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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathologic features, clinical presentation and natural history of hepatocellular carcinoma (HCC) developing in the noncirrhotic liver were studied in 61 patients against a background of 63 patients seen concurrently with HCC complicating cirrhosis. Noncirrhotic HCC had a bimodal age distribution, with females predominating the first age-clustering (10-50 years) and males predominating the second age-clustering (50-90 years). Cirrhotic HCC had a unimodal age distribution (40-90 years) with male dominance throughout. Estrogen exposure was noted in 57% of the noncirrhotic HCC women overall and in 80% of those in the younger age-clustering. The majority of noncirrhotic HCC presented with a single hepatic mass or a dominant primary with satellite lesions in contrast to the usual multinodular or diffuse disease seen with cirrhosis. Twenty-nine noncirrhotic patients survived complete resection of disease limited to the liver and exhibited a median survival of 2.7 years with a 5-year survival of 25%. Low histologic grade, minimal necrosis, and the absence of hemoperitoneum, hepatomegaly, and adjacent organ involvement were all favorable prognostic variable. Patients with metastatic or locally unresectable noncirrhotic HCC had a median survival of 9 months, and 24% survived in excess of 2 years. This survival experience is significantly more favorable than cirrhotic HCC patients, who had only a 1.2-month median and a 3% 2-year survival. Low histologic grade, mild mitotic activity and the presence of some fibrosis within the specimen were associated with a favorable outcome in advanced noncirrhotic HCC. The favorable prognosis and heterogeneous composition of the noncirrhotic, when compared to the cirrhotic HCC cohort, may be important considerations in the design and evaluation of future clinical trials.
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PMID:Hepatoma in the noncirrhotic liver. 284 80

Morris hepatoma 44, whose growth is sensitive to thyroid hormones and prolactin, contains specific receptors for these hormones. In the present experiments, male Buffalo rats bearing Morris hepatoma 7787 were studied to determine the effects of several sex steroid hormones. Castration 1 week postimplantation inhibited tumor growth relative to controls (-53%). Replacement with testosterone propionate (1 mg per day s.c. injection) restored tumor growth to control levels, whereas administration of testosterone (2 mg per day s.c. injection) to castrated controls resulted in significant stimulation. Testosterone administered to control animals at a dose of 1 mg per day stimulated tumor growth (62%), whereas 2 mg per day failed to do so. Progesterone (4-pregnon-3,20-dione) at doses of 125 or 250 micrograms per day (Silastic implants) had no effect on tumor growth, whereas 500 micrograms per day stimulated tumor growth relative to controls. Estrogen (17 beta-estradiol) at doses of 6, 12, or 24 micrograms per day (Silastic implants) did not influence tumor growth. Cytoplasmic testosterone receptors have been demonstrated in tumors (2.2 +/- 0.8 fmoles per mg cytoplasm), although specific cytoplasmic estrogen and progesterone receptors could not be identified in this model. In female rats bearing either Morris hepatoma 44, 7787 or 5123-D, testosterone markedly stimulated tumor growth (226, 328 and 58%, respectively, relative to controls). In conclusion, although Morris hepatoma 7787 appears to be androgen (testosterone) dependent and contains cytoplastic androgen receptors, it lacks specific cytoplasmic receptors for estrogen and progesterone and is not influenced by these hormones except at very high doses of progesterone.
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PMID:The effect of several sex steroid hormones on the growth rate of three Morris hepatoma tumor lines. 292 66

Estrogen receptors (ER) were assayed on hepatocellular carcinoma (HCC) and surrounding liver tissue in 30 adult patients. All specimens were obtained at the time of surgery. Cirrhosis of the liver was associated with 28 patients and chronic hepatitis in 2 patients. ERs were detected in 12 of 30 HCCs. The value ranged from 1.4 to 9.2 fmol/mg cytosol protein with the dissociation constant (Kd) value less than 1 nanomol. On the other hand, 13 of 28 cirrhotic livers had measurable amounts of the receptors that ranged from 1.5 to 4.1 fmol/mg cytosol protein. Two livers with chronic hepatitis did not have detectable amounts of ERs. The receptors were not detected in both the tumor and liver in ten patients. The ER titers in HCC did not have any correlation with serum levels of alpha-fetoprotein or carcinoembryonic antigen, hepatitis B virus profiles, and histologic types of the tumor. In the light of the current results, it would be of great interest whether hormone therapy can be used or not as a treatment of naturally occurring HCC in humans.
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PMID:Estrogen receptors in hepatocellular carcinoma. 300 May 73

