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

doi:10.1016/j.biopha.2019.109093

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

Biomed Pharmacother. 2019 Sep:117:109093. doi: 10.1016/j.biopha.2019.109093. Epub 2019 Jun 11.

Authors

Kentaro Miyake¹, Takashi Higuchi², Hiromichi Oshiro², Zhiying Zhang², Norihiko Sugisawa², Jun Ho Park², Sahar Razmjooei², Yuki Katsuya², Maryam Barangi², Yunfeng Li³, Scott D Nelson³, Takashi Murakami⁴, Yuki Homma⁴, Yukihiko Hiroshima⁴, Ryusei Matsuyama⁴, Michael Bouvet⁵, Sant P Chawla⁶, Shree Ram Singh⁷, Itaru Endo⁸, Robert M Hoffman⁹

Affiliations

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

PMID: 31200257
DOI: 10.1016/j.biopha.2019.109093

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.

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

MeSH terms

Animals
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Deoxycytidine / analogs & derivatives*
Deoxycytidine / pharmacology
Disease Models, Animal
Docetaxel / pharmacology*
Doxorubicin / pharmacology*
Drug Resistance, Neoplasm / drug effects*
Gemcitabine
Heterografts / drug effects
Humans
Indazoles
Liposarcoma / drug therapy*
Male
Mice
Mice, Nude
Neoplasm Recurrence, Local / drug therapy
Pyrimidines / pharmacology
Sulfonamides / pharmacology
Tumor Burden / drug effects
Xenograft Model Antitumor Assays / methods

Substances

Indazoles
Pyrimidines
Sulfonamides
Deoxycytidine
Docetaxel
pazopanib
Doxorubicin
Gemcitabine