Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) Passive hemagglutination and radioimmunoassay are suitable methods for the detection of AFP in the low concentration range. (2) In 3.72% of the cases a clinically unknown carcinoma was found in an unselected group of patients with liver cirrhosis. (3) 21.9% of the patients showed AFP elevations up to 2000 ng/ml. In 10.6% of this group, increasing titers demonstrated a primary liver cell carcinoma. In 89.4% a transitory rise of AFP was not associated with tumor growth. Levels return to normal values within three months in 90% of the cases. (4) Transitory AFP elevations are not correlated to clinical conditions (praecoma, coma, delirium, bleeding, ascites, shunt) or to biochemical parameters (GOT, GPT, bilirubin, prothrombin complex time, gamma-globulin). (5) A temporary rise in AFP is more frequently observed in groups with high hepatoma incidence than in groups with low hepatoma incidence. (6) Therefore, it may be suggested that a transitory rise of AFP could reflect a "primary reaction" of carcinogenesis. (7) Primary liver cell carcinoma is found to be more frequent in posthepatitic than in postalcoholic, cryptogenic, and other cirrhosis and to be more frequent in australia-antigen positive than in australia-antigen negative cases. (8) Routine serological tumor antigen screening of patients with a precancerous disease is useful.
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PMID:Early detection of hepatoma: prospective study in liver cirrhosis using passive hemagglutination and the radioimmunoassay. 5 21

Active or passive immunization of rats to alpha1-fetoprotein (AFP) does not consistently inhibit the growth of AFP-producing transplantable hepatomas in vivo, and anti-AFP does not kill these hepatomas in vitro. However, 3 of 14 rats in 1 experiment responded to passive immunization by reversal of tumor growth as evidenced by normalization of elevated AFP serum concentrations, and 1 of 9 rats actively immunized with rat AFP in complete Freund's adjuvant had suppressed growth of transplantable hepatoma 7777.
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PMID:Effect of anti-alpha1-fetoprotein on alpha1-fetoprotein-producing rat tumors in vivo and in vitro. 5 92

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...
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PMID:Expression of an oncodevelopmental gene product (alpha-fetoprotein) during fetal development and adult oncogenesis. 6 4

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.
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PMID:Carcinogenicity of aflatoxin B1 in rhesus monkeys: two additional cases of primary liver cancer. 6 57

Sixteen necropsies and 4 cases of hepatic resection in which the liver had a solitary hepatocellular carcinoma smaller than 4.5 cm, or a few tumor nodules smaller than 3.5 cm, have been analyzed. Clinically, these patients presented with signs and symptoms compatible with cirrhosis and, of the 16 autopsy cases only 2 had been diagnosed correctly. In all but 4 cases, the noncancerous parenchyma showed advanced cirrhosis of the mixed type, with irregularly sized multilobular nodules and thin strands of stroma, different from typical alcoholic cirrhosis. The primary lesion was grossly encapsulated in the majority, suggesting a slow, expanding growth. Histologically, most primaries were relatively well differentiated. Serum alpha-fetoprotein was generally low, and it served as the major diagnostic clue in only 5 cases. In patients with mildly abnormal alpha-fetoprotein levels, continuous monitoring seems important in order to detect a steady rise, the first warning for tumor growth.
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PMID:Clinicopathological studies of minute hepatocellular carcinoma. Analysis of 20 cases, including 4 with hepatic resection. 6 81

Antibodies to autologous alpha-fetoprotein (AFP) were produced in mice by immunization with rat AFP. C57L/J mice with or without such antibodies were inoculated sc or ip with controlled numbers of cells of the syngeneic, AFP-producing, BW 7756 hepatoma. There was a linear relationship between circulating AFP and tumor mass, with elevated AFP being detectable earlier than the tumor. The AFP levels of the immunized mice were generally lower than those of control mice, and tumors could be detected before elevated concentrations of AFP appeared in the circulation. An extensive series of transplantations with varying protocols for immunization did not protect against tumor and did not affect the rate of tumor growth.
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PMID:Effect of specific immunotherapy with preimmunization against alpha-fetoprotein on a mouse transplantable hepatoma. 6 32

