Temozolomide targets and arrests a doxorubicin-resistant follicular dendritic-cell sarcoma patient-derived orthotopic xenograft mouse model

Hiromichi Oshiro, Yasunori Tome, Tasuku Kiyuna, Kentaro Miyake, Kei Kawaguchi, Takashi Higuchi, Masuyo Miyake, Zhiying Zang, Sahar Razmjooei, Maryam Barangi, Sintawat Wangsiricharoen, Scott D. Nelson, Yunfeng Li, Michael Bouvet, Shree Ram Singh, Fuminori Kanaya, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Follicular dendritic cell sarcoma (FDCS) is a very rare and highly recalcitrant disease. A patient's doxorubicin-resistant FDCS was previously established orthotopically on the right high thigh into the biceps femoris of mice to establish a patient-derived orthotopic xenograft (PDOX) model. The aim of the present manuscript was to identify an effective drug for this recalcitrant tumor. Here, we evaluated the efficacy of temozolomide (TMZ), trabectedin (TRAB) and pazopanib (PAZ) on the FDCS PDOX model. PDOX mouse models were randomized into five groups of eight to nine mice, respectively. Group 1, untreated control with PBS, i.p.; Group 2, treated with doxorubicin (DOX), 2.4 mg/kg, i.p., weekly for 3 weeks; Group 3, treated with PAZ, 50 mg/kg, oral gavage, daily for 3 weeks; Group 4, treated with TMZ, 25 mg/kg, oral gavage, daily for 3 weeks; Group 5, treated with TRAB, 0.15 mg/kg, i.v., weekly for 3 weeks. Body weight and tumor volume were assessed 2 times per week. TMZ arrested the FDCS PDOX model compared to the control group (p < 0.05). PAZ and TRAB did not have significant efficacy compared to the control group (p = 0.99, p = 0.69 respectively). The PDOX tumor was resistant to DOX (p= 0.99). as was the patient. The present study demonstrates that TMZ is effective for a PDOX model of FDCS established from a patient who failed DOX treatment, further demonstrating the power of PDOX to identify effective therapy including for tumors that failed first line therapy.

Original languageEnglish
Pages (from-to)17-23
Number of pages7
JournalTissue and Cell
Volume58
DOIs
Publication statusPublished - 2019 Jun
Externally publishedYes

Keywords

  • Doxorubicin
  • Follicular dendritic cell sarcoma
  • Patient-derived orthotopic xenograft
  • PDOX
  • Soft-tissue
  • Temozolomide

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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