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)

Rats bearing Novikoff hepatoma ascites cells were given i.p. injections of actinomycin D, doxorubicin, or daunorubicin. Four hours after injection, tumor cells were removed from the ascites fluid and analyzed for protein B23 translocation using an immunofluorescence technique. Bright nucleolar fluorescence was observed in untreated cells. Treatment with actinomycin D (1.25 mg/kg), doxorubicin (25 mg/kg), or daunorubicin (12.5 mg/kg) produced a uniform nucleoplasmic fluorescence. This change in immunofluorescence distribution indicated that protein B23 translocated from the nucleolus to the nucleoplasm after drug treatment. These results are an extension of previous studies with HeLa cells (Yung et al., Cancer Res. 46: 922-925, 1986). Doxorubicin-resistant and -sensitive mouse leukemia cells (P388) were cultured in medium containing various doses of doxorubicin for 4 h, and the responsive levels of the cells to doxorubicin were compared. At 50 micrograms/ml doxorubicin, 86% of the doxorubicin-sensitive cells showed uniform nucleoplasmic fluorescence, and less than 2% of the cells retained nucleolar fluorescence. At this same dose, only 9% of the resistant cells showed nucleoplasmic fluorescence, and 75% of the cells retained nucleolar fluorescence. At 100 micrograms/ml, about 26% of the resistant cells showed translocation, in contrast to 100% of the sensitive cells that showed B23 translocation. About 57% of the resistant cells showed an intermediate effect, and about 17% of the resistant cells maintained bright nucleolar fluorescence at this dose. The resistant cells also showed less responsiveness to actinomycin D. These results suggest that identification of "B23 translocation" may be used to detect drug-resistant cells and to study the efficacy of certain antitumor agents.
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PMID:Nucleolar protein B23 translocation after doxorubicin treatment in murine tumor cells. 243 99

Vinblastine-C4 acyl derivatives were synthesized by linking alkyl maleoyl or amino acid maleoyl compounds through an ester linkage at C4 position of the Vindoline moiety of Vinblastine. To target these derivatives selectively to hepatoma, conjugates were prepared with a neoglycoprotein i.e. lactosaminated human albumin, as a specific carrier. The method of preparation of lactosaminated albumin and of coupling to Vinca alkaloid derivatives is described and the mechanism of addition of the protein to the derivative is discussed. The experimental antitumor activity of these conjugates has been screened against the experimental P-388 Leukemia. The activity of the best conjugate has been evaluated in several human tumor xenografts. Further, the therapeutic potential of this type of conjugate has been demonstrated in a model of hepatoma xenograft developed in our laboratory, the HepG2 carcinoma.
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PMID:Vinblastine-C4 alkyl maleoyl and amino acid maleoyl derivatives: III. Experimental antitumor activities of lactosaminated serum albumin conjugates. 251 May 84

A retrospective cohort study was carried out in 1982-1983 among 28,460 benzene-exposed workers (15,643 males, 12,817 females) from 233 factories and 28,257 control workers (16,621 males, 12,366 females) from 83 factories in 12 large cities in China. All-cause mortality was significantly higher among the exposed (265.46/100,000 person-years) than among the unexposed (139.06/100,000 person-years), as was mortality from all malignant neoplasms (123.21/100,000 versus 54.7/100,000, respectively). For certain cancers, increased mortality was noted among benzene-exposed males in comparison with that among unexposed males; the standardized mortality ratios (SMR) were elevated for leukemia (SMR = 5.74), lung cancer (SMR = 2.31), primary hepatocarcinoma (SMR = 1.12), and stomach cancer (SMR = 1.22). For females only leukemia occurred in excess among the exposed. Risk of leukemia rose as duration to exposure to benzene increased up to 15 years, and then declined with additional years of exposure. Leukemia occurred among some workers with as little as 6 to 10 ppm average exposure and 50 ppm-years (or possibly less) cumulative lifetime exposure (based on all available measurements for the exposed work units). Among the 30 leukemia cases identified in the exposed cohort, the proportion of subjects with acute lymphocytic leukemia was substantially lower and the proportion with acute nonlymphocytic leukemias was higher than in the general population. During 1972 to 1981, the annual incidence of leukemia ranged from 5.83 to 28.33 per 100,000 with higher rates occurring in the interval 1977 to 1981 than in the earlier years of the study period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A retrospective cohort study of leukemia and other cancers in benzene workers. 279 42

