosarcoma: long term results of the Karolinska Hospital series. Acta Oncologica, 44, 475–480.PubMedCrossRefGoogle Scholar
  88. 88.
    Strander, H., Aparisi, T., Blomgren, H., Broström, L. A., Cantell, K., Einhorn, S., et al. (1982). Adjuvant interferon treatment of human osteosarcoma. Recent Results Cancer Research, 80, 103–107.Google Scholar
  89. 89.
    Strander, H., Bauer, H. C., Brosjö, O., Kreicbergs, A., Lindholm, J., Nilsonne, U., et al. (1993). Adjuvant interferon treatment in human osteosarcoma. Cancer Treatment and Research, 62, 29–32.PubMedGoogle Scholar
  90. 90.
    Winkler, K., Beron, G., Kotz, R., Salzer-Kuntschik, M., Beck, J., Beck, W., et al. (2004). Adjuvant chemotherapy in osteosarcoma—Effects of cisplatinum, BCD, and fibroblast interferon in sequential combination with HD-MTX and adriamycin. Journal of Cancer Research and Clinical Oncology, 106, 1–7.CrossRefGoogle Scholar
  91. 91.
    Stanton, G. J., Weigent, D. A., Fleischmann, W. R. J., Dianzani, F., & Baron, S. (1987). Interferon review. Investigative Radiology, 22, 259–273.PubMedCrossRefGoogle Scholar
  92. 92.
    Jonasch, E., & Haluska, F. G. (2001). Interferon in oncological practice: Review of interferon biology, clinical applications, and toxicities. Oncologist, 1, 34–55.CrossRefGoogle Scholar
  93. 93.
    Strander, H. (1989). The action of interferon on virus-associated human neoplasms. Cancer Surveys, 8, 755–792.PubMedGoogle Scholar
  94. 94.
    Glasgow, L. A., Crane, J. L. Jr., Kern, E. R., & Youngner, J. S. (1978). Antitumor activity of interferon angainst murine osteogenic sarcoma in vitro and in vivo. Cancer Treatment Reports, 62, 1881–1888.PubMedGoogle Scholar
  95. 95.
    Glasgow, L. A., & Kern, E. R. (1981). Effect of interferon administration on pulmonary osteogenic sarcomas in an experimental murine model. Journal of the National Cancer Institute, 67, 207–212.PubMedGoogle Scholar
  96. 96.
    Jia, S. F., An, T., Worth, L., & Kleinerman, E. S. (1999). Interferon-alpha Enhances the Sensitivity of Human Osteosarcoma Cells to Etoposide. Journal of Interferon and Cytokine Research, 19, 617–624.PubMedCrossRefGoogle Scholar
  97. 97.
    Yuan, X.-w., Zhu, X.-f., Huang, X.-f., Sheng, P.-y., He, A.-s., Yang, Z.-b., et al. (2007). Interferon-a enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis. Acta Pharmacologica Sinica, 28, 1835–1841.PubMedCrossRefGoogle Scholar
  98. 98.
    Inaba, H., Glibetic, M., Buck, S., Ravindranath, Y., & Kaplan, J. (2004). Interferon-alpha sensitizes osteosarcoma cells to Fas-induced apoptosis by up-regulating Fas receptors and caspase-8. Pediatrica Blood Cancer, 43, 729–736.CrossRefGoogle Scholar
  99. 99.
    Waldmann, T. A. (2006). The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nature reviews. Immunology, 6, 595–601.PubMedCrossRefGoogle Scholar
  100. 100.
    Waldmann, T. A., & Tagaya, Y. (1999). The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annual Review of Immunology, 17, 19–49.PubMedCrossRefGoogle Scholar
  101. 101.
    Luksch, R., Perotti, D., Cefalo, G., Gambacorti Passerini, C., Massimino, M., Spreafico, F., et al. (2003). Immunomodulation in a treatment program including pre- and post-operative interleukin-2 and chemotherapy for childhood osteosarcoma. Tumorigenesis, 89, 263–268.Google Scholar
  102. 102.
    Schwartz, Y., Avraham, R., Benish, M., Rosenne, E., & Ben-Eliyahu, S. (2008). Prophylactic IL-12 treatment reduces postoperative metastasis: mediation by increased numbers but not cytotoxicity of NK cells. Breast Cancer Research and Treatment, 107, 211–223.PubMedCrossRefGoogle Scholar
  103. 103.
