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

Steroid metabolism in hepatoma tissue culture (HTC) cells derived from a male rat was investigated. Steroids in ethanol were incubated with the cells for various lengths of time. Volume of ethanol never exceeded 1% of incubation volume. Thin-layer and paper chromatography were used. Incubation was with tritiated steroids. It was demonstrated that testosterone as well as dihydrotestosterone is transformed. The main enzyme activities detected were 5alpha-reduction and 3alpha-, 3beta, and 17beta-hydroxysteroid dehydrogenation. The pattern of metabolism was reproducible and varied with time, substrate concentration, and number of cells incubated. Some steroids interfered with androgen metabolism. 17beta-estradiol, 17-epitestosterone, and progesterone competed for the 17beta-hydroxyprogesterone dehydrogenase. it is concluded that 3beta and 17beta reduction in the HTC cells may be catalyzed by the same enzyme which might differ considerably from the 3beta-hydroxysteroid dehydrogenase assayed in intact liver cells. A hepatoma derived from a female rat also produced considerable amounts of 3beta-derivatives of testosterone.
 ...
PMID:Metabolism of testosterone and dihydrotestosterone in cultured rat hepatoma cells. 17 19

The steroidal 20-carboxamides [(20R)- and (20S)-21-(N-substituted amino)-11 beta,17,20-trihydroxy-3,21-dioxo-1,4-pregnadiene] recently have been shown to possess anti-inflammatory activity in animal models of inflammation. These N-substituted methyl, ethyl, n-propyl, and benzyl derivatives also exhibited suppressive effects on plasma corticosterone and thymus function. Generally, the (20R)-hydroxy-20-carboxamides were more potent than the corresponding (20S)-epimers. In continuing investigations on the glucocorticoid effects of these compounds, we have studied their ability to induce tyrosine aminotransferase (TAT), inhibit uptake of [3H]thymidine into DNA, and complete with [3H] dexamethasone for binding to the hepatoma tissue culture glucocorticoid receptor. Results indicated that the N-substituted methyl, ethyl, and n-propyl derivatives were full glucocorticoid agonists in the three measurements. Receptor binding affinities of the N-substituted carboxamides correlated well with their ability to induce TAT activity and to inhibit thymocyte proliferation. Structure-activity relationships indicated that the larger the N-substituent, the weaker the agonist activity in this system, and 20R isomers exhibited higher glucocorticoid agonist activity than the corresponding 20S isomers. This investigation is part of our effort to elucidate structure-activity relationships of steroidal carboxamides synthesized on the basis of the antedrug concept.
Steroids 1992 Jul
PMID:Enzyme induction and receptor-binding affinity of steroidal 20-carboxamides in rat hepatoma tissue culture cells. 135 84

Rat hepatoma cells (H4-II-E-C3) efficiently converted a dietary supplement of [2-3H]24,25-dihydrolanosterol (1) to [3H]cholesterol while [2-3H]lanostanol (4,4,14 alpha-trimethylcholestanol (2) was recovered from the cells without apparent transformation, although it was esterified and induced an accumulation of lanosterol. A comparison of the chromatographic (TLC, GLC and HPLC), spectral (MS and 1H-NMR) and physical properties of 1 and 2 is given for the first time. The inability to detect 2 in nature coupled with our findings that 1 but not 2 is metabolized to cholesterol by H4 cells is interpreted to imply that the biosynthetic inclusion of the delta 8(9)-bond during the cyclization process of squalene-oxide to a tetracyclic product is an evolutionary adaptation selected for because the olefinic linkage is structually important in the subsequent conversion of lanosterol and its stereoisomers, e.g., cycloartenol, to delta 5-sterols.
Steroids
PMID:Concerning the role of 24,25-dihydrolanosterol and lanostanol in sterol biosynthesis by cultured cells. 279 54

The oxysterols 3 beta-hydroxy-5 alpha-cholest-8-en-11-one, 3 beta-hydroxy-5 alpha-cholest-8-en-7-one, 3 beta-hydroxy-5 alpha-cholest-8(14)-en-7-one, 3 beta-hydroxy-4,4'-dimethylcholest-5-ene-7 one, 4,4'-dimethylcholest-5-ene-3 beta, 7 alpha-diol, 4,4'-dimethylcholest-5-ene-3 beta, 7 beta-diol, lanost-8-ene-3 beta, 25-diol, 25-hydroxylanost-8-en-3-one, 9 alpha, 11 alpha-epoxy-5 alpha-cholest-7-en-3 beta-ol, 3 beta-hydroxycholest-5 alpha-en-22-one, and 3 beta-hydroxycholest-5-en-22-one oxime were evaluated with respect to their ability to inhibit cell growth. All of the sterols were found to possess cytotoxicity when incubated with hepatoma (HTC) and lymphoma (RDM-4) cells in culture at 10-30 microM concentrations.
Steroids
PMID:Studies of the oxysterol inhibition of tumor cell growth. 279 58

