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30.03.2019 | Original Article

The combination of olaratumab with gemcitabine and docetaxel arrests a chemotherapy-resistant undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft mouse model

verfasst von: Takashi Higuchi, Kentaro Miyake, Norihiko Sugisawa, Hiromichi Oshiro, Zhiying Zhang, Sahar Razmjooei, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Michael Bouvet, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M. Hoffman

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2019

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Abstract

Purpose

Olaratumab (OLA) is a monoclonal antibody against platelet-derived growth factor receptor alpha. OLA has recently been used against soft-tissue sarcoma (STS) combined with doxorubicin (DOX), but with limited efficacy. The goal of present study was to determine the efficacy of OLA combined with gemcitabine (GEM) and docetaxel (DOC) on a chemotherapy-resistant STS patient-derived orthotopic xenograft (PDOX).

Methods

Undifferentiated soft-tissue sarcoma (USTS) from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish the PDOX model. The USTS PDOX was treated with GEM alone, GEM combined with DOC, OLA combined with DOX or GEM, and OLA combined with GEM and DOC. Tumor size and body weight were measured during the 14 days of treatment.

Results

Tumor growth was arrested only by OLA combined with GEM and DOC. Tumors treated with OLA combined with GEM and DOC also had the most necrosis.

Conclusions

The present study demonstrates the power of the PDOX model to identify the novel effective treatment strategy of the combination of OLA, GEM and DOC for drug-resistant soft-tissue sarcoma.

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Titel: The combination of olaratumab with gemcitabine and docetaxel arrests a chemotherapy-resistant undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft mouse model
verfasst von: Takashi Higuchi
Kentaro Miyake
Norihiko Sugisawa
Hiromichi Oshiro
Zhiying Zhang
Sahar Razmjooei
Norio Yamamoto
Katsuhiro Hayashi
Hiroaki Kimura
Shinji Miwa
Kentaro Igarashi
Michael Bouvet
Shree Ram Singh
Hiroyuki Tsuchiya
Robert M. Hoffman
Publikationsdatum: 30.03.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 6/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03824-3

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The combination of olaratumab with gemcitabine and docetaxel arrests a chemotherapy-resistant undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft mouse model

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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