Oral Recombinant Methioninase, Combined With Oral Caffeine and Injected Cisplatinum, Overcome Cisplatinum-Resistance and Regresses Patient-derived Orthotopic Xenograft Model of Osteosarcoma

被引：45

作者：

Higuchi, Takashi ^{[1
,2
,3
]}

Oshiro, Hiromichi ^{[1
,2
]}

Miyake, Kentaro ^{[1
,2
]}

Sugisawa, Norihiko ^{[1
,2
]}

Han, Qinghong ^{[1
]}

Tan, Yuying ^{[1
]}

Park, Junho ^{[1
,2
]}

Zhang, Zhiying ^{[1
,2
]}

Razmjooei, Sahar ^{[1
]}

Yamamoto, Norio ^{[3
]}

Hayashi, Katsuhiro ^{[3
]}

Kimura, Hiroaki ^{[3
]}

Miwa, Shinji ^{[3
]}

Igarashi, Kentaro ^{[3
]}

Bouvet, Michael ^{[2
]}

Chawla, Sant P. ^{[4
]}

Singh, Shree Ram ^{[5
]}

Tsuchiya, Hiroyuki ^{[3
]}

Hoffman, Robert M. ^{[1
,2
]}

机构：

[1] AntiCanc Inc, 7917 Ostrow St, San Diego, CA 92111 USA

[2] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA

[3] Kanazawa Univ, Dept Orthoped Surg, 13-1 Takara Machi, Kanazawa, Ishikawa 9208641, Japan

[4] Sarcoma Oncol Ctr, Santa Monica, CA USA

[5] NCI, Basic Res Lab, Frederick, MD 21702 USA

来源：

ANTICANCER RESEARCH | 2019年 / 39卷 / 09期

基金：

日本学术振兴会;

关键词：

Osteosarcoma; PDOX; o-rMETase; caffeine; CDDP; regression;

D O I：

10.21873/anticanres.13646

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：4653 / 4657

页数：5

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