Surgery combined with controlled-release doxorubicin silk films as a treatment strategy in an orthotopic neuroblastoma mouse model

B Chiu, M Pilichowska, Philipp Seib, A Charest, DL Kaplan

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Abstract

Background: Neuroblastoma tumour resection goal is maximal tumour removal. We hypothesise that combining surgery with sustained, local doxorubicin application can control tumour growth.methods: We injected human neuroblastoma cells into immunocompromised mouse adrenal gland. When KELLY cell-induced tumour volume was >300 mm3, 80–90% of tumour was resected and treated as follows: instantaneous-release silk film with 100 μg doxorubicin (100IR), controlled-release film with 200 μg (200CR) over residual tumour bed; and 100 and 200 μg intravenous doxorubicin (100IV and 200IV). Tumour volume was measured and histology analysed.results: Orthotopic tumours formed with KELLY, SK-N-AS, IMR-32, SH-SY5Y cells. Tumours reached 1800±180 mm3 after 28 days, 2200±290 mm3 after 35 days, 1280±260 mm3 after 63 days, and 1700±360 mm3 after 84 days, respectively. At 3 days post KELLY tumour resection, tumour volumes were similar across all groups (P=0.6210). Tumour growth rate was similar in untreated vs control film, 100IV vs 100IR, and 100IV vs 200IV. There was significant difference in 100IR vs 200CR (P=0.0004) and 200IV vs 200CR (P=0.0003). Tumour growth with all doxorubicin groups was slower than that of control (P: <0.0001–0.0069). At the interface of the 200CR film and tumour, there was cellular necrosis, surrounded by apoptotic cells before reaching viable tumour cells.conclusions: Combining surgical resection and sustained local doxorubicin treatment is effective in tumour control. Administering doxorubicin in a local, controlled manner is superior to giving an equivalent intravenous dose in tumour control.
Original languageEnglish
Number of pages708
JournalBritish Journal of Cancer
Volume111
Early online date12 Jun 2014
DOIs
Publication statusPublished - 12 Aug 2014

Keywords

  • neuroblastoma tunmour
  • tumour resection
  • tumour removal
  • doxorubicin
  • chemotherapy
  • controlled release
  • animal model

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