Neureiter D, Stintzing S, Kiesslich T, Ocker M. Hepatocellular carcinoma: Therapeutic advances in signaling, epigenetic and immune targets. World J Gastroenterol 2019; 25(25): 3136-3150 [PMID: 31333307 DOI: 10.3748/wjg.v25.i25.3136]
Corresponding Author of This Article
Matthias Ocker, MD, Professor, Translational Medicine Oncology, Bayer AG, Muellerstrasse 178, Berlin 13353, Germany. matthias.ocker@bayer.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
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Table 4 Available techniques for induction of hepatocellular carcinoma in relation to temporal and technical aspects as well as major advantages and disadvantages (summarized from[92])
Method and specification
Time to HCCshort (+) to long (+++)
Technical effortslow (+) to high (+++)
Major “Pros” (+) vs “Contras” (-)
Chemotoxic agents linked models
Diethylnitrosamine
++
+
(+) good combination options with other methods
9,10-dimethyl-1,2-benzanthracene
(-) time to HCC not easily predictable
Direct implantation of tumor cells or tissue
Heterotopic/orthotopic
+
+/++
(+) heterotopic xenografts are often and easily done
(+) syngeneic orthotopic models better reflect the natural liver microenvironment
Syngeneic/xenografts
(-) xenografts need immunocompromised mice
(-) orthotopic tumor implants need surgical and imaging experience
Genetically engineered mouse models
Mouse embryo manipulation
++/+++
+++
(+) hepatocarcinogenesis can be analyzed stepwise
Cre-Lox recombination
(-) effects of manipulated gene(s) could have heterogeneous latency and genetic penetrance
Hydrodynamic injection
CRISPR-Cas9
Humanized mouse models
Immunologically humanized mice
+++
+++
(+) immunotherapeutical issues can be studied based on human cell lines in mice
Genetically humanized mice
(-) establishment difficult due to engraftment failure and development of stable stem cell-derived hepatocytes
Citation: Neureiter D, Stintzing S, Kiesslich T, Ocker M. Hepatocellular carcinoma: Therapeutic advances in signaling, epigenetic and immune targets. World J Gastroenterol 2019; 25(25): 3136-3150