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Biochem Biophys Res Commun. 2019 Feb 19;509(4):1041-1046. doi: 10.1016/j.bbrc.2019.01.046. Epub 2019 Jan 16.

Gemcitabine combined with docetaxel precisely regressed a recurrent leiomyosarcoma peritoneal metastasis in a patient-derived orthotopic xenograft (PDOX) model.

Author information

1
AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
2
AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
3
AntiCancer Inc, San Diego, CA, USA.
4
Dept. of Pathology, University of California, Los Angeles, CA, USA.
5
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
6
Department of Surgery, University of California, San Diego, CA, USA.
7
Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov.
8
Sarcoma Oncology Center, 2811 Wilshire Blvd, Suite 414, Santa Monica, CA, 90403, USA.
9
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: endoit@med.yokohama-cu.ac.jp.
10
AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.

Abstract

There are no effective treatments for leiomyosarcoma (LMS) spreading intraabdominally. The aim of this study was to develop precision chemotherapy for recurrent peritoneal LMS metastases in a patient-derived orthotopic xenograft (PDOX) model. The LMS PDOX models were established orthotopically on the dome of the bladder of nude mice. The LMS PDOX models were randomized into 6 groups when the tumor volume reached 80 mm3: G1: untreated control; G2: doxorubicin (DOX) (DOX: i.p., 3 mg/kg, weekly, 3 weeks); G3: DOX combined with olaratumab (OLA) (DOX: i.p., 3 mg/kg, weekly, 3 weeks; OLA: i.p., 40 mg/kg, 3 times/week, 3 weeks); G4: gemcitabine (GEM) combined with docetaxel (DOC) (GEM: i.p., 100  mg/kg, weekly, 3 weeks; DOC: i.p., 20  mg/kg, weekly, 3 weeks); G5: pazopanib (PAZ) (PAZ: p.o., 100  mg/kg, daily, 3 weeks); G6: palbociclib (PAL) (PAL: p.o., 100  mg/kg, daily, 3 weeks). All mice were sacrificed on day 22. Body weight was assessed twice a week. Tumor volume was measured on day 0 and day 22. Although all regimens had a significant efficacy compared to the untreated group (P < 0.001), only GEM combined with DOC regressed the tumor significantly (P < 0.001), suggesting GEM combined with DOC has clinical potential for this LMS patient.

KEYWORDS:

Docetaxel; Gemcitabine; Leiomyosarcoma; Nude mice; PDOX; Patient-derived orthotopic xenograft

PMID:
30660363
DOI:
10.1016/j.bbrc.2019.01.046

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