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. 2008 Jan 23:7:9.
doi: 10.1186/1476-4598-7-9.

Intravenous administration of the conditionally replicative adenovirus Ad5-Delta24RGD induces regression of osteosarcoma lung metastases

Harm C A Graat  1 , Victor W van Beusechem, Frederik H E Schagen, M Adhiambo Witlox, Eugenie S Kleinerman, Marco N Helder, Winald R Gerritsen, Gertjan J L Kaspers, Paul I J M Wuisman
Affiliations

Intravenous administration of the conditionally replicative adenovirus Ad5-Delta24RGD induces regression of osteosarcoma lung metastases

Harm C A Graat et al. Mol Cancer. .

Abstract

Metastatic osteosarcoma (OS) has a very poor prognosis. New treatments are therefore wanted. The conditionally replicative adenovirus Ad5-Delta24RGD has shown promising anti-tumor effects on local cancers, including OS. The purpose of this study was to determine whether intravenous administration of Ad5-Delta24RGD could suppress growth of human OS lung metastases. Mice bearing SaOs-lm7 OS lung metastases were treated with Ad5-Delta24RGD at weeks 1, 2 and 3 or weeks 5, 6 and 7 after tumor cell injection. Virus treatment at weeks 1-3 did not cause a statistically significant effect on lung weight and total body weight. However, the number of macroscopic lung tumor nodules was reduced from a median of >158 in PBS-treated control mice to 58 in Ad5-Delta24RGD-treated mice (p = 0.15). Moreover, mice treated at weeks 5-7 showed a significantly reduced lung weight (decrease of tumor mass, p < 0.05), a significantly increased body weight gain (decrease of disease symptoms, p < 0.005) and a reduced number of macroscopic lung tumor nodules (median 60 versus > 149, p = 0.12) compared to PBS treated control animals. Adenovirus hexon expression was detected in lung tumor nodules at sacrifice three weeks after the last intravenous adenovirus administration, suggesting ongoing viral infection. These findings suggest that systemic administration of Ad5-Delta24RGD might be a promising new treatment strategy for metastatic osteosarcoma.

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Figures

Figure 1
Figure 1
Therapeutic effect of Ad5-Δ24RGD infusion 1–3 (left panel figure a & b) or 5–7 (right panel figure a & b) weeks after SaOs-lm7 injection. (a) Effect of intravenous administration of Ad5-Δ24RGD on OS pulmonary tumor burden. Lungs were removed and weighed. Open circles depict lung weight of each mouse and black lines show the median of each group. (b) Macroscopic appearance of dissected lungs. (c) Number of lung tumor nodules per mouse. (d) Immunohistochemical staining for expression of the adenovirus hexon protein in lungs of mice treated at weeks 5–7. Ten weeks after tumor cell injection and three weeks after the last virus injection lungs were isolated and analyzed for hexon expression. Representative pictures of the lungs from a PBS control mouse and two Ad5-Δ24RGD treated mice (A & B) are shown at 10× and 40× magnification.
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References

    1. Fletcher CDM, Unni KK, Mertens F. WHO Classification of tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon, IARC Press; 2002.
    1. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jurgens H, Winkler K. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20:776–790. doi: 10.1200/JCO.20.3.776. - DOI - PubMed
    1. Goorin AM, Schwartzentruber DJ, Devidas M, Gebhardt MC, Ayala AG, Harris MB, Helman LJ, Grier HE, Link MP. Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol. 2003;21:1574–1580. doi: 10.1200/JCO.2003.08.165. - DOI - PubMed
    1. Bacci G, Ferrari S, Longhi A, Perin S, Forni C, Fabbri N, Salduca N, Versari M, Smith KV. Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy. Eur J Cancer. 2001;37:32–38. doi: 10.1016/S0959-8049(00)00361-0. - DOI - PubMed
    1. Lewis IJ, Nooij MA, Whelan J, Sydes MR, Grimer R, Hogendoorn PC, Memon MA, Weeden S, Uscinska BM, van Glabbeke M, Kirkpatrick A, Hauben EI, Craft AW, Taminiau AH. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. 2007;99:112–128. doi: 10.1093/jnci/djk015. - DOI - PubMed

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