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Combination of gemcitabine and docetaxel regresses both gastric leiomyosarcoma proliferation and invasion in an imageable patient-derived orthotopic xenograft (iPDOX) model

Kei KawaguchiAntiCancer, Inc., San Diego, CA, USA;Department of Surgery, University of California, San Diego, CA, USA;Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan

Kentaro IgarashiAntiCancer, Inc., San Diego, CA, USA;Department of Surgery, University of California, San Diego, CA, USA

Takashi MurakamiAntiCancer, Inc., San Diego, CA, USA;Department of Surgery, University of California, San Diego, CA, USA

Tasuku KiyunaAntiCancer, Inc., San Diego, CA, USA;Department of Surgery, University of California, San Diego, CA, USA

Scott D. NelsonDepartment of Pathology, University of California, Los Angeles, CA, USA

Sarah M. DryDepartment of Pathology, University of California, Los Angeles, CA, USA

Yunfeng LiDepartment of Pathology, University of California, Los Angeles, CA, USA

Tara A. RussellDivision of Surgical Oncology, University of California, Los Angeles, CA, USA

http://orcid.org/0000-0002-3912-3601

Arun S. SinghDivision of Hematology-Oncology, University of California, Los Angeles, CA, USA;PDOX Inc., San Diego, CA, USA

Bartosz ChmielowskiDivision of Hematology-Oncology, University of California, Los Angeles, CA, USA

http://orcid.org/0000-0002-2374-3320

Michiaki UnnoDepartment of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan

Fritz C. EilberDivision of Surgical Oncology, University of California, Los Angeles, CA, USA;PDOX Inc., San Diego, CA, USACorrespondence[email protected]

http://orcid.org/0000-0003-3336-9333

Robert M. HoffmanAntiCancer, Inc., San Diego, CA, USA;Department of Surgery, University of California, San Diego, CA, USA;PDOX Inc., San Diego, CA, USACorrespondence[email protected]

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Figures & data

Figure 1. Imaging of drug efficacy on a leiomyosarcoma iPDOX. The PDOX model treated with GEM combined with DOC (GEM/DOC) demonstrated tumor regression. Scale bar: 5 mm.

Figure 2. Efficacy of treatment on leiomyosarcoma iPDOX. Bar graph shows relative tumor volume at a post-treatment point relative to the initial pre-treatment tumor volume. All treatments except for PAZ significantly inhibited tumor growth compared with untreated control (CTR). GEM/DOC was the strongest and significantly more effective than other therapies (DOX: p < 0.01, CPA: p < 0.01, TEM: p < 0.01, YON: p < 0.01, PAZ: p < 0.01). **p < 0.01. Error bars: ± SD.

Figure 3. Treatment efficacy for leiomyosarcoma iPDOX. Bar graphs show the tumor fluorescent area (mm²) (A) and fluorescence intensity (B). All treatments significantly inhibited the leiomyosarcoma iPDOX compared with untreated control. **p < 0.01, *p < 0.05. Error bars: ± SD.

Figure 3. Treatment efficacy for leiomyosarcoma iPDOX. Bar graphs show the tumor fluorescent area (mm2) (A) and fluorescence intensity (B). All treatments significantly inhibited the leiomyosarcoma iPDOX compared with untreated control. **p < 0.01, *p < 0.05. Error bars: ± SD.

Figure 4. Correlation of tumor fluorescent area and tumor fluorescence intensity. Tumor area significantly correlated with fluorescence intensity (R² = 0.9105, p < 0.0001). Please see Materials and methods for details.

Figure 5. Correlation of fluorescence intensity and fluorescent area with tumor volume. Both relative tumor fluorescent area (A) and relative fluorescence intensity (B) demonstrated a strong positive correlation with relative tumor volume (R² = 0.8927, p < 0.0001; R² = 0.8967, p < 0.0001; respectively).

Figure 6. Effect of each treatment on mouse body weight. Bar graph shows relative body weight at post-treatment relative to the pre-treatment. There were no significant differences between each treatment group including untreated control.

Figure 7. Histological response. A. The untreated control comprised viable cells without necrosis. B. The tumor treated with GEM and DOC exhibited necrosis. Scale bars: 100 μm.

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Combination of gemcitabine and docetaxel regresses both gastric leiomyosarcoma proliferation and invasion in an imageable patient-derived orthotopic xenograft (iPDOX) model

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Combination of gemcitabine and docetaxel regresses both gastric leiomyosarcoma proliferation and invasion in an imageable patient-derived orthotopic xenograft (iPDOX) model

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