Patient-derived orthotopic xenograft (PDOX) mouse model of adult rhabdomyosarcoma invades and recurs after resection in contrast to the subcutaneous ectopic model

Igarashi, Kentaro; Kawaguchi, Koji; Kiyuna, Tasuku; Murakami, Takashi; Miwa, Shinji; Nelson, Scott D.; Dry, Sarah M.; Li, Yunfeng; Singh, Arun S.; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Tsuchiya, Hiroyuki; Eilber, Fritz C.; Hoffman, Robert M.

doi:10.1080/15384101.2016.1252885

Cited by 47 publications

(55 citation statements)

References 27 publications

(24 reference statements)

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“…PDOX models thus far developed are pancreatic [Fu et al, ; Hiroshima et al, ,, ], breast [Fu et al, ], ovarian [Fu and Hoffman, ], lung [Wang et al, ], cervical [Hiroshima et al, ; Murakami et al, ], colon [Fu et al, ; Metildi et al, ; Hiroshima et al, ], and stomach cancers [Furukawa et al, ], sarcoma [Hiroshima et al, ,; Kiyuna et al, ; Murakami et al, ,], and melanoma [Yamamoto et al, ; Kawaguchi et al, ,]. PDOX models of sarcoma that we have developed include undifferentiated pleomorphic sarcoma (UPS) [Murakami et al, ; Kiyuna et al, ], follicular dendritic cell sarcoma (FDCS) [Kiyuna et al, ], rhabdomyosarcoma (RMS) [Igarashi et al, ], Ewing's sarcoma [Murakami et al, ], and osteosaroma [Murakami et al, ]. The present manuscript describes a PDOX model of undifferentiated spindle‐cell sarcoma (USCS).…”

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confidence: 99%

High Efficacy of Pazopanib on an Undifferentiated Spindle-Cell Sarcoma Resistant to First-Line Therapy Is Identified With a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model

et al. 2017

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Undifferentiated spindle‐cell sarcoma (USCS) is a recalcitrant cancer. Our laboratory pioneered the patient‐derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). In the present study, we evaluated the efficacy of standard first‐line chemistry of doxorubicin (DOX), gemcitabine (GEM) combined with docetaxel (DOC), compared to pazopanib (PAZ), a multi‐targeting tyrosine‐kinase inhibitor, in an USCS PDOX model. A high‐grade USCS from a striated muscle of the patients was grown orthotopically in the right biceps femoris muscle of nude mice to establish the PDOX model. The PDOX models were randomized into the following groups when tumor volume reached 100 mm3: G1, control without treatment; G2, DOX (3 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, GEM (100 mg/kg, i.p., weekly, for 2 weeks) combined with DOC (20 mg/kg, i.p., once); G4, PAZ (100 mg/kg, p.o., daily, for 14 days). All treatments except DOX significantly inhibited tumor growth compared to untreated control on day 14 after treatment initiation. Tumor sizes were as fallows: control (G1): 332.0 ± 58.7 mm3; DOX (G2): 316.9 ± 55.9 mm3, P = 0.605; GEM + DOC (G3): 228.9 ± 39.8 mm3, P = 0.001; PAZ (G4): 173.8 ± 23.3 mm3, P < 0.0001. PAZ showed significantly more efficacy compared to other therapies evaluated: DOX (P < 0.0001), GEM + DOC (P = 0.006). There were no animal deaths in any group and body weight of treated mice was not significantly different in each group. The present results demonstrate that the PDOX model of USCS can identify a promising novel agent with significantly greater efficacy than first‐line therapy for this recalcitrant disease. J. Cell. Biochem. 118: 2739–2743, 2017. © 2017 Wiley Periodicals, Inc.

