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)

Three hundred and ninety-five four-week-old SPF female ddY mice were each exposed to 5 or 6 cercariae of Schistosoma japonicum (Japanese strain) on their shaved abdomens and were maintained in a conditioned clean environment and fed on sterilized food and water. Fecal examinations at 8 to 10 weeks postinfection (PI) revealed 169 mice to be infected. More than half of them died within 30 weeks PI and 70 mice that survived to the 50th week PI were sacrificed. At autopsy, we could find no schistosome eggs in the liver or intestinal wall of 9 mice, and they were excluded. Out of 61 mice which showed S. japonicum eggs in their livers, 48 had single or multiple hepatoma, while no tumor was observed in the livers of the 60 control mice. The tumors were yellowish-white in color with distinct boundaries and the centers of the tumors were depressed in some cases. The size of the tumors varied from 1 to 20 mm in diameter. Most of the tumors retained the normal trabecular pattern, but in some cases the trabeculae were thickened, having wide vascular spaces. The tumor cells were PAS-negative and showed varieties of pleomorphism. The sizes of cells and nuclei varied greatly. These findings suggested some causal relationship between S. japonicum infection and the hepatoma formation in the host's liver. In the chronic course of schistosomiasis japonica in the endemic areas, S. japonicum infection probably plays a role in hepatoma formation of patients.
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PMID:Hepatoma formation in ddY mice with chronic schistosomiasis japonica. 313 Mar 51

Although the separation of water-soluble glycoproteins by high-performance (HP) concanavalin A (ConA) affinity chromatography (AC) is feasible, irregularities may be encountered with hydrophobic glycoproteins. The separation of plasma membrane glycoproteins from liver and Morris hepatoma 7777, used as a model, showed that not only the interaction between the lectin and the oligosaccharide portion of the glycoproteins plays a role in the chromatographic process, but also the hydrophobic interactions between sample and lectin and between sample and support. In this, the characteristics of the support, such as surface hydrophobicity and pore size, play an important part. It was found that a portion of the ConA is not covalently bound to the column, especially when elution is carried out with buffers containing detergents. Moreover, some extremely hydrophobic proteins could only be eluted from the column when high concentrations of detergents [1% (w/v) or higher] were applied. Despite these difficulties, four membrane glycoproteins from the liver with apparent molecular weights of 60, 80, 100 and 110-120 kilodaltons could be highly enriched by ConA HPAC. These proteins were further fractionated according to their strength of binding to the ConA and their different hydrophobic characteristics, using various detergents as eluents.
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PMID:High-performance concanavalin A affinity chromatography of liver and hepatoma membrane proteins. 320 36

A simple micromethod was developed for the accurate measurement of the activity of dTMP synthase in rat liver crude extracts. The reaction product of dTMP synthase activity assay, i.e., tritiated water, generated by the release of tritium from carbon-5 of [5-3H]deoxyuridine 5'-monophosphate (dUMP), was separated simply by 100% KOH absorption from [5-3H]deoxyuridine (dUrd), which is the side-product by dephosphorylation of [5-3H]deoxyuridine (dUrd), which is the side-product by dephosphorylation of [5-3H]dUMP during the enzyme reaction. Tritiated water was trapped in three droplets of 100% KOH deposited on the underside of the vessels' lids, while [3H]dUrd remained in the bottom of vessels after absorption of the substrate, [5-3H]dUMP, from the reaction mixture by charcoal treatment. Under standard assay conditions in the crude extract of rat liver, the specific activities of dTMP synthase and dUMP phosphatase were 0.092 +/- 0.002 and 0.351 +/- 0.013 nmol/h/mg protein, respectively. This method was also adapted for dTMP synthase assay in crude extracts of rat hepatoma 3924A. The major advantages of this procedure are the elimination of the phosphatase activity which interferes with the estimation of dTMP synthase activity in crude extracts, one-step separation of 3H2O, high sensitivity (with a limit of detection of 10 pmol of 3H2O production), high reproducibility (less than +/- 4.3%), and capability to measure activity in small amounts of sample (30-45 micrograms protein).
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PMID:Simple separation of tritiated water and [3H]deoxyuridine from [5-3H]deoxyuridine 5'-monophosphate in the thymidylate synthase assay. 344 29

Sphingomyelin synthesis was studied in cultured Novikoff rat hepatoma cells by following transfer of [14C]choline label into sphingomyelin (SPH). The study was facilitated by the fact that prelabeling of the cells with [methyl-14C]choline resulted in rapid accumulation of essentially all the label (approximately 95%) in phosphatidylcholine (PC). The redistribution of PC label during a 15-hr chase was dependent upon the extracellular choline concentration. Under conditions of free choline diffusion (500 microM choline), loss of label from PC was most pronounced, and the percentage of total radioactivity that became trapped in the extracellular water-soluble choline pool was an order of magnitude greater than in low choline medium (27 microM choline). Despite the significant loss of water-soluble label from the cells in high choline medium, SPH labeling proceeded at essentially the same rate at either choline concentration. During the label chase in 500 microM choline, the specific radioactivity of PC decreased, but the specific radioactivity of SPH continued to increase for 9-12 hr until it reached the specific radioactivity of PC. In the presence of 300 microM neophenoxine (NPO), transfer of label from PC into SPH was stimulated. NPO also decreased the specific radioactivity of PC to about the same extent as that of SPH was increased. Because transfer of choline label from PC to SPH was not affected by loss or dilution of water-soluble precursors, and because the specific radioactivity of PC and SPH, in the absence or presence of NPO, responded in a characteristic precursor product fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphatidylcholine as the choline donor in sphingomyelin synthesis. 360 Feb 11

