In vivo modeling of metastatic human high-grade serous ovarian cancer in mice

Autoři: Olga Kim aff001;  Eun Young Park aff001;  David L. Klinkebiel aff002;  Svetlana D. Pack aff003;  Yong-Hyun Shin aff001;  Zied Abdullaev aff003;  Robert E. Emerson aff004;  Donna M. Coffey aff005;  Sun Young Kwon aff006;  Chad J. Creighton aff007;  Sanghoon Kwon aff008;  Edmund C. Chang aff009;  Theodore Chiang aff009;  Alexander N. Yatsenko aff010;  Jeremy Chien aff011;  Dong-Joo Cheon aff012;  Yang Yang-Hartwich aff013;  Harikrishna Nakshatri aff014;  Kenneth P. Nephew aff015;  Richard R. Behringer aff016;  Facundo M. Fernández aff017;  Chi-Heum Cho aff018;  Barbara Vanderhyden aff019;  Ronny Drapkin aff020;  Robert C. Bast, Jr aff021;  Kathy D. Miller aff022;  Adam R. Karpf aff023;  Jaeyeon Kim aff001
Působiště autorů: Department of Biochemistry and Molecular Biology, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America aff001;  Department of Biochemistry and Molecular Biology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, United States of America aff002;  Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America aff003;  Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America aff004;  Department of Pathology and Genomic Medicine, Houston Methodist and Weill Cornell Medical College, Houston, Texas, United States of America aff005;  Department of Pathology, School of Medicine, Keimyung University, Daegu, Republic of Korea aff006;  Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America aff007;  Research and Development Center, Bioway Inc, Seoul, Republic of Korea aff008;  Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America aff009;  Department of Obstetrics, Gynecology & Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America aff010;  Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, California, United States of America aff011;  Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY, United States of America aff012;  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, United States of America aff013;  Department of Surgery, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America aff014;  Medical Sciences Program, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Bloomington, Indiana, United States of America aff015;  Departments of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America aff016;  School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff017;  Department of Obstetrics and Gynecology, School of Medicine, Keimyung University, Daegu, Republic of Korea aff018;  Department of Cellular and Molecular Medicine, University of Ottawa, and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada aff019;  Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff020;  Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America aff021;  Department of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine Indianapolis, Indiana, United States of America aff022;  Eppley Institute for Cancer Research, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, United States of America aff023
Vyšlo v časopise: In vivo modeling of metastatic human high-grade serous ovarian cancer in mice. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008808
Kategorie: Research Article


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.

Klíčová slova:

Animal models of disease – Chromosomes – Mammalian genomics – Metastasis – Metastatic tumors – Mouse models – Ovarian cancer – Fallopian tubes


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Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

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