Establishment of a human pancreatic tumor xenograft model: Potential application for preclinical evaluation of novel therapeutic agents
Establishment of a human pancreatic tumor xenograft model: Potential application for preclinical evaluation of novel therapeutic agents
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DOI：
10.1097/00006676-199801000-00004
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发表时间：
1998-01-01
期刊：
影响因子：
2.9
通讯作者：
Sarkar, FH
中科院分区：
文献类型：
--
作者：
Mohammad, RM;Dugan, MC;Sarkar, FH
胰腺腺癌目前是美国第五大死因。通过现有的治疗方式，它通常仍然无法治愈。我们在此报告永久胰腺细胞系 (KCl-MOH1) 的特征，该细胞系是在严重联合免疫缺陷 (SCID) 小鼠中建立的异种移植物，该小鼠来自一名被诊断患有胰腺癌的 74 岁非裔美国男性患者。从 SCID 小鼠身上切除的石蜡包埋肿瘤切片显示出典型的胰腺腺癌。对 SCID 小鼠肿瘤培养细胞的核型分析揭示了具有多个克隆畸变的雄性核型：42、XY、add (3)(p11.2)、der(7) t(7;12) (p22;q12)、-10、-12、add (14)(p11)、-18、add (20)(q13)-22/84、同上x2。 KCI-MOH1 组织的免疫染色显示 p53 和 p21 蛋白的强表达。通过将 KCI-MOH1 细胞皮下移植到 SCID 小鼠中建立异种移植模型。当皮下肿瘤移植到其他SCID小鼠体内时，成功率为100%，倍增时间为8.5天。 SCID 小鼠异种移植模型用于测试选定的标准化疗药物（紫杉醇、吉西他滨、5-氟尿嘧啶和 Ara-C）和新型生物制剂（Bryostatin 1 和 Auristatin-PE）的疗效。结果表明，吉西他滨、Ara-C 和苔藓抑素 1 对 KCI-MOH1 具有活性。本文描述的异种移植物可以用作动物模型以促进针对人类胰腺癌的新型治疗剂的开发。
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.