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Ann Thorac Surg 2001;71:1120-1125
© 2001 The Society of Thoracic Surgeons

Original article: general thoracic

Validation of an orthotopic model of human lung cancer with regional and systemic metastases

Michael R. Johnston, MDa, John B.M. Mullen, MDb, Marco E. Pagura, BSca, Randy B. Howard, PhDa

a Division of Thoracic Surgery and the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada
b Department of Pathology, Mount Sinai Hospital, University of Toronto, Toronto, Canada

Accepted for publication November 19, 2000.

Address reprint requests to Dr Johnston, Division of Surgical Oncology, Princess Margaret Hospital, 610 University Ave, Suite 3-130, Toronto, Ontario, Canada M5G 2M9
e-mail: michael.johnston{at}uhn.on.ca

Background. We developed an orthotopic model of human lung cancer that exhibits highly predictable regional and systemic metastases. This study examines the response of the model when treated with conventional and experimental chemotherapy.

Methods. NCI-H460 tumor fragments were implanted into the right caudal lung lobe of a nude rat. Treatment commenced 2 weeks later. We assessed response by comparing primary tumor and mediastinal lymph node weights, total body weight, and length of survival with untreated, tumor-bearing control animals. We also calculated the incidence of metastasis to kidney, bone, brain, and contralateral lung in treated versus untreated animals.

Results. Mitomycin and cisplatin showed broad activity against primary and metastatic disease. The matrix metalloproteinase inhibitor batimastat, low-dose cisplatin, and mitomycin significantly prolonged survival. High-dose cisplatin caused renal toxicity that shortened survival. Brain metastases did not respond to mitomycin, consistent with its poor blood-brain barrier penetration.

Conclusions. Responses were similar to NCI-H460 in vitro data and consistent with clinical experience for these drugs. Drug-related toxicities similar to those seen in clinical practice were detected.




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