    Nardin, A., Lefebvre, M. L., Labroquere, K., Faure, O., & Abastado, J. P. (2006). Liposomal muramyl tripeptide phosphatidylethanolamine: Targeting and activating macrophages for adjuvant treatment of osteosarcoma. Current Cancer Drug Targets, 6, 123–133.PubMedCrossRefGoogle Scholar
  104. 104.
    Chawla, S. P., Tolcher, A. W., Staddon, A. P., Schuetze, S. M., D’Amato, G. Z., Blay, J. Y., et al. (2006). Updated results of a phase II trial of AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas (Abstract). Journal of Clinical Oncology, ASCO Annual Meeting Proceedings, Part I., 24 (June 20 Supplement), Abstract 9505.Google Scholar
  105. 105.
    Quan, G. M. Y., & Choong, P. F. M. (2006). Anti-angiogenic therapy for osteosarcoma. Cancer Metastasis Review, 25, 707–713.CrossRefGoogle Scholar
  106. 106.
    Folkman, J. (2004). Endogenous angiogenesis inhibitors. Acta pathologica, microbiologica, immunologica Scandinavica, 112, 496–507.Google Scholar
  107. 107.
    Tjin Tham Sjin, R. M., Naspinski, J., Birsner, A. E., Li, C., Chan, R., Lo, K. M., et al. (2006). Endostatin therapy reveals a U-shaped curve for antitumor activity. Cancer Gene Therapy, 13, 619–627.PubMedCrossRefGoogle Scholar
  108. 108.
    Mohammed, R. A., Green, A., El-Shikh, S., Paish, E. C., Ellis, I. O., & Martin, S. G. (2007). Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. British Journal of Cancer, 96, 1092–1100.PubMedCrossRefGoogle Scholar
  109. 109.
    Kaya, M., Wada, T., Akatsuka, T., Kawaguchi, S., Nagoya, S., Shindoh, M., et al. (2000). Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clinical Cancer Research, 6, 572–577.PubMedGoogle Scholar
  110. 110.
    Hara, H., Akisue, T., Fujimoto, T., Imabori, M., Kawamoto, T., Kuroda, R., et al. (2006). Expression of VEGF and its receptors and angiogenesis in bone and soft tissue tumors. Anticancer Research, 26, 4307–4311.PubMedGoogle Scholar
  111. 111.
    Mantadakis, E., Kim, G., Reisch, J., McHard, K., Maale, G., Leavey, P. J., et al. (2001). Lack of prognostic significance of intratumoral angiogenesis in non metastatic osteosarcoma. Journal of Pediatric Hematology/Oncology, 23, 286–289.PubMedCrossRefGoogle Scholar
  112. 112.
    Ek, E. T. H., Ojaimi, J., Kitagawa, Y., & Choong, P. F. M. (2006). Does the degree of intratumoral microvessel density and VEGF expression have prognostic significance in osteosarcoma? Oncology Reports, 16, 17–23.PubMedGoogle Scholar
  113. 113.
    Kreuter, M., Bieker, R., Bielack, S. S., Auras, T., Buerger, H., Gosheger, G., et al. (2004). Prognostic relevance of increased angiogenesis in osteosarcoma. Clinical Cancer Research, 10, 8531–8537.PubMedCrossRefGoogle Scholar
  114. 114.
    Dawson, D. W., Volpert, O. V., Gillis, P., Crawford, S. E., Xu, H., & Benedict, W. (1999). Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science, 285, 245–248.PubMedCrossRefGoogle Scholar
  115. 115.
    Volpert, O. V., Zaichuk, T., Zhou, W., Reiher, F., Ferguson, T. A., & Stuart, P. M. (2002). Inducer-stimulated Fas targets activates endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor. Nature Medicine, 8, 349–357.PubMedCrossRefGoogle Scholar
  116. 116.
    Cai, J., Jiang, W. G., Grant, M. B., & Boulton, M. (2006). Pigment epithelium-derived factor inhibits angiogenesis via regulated intracellular proteolysis of VEGFR-1. Journal of biological chemistry, 281, 3604–3613.PubMedCrossRefGoogle Scholar
  117. 117.
