Gemcitabine combined with docetaxel precisely regressed a recurrent leiomyosarcoma peritoneal metastasis in a patient-derived orthotopic xenograft (PDOX) model

Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Kei Kawaguchi, Zhiying Zhang, Sintawat Wangsiricharoen, Sahar Razmjooei, Hiromichi Oshiro, Takashi Higuchi, Yunfeng Li, Scott D. Nelson, Takashi Murakami, Yukihiko Hiroshima, Takafumi Kumamoto, Ryusei Matsuyama, Michael Bouvet, Shree Ram Singh, Sant P. Chawla, Itaru Endo, Robert M. Hoffman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

There are no effective treatments for leiomyosarcoma (LMS) spreading intraabdominally. The aim of this study was to develop precision chemotherapy for recurrent peritoneal LMS metastases in a patient-derived orthotopic xenograft (PDOX) model. The LMS PDOX models were established orthotopically on the dome of the bladder of nude mice. The LMS PDOX models were randomized into 6 groups when the tumor volume reached 80 mm 3 : G1: untreated control; G2: doxorubicin (DOX) (DOX: i.p., 3 mg/kg, weekly, 3 weeks); G3: DOX combined with olaratumab (OLA) (DOX: i.p., 3 mg/kg, weekly, 3 weeks; OLA: i.p., 40 mg/kg, 3 times/week, 3 weeks); G4: gemcitabine (GEM) combined with docetaxel (DOC) (GEM: i.p., 100 mg/kg, weekly, 3 weeks; DOC: i.p., 20 mg/kg, weekly, 3 weeks); G5: pazopanib (PAZ) (PAZ: p.o., 100 mg/kg, daily, 3 weeks); G6: palbociclib (PAL) (PAL: p.o., 100 mg/kg, daily, 3 weeks). All mice were sacrificed on day 22. Body weight was assessed twice a week. Tumor volume was measured on day 0 and day 22. Although all regimens had a significant efficacy compared to the untreated group (P < 0.001), only GEM combined with DOC regressed the tumor significantly (P < 0.001), suggesting GEM combined with DOC has clinical potential for this LMS patient.

Original languageEnglish
Pages (from-to)1041-1046
Number of pages6
JournalBiochemical and biophysical research communications
Volume509
Issue number4
DOIs
Publication statusPublished - 2019 Feb 19
Externally publishedYes

Keywords

  • Docetaxel
  • Gemcitabine
  • Leiomyosarcoma
  • Nude mice
  • Patient-derived orthotopic xenograft
  • PDOX

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Miyake, K., Kiyuna, T., Miyake, M., Kawaguchi, K., Zhang, Z., Wangsiricharoen, S., Razmjooei, S., Oshiro, H., Higuchi, T., Li, Y., Nelson, S. D., Murakami, T., Hiroshima, Y., Kumamoto, T., Matsuyama, R., Bouvet, M., Singh, S. R., Chawla, S. P., Endo, I., & Hoffman, R. M. (2019). Gemcitabine combined with docetaxel precisely regressed a recurrent leiomyosarcoma peritoneal metastasis in a patient-derived orthotopic xenograft (PDOX) model. Biochemical and biophysical research communications, 509(4), 1041-1046. https://doi.org/10.1016/j.bbrc.2019.01.046