The combination of gemcitabine and nab-paclitaxel as a novel effective treatment strategy for undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model

Takashi Higuchi; Kei Kawaguchi; Kentaro Miyake; Hiromichi Oshiro; Zhiying Zhang; Sahar Razmjooei; Sintawat Wangsiricharoen; Kentaro Igarashi; Norio Yamamoto; Katsuhiro Hayashi; Hiroaki Kimura; Shinji Miwa; Scott D. Nelson; Sarah M. Dry; Yunfeng Li; Sant P. Chawla; Frederick C. Eilber; Shree Ram Singh; Hiroyuki Tsuchiya; Robert M. Hoffman

Biomedicine & Pharmacotherapy (Mar 2019)

The combination of gemcitabine and nab-paclitaxel as a novel effective treatment strategy for undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model

Takashi Higuchi,
Kei Kawaguchi,
Kentaro Miyake,
Hiromichi Oshiro,
Zhiying Zhang,
Sahar Razmjooei,
Sintawat Wangsiricharoen,
Kentaro Igarashi,
Norio Yamamoto,
Katsuhiro Hayashi,
Hiroaki Kimura,
Shinji Miwa,
Scott D. Nelson,
Sarah M. Dry,
Yunfeng Li,
Sant P. Chawla,
Frederick C. Eilber,
Shree Ram Singh,
Hiroyuki Tsuchiya,
Robert M. Hoffman

Affiliations

Takashi Higuchi: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Kei Kawaguchi: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Kentaro Miyake: 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
Sahar Razmjooei: AntiCancer, Inc., San Diego, CA, USA
Sintawat Wangsiricharoen: AntiCancer, Inc., San Diego, CA, USA
Kentaro Igarashi: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Norio Yamamoto: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Katsuhiro Hayashi: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Hiroaki Kimura: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Shinji Miwa: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
Scott D. Nelson: Department of Pathology, University of California, Los Angeles, CA, USA
Sarah M. Dry: Department of Pathology, University of California, Los Angeles, CA, USA
Yunfeng Li: Department of Pathology, University of California, Los Angeles, CA, USA
Sant P. Chawla: Sarcoma Oncology Center, Santa Monica, CA, USA; Corresponding author at: Sarcoma Oncology Center, Santa Monica, CA, USA.
Frederick C. Eilber: Division of Surgical Oncology, University of California, Los Angeles, 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, USA.
Hiroyuki Tsuchiya: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan; Corresponding author at: Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan.
Robert M. Hoffman: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Corresponding author at: AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, USA.

Journal volume & issue: Vol. 111
pp. 835 – 840

Abstract

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Undifferentiated/unclassified soft-tissue sarcomas (USTS) is recalcitrant neoplasms that is usually treated with doxorubicin (DOX)-containing regimens as first-line therapy. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a nanotechnology-based drug and is widely used in pancreatic cancer in combination with gemcitabine (GEM). The major goal of the present study was to determine the efficacy of nab-PTX in combination with GEM, compared to conventional drugs such as docetaxel (DOC), GEM combined with DOC, or first-line drug DOX on a USTS not-otherwise specified (USTS/NOS) from a striated muscle implanted in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. USTS PDOX models were randomized into six groups: untreated control; DOX; DOC; nab-PTX; GEM combined with DOC; and GEM combined with nab-PTX. Tumor size and body weight were measured. Tumor growth was inhibited to the greatest extent by GEM combined with nab-PTX. Tumors treated with GEM combined with nab-PTX had the most necrosis. Body weight of the treated mice was not significantly different from the untreated controls. The present study demonstrates the power of the PDOX model to identify a novel effective treatment strategy of the combination of GEM and nab-PTX for recalcitrant soft-tissue sarcomas. These results suggest that combination of GEM and nab-PTX could be a promising therapeutic strategy for USTS.

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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