Glycolipid A1 isolated from Mycobacterium bovis BCG, when dissolved in olive oil and injected together with Line 10 transplantable hepatoma cells, is able to elicit a host response which results in the abrogation or retardation of tumor growth in syngeneic guinea pigs. Glycolipid A1 does not have adjuvant activity for delayed type hypersensitivity, and antibodies to A1 have not been detected in the sera of guinea pigs during or after the tumor abrogation induced by A1 injection Glycolipid A1 does not share antigenic determinants with Line 10 cell lipid fractions. The possible role of the granuloma response elicited by A1 in controlling tumor growth is discussed.
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PMID:Antitumor activity of mycobacterial glycolipid A1. 8 9

Serum alpha 1 antitrypsin, alpha 1 acid glycoprotein and beta 2 glycoprotein I concentrations were determined in 36 patients with malignant hepatocellularcarcinoma, 30 with cirrhosis and 35 with hepatitis by quantitative immunoelectrophoresis. Serum alpha 1 antitrypsin and alpha 1 acid glycoprotein levels were significantly higher in patients with hepatocellularcarcinoma than in those with cirrhosis (p less than 0.001) or hepatitis (p less than 0.001). Elevated levels of alpha 1 antitrypsin were found in 88.9% of patients with hepatoma compared to 23.3% of patients with cirrhosis and 28.6% of patients with hepatitis. Raised levels of alpha 1 acid glycoprotein were also found in 80.6% of patients with hepatoma compared to 20% of patients with cirrhosis and in only 5.7% of patients with hepatitis. beta 2 glycoprotein I levels were similar in the three conditions and therefore not useful for differential diagnosis. In monitoring the progress of tumor growth alpha 1 antitrypsin and alpha 1 acid glycoprotein levels were found to increase during the growth phase. Measurements of these two glycoproteins are suggested for differential diagnosis of these liver diseases, as tumor markers for the detection of hepatocarcinoma, and for the monitoring of the progress during treatment.
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PMID:Changes in serum alpha 1 antitrypsin, alpha1 acid glycoprotein and beta 2 glycoprotein I in patients with malignant hepatocellular carcinoma. 8 7

Mice bearing the BW7756 hepatoma were passively immunized using rabbit antiserum to murine alpha-fetoprotein (AFP) administered in constant or increasing doses. Control tumor-bearing mice were inoculated with saline or nonimmune rabbit serum (NRS) (constant or increasing doses), or were left untreated. The tumor growth curves from mice receiving constant or increasing doses of anti-AFP or constant doses of NRS showed suppression of hepatoma growth; but in both groups of anti-AFP-treated mice this was accompanied by gross anatomical changes, including necrosis, more extensive than in the NRS-treated or other control mice. AFP blood levels roughly paralleled the tumor growth responses. Since an immunological response against the rabbit serum was elicited in the host, it is possible that circulating immune complexes play some role in tumor suppression. Changes observed in liver- and spleen-to-body weight ratios may also reflect a response to circulating immune complexes.
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PMID:Immunobiologic studies in hepatoma-bearing mice passively immunized to alpha-fetoprotein. 9 91

The inhibitory effect of vitamin A on tumor establishment and growth has been studied in two animal models. The C57L/J hepatoma, when placed in C57L/J mice receiving inoculations of vitamin A, showed slow growth and the hosts had significantly prolonged survival over untreated mice. The V-2 carcinoma, when implanted in the corneas of New Zealand white rabbits receiving injections of vitamin A, showed decreased vascular response in the limbic vessels. The absence of an induced vascular response prevents vascularization of the tumor and subsequent tumor growth. The evidence suggests that vitamin A may exert its inhibitory effect by modifying the normal vascular response to neoplastic tissue.
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PMID:Vitamin A effect on tumor angiogenesis. 9 97


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