In:
Chemotherapy, S. Karger AG, Vol. 63, No. 5 ( 2018), p. 278-283
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Ewing’s sarcoma (ES) is a recalcitrant disease in need of transformative therapeutics. 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 The aim of this study was to investigate the efficacy of tumor-selective 〈 i 〉 Salmonella typhimurium 〈 /i 〉 A1-R combined with tumor metabolism targeting with oral administration of recombinant methioninase (o-rMETase), on an ES patient-derived orthotopic xenograft (PDOX) model. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The ES PDOX models were previously established in the right chest wall. The ES PDOX models were randomized into 5 groups when the tumor volume reached 80 mm 〈 sup 〉 3 〈 /sup 〉 : G1: untreated control; G2: doxorubicin; G3: 〈 i 〉 S. typhimurium 〈 /i 〉 A1-R; G4: o-rMETase; G5: 〈 i 〉 S. typhimurium 〈 /i 〉 A1-R combined with o-rMETase. All mice were sacrificed on day 15. Body weight and tumor volume were assessed twice a week. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 〈 i 〉 S. typhimurium 〈 /i 〉 A1-R and o-rMETase respectively suppressed tumor growth as monotherapies ( 〈 i 〉 p 〈 /i 〉 = 0.050 and 〈 i 〉 p 〈 /i 〉 = 0.032). 〈 i 〉 S. typhimurium 〈 /i 〉 A1-R combined with o-rMETase regressed tumor growth significantly compared to untreated group on day 15 ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.032). 〈 i 〉 S. typhimurium 〈 /i 〉 A1-R combined with o-rMETase group was significantly more effective than 〈 i 〉 S. typhimurium 〈 /i 〉 A1-R or o-rMETase monotherapy ( 〈 i 〉 p 〈 /i 〉 = 0.032, 〈 i 〉 p 〈 /i 〉 = 0.032). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The present results suggest that the combination of 〈 i 〉 S. typhimurium 〈 /i 〉 A1-R and o-rMETase has promise to be a transformative therapy for ES.
Type of Medium:
Online Resource
ISSN:
0009-3157
,
1421-9794
Language:
English
Publisher:
S. Karger AG
Publication Date:
2018
detail.hit.zdb_id:
1482111-4
detail.hit.zdb_id:
6708-8
SSG:
15,3
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