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)

Two human hepatoma cell lines, Hep G2 and Hep 3B, were screened for vitamin D3-25-hydroxylase enzyme activity by incubation with radioactive vitamin D3. A compound co-chromatographing with 25-OH-D3 was synthesized in both cell lines but its rate of synthesis was tenfold greater in Hep 3B than in Hep G2 cells. The identity of the compound was confirmed by comparing its chromatographic properties with authentic 25-OH-D3 on three different high pressure liquid chromatography systems. Its production was suppressed by adding fetal calf serum (10%), lipoprotein-deficient fetal calf serum, or pure vitamin D-binding globulin to the medium. The mechanism of action of these plasma proteins appears to involve retardation of uptake of the substrate. These two cell lines offer considerable potential as defined in vitro models for studying the effects of physiological factors on the 25-hydroxylation of vitamin D3.
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PMID:25-Hydroxylation of vitamin D3 in the human hepatoma cell lines Hep G2 and Hep 3B. 285 52

The metabolism of vitamin D3-3H was studied in a small group of controls and subjects with tropical sprue after the oral or intravenous administration of 8 to 10 microCi of D3-3H. The biological half life of D3-3H upon the administration of the isotope by the intravenous route was normal in 2 controls, very low in a subject with tropical sprue who had steatorrhea, and decreased in a subject with tropical sprue who did not present steatorrhea. After the administration of the isotope by the oral route, the biological half life was 35 hours in the control and no radioactivity could be detected in the plasma of the subject with tropical sprue who had steatorrhea. Twenty four hours after the intravenous dose the percentage of radioactivity in the plasma as HCC-3H was two times higher in the tropical sprue subjects than in the controls. When the dose was given orally the net absorption was 50.5% in the subject with tropical sprue and steatorrhea and 86.8% in the subject with tropical sprue who was partially treated. These results showed rapid clearance of the D3-3H in the subject with tropical sprue and steatorrhea indicating depletion of vitamin D stores in the tissues and decrease in the net absorption of the dose when given orally. The presence of a higher percentage of the dose in the plasma as HCC-3H after the intravenous and oral administrations in the tropical sprue subjects when compared to controls indicates that the diseased state does not alter vitamin D3 metabolism.
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PMID:The kinetics of D3-3H metabolism in tropical sprue. 300 14

Plasma levels of 25-hydroxycholecalciferol (25-HCC) were measured by a specific competitive protein-binding assay. Mean levels in both normal London adults and adolescent schoolchildren were 16 ng/ml and the mean level in a group of epileptic patients on high-dosage anticonvulsant therapy was 5 ng/ml, (difference from normals P < 0.001). Two further epileptic patients, with well-marked anticonvulsant osteomalacia, were treated with small doses of 25-HCC during full metabolic balance studies; rapid healing followed administration of 25-HCC by mouth in doses of 10-45 mug daily, which is well below the effective dose range of calciferol in this condition. These findings provided further evidence that anticonvulsant osteomalacia results from hepatic enzyme induction which, by increasing the metabolism of cholecalciferol to inactive compounds, lowers 25-HCC levels in patients whose dietary vitamin D intake and exposure to sunlight are otherwise adequate. Results also indicated that under certain circumstances 25-HCC may have considerably stronger antirachitic potency in man than has hitherto been recognized.
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PMID:Plasma levels and therapeutic effect of 25-hydroxycholecalciferol in epileptic patients taking anticonvulsant drugs. 434 60

