PT  - JOURNAL ARTICLE
AU  - TAKASHI HIGUCHI
AU  - HIROMICHI OSHIRO
AU  - KENTARO MIYAKE
AU  - NORIHIKO SUGISAWA
AU  - QINGHONG HAN
AU  - YUYING TAN
AU  - JUNHO PARK
AU  - ZHIYING ZHANG
AU  - SAHAR RAZMJOOEI
AU  - NORIO YAMAMOTO
AU  - KATSUHIRO HAYASHI
AU  - HIROAKI KIMURA
AU  - SHINJI MIWA
AU  - KENTARO IGARASHI
AU  - MICHAEL BOUVET
AU  - SANT P. CHAWLA
AU  - SHREE RAM SINGH
AU  - HIROYUKI TSUCHIYA
AU  - ROBERT M. HOFFMAN
TI  - Oral Recombinant Methioninase, Combined With Oral Caffeine and Injected Cisplatinum, Overcome Cisplatinum-Resistance and Regresses Patient-derived Orthotopic Xenograft Model of Osteosarcoma
AID  - 10.21873/anticanres.13646
DP  - 2019 Sep 01
TA  - Anticancer Research
PG  - 4653--4657
VI  - 39
IP  - 9
4099  - http://ar.iiarjournals.org/content/39/9/4653.short
4100  - http://ar.iiarjournals.org/content/39/9/4653.full
SO  - Anticancer Res2019 Sep 01; 39
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.