Transplantable mouse hepatoblastoma: histologic, ultrastructural and immunohistochemical study

Kharkovskaya, N.A.; Svinolupova, S I; Khrustalev, S. A.; Engelhardt, Natalia V.; Kondalenko, V. F.; Полторанина, В. С.; Turusov, V. S.

doi:10.1016/s0232-1513(11)80313-0

Cited by 7 publications

(6 citation statements)

References 13 publications

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“…However, the already available observations are of great interest given the role of reverse cholesterol transport in atherosclerosis. Moreover, as fatty acid-enriched diets reproduce the effects of PPAR␤ agonists on both intestinal NPC1L1 gene expression (16,285) and TICE (609) in rodents, it can be proposed that high concentrations of fatty acids in intestinal lumen are acting as natural activators of PPAR␤ in regulation of fecal cholesterol excretion. This hypothesis must be validated by more direct experimental evidence based on the use of PPAR␤-deficient transgenic models or specific PPAR␤ antagonists to exclude implication of other fatty acid-activated transcription factors such as PPAR␣ that also exerts inhibitory action on intestinal cholesterol absorption by downregulating NPC1L1 expression in mice (606).…”

Section: Regulatory Functions Of Ppar␤ In Intestinal Physiologymentioning

confidence: 99%

Physiological Functions of Peroxisome Proliferator-Activated Receptor β

Neels

Grimaldi

2014

Physiological Reviews

146

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The peroxisome proliferator-activated receptors, PPARα, PPARβ, and PPARγ, are a family of transcription factors activated by a diversity of molecules including fatty acids and fatty acid metabolites. PPARs regulate the transcription of a large variety of genes implicated in metabolism, inflammation, proliferation, and differentiation in different cell types. These transcriptional regulations involve both direct transactivation and interaction with other transcriptional regulatory pathways. The functions of PPARα and PPARγ have been extensively documented mainly because these isoforms are activated by molecules clinically used as hypolipidemic and antidiabetic compounds. The physiological functions of PPARβ remained for a while less investigated, but the finding that specific synthetic agonists exert beneficial actions in obese subjects uplifted the studies aimed to elucidate the roles of this PPAR isoform. Intensive work based on pharmacological and genetic approaches and on the use of both in vitro and in vivo models has considerably improved our knowledge on the physiological roles of PPARβ in various cell types. This review will summarize the accumulated evidence for the implication of PPARβ in the regulation of development, metabolism, and inflammation in several tissues, including skeletal muscle, heart, skin, and intestine. Some of these findings indicate that pharmacological activation of PPARβ could be envisioned as a therapeutic option for the correction of metabolic disorders and a variety of inflammatory conditions. However, other experimental data suggesting that activation of PPARβ could result in serious adverse effects, such as carcinogenesis and psoriasis, raise concerns about the clinical use of potent PPARβ agonists.

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Section: Regulatory Functions Of Ppar␤ In Intestinal Physiologymentioning

confidence: 99%

Physiological Functions of Peroxisome Proliferator-Activated Receptor β

Neels

Grimaldi

2014

Physiological Reviews

146

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“…Hepatoblastomas are distinctive tumors and are well described in the toxicology literature (10,12,21,47). Furthermore, a second pathologist reevaluates all tumors in NTP studies and diagnostic differences are reviewed by Pathology Working Groups (3).…”

Section: Genotoxicity Of Compounds Producing High Incidence Of Mice Wmentioning

confidence: 99%

“…The sampling of the liver has remained consistent for the past 15 years. The histology of hepatoblastomas is very distinctive, and has been part of the rodent literature for nearly 30 years (10,12,21,37,47). The change in incidence of mice with hepatoblastoma occurred during the period in which the mice were fed the NIH-07 rodent diet.…”