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High Efficacy of Pazopanib on an Undifferentiated Spindle-Cell Sarcoma Resistant to First-Line Therapy Is Identified With a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model

et al. 2017

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“…Tumors were prepared for histological analysis using including hematoxylin and eosin (H&E) staining using previously published protocols (26).…”

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Choline-Deficient-Diet-Induced Fatty Liver Is A Metastasis-Resistant Microenvironment

Nakamura

Suetsugu

Hasegawa

et al. 2017

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Abstract. Background Non-alcoholic fatty liver disease (NAFLD) has increased in developed countries, with a prevalence of 20-30% in Europe and the United States and 12-30% in Asia (1-8). Obesity is a risk factor for NAFLD and has influenced the increase in NAFLD (9). An important question is whether fatty liver has an influence on cancer metastasis.We have previously shown that murine EL4-RFP malignant lymphoma cells metastasize to multiple sites including the liver (10, 11). We have previously described color-coded imaging of the tumor microenvironment (TME) of cancer cells (11)(12)(13)(14)(15)(16)(17)(18)(19)(20).A syngeneic color-coded imageable lymphoma model, using the EL4 cell line, was previously developed to visualize recruitment of host stromal cells in the TME during metastasis. Large EL4-RFP liver metastases in C57BL/6-GFP mice contained GFP-expressing stromal cells derived from the host (10). A subsequent study whereby liver metastases were formed after splenic injection of EL4-RFP cells also demonstrated that the liver metastases were rich in stromal cells including macrophages, fibroblasts, dendritic cells and normal lymphocytes (11).In the present report, the TME of EL4-RFP metastasis in mice with fatty liver and normal liver were compared, with the use of EL4-RFP. Materials and MethodsGFP transgenic mice. Transgenic C57BL/6-GFP mice were obtained from the

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“…Recently, PDOX models of sarcoma (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64), cervical cancer (65-67) as well as melanoma (68)(69)(70)(71)(72)(73)(74) have also been developed.…”

Section: Patient-derived Orthotopic Xenograft (Pdox) Mouse Models Of mentioning

confidence: 99%

Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse Models of Cancer

Suetsugu

Shimizu

Saji

et al. 2018

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Abstract. The tumor microenvironment (TME) contains stromal cells in a complex interaction with cancer cells. This relationship has become better understood with the use of fluorescent proteins for in vivo imaging cancer-cell or stromal-cell targeting by potential therapeutics can be visualized. Color-coded imaging enabled the visualization of apparent fusion of cancer and stromal cells. Color-coded imaging is a powerful tool visualizing the interaction of cancer and stromal cells during cancer progression and treatment.In vivo imaging with fluorescent proteins was pioneered by our laboratories and has been particularly useful for studying tumor growth, invasion, cancer-cell trafficking, metastasis, angiogenesis, and other aspects of tumor progression (1-5). Multicolored proteins have allowed the color-coding of cancer cells growing in vivo such as between highly-and poorly-metastatic cells, cancer stem and non-stem cells, and gene transfer between cancer cells (3, 4,(6)(7)(8)(9)(10)(11)(12)(13).The present review focuses on color-coded imaging of cancer and stromal cells in the tumor microenvironment (TME).Transgenic nude mice expressing fluorescent proteins for colorcode imaging of the TME. The green fluorescent protein (GFP)-expressing athymic nude mouse was obtained by crossing nontransgenic nude mice with the transgenic C57/B6 GFP mouse in which the β-actin promoter drives GFP. In the adult GFP nude mice, most organs brightly expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, duodenum, and the entire digestive system from the tongue to the anus; the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The bared skeleton also highly expressed GFP (14).

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Patient-derived orthotopic xenograft (PDOX) mouse model of adult rhabdomyosarcoma invades and recurs after resection in contrast to the subcutaneous ectopic model

Cited by 47 publications

References 27 publications

High Efficacy of Pazopanib on an Undifferentiated Spindle-Cell Sarcoma Resistant to First-Line Therapy Is Identified With a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model

High Efficacy of Pazopanib on an Undifferentiated Spindle-Cell Sarcoma Resistant to First-Line Therapy Is Identified With a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model

Choline-Deficient-Diet-Induced Fatty Liver Is A Metastasis-Resistant Microenvironment

Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse Models of Cancer

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