Sorafenib inhibits tumor growth and improves survival in a transgenic mouse model of pancreatic islet cell tumors.
The purpose of the study was to evaluate Sorafenib (BAY 43-9006) derived receptor tyrosine kinase inhibition on tumor progression in murine islet cell tumors. Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors. Rip1Tag2 mice were treated in two different groups according to the model of tumor progression: the early treatment group received vehicle or Sorafenib from 10 to 14 weeks of age and the late treatment group from week 12 until death. Tumor surface, tumor cell proliferation, and apoptosis were measured in both treatment groups to assess the in vivo effects of Sorafenib. Survival was recorded for the late treatment group. In the early treatment group Sorafenib led to a dramatic decrease in tumor volume compared to the control group. Apoptosis was significantly augmented and cell proliferation was inhibited. As a single therapy Sorafenib significantly improved survival in the late treatment group. Conclusion. Sorafenib may provide a new paradigm for the therapy of islet cell tumors.
Department of Surgery, University Hospital Giessen and Marburg, Baldinger Strasse, 35043 Marburg, Germany.
Volker
V
Fendrich
Katja
K
Maschuw
Johannes
J
Rehm
Malte
M
Buchholz
Julia P
JP
Holler
Emily P
EP
Slater
Detlef K
DK
Bartsch
Jens
J
Waldmann
D007516:Adenoma, Islet Cell; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D000952:Antigens, Polyomavirus Transforming; D007328:Insulin; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib