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)

We analyzed in isolated rat liver cell populations and in fetal and neoplastic livers the distribution of RNA sequences which hybridize with alpha-fetoprotein (AFP) complementary DNA clones. Parenchymal and nonparenchymal cell populations were isolated from normal, regenerating, preneoplastic, and bile duct-ligated rat livers. We found that oval cells, fetal liver, and a primary hepatocellular carcinoma contain the full length 2.3-kilobase AFP messenger RNA (mRNA); in normal adult rat liver, 2.3-kilobase AFP mRNA is found at low levels in an unidentified subpopulation of nonparenchymal cells but is not detected in hepatocytes; both parenchymal and nonparenchymal cells from normal or preneoplastic livers contain in variable proportion a smaller AFP RNA which hybridizes only with complementary DNA clones containing sequences located near the 5' end of the rat AFP gene; during liver regeneration induced by CCl4, elevation of the full length AFP mRNA occurs in nonparenchymal cells but seemingly not in hepatocytes. The results suggest that some cells in the nonparenchymal cell fraction of normal adult rat liver might retain the capacity to produce the 2.3-kilobase AFP mRNA found in large amounts in fetal livers, oval cells, and hepatic tumors. Although the nature of these cells remains to be determined, we suggest that such cells might be the source of the small amounts of AFP synthesized in normal rat liver and may constitute the proposed but as yet uncharacterized "facultative stem cell" compartment in rat liver.
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PMID:Cell lineages in liver carcinogenesis: possible clues from studies of the distribution of alpha-fetoprotein RNA sequences in cell populations isolated from normal, regenerating, and preneoplastic rat livers. 241 96

Our earlier studies have revealed that direct hyperplasia induced by liver mitogens such as lead nitrate, ethylene dibromide, nafenopin and cyproterone acetate, unlike compensatory cell proliferation induced by partial hepatectomy and CCl4, does not support the formation of enzyme-altered islands induced by chemical carcinogens in the liver. In the previous studies carcinogens were given at the peak of DNA synthesis induced by the liver mitogens. If the mitogens have altered the sensitive phase of the hepatocyte to the carcinogenic attack, administering the carcinogen at one time point following the mitogenic stimulus might have missed the sensitive phase. In order to overcome this possibility in the present study male Wistar rats weighing 200-250 g were given N-methyl-N-nitrosourea (MNU; 60 mg/kg, i.p.) at three points representing G1, S and G2/M phases of the cell cycle following different types of liver cell proliferative stimuli. In another experiment MNU (60 mg/kg, i.p.) and diethylnitrosamine (15 mg/kg, i.p.) were given prior to the administration of proliferative stimuli. The initiated hepatocytes were also assayed following promotion by two different promoting regimens, namely phenobarbital and the resistant-hepatocyte model. Further, the initiated hepatocytes were monitored not only by using the appearance of islands of enzyme-altered hepatocytes but also using the incidence of hepatocellular carcinoma. The results of this study clearly revealed that irrespective of the protocol used, only the compensatory liver cell proliferation but not the mitogen-induced direct hyperplasia supported the formation and the growth of enzyme-altered islands in the liver induced by chemical carcinogens.
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PMID:Further evidence that mitogen-induced cell proliferation does not support the formation of enzyme-altered islands in rat liver by carcinogens. 256 71

Specific antibodies to fibronectin and type I collagen in rat livers were used to demonstrate these matrix proteins with direct immunoperoxidase method in paraffin sections of normal liver, DAB-induced hepatoma and CCl4-induced fibrotic liver. In normal livers, the immunoreactive products of both matrix proteins were found in the periportal regions, while the hepatocytes and most of the interstitial matrix remained unstained. The specimens obtained from DAB-treated liver showed a more intense reaction with fibronectin antibody in the perisinusoidal space including proliferated cholangiolar cells, as compared to no reaction with type I collagen antibody. In CCl4-fibrotic liver, apparent reactions were also found for both matrix proteins in the periportal interstitium and in progressing fibrotic area with severe fatty metamorphosis. These findings suggest that these matrix proteins have an advantage in the attempt to distinguish different patterns of neoplastic alteration in experimental rat livers.
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PMID:Distribution pattern of liver matrix proteins, fibronectin and type I collagen, in DAB-induced hepatoma of rat. 300 24

Among the patients with liver cirrhosis (LC) who undergo the operation, the postoperative complications are not infrequent and sometimes prove fatal. The impaired hepatic function, especially the impaired reticuloendothelial system (RES) function, has been claimed to be a possible pathogenic factor for these complications. The present experimental and clinical studies were undertaken to investigate the RES function and the effect of preoperative OK-432 administration as an RES potentiator in LC. The results are as follows: 1) CCl4-induced LC rats were evaluated for RES global phagocytic function, Kupffer cell phagocytic function, plasma opsonic activity and plasma opsonic substances such as fibronectin, C3 and IgG. All parameters except IgG showed significant depression compared to those values in normal rats. However, the administration of OK-432 (0.1 KE/rat, ip) improved all these depressed parameters. The OK-432 administration also significantly improved the survival following panperitonitis in LC rats. 2) Among 18 LC patients with hepatocellular carcinoma undergoing partial hepatectomy, the RES global phagocytic function, plasma opsonic activity and plasma opsonic substances were evaluated. Same as the experimental study, all parameters except IgG were significantly depressed among the LC patients compared to those values in the patients with normal liver. However, the preoperative OK-432 administration (5 KE/day sc for 4 days) significantly improved these parameters and consequently decreased the postoperative complications. These results indicate that the preoperative RES activation by the OK-432 was effective and useful for the prevention of the postoperative complications in the LC patients.
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PMID:[Experimental and clinical studies on the effect of reticuloendothelial system (RES) potentiator in the depressed RES function in cirrhotics]. 362 94

Platelet-poor plasma (PPP) from F-344 rats with chemically-induced preneoplastic liver nodules or hepatocellular carcinoma stimulated S-phase DNA synthesis in monolayer cultures of normal rat hepatocytes. Similar mitogenic activity was detected in PPP 6 hrs to 1 week after partial hepatectomy (PH) or after necrotizing doses of CCl4 or diethylnitrosamine (DENA). Very little activity was found in PPP4 from control rats. The mitogenic activity in PPP from animals with nodules was non-dialyzable (greater than 14 kd) and bound to a heparin-sepharose affinity column. None of the mitogenic PPPs competed with [125I] epidermal growth factor (EGF) for binding sites on A431 cells or normal rat hepatocytes. These studies indicate that persistent proliferation of preneoplastic and neoplastic hepatocytes is associated with increased circulating levels of mitogenic hepatocyte growth factor.
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PMID:Mitogenic activity in platelet-poor plasma from rats with persistent liver nodules or liver cancer. 367 91

Our previous studies have claimed that cirrhotic rats, induced with CCl4, showed depressed reticuloendothelial system (RES) function and increased susceptibility to infection. We have also shown that OK-432, a non-specific immunopotentiator, and ATP-MgCl2, which improves depressed intracellular energy metabolism, improve RES function of cirrhotic rats and that thereby improve survival following peritonitis or hepatectomy. The present study was undertaken to investigate whether OK-432 or ATP-MgCl2 could be beneficial for the prevention of multiple organ failure (MOF) following hepatectomy among the cirrhotics. The cirrhotics with hepatocellular carcinoma, who underwent partial hepatectomy (segmentectomy or subsegmentectomy) were given OK-432 (5 KE/day for 4 days) preoperatively or ATP-MgCl2 (50 mumole/kg) within 24 hours following the operation. The rates of postoperative pulmonary complication and the operative mortality were compared among OK-432 group, ATP-MgCl2 group and controls. The rates of posthepatectomy pulmonary complication and operative mortality were decreased with these treatments compared to the controls. The RES function was also improved with these treatments. These data suggest that the cirrhotic patients are the immunocompromised hosts showing the depressed RES function and that the enhancement of RES function with OK-432 or ATP-MgCl2 is beneficial for the prevention of posthepatectomy MOF among cirrhotics.
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PMID:[Pathophysiology and treatment of multiple organ failure among hepatectomized cirrhotic patients]. 408 45

