Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin B6 metabolism has been investigated in several highly and well-differentiated Morris hepatomas. Comparisons have been made with two poorly differentiated Morris hepatomas, with host livers obtained from tumor-bearing animals, and with fetal, neonatal, and adult rat liver. The pyridoxal phosphate content and the activities of pyridoxine kinase and pyridoxine phosphate oxidase of all Morris hepatomas examined were significantly less than those in adult host or control livers and generally fell in the range determined for fetal and neonatal liver. A similar pattern was not evident for the activity of pyridoxine phosphate phosphatase. Relative to control and host livers, the activity in hepatomas of the pyridoxal phosphate (PLP)-dependent enzyme, ornithine decarboxylase, was generally elevated. Dexamethasone, at a dose which caused an elevation in the activity of PLP-dependent tumor tyrosine aminotransferase, had no effect on PLP metabolism. The data indicate that tumor progression in the Morris hepatoma spectrum in relation to vitamin b6 metabolism falls into an onco-developmental pattern characterized by a diminished amount of tissue PLP and a diminished capability to metabolize precursor vitamer forms to PLP.
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PMID:Vitamin B6 metabolism in liver and liver-derived tumors. 612 59

The natural vitamin, pyridoxine, in the millimolar range is toxic to cultured rat hepatoma cells. A pyridoxine-resistant Fu5-5 rat hepatoma cell line was established by a stepwise increase in the concentration of pyridoxine in the medium. The newly established cell line, referred to as clone 10 (Cl.10), is resistant to killing by pyridoxine in concentrations up to 5 mM. Saturation kinetics for the uptake of [3H]pyridoxine into Fu5-5 and Cl.10 cells revealed that Fu5-5 cells take up 10 times more [3H]pyridoxine than do Cl.10 cells. Whereas the Vmax value for the uptake of [3H]pyridoxine was the same for both cell lines, the apparent Km for the Cl.10 cells was 12.5 microM compared to 0.71 microM for the Fu5-5 cells. However, intracellular levels of pyridoxal 5'-phosphate were 69% higher in Cl.10 cells than in the parental line. The resistant line is neither a permeability mutant nor deficient in pyridoxal kinase. Cl.10 cells contain 37% more adenosine 5'-triphosphate than do Fu5-5 cells and have a mitochondrial volume that is 50% greater than that of the parental line. In the absence of pyridoxine in the medium, Cl.10 cells revert to parental type with respect to pyridoxine uptake but not with respect to resistance to killing. They also maintain an enlarged mitochondrial volume. Thus, increased mitochondrial volume may be related to the development of resistance to high levels of pyridoxine.
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PMID:Pyridoxine resistance in a rat hepatoma cell line. 707 15

Previous studies have shown that all-trans retinoic acid (ATRA) suppresses growth of hepatocarcinoma cell in vitro. To understand the underlying mechanisms, we investigated the protein expression profiles by 2-DE in hepatocarcinoma cell line SMMC-7721 treated with ATRA. Our results reveal that six proteins were differently expressed in response to ATRA. Using MS and database searching, they were identified as profilin 1, phosphoglycerate kinase 1, RuvB-like 1, alpha-enolase, pyridoxal kinase and F-actin capping protein. We selected the up-regulated protein, profilin 1 (PFN1), for further studies. The PFN1 expression was increased in response to ATRA in a dose- and time-dependent manner. The PFN1 expression was reduced dramatically in four hepatoma cell lines compared to L02 cell line of non-tumor origin. The PFN1 expression was also examined in 4 cases of primary hepatocarcinoma tissues by Western blot and 30 cases by tissues microarray. It was found that the protein level of PFN1 was lower in hepatocarcinoma tissues compared to that in the adjacent tissues. Similar to ATRA, overexpression of PFN1 led to inhibition of cell proliferation and migration. Furthermore, RNAi-based PFN1 knockdown could rescue the inhibitory effect of ATRA on cell proliferation and migration. In conclusion, ATRA inhibited cell proliferation and migration through up-regulation of PFN1.
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PMID:Profilin 1 obtained by proteomic analysis in all-trans retinoic acid-treated hepatocarcinoma cell lines is involved in inhibition of cell proliferation and migration. 1705 35