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)

Serum thyroxine-binding globulin (TBG), the major plasma transport protein for thyroid hormones in man, was shown to be altered under the influence of estrogen and in hypothyroidism. In order to study these alterations, we used an animal model. Synthesis of TBG was demonstrated in hepatocytes isolated from adult Rhesus monkeys, and in a monkey hepatocarcinoma continuous cell culture line (NCLP-6-E). When the hepatocytes were obtained from monkeys pretreated with beta-estradiol (E2), a specific 2.5-2.9 fold increase of TBG synthesis and secretion was shown; similar data were obtained with the tumor line. Furthermore, an increased TBG production was shown with these cells when T4 (from 10(-14) to 10(-11) M) was added to the culture medium. The in vitro results were correlated with in vivo data obtained by investigating the metabolism of TBG after iv injection of tracer doses of purified, radiolabelled TBG to normal, E2-treated and thyroidectomized monkeys. The main effect of estrogen administration was a marked increase of the production rate. During hypothyroidism, the catabolism and the production rate of TBG were decreased. In both conditions, there were significant changes in the distribution volume of TBG, the physiologic relevance of which remains to be investigated.
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PMID:[Hormonal control of thyroxine-binding globulin synthesis and metabolism (author's transl)]. 9 75

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

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

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

Effects of additions of amino acids to a 20% casein diet on serum cholesterol (Ch) were studied in hypothyroid and hepatoma-bearing rats with endogenous hypercholesterolemia as well as in normal rats. In normal Wistar rats, methionine (Met) was hypercholesterolemic at the "nutritional" level (0.2-0.4%), but hypocholesterolemic at the "excess" level (1.2-2.4%). In Wistar rats with hypothyroidism induced by thiouracil, the addition of excess (1.2%) Met to the 20% casein diet reduced an endogenous hypercholesterolemia due to hypothyroidism by suppressing an elevation in (VLDL + LDL)-Ch with no significant influence on HDL-Ch. In Donryu rats received a subcutaneous implantation of AH109A cells (an ascites hepatoma line), either 1.2% Met, 1.2% cystine (Cys), or 1.2% Met and 2.5% glycine (Gly) in combination improved a hepatoma-induced hypercholesterolemia and abnormal serum lipoprotein profiles by suppressing a hepatoma-induced increase in (VLDL + LDL)-Ch. From Ch turnover studies in hepatoma-bearing rats, an impaired catabolism of Ch in the liver was suggested to be one cause for the hepatoma-induced elevation in (VLDL + LDL)-Ch. One of the dietary manipulations. met and Gly in combination (Met + Gly), was found to improve the impaired Ch catabolism, this leading to a reduction of the (VLDL + LDL)-Ch level by Met + Gly in hepatoma-bearing rats.
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PMID:Effects of dietary supplemented amino acids on endogenous hypercholesterolemia in rats. 213 Jan 51

The influence of hypothyroidism on AFB1 carcinogenesis in inbred Wistar rats was studied. The primary AFB1 hepatocarcinogenesis was significantly delayed and reduced. The transplantable hepatomas showed prolonged latency periods in rats of both sexes, and in males decreased tumor weights and a lower number of lung metastases were observed. The level of GGTP in serum and liver paralleled the advancement of morphological hepatic lesions, and the activity of serum GGTP in hypothyroid bearers of the transplantable hepatoma was lower in females than in males. It was concluded that the lack of thyroid hormones during the latency period of primary and transplantable hepatomas is decisive for delayed AFB1 carcinogenesis.
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PMID:Primary and transplantable hepatomas induced by aflatoxin B1 in hypothyroid rats. 256 20

