Malignant Hepatoma Research Articles

Effect of benzo(a)pyrene on monolayer cultures of normal and malignant mouse liver cells

Both the cells of monolayer culture of mouse embryonic liver and that of highly malignant hepatoma 22A transplanted for 20 years actively metabolized the carcinogenic hydrocarbon benz(a)pyrene and were highly sensitive to iits toxic action. Since hepatic tissue was resistant in vivo to carcinogenic carbohydrates it is suggested that the resistance depended on factors acting at the organ or the organism but not as the cellular level. The mechanism of retention of hepatoma 22A sensitivity to the toxic action of benz(a)pyrene is also discussed.

Alpha-Fetoprotein screening in patients with idiopathic hemochromatosis and liver cirrhosis.

The serum alpha-fetoprotein level was measured by radioimmunoassay in 200 patients when admitted to hospital, 63 with idiopathic hemochromatosis and 137 with liver cirrhosis. In addition, repeated controls were performed in 19 subjects of each group for a mean period of 11 months (range 3--18 months). Elevated alpha-fetoprotein levels were observed initially or during the study period in 15 patients, a malignant liver tumor being demonstrated in 12 of them. In 4 of these patients, the abnormal alpha-fetoprotein concentration was the clue to the diagnosis of an unsuspected malignant hepatoma, but in none of these cases could the tumor be resected. The present results indicate that screening the serum alpha-fetoprotein level may contribute to the detection of malignant hepatoma in high-risk clinical groups, but the practical interest of such screenings may keep limited until more efficient therapeutic methods are developed.

A STUDY ON MALLORY BODIES

Mallory bodies (MBs) were isolated from the livers of 8 alcoholic patients and a malignant hepatoma occurring in a non-alcoholic patient. MBs were isolated in large quantity and high purity. The isolates were devoid of liver cell organelles except in the case of malignant hepatoma where dense and membranous material resembling nuclear substances and endoplasmic reticulum were found. The "nuclear" material had continuity with MBs. Electron microscopic examination suggested the presence of a dense body and very fine filaments within in situ and isolated MBs in addition to the tubular structure of so-called MB fibers. Amino acid analysis indicated that the major component of MBs is a protein which does not contain unusual amino acids or any particular amino acid in a large quantity to characterize this protein. The isolated fractions were solubilized in 6 M guaindine hydrochloride by sonication or in 1% sodium dodecyl sulfate (SDS) with 2 mercaptoethanol and 8 M urea. The solubilized MB protein produced 3 peaks by Sephadex G 100 chromatography and at least five intense protein bands by SDS polyacrylamide gel electrophoresis. Serum sample and the fractions from control livers contained several protein bands which were similar to the major components of isolated MB protein. These morphological and biochemical findings suggest that MBs are not homogeneous protein, but they are probably complexes of various proteins and that some components of MBs are present in normal hepatocytes.

Long Term Results of Venesection Therapy in Idiopathic Haemochromatosis

Observations on the clinical effects of venesection therapy in 85 treated, as compared with 26 untreated, patients with idiopathic haemochromatosis showed decreased pigmentation and hepatomegaly together with a return to normal tests of liver function in half the patients who had abnormal tests at presentation. Control improved in 28 per cent of those patients with diabetes mellitus, although some patients developed it during the period of observation, despite venesection. Portal hypertension, testicular atrophy and arthropathy were not improved. In only 12 patients was there sufficient reaccumulation of iron after the initial course of venesection to merit further treatment. Rates of iron accumulation in these patients varied between 1-4 mg and 4-8 mg per day and chelatable iron levels were noted to be inappropriately high in relation to body iron stores during the early stages of the reaccumulation period. Life table data shows that the percentage survival five and ten years after diagnosis was 66 and 32 per cent respectively for the treated patients, and 18 and 6 per cent respectively for the untreated patients, both statistically highly significant differences (p less than 0-01). Possible clinical differences such as age of presentation, the presence of diabetes mellitus, cirrhosis, clinical hepatic failure and hepatoma between the treated and untreated groups that might otherwise have weighted survival in favour of the treated group were corrected by the use of covariant analysis. This gave mean log survival values of 4-15 and 2-88 for the treated and untreated patients respectively, equivalent to 63-4 months and 17-8 months, a highly significant difference (p less than 0-01). Ten patients, all of whom had cirrhosis at the time of diagnosis, died of malignant hepatoma between three and 15 years after completing venesection therapy. There was also a high rate of death from neoplasms in a variety of other sites--22 per cent in the venesected group, strikingly higher than that rate predicted for a similarly aged population using national cancer mortality rates.

