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Oral recombinant methioninase combined with oxaliplatinum and 5-fluorouracil regressed a colon cancer growing on the peritoneal surface in a patient-derived orthotopic xenograft mouse model.
Tissue & Cell ( IF 2.6 ) Pub Date : 2019-11-25 , DOI: 10.1016/j.tice.2019.09.006
Jun Ho Park 1 , Qinghong Han 2 , Ming Zhao 2 , Yuying Tan 2 , Takashi Higuchi 3 , Sang Nam Yoon 2 , Norihiko Sugisawa 3 , Jun Yamamoto 3 , Michael Bouvet 4 , Bryan Clary 4 , Shree Ram Singh 5 , Robert M Hoffman 3
Affiliation  

The aim of this study was to determine the efficacy of oral recombinant methioninase (o-rMETase) on a model of colon cancer growing on the peritoneal surface using a patients-derived orthotopic xenograft (PDOX) nude mouse model. Forty PDOX mouse models with colon cancer growing on the peritoneum were divided into 4 groups of 10 mice each by measuring the tumor size and fluorescence intensity: untreated control; 5-fluorouracil (5-FU) (50 mg/kg, once a week for two weeks, ip) and oxaliplatinum (OXA) (6  mg/kg, once a week for two weeks, ip); o-rMETase (100 units/day, oral 14 consecutive days); combination 5-FU + OXA and o-rMETase. All treatments inhibited tumor growth compared to the untreated control. The combination of 5-FU + OXA plus o-rMETase was significantly more efficacious than the control and each drug alone and was the only treatment that caused tumor regression. The present study is the first demonstrating the efficacy of o-rMETase combination therapy on a PDOX model of peritoneal colon cancer, suggesting potential clinical development of o-rMETase in a recalcitrant cancer.

中文翻译:

口服重组蛋氨酸酶与奥沙利铂和5-氟尿嘧啶的结合在患者源性原位异种移植小鼠模型中使结肠癌在腹膜表面上生长。

这项研究的目的是确定口服重组蛋氨酸酶(o-rMETase)在使用源自患者的原位异种移植(PDOX)裸鼠模型的腹膜表面生长的结肠癌模型中的功效。通过测量肿瘤大小和荧光强度,将40只在腹膜上生长有结肠癌的PDOX小鼠模型分为4组,每组10只小鼠。5-氟尿嘧啶(5-FU)(50 mg / kg,每周一次,连续两周,腹腔注射)和奥沙利铂(OXA)(6 mg / kg,每周一次,连续两周,腹腔注射);o-rMETase(100单位/天,连续14天口服);5-FU + OXA和o-rMETase的组合。与未治疗的对照相比,所有治疗均抑制肿瘤生长。5-FU + OXA加o-rMETase的组合比对照组和单独使用每种药物的疗效明显更高,并且是导致肿瘤消退的唯一治疗方法。本研究是第一个证明o-rMETase联合疗法对腹膜结肠癌PDOX模型的疗效的研究,表明o-rMETase在顽固性癌症中的潜在临床开发。
更新日期:2019-11-01
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