Elkas John C, Baldwin Rae Lynn, Pegram Mark, Tseng Yiou, Slamon Dennis, Karlan Beth Y
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Gynecol Oncol. 2002 Nov;87(2):200-6. doi: 10.1006/gyno.2002.6819.
To establish a murine xenograft model of human ovarian carcinoma.
A slurry of fresh human tumor from patients with intraperitoneal malignancies was heterotransplanted intraperitoneally into nude (nu/nu) and severely combined immunodeficient mice (CB-17, SCID). Xenograft growth was assessed by serial examination and necropsy. The xenografts were passaged to new animals when tumors were palpably greater than 1 cm(3). Histopathologic analysis of the xenografts was performed at each passage as well as immunohistochemical staining for p53 mutations. Persistent expression of human genes by the xenografts at higher passages was assessed by RT-PCR amplification of the human beta-globin gene. This xenograft model was used in the preclinical evaluation of an adenoviral vector containing a beta-galactosidase reporter gene and a wild-type p53 gene.
Tumor growth was not established in any of the nude mice heterotransplanted with tissue from six different ovarian cancer patients. Eleven of 13 specimens established xenograft growth when injected in SCID mice. Nine xenografts have been subsequently passaged between 6 and 24 animal generations to date. All xenografts retained histopathologic similarities to their original human tumors and the p53 expression patterns remained stable through higher passages. Within 24 h after intraperitoneal administration of an adenoviral vector, transduction of the reporter gene was evident in the xenografts. In addition, administration of an adenoviral vector containing a wild-type p53 gene significantly decreased the tumor burden compared to controls (P < 0.04).
This murine xenograft model of human ovarian carcinoma appears to be reliable and reproducible and has utility for the study of novel therapeutics.
建立人卵巢癌小鼠异种移植模型。
将来自腹腔恶性肿瘤患者的新鲜人肿瘤组织制成匀浆，经腹腔内移植到裸鼠（nu/nu）和严重联合免疫缺陷小鼠（CB-17，SCID）体内。通过连续检查和尸检评估异种移植瘤的生长情况。当肿瘤可触及且体积大于1 cm³时，将异种移植瘤传代至新的动物体内。每次传代时对异种移植瘤进行组织病理学分析，并对p53突变进行免疫组化染色。通过对人β-珠蛋白基因进行RT-PCR扩增，评估高代异种移植瘤中人基因的持续表达情况。该异种移植模型用于含β-半乳糖苷酶报告基因和野生型p53基因的腺病毒载体的临床前评估。
用来自6例不同卵巢癌患者的组织对裸鼠进行异种移植，均未形成肿瘤生长。将13个标本中的11个注射到SCID小鼠体内后形成了异种移植瘤生长。迄今为止，9个异种移植瘤已在6至24个动物代次之间传代。所有异种移植瘤在组织病理学上均与其原始人肿瘤相似，且p53表达模式在高代传代过程中保持稳定。腹腔内给予腺病毒载体后24小时内，报告基因在异种移植瘤中的转导明显。此外，与对照组相比，给予含野生型p53基因的腺病毒载体可显著降低肿瘤负荷（P < 0.04）。
这种人卵巢癌小鼠异种移植模型似乎可靠且可重复，对新型治疗方法的研究具有实用性。
