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1.
Comp Hepatol ; 3(1): 9, 2004 Nov 26.
Article in English | MEDLINE | ID: mdl-15566568

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most worldwide frequent primary carcinomas resulting in the death of many cirrhotic patients. Unfortunately, the molecular mechanisms of this cancer are not well understood; therefore, we need a good model system to study HCC. The dog is recognized as a promising model for human medical research, namely compared with rodents. The objective of this study was to establish and characterize a spontaneous canine tumor cell line as a potential model for studies on HCC. RESULTS: Histomorphological, biochemical, molecular biological and quantitative assays were performed to characterize the canine HCC cell line that originated from a dog with a spontaneous liver tumor. Morphological investigations provided strong evidence for the hepatocytic and neoplastic nature of the cell line, while biochemical assays showed that they produced liver-specific enzymes. PCR analysis confirmed expression of ceruloplasmin, alpha-fetoprotein and serum albumin. Quantitative RT-PCR showed that the canine HCC cell line resembles human HCC based on the measurements of expression profiles of genes involved in cell proliferation and apoptosis. CONCLUSIONS: We have developed a novel, spontaneous tumor liver cell line of canine origin that has many characteristics of human HCC. Therefore, the canine HCC cell line might be an excellent model for comparative studies on the molecular pathogenesis of HCC.

2.
Am J Physiol Gastrointest Liver Physiol ; 296(4): G963-8, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19246633

ABSTRACT

The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver regeneration after partial hepatectomy. We have recently generated serotonin transporter knockout rats and demonstrated that their platelets were almost completely depleted of serotonin. Here we show that these rats exhibit impaired hemostasis and contain about 1-6% of wild-type serotonin levels in the blood. Despite the marked reduction of serotonin levels in blood and platelets, efficient liver regeneration and collagen-induced platelet aggregation occur in rats lacking the serotonin transporter. These results provide evidence that liver regeneration is not dependent on the release of serotonin from platelets. Our findings indicate that very low levels of serotonin in blood are sufficient for liver regeneration.


Subject(s)
Liver Regeneration/genetics , Liver Regeneration/physiology , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin/pharmacology , Animals , Bleeding Time , Blood Platelets/metabolism , Gene Deletion , Hepatectomy , Homeostasis/genetics , Homeostasis/physiology , Rats , Serotonin Plasma Membrane Transport Proteins/metabolism
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