Background: Synovial sarcoma (SS) is representative sarcoma types, which is account for 6% of sarcomas. Although the gold-standard of treatment is surgery, SS is often diagnosed in an advanced clinical stage. Chemotherapy is the primary treatment modality. Amrubicin (AMR), an anthracycline agent, is converted in the body to amrubicinol (AMRol) by reduction of the 13-position ketone, which has a higher antitumor activity than the parentmolecule. In this study, we evaluate the effectiveness in vitro and in vivo.

Materials and Methods: Cell lines and reagent. The SS cell lines, SW982, HSSYII and SS1. Cell viability assay. WST-1 mixture was used. Cell-cycle analysis. To evaluate the cell cycle, FITC BrdU Kit Flow Kit was used. HSSY-II, SW982 were treated with AMRol for 4 hours and analyzed by flow cytometry using BD FACSVerseTM. Animal experiments. Severe Combined Immuno-Deficiency mice were used. SS cells were injected subcutaneously or into right intrathoracic space. These mice were assigned randomly to AMR group and normal saline group (NS). Micro-computed tomography (μCT). The R-mCT system was used to measure the diameter of tumor in intrathoracic space.

Statistical analysis: All of the results are expressed as meanSEM. The Kaplan-Meier method was used to estimate survival. Treatment groups were compared using a two-sided log-rank test.

Results: Cell viability assay. AMR was highly metabolized into AMRol in tumor tissue and AMRol was more toxic than AMR. AMRol was used to in vitro assay. AMRol was equivalent to, or even more toxic than DXR in this experiments. Cell-cycle analysis. After AMRol treatment, more cells were found in S-phase compared with no treatment control. Subcutaneous SS model. AMR showed cytostatic effect compared with normal saline (NS) in each of HSSYII and SW982. Intrathoracic space SS model. SS-1 was established from primary pleural SS patient. In preliminary experiments, location of tumor was confirmed on μCT. Tumor growth was suppressed in AMR group compared with in NS group and AMR showed cytostatic effect. In survival analysis, it was shown that AMR group was tend to survive longer than NS group.

Discussion: It was shown that AMR is effective for SS in vitro and in vivo. Our results suggest an alternative treatment of SS patients, including primary pleural SS. The effectiveness and safety should be addressed in future studies.

Citation Format: Shinnosuke Takemoto, Hiroshi Gyotoku, Hiroaki Senjuu, Takayuki Suyama, Noritaka Honda, Kosuke Mizoguchi, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Yoichi Nakamura, Minoru Fukuda, Hiroshi Mukae. Amrubicin is effective for synovial sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4133. doi:10.1158/1538-7445.AM2017-4133