loading page

Establishment of a new valid animal model for the evaluation of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric rhabdomyosarcoma
  • +5
  • Benedikt Wagner,
  • Anna Adamus,
  • Dörthe Sönnecken,
  • Reza Vahdad,
  • Paul Jank,
  • Carsten Denkert,
  • Andreas Mahnken,
  • Guido Seitz
Benedikt Wagner
University Hospital of Giessen and Marburg Campus Marburg
Author Profile
Anna Adamus
University Hospital of Giessen and Marburg Campus Marburg
Author Profile
Dörthe Sönnecken
University Hospital of Giessen and Marburg Campus Marburg
Author Profile
Reza Vahdad
University Hospital of Giessen and Marburg Campus Marburg
Author Profile
Paul Jank
University Hospital of Giessen and Marburg Campus Marburg
Author Profile
Carsten Denkert
University Hospital of Giessen and Marburg Campus Marburg
Author Profile
Andreas Mahnken
University Hospital of Giessen and Marburg Campus Marburg
Author Profile
Guido Seitz
University Hospital of Giessen and Marburg Campus Marburg
Author Profile

Abstract

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/m2) as treatment group for 60 minutes at 37 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. While 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.

Peer review status:IN REVISION

23 Apr 2021Submission Checks Completed
23 Apr 2021Assigned to Editor
23 Apr 2021Submitted to Pediatric Blood & Cancer
26 Apr 2021Reviewer(s) Assigned
28 May 2021Review(s) Completed, Editorial Evaluation Pending
30 May 2021Editorial Decision: Revise Minor
08 Jun 20211st Revision Received
08 Jun 2021Submission Checks Completed
08 Jun 2021Assigned to Editor