Combination of gemcitabine and docetaxel regresses both gastric leiomyosarcoma proliferation and invasion in an imageable patient-derived orthotopic xenograft (iPDOX) model. Issue 11 (3rd June 2017)

• Record Type: Journal Article
• Authors: Kawaguchi, Kei; Igarashi, Kentaro; Murakami, Takashi; Kiyuna, Tasuku; Nelson, Scott D.; Dry, Sarah M.; Li, Yunfeng; Russell, Tara A.; Singh, Arun S.; Chmielowski, Bartosz; Unno, Michiaki; Eilber, Fritz C.; Hoffman, Robert M.
• Is Part Of: Cell cycle. Volume 16:Issue 11(2017)
• Page Start: 1063
• Page End: 1069
• Publication Date: 2017-06-03
• Subjects: docetaxel -- drug-response -- gemcitabine -- gastric leiomyosarcoma -- nude mice -- orthotopic -- PDOX -- precision therapy -- red fluorescent protein -- tumor regression; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2017.1314406
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Gastric leiomyosarcoma is a recalcitrant cancer and the chemotherapy strategy is controversial. The present study used a patient-derived orthotopic xenograft (PDOX) nude mouse model of gastric leiomyosarcoma to identify an effective therapeutic regimen to develop individualized precision medicine for this disease. The gastric leiomyosarcoma obtained from a patient was first grown in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP) to stably label the tumor stroma. The RFP-expressing tumor was then passaged orthotopically in the gastric wall of non-transgenic nude mice to establish an imageable PDOX (iPDOX) model. The bright fluorescent tumor was readily imaged over time to determine drug efficacy. Four weeks after implantation, 70 PDOX nude mice were divided into 7 groups: control without treatment (n = 10); doxorubicin (DOX) (2.4 mg/kg, intraperitoneally (i.p.), once a week for 2 weeks, n = 10); gemcitabine (GEM)/ docetaxel (DOC) (GEM: 100 mg/kg, DOC: 20 mg/kg, i.p., once a week for 2 weeks, n = 10); cyclophosphamide (CPA) (140 mg/kg, i.p., once a week for 2 weeks, n = 10); temozolomide (TEM) (25 mg/kg, orally, daily for 14 consecutive days, n = 10); yondelis (YON) (0.15 mg/kg, i.v., once a week for 2 weeks, n = 10); pazopanib (PAZ) (100 mg/kg, orally, daily for 14 consecutive days, n = 10). On day 14 from initiation of treatment, all treatments except PAZ significantly inhibited tumor growth compared with untreated control (DOX: p < 0.01, GEM/DOC: p < 0.01, CPA: p < 0.01, TEM: p < 0.01, YON: p < 0.01) on day 14 after initiation. In addition, only GEM/DOC was more significantly effective than DOX ( p < 0.05). GEM/DOC could regress the leimyosarcoma in the PDOX model and has important clinical potential for precision individual treatment of leiomyosarcoma patients.