A novel patient-derived orthotopic xenograft (PDOX) mouse model of highly-aggressive liver metastasis for identification of candidate effective drug-combinations.
A novel patient-derived orthotopic xenograft (PDOX) mouse model of highly-aggressive liver metastasis for identification of candidate effective drug-combinations.
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DOI：
10.1038/s41598-020-76708-9
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发表时间：
2020-11-18
影响因子：
4.6
通讯作者：
Hoffman RM
中科院分区：
文献类型：
--
作者：
Zhang Z;Hu K;Miyake K;Kiyuna T;Oshiro H;Wangsiricharoen S;Kawaguchi K;Higuchi T;Razmjooei S;Miyake M;Chawla SP;Singh SR;Hoffman RM
肝转移是一种易复发的疾病，常导致患者死亡。本研究建立了一种独特的患者来源的高度侵袭性结肠癌肝转移原位异种移植（PDOX）裸鼠模型。本研究的目的是证明候选药物组合可以显著抑制这种恶性肿瘤的生长和再转移的概念验证。首先在裸鼠皮下建立患者的肝转移，然后将皮下肿瘤组织原位植入裸鼠的肝脏中以建立PDOX模型。进行了两项研究以测试不同的药物或药物组合，表明5-氟尿嘧啶（5-FU）+伊立替康（IRI）+贝伐珠单抗（BEV）和瑞格非尼（REG）+司美替尼（SEL）显著抑制肝转移生长（分别为p = 0.013和p = 0.035），并预防肝卫星转移。这项研究证明了高度侵袭性结肠癌转移的PDOX模型可以识别有效的药物组合，并且该模型具有未来的临床潜力。
Liver metastasis is a recalcitrant disease that usually leads to death of the patient. The present study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model of a highly aggressive liver metastasis of colon cancer. The aim of the present study was to demonstrate proof-of-concept that candidate drug combinations could significantly inhibit growth and re-metastasis of this recalcitrant tumor. The patient’s liver metastasis was initially established subcutaneously in nude mice and the subcutaneous tumor tissue was then orthotopically implanted in the liver of nude mice to establish a PDOX model. Two studies were performed to test different drugs or drug combination, indicating that 5-fluorouracil (5-FU) + irinotecan (IRI) + bevacizumab (BEV) and regorafenib (REG) + selumetinib (SEL) had significantly inhibited liver metastasis growth (p = 0.013 and p = 0.035, respectively), and prevented liver satellite metastasis. This study is proof of concept that a PDOX model of highly aggressive colon-cancer metastasis can identify effective drug combinations and that the model has future clinical potential.
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影响因子：
3.4
作者：
Gardner ER;Kelly M;Springman E;Lee KJ;Li H;Moore W;Figg WD
通讯作者：
Figg WD
影响因子：
4
作者：
ASTOUL, P;COLT, HG;HOFFMAN, RM
通讯作者：
HOFFMAN, RM
影响因子：
3.7
作者：
Daudigeos-Dubus E;Le Dret L;Lanvers-Kaminsky C;Bawa O;Opolon P;Vievard A;Villa I;Pagès M;Bosq J;Vassal G;Zopf D;Geoerger B
通讯作者：
Geoerger B
DOI：
10.1073/pnas.94.21.11573
发表时间：
1997-10-14
影响因子：
11.1
作者：
Chishima, T;Yang, M;Hoffman, RM
通讯作者：
Hoffman, RM
影响因子：
--
作者：
Hiroshima Y;Maawy A;Zhang Y;Zhang N;Murakami T;Chishima T;Tanaka K;Ichikawa Y;Bouvet M;Endo I;Hoffman RM
通讯作者：
Hoffman RM