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

Kentaro Miyake; Takashi Higuchi; Hiromichi Oshiro; Zhiying Zhang; Norihiko Sugisawa; Jun Ho Park; Sahar Razmjooei; Yuki Katsuya; Maryam Barangi; Yunfeng Li; Scott D. Nelson; Takashi Murakami; Yuki Homma; Yukihiko Hiroshima; Ryusei Matsuyama; Michael Bouvet; Sant P. Chawla; Shree Ram Singh; Itaru Endo; Robert M. Hoffman

Biomedicine & Pharmacotherapy (Sep 2019)

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

Kentaro Miyake,
Takashi Higuchi,
Hiromichi Oshiro,
Zhiying Zhang,
Norihiko Sugisawa,
Jun Ho Park,
Sahar Razmjooei,
Yuki Katsuya,
Maryam Barangi,
Yunfeng Li,
Scott D. Nelson,
Takashi Murakami,
Yuki Homma,
Yukihiko Hiroshima,
Ryusei Matsuyama,
Michael Bouvet,
Sant P. Chawla,
Shree Ram Singh,
Itaru Endo,
Robert M. Hoffman

Affiliations

Kentaro Miyake: 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
Takashi Higuchi: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Hiromichi Oshiro: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Zhiying Zhang: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Norihiko Sugisawa: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Jun Ho Park: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Sahar Razmjooei: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Yuki Katsuya: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Maryam Barangi: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Yunfeng Li: Dept. of Pathology, University of California, Los Angeles, CA, USA
Scott D. Nelson: Dept. of Pathology, University of California, Los Angeles, CA, USA
Takashi Murakami: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Yuki Homma: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Yukihiko Hiroshima: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Ryusei Matsuyama: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Michael Bouvet: Department of Surgery, University of California, San Diego, CA, USA
Sant P. Chawla: Sarcoma Oncology Center, Santa Monica, CA, USA
Shree Ram Singh: Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA; Corresponding author at: Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA.
Itaru Endo: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Corresponding author at: Department of Gastroenterological Surgery, Yokohama City University, Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Robert M. Hoffman: AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Corresponding author at: 7917 Ostrow Street, San Diego, CA 92111 USA.

Journal volume & issue: Vol. 117

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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