Gangliosides of Hepatoma 27, Normal and Regenerating Rat Liver

The highly malignant rat hepatoma 27 was found to have increased amounts of lipid-bound sialic acid as compared with normal liver whereas in regenerating liver the lipid-bound sialic acid level was reduced. In contrast to the liver the hepatoma contained higher amounts of disialogangliosides and no trisialogangliosides, which are abundant in the liver. The main disialoganglioside of the hepatoma had no analogue among the liver gangliosides and was identified as Gal-GalNAc(AcNeu-AcNeu)-Glc-Cer (GD1b), which in other tissues is known to be a precursor of trisialogangliosides. These findings may be explained by a reduced activity of glycosyltransferases in the hepatoma and apparently do not simply reflect differences in growth rate since the ganglioside pattern of regenerating rat liver was not altered significantly in comparison with the liver. Liver and hepatoma microsomes were found to be enriched in gangliosides as compared with whole cells, liver mitochondria were slightly poorer, while the ganglioside level of hepatoma mitochondria was much higher than that of the hepatoma cells. It thus appears that the existing image of the plasma membranes as the only sites of high ganglioside concentration may not hold true for weakly differentiated hepatomas of high malignancy.

Alpha-l-antitrypsin Deficiency and Liver Disease in Adults

Thirteen adult patients (aged 16 to 73 years) from 12 families are described with liver disease and alpha-l-antitrypsin deficiency. Long-term observation of several of these patients suggests that the liver disease may be only slowly progressive, but review of possible factors aggravating this has failed to reveal any obvious clues. Progression to death from hepatic failure was the commonest outcome, but one patient developed a malignant hepatoma and two others died because of intraperitoneal haemorrhage due to ruptured cirrhotic nodules—a complication not hitherto described in association with this condition. Diagnosis of alpha-l-antitrypsin deficiency was based on serological, histological, immunopathological and genetic studies. The most useful screening test in liver disease was found to be the demonstration of PAS positive globules in liver biopsy material which is diagnostic when shown to be antigenically identical with alpha-l-antitrypsin by immunofluorescence or immunoperoxidase, the latter being a superior technique. Serum estimation of alpha-l-antitrypsin deficiency was performed by immunoelectrophoretic and immunodiffusion techniques, the former being preferred because it gave more consistent results. Both methods, however, were of limited value since wide variations in the serum values are commonly found in normal and abnormal states. Genotyping was carried out using starch gel electrophoresis and although of value in family studies, its value as a diagnostic aid is limited because of technical difficulties and also because alpha-l-antitrypsin accumulation in the liver may be found in both homozygous and heterozygous states. It is suggested that adult liver disease associated with abnormalities in alpha-l-antitrypsin may be more common than has hitherto been reported. This condition should be systematically sought in all cases of liver disease of uncertain aetiology.

Hepatic Changes in Young Women Ingesting Contraceptive Steroids

Primary hepatic tumors developed in 13 young women who had been ingesting contraceptive steroids. Nine tumors were benign, and four malignant. Six tumors ruptured spontaneously and caused life-threatening hemorrhage. Benign tumors were successfully resected in eight women. One woman died during hepatic resection for malignant hepatoma; in two other cases of hepatocellular carcinoma, tumors were nonresectable. In two patients, the tumor was left in situ after neoplasm had been excluded by biopsy. The increase of such tumors in women of childbearing age warrants the suspicion that these contraceptive steroid hormones play an etiologic role.

Malignant Hepatoma Associated With Acquired Hepatic Cutaneous Porphyria

A 60-year-old woman with a three-year history of an acquired hepatic cutaneous porphyria was discovered to have a porphyrin-producing malignant hepatoma. An attempt was made to treat her with fluorouracil perfused through a hepatic artery catheter. It did not produce shrinkage of the tumor, but the patient remains alive and ambulant a year after the infusion, although her skin lesions (scarring, bulla formation, and hyperpigmentation) on the fingers, back of hands, and face persist and she continues to excrete abnormally high quantities of porphyrin in her feces.

