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A SYNGENEIC IMMUNOCOMPETENT MURINE FIBROSARCOMA (BFS-1) MODEL TO STUDY HOST DEFENSE-LIKE LYTIC PEPTIDE AND DOXORUBICIN COMBINATION THERAPY
Presenter: Philip Suppelna, MD
Co-Authors: Jacobsen F; Al- Benna S; Becerikli M; Merwart B; Rittig A; Stricker I; Lehnhardt M; Steinstraesser L
BG University Hospital Bergmannsheil

Objective: The gold standard in the treatment of soft tissue sarcomas (STS) remains the surgical resection with clear margins and radiation therapy. It is still questionable whether a systemic therapy with chemotherapeutics has a positive impact on the overall survival. Doxorubicin is currently one of the most commonly used chemotherapeutic agents, but options are limited both in number and efficacy for patients with advanced disease. The aim of this study was to establish a syngeneic immunocompetent murine fibrosarcoma (BFS-1) model that would allow study of host defense-like lytic peptide ([D]-K3H3L9) and Doxorubicin combination therapy.

Methods: Murine fibrosarcoma BFS-1 cells in Matrigel (BD Biosciences, San Jose, CA, USA) were injected subcutaneously (1?106 cells) into the animal's flank. Every second day mice were weighed and tumor volume was determined with the formula of length?width?depth?0.5 in mm3. When the tumors reached an average volume of 130 mm3 the animals were grouped according to the principles of a randomized controlled trial. The oncolytic designer peptide [D]-K3H3L9 (5 mg/kg intratumorally, n=5), Doxorubicin (1,2 mg/kg intraperitoneally, n=5) or a combination of [D]-K3H3L9 and Doxorubicin (n=5) therapy were injected for three weeks three times a week. PBS (pH 7.4) will be applied as a control substance.

Results: The single agent therapy with Doxorubicin did not lead to a significant inhibition of tumor growth. The oncolytic peptide worked in a dose dependent manner. Combination treatment inhibited both the tumor growth and the tumor weight significantly (p < 0.05). Histological examinations revealed a decreased cell proliferation as well as a decreased vascularization of the tumors treated with the oncolytic peptide and Doxorubicin simultaneously.

Summary: Successful transplantation of BFS-1 fibrosarcoma cells in syngeneic mice was established. The low dose schedule inhibited the tumor growth significantly. However, a complete remission was not observed. Further studies are needed to evaluate optimal dose applications for future sarcoma treatment regimens.


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