Glucocorticoid administration is known to decrease calcium absorption in vivo and the vitamin D-dependent active transport of calcium by rat duodenum in vitro. The basis for this antivitamin D-like effect of glucocorticoids is unclear. Previous studies in the rat failed to demonstrate an effect of glucocorticoid treatment on the hepatic conversion of the parent vitamin to 25-hydroxycholecalciferol (25-HCC). Moreover, pharmacologic doses of 25-HCC did not restore intestinal calcium transport to normal. The results of these experiments suggested that if indeed glucocorticoids interfere with the metabolism of vitamin D, the step involved must be subsequent to 25-hydroxylation. The present studies demonstrate that the administration of cortisone to vitamin D-deficient rats does not affect the rate of conversion of a physiologic dose of [(3)H]25-HCC to the biologically important metabolite, 1,25-dihydroxycholecalciferol (1,25-DHCC). Furthermore, pretreatment with glucocorticoids affects neither the tissue distribution nor the subcellular localization on or in intestinal mucosal cell nuclei of 1,25-DHCC. Of note is the fact that 1,25-DHCC is currently considered to be the "tissue-active" form of the vitamin in the intestine. Whereas tissues from cortisone-treated animals had increased concentrations of the biologically less active 24,25-DHCC, the physiologic significance of this observation remains unclear. The results of the present studies strongly support the concept that the antivitamin D-like effects of glucocorticoids in the intestine are due to hormonal influences on the biochemical reactions responsible for calcium transport. While the effects of these hormones are opposite in direction to those of vitamin D, they occur by a mechanism that is independent of a direct interaction with either the vitamin or its biologically active metabolites.
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PMID:Effects of cortisone administration on the metabolism and localization of 25-hydroxycholecalciferol in the rat. 470 22

1. Rats were fed various diets ranging from the normal chow, pure flour containing large amounts of phytic acid, Ca-enriched flour and mixtures of flour and normal food with various levels of calcium. 2. It was found that the animals eating the pure flour grew less and were smaller. 3. They suffered from hypocalcemia and had low plasma alkaline phosphatase and 25-HCC-vitamin D3 levels. 4. These animals had rib-cage deformities. 5. Additional calcium in the flour improved the animals' growth and calcification. 6. The mixed food did not greatly affect the animals and additional calcium did not improve growth or bone mineralisation. 7. The Bedouin eat large amounts of unleavened bread containing large amounts of phytates. 8. It is concluded that uptake of large amounts of phytates by the Bedouin eating unleavened bread is due to the flour and that the clinical manifestations are a direct result of the flour and not the lack of vitamin D due to covering the skin from sunlight.
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PMID:Growth and bone mineralisation as affected by dietary calcium, phytic acid and vitamin D. 612 64

Screening of three human hepatoma-derived cell lines revealed the presence of an immunologically similar plasma binding protein for vitamin D and its metabolites in media from Hep 3B cells. Approximately 3% of protein synthesized and secreted by these cells was immunoprecipitated by specific antiserum to the D-binding protein. Medium content of the protein increased over 11 days following cell seeding, and negligible amounts of 125I-labeled binding protein added to cultures were degraded over 48 h. The hepatoma-derived binding protein was indistinguishable from plasma binding protein or reference pure protein in gel filtration, sucrose gradient ultracentrifugation, and polyacrylamide gel electrophoresis systems. The Hep 3B cell product was found to bind mole/mol with monomeric actin, and bind vitamin D sterols with an affinity and specificity characteristic of the human plasma binding protein. The findings argue strongly for the identity of the Hep 3B cell product and the human plasma protein. The continuous availability of the Hep 3B cell line provides a reasonable model for investigations of biosynthesis and release of this important plasma protein.
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PMID:Characterization of the human plasma binding protein for vitamin D and its metabolites synthesized by the human hepatoma-derived cell line, Hep 3B. 630 61

Bone histology and its relationship with calcium metabolism was evaluated in adult patients with nephrotic syndrome: 29 had normal renal function (GFR 103 +/- 4 ml/min/1.73 m2) (group 1) and 20 had renal insufficiency (GFR 31 +/- 4 ml/min/1.73 m2) (group 2). In group 1, serum PTH, 1.25-HCC and 24.25-HCC levels were normal, while 25-HCC values were reduced. Bone histology was normal in 76% of the patients, while 17% had isolated osteomalacia and 7% an associated bone resorption. Group 2 showed a higher incidence of bone resorption when compared with a matched group of patients with renal failure and no proteinuria (40% vs. 13%) and a comparable frequency of isolated mineralization defect (25% vs. 34%). PTH levels were definitely increased and serum total calcium and all the vitamin D metabolites were reduced. A significant correlation between the apparent duration of the disease and the severity of osteodystrophy was found only in group 2. In conclusion, no constant derangement of calcium metabolism and bone histology is evident in patients with nephrotic syndrome and normal renal function, while patients with persistent proteinuria are at high risk of osteodystrophy even in the early phases of renal failure.
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PMID:Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function. 673 66