    Pignolo, R. J., Francis, M. K., Rotenberg, M. O., & Cristofalo, V. J. (2003). Putative role for EPC-1/PEDF in the growth arrest of human diploid fibroblasts. Journal of cellular physiology, 195, 12–20.PubMedCrossRefGoogle Scholar
  118. 118.
    Abe, R., Shimizu, T., Yamagishi, S., Shibaki, A., Amano, S., & Inagaki, Y. (2004). Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. The American Journal of Pathology, 164, 1225–1232.PubMedGoogle Scholar
  119. 119.
    Foukas, A. F., Deshmukh, N. S., Grimer, R. J., Mangham, D. C., Mangos, E. G., & Taylor, S. (2002). Stage-IIB osteosarcoma around the knee. A study of MMP-9 in surviving tumour cells. The Journal of Bone and Joint Surgery, British volume, 84, 706–711.CrossRefGoogle Scholar
  120. 120.
    Vinodhkumar, R., Song, Y. S., Ravikumar, V., Ramakrishnan, G., & Devaki, T. (2007). Depsipeptide a histone deacetylase inhibitor down regulates levels of matrix metalloproteinases 2 and 9 mRNA and protein expressions in lung cancer cells (A549). Chemico-Biological Interactions, 165, 220–229.PubMedCrossRefGoogle Scholar
  121. 121.
    Shin, C. Y., Lee, W. J., Choi, J. W., Choi, M. S., Ryu, J. R., Oh, S. J., et al. (2007). Down-regulation of matrix metalloproteinase-9 expression by nitric oxide in lipopolysaccharide-stimulated rat primary astrocytes. Nitric Oxide, 16, 425–432.PubMedCrossRefGoogle Scholar
  122. 122.
    Kang, H. G., Kim, H. S., Kim, K. J., Oh, J. H., Lee, M. R., Seol, S. M., et al. (2007). RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness. Journal of Orthopaedic Research, 25, 696–702.PubMedCrossRefGoogle Scholar
  123. 123.
    Takahashi, C., Sheng, Z., Horan, T. P., Kitayama, H., Maki, M., Hitomi, K., et al. (1998). Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proceedings of the National Academy of Sciences of the United States of America, 95, 13221–13226.PubMedCrossRefGoogle Scholar
  124. 124.
    Oh, J. H., Takahashi, R., Kondo, S., Mizoguchi, A., Adachi, E., Sasahara, R. M., et al. (2001). The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell, 107, 789–800.PubMedCrossRefGoogle Scholar
  125. 125.
    Choong, P. F. M., & Nadesapillai, A. P. W. (2003). Urokinase plasminogen activator system: a multifunctional role in tumor progression and metastasis. Clinical orthopaedics and related research, 415(Suppl), S46–S58.PubMedCrossRefGoogle Scholar
  126. 126.
    Choong, P. F. M., Ferno, M., Akerman, M., Willen, H., Langstrom, E., Gustafson, P., et al. (1996). Urokinase-plasminogen-activator levels and prognosis in 69 soft-tissue sarcomas. International Journal of Cancer, 69, 268–273.CrossRefGoogle Scholar
  127. 127.
    Dass, C. R., Nadesapillai, A. P. W., Robin, D., Howard, M. L., Fisher, J. L., Zhou, H., et al. (2005). Downregulation of uPAR cofirms link in growth and metatasis of osteosarcoma. Clinical and Experimental Metastasis, 22, 643–652.PubMedCrossRefGoogle Scholar
  128. 128.
    Dass, C. R., & Choong, P. F. M. (2008). uPAR mediates anticancer activity of PEDF. Cancer Biology and Therapy, 7, 1262–1270.PubMedCrossRefGoogle Scholar
  129. 129.
    Baldini, N., Scotlandi, K., Serra, M., Picci, P., Bacci, G., Sottili, S., et al. (1999). P-glycoprotein expression in osteosarcoma: a basic for risk-adapted adjuvant chemotherapy. Journal of Orthopaedic Research, 17, 629–632.PubMedCrossRefGoogle Scholar
  130. 130.
    Chan, H. S., Grogan, T. M., Haddad, G., DeBoer, G., & Ling, V. (1997). P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy. Journal of the National Cancer Institute, 89, 1706–1715.PubMedCrossRefGoogle Scholar
  131. 131.
