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)

The effect of starvation on thyroid hormone metabolism was studied in monkey hepatocarcinoma monolayer cultures. Nonphenolic ring monodeiodination of thyroxine, 3, 5, 3'-triiodothyronine and 3, 3'-diiodothyronine was accelerated. Since phenolic ring deiodination of 3, 3',5'-triiodothyronine (reverse T3) was unaffected, this metabolite accumulated in the medium during thyroxine metabolism. This suggests that increased serum reverse T3 in malnourished humans may be caused by enhanced deiodination of thyroxine rather than decreased rT3 catabolism.
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PMID:Thyroxine inactivation by starvation in cultured hepatocarcinoma cells, Formation of reverse triiodothyronine. 10 81

The activity of hexokinase (HK), its isoenzymes, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase, and the triiodothyronine (T3) effect on this activity in the liver tissue of mice bearing transplantable hepatoma 22a were studied in different periods of the tumor growtn. It was shown that alterations in the activity of the enzymes in the liver of tumor-bearing mice occurred already in the presence of a small tumor. More profound alterations in the activity of all enzymes studied, apart from those in the enzymatic pattern of HK, could be observed starting from day 21after the tumor transplantation. In the initial stages of the hepatoma growth the activity of the test enzymes in the liver was regulated by thyroid hormone. The effect of Ta on the activity of the enzymes in the host liver was gradually lost in the course of the tumor growth.
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PMID:[Carbohydrate metabolism enzymatic activity and its alteration under the influence of thyroid hormone during tumor growth]. 22 89

The growth rate of Morris Hepatoma No. 44 (generation time, 6 mo) was inhibited after the induction of hypothyroidism by Propylthiouracil (PTU) (0.1% in Purina Chow), I131 (1 mCi/100 g body wt i.p.), or surgical thyroidectomy. After 11 wk of treatment, hepatoma weight was 66%, 87%, and 75% (after correction for total body wt) relative to controls in PTU-fed, I131 injected, and thyroidectomized rats, respectively. In each case, exogenous thyroxine (T4) (8 microgram/kg body wt i.p.) reversed these inhibitory effects, while T4 administered to euthyroid rats stimulated hepatoma growth. The degree of growth-inhibition achieved with PTU was not observed in pair-fed rats. In addition, after correction for differences in body weight, the sex of the tumor-bearing rats did not influence the response to PTU. Pretreatment with PTU for 2 wk before implantation did not give any added advantage over the effects of PTU administered approximately 10 days after implantation. Serum levels of triiodothyronine (T3) and T4, as well as the concentration of various biochemic parameters, were determined at the time of death. These results suggest that the growth rate of Morris Hepatoma No. 44 is thyroid hormone dependent.
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PMID:Inhibition of the growth of Morris hepatoma No. 44 in rats after induction of hypothyroidism: evidence that Morris hepatomas are thyroid dependent. 45 48

We have studied the effects of triiodothyronine (T3) on the production of hepatic triacylglycerol lipase (HTGL) in the human hepatocellular carcinoma cell line, HepG2, by measuring its activity and mRNA levels. The HTGL activity released into the medium by heparin, increased after the addition of T3 in a both time- (27% increase after 24 and 75% increase after 48 h) and dose-dependent manner (maximum activity with over 0.2 micrograms/ml of T3 in the medium). Messenger RNA levels of HTGL in cells incubated with T3 for 24 and 48 h were increased by 33% and 98% compared to those of the control. These results suggest that the production of HTGL may be regulated by thyroid hormone at the level of gene expression.
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PMID:Stimulation of the activity and mRNA level of hepatic triacylglycerol lipase by triiodothyronine in HepG2 cells. 132 33

