Comparative Histomorphological Review of Rat and Human Hepatocellular Proliferative Lesions

Thoolen, Bob; Kate, Fiebo J.W. ten; Diest, Paul J. van; Malarkey, David E.; Elmore, Susan A.; Maronpot, Robert R.

doi:10.1293/tox.25.189

Cited by 35 publications

(24 citation statements)

References 89 publications

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“…In a "comparative histomorphological review of rat and human hepatocellular proliferative lesions", Thoolen and colleagues 1 stated that "there are major similarities in the diagnostic features, growth patterns and behavior of both rat and human proliferative hepatocellular lesions and in the process of hepatocarcinogenesis". I fully agree with this statement, but in view of its far-reaching consequences for the evaluation of rodent carcinogenesis bioassays and the early detection of precursors of human hepatocellular adenomas (HCA) and carcinomas (HCC) I draw your attention to several critical comparisons and conclusions concerning the significance of preneoplastic foci of altered hepatocytes (FAH), called "foci of cellular alteration" in the review.…”

Section: Comparative Aspects Of Rat and Human Hepatocellular Preneoplmentioning

confidence: 99%

Comparative Aspects of Rat and Human Hepatocellular Preneoplasia and Neoplasia

Bannasch

2013

J Toxicol Pathol

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Section: Comparative Aspects Of Rat and Human Hepatocellular Preneoplmentioning

confidence: 99%

Comparative Aspects of Rat and Human Hepatocellular Preneoplasia and Neoplasia

Bannasch

2013

J Toxicol Pathol

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“…Given that carcinogenesis has multiple steps starting with benign (initiation) to precancerous (promotion) and finally to malignant lesion (progression), there is a strong mandate for using experimental hepatocarcinogenesis models including mice and rats to give a deep insight into the pathological characteristics during liver cancer development under controlled conditions [49]. Preclinical experimental animal models of HCC enables longitudinal studies that include monitoring of the tumour growth as well as drug uptake and response to treatment.…”

Section: Animal Models Of Hepatocarcinogenesismentioning

confidence: 99%

“…Similar to in humans, the cytological criteria of DN in rodents such as nuclear to cytoplasmic changes, nuclear crowding, and hyperchromasia are commonly seen suggesting that DN is the intermediate step to early HCC [49,53]. Rat models of HCC are commonly used because they share features with human carcinomas at different time points [54].…”

Section: Animal Models Of Hepatocarcinogenesismentioning

confidence: 99%

“…Rat models of HCC are commonly used because they share features with human carcinomas at different time points [54]. For example, eosinophilia and basophilic alterations in rats are the counterparts of DN in humans [49,55]. This introduction highlights the most currently used animal models for HCC with emphasis on chemical carcinogenesis induced by diethylnitrosamine, diet-induced carcinogenesis (choline deficient amino acid diet), and genetically modified models ( cancer by forming DNA adducts, and defined as DNA reactive due to the reaction of multiple enzymes of P450 including cytochrome (Cy) p2E1 [62].…”

Section: Animal Models Of Hepatocarcinogenesismentioning

confidence: 99%

“…According to Thoolen et al. [169] classification, these lesions are: These focal lesions in rat experiment models occur in association with a high incidence of hepatocellular carcinoma and thus considered as an indicative of progression towards HCC [169,224]. …”

Section: Other Histological Findingsmentioning

confidence: 99%

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Magnetic resonance characterisation of developing hepatocellular carcinoma in a diet induced model of liver cancer in the rat

Alghamdi¹

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Non-alcoholic fatty liver disease (NAFLD), a disorder associated with abnormal lipid accumulation within hepatocytes, is considered benign disorder in nature. However, in some cases it may progress to inflammation, nonalcoholic steatohepatitis (NASH), then cirrhosis, precancerous nodules and finally to hepatocellular carcinoma (HCC). NAFLD and NASH are both reversible with appropriate clinical intervention and lifestyle changes. In developed countries, the non-alcoholic fatty liver disease (NAFLD) is becoming one of the most common causes of precancerous and HCC lesions [1]. Unfortunately, most nodular lesions are detected too late with a poor prognosis. The discovery of markers that can predict which livers may progress to HCC would allow early intervention and potentially halting progress to HCC. This would be of great benefit at any stage up to precancerous lesions, however the earlier the better.Development of end stage liver malignancy would be decreased, resulting in decreased mortality from this disease.Histology is considered the reference standard for the assessment of fatty disease and nodular lesion in liver. However, there are significant drawbacks including invasiveness, small sample size and observer-dependence which limits its usefulness in evaluating liver disease.Magnetic resonance imaging is a non-invasive modality that can provide information on anatomical and physiological changes in the liver (e.g. fatty liver disease and HCC). MRI images are primarily assessed visually by expert radiologists looking for anatomical and contrast changes in the images compared to normal tissue. This qualitative method requires inspection of all datasets for abnormalities. Visual interpretation is subjective, labour intensive, and depends on the experience of the radiologist. This can introduce inter-observer variation and is suitable only when the pathology leads to sufficient contrast changes in the images acquired.MRI also allows the calculation of quantitative parameters like T1, T2 and diffusion values. These parameters are dependent on physical, chemical and microstructural properties of the tissue. When standard protocols are used, the calculation of these parameters should be independent of the observer. This has the potential for more precise characterization of changes that occur over time. Clinically, here has been limited utilization of these methods, as they generally require longer acquisition times and significant post processing of the images. Declaration by authorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text.

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Target Organ Pathology

McInnes¹

2017

Pathology of Taxicologists

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Comparative Histomorphological Review of Rat and Human Hepatocellular Proliferative Lesions

Cited by 35 publications

References 89 publications

Comparative Aspects of Rat and Human Hepatocellular Preneoplasia and Neoplasia

Comparative Aspects of Rat and Human Hepatocellular Preneoplasia and Neoplasia

Magnetic resonance characterisation of developing hepatocellular carcinoma in a diet induced model of liver cancer in the rat

Target Organ Pathology

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