We have demonstrated recently that the local metastatic growth of Morris hepatoma 44 is thyroid dependent ( Mishkin , S., Morris, H. P., Yalovsky , M., and Murthy , P. V. N. Gastroenterology, 77; 547-555, 1979; Mishkin , S. Y., Pollack , R., Morris, H. P., Yalovsky , M., and Mishkin , S. Cancer Res., 41: 3040-3045, 1981) and that exogenous thyroxine (8 micrograms/kg/day) and prolactin (100 micrograms/day) significantly stimulated tumor growth, while growth hormone (100 micrograms/day) failed to do so ( Pollack , R., Mishkin , S. Y., Morris, H. P., and Mishkin , S. Hepatology, 2: 836-842, 1982). In the present study, thyroid ablation (hypothyroidism) and hypophysectomy inhibited tumor growth significantly. These effects were almost totally reversed by administration of exogenous thyroxine to hypothyroid rats. While prolactin or growth hormone or thyroxine alone failed to restore tumor growth in hypophysectomized animals, administration of all three hormones partially but significantly reversed the inhibition of tumor growth. The number and size of pulmonary metastases paralleled local growth in all the above-mentioned conditions. Plasma membrane lactogenic receptors, measured using human growth hormone, were decreased in hypothyroidism and hypophysectomy groups. Binding levels were restored in those groups in which tumor growth was stimulated. In summary, the local and metastatic growth of Morris hepatoma 44 is affected by anterior pituitary hormones. Plasma membrane lactogenic receptors may mediate these effects.
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PMID:Effects of hypophysectomy and hormone replacement on the local and metastatic growth of Morris hepatoma 44. 632 29

The local growth rate of Morris Hepatoma 44 (generation time, 6 months) was inhibited by 66 to 87%, and host survival was prolonged by 36 to 78% after the induction of hypothyroidism within 2 weeks of tumor implantation by propylthiouracil (0.1% in Purina chow), 131I(1 mCi/100 g body weight i.p.), or surgical thyroidectomy. In additional experiments, we studied the effects of inducing hypothyroidism (131I) at different stages in the natural history of Morris Hepatoma 44 on local and metastatic growth as well as on host survival. Induction of hypothyroidism within 2 weeks of tumor implantation (Group I) reduced local tumor growth as well as the number and size of pulmonary metastases, and prolonged survival by 70 to 80%. Induction of hypothyroidism at 6 weeks postimplantation when tumors were palpable (Group II) inhibited local growth by 39%, reduced the number and size of pulmonary metastases by approximately 80%, and prolonged host survival by 35%. Initiation of 131I treatment at 11 weeks when microscopic pulmonary emboli were present in most animals (Group III) reduced local growth by 19% and the number and size of pulmonary metastases by 72 and 50%, respectively. In this case, survival was prolonged by 17%. We conclude from these results that the local and metastatic growth of Morris hepatoma 44 as well as host survival are thyroid hormone-dependent processes. The mechanisms responsible for these observations remain to be explained.
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PMID:Inhibition of local and metastatic hepatoma growth and prolongation of survival after induction of hypothyroidism. 724 60

The v-erbA oncogene consists of an avian retroviral gag gene fused to a mutated thyroid hormone receptor. To define better its role as an oncogene in mammals and its ability to function as a dominant negative transcription factor, transgenic mice expressing v-erbA ubiquitously were generated. The effects of v-erbA are pleiotropic, tissue-specific and dose dependent. Mice have breeding disorders, abnormal behavior, reduced adipose tissue, hypothyroidism with inappropriate TSH response, and enlarged seminal vesicles. This provides an animal model consistent with the proposal that v-ErbA functions as a dominant negative receptor by transcriptional interference or squelching of normal receptors or associated proteins. Finally, male animals develop hepatocellular carcinoma, demonstrating that v-erbA can promote neoplasia in mammals.
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PMID:Thyroid abnormalities and hepatocellular carcinoma in mice transgenic for v-erbA. 792 69

Apolipoprotein E (apo E) exerts a protective effect against atherosclerosis, related to its role in intracellular cholesterol removal and remnants clearance. In this study we investigated the effect of dietary and hypothyroid hypercholesterolemia, induced respectively by a high cholesterol diet and by propylthiouracil, on hepatic apo E expression in Wistar male rats. The Northern and Western blot analysis of hepatic mRNA and protein levels showed a 2-3-fold increase of apo E in hypercholesterolemic rats compared to controls. The incubation of FAO rat hepatoma cells with 25-OH cholesterol and mevalonate led to a three-fold increase of apo E mRNA, demonstrating a direct role of cholesterol on apo E expression. This effect was completely abolished by elevating intracellular cAMP levels with forskolin. Immunoblot and immunofluorescence analysis revealed that 25-OH cholesterol/mevalonate strongly increased also apo E protein synthesis and secretion in FAO cells. Our data demonstrate that hypercholesterolemia, apart of the cause (diet or hypothyroidism) induces liver apo E expression in the rat and that this effect can be directly related, via cAMP, to cholesterol.
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PMID:Dietary and hypothyroid hypercholesterolemia induces hepatic apolipoprotein E expression in the rat: direct role of cholesterol. 1060 43


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