Anti-Tumor Effect and Neurotoxicity of Ethanol Adjuvant Therapy after Surgery of a Soft Tissue Sarcoma

Author:

Ban Yoshitaka1,Hoshi Manabu2,Oebisu Naoto2,Orita Kumi2,Iwai Tadashi2ORCID,Yao Hana1,Nakamura Hiroaki2

Affiliation:

1. Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-Machi, Abeno-ku, Osaka 545-8585, Japan

2. Department of Orthopedic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-Machi, Abeno-ku, Osaka 545-8585, Japan

Abstract

Wide resection is the main treatment for sarcomas; however, when they are located near major nerves, their sacrifices might affect limb function. The efficacy of ethanol adjuvant therapy for sarcomas has not been established. In this study, the anti-tumor effect of ethanol, as well as its neurotoxicity, were assessed. In vitro anti-tumor effect of ethanol as evaluated using MTT, wound healing, and invasion assays on a synovial sarcoma cell line (HS-SY-II). In vivo, an assessment was conducted in nude mice (implanted with subcutaneous HS-SY-II) treated with different ethanol concentrations after surgery with a close margin. Sciatic nerve neurotoxicity was assessed with electrophysiological and histological examination. In vitro, ethanol concentrations at 30% and higher showed cytotoxic effects in MTT assay and markedly reduced migration and invasive ability of HS-SY-II. In vivo, both 30% and 99.5% ethanol concentrations, compared to 0% concentration, significantly reduced the local recurrence. However, in the group treated with 99.5% ethanol, nerve conduction tests showed prolonged latency and decreased amplitude, and morphological changes suggestive of nerve degeneration were observed in the sciatic nerve, while the 30% ethanol did not cause neurological damage. In conclusion, 30% is the optimal concentration for ethanol adjuvant therapy after close-margin surgery for sarcoma.

Funder

Japan Society for the Promotion of Science (JSPS) KAKENHI

Publisher

MDPI AG

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