Establishment of a human pancreatic tumor xenograft model: Potential application for preclinical evaluation of novel therapeutic agents

被引:40
作者
Mohammad, RM
Dugan, MC
Mohamed, AN
Almatchy, VP
Flake, TM
Dergham, ST
Shields, AF
Al-Katib, AA
Vaitkevicius, VK
Sarkar, FH
机构
[1] Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48201 USA
[2] Wayne State Univ, Sch Med, Dept Internal Med, Div Hematol & Oncol,Karmanos Canc Inst, Detroit, MI 48201 USA
[3] Wayne State Univ, Sch Med, Dept Surg, Karmanos Canc Inst, Detroit, MI 48201 USA
关键词
pancreatic tumor line; KCI-MOH1; xenograft; SCID mice; gemcitabine; taxol; cytarabine; 5-fluorouracil; Bryostatin; 1;
D O I
10.1097/00006676-199801000-00004
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Adenocarcinoma of the pancreas is currently the fifth leading cause of death in the United States. It remains generally incurable by available treatment modalities. We report here on the characterization of a permanent pancreatic cell line (KCl-MOH1), established as a xenograft in severe combined immune deficient (SCID) mice, from a 74 year-old African 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) (p22;q12), -10, -12, add (14)(p11), -18, add (20)(q13)-22/84, idemx2. Immunostaining of KCI-MOH1 tissues shows strong expression of p53 and p21 proteins. The xenograft model was established by transplanting the KCI-MOH1 cells subcutaneously (sc) in SCID mice. When the sc tumor was transplanted in vivo to other SCID mice, the success rate was 100%, with a doubling time of 8.5 days. The SCID mouse xenograft model was used to test the efficacy of selected standard chemotherapeutic drugs (taxol, gemcitabine, 5-fluorouracil, and Ara-C) and novel biological agents (Bryostatin 1 and Auristatin-PE). Results show that gemcitabine, Ara-C, and Bryostatin 1 were active against KCI-MOH1. The xenograft described herein can be used as an animal model to facilitate the development of novel therapeutic agents against human pancreatic cancers.
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页码:19 / 25
页数:7
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