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)

The effect of bleomycin on [3H]thymidine 5'-triphosphate ([3H]TTP) incorporation into isolated sucrose nuclei from host liver and Morris hepatomas has been compared. Bleomycin stimulates [3H]TTP incorporation 13-fold in host liver and hepatoma 16 nuclei, 8-fold in hepatoma 7800 nuclei, and 3-fold in hepatoma 7777 nuclei. Differences in the nuclear membranes are not responsible for the different response of the nuclei. Nuclei, denuded of their membranes by Triton X-100 treatment, give similar results to sucrose nuclei. Analysis of DNA extracted from liver or hepatoma nuclei incubated with bleomycin indicates that bleomycin produces scissions in the nuclear DNA and that some repair synthesis takes place. Incubation of nuclei with 111indium-labeled bleomycin shows an equal binding capacity of liver and hepatoma nuclei for bleomycin. Bleomycin also stimulates incorporation of [3H]TTP in a system using chromatin or calf thymus DNA as primer. Host liver or hepatoma chromatin incubated with a DNA polymerase extracted from normal rat liver nuclei is stimulated approximately to the same extent by bleomycin. When DNA polymerase extracts from host liver and hepatoma nuclei are assayed with calf thymus DNA as primer, bleomycin has a greater stimulatory effect on [3H]TTP incorporation with host liver DNA polymerase than with hepatoma DNA polymerase in the system. We suggest that a defect in the repair system in hepatoma nuclei is responsible for the relatively lower response to bleomycin.
Cancer Res 1976 Apr
PMID:Effect of bleomycin on [3H]Thymidine 5'-Triphosphate incorporation into host liver and hepatoma nuclei. 5 97

The plasma level of alpha1-fetoprotein in 35 hepatic patients with a "cold" area showed by liver scanning has been detected by means of the radioimmunoassay technique. High levels (more than 320 ng/ml) of AFP were found in 4 cases of primary carcinoma of the liver; low concentration of AFP was found in 1 case of hepatoma. In 4 cases of liver metastasis the plasma levels of AFP were very low; the highest concentration (10 ng/ml) was found in a patient with a cancer of the colon. Low levels of AFP were found in all the cases (26) of hepatic cirrhosis, whereas high level of AFP was detected in 1 case of chronic hepatitis. The detection of alpha1-fetoprotein by the radioimmunoassay technique may be of value in the differential diagnosis between hepatoma and cirrhosis.
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PMID:[Radioimmunologic determination of alpha fetoprotein in diagnosis of primary tumors of the liver]. 5 25

This study was undertaken to investigate the possibility that Listeria monocytogenes, Brucella abortus, and Salmonella typhimurium share antigenic components with guinea pig line 10 hepatocarcinoma cells. Rabbits were immunized with sonicates of these bacteria or line 10 tumor cells. Other rabbits were immunized with line 1 cells, a tumor with antigenic characteristics different from those of line 10. The binding of antibodies to radiolabeled antigens prepared from extracts of bacteria and line 10 cells was studied by precipitation of radiolabeled antigen-antibody complexes with anti-rabbit immunoglobulin. Antibodies in sera from rabbits immunized with these bacteria and line 10 cells bound both the labeled bacteria and line 10 antigens. Antibodies in sera from rabbits immunized with line 1 cells did not bind the bacterial antigens. Inhibition studies involving reactions between radiolabeled Listeria and line 10 antigens and antibodies to Listeria and line 10 cells confirmed that the binding reactions were specific and that line 10 cells shared antigens with Listeria cells. The possibility that B. abortus and S. typhimurium also shared antigens with line 10 cells was suggested. Whether antigens shared by these bacteria and line 10 cells are identical with tumor-specific antigens was not determined.
Cancer Res 1976 May
PMID:Shared antigens between bacteria and guinea pig line 10 hepatocarcinoma cells. 5 23

The mechanism of increased alpha-fetoprotein (AFP) production following a single injection of ethionine was investigated by using rats aged 5 weeks at the time of killing. Marked elevations of serum AFP concentrations occurred within 4 days in both male and female rats after administration of DL-ethionine or L-ethionine, although the increased levels of serum AFP and liver triglyceride in the adults were less marked in the male than in the female. No apparent necrosis of liver cells was observed in ethionine-treated rats. Frequent administrations of adenosine triphosphate after a single dose of ethionine prevented the increases in liver triglyceride and serum AFP levels. The increased concentrations of serum AFP, reaching a maximum level within 4 days, occurred before a slight increase in incorporation of 3H-thymidine into liver DNA. The serum AFP from ethionine-treated rats was immunologically and electrophoretically indistinguishable from that of fetal, carbontetrachloride-treated or hepatoma-bearing rats. These observations suggest that the increased production of AFP in ethionine-treated rats is closely associated with hepatic injury and is not the consequence of liver cell regeneration.
Int J Cancer 1976 Apr 15
PMID:Prompt elevation of rat serum alpha-fetoprotein by acute liver injury following a single injection of ethionine. 5 43

The level of serum alpha-fetoprotein (AFP) was estimated by radioimmunoassay in 153 normal healthy Malysians of different ethnic groups. The mean level was 7.5 In1/ml (SD 2.28InU/ml). Among 330 patients with malignant tumors, 11 had increased levels of AFP. The only patient who had hepatoma had a very high level of serum AFP. High levels were also found in three of four patients with dysgerminoma of the ovary, in the only two patients with carcinoma of the testis, and in one patient with secondary carcinoma of the humerus of unknown origin. Lower, but significantly increased levels were observed in one patient (of 48) with breast carcinoma, one patient (of 8) with basal cell carcinoma of the nose, one patient (0f 27) with carcinoma of the lung, and one patient (of 59) with nasopharynegeal carcinoma.
Cancer 1976 Jul
PMID:Radioimmunoassay of serum alpha-fetoprotein in patients with different maliganant tumors. 5 26

The synthesis of the male rat hepatic protein alpha2U-globulin has been examined in Morris hepatoma 5123D and male host liver using pulse incorporation of labeled amino acids in vivo, followed by immunoprecipitation of the newly synthesized alpha2U-globulin from the soluble protein fraction of liver and hepatoma tissue. It was found that no alpha2U-globulin synthesizes alpha2U-globulin at a normal level (0.9 to 1.0% of total hepatic protein synthesis). A variety of liver-derived cell culture lines also did not have alpha2U-globulin synthesis. The level of the specific mRNA coding for alpha2U-globulin can be quantitated using in vitro translation of polyadenylate-containing RNA in a Krebs II ascites cell-free translational system, followed by immunoprecipitation of the alpha2U-globulin synthesized in vitro. Using this technique, it was found that host liver contained alpha2U-globulin mRNA at normal levels, whereas hepatoma tissue contained no detectable mRNA coding for this protein. Thus, alpha2U-globulin synthesis is deleted in the minimal-deviation hepatoma 5123D as a consequence of the inability of that tissue to produce functional mRNA coding for alpha2U-globulin. The implications for the regulation of gene expression in malignant cells are discussed.
Cancer Res 1976 Oct
PMID:Comparison of in vivo translation rates and messenger RNA levels of alpha2U-globulin in rat liver and Morris hepatoma 5123D. 6 Jan 71

The expression of an "oncodevelopmental" protein, alpha-fetoprotein (AFP), has been systematically studied in rats during normal development and during regeneration of the liver by fetal rat hepatocytes in vitro, in rats bearing transplantable hepatomas, in rats fed chemical carcinogens, and in mice that spontaneously develop hematomas. AFP is a serum protein made normally during fetal and neonatal stages by liver and yolk sac cells. In newborn rats at approximately 4 weeks of age, the production of AFP is abruptly terminated, a process which is closely associated with cessation of liver cell proliferation. In adult rats, AFP production recurs following the reinitiation of hepatic DNA synthesis induced by partial hepatectomy or by the administration of heaptotoxic chemicals. Detailed metabolic and direct labeling studies of fetal rat hepatocytes in vitro also demonstrate a kinetically similar pattern of hepatocyte DNA synthesis and AFP production. In vitro studies utilizing combined autoradiography for DNA-synthesizing cells and immunofluorescence for AFP-containing cells demonstrates that replicating hepatocytes produce AFP, however, available data do not yet permit a distinction between G1 (pre- or postmitotic) and/or G2 production. During growth of an AFP- producing tumor, the serum concentration of AFP may be used as a accurate index of tumor growth, and, if a transplanted tumor is removed, as a marker for metastatic growth of the tumor. Using this model, we have shown that radiation to the lung at the time of surgical removal of a growing tumor in the leg will prevent establishment and growth of pulmonary metastases and that anti-AFP serum treatment may inhibit growth of a transplantable hepatoma that produces AFP. The exposure of rats to chemical hepatocarcinogens results in the appearance of evaluated serum AFP concentration as early as within 1 week of feeding; noncarcinogenic chemical analogs do not cause an elevation. AFP elevation also occurs with low doses of the hepatocarcinogen in the absence of detectable cell injury (by morphological examination of serum enzyme levels) or any other known morphological or biochemical change. This may represent a highly selective derepression of protein synthesis that occurs following the formation of a complex between the metabolites of the carcinogen and specific chromatin loci. Although every rat so far treated with even subcarcinogenic doses of hepatocarcinogens has elevated serum AFP concentrations, many primary carcinogen-induced hepatomas do not produce detectable AFP. Either there is a subsequent change in the preneoplastic AFP-producing cell that occurs prior to irreversible neoplastic alteration, or the hepatocytes originally influenced by the carcinogens to produce AFP are not necessarily the same cells that are the progenitors of the hepatoma produced by more prolonged exposure...
Cancer Res 1976 Nov
PMID:Expression of an oncodevelopmental gene product (alpha-fetoprotein) during fetal development and adult oncogenesis. 6 4

Transplabtable Zajdela rat ascites hepatoma cells, previously considered "nonproducers," synthesize detectable amounts of intracellular alpha-fetoprotein (AFP) and fibrinogen, but fail to secret or release these serum proteins. Evidence for defective secretory mechanisms for serum proteins in these hepatoma cells (a) explains the failure to detect AFP in either the serum or ascitic fluid of rats bearing this hepatoma, (b) indicates that some hepatoma cells should be classified as "nonsecretors," rather than nonproducers of AFP, and (c) suggests that failure to detect AFP in some human and animal hepatomas in vivo and in vitro may also reflect failure of secretion rather than failure of intracellular synthesis.
Cancer Res 1976 Sep
PMID:Intracellular synthesis of alpha-fetoprotein and fibrinogen without secretion by Zajdela rat ascites hepatoma cells. 6 10

In studies in this and other laboratories, induction of hepatocardinoma by several different chemical carcinogens was enhanced in rats fed diets deficient in lipotropes (choline, methionine, folic acid), amino acids, and niacin, and high in fat. In some cases, specific supplementation with lipotropes blocked carcinogenesis. In studies reported here, specific supplementation of a marginally deficient diet that enhanced carcinogenesis in rats, with the amino acids or lipotropes in which it was deficient, significantly decreased induction of hepatocarcinoma by N-nitrosodiethylamine. Niacin supplementation decreased hepatocarcinoma incidence only slight; the addition of beef fat to an adequate diet did not enhance tumor induction. Rats fed the amino acid- or lipotrope-supplemented diets had an increased incidence of hepatic hemangioendothelial sarcomas, compared to deficient rats or to rats fed the adequate control diet. Methionine was contained in both the amino acid and the lipotrope supplement and probably was responsible for reducing hepatocarcinoma incidence. Methionine has been found to have an anticarcinogenic effect in other studies and also to block the depletion of hepatic folate stores that is induced by N-nitrosodiethylamine. Interactions between carcinogens, S-adenosylmethionine, and folate may be significant in hepatic or other tissue carcinogenesis. One of more hepatic microsomal oxidases were depressed in rats fed any of the high-fat diets but were not correlated with tumor incidence.
Cancer Res 1977 Jan
PMID:Reduction of N-nitrosodiethylamine carcinogenesis in rats by lipotrope or amino acid supplementation of a marginally deficient diet. 6 28

Three of 42 (7%) monkeys given aflatoxin B1 (AFB1) for longer than 2 years have developed primary malignant neoplasms of the liver. Liver biopsies performed at intervals during aflatoxin administration revealed that neoplasia was preceded by pathologic lesions of the liver, including toxic hepatitis, proliferation of pseudotubules, and hyperplastic nodules. Serum alpha-fetoprotein levels, monitored in one of the monkeys by radioimmunoassay, paralleled tumor growth and recurrence of the hepatocellular carcinoma. Normal serum alpha-fetoprotein levels were noted for a monkey with hemangioendothelial sarcoma. Our results implicate AFB1 as a liver carcinogen in monkeys and add additional support to the hypothesis that humans exposed to this substance may be at risk of developing liver cancer.
J Natl Cancer Inst 1976 Jul
PMID:Carcinogenicity of aflatoxin B1 in rhesus monkeys: two additional cases of primary liver cancer. 6 57


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