当前位置: X-MOL 学术PLOS Genet. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
In vivo modeling of metastatic human high-grade serous ovarian cancer in mice.
PLOS Genetics ( IF 4.5 ) Pub Date : 2020-06-04 , DOI: 10.1371/journal.pgen.1008808
Olga Kim 1 , Eun Young Park 1 , David L Klinkebiel 2 , Svetlana D Pack 3 , Yong-Hyun Shin 1 , Zied Abdullaev 3 , Robert E Emerson 4 , Donna M Coffey 5 , Sun Young Kwon 6 , Chad J Creighton 7 , Sanghoon Kwon 8 , Edmund C Chang 9 , Theodore Chiang 9 , Alexander N Yatsenko 10 , Jeremy Chien 11 , Dong-Joo Cheon 12 , Yang Yang-Hartwich 13 , Harikrishna Nakshatri 14 , Kenneth P Nephew 15 , Richard R Behringer 16 , Facundo M Fernández 17 , Chi-Heum Cho 18 , Barbara Vanderhyden 19 , Ronny Drapkin 20 , Robert C Bast 21 , Kathy D Miller 22 , Adam R Karpf 23 , Jaeyeon Kim 1
Affiliation  

Metastasis is responsible for 90% of human cancer mortality, yet it remains a challenge to model human cancer metastasis in vivo. Here we describe mouse models of high-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), the most common and deadliest human ovarian cancer type. Mice genetically engineered to harbor Dicer1 and Pten inactivation and mutant p53 robustly replicate the peritoneal metastases of human HGSC with complete penetrance. Arising from the fallopian tube, tumors spread to the ovary and metastasize throughout the pelvic and peritoneal cavities, invariably inducing hemorrhagic ascites. Widespread and abundant peritoneal metastases ultimately cause mouse deaths (100%). Besides the phenotypic and histopathological similarities, mouse HGSCs also display marked chromosomal instability, impaired DNA repair, and chemosensitivity. Faithfully recapitulating the clinical metastases as well as molecular and genomic features of human HGSC, this murine model will be valuable for elucidating the mechanisms underlying the development and progression of metastatic ovarian cancer and also for evaluating potential therapies.



中文翻译:

小鼠转移性人高级别浆液性卵巢癌的体内建模。

转移是造成 90% 的人类癌症死亡率的原因,但在体内模拟人类癌症转移仍然是一个挑战。在这里,我们描述了高级别浆液性卵巢癌的小鼠模型,也称为高级别浆液性癌 (HGSC),这是最常见和最致命的人类卵巢癌类型。基因工程小鼠携带Dicer1Pten灭活和突变 p53 以完全外显率有力地复制人 HGSC 的腹膜转移。肿瘤起源于输卵管,扩散到卵巢并转移到整个盆腔和腹腔,总是引起出血性腹水。广泛和丰富的腹膜转移最终导致小鼠死亡 (100%)。除了表型和组织病理学的相似性外,小鼠 HGSC 还显示出显着的染色体不稳定性、DNA 修复受损和化学敏感性。该小鼠模型忠实地概括了人类 HGSC 的临床转移以及分子和基因组特征,对于阐明转移性卵巢癌的发展和进展的潜在机制以及评估潜在疗法具有重要价值。

更新日期:2020-06-04
down
wechat
bug