Several related human transforming DNA sequences, hhc, and a putative normal liver homologue, c-hhc, have been molecularly cloned from the genomic DNAs of individual African and Asian hepatomas and from normal liver respectively. hhcM (Mahlavu) and hhcK3 (Korean), but not c-hhc, transformed NIH3T3 cells in DNA-mediated gene transfer assays. Transformed cells were found tumorigenic in athymic NIH Swiss nu/nu mice. In view of recent epidemiological studies implicating hepatitis B virus (HBV) infection early in life as causative for the eventual development of primary hepatocellular carcinoma in humans in Southeast Asia, the Far-East, and certain areas of Africa, we hereby analyzed the relationship between these hhcs and HBV in a survey of 20 hepatomas for DNA sequences homologous to hhcM and HBV by sequential hybridizations against [32p]hhcM and [32p]HBV probes. hhcM related DNA sequence were found highly amplified in 80% of the 20 hepatomas but HBV DNA sequence was rare or low. hhcM lends itself as a marker for human hepatomas. However, overall results indicated that patients with integrated HBV DNA sequences showed high copy number of hhcM sequence. Furthermore, EcoR1-restricted hepatoma DNAs showed that HBV and hhcM DNA sequences resided at different fragments in hepatomas. Our results suggest that HBV contributes to hepatocarcinogenesis probably via an activation mechanism involving possibly an integration or transient interaction of HBV DNA with hepatocyte DNA sequences, leading to recombination and eventual amplifications of the hhcM sequence in Mahlavu.
Leukemia 1988 Dec
PMID:Transforming DNA sequences of human hepatocellular carcinomas, their distribution and relationship with hepatitis B virus sequence in human hepatomas. 284 89

Lidoflazine strongly inhibited the equilibrium exchange of uridine in human erythrocytes (Ki approximately 16 nM). Uridine zero-trans influx was similarly inhibited by lidoflazine in cultured HeLa cells (IC50 approximately to 80 nM), whereas P388 mouse leukemia and Novikoff rat hepatoma cells were three orders of magnitude more resistant (IC50 greater than 50 microM). Uridine transport was also inhibited by nifedipine, verapamil, diltiazem, prenylamine and trifluoperazine, but only at similarly high concentrations in both human erythrocytes and the cell lines. IC50 values ranged from about 10 microM for nifedipine and about 20 microM for verapamil to more than 100 microM for diltiazem, prenylamine and trifluoperazine. The concentrations required for inhibition of nucleoside transport are several orders higher than those blocking Ca2+ channels. Lidoflazine competitively inhibited the binding of nitrobenzylthioinosine to high-affinity sites in human erythrocytes, but did not inhibit the dissociation of nitrobenzylthioinosine from these sites on the transporter as is observed with dipyridamole and dilazep.
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PMID:Effects of Ca2+-channel antagonists on nucleoside and nucleobase transport in human erythrocytes and cultured mammalian cells. 356 29

Equilibrium binding of [3H]dipyridamole identified high-affinity (Kd approximately 10 nM) binding sites on human erythrocytes (approximately 5 X 10(5) sites/cell) and on HeLa cells (approximately 5 X 10(6) sites/cell). The equilibration of dipyridamole with these sites on human erythrocytes was compatible with a second-order process which proceeded at 22 degrees C with a rate constant of about 6 X 10(6) M-1 sec-1. Binding of dipyridamole to these sites correlated kinetically with the inhibition of the equilibrium exchange of 500 microM uridine in these cells and was inhibited in a concentration-dependent manner by nucleosides and other inhibitors of nucleoside transport, such as nitrobenzylthioinosine, dilazep and lidoflazine, but not by hypoxanthine, which is not a substrate for the nucleoside transporter of human erythrocytes. The results indicate that the substrate binding site of the transporter is part of the high-affinity dipyridamole binding site. Bound [3H]dipyridamole became displaced from these sites on human erythrocytes by incubation with an excess of unlabeled dipyridamole or high concentrations of nucleosides and inhibitors of nucleoside transport, but neither by hypoxanthine nor sugars. Dissociation of [3H]dipyridamole behaved as a simple first-order process, but the rate constant was about one order of magnitude lower (about 3 X 10(-3) sec-1) than anticipated for typical ligand-protein binding on the basis of the measured association rate and equilibrium constants. The reason for this discrepancy has not been resolved. No high-affinity dipyridamole binding sites were detected on Novikoff rat hepatoma cells, P388, L1210 and S49 mouse leukemia cells or Chinese hamster ovary cells, and their absence correlated with a greater resistance of nucleoside transport in these cells to inhibition by dipyridamole. All cells expressed considerable low affinity (Kd greater than 0.5 microM) and nonspecific binding of dipyridamole.
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PMID:Interaction of [3H]dipyridamole with the nucleoside transporters of human erythrocytes and cultured animal cells. 366 65

