Changes of the redox-regulatory system in tumor and its surrounding tissues in patients with soft tissue sarcoma (STS) after neoadjuvant chemotherapy (NC).

Abstract

e23522 Background: The disruptions in redox homeostasis in the nonmalignant tissues surrounding neoplasm can promote the tumor progression. The aim of this work was to assess the changes of the redox-regulatory system in the tumor and tumor-surrounding tissues in STS patients (pts) under the influence of a mofified metod of NC. Methods: The activity of glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), content of reduced glutathione (GSH) and malondialdehyde (MDA) were determined by spectrophotometric methods. All markers were measured in the samples of tumor, peritumoral area and healthy tissues (taken along the line of resection) obtained during the surgery from 42 STS pts (T2a-bN0M0). The control group consisted of 21 primary pts who underwent resection only. Patients of the experimental group (21) received NC comprising systemic and local administration of antitumor drugs. Doxorubicin (40 mg/m2) was injected intravenously on the 1st and 7th days with autologous red blood cells as drug carriers; at the same time, cyclophosphamide (600 mg/m2) and methotrexate (40 mg/m2) were injected along the tumor periphery, on autologous plasma as a carrier. After 14 days, tumor removal surgery performed. All STS pts received standard postoperative chemoradiotherapy. Results: The level of GSH in tumor without NC treatment was higher than in the healthy and peritumoral tissue (by 2.3-2.5 times), and the activity of all glutathione-dependent enzymes was higher by 53.0-147.0 % (p = 0.0413-0.00124). The content of MDA in tumor was lower than in other tissues by 30.0-46.0 % (p = 0.00061). We did not find any differences between the healthy and peritumoral areas. In tumor samples of the experimental group, we also observed statistically significant increase in the level of GSH (by 2.8–3.0 times) and activation of GPO (by 37.3-95.8 %) and GR (by 2.0-3.2 times) vs. other tissues. However, after NC, the studied samples showed an increase in GSH by 3.1–3.8 times (p = 0.0143–0.00112), compared with the corresponding control samples. Also, the activity of GPO (by 54.5 %) and GsT (by 38.9 %) was significantly increased in peritumoral tissue vs similar area in the control group. After NC, the content of MDA was reduced in the healthy and tumor tissues vs control by 52.0 % (p = 0.0074) and 30.6 % (p = 0.04815), respectively. Clinical efficacy of NC was confirmed by reduced tumor volume in most patients by 30-40 %; the 5-year monitoring of STS pts showed that local recurrence and metastasis occurred in 14 of 21 pts in the control group, and in 6 of 21 in the main group (p = 0.0294). Conclusions: The NC treatment modifies the redox balance in the tumor-surrounding tissues and, as a result, decreases the oxidation damages in the healthy tissues. This effect, apparently, is an additional factor that improves the effectiveness of the proposed NC method.