Malignant hepatoma associated with acquired hepatic cutaneous porphyria

Malignant hepatoma associated with acquired hepatic cutaneous porphyria

Leberkarzinom bei einem Kind nach siebenjähriger kompletter Remission einer akuten Lymphoblastenleukämie

A malignant hepatoma occurred in a 12-year-old girl who eight years previously had developed an acute lymphoblastic leukaemia which for eight years had been in complete haematological remission. Fourteen months after the last re-induction treatment period had been discontinued, but while on methotrexate and 6-mercaptopurine maintenance, a hepatocellular liver carcinoma developed of which the patient died after a fulminating course, still in complete haematological remission. As far as is known, no direct carcinogenic effect can be ascribed to the two antimetabolites, but it must be assumed that these two drugs, taken by the patient for over seven years, led to cirrhosis of the liver whose malignant transformation was significantly influenced by the immunosuppressive effects of methotrexate and 6-mercaptopurine, given as maintenance therapy according to protocol 02 LA 64, Paris.

Australia Antigen and Malignant Hepatoma

Excerpt In 1970 Sherlock and co-workers (1) were the first to describe five cases of malignant hepatoma associated with a positive Au(1) serologic test. Some months later, there was a report of a h...

Systemic effect of the tumor on the host: Biochemical and endocrine manifestations

A few illutrations of the specific effect of different tumors on the remote tissues of the host are given. There was a significant reduction in the proportion of liver polyribosomes synthesizing serum albumin in rats bearing Guérin carcinoma and Schwetz leukemia and a 2- to 3-fold increase in the relative amount of liver free ribosomes versus membrane-bound ones in the rats with Zaidela hepatoma, a phenomenon typical of the tumor itself. In liver cell plasma membranes (PM) of C3HA mice carrying a highly malignant Guelstein hepatoma 22a a hexokinase appeared whose activity could be revealed at very low concentrations of substrate like hepatoma PM enzyme, whereas PM hexokinase of liver from “benign” guelstein hepatoma's host did not differ from that of normal liver. A reduced response to cortisol of rat liver from the Zaidela hepatoma's host was observed in the in vitro system (only a slight stimulation of RNA synthesis in isolated nuclei). No stimulation of glycogen synthesis in liver by insulin in mice bearing Ehrlich carcinoma could be detected. All the metabolic alterations listed above are regarded as the manifestations of the way the tumor destroys the homeostasis of the host.

Radioimmunoassay of alpha-fetoprotein in human serum: clinical value in patients with liver diseases.

A radioimmunoassay for human α1-fetoprotein (AFP) has been developed. Serum AFP level was measured in 136 healthy adults, the mean value±sd being 3.8±1.3 ng/ml of serum. 34 patients with primary hepatocellular carcinomas all had abnormal serum AFP concentrations, values in 5 of them (14%) being lower than 500 ng/ml. 4 of 19 patients with liver metastasis and 39 of 118 patients with nonneoplastic liver diseases had AFP concentrations scattered between the upper limit of normal (7.7 ng/ml) and 500 ng/ml. Thus, a moderately elevated serum AFP level cannot be granted for the diagnosis of malignant hepatoma. Although a transitory rise of AFP concentration was observed in a patient with hemochromatosis and no detectable liver tumor, serum AFP level was found stable with time. Sensitive radioimmunoassays for AFP may prove useful for the follow-up of patients with nonneoplastic liver diseases and a high risk of hepatocellular carcinoma.

Specific immunodiagnosis of hepatocellular carcinoma by leucocyte adherence inhibition.

The leucocyte adherence inhibition test provides a rapid, reliable, and specific technique for the immunodiagnosis of primary hepatocellular carcinoma (malignant hepatoma). The patient's blood leucocytes are tested in vitro for cell-mediated immunity against tumour-associated antigens and the serum is tested for blocking factor which interferes with the immunological reaction. Specific reactivity of both leucocytes and serum was consistently detected in patients with malignant hepatoma, and negative reactions were obtained in other liver diseases including secondary tumours of the liver. The test has provided positive evidence for the presence of hepatoma when more conventional methods gave doubtful or negative results. A positive result preceded the clinical appearance of tumour by up to three years in two patients.