It has been shown previously that the rat hepatoma no. 7288C grown in vivo or in vitro expresses fewer receptors which recognize chylomicron remnants than does normal rat liver, and it was suggested that this may contribute to the deletion of dietary cholesterol-induced regulation of cholesterol synthesis in hepatomas (Barnard, G., Erickson, S. and Cooper, A. (1984) J. Clin. Invest. 74, 173-184). To investigate this further, Buffalo rats bearing hepatomas (HTC no. 7288C) were made hypercholesterolemic by feeding an atherogenic diet and hypocholesterolemic by ethinyl estradiol injections. Under all circumstances, tumor membranes had fewer receptors than liver membranes as measured by specific binding of [125I]chylomicron remnants. Ethinyl estradiol treatment increased the number of lipoprotein receptors 1.7-fold in liver membranes and 1.2-1.6-fold in tumor membranes, but hypercholesterolemia did not produce any significant changes in remnant binding to either liver or hepatoma membranes. Feeding an atherogenic diet induced a 2.4-fold increase in total cholesterol content in the liver, primarily as cholesterol ester; however, there was no change in total, free or ester cholesterol in the hepatomas. Acyl coenzyme A:cholesterol acyltransferase activity was low in this hepatoma line and neither treatment significantly affected its activity. One explanation for the lack of effect of the atherogenic diet on hepatoma cholesterol metabolism in addition to the decreased number of lipoprotein receptors might be the failure of access of lipoproteins to the tumor cell. To assess this, radioiodinated apo E-rich lipoproteins of various sizes were injected intravenously into rats with hepatomas. Their disappearance from the circulation was followed, and the uptake of each lipoprotein into a variety of tissues was determined. Chylomicron remnants were the most avidly removed particles. VLDLH, IDLH and HDLC were removed more slowly and less completely. None of the lipoproteins accumulated substantially in the tumors suggesting a limited access to the hepatoma tissue. Thus, in addition to the observed reduction in lipoprotein receptor number, limited lipoprotein access to the hepatoma tissue may be a significant factor in contributing to the apparent lack of feedback regulation of cholesterol synthesis by hepatoma tissue in vivo.
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PMID:Regulation of lipoprotein receptors on rat hepatomas in vivo. 302 19

The role of the low density lipoprotein (LDL) receptor in the binding of chylomicron remnants to liver membranes and in their uptake by hepatocytes was assessed using a monospecific polyclonal antibody to the LDL receptor of the rat liver. The anti-LDL receptor antibody inhibited the binding and uptake of chylomicron remnants and LDL by the poorly differentiated rat hepatoma cell HTC 7288C as completely as did unlabeled lipoproteins. The antireceptor antibody, however, decreased binding of chylomicron remnants to liver membranes from normal rats by only about 10%. This was true for intact membranes and for solubilized reconstituted membranes and with both a crude membrane fraction as well as with purified sinusoidal membranes. Further, complete removal of the LDL receptor from solubilized membranes by immunoprecipitation with antireceptor antibody only decreased remnant binding to the reconstituted supernatant by 10% compared to solubilized, nonimmunoprecipitated membranes. Treatment of rats with ethinyl estradiol induced an increase in remnant binding by liver membranes. All of the increased binding could be inhibited by the antireceptor antibody. The LDL receptor-independent remnant binding site was not EDTA sensitive and was not affected by ethinyl estradiol treatment. LDL receptor-independent remnant binding was competed for by beta-VLDL = HDLc greater than rat LDL greater than human LDL (where VLDL is very low density lipoprotein, and HDL is high density lipoprotein). There was weak and incomplete competition by apoE-free HDL, probably due to removal of apoE from the remnant. The LDL receptor-independent remnant-binding site was also present in membranes prepared from isolated hepatocytes and had the same characteristics as the site on membranes prepared from whole liver. In contrast, when chylomicron remnants were incubated with a primary culture of rat hepatocytes, the anti-LDL receptor antibody prevented specific cell association by 84% and degradation of chylomicron remnants completely. Based on these studies, we conclude that although binding of chylomicron remnants to liver cell membranes is not dependent on the LDL receptor, their intact uptake by hepatocytes is.
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PMID:Role of low density lipoprotein receptor-dependent and -independent sites in binding and uptake of chylomicron remnants in rat liver. 317 May 77