Recently, it was shown that lipoprotein lipase (LPL) was produced in neonatal but not in adult rat liver. In an attempt to further define the mechanism involved in liver LPL expression, we identified a neonatal mouse hepatoma cell line, BWTG3, capable of producing LPL. The regulation of LPL expression by various extracellular stimuli was investigated in this cell line. Progesterone caused a rise in LPL production by BWTG3 cells. Other hormones tested, such as insulin, glucagon, adrenalin, testosterone, and thyroid hormone, had no effect on LPL production. The effects of progesterone on LPL production showed slow kinetics reaching a maximum 24 h after addition. Cotransfection of a progesterone receptor expression vector with a 5'-LPL-CAT reporter construct resulted in an induction of CAT activity, suggesting that the increase in LPL accumulation after progesterone was linked to transcriptional induction of the LPL gene. Stimuli causing an elevation of protein kinase A activity in the cells also increased LPL production. Three agents capable of elevating intracellular cAMP levels, i.e., forskolin, dBcAMP, and choleratoxin, caused an elevation of LPL production. The increase in LPL activity caused by forskolin and choleratoxin was paralleled by an elevation of LPL mRNA levels, while dBcAMP only induced a small elevation of LPL mRNA levels. The increase in LPL production was shown to be linked to the stimulation of the PKA signal transduction pathway and was apparently transmitted via the transcription factor CREB. No effect of the stimulation of protein kinase C or calcium/calmodulin-dependent kinase on LPL production was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein lipase expression in undifferentiated hepatoma cells is regulated by progesterone and protein kinase A. 132 33

Treatment of malignant disease with interleukin-2 and lymphokine-activated killer cells activates autoreactive T lymphocytes, stimulates release of cytokines and induces expression of HLA-class II antigens by tumour cells. We studied eight patients with hepatocellular carcinoma treated with a total of 16 courses of recombinant human interleukin-2 and lymphokine-activated killer cells and observed them for features of autoimmune thyroid disease. During the course of treatment there were significant decreases in total serum T4 and T3 and free thyroxine levels, but no change in TSH levels when all patients were analysed as a group. This was due to a number of factors including suppression of thyroid hormone release, haemodilution during interleukin-2 infusion and actual removal of thyroid hormones from the circulation during leukapheresis. Thyroid hormones returned to normal levels during resting period. One patient subsequently developed compensated hypothyroidism (normal total T4, total T3 and free T4 but elevated TSH) and four patients had features of 'sick euthyroid syndrome' (low total T4, total T3 or free T4 but normal TSH). None of the patients studied developed antibodies to thyroglobulin or microsomes. In contrast, no abnormality of thyroid function was seen in any of the nine subjects who received no active treatment. In conclusion, thyroid dysfunction was associated with immunotherapy of malignant disease with interleukin-2 and lymphokine-activated killer cells. This may arise from direct hormonal effects of the cytokines on thyroid hormone production.
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PMID:Thyroid functions in patients treated with interleukin-2 and lymphokine-activated killer cells. 133 2

The induction of rat hepatic mRNA S11 by L-T3 (T3) is a useful model for studying the mechanisms of thyroid hormone action. Although numerous reports have examined the response of mRNA S11 to various physiological and hormonal manipulations, the role of S11 protein in cellular metabolism remains unknown. In this study we show that mRNA S11 is abundantly expressed and regulated by T3 only in liver and small intestine. High levels of the mRNA are present at birth, but drop sharply between 30-60 days of age. These and other features of the S11 gene product were similar to those of rat apolipoprotein-A1 (Apo-A1). The sequence of S11 cDNA was identical to a portion of the Apo-A1 mRNA, thus confirming identity of the S11 mRNA. To examine whether DNA sequences immediately adjacent to the transcription start site mediate the effects of thyroid hormone, we measured the activity of an Apo-A1 gene fragment, U-1 (-474 to -7) using a transient transfection assay. The activity of the full-length U-1 DNA in HuH-7 hepatoma cells was 2- to 2.5-fold higher in the presence of thyroid hormone. This finding closely matched previous results using the in vitro nuclear run-on assay. Internal deletion of a motif that resembles a thyroid hormone response element from U-1 DNA not only abolished the induction by T3, but suppressed promoter activity by 3- to 4-fold in response to the hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of the thyroid hormone-responsive messenger RNA spot 11 as apolipoprotein-A1 messenger RNA and effects of the hormone on the promoter. 149 93