    Laverdiere, C., Hoang, B. H., Yang, R., Sowers, R., Qin, J., Meyers, P. A., et al. (2005). Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clinical Cancer Research, 11, 2561–2567.PubMedCrossRefGoogle Scholar
  132. 132.
    Perissinotto, E., Cavalloni, G., Leone, F., Fonsato, V., Mitola, S., Grignani, G., et al. (2005). Involvement of chemokine receptor 4/stromal cell-derived factor 1 system during osteosarcoma tumor progression. Clinical Cancer Research, 11(2 Pt 1), 490–497.PubMedGoogle Scholar
  133. 133.
    Teodoro, J. G., Evans, S. K., & Green, M. R. (2007). Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome. Journal of Molecular Medicine, 85, 1175–1186.PubMedCrossRefGoogle Scholar
  134. 134.
    Miller, C. W., Aslo, A., Won, A., Tan, M., Lampkin, B., & Koeffler, H. P. (1996). Alterations of the p53, Rb and MDM2 genes in osteosarcoma. Journal of Cancer Research and Clinical Oncology, 122, 559–565.PubMedCrossRefGoogle Scholar
  135. 135.
    McIntyre, J. F., Smith-Sorensen, B., Friend, S. H., Kassel, J., Borresen, A. L., Yan, Y. X., et al. (1994). Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma. Journal Clinical Oncology, 12, 925–930.Google Scholar
  136. 136.
    Nakase, M., Inui, M., Okumura, K., Kamei, T., Nakamura, S., & Tagawa, T. (2005). p53 gene therapy of human osteosarcoma using a transferrin-modified cationic liposome. Molecular Cancer Therapeutics, 4, 625–631.PubMedCrossRefGoogle Scholar
  137. 137.
    Densmore, C. L., Kleinerman, E. S., Gautam, A., Jia, S.-F., Xu, B., Worth, L. L., et al. (2001). Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI-p53 complexes. Cancer Gene Therapy, 8, 619–627.PubMedCrossRefGoogle Scholar
  138. 138.
    Onda, M., Matsuda, S., Higaki, S., Ijima, T., Fukushima, J., Yokokura, A., et al. (1996). ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer, 77, 71–78.PubMedCrossRefGoogle Scholar
  139. 139.
    Zhou, H., Randall, R. L., Brothman, A. R., Maxwell, T., Coffin, C. M., & Goldsby, R. E. (2003). Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. Journal of Pediatric Hematology/Oncology, 25, 27–32.PubMedCrossRefGoogle Scholar
  140. 140.
    US-National-Cancer-Institute. (2001). Phase II Study of Chemotherapy With or Without Trastuzumab (Herceptin®) in Patients With Metastatic Osteosarcoma. http://www.cancer.gov/clinicaltrials/COG-AOST0121. Accessed 30-09 2008.
  141. 141.
    Hunter, K. W. (2004). Ezrin, a key component in tumor metastasis. Trends in Molecular Medicine, 10, 201–204.PubMedCrossRefGoogle Scholar
  142. 142.
    Khanna, C., Wan, X., Bose, S., Cassaday, R., Olomu, O., Mendoza, A., et al. (2004). The membrane-cyto-skeleton linker ezrin is necessary for osteosarcoma metastasis. Nature Medicine, 10, 182–186.PubMedCrossRefGoogle Scholar
  143. 143.
    Wan, X., Mendoza, A., Khanna, C., & Helman, L. J. (2005). Rapamycin inhibits ezrin-mediated metastatic behaviour in a murine model of osteosarcoma. Cancer Research, 65, 2406–2411.PubMedCrossRefGoogle Scholar
  144. 144.
    Pasquini, G. M., Davey, R. A., Ho, P. W., Michelangeli, V. P., Grill, V., Kaczmarczyk, S. J., & Zajac, J. D. (2002). Local secretion of parathyroid hormone-related protein by an osteoblastic osteosarcoma (UMR 106–01) cell line results in growth inhibition. Bone, 31, 598–605.PubMedCrossRefGoogle Scholar
  145. 145.
    Yang, R., Hoang, B. H., Kubo, T., Kawano, H., Chou, A., Sowers, R., et al. (2007). Over-expression of parathyroid hormone Type 1 receptor confers an aggressive phenotype in osteosarcoma. International Journal of Cancer, 121, 943–954.CrossRefGoogle Scholar
  146. 146.
