ESTABLISHMENT OF A HUMAN PANCREATIC TUMOR XENOGRAFT MODEL - POTENTIALAPPLICATION FOR PRECLINICAL EVALUATION OF NOVEL THERAPEUTIC AGENTS

Adenocarcinoma of the pancreas is currently the fifth leading cause of death in the United States. It remains generally incurable by availab le treatment modalities. We report here on the characterization of a p ermanent pancreatic cell line (KCl-MOH1), established as a xenograft i n severe combined immune deficient (SCID) mice, from a 74 year-old Afr ican American male patient diagnosed with pancreatic cancer. Sections from paraffin-embedded tumors excised from SCID mice revealed typical adenocarcinoma of the pancreas. Karyotypic analysis of cultured cells derived from tumors grown in SCID mice revealed a male karyotype with multiple clonal aberrations: 42, XY, add (3)(p11.2), der(7) t(7;12) (p 22;q12), -10, -12, add (14)(p11), -18, add (20)(q13)-22/84, idemx2. Im munostaining of KCI-MOH1 tissues shows strong expression of p53 and p2 1 proteins. The xenograft model was established by transplanting the K CI-MOH1 cells subcutaneously (sc) in SCID mice. When the sc tumor was transplanted in vivo to other SCID mice, the success rate was 100%, wi th a doubling time of 8.5 days. The SCID mouse xenograft model was use d to test the efficacy of selected standard chemotherapeutic drugs (ta xol, gemcitabine, 5-fluorouracil, and Ara-C) and novel biological agen ts (Bryostatin 1 and Auristatin-PE). Results show that gemcitabine, Ar a-C, and Bryostatin 1 were active against KCI-MOH1. The xenograft desc ribed herein can be used as an animal model to facilitate the developm ent of novel therapeutic agents against human pancreatic cancers.