Estrogen binding protein activities were determined in the cytosol from adult male Buffalo rat liver and Morris hepatoma 7777. Estrogen receptors were prepared using the protamine sulfate precipitation technique of Chamness. The ability of various unlabeled steroids competing with [3H]estradiol was examined to establish the binding specificity. Estradiol binding in Morris hepatoma 7777 cytosol was greatly decreased compared with that present in hepatic cytosol prepared from normal rat liver. The receptor concentration expressed as femtomoles per milligram of cytoplasmic protein was 31.1 +/- 2.9 SD for normal rat liver and 0.41 +/- 0.88 SD for the hepatoma. Gel filtration chromatography revealed the presence of an estrogen binder in hepatoma cytosol which was not present in either normal liver or in the protamine sulfate precipitates of hepatoma cytosol. The molecular weight, binding specificity, and precipitation of this protein by specific antiserum suggests that it is alpha-fetoprotein.
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PMID:Estrogen binding protein activity in Morris hepatoma 7777 compared with normal rat liver. 620 12

The hormonal milieu that follows the ingestion of contraceptive agents promotes the growth of hepatic tumors, particularly hepatocellular adenomas. Evidence that the use of contraceptive drugs can also cause carcinoma of the liver is less convincing; this article describes the cases of 2 young women who had taken contraceptives and contracted hepatocellular carcinoma. Both women had no prior history of liver disease and died as a result of the carcinoma. Hepatocellular carcinoma has been a distinctly uncommon disease in the U.S. ranging in incidence from 0.23-0.47% in reported autopsy cases and being typically described as occurring mostly in men over 50 and associated with preexisting cirrhosis. Recent surveys show a greater proportion of female patients; in the U.S. patients at risk now include women in the reproductive age group with no history of prior liver disease. Some recorded changes in the human liver caused by oral contraceptives (OCs) include: 1) impairment of bile secretory function, 2) hepatomegaly associated with peripheral and midzonal sinusoidal congestion, and 3) peliosis hepatis. Significant risk factors in the occurrence of hepatic tumors in OC users are: 1) prolonged usage (1-3 years), 2) age over 30, and 3) use of compounds of high hormonal potency. Products containing mestranol have been implicated to a greater degree than those containing ethinyl estradiol. The link between use of OCs and development of hepatocellular carcinoma is not certain; however, the latter has been firmly linked with the use of anabolic steroids in men. Specifically only the C-17 substituted anabolic steroids oxymetholone and methyltestosterone have been implicated which are closely related to the C-17 substituted 19-norsteroids used in OCs. The following observations have also been made: 1) when hepatocellular carcinoma occurs in women it is mostly in those of reproductive age, and 2) OCs are associated with the development of benign hepatic tumors. Withdrawal from OCs is almost uniformly recommended after definitive diagnosis of a hepatic tumor along with surgery to avoid the risk of rupture and possible mortality.
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PMID:Oral contraceptives and cancer of the liver: a review with two additional cases. 628 82

