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在患者来源的原位异种移植(PDOX)模型中,一种新型阴离子磷酸铂络合物比顺铂和阿霉素更有效地靶向未分化多形性肉瘤。

A novel anionic-phosphate-platinum complex effectively targets an undifferentiated pleomorphic sarcoma better than cisplatinum and doxorubicin in a patient-derived orthotopic xenograft (PDOX).

作者信息

Igarashi Kentaro, Kawaguchi Kei, Murakami Takashi, Kiyuna Tasuku, Miyake Kentaro, Yamamoto Norio, Hayashi Katsuhiro, Kimura Hiroaki, Nelson Scott D, Dry Sarah M, Li Yunfeng, Singh Arun S, Miwa Shinji, Odani Akira, Eilber Fritz C, Tsuchiya Hiroyuki, Hoffman Robert M

机构信息

AntiCancer, Inc., San Diego, California, USA.

Department of Surgery, University of California, San Diego, California, USA.

出版信息

Oncotarget. 2017 Jun 28;8(38):63353-63359. doi: 10.18632/oncotarget.18806. eCollection 2017 Sep 8.

DOI:10.18632/oncotarget.18806
PMID:28968995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5609927/
Abstract

A patient high-grade undifferentiated pleomorphic soft-tissue sarcoma (UPS) from a striated muscle was previously orthotopically implanted in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) nude-mouse model. In the present study, two weeks after orthotopic transplantation of the UPS, mice were treated intraperitoneally with cisplatinum (CDDP), doxorubicin (DOX) or a novel anionic-phosphate-platinum compound 3Pt. Treatments were repeated weekly for a total of 3 times. Six weeks after transplantation, all mice were sacrificed and evaluated. After two weeks treatment, tumor sizes were as follows: control (G1): 2208.3 mm; CDDP (G2): 841.8±3 mm, p=0.0001; DOX (G3): 693.1±3 mm, p=6.56E-7; 3Pt (G4): 333.7±1 mm, p=4.8E-8. 3Pt showed significantly more efficacy compared to other therapy drugs tested: CDDP (p=0.0002), DOX (p=0.001). There were no animal deaths in any of the four groups. The present results suggest 3Pt is a promising new candidate for UPS since it was demonstrated to be effective in a PDOX model.

摘要

一名来自横纹肌的高级别未分化多形性软组织肉瘤(UPS)患者的肿瘤组织,先前已原位植入裸鼠的右股二头肌中,以建立患者来源的原位异种移植(PDOX)裸鼠模型。在本研究中,UPS原位移植两周后,给小鼠腹腔注射顺铂(CDDP)、阿霉素(DOX)或新型阴离子磷酸铂化合物3Pt。每周重复治疗一次,共进行3次。移植六周后,处死所有小鼠并进行评估。治疗两周后,肿瘤大小如下:对照组(G1):2208.3立方毫米;顺铂组(G2):841.8±3立方毫米,p = 0.0001;阿霉素组(G3):693.1±3立方毫米,p = 6.56×10⁻⁷;3Pt组(G4):333.7±1立方毫米,p = 4.8×10⁻⁸。与其他测试治疗药物相比,3Pt显示出显著更高的疗效:与顺铂相比(p = 0.0002),与阿霉素相比(p = 0.001)。四组中均无动物死亡。目前的结果表明,3Pt是UPS有前景的新候选药物,因为它在PDOX模型中被证明是有效的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/ac43a53c923c/oncotarget-08-63353-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/ea654776237a/oncotarget-08-63353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/7a4c6d5b2ce3/oncotarget-08-63353-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/710f185da367/oncotarget-08-63353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/07d7fa7bcc08/oncotarget-08-63353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/a438c135f61e/oncotarget-08-63353-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/ac43a53c923c/oncotarget-08-63353-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/ea654776237a/oncotarget-08-63353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/7a4c6d5b2ce3/oncotarget-08-63353-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/710f185da367/oncotarget-08-63353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/07d7fa7bcc08/oncotarget-08-63353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/a438c135f61e/oncotarget-08-63353-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/910e/5609927/ac43a53c923c/oncotarget-08-63353-g006.jpg

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