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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)835-840
Number of pages6
JournalBiomedicine and Pharmacotherapy
Volume111
DOIs
Publication statusPublished - 2019 Mar
Externally publishedYes

Keywords

  • Combination therapy
  • Efficacy
  • Gemcitabine
  • Nab-paclitaxel
  • Nude mice
  • PDOX
  • Undifferentiated soft-tissue sarcoma

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Higuchi, T., Kawaguchi, K., Miyake, K., Oshiro, H., Zhang, Z., Razmjooei, S., Wangsiricharoen, S., Igarashi, K., Yamamoto, N., Hayashi, K., Kimura, H., Miwa, S., Nelson, S. D., Dry, S. M., Li, Y., Chawla, S. P., Eilber, F. C., Singh, S. R., Tsuchiya, H., & Hoffman, R. M. (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. Biomedicine and Pharmacotherapy, 111, 835-840. https://doi.org/10.1016/j.biopha.2018.12.110