The effects of four isomeric forms of aminophenols, ortho-, meta-, para-aminophenol and acetaminophen (o-, m-, p-AP and AAP, respectively) on liver and kidney carcinogenesis initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested. Rats were given 0.1% EHEN (in their drinking water for 2 weeks) and then diet containing these compounds at concentrations of 0.8% for 49 weeks. Administration of o-AP and AAP significantly decreased the number and area of preneoplastic foci staining immunohistochemically for glutathione S-transferase placental type (GST-P) per unit area of liver section as compared with the values for rats given EHEN alone. o-AP and AAP also significantly decreased the incidence of hepatocellular carcinoma. In contrast, p-AP and AAP significantly increased quantitative values for kidney preneoplastic lesions and renal cell adenoma. It is suggested that the cytotoxic effects of these chemicals preferentially suppressed the proliferation of preneoplastic liver cells, but stimulated the mitotic activity of preneoplastic tubular lesions in the kidney.
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PMID:Reciprocal modifying effects of isomeric forms of aminophenol on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine. 362 66

Morpholine oleic acid salt (MOAS) was administered to groups of 50 male and 50 female B6C3F1 mice in the drinking-water at levels of 0, 0.25 and 1.0%. Both sexes given 1.0% MOAS and females given 0.25% showed growth retardation. Significant increases in blood-urea nitrogen concentrations were only observed in the 1.0% male group. The incidence of squamous-cell hyperplasia of the forestomach epithelium was significantly higher in the males given 1.0% than in the controls. The male mice given 0.25% MOAS had a significantly reduced incidence of hepatocellular carcinoma in comparison with the control group and this trend was indicated also in the 1.0% group. This experiment did not demonstrate any carcinogenic effect of MOAS in mice at levels up to 1.0% in the drinking-water.
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PMID:Combined chronic toxicity and carcinogenicity studies of morpholine oleic acid salt in B6C3F1 mice. 362 48

The effects of 2-chloroethylisocyanate, ethylisocyanate and sodium cyanate on the uptake of isotope-labeled thymidine, leucine and H2O were compared in rat liver and hepatomas. The data suggested that carbamoylating agents may have a common property of inhibiting uptake of compounds in hepatomas under conditions in which there is a smaller effect or no action in the liver of tumor-bearing rats. The distinction between tissues may have been mediated, in part, through effects on tumor circulation and was less apparent when isolated cells were studied in vitro. Preferential inhibitory effects of carbamoylating agents on the uptake of leucine and H2O were also observed with a murine hepatoma, but they were not as great as with rat hepatomas.
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PMID:Action of carbamoylating agents on the uptake of metabolites in hepatomas and liver. 363 5

The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210 was compared with that of CPT and known derivatives, CPT-11 was most effective, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range. The antitumor activity of CPT-11 was shown against tumors not only in the ascites form but also in the solid form. Included among the more susceptible murine tumors are S180, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, L1210, and P388 leukemia. Probable cures of these tumors were induced frequently by CPT-11. The antitumor activity of CPT-11 against i.p.-implanted L1210 was superior to that of Adriamycin in maximum ILS, the number of cured mice, and the therapeutic ratio. CPT-11 at a dose of 100 mg/kg produced an ILS in excess of 300% with five of six mice surviving tumor free, and effected 100% tumor regression at 200 mg/kg, whereas the optimum dose of Adriamycin, 12.5-25 mg/kg, brought about 114-129% ILS with one of six mice surviving. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration. CPT-11 is expected to be clinically useful.
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PMID:Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors. 366 96

The pharmaceutical properties of quinonyl-MDP-66 were discussed with special reference to the stability of oil-in-water emulsion, distribution capacity into regional lymph nodes and tumor regressive activity. The oil-in-water emulsion of quinonyl-MDP-66, which was prepared by treatment of quinonyl-MDP-66 with squalane (25 x) and emulsified with aqueous solution of 5% HCO-60 and 5.6% d-mannitol, was kept in lyophylized state and used after reconstitution by the addition of water before use. The reconstituted suspension of quinonyl-MDP-66 in oil-in-water emulsion was stable for more than 24 hrs. The oil-in-water emulsion of quinonyl-MDP-66 as prepared above was effective for the distribution of quinonyl-MDP-66 into regional lymph node in rats and for the regression of line 10 hepatoma in strain 2 guinea pigs by intralesional injection.
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PMID:Antitumor activity on line 10 hepatoma in strain 2 guinea pigs and pharmaceutical properties of quinonyl-MDP preparations. 370 41

The dose-response relationship was determined in rats for the enhancement by phenobarbital of diethylnitrosamine (DENA)-initiated neoplastic nodules and hepatocellular carcinomas. Male Sprague-Dawley rats received a single oral dose of either 80 mg/kg DENA or water. Seven days later, the animals were divided into groups that started to receive 0, 62.5, 125, 250, 500 or 1000 ppm sodium phenobarbital in the drinking water. Animals from each group were killed at 48 and 70 weeks after the DENA. No significant difference was observed in the low response of neoplastic nodules among the DENA-initiated groups. The incidence of DENA-initiated hepatocellular carcinoma was enhanced at 70 weeks by 250, 500 and 1000 ppm sodium phenobarbital but not by 62.5 or 125 ppm sodium phenobarbital. Equal enhancement of the incidence of hepatocellular carcinomas was obtained with 250, 500 and 1000 ppm sodium phenobarbital. In non-DENA-initiated rats, phenobarbital did not induce neoplastic nodules or hepatocellular carcinomas. Our results suggest that a daily dose of at least 250 ppm sodium phenobarbital is required in order for it to exert tumor promoting activity.
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PMID:Dose-response relationship of phenobarbital promotion of diethylnitrosamine initiated tumors in rat liver. 376 56


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