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)

Forty-five human malignant tumour specimens were cultivated in vitro in an attempt to determine the necessary conditions for tumour cell maintenance and to establish permanently-growing cell lines. Continuously-growing cultures were derived from five tumours, including carcinomas of the oesophagus and colon, a hepatoma, a mesothelioma and a retroperitoneal sarcoma. The carcinoma of the oesophagus and the hepatoma, which have adapted fully to in vitro conditions, can be regarded as established cell lines.
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PMID:Adaptation of cells derived from human malignant tumours to growth in vitro. 18 51

2,6-Dichlorobenzonitrile (Dichlobenil) is the active principle of a commercial herbicide that was previously shown to be carcinogenic for animals. Dichlobenil was administered to male Swiss albino mice in order to assess the possible oncogenic properties of the active principle alone. The substance at 2 ppm concentration was injected (0.0005 mg/injection) either by subcutaneous or intraperitoneal route to 2 randomized groups of 30 animals each every third day for 13 times. Dichlobenil induced a significant increase of malignant tumors (lymphoma, mesothelioma, hepatocellular carcinoma, and pulmonary alveologenic carcinoma) with respect to the controls (p less than 0.01 in both treated groups). As for tumor histotypes, only lymphoma incidence was significantly increased in the intraperitoneally treated animals (p less than 0.05). Dichlobenil can be suspected of being a possible carcinogen in Swiss mice but the mechanism of its action is not precisely known.
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PMID:A one-year carcinogenicity study with 2,6-dichlorobenzonitrile (Dichlobenil) in male Swiss mice: preliminary note. 204 73

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.
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PMID:Efficacy of mitoxantrone against various neoplasms in dogs. 206 Nov 77

An unusual case of extrahepatic disseminating hepatocellular carcinoma in a 64-year-old man is reported. The initial symptom was abdominal fullness and progressive ascites. Alpha-fetoprotein in the serum was 117,000 ng/ml. Exploratory laparotomy disclosed dissemination of tumor nodules throughout the abdominal cavity without any other possible primary tumor. CT scan, ultrasonography and hepatic angiography were unable to detect any tumor lesion in the liver. The final histologic diagnosis was hepatocellular carcinoma, although at first epithelioid mesothelioma was suspected. The present case of hepatocellular carcinoma was thought to have possibly developed from ectopic liver on the peritoneum.
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PMID:Hepatocellular carcinoma arising in the abdominal cavity. An autopsy case of ectopic liver origin. 246 14

CB 3717, N10-propargyl-5,8-dideazafolic acid, is a tight-binding inhibitor of thymidylate synthase (TS) whose cytotoxicity is mediated solely through the inhibition of this enzyme. Recent preclinical studies have focused on the intracellular formation of CB 3717 polyglutamates. Following a 12-hour exposure of L1210 cells to 50 microM [3H]CB 3717, 30% of the extractable radioactivity could be accounted for as CB 3717 tetra- and pentaglutamate, as determined by high-pressure liquid chromatography (HPLC) analyses. As inhibitors of isolated L1210 TS, CB 3717 di-, tri-, tetra- and pentaglutamate are 26-, 87-, 119- and 114-fold more potent than CB 3717, respectively, and their formation may, therefore, be an important determinant of CB 3717 cytotoxicity. In early clinical studies with CB 3717, activity has been seen in breast cancer, ovarian cancer, hepatoma, and mesothelioma. Toxicities included hepatotoxicity, malaise, and dose-limiting nephrotoxicity. This latter effect is thought to be due to drug precipitation within the renal tubule as a result of the poor solubility of CB 3717 under acidic conditions. In an attempt to overcome this problem, a clinical trial of CB 3717 administered with alkaline diuresis is under way. Preliminary results at 400 and 500 mg/m2 suggest that a reduction in nephrotoxicity may have been achieved with only 1 instance of renal toxicity in 10 patients. Hepatotoxicity and malaise are again the most frequent side effects. Evidence of antitumor activity has been seen in 3 patients. Pharmacokinetic investigations have shown that alkaline diuresis does not alter CB 3717 plasma levels or urinary excretion and that satisfactory urinary alkalinization can be readily achieved.
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PMID:Recent preclinical and clinical studies with the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid (CB 3717). 343 91

Xenobiotic induction of liver peroxisomes is associated with hypolipidemia. To test the involvement of the peroxisome proliferation with the hypolipidemia, male rats were inoculated in the groin with five different tumors: an aflatoxin-induced hepatoma, a lasiocarpine-induced hepatoma, an actinomycin-D-induced mesothelioma, a lasiocarpine-induced squamous cell carcinoma, and a methylnitrosourea-induced fibrosarcoma. After the tumours reached a suitable size, the rats were fed diets containing the peroxisome-proliferating hypolipidemic agents tibric acid (2-chloro-5-[3,5-dimethylpiperidinosulfonyl] benzoic acid) or Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid) for 2 weeks. Liver and tumor tissues were then assayed for the peroxisome-associated enzymes, catalase and carnitine acetyltransferase, and correlated with serum levels of triglyceride and cholesterol. The presence of the tumors caused a predictable decrease in liver catalase and a slight elevation of liver carnitine acetyltransferase. Serum cholesterol was elevated slightly, while serum triglyceride levels were elevated, unchanged, or decreased in the tumor-bearing rats maintained on control diet. Inclusion of the xenobiotics in the diet caused increases in liver weight, catalase, and carnitine acetyltransferase. Serum triglycerides were decreased in the three groups which were not already decreased, but a decrease in serum cholesterol was only found in one group after only one of the treatments. The latter finding demonstrates that peroxisomal enzyme induction can be dissociated from the decrease in serum cholesterol. The data were further evaluated by testing for correlations between the changes in these components, comparing changes within groups and between groups. These correlations indicate an inverse biological association between liver catalase and serum cholesterol and between liver carnitine acetyltransferase and serum triglyceride. The latter correlation was inverse only for comparisons between groups, suggesting that carnitine acetyltransferase activity is associated with serum triglycerides only during the perturbational state.
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PMID:Peroxisome-associated enzymes and serum lipids in tumour-bearing rats treated with peroxisome-proliferating agents. 643 85

Eighteen patients received a continuous intravenous infusion of adriamycin for 14-60 days in a phase I study in which the dose rates were escalated from 2 mg/sq m/day to 5 mg/sq m/day to establish the optimal dose to be delivered over a 30-day period. The drug was delivered via a tunneled subclavian catheter by a portable infusion pump (Cormed model ML-6) primed to provide a volume of diluted drug of 10 cc/day. Leukopenia and stomatitis were observed at 4 mg/sq m/day doses or greater in 50% of courses. At doses less than 4 mg/sq m/day, only 3/17 courses (18%) were associated with stomatitis. Partial alopecia developed in all patients, but less than 50% of scalp hair was affected. The cumulative dose of continuous infusion adriamycin at 30 days is comparable to the dose delivered by standard bolus intermittent schedules (60-90 mg/sq m g 21 days), but the adverse drug effects are eliminated or substantially reduced. Cardiac toxicity was assessed in selected patients treated to 450 mg/sq m or greater by cardiac biopsy and/or gated pool studies. No histopathologic lesions were noted in 3 patients receiving 450 mg/sq m or greater. The recommended daily dose rate of adriamycin in this protracted infusion regimen is 3 mg/sq m/day. The phase II study of this schedule and dose rate in 38 additional patients (a total of 52 evaluable patients) demonstrated objective responses in 1/9 soft tissue sarcoma, 1/3 mesothelioma, 1/3 hepatoma, and 2/13 breast cancer. Phase III studies of the protracted continuous infusion schedule for adriamycin are indicated in that clinical activity is demonstrated at a substantial reduction in toxicity. Pharmacologic studies expanding the existing data base are also necessary.
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PMID:Constant infusion schedule for adriamycin: a phase I-II clinical trial of a 30-day schedule by ambulatory pump delivery system. 666 81

A patient with biopsy-proved biliary cirrhosis and previous gastrojejunostomy and portacaval anastomosis experienced episodes of severe hypoglycemia. She was found to have hyperinsulinemia and hyperglucagonemia. An oral glucose tolerance test showed postgastrectomy hypoglycemia. Results of the intravenous tolbutamide test were diagnostic for insulinoma, but results of the intravenous glucagon test and prolonged fast (96 hours) were not. Failure, on two occasions, to suppress C-peptide normally during insulin-induced hypoglycemia led to a diagnosis of pancreatogenous hyperinsulinemia. The pancreas showed a 10-fold increase in islet volume, with intensely positive staining with anti-insulin and anti-glucagon antiserums in addition to anti-somatostatin and anti-pancreatic polypeptide antiserums. Incidental findings at pancreatic exploration were a mesothelioma, which did not stain with anti-insulin antiserum, and, at autopsy one year later, a hepatoma.
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PMID:Diagnosis of pancreatic islet hyperplasia causing hypoglycemia in a patient with portacaval anastomosis. 699 72

To determine if hyperplastic and neoplastic lesions from medaka showed similar immunoreactivity to intermediate filament antibodies as the tissues of origin, two week old medaka were exposed to 10 or 20 mg/L of methylazoxymethanol acetate for two hours and transferred to clean water for up to six months. Using a streptavidin peroxidase method, paraffin embedded Bouins fixed neoplasms were incubated with cytokeratin, vimentin, or neurofilament antibodies. Like their nonneoplastic cellular counterparts, hepatocellular carcinoma, pancreatic acinar carcinoma and mesenchymal neoplasms including hemangioma and hemangiopericytoma reacted negatively to cytokeratin antibodies. Cholangiocarcinoma, mesothelioma, and proliferative lesions containing biliary epithelial cells reacted positively to cytokeratin antibodies. All neoplasms and proliferative lesions were negative with vimentin and neurofilament antibodies. These data indicate that while some epithelial neoplasms showed cytokeratin reactivity similar to the parent tissues, additional markers are needed to identify mesenchymal tissues and neoplasms.
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PMID:Intermediate filament reactivity in hyperplastic and neoplastic lesions from medaka (Oryzias latipes). 753 29

The spectrum of p53 mutations differs among human cancer types. We have hypothesized that the p53 mutational spectrum observed in particular tumor types reflects the functional ability of different p53 mutants to modulate wild-type (WT) p53-dependent gene transcription. Missense p53 mutants representing several mutational hotspot codons were cotransfected with WT p53 and analysed for their effects on p53-dependent transactivation of a reporter construct containing a specific p53 binding sequence (PG13-CAT) in human tumor cell lines lacking endogenous p53. Our results show that the ability of p53 mutants to inhibit WT p53-mediated transactivation is cell type dependent. In cell lines derived from a lung adenocarcinoma and a mesothelioma, the transactivation function of WT p53 was strongly inhibited by all p53 mutants examined. However, in cell lines derived from a prostate carcinoma and an osteosarcoma, the mutants examined generally had only minimal dominant negative effects. In cell lines derived from a hepatocellular carcinoma and an ovarian carcinoma, two mutants (248trp and 273his) enhanced WT p53-mediated transactivation of the reporter construct. Additional mutants retained the ability to inhibit WT p53-mediated transactivation in these cell lines. In addition, in a series of four breast tumor cell lines, the p53 mutants examined had similar effects on WT p53 transactivation ability including enhanced transactivation activity in the 273his cotransfectants. The p53 mutants were incapable of transactivating the PG13-CAT reporter in the absence of WT p53 expression. Therefore, the dominant negative effects of p53 mutants on WT p53 function may vary depending on the particular cell type. In addition, mutants with stronger inhibitory capabilities may confer a selective advantage during the tumorigenic process.
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PMID:Effects of p53 mutants on wild-type p53-mediated transactivation are cell type dependent. 778 55


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