RT Journal Article
SR Electronic
T1 Oral Recombinant Methioninase, Combined With Oral Caffeine and Injected Cisplatinum, Overcome Cisplatinum-Resistance and Regresses Patient-derived Orthotopic Xenograft Model of Osteosarcoma
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4653
OP 4657
DO 10.21873/anticanres.13646
VO 39
IS 9
A1 TAKASHI HIGUCHI
A1 HIROMICHI OSHIRO
A1 KENTARO MIYAKE
A1 NORIHIKO SUGISAWA
A1 QINGHONG HAN
A1 YUYING TAN
A1 JUNHO PARK
A1 ZHIYING ZHANG
A1 SAHAR RAZMJOOEI
A1 NORIO YAMAMOTO
A1 KATSUHIRO HAYASHI
A1 HIROAKI KIMURA
A1 SHINJI MIWA
A1 KENTARO IGARASHI
A1 MICHAEL BOUVET
A1 SANT P. CHAWLA
A1 SHREE RAM SINGH
A1 HIROYUKI TSUCHIYA
A1 ROBERT M. HOFFMAN
YR 2019
UL http://ar.iiarjournals.org/content/39/9/4653.abstract
AB Background/Aim: Osteosarcoma is a recalcitrant neoplasm which occurs predominantly in adolescents and young adults. Recently, using a patient-derived orthotopic xenograft (PDOX) model of malignant soft-tissue sarcoma (STS), we showed that oral recombinant methioninase (o-rMETase), in combination with caffeine, was more efficacious than o-rMETase alone in inhibiting STS tumor growth. In the present report, we determined the efficacy of o-rMETase combined with oral caffeine on a cisplatinum (CDDP)-resistant osteosarcoma PDOX model. Materials and Methods: Osteosarcoma PDOX models were randomly divided into seven treatment groups (6 mice in each group): untreated control; CDDP alone; o-rMETase alone; o-rMETase with caffeine; CDDP plus o-rMETase; CDDP plus caffeine; and CDDP plus o-rMETase with caffeine. Tumor size and body weight were measured throughout the treatment. Results: Tumors regressed after treatment with CDDP plus o-rMETase with caffeine. Tumors treated with CDDP plus o-rMETase with caffeine also had the most necrosis. Conclusion: The combination of o-rMETase and caffeine together with first-line chemotherapy was efficacious for drug-resistant osteosarcoma and has clinical potential in the treatment of this highly-resistant neoplasm.