Section: Metastatic Sites For Hepatoblastomamentioning

confidence: 99%

Hepatoblastomas in Mice in the US National Toxicology Program (NTP) Studies

et al. 2002

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Over the last 8 years, a 5-fold increase in the incidence of mice with spontaneous hepatoblastoma s and a moderate increase in the incidence of chemically induced hepatoblastoma s in B6C3F1 mice occurred in 2-year NTP studies compared to the previous 7 years. There was a positive association between an increased incidence of mice with hepatoblastom a and an increased incidence of mice with hepatocellular tumors in the treated mice. The rate of pulmonary metastases for hepatoblastom a was similar to that of pulmonary metastasis for hepatocellular carcinomas. Although a variety of chemicals caused an increased incidence of mice with hepatoblastoma, there was no apparent association between a speci c chemical structure or a biological class of compounds and their capacity to induce hepatoblastomas. Hepatoblastoma s frequently arose within hepatocellular carcinomas or adenomas and were induced by the same compound s that induced hepatocellular neoplasms. Therefore, it seems reasonable to combine the incidence of mice with hepatoblastomas and the incidence of mice with hepatocellular carcinomas in hazard identi cation studies.

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“…Nonoyama et al [19] earlier reported 7 of 16 mouse HBs with squamous metaplasia to show positive reactions for keratin. Differentiation into ductal structures has also been described [12,20]. In man, it is considered that the 'small cell' type HB, positive for low molecular-weight keratin, differentiates into the embryonal or fetal type.…”

Section: Discussionmentioning

confidence: 99%

“…Mouse HBs, however, lack a variety of subtypes and are histologically less differentiated. Previous immunohistochemical examination of the tumors revealed frequently positive for keratin, but no other specific immunoreactivity has been demonstrated so far [12,19]. Although several pathways can be conceived in the development of mouse HBs, no clear answer has been available so far due to their poorly differentiation.…”

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confidence: 90%

Immunohistochemical Characterization of Hepatoblastomas in B6C3F1 Mice Treated with Diethylnitrosamine and Sodium Phenobarbital.

Sakairi¹,

Kobayashi²,

Goto³

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. Hepatoblastomas (HBs) were induced in B6C3F1 male mice by diethylnitrosamine (DEN) and sodium phenobarbital (PB). Six-week-old mice received a single intraperitoneal dose of DEN followed by a continuous treatment with PB in diet at a concentration of 0 (group 1) or 500 (group 2) ppm for 50 weeks. HBs were observed in 13 of 21 (62%) group 2 mice, with typical histologic features as reported previously, while no such tumors were observed in group 1. Seven of 13 (54%) HBs were found in and/or adjacent to hepatocellular adenomas (HCAs) or hepatocellular carcinomas (HCCs). Immunohistochemically, all HBs were positive for S-100 protein but negative for keratin, α-fetoprotein (AFP), albumin (ALB) and vimentin, while HCC cells occasionally reacted positively for AFP with a mosaic pattern. HCC and HCA cells were occasionally positive for ALB. Non-neoplastic hepatocytes and normal bile ducts were positively stained for ALB and keratin/S-100 protein, respectively. S-100 protein is known to be expressed in many mesenchymal tissues and neoplasms including neuroectodermal elements but negative in cells of the hepatic lineage. Thus, the present immunohistochemical results suggested that mesenchymal differentiation occurs in mouse HB cells as observed in human HBs, one of the most frequent infant liver tumors in humans. Although the susceptibility of mouse HBs to PB-promotion suggests a hepatocytic histogenesis, the present immunohistochemical results support the hypothesis that the mouse HB is derived from pluripotent endodermal stem-like cells. KEY WORDS: hepatoblastoma, immunohistochemistry, mouse, S-100 protein.

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Transplantable mouse hepatoblastoma: histologic, ultrastructural and immunohistochemical study

Cited by 7 publications

References 13 publications

Physiological Functions of Peroxisome Proliferator-Activated Receptor β

Physiological Functions of Peroxisome Proliferator-Activated Receptor β

Hepatoblastomas in Mice in the US National Toxicology Program (NTP) Studies

Immunohistochemical Characterization of Hepatoblastomas in B6C3F1 Mice Treated with Diethylnitrosamine and Sodium Phenobarbital.

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