Mohammad R M, Dugan M C, Mohamed A N, Almatchy V P, Flake T M, Dergham S T, Shields A F, Al-Katib A A, Vaitkevicius V K, Sarkar F H
Department of Internal Medicine, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
Pancreas. 1998 Jan;16(1):19-25. doi: 10.1097/00006676-199801000-00004.
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 (KCI-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 (s.c.) in SCID mice. When the s.c. 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.
胰腺癌目前是美国第五大死因。现有治疗方式通常仍无法治愈该病。我们在此报告了一株永久性胰腺细胞系（KCI-MOH1）的特征，该细胞系取自一名74岁的非裔美国男性胰腺癌患者，在严重联合免疫缺陷（SCID）小鼠体内建立成异种移植瘤。从SCID小鼠体内切除的石蜡包埋肿瘤切片显示为典型的胰腺腺癌。对在SCID小鼠体内生长的肿瘤所衍生的培养细胞进行核型分析，结果显示为男性核型，伴有多个克隆畸变：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。KCI-MOH1组织的免疫染色显示p53和p21蛋白呈强表达。通过将KCI-MOH1细胞皮下接种到SCID小鼠体内建立了异种移植模型。当将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。利用SCID小鼠异种移植模型测试了所选标准化疗药物（紫杉醇、吉西他滨、5-氟尿嘧啶和阿糖胞苷）及新型生物制剂（苔藓抑素1和奥瑞他汀-PE）的疗效。结果表明，吉西他滨、阿糖胞苷和苔藓抑素1对KCI-MOH1有活性。本文所述的异种移植模型可作为动物模型，以促进针对人类胰腺癌的新型治疗药物的研发。
