title: Animal models as a tool in hepatocellular carcinoma research: A Review.
abstract: Cancer is the first cause of death in developed countries and the second in developing countries. Concerning the most frequent worldwide-diagnosed cancer, primary liver cancer represents approximately 4% of all new cancer cases diagnosed globally. However, among primary liver cancer, hepatocellular carcinoma is by far the most common histological subtype. Notwithstanding the health promotion and disease prevention campaigns, more than half a million new hepatocellular carcinoma cases are reported yearly, being estimated to growth continuously until 2020. Taking this scenario under consideration and the fact that some aspects concerning hepatocellular carcinoma evolution and metastasize process are still unknown, animal models assume a crucial role to understand this disease. The animal models have also provided the opportunity to screen new therapeutic strategies. The present review was supported on research and review papers aiming the complexity and often neglected chemically induced animal models in hepatocarcinogenesis research. Despite the ongoing debate, chemically induced animal models, namely, mice and rat, can provide unique valuable information on the biotransformation mechanisms against xenobiotics and apprehend the deleterious effects on DNA and cell proteins leading to carcinogenic development. In addition, taking under consideration that no model achieves all hepatocellular carcinoma research purposes, criteria to define the " ideal" animal model, depending on the researchers' approach, are also discussed in this review.
authors.affiliation: 1 Department of Veterinary Sciences, Veterinary and Animal Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.|2 Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Nuno Paula
authors.initials: NP
authors.lastname: Santos
authors.affiliation: 1 Department of Veterinary Sciences, Veterinary and Animal Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Aura Antunes
authors.initials: AA
authors.lastname: Colaço
authors.affiliation: 1 Department of Veterinary Sciences, Veterinary and Animal Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.|2 Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Paula Alexandra
authors.initials: PA
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics; D051379:Mice; D051381:Rats
keywords: Chemical carcinogens; genetically engineered mouse; liver; orthotopic; rodents; syngeneic; xenograft