Type III iodothyronine deiodinase (ID-III) catalyzes the inner ring deiodination of T4 to rT3 and of T3 to 3,3'-T2, representing an important pathway for the inactivation of thyroid hormone. High activities of this "oncofetal" enzyme are found in rat brain, skin and fetal intestine, rat and human placenta, chick embryo liver, monkey hepatocarcinoma cells, human colon carcinoma cells, and tadpole liver. ID-III shows substrate preference for T3 over T4; Km values are approximately 10-fold lower for T3 than for T4 but Vmax values are similar. In contrast to the marked ontogenic pattern of ID-III in different tissues, the enzyme shows little change under pathophysiological conditions, such as fasting and thyroid dysfunction. Brain ID-III activity is decreased in hypo- and increased in hyperthyroidism, but the changes are small. Reaction of brain and placenta microsomes with BrAc 125I-T3 results in extensive labeling of a 32 kDa protein (p32). However, the relationship of p32 with ID-III is not clear, since labeling of p32 is also observed in tissues without ID-III activity and is not inhibited with a large excess of substrate.
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PMID:Characteristics of type III iodothyronine deiodinase. 151 45

We examined the effect of chronic hypo- and hyper- thyroidism on angiotensinogen (AOG) gene expression in rat liver and brain. Chronic hypothyroidism resulted in approximately a 50% decrease in plasma AOG and AOG messenger RNA (mRNA) concentrations in liver, diencephalon, and brain stem. In contrast, plasma AOG and liver AOG mRNA concentrations were elevated by about 75% during hyperthyroidism, but no change was seen in diencephalon and brain stem. In vitro, the effect of T3 on AOG secretion by rat hepatoma cell lines H35 and H4IIEC-3 depended on the type of cell line used and on the growth status of the cells. At confluency, H35 cells were more responsive to T3 than H4IIEC-3 cells. In addition, subconfluent H35 cells were less responsive to T3 than confluent ones, although no difference was observed in the number of nuclear T3 binding sites or in the responsiveness to dexamethasone. T3 also increased AOG mRNA concentration in confluent H35 cells. Finally, AOG secretion by primary cultures of rat astrocytes increased approximately 1.8-fold following exposure to T3. The fact that T3 increased the production of AOG by these various types of cell culture in vitro suggests that it acted directly upon these cells, and that the effect of thyroid hormone was not dependent on the prior stimulation of another hormone. However, the difference in responsiveness between confluent and subconfluent H35 cells indicates that the action of thyroid hormones may be dependent on the induction of secondary genes within these cells.
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PMID:Effects of thyroid hormones on angiotensinogen gene expression in rat liver, brain, and cultured cells. 153 89

Transthyretin (TTR) is a circulatory protein which plays an important role in the transport of both thyroid hormone and retinol. Hep G2 cells, a human hepatoma-derived cell line, have been used extensively in studies of protein secretion by liver cells. The original description of this cell line indicated that this line, unlike primary hepatocytes, does not secrete TTR. We now report studies which reexamine the ability of Hep G2 cells to synthesize and secrete TTR. For this purpose, total RNA was isolated from Hep G2 cells grown on both uncoated and collagen-coated plastic plates and was examined for TTR expression by Northern blot analysis. TTR mRNA was found to be present in nearly equal amounts in Hep G2 cells cultured in either condition. When Hep G2 cells were cultured in [35S]methionine-containing medium, the cells were found both to synthesize and to secrete immunoprecipitable [35S]TTR. Hep G2 cells were found, by sensitive and specific radioimmunoassay, to contain 142 +/- 91 ng TTR/10(6) cells and to secrete TTR into the medium at a nearly constant rate for at least 24 h after medium change. Our data demonstrate that Hep G2 cells do synthesize and secrete TTR and suggest that this cell line might be useful for studies of the secretion of TTR.
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PMID:Studies on the synthesis and secretion of transthyretin by the human hepatoma cell line Hep G2. 165 60


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