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Article

Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents

  • Authors:
    • Marc Becker
    • Claudine Graf
    • Marcus Tonak
    • Markus P. Radsak
    • Tobias Bopp
    • Robert Bals
    • Rainer M. Bohle
    • Matthias Theobald
    • Pol‑Maria Rommens
    • Dirk Proschek
    • Thomas C. Wehler
  • View Affiliations / Copyright

    Affiliations: Institute of Pathology, Saarland University Medical Center, Homburg, Saarland D‑66421, Germany, III Department of Internal Medicine, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland‑Palatinate D‑55131, Germany, Interdisciplinary Sarcoma Working Group, Center of Orthopaedic and Trauma Surgery, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland‑Palatinate D‑5513, Germany, Institute for Immunology, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland‑Palatinate D‑55131, Germany, Department of Internal Medicine V ‑ Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University Medical Center, Homburg, Saarland D‑66421, Germany
  • Pages: 1257-1264
    |
    Published online on: June 24, 2016
       https://doi.org/10.3892/ol.2016.4784
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Abstract

Undifferentiated pleomorphic sarcoma not otherwise specified belongs to the heterogeneous group of soft tissue tumors. It is preferentially located in the upper and lower extremities of the body, and surgical resection remains the only curative treatment. Preclinical animal models are crucial to improve the development of novel chemotherapeutic agents for the treatment of undifferentiated pleomorphic sarcoma. However, this approach has been hampered by the lack of reproducible animal models. The present study established two xenograft animal models generated from stable non‑clonal cell cultures, and investigated the difference in chemotherapeutic effects on tumor growth between undifferentiated pleomorphic sarcoma in vivo and in vitro. The cell cultures were generated from freshly isolated tumor tissues of two patients with undifferentiated pleomorphic sarcoma. For the in vivo analysis, these cells were injected subcutaneously into immunodeficient mice. The mice were monitored for tumor appearance and treated with the most common or innovative chemotherapeutic agents available to date. Furthermore, the same drugs were administered to in vitro cell cultures. The most effective tumor growth inhibition in vitro was observed with doxorubicin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), also known as vorinostat. In the in vivo xenograft mouse model, the combination of doxorubicin and the tyrosine kinase inhibitor pazopanib induced a significant tumor reduction. By contrast, treatment with vorinostat did not reduce the tumor growth. Taken together, the results obtained from drug testing in vitro differed significantly from the in vivo results. Therefore, the novel and reproducible xenograft animal model established in the present study demonstrated that in vivo models are required to test potential chemotherapeutic agents for the treatment of undifferentiated pleomorphic sarcoma prior to clinical use, since animal models are more similar to humans, compared with in vitro cell cultures.
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Copy and paste a formatted citation
Spandidos Publications style
Becker M, Graf C, Tonak M, Radsak MP, Bopp T, Bals R, Bohle RM, Theobald M, Rommens PM, Proschek D, Proschek D, et al: Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents. Oncol Lett 12: 1257-1264, 2016.
APA
Becker, M., Graf, C., Tonak, M., Radsak, M.P., Bopp, T., Bals, R. ... Wehler, T.C. (2016). Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents. Oncology Letters, 12, 1257-1264. https://doi.org/10.3892/ol.2016.4784
MLA
Becker, M., Graf, C., Tonak, M., Radsak, M. P., Bopp, T., Bals, R., Bohle, R. M., Theobald, M., Rommens, P., Proschek, D., Wehler, T. C."Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents". Oncology Letters 12.2 (2016): 1257-1264.
Chicago
Becker, M., Graf, C., Tonak, M., Radsak, M. P., Bopp, T., Bals, R., Bohle, R. M., Theobald, M., Rommens, P., Proschek, D., Wehler, T. C."Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents". Oncology Letters 12, no. 2 (2016): 1257-1264. https://doi.org/10.3892/ol.2016.4784
Copy and paste a formatted citation
x
Spandidos Publications style
Becker M, Graf C, Tonak M, Radsak MP, Bopp T, Bals R, Bohle RM, Theobald M, Rommens PM, Proschek D, Proschek D, et al: Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents. Oncol Lett 12: 1257-1264, 2016.
APA
Becker, M., Graf, C., Tonak, M., Radsak, M.P., Bopp, T., Bals, R. ... Wehler, T.C. (2016). Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents. Oncology Letters, 12, 1257-1264. https://doi.org/10.3892/ol.2016.4784
MLA
Becker, M., Graf, C., Tonak, M., Radsak, M. P., Bopp, T., Bals, R., Bohle, R. M., Theobald, M., Rommens, P., Proschek, D., Wehler, T. C."Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents". Oncology Letters 12.2 (2016): 1257-1264.
Chicago
Becker, M., Graf, C., Tonak, M., Radsak, M. P., Bopp, T., Bals, R., Bohle, R. M., Theobald, M., Rommens, P., Proschek, D., Wehler, T. C."Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents". Oncology Letters 12, no. 2 (2016): 1257-1264. https://doi.org/10.3892/ol.2016.4784
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