The binding characteristics and quantitation of the recently reported fetal steroid binding protein (FSBP) cannot be determined on unpurified samples; an immunoassay was therefore desirable. The protein was purified to homogeneity in order to raise a highly specific polyclonal antibody. An enzyme-linked immunosorbent assay applicable to unpurified samples was developed. Intra- and inter-assay coefficients of variation are 8.0% and 9.2% respectively; there is a sensitivity of 30 fmol FSBP per well, and there is no cross-reactivity with other binding proteins. Results obtained with the assay correlate with the more complex ligand binding assay (r = 0.85; p less than 0.02). Measurement of sera showed that FSBP levels are higher in women than in men (51.2 +/- 10.62 nM; 41.2 +/- 13.65 respectively; p less than 0.05) and are elevated in cirrhotic women (66.4 +/- 18.67; p less than 0.05) and in males with hepatocellular carcinoma (62.2 +/- 13.05; p less than 0.002). Use of the enzyme-linked immunosorbent assay confirmed the identity of FSBP separate from sex hormone binding globulin.
Steroids 1985 Jan
PMID:An enzyme-linked immunosorbent assay for fetal steroid binding protein of human serum. 300 70

A radioimmunoassay for 3 beta-hydroxy-5-cholenoyl glycine in human urine has been developed. The antiserum was elicited with the antigen in which the steroid hapten is linked to a bovine serum albumin through the C-19 position. The [125I]-tyrosine derivative of the hapten was used as radioligand. The standard curves were linear ranging from 10 to 320 ng/mL. The cross-reactivities with other bile acids were not detectable and below 0.3% with cholesterol. Sample preparation includes extraction of 3 beta-hydroxy-5-cholenoyl glycine from urine and solvolysis of the sulfates--main form present in urine. Urinary excretion of 3 beta-hydroxy-5-cholenoyl glycine was 0.373 +/- 0.133 mumol/day in healthy adults. Urinary excretion of 3 beta-hydroxy-5-cholenoyl glycine increased in chronic liver dysfunction, hepatoma and obstructive jaundice in this order.
Steroids
PMID:Radioimmunoassay of urinary 3 beta-hydroxy-5-cholenoyl glycine in hepatobiliary disease. 303 57

The presence of angiotensinogen messenger RNA (mRNA) was assessed in total RNA extracted from hepatoma, glioma, neuroblastoma, and glioma-neuroblastoma hybrid cell lines. Total RNA from 1 X 10(7) cells was extracted, transferred to a membrane, and hybridized with a 32P-labeled, full-length (1650-base pair) rat angiotensinogen complementary DNA (cDNA). Angiotensinogen RNA sequences could be definitively detected only in hepatoma cells. Steroids were used in an attempt to increase the angiotensinogen mRNA level. Dexamethasone (2 X 10(-6) M) or 17 beta-estradiol (1 X 10(-7) M) was added to the cultures 18 to 24 hours prior to harvest. Dexamethasone treatment of the hepatoma cells resulted in a large increase in angiotensinogen mRNA, whereas estradiol had no effect. Steroids failed to induce detectable levels of angiotensinogen mRNA in total RNA from the other cell lines. That the RNA was intact was ensured by hybridizing duplicate Northern blots to a 32P-labeled actin cDNA. Actin mRNA sequences were detected in all cell lines. Blot hybridization of poly(A)+RNA resulted in the visualization of a weak angiotensinogen mRNA signal for a glioma cell line and a glioma-neuroblastoma hybrid line. However, the ability to detect angiotensinogen mRNA in a cell may depend on the phenotype expressed, which can be governed by culture conditions.
 ...
PMID:Presence of angiotensinogen messenger RNA in various cultured cell lines. 359 87

The uptake of corticosterone by highly purified plasma membrane vesicles of rat liver was studied by a rapid-centrifugation technique which allows uptake measurements within 5 s. The vesicles are free of soluble cytoplasmic constituents. Therefore, association of hormone with the vesicle is attributed entirely to components of the vesicle-membrane. Half maximal uptake is reached at 8 s at 21 degrees C. At 15 degrees C transition of the lipid state in the membrane leads to a decrease of uptake, a characteristic property common to membrane mediated processes. The uptake of corticosterone is saturable and reversible but does not follow normal saturation kinetics. The apparent dissociation constants of three uptake systems bear direct relation to the concentration of free corticosterone in rat plasma (4-16 nM) supporting a physiological role for the system. Uptake of corticosterone decreases with decreases in vesicular volume; about 50% of the hormone is bound specifically and 50% is transported to the lumen of the vesicle. Since outflow of intravesicular hormone also occurs readily, the uptake and transport is proposed to be mediated by putative "carriers". The "carrier" preferentially transports glucocorticoids; dexamethasone is not taken up by this putative molecule. Steroids with 5 alpha conformation are more potent inhibitors of the "carrier" for corticosterone than 5 beta-steroids. Androgens and estrogens are weak competitors of corticosterone. The affinity of the "carrier" for several hormones differs considerably from that of the cytoplasmic receptor. Morris hepatoma cells (MH 3924) do not take up corticosterone. Our results prompt us to propose the hypothesis that the transport function of the "carrier" and the binding of the hormone by the cytoplasmic receptor are two different entities; perturbation of the "carrier" may lead to steroid unresponsiveness. Normal expression of steroid hormone activity is manifested in the concerted action of the functionally sound cell membrane "carrier" and the intracellular receptor.
 ...
PMID:Characteristics and specificity of the glucocorticoid "carrier" of rat liver plasma membrane. 371 25

In the course of the foetal development of numerous animal species elevated serum concentrations of alpha-1-foetoprotein (AFP) are observed. The level of this foetal protein decreases after birth, but reappears in several pathological cases characterized by a cellular proliferation, in particular in neoplasia such as hepatoma and teratoblastoma. Little was known until 1971 on the biological role of this carcino-embryonic antigen. It has been since evidenced [Nunez and al., 1971, C.R. Acad. Sci., Paris, 273, 834-841]. That rat and mouse AFPs bind oestrogens with high affinity (Ka = 10(8) M-1) [Savu and al., 1972, F.E.B.S. Let., 22, 113-116]. Human AFP does not possess this property. We have recently shown [Benassayag and al., 1977, Steroids, 30, 771-785] that the sera from pregnant rats, rat and human foetuses contain compounds which behave as competitive inhibitors of the estrogen binding on rat or mouse AFP. We have subsequently identified this substances as a mixture of non-esterified fatty acids (NEFA) [Vallette and al., XXVII Colloquium "Protides of the biological fluids", Bruxelles, H. Peeters Ed., Pergamon Presse, 1979]. We have measured [BENASSAYAG and al., Oncodevelopmental biology and medicine, in press] the association constants of each NEFA of the serum mixture with rat AFP, the polyunsaturated fatty acids (PUFA) (C 20:4, C 22:4, C 22:6) show the highest association constants (Ka = 10(5)-10(6) M-1). We have also confirmed that human AFP binds the PUFA with high affinity. The biological perspectives opened up by these novel data will be discussed.
 ...
PMID:[Free polyunsaturated fatty acids, estrogens and fetoproteins]. 615 14

Studies have indicated a correlation between a high level of urinary lignans and isoflavonoid phytoestrogens, particularly genistein, and a low incidence of hormone-dependent cancers, such as breast and prostate cancer. Previously it has been observed that a vegetarian diet is associated with high plasma levels of sex hormone-binding globulin (SHBG), reducing clearance of sex hormones and probably risk of breast and prostate cancer. In the present study we investigated the in vitro effect of genistein on the production of SHBG by human hepatocarcinoma (Hep-G2) cells in culture and its effect on cell proliferation. We found that genistein not only highly significantly increases the SHBG production by Hep-G2 cells, but also suppresses the proliferation of these cancer cells already at a stage when SHBG production continues to be high. We conclude that, in addition to the lignan enterolactone, the most abundant urinary isoflavonoid genistein stimulates SHBG production and inhibits Hep-G2 cancer cell proliferation.
Steroids 1993 Jul
PMID:Genistein is an effective stimulator of sex hormone-binding globulin production in hepatocarcinoma human liver cancer cells and suppresses proliferation of these cells in culture. 821 77


1 2 3 4 Next >>