The combination of gemcitabine and docetaxel arrests a doxorubicin-resistant dedifferentiated liposarcoma in a patient-derived orthotopic xenograft model - 31/07/19

Doi : 10.1016/j.biopha.2019.109093

Kentaro Miyake ^a,^b,^c, Takashi Higuchi ^a,^b, Hiromichi Oshiro ^a,^b, Zhiying Zhang ^a,^b, Norihiko Sugisawa ^a,^b, Jun Ho Park ^a,^b, Sahar Razmjooei ^a,^b, Yuki Katsuya ^a,^b, Maryam Barangi ^a,^b, Yunfeng Li ^d, Scott D. Nelson ^d, Takashi Murakami ^c, Yuki Homma ^c, Yukihiko Hiroshima ^c, Ryusei Matsuyama ^c, Michael Bouvet ^b, Sant P. Chawla ^e, Shree Ram Singh ^f,^⁎ , Itaru Endo ^c,^⁎ , Robert M. Hoffman ^a,^b,^⁎
^a AntiCancer Inc., San Diego, CA, USA
^b Department of Surgery, University of California, San Diego, CA, USA
^c Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
^d Dept. of Pathology, University of California, Los Angeles, CA, USA
^e Sarcoma Oncology Center, Santa Monica, CA, USA
^f Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA

^⁎Corresponding author at: 7917 Ostrow Street, San Diego, CA 92111 USA.Basic Research LaboratoryNational Cancer InstituteFrederickMD21702USA^⁎⁎Corresponding author at: Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA.7917 Ostrow StreetSan DiegoCA92111USA^⁎⁎⁎Corresponding author at: Department of Gastroenterological Surgery, Yokohama City University, Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.Department of Gastroenterological SurgeryYokohama City UniversityGraduate School of Medicine3-9 FukuuraKanazawa-kuYokohama236-0004Japan

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Highlights

•	Liposarcoma (LS) is a chemotherapy-resistant disease.
•	Developed dedifferentiated liposarcoma (DDLS) patient-derived orthotopic xenograft (PDOX) model.
•	Gemcitabine (GEM) combined with docetaxel (DOC) arrested the tumor growth of DDLS PDOX.
•	GEM combined with DOC has clinical potential for this and possibly other DDLS patients.

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Abstract

Liposarcoma (LS) is a chemotherapy-resistant disease. The aim of the present study was to find precise therapy for a recurrent dedifferentiated liposarcoma (DDLS) in a patient-derived orthotopic xenograft (PDOX) model. The DDLS PDOX models were established orthotopically in the right inguinal area of nude mice. The DDLS PDOX models were randomized into five groups: untreated; doxorubicin (DOX); gemcitabine (GEM) combined with docetaxel (DOC); pazopanib (PAZ); and yondelis (YON). On day 15, all mice were sacrificed. Measurement of tumor volume and body weight were done two times a week. The DDLS PDOX was resistant to DOX (P > 0.184). YON suppressed tumor growth significantly compared to control group (P < 0.027). However, only GEM combined with DOC arrested the tumor growth (P < 0.001). These findings suggest that GEM combined with DOC has clinical potential for this and possibly other DDLS patients.

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Keywords : Liposarcoma, Patient-derived orthotopic xenograft, PDOX, Nude mice, Gemcitabine, Docetaxel

Plan

Introduction

Materials and methods

Mice

Establishing DDLS PDOX model

Treatment study design for the DDLS PDOX models

Tumor histology

Statistical analysis

Results

Treatment efficacy on the DDLS

Effect of treatment on body weight

Histology of the DDLS PDOX

Discussion

Conflict of interest

Funding

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Vol 117

Article 109093- septembre 2019 Retour au numéro

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The combination of gemcitabine and docetaxel arrests a doxorubicin-resistant dedifferentiated liposarcoma in a patient-derived orthotopic xenograft model - 31/07/19

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