Uncovering Biological Factors That Regulate Hepatocellular Carcinoma Growth Using Patient‐Derived Xenograft Assays
| Autor: | Veronica Renteria, Amit G. Singal, Lin Li, Hao Zhu, Sofia Kagan, Hyesun Yoo, Purva Gopal, Tianshi Lu, Matthew R. Porembka, Akbar K. Waljee, Sam C. Wang, Tao Wang, Min Zhu, Nicole E. Rich, Mobolaji Odewole, Ji Zhu, Adam C. Yopp |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Sorafenib Carcinoma Hepatocellular Biopsy Gene Expression Antineoplastic Agents Biology medicine.disease_cause Article Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Regorafenib Tumor Microenvironment Carcinoma medicine Animals Hepatectomy Humans neoplasms Neoplasm Staging Hepatitis B virus Tumor microenvironment Hepatology medicine.diagnostic_test Liver Neoplasms Middle Aged HCCS medicine.disease Xenograft Model Antitumor Assays digestive system diseases 030104 developmental biology Liver chemistry Hepatocellular carcinoma Cancer research Female 030211 gastroenterology & hepatology medicine.drug |
| Zdroj: | Hepatology |
| ISSN: | 1527-3350 0270-9139 |
| DOI: | 10.1002/hep.31096 |
| Popis: | Background and aims Several major factors limit our understanding of hepatocellular carcinoma (HCC). First, human HCCs are infrequently biopsied for diagnosis and thus are not often biologically interrogated. Second, HCC initiation and progression are strongly influenced by the cirrhotic microenvironment, and the exact contributions of intrinsic and extrinsic tumor factors are unclear. A powerful approach to examine the personalized biology of liver cancers and the influence of host tissues is with patient-derived xenograft (PDX) models. In Asia, HCCs from patients with hepatitis B virus have been efficiently converted into PDXs, but few parallel efforts from the west have been reported. Approach and results In a large-scale analysis, we implanted 93 HCCs and 8 cholangiocarcinomas (CCAs) to systematically analyze host factors and to define an optimized platform for PDX development from both surgical and biopsy samples. NOD Scid IL-2Rγ-/- (NSG) mice that had undergone partial hepatectomy (PHx) represented the best combination of engraftability, growth, and passageability, but overall rates were low and indicative of a unique intrinsic biology for HCCs in the United States. PDX models preserved the histology and genetic features of parental tumors, and ultimately, eight models were usable for preclinical studies. Intriguingly, HCC PDXs were differentially sensitive to regorafenib and sorafenib, and CCA PDXs were also highly sensitive to regorafenib. Conclusions PDX models functionalize early and advanced stage HCCs and revealed unique biological features of liver cancers from the United States. |
| Databáze: | OpenAIRE |
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