Successful transplantation of human hepatoblastoma into immunodeficient mice

Fuchs, Jörg; Schmidt, Dagmar; Pietsch, Torsten; Miller, Konstantin; Schweinitz, Dietrich von

doi:10.1016/s0022-3468(96)90242-0

Cited by 28 publications

(37 citation statements)

References 11 publications

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“…Accordingly, we observed a destabilization of cell integrity in both tested cell lines together with an altered nucleus-cytoplasm relation on the basis of increased numbers of nuclei (30,31). An animal model with exposure to CDDP was used to overcome the problem of reduced cell-cell adhesions (17). After re-culturing, xenograft derived HB cells from HepT1, but not from HUH6, showed an enhanced IC 50 for CDDP.…”

Section: Discussionmentioning

confidence: 99%

“…For the generation of cisplatin resistant tumour cells we used a previously described animal model (17,22). HUH6 and HepT1 cells were xenotransplanted into 6 to 8-week-old, female athymic NMRI (nu/nu) mice.…”

Section: Animals and Xenotransplantationmentioning

confidence: 99%

“…Some continuous cell lines of HB are available for in vitro studies (14)(15)(16). To closer reflect the microenvironment of HB tumours, an animal model using nude mice (NMRI, nu/nu) was established (17). However, there exists no model to investigate the impact of substances on drug resistant HB.…”

Section: Introductionmentioning

confidence: 99%

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Development of a drug resistance model for hepatoblastoma

Eicher

Dewerth²,

Kirchner³

et al. 2011

Int J Oncol

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Abstract. Multidrug resistance (MDR) is a major reason for poor treatment results in hepatoblastoma (HB). The objective of this study was to establish a drug resistance model for HB to analyse alternative treatment options in vitro. Both HB cell lines HUH6 and HepT1 were xenotransplanted in NMRI mice (nu/nu) and 2 cycles of cisplatin (CDDP) treatment were administered. Thereafter, xenotransplants were excised and viable tumour cells were re-cultured. 3D cultures of HUH6 and HepT1 cells were generated on a low binding culture surface. Cell viability in response to CDDP/DOXO (doxorubicin) and apoptosis was assessed by MTT-assay and caspase 3 activity, respectively. Efflux of doxorubicin was measured by flow cytometry. Cellular levels of ABC-transporters (MDR1, MRP1, cMOAT and BRCP) were determined by real time RT-PCR. Only HepT1 cells isolated from HB xenografts showed resistance to CDDP, but did not survive repeated passages. Culturing HUH6 and HepT1 cells as spheroids was successful and 3D cultures showed an IC 50 -drift to higher drug concentrations for CDDP and DOXO compared to 2D cultures. Treatment with CDDP and DOXO led to homogeneous apoptosis in spheroids. Increased doxorubicin efflux in HUH6 spheroids was not influenced by the P-glycoprotein inhibitor tariquidar. Expression levels of MDR1, MRP1, cMOAT and BRCP in 3D cultures were similar to those in 2D cultures and were higher in HepT1 than in HUH6 cells. In conclusion, a 3D cell culture model for multidrug resistance was established for hepatoblastoma. The underlying mechanism involves altered accessibility of the cells for drugs rather than up-regulation of ABC-transporters.

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Section: Discussionmentioning

confidence: 99%

Section: Animals and Xenotransplantationmentioning

confidence: 99%

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Development of a drug resistance model for hepatoblastoma

Eicher

Dewerth²,

Kirchner³

et al. 2011

Int J Oncol

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“…In 1984, Rousseau-Merck et al reported a stable xenotransplantation of nephroblastoma, and revealed that a constant amount of stroma within 10 tumor passages demonstrated tumor stability (8). In 1996, Fuchs et al established the first stable and reproducible model for xenotransplantation of human hepatoblastoma into immunocompromised NMRI nu/nu mice (9). High levels of the tumor marker α-fetoprotein (AFP) were detected in the serum of the animals.…”

Section: Xenograftsmentioning

confidence: 99%

“…In pediatric oncology, this is the case for hepatoblastoma and certain types of germ cell tumors, which secrete AFP or β-HCG. Hepatoblastoma xenografts also secrete human AFP, which is measurable in the serum of transplanted animals (9).…”

Section: Small Animal Imagingmentioning

confidence: 99%

Animal models of extracranial pediatric solid tumors

et al. 2012

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Abstract. Animal models, including xenografts, models of metastatic invasion, syngeneic models and transgenic models, are important tools for basic research in solid pediatric tumors, while humanized animal models are useful for novel immunotherapeutical approaches. Optical and molecular imaging techniques are used for in vivo imaging and may be used in conjunction with alternative treatment approaches, including photodynamic therapy. The aim of this review is to highlight the various animal models that may be used for basic research in pediatric solid tumors.

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