Calcium metabolism was studied in 83 patients during eighteen months' rifampicin and isoniazid therapy for tuberculosis by measurements including calcium, alkaline phosphatase and 25-hydroxycholecalciferol (25-HCC). Five out of 52 Indian patients in the series were found to have osteomalacia, a prevalence probably no higher than in the Asian population in the UK at large. Moreover, osteomalacia responded to physiological supplementation with vitamin D. One European out of 31 had osteomalacia due to low vitamin D intake. Serum calcium was compared in 17 patients before and after six months of antituberculous chemotherapy but no significant difference was detected (P greater than 0.1). Two Indian patients were in positive calcium balance with low to normal plasma 25-HCC levels, indicating that an effect on 1,25 dihydroxyvitamin D activity during therapy was unlikely. It is concluded that rifampicin when combined with isoniazid has no significant effect on calcium metabolism over an eighteen-month treatment period.
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PMID:Calcium metabolism during rifampicin and isoniazid therapy for tuberculosis. 708 5

The serum concentrations of calcium and phosphate and parathyroid morphology were studied in rats treated with vitamin D metabolites. Twenty hours after a single injection of 1.25-dihydroxycholecalciferol (1.25-DHCC) or 25-hydroxycholecalciferol (25-HCC) the serum calcium and phosphate concentrations were not significantly altered in any group, but the 1.25-DHCC treated rats exhibited an increased number of dark chief cells and occurrence of a few atrophic chief cells. Four to eight weeks after daily injections of the vitamin D metabolites the 1.25-DHCC treated rats exhibited significantly increased serum calcium concentrations and parathyroid glands composed of atrophic and dark chief cells in solid and follicular arrangement, whereas the rats treated with 25-HCC showed unaffected serum calcium concentrations and parathyroid glands composed of solid sheets of light chief cells, often with vacuolated cytoplasm, a few dark chief cells, but no atrophic cells. The findings suggest a direct or indirect suppressive influence of 1.25-DHCC on parathyroid activity in rats.
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PMID:Serum calcium and phosphate concentrations and parathyroid morphology in rats treated with vitamin D metabolites. 742 98

A full-length cDNA for the human liver mitochondrial cytochrome P-450 CYP27 was cloned from a human hepatoma HepG2 cDNA library and then subcloned into the mammalian expression vector pSG5. When CYP27 cDNA was transfected into COS-1 transformed monkey kidney cells along with adrenodoxin cDNA, transfected cells revealed a 10- to 20-fold higher vitamin D3-25-hydroxylase activity than nontransfected cells. Transfected cells were capable of 25-hydroxylation of vitamin D3, 1 alpha-hydroxyvitamin D3 and 1 alpha-hydroxydihydrotachysterol3. In each case they also showed the ability to 26(27)-hydroxylate the cholesterol-like (D3) side chain. The relative rates of 25- and 26(27)-hydroxylation of 1 alpha-hydroxyvitamin D3 approximately mimicked the ratio of products observed in HepG2 cells. Vitamin D2 and 1 alpha-hydroxyvitamin D2, both with the ergosterol-like side chain, were 24- and 26(27)-hydroxylated by CYP27. The rate of side-chain 24-, 25-, or 26(27)-hydroxylation was greater for 1 alpha-hydroxylated vitamin D analogs than for their nonhydroxylated counterparts. We conclude that CYP27 is capable of 24-, 25-, and 26(27)-hydroxylation of vitamin D analogs and that the nature of products is partially dictated by the side chain of the substrate. This work has revealed that the cytochrome P-450 CYP27 may be important in the metabolism of vitamin D analogs used as drugs.
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PMID:Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions. 769 Sep 68


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