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Establishment of a new valid animal model for the evaluation of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric rhabdomyosarcoma
Author(s) -
Wagner Benedikt R.,
Adamus Anna L.,
Sönnecken Dörthe,
Vahdad Reza,
Jank Paul,
Denkert Carsten,
Mahnken Andreas H.,
Seitz Guido
Publication year - 2021
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.29202
Subject(s) - medicine , rhabdomyosarcoma , tunel assay , cisplatin , hyperthermic intraperitoneal chemotherapy , apoptosis , intraperitoneal injection , chemotherapy , pathology , cancer research , cancer , immunohistochemistry , ovarian cancer , sarcoma , cytoreductive surgery , biology , biochemistry
Background Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy has been established as a novel treatment approach for peritoneal sarcomatosis. Despite promising clinical reports, there is still a lack of knowledge regarding optimal drug usage and local effects. Therefore, we intended to establish a murine animal model for further evaluation. Procedure Alveolar rhabdomyosarcoma cells were xenotransplanted into NOD/LtSz‐scid IL2Rγnullmice ( n = 100). The mice received a continuous intraperitoneal lavage with isotonic saline solution as control or with cisplatin (30 or 60 mg/m 2 ) as treatment group for 60 minutes at 37°C or 42°C (6 subgroups, each n = 16). Tumor spread was documented by an adapted peritoneal cancer index and MRI ( n = 4). Tumor and tissue samples, harvested at the end of the perfusion, were evaluated regarding morphology, proliferation, and apoptosis (H&E‐, Ki‐67‐, cleaved caspase 3–staining, TUNEL assay). Results Extensive peritoneal sarcomatosis in over 91% of the cases was observed. HIPEC was feasible without acute side effects. Ki‐67 staining revealed concentration‐ or temperature‐dependent effects of cisplatin‐based HIPEC on the tumors. Although cleaved caspase‐3 showed only sporadic apoptotic effects. TUNEL assay detected concentration‐ or temperature‐dependent apoptotic effects at the outer tumor surface. MRI scans confirmed the observed tumor dissemination. Conclusion This is the first animal model for evaluation of HIPEC in pediatric RMS in mice. Cisplatin‐based HIPEC had early effects on the proliferation whereas circumscribed apoptotic effects could be detected at the tumor surface. This model allows further insights on the possible efficiency of HIPEC in RMS. Further studies using other drug combinations and treatment will follow.