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Br J Cancer. 2014 Aug 12;111(4):708-15. doi: 10.1038/bjc.2014.324. Epub 2014 Jun 12.

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

Author information

1
Department of Surgery, University of Illinois at Chicago, 840 S. Wood Street, Suite 416, Chicago, IL 60612, USA.
2
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
3
Department of Pathology, Tufts Medical Center, 800 Washington Street, Box 115, Boston, MA 02111, USA.
4
Tufts Clinical and Translational Science Institute, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
5
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
6
Department of Neurosurgery, Tufts Medical Center, 800 Washington Street, Tufts Medical Center, Box 5609, Boston, MA 02111, USA.

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 mm(3), 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 mm(3) after 28 days, 2200±290 mm(3) after 35 days, 1280±260 mm(3) after 63 days, and 1700±360 mm(3) 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.

PMID:
24921912
PMCID:
PMC4134491
DOI:
10.1038/bjc.2014.324
[Indexed for MEDLINE]
Free PMC Article

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