Microcirculatory responses to estradiol benzoate (ES) under condition of chronic liver damage induced by long-term administration of carbon tetrachloride (CCl4) was investigated in the rat. One hundred and five male rats were divided into the following groups receiving 0.1 mg/100 g body weight ES injected intraperitoneally 5 times per week: controls, exposed to CCl4 alone; rats treated with ES from the fourth week of CCl4 exposure; animals treated with ES from the 11th week of CCl4 exposure. In rats receiving CCl4 alone, liver cirrhosis was induced by 10 consecutive weeks of exposure. Microangiograms of the liver demonstrated conspicuous rarefaction of the vascular tree. On the other hand, animals treated with ES had neither atrophic liver nor rarefaction of the intrahepatic vascular tree. ES produced also intrahepatic neovascular proliferation in the cirrhotic liver. After long-term CCl4 administration, ES treated rats had extremely enlarged nodules with tumor-stain like findings, giving rise to a structure differing from hepatocellular carcinoma which latter generally displays a broom-swept appearance. It is concluded that in providing potent angiogenesis in the liver, ES protects the liver against microcirculatory dearangement and parenchymal damage induced by CCl4.
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PMID:Microcirculatory responses to estradiol benzoate in chronic liver damage induced by carbon tetrachloride in the rat. 608 95

The enhancing or inhibitory action of the hepatotoxic agents, carbon tetrachloride (CCl4) and azathioprine (AZP), on the evolution of hyperplastic liver nodule (HN) and hepatocellular carcinoma (HCC) in diethylnitrosamine (DEN)- and N-2-fluorenylacetamide (FAA)-treated rats (control group) was tested. The area of gamma-glutamyl transpeptidase(gamma-GTP)-positive HN and/or foci in the eighth week was remarkably small in rats fed on a diet containing FAA and AZP (the AZP group), but was quite large in rats fed a diet containing FAA in addition to repeated CCl4 injections (the CCl4 group). HCC was first detected in the 21st week and the incidence of HCC within the 36 weeks of the experiment was very high in the CCl4 group. However, no tumor, including HCC, was detected in the AZP group during this observation period. No essential differences in the biochemical characteristics of HCC between the control group and the CCl4 group were observed with respect to several enzyme activities. The increased activity of liver aniline hydroxylase observed 12 hr after the administration of FAA, AZP, or DEN decreased when AZP was administered simultaneously with FAA to rats treated with DEN in advance. The mechanisms of the enhancing of inhibitory effect observed are discussed with special reference to the drug-drug interactions.
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PMID:Effect of azathioprine and carbon tetrachloride on induction of hyperplastic liver nodule and hepatocellular carcinoma by diethylnitrosamine and N-2-fluorenylacetamide in rats. 614 75

In 12 cirrhotic patients who developed primary hepatocellular carcinomas during long-term follow-up, surveillance by frequent serum alpha-fetoprotein (AFP) measurements was not useful for their earlier detection. Difficulty was encountered in deciding whether or not hepatomas had already developed in cirrhotic patients with serum AFP levels over 200 ng/ml. Simultaneous injections of pyridoxine and adenosine 5'-triphosphate (ATP) resulted insignificant decreases of elevated serum AFP levels in carbon tetrachloride (CCl4)-injured rats but in 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB)-induced hepatoma-bearing rats. On clinical application of this procedure, it was found that cirrhotic patients without hepatomas could be differentiated from those with primary hepatomas since in the former a clear reduction of AFP levels following the administration of pyridoxine and ATP took place. This may be a new approach to the earlier diagnosis of primary hepatomas in cirrhotic patients with elevated serum AFP levels.
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PMID:Altered dynamics of alpha-fetoprotein production following pyridoxine and adenosine 5'-triphosphate administration to cirrhotic patients with or without primary hepatomas and to liver-injured and hepatoma-bearing rats. 617 68

Adult male Fischer rats were exposed to a necrogenic dose (200 mg/kg) of diethylnitrosamine or to nonnecrogenic doses of N-methyl-N-nitrosourea, 1,2-dimethylhydrazine, or benzo(a)pyrene following partial hepatectomy or sham hepatectomy. This treatment by itself led to no hepatocellular carcinomas by 8 to 18 months, except in animals given N-methyl-N-nitrosourea, which showed a 30% incidence by 12 months. With each treatment regimen, exposure to dietary 2-acetylaminofluorene for 2 weeks coupled with partial hepatectomy or the administration of a necrogenic dose of CCl4, was associated with an incidence of 68 to 94% of cancer at 8, 12, or 18 months, depending upon the initiating carcinogen used. Appropriate controls showed either no hepatocellular carcinoma or a much lower incidence. It is concluded that the 2-week exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or the administration of CCl4 has a strong promoting effect on liver carcinogenesis with four different chemical carcinogens.
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PMID:Promotion of liver cancer development by brief exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or carbon tetrachloride. 629 53


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