    Dass, C. R., & Choong, P. F. (2008). C-jun: pharmaceutical target for DNAzyme therapy of multiple pathologies. Pharmazie, 63, 411–414.PubMedGoogle Scholar
  147. 147.
    Bohmann, D., Bos, T. J., Admon, A., Nishimura, T., Vogt, P. K., & Tjian, R. (1987). Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science, 238, 1386–1392.PubMedCrossRefGoogle Scholar
  148. 148.
    Dass, C. R., Khachigian, L. M., & Choong, P. F. M. (2008). c-Jun is critical for the progression of osteosarcoma: proof in an orthotopic spontaneously metastasizing model. Molecular Cancer Research, 6, 1289–1292.PubMedCrossRefGoogle Scholar
  149. 149.
    Dass, C. R., Friedhuber, A. M., Khachigian, L. M., Dunstan, D. E., & Choong, P. F. (2008). Downregulation of c-jun results in apoptosis-mediated anti-osteosarcoma activity in an orthotopic model. Cancer biology & therapy, 7, 1033–1036.CrossRefGoogle Scholar
  150. 150.
    Dass, C. R., Friedhuber, A. M., Khachigian, L. M., Dunstan, D. E., & Choong, P. F. (2008). Biocompatible chitosan-DNAzyme nanoparticle exhibits enhanced biological activity. Journal of Microencapsulation, 25, 421–425.PubMedCrossRefGoogle Scholar
  151. 151.
    Dass, C. R., Khachigian, L. M., & Choong, P. F. M. (2008). c-Jun knockdown sensitizes osteosarcoma to doxorubicin. Molecular Cancer Therapeutics, 7, 1909–1912.PubMedCrossRefGoogle Scholar
  152. 152.
    MacEwen, E. G., Pastor, J., Kutzke, J., Tsan, R., Kurzman, I. D., Thamm, D. H., et al. (2004). IGF-1 receptor contributes to the malignant phenotype in human and canine osteosarcoma. Journal of Cellular Biochemistry, 92, 77–91.PubMedCrossRefGoogle Scholar
  153. 153.
    Sekyi-Otu, A., Bell, R. S., Ohashi, C., Pollak, M., & Andrulis, I. L. (1995). Insulin-like growth factor 1 (IGF-1) receptors, IGF-1, and IGF-2 are expressed in primary human sarcomas. Cancer Research, 55, 129–134.PubMedGoogle Scholar
  154. 154.
    Pollak, M., Sem, A. W., Richard, M., Tetenes, E., & Bell, R. (1992). Inhibition of metastatic behavior of murine osteosarcoma by hypophysectomy. Journal of the National Cancer Institute, 84, 966–971.PubMedCrossRefGoogle Scholar
  155. 155.
    Burrow, S., Andrulis, I. L., Pollak, M., & Bell, R. S. (1998). Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcoma. Journal of Surgical Oncology, 69, 21–27.PubMedCrossRefGoogle Scholar
  156. 156.
    Frincu-Mallos, C. (2007). Novel anti-IGF-1 receptor drug, R1507, shows potential in sarcoma patients. http://www.pslgroup.com/dg/216426.htm. Accessed 30/09 2008.
  157. 157.
    Pollak, M., Sem, A. W., Richard, M., Tetenes, E., & Bell, R. (1992). Inhibition of metastatic behavior of murine osteosarcoma by hypophysectomy. Journal of the National Cancer Institute, 84, 966–971.PubMedCrossRefGoogle Scholar
  158. 158.
    Mansky, P. J., Liewehr, D. J., Steinberg, S. M., Chrousos, G. P., Avila, N. A., Long, L., et al. (2002). Treatment of metastatic osteosarcoma with the somatostatin analog OncoLar: significant reduction of insulin-like growth factor-1 serum levels. Journal of Pediatric Hematology/Oncology, 24, 440–446.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Hang T. Ta
    • 1
  • Crispin R. Dass
    • 2
  • Peter F. M. Choong
    • 2
    • 3
  • Dave E. Dunstan
    • 1
  1. 1.Department of Chemical and Biomolecular EngineeringUniversity of MelbourneMelbourneAustralia
  2. 2.Departments of Orthopaedics and SurgerySt Vincent’s Hospital MelbourneMelbourneAustralia
  3. 3.Sarcoma ServicePeter MacCallum Cancer CentreMelbourneAustralia

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