title: Surgery combined with controlled-release doxorubicin silk films as a treatment strategy in an orthotopic neuroblastoma mouse model.
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.
authors.affiliation: Department of Surgery, University of Illinois at Chicago, 840 S. Wood Street, Suite 416, Chicago, IL 60612, USA.
authors.forename: B
authors.initials: B
authors.lastname: Chiu
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: J
authors.initials: J
authors.lastname: Coburn
authors.affiliation: Department of Pathology, Tufts Medical Center, 800 Washington Street, Box 115, Boston, MA 02111, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pilichowska
authors.affiliation: Tufts Clinical and Translational Science Institute, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
authors.forename: C
authors.initials: C
authors.lastname: Holcroft
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
authors.forename: F P
authors.initials: FP
authors.lastname: Seib
authors.affiliation: Department of Neurosurgery, Tufts Medical Center, 800 Washington Street, Tufts Medical Center, Box 5609, Boston, MA 02111, USA.
authors.forename: A
authors.initials: A
authors.lastname: Charest
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Kaplan
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009447:Neuroblastoma / Q000473:pathology / Q000628:therapy*; D047011:Silk / Q000737:chemistry; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D047011:Silk; D004317:Doxorubicin