The transport of 500 microM uridine by human erythrocytes and S49, P388 and L1210 mouse leukemia cells, Chinese hamster ovary (CHO) cells and Novikoff rat hepatoma cells was inhibited strongly by dilazep and hexobendine with similar concentration dependence, but the sensitivity of transport in the various cell types varied greatly; IC50 values ranged from 5-30 nM for human erythrocytes and S49 and P388 cells to greater than 1 microM for CHO and Novikoff cells. The binding of nitrobenzylthioinosine (NBTI) to high-affinity sites on these cells (Kd approximately equal to 0.5 nM) was inhibited by hexobendine and dilazep in a similar pattern. Furthermore, these drugs, just as dipyridamole and papaverine, inhibited the dissociation of NBTI from high-affinity binding sites but only at concentrations 10-100 times higher than those inhibiting uridine transport. In contrast, high uridine concentrations (greater than 2 mM) accelerated the dissociation of NBTI. Dilazep also inhibited the transport of hypoxanthine, but only in those cell lines whose transporter is sensitive to inhibition by uridine and dipyridamole. Adenine transport was not inhibited significantly by dilazep in any of the cell lines tested, except for a slight inhibition in Novikoff cells. [14C]Hexobendine equilibrated across the plasma membrane in human erythrocytes within 2 sec of incubation at 25 degrees, but accumulated to 6-10 times the extracellular concentration in cells of the various cultured lines. Uptake was not affected by high concentrations of uridine, NBTI or dipyridamole. Hexobendine inhibited the growth of various cell lines to a lesser extent (IC50 = greater than or equal to 100 microM) than dipyridamole (IC50 = 15-40 microM). At 40 microM, however, it completely inhibited the growth of S49 cells that had been made nucleoside dependent by treatment with methotrexate or pyrazofurin.
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PMID:Inhibition of nucleoside and nucleobase transport and nitrobenzylthioinosine binding by dilazep and hexobendine. 374 59

It was found that AH66, a rat ascites hepatoma inherently refractory to vincristine, exhibited definite resistance to a different class of antitumor agents- adriamycin and actinomycin D. In comparative studies with AH13, a sensitive strain of rat hepatoma, significantly lower levels of cellular retention as well as uptake of these drugs were observed with AH66 cells. However, in the presence of 2, 4-dinitrophenol in glucose-free medium, the uptake of vincristine by AH66 cells was remarkably increased, and addition of glucose induced a spontaneous efflux of drug that had been taken up. These results, in good accord with those for a subline of P388 mouse leukemia which acquired resistance to either adriamycin or vincristine, suggest that there exists an active efflux system common to these different kinds of antitumor agents in naturally resistant rat tumor cells. Further studies revealed that Tween 80 also enhanced the uptake of vincristine by AH66 cells by interfering with the efflux of this drug and thus partially restored the sensitivity in vitro of AH66 cells to vincristine.
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PMID:Mechanism of natural resistance to vincristine in rat ascites hepatoma AH66. 730 68

PSK, a protein-bound polysaccharide obtained from cultured mycelia of Coriolus versicolor in basidiomycetes, is a biological response modifier, diverse operations of which include an antitumor action. We have previously reviewed recent research which had demonstrated that in animals, PSK has a preventive effect on chemical carcinogen-induced, radiation-induced, and spontaneously developed carcinogenesis (Kobayashi et al., Cancer Epidemiol., Biomarkers & Prev., 2: 271-276, 1993). We now focus on the effects of PSK once the progression of carcinogenesis has begun, and review what is now known of the preventive action of PSK on cancer metastasis. Recent research reports that PSK suppresses pulmonary metastasis of methylcholanthrene-induced sarcomas, human prostate cancer DU145M, and lymphatic metastasis of mouse leukemia P388, and that it has prolonged the survival period in spontaneous metastasis models. PSK also suppresses the metastasis of rat hepatoma AH60C, mouse colon cancer colon 26, and mouse leukemia RL male 1 in artificial metastasis models. PSK influences the steps of cancer metastasis in a number of ways: (a) by suppression of intravasation through the inhibition of tumor invasion, adhesion and production of cell matrix-degrading enzymes; (b) by suppression of tumor cell attachment to endothelial cells through the inhibition of tumor cell-induced platelet aggregation; (c) by suppression of tumor cell migration after extravasation through the inhibition of tumor cell motility; and (d) by suppression of tumor growth after extravasation through the inhibition of angiogenesis, the modulation of cytokine production, and the augmentation of effector cell functions. In addition, PSK has suppressed the malignant progression of mouse tumor cells through superoxide trapping.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. 760 3

In this paper we report the presence and function of the 5' untranslated region (5'UTR) from the mRNA encoding human gamma-glutamyltransferase (GGT) in three different hematopoietic cell lines (HL-60, U-937 and K-562) as well as in the RNA of the leukocyte fraction from six acute lymphoblastic leukemias (ALL). Results obtained by RNase protection analysis demonstrate the presence of a unique form of 5'UTR expressed in most human tissues. In order to investigate the possible role of this type of sequence on regulation of GGT in hematopoietic cells, plasmid constructs carrying human hepatoma GGT 5'UTR and a luciferase reporter gene were transfected into the three blood cell lines. Compared to control untransfected cells, transfected HL-60 and K-562 showed a decrease in reporter gene activity of 51 and 73%, respectively. In contrast, transfected U-937 showed a 139% increase of reporter gene activity. Results were compared to GGT activity in the relevant cells and we concluded that the 5'UTR appears to have a regulatory role in GGT expression as a tissue-specific modulator of translation.
Leukemia 1995 Aug
PMID:Characterization and regulatory effect of gamma-glutamyltransferase messenger RNA untranslated regions in human leukemia. 764 21


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