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

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.

• Authors: 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
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 117 Pg. 109093 (Sep 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 31200257 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Indazoles
• Pyrimidines
• Sulfonamides
• Deoxycytidine
• Docetaxel
• pazopanib
• Doxorubicin
• Gemcitabine

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Disease Models, Animal
• Docetaxel (pharmacology)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• 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)
• Gemcitabine