Adjuvant treatment of pancreatic carcinoma in a clinically adapted mouse resection model.
BACKGROUND
The high rate of local recurrence after radical resection of pancreatic adenocarcinoma fosters intensive efforts to develop new approaches for adjuvant treatment. The established animal models show significant limitations in simulating an adjuvant therapeutic setting. For optimal approximation to the clinical situation we therefore improved a murine orthotopic human xenotransplantation model.


METHODS
Subtotal pancreatectomy in mice was performed after orthotopic inoculation of human pancreatic cancer cells and manifestation of solid tumours. The natural course of disease, tumour growth and metastases were analysed. Gemcitabine as a cytotoxic drug was tested in vitro on the cell line used in this model and the effect of adjuvant treatment with gemcitabine in vivo was investigated.


RESULTS
All tumour-resected animals showed local recurrence. Organ metastases occurred in 67% in resected compared to 25% of non-resected animals. Gemcitabine in vitro was ineffective, but as adjuvant monotherapy resulted in a highly significant reduction of tumour weight and metastatic events.


CONCLUSIONS
Subtotal pancreatectomy for xenotransplanted pancreatic cancer in SCID beige mice is feasible. Due to high rates of local recurrence and increased organ metastases, this model offers a relevant option for preclinical adjuvant testing, especially as in vitro and in vivo effects of cytotoxic drugs differ enormously.
Tepel
Juergen
J
Clinic for General Surgery and Thoracic Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany. jtepel@klinikum.uni-kiel.de
Kruse
Marie-Luise
ML
Kapischke
Matthias
M
Haye
Sieglinde
S
Sipos
Bence
B
Kremer
Bernd
B
Kalthoff
Holger
H
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000818:Animals; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D003841:Deoxycytidine; D000093542:Gemcitabine