The effect of dietary exposure to synthetic estrogens on hepatocarcinogenesis was evaluated. Diethylnitrosamine-initiated and 0.85% NaCl solution-treated noninitiated female Sprague-Dawley rats were transferred to semisynthetic diets containing mestranol (0, 0.1, or 0.5 ppm), ethinyl estradiol (0.5 ppm), estradiol (0.6 ppm), or mestranol plus beta-methasone (0.5 and 0.2 ppm, respectively). gamma-Glutamyl transferase (GGT)-positive transections and hematoxylin and eosin-detectable nodules and carcinomas were scored at 9 and 12 months. Quantitative stereological calculations were performed to determine GGT lesion number and size. At 9 months, in diethylnitrosamine-initiated rats, ethinyl estradiol and mestranol caused 3.5- and 4.4-fold increases, respectively, in the number of GGT lesions per liver and an increased incidence of hepatocellular carcinomas while estradiol had no enhancing effect. Addition of beta-methasone to the mestranol-containing diet caused a significant decrease in GGT lesion number but not carcinoma incidence compared to mestranol alone. At 12 months, in diethylnitrosamine-initiated rats, mestranol caused a dose-dependent increase in GGT lesion number. The hepatocellular carcinoma incidence was significantly increased at the high mestranol dose. Small increases in the numbers of larger GGT lesions were also observed in noninitiated animals treated with mestranol and ethinyl estradiol and are most probably due to promotion of spontaneously initiated hepatocytes. These results indicated that the synthetic estrogens cause dramatic increases in the number of presumptive preneoplastic GGT lesions. Carcinoma incidence is also enhanced. Thus, these results confirm and extend our previous studies which together with the results of others have shown that synthetic estrogens can act as promoters of hepatocarcinogenesis.
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PMID:Enhancement of hepatocarcinogenesis in female rats by ethinyl estradiol and mestranol but not estradiol. 674 3

Since the initial report in 1973 of 7 women who developed liver tumors while using oral contraceptives (OCs) over 300 cases have been reported. Hapatic tumors associated with OCs are benign (focal nodular hyperplasia or hepatocellular adenoma) or malignant (hepatocellular carcinoma, angiosarcoma, or cholangiocellular carcinoma). Mestranol is the main estrogen related to the development of hepatic adenoma but other OCs containing combinations of ethinyl estradiol, ethyl estradiol, mestranol, norethynodrel, norethisterone, and norgestrol are also associated with the tumors. Longterm OC users have an estimated annual incidence of 3-4/100,000. Hepatic tumors may present with abdominal pain or be an incidental finding on physical examination or at laparotomy. Diagnosis is confirmed by scintigraphy, echography, CT-scanning, angiography, or laparoscopy. Dynamic isotopic scanning may help differentiate between benign and malignant lesions. Symptomatic benign tumors and malignant tumors are best treated by partial hepatectomy and a ban on estrogens. The use of OCs should be forbidden following resections. Surgery is indicated for patients with persistent or recurrent pain, those with intraperitoneal hemorrhage and those in whom a carcinoma is suspected. The administration of synthetic estrogens to experimental animals results in a variety of morphological and functional changes within the hepatocyte. Other possibilities are that the estrogen potentiates the carcinogenicity of other compounds, either by changing their metabolism or by interfering with their excretion due to the cholestatic effects of synthetic estrogens.
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PMID:Oral contraceptives and hepatic tumors. 708 79

The final decade of the century confirms the importance of latest generation progestogens in terms of decreased risks associated with the use of doses of ethinyl estradiol of 50 gamma or more, equally effective in contraception of this type. These new combination very considerably limit the untoward effects seen in the past regarding carbohydrate and lipid metabolism, as well as cardiovascular disease. Concerning carcinogenesis, the long term protective effect against carcinomas of the endometrium and ovary is now accepted, while studies of breast cancer are not unanimous in their condemnation, the same applying to the risk of hepatocarcinoma. Regulation of cycles is satisfactory and the vaginal flora little affected. Moderate and stable fibroids seem to be well controlled, the same applying to mucosal hyperplasia. Pregnancy, particularly rare, is not influenced unfavourably and the effect on lactation appears to be nil. Provided that regular monitoring is ensured and contraindications are respected, age does not appear to be an absolute limiting factor to its use but the risk of concomitant smoking remains.
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PMID:[Current status of estrogen-progestational contraception]. 797 41


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