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Increasing the efficiency of hyperthermic intraperitoneal chemotherapy (HIPEC) by combination with a photosensitive drug in pediatric rhabdomyosarcoma in an animal model.
Wagner, Benedikt R; Adamus, Anna L; Hempfling, Laura; Vahdad, Reza; Haap-Hoff, Antje; Heinrich, Benedikt; Vázquez, Olalla; Jank, Paul; Denkert, Carsten; Seitz, Guido.
Afiliación
  • Wagner BR; Department of Pediatric Surgery, University Hospital Marburg, Marburg, Germany.
  • Adamus AL; Department of Pediatric Surgery, University Hospital Marburg, Marburg, Germany.
  • Hempfling L; Department of Pediatric Surgery, University Hospital Marburg, Marburg, Germany.
  • Vahdad R; Department of Pediatric Surgery, University Hospital Marburg, Marburg, Germany.
  • Haap-Hoff A; KARL STORZ SE & Co. KG, Tuttlingen, Germany.
  • Heinrich B; Department of Chemical Biology, Philipps-University Marburg, Marburg, Germany.
  • Vázquez O; Department of Chemical Biology, Philipps-University Marburg, Marburg, Germany.
  • Jank P; Center for Synthetic Microbiology (SYNMIKRO), Marburg, Germany.
  • Denkert C; Department of Pathology, University Hospital Marburg, Marburg, Germany.
  • Seitz G; Department of Pathology, University Hospital Marburg, Marburg, Germany.
Pediatr Blood Cancer ; 69(11): e29864, 2022 Nov.
Article en En | MEDLINE | ID: mdl-35731577
BACKGROUND: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. An enhancement of HIPEC using photodynamic therapy (PDT) might be beneficial. Therefore, a combination of the photosensitizer hypericin (HYP) with HIPEC was evaluated in an animal model. PROCEDURE: An established HIPEC animal model for rhabdomyosarcoma (NOD/LtSz-scid IL2Rγnullmice, n = 80) was used. All groups received HYP (100 µg/200 µl) intraperitoneally with and without cisplatin-based (30 or 60 mg/m2 ) HIPEC (37°C or 42°C, for 60 minutes) (five groups, each n = 16). Peritoneal cancer index (PCI) was documented visually and by HYP-based photodynamic diagnosis (PDD). HYP-based PDT of the tumor was performed. Tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (TUNEL). RESULTS: HYP uptake was detected even in smallest tumor nodes (<1 mm) with improved tumor detection during PDD (PCI with PDD vs. PCI without PDD: 8.5 vs. 7, p < .001***). Apoptotic effects after PDT without HIPEC were limited to the tumor surface, whereas PDT after HIPEC (60 mg/m2 , 42°C) showed additional reduction of tumor proliferation in the top nine to 11 cell layers (50 µm). CONCLUSION: HYP as fluorescent photosensitizer offers an intraoperative diagnostic advantage detecting intraperitoneal tumor dissemination. The combination of HYP and cisplatin-based HIPEC was feasible in vivo, showing enhanced effects on tumor proliferation and apoptosis induction across the tumor surface. Further studies combining HYP and HIPEC will follow to establish a clinical application.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Peritoneales / Rabdomiosarcoma / Rabdomiosarcoma Embrionario / Hipertermia Inducida Límite: Animals / Humans Idioma: En Revista: Pediatr Blood Cancer Asunto de la revista: HEMATOLOGIA / NEOPLASIAS / PEDIATRIA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Peritoneales / Rabdomiosarcoma / Rabdomiosarcoma Embrionario / Hipertermia Inducida Límite: Animals / Humans Idioma: En Revista: Pediatr Blood Cancer Asunto de la revista: HEMATOLOGIA / NEOPLASIAS / PEDIATRIA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos