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)

Fluorescence microphotolysis (photobleaching) was used to measure, in single polyethylene glycol-induced polykaryons of hepatoma tissue culture cells, nucleocytoplasmic flux and intracellular mobility for a series of dextrans ranging in molecular mass from 3 to 150 kD and for bovine serum albumin. For the dextrans, the cytoplasmic and the nucleoplasmic translational diffusion coefficients amounted to approximately 9 and approximately 15%, respectively, of the value in dilute buffer. The diffusion coefficients depended inversely on molecular radius, suggesting that diffusion was dominated by viscosity effects. By application of the Stokes-Einstein equation, cytoplasmic and nucleoplasmic viscosities were derived to be 6.6 and 8.1 cP, respectively, at 23 degrees C. Between 10 and 37 degrees C nucleoplasmic diffusion coefficients increased by approximately 45-85%, whereas cytoplasmic diffusion coefficients were virtually independent of temperature. In contrast to that of the dextrans, diffusion of bovine serum albumin was more restricted. In the cytoplasm the diffusion coefficient was approximately 1.5% of the value in dilute buffer; in the nucleus albumin was largely immobile. This indicated that albumin mobility is dominated by association with immobile cellular structures. Nucleocytoplasmic flux of dextrans depended inversely on molecular mass with an exclusion limit between 17 and 41 kD. This agrees with previous measurements on primary hepatocytes (Peters, R., 1984, EMBO [Eur. Mol. Biol. Organ.] J. 3:1831-1836), suggesting that in both cell types the nuclear envelope has properties of a molecular sieve with a functional pore radius of approximately 55 A.
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PMID:Molecular mobility and nucleocytoplasmic flux in hepatoma cells. 242 Aug 4

Previous studies in this laboratory suggested that in adult liver, either the gene for the tumor-type poly(A) polymerase is poorly transcribed or the mRNA for this enzyme is largely not expressed. To test these possibilities, total RNA from rat liver and Morris hepatoma 3924A RNA were isolated by using a guanidine thiocyanate method; poly(A+) RNA and poly(A-) RNA were separated by oligo(dT)-cellulose chromatography and used for translation in a rabbit reticulocyte lysate system. After in vitro translation, the products were immunoprecipitated with either purified anti-tumor poly(A) polymerase antibodies or control immunoglobulins. When the polypeptides translated from poly(A+) or poly(A-) hepatoma RNA were precipitated with immune sera, a unique [35S]methionine-labeled 35-kilodalton (kDa) protein was observed. This band was not apparent when control serum was used for the immunoprecipitation. The radiolabeled 35-kDa polypeptide was not evident when the products were incubated with highly purified tumor nuclear poly(A) polymerase prior to immunoprecipitation. Prior incubation of the translation products with bovine serum albumin instead of poly(A) polymerase had no effect on the immunoprecipitation. This 35-kDa protein was not apparent when liver poly(A+) RNA was used to direct translation. These data demonstrate that (a) the tumor enzyme is not synthesized as a precursor, (b) tumor mRNA, but not normal liver mRNA, contains detectable sequences coding for tumor-type poly(A) polymerase, and (c) poly(A) polymerase mRNA also exists as a poly(A-) population.
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PMID:Cell-free synthesis of tumor-type poly(A) polymerase. 242 13

Treatment of cultured H4-II-E rat hepatoma cells with insulin causes a large decrease in cytoplasmic serum albumin mRNA. This effect is observed at low doses of insulin (ED50 = 2 pM), consistent with the effect being mediated by interaction of insulin with high affinity insulin receptors. The reduction in cytoplasmic albumin mRNA is first observed 8-12 h following insulin addition, and albumin mRNA continues to decrease up to 28 h following hormone addition. Northern blot analysis of purified poly(A)+ RNA has indicated that insulin causes a decrease in albumin mRNA relative to total cytoplasmic poly(A)+ RNA. In addition, one other specific mRNA, that encoded by the alpha-tubulin gene, is not decreased following insulin treatment. These results indicate that insulin induces a specific decrease in albumin mRNA. This effect is largely reversed if essential amino acids are added along with the insulin, suggesting that the insulin effect is related to limitation of the cells for essential amino acids. Insulin reduces transcription of the albumin gene 4.7-fold, as measured by nuclear transcription assays. However, this inhibition of albumin gene transcription does not fully account for the 57-fold decrease in albumin mRNA, indicating that insulin also exerts a negative effect on albumin mRNA at a post-transcriptional step.
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PMID:Insulin negatively regulates albumin mRNA at the transcriptional and post-transcriptional level in rat hepatoma cells. 243 75

A serum-free culture system of human hepatoma cell lines (HuH-6 and HuH-7) was used to investigate the activity of bovine serum (BS) and of serum-derived factors on the growth and production of alpha-fetoprotein (AFP) and albumin. At higher concentrations, dialyzed BS was inhibitory to the growth of HuH-6 and caused reduction of the level of AFP production by the cells. AFP and albumin levels in HuH-6 and HuH-7 were reduced or unchanged by fetuin, bovine serum albumin (BSA) and transferrin (TF), although no cytotoxicity was shown by any of them. Commercial preparations of platelet-derived growth factor exhibited cytotoxicity to HuH-6 and HuH-7 and induced a decrease of AFP and albumin levels in a dose-dependent manner. Transforming growth factor (TGF-beta) exhibited no cytotoxicity to HuH-6. AFP levels in HuH-6 were unchanged with 1000 pg/ml TGF-beta, but albumin levels were decreased. TGF-beta at a concentration of 1000 pg/ml was cytotoxic to HuH-7 and AFP levels were a little increased. Albumin levels, however, were unchanged. Following exposure to cycloheximide, AFP and albumin levels in HuH-6 were inhibited.
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PMID:Effects of serum and serum-derived factors on the growth and production of alpha-fetoprotein and albumin by human hepatoma cell lines. 247 26

To evaluate the level of serum thyroxine-binding globulin (TBG) in various liver diseases, TBG and T4, T3, FT4 were measured by radioimmunoassay in 29 HBsAg carriers (C), 27 patients with acute hepatitis (AH), 18 patients with inactive chronic hepatitis, 70 patients with chronic active hepatitis (CAH), 31 patients with active cirrhosis (AC), 20 patients with inactive cirrhosis (IC), 38 patients with hepatocellular carcinoma (HCC), 12 patients with metastatic Ca to the liver (Met.) and in 81 normal controls. All the patients were clinically euthyroid. The TBG as well as T4 in patients with AH, CAH, AC HCC and, Met. were significantly higher than those in controls. The T3 level was significantly elevated in CAH and AC patients. The TBG level did not correlate with serum albumin or bilirubin levels, but did correlate significantly with alanine transaminase (ALT) (r = 0.54, p less than 0.01). However, the correlation was positive in chronic active hepatitis (r = 0.40, p less than 0.01) but negative in hepatocellular carcinoma (r = -0.32, p less than 0.05). The data suggested: (1) Significant TBG and T4 elevation was found in all active liver diseases and HCC. (2) In the presence of high T4 in patients with liver disease, normal FT4 excluded the diagnosis of hyperthyroidism. (3) The elevation of TBG levels in chronic hepatitis appeared to parallel the severity of hepatocytolysis, and therefore might be the result of hepatocytolysis; while the elevation of TBG in HCC might be due to increased synthesis by the malignant cells.
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PMID:[Changes in thyroid hormone concentration in liver disease]. 250 36

This report attempts to elucidate the manner in which the surgical margin is linked to a recurrence after curative hepatectomy for hepatocellular carcinoma (HCC) in patients with cirrhosis. Forty patients were divided into two groups: those in whom the margin from the cut surface to HCC in the fresh resected specimen was less than 10 mm wide, and patients in whom the surgical margin was equal to or exceeded 10 mm. These margins were expressed as tumor wedge positive [TW(+)], and tumor wedge negative [TW(-)], respectively. There were 24 and 16 patients in the TW(+) and TW(-) groups, respectively. There was no statistically significant difference in clinicopathologic variables, except for age and values of serum albumin between the two groups. There was a recurrence in ten of 24 patients (42%) of the TW(+) group and in eight of 16 patients (50%) of the TW(-) group. Mean disease-free periods were 21.4 months in the TW(+) group and 23.6 months in TW(-) group. These 40 patients were also divided with regard to the time of recurrence, the early recurrence within 24 months, and the late recurrence after 24 months. There was no statistically significant difference in the rate of recurrence and mean disease-free period between the TW(+) and TW(-) groups in the early and late recurrence groups. In both the TW(+) and TW(-) groups, there were no recurrences in 13 of 16 patients (81.3%) with a tumor less than 4 cm in diameter, yet there were recurrences in seven of eight patients (87.5%) with a tumor exceeding 4 cm in diameter, regardless of the time to recurrence. These results suggest that in patients with a tumor less than 4 cm, the extent of TW is not linked to an early recurrence. However, when the tumor size exceeds 4 cm, 10 mm of TW is inadequate to achieve curability. When a wide resection is not feasible, then adjuvant chemotherapy should be aggressive.
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PMID:Surgical margin and recurrence after resection of hepatocellular carcinoma in patients with cirrhosis. Further evaluation of limited hepatic resection. 253 6

Gallbladder wall thickness (GBWT) and serum albumin were determined in 54 patients with ascites. The statistical analysis of the results reveals a significant difference in GBWT between benign and malignant conditions (p less than 0.01). GBWT was significantly thicker in patients with cirrhosis than in those with malignant ascites (p less than 0.01) and other benign conditions. However, no significant differences were found between either cirrhotic cases with and without overlying hepatocarcinoma, or between noncirrhotic patients, malignant or otherwise. On comparing GBWT and simple routine sonography in establishing the etiology of ascites, the diagnostic reliability indices decreased with GBWT. This shows that GBWT determination lacks diagnostic importance in routine practice. No correlation was found between serum albumin and GBWT, which suggests that the increase in GBWT observed in cirrhotic patients is mainly the result of accompanying portal hypertension.
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PMID:Sonographic relationship between gallbladder wall thickness and the etiology of ascites. 255 May 22

Antipyrine (AP) clearance was determined in 23 cases with liver cirrhosis (LC), 12 with chronic active hepatitis (CAH), 12 with hepatocellular carcinoma (mcHCC), 20 with non-hepatic diseases and 70 healthy controls. ICG Clearance was performed simultaneously in 9 cases of them. The results showed that AP clearance was significantly decreased in patients with LC and moderately decreased in CAH and HCC, its diagnostic sensitivity in LC was significantly higher than that of GPT. The significant positive correlation between the AP and ICG clearance was noted and AP clearance also well correlated with serum albumin level and prothrombin time. It is suggested that AP clearance may be used as a quantitative test to determine the reserve capacity of liver and as a substitutive test for ICG clearance.
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PMID:[Evaluation of antipyrine clearance in chronic liver diseases]. 255 53

An expression vector capable of encoding full-length CCAAT/enhancer-binding protein (C/EBP) has been constructed and tested in transient transfection assays for its capacity to activate transcription from the promoter of the serum albumin gene. When tested in cultured hepatoma cells, the C/EBP expression vector achieved potent trans-activation of the albumin promoter. Less substantial activation was observed when the same experiment was conducted using cultured mouse fibroblasts. Expression vectors that encoded defective forms of C/EBP failed to activate the albumin promoter. Moreover, mutated variants of the albumin promoter that lack the C/EBP-binding site failed to be trans-activated. The data are consistent with the interpretation that C/EBP is a bona fide transcription factor. During the course of these experiments it was noted also that C/EBP is more than an order of magnitude less concentrated in cultured hepatoma cells than it is in adult liver cells. Given these findings, we speculate that C/EBP may play a general role in establishing and maintaining the differentiated, nonproliferative state.
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PMID:CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells. 255 52

In order to increase the selective localization of anti-cancer drugs to the target tumor cells, polyclonal or monoclonal anti alpha-fetoprotein antibody (aAFP) was conjugated with anti-cancer drugs such as daunomycin (DM), adriamycin (AM) and mitomycin C (MMC) by chemical modification. Dextran (Dex) or poly L-glutamic acid (PLGA) was used to bind aAFP with DM (AM) as an intermediate drug carrier. For the conjugation of aAFP with MMC, a direct binding method through the aziridine ring of the activated MMC derivative or an indirect binding method through serum albumin as an intermediate drug carrier was employed. These conjugates caused greater inhibition of both in vitro and in vivo tumor growth of AFP-producing target tumor cells than did a mixture of aAFP and anti-cancer drugs or a simular conjugate of these drugs with normal horse immunoglobulin. AFP has high affinity to unsaturated fatty acids (UFA) such as arachidonic acid (C20:4) and so on. The antitumor effect of UFA-DM conjugate was also assessed using AFP-producing rat ascites hepatoma cells. It was found that UFA-DM conjugated showed highly selective cytocidal effects against the hepatoma cells.
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PMID:[Chemical modification of anti-cancer drugs to increase their affinity to tumor antigens]. 258 Apr 85


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