Cirrhosis and malignant hepatoma in alpha 1-antitrypsin deficiency.

Abstract. Clinical and laboratory findings in 9 adults with homozygous (Pizz) α1‐antitrypsin (AAT) deficiency and cirrhosis of the liver are described. This clinical entity is characterized by rapidly progressive cirrhosis in non‐alcoholics above 50 years of age, resulting in severe portal hypertension and death in hepatic coma or bleeding. Concomitant emphysema, often subclinical, is usually present and malignant hepatoma is common. Histologically typical PAS‐positive inclusion bodies are always demonstrable. Cholestatic features are not prominent. The entity is not associated with the HAA antigen, and serum “auto‐antibodies” are lacking. In addition to AAT deficiency the serum protein analysis reveals the pattern seen in cirrhosis of other etiology, but in most cases the IgM level was unusually high. The pathogenetic mechanism leading to cirrhosis in a minority, at most 10% of adult patients with the Pizz phenotype remains obscure.

Hepatic Parenchyma Weight Changes in the Presence of Primary and Secondary Tumors of the Liver: A Morphometric Study

Fifty livers with carcinoma and sarcoma metastases, malignant lymphoma, or malignant hepatoma were studied; 47 livers were from adult patients. Although most livers had widespread tumor involvement (particularly in the anatomic right lobe), morphometric studies revealed that the hepatic parenchyma of all but six (13%) of the adult livers weighed more than 1 kg. Only two of the eight cases with hepatic failure had parenchyma that weighed less than 1 kg. Twenty-eight per cent of the tumor-bearing livers had parenchyma weights that exceeded the estimated 95 th percentile in nontumor controls. The hepatic parenchyma weight in these instances more often seems to be increased rather than decreased. If there is a decrease of hepatic parenchyma, this is rarely sufficient to cause hepatic failure. The median hepatic parenchyma weight in livers with tumor was greater than of a tumor-free control group. No relationship was noted between hepatic parenchyma weight and clinical evidence of hepatic failure, body weight changes, sex, age, and type, distribution or weight of tumor within the liver. Fünfzig Lebern mit Karzinom- und Sarkommetastasen, malignen Lymphomen oder malignen Hepatomen wurden untersucht: 47 Lebern stammten von Erwachsenen. Obwohl die meisten Lebern stark von Tumormetastasen durchsetzt waren (besonders im anatomischen rechten Lappen), ergaben morphometrische Untersuchungen, daβ mit Ausnahme von 6 Fällen (13%)) alle Erwachsenenlebern Parenchymgewichte von mehr als 1 kg hatten. In nur 2 der 8 Fälle, die im hepatischen Koma oder Präkoma gestorben waren, lag das Leberparenchymgewicht unter 1 kg. Achtundzwanzig Prozent der tumortragenden Lebern hatten höhere Parenchymgewichte als die, die als obere Norm der tumorfreien Kontrollen bestimmt worden waren. Das Parenchymgewicht tumortragender Lebern scheint häufiger vermehrt anstatt verringert zu sein. Selbst wenn eine Leberparenchymverminderung vorhanden ist, scheint sie selten schwer genug zu sein, um ein Leberversagen zu verursachen. Das mittlere Parenchymgewicht in tumortragenden Lebern war gröβer als das der tumorfreien Kontrollen. Wir fanden keine Zusammenhänge zwischen Leberparenchymgewichten und anderen Faktoren, wie Leberversagen, Körpergewichtsveränderungen, Geschlecht, Alter und Art, Verteilung oder Gewicht der Tumoren in der Leber.

Differential diagnosis of primary malignant hepatoma in 569 Bantu mineworkers.

Five hundred and sixty-nine Bantu male patients with hepatomegaly were referred for investigation for possible primary cancer of the liver. This diagnosis was confirmed histologically in 353 patients, and there were an additional 10 probable cases not proved histologically. Other diagnoses were: cirrhosis—63 patients (11.0%); tuberculosis—43 patients (7.5%); amebiasis—29 patients (5.1%); heart failure—16 patients (2.8%); infective hepatitis—12 patients (2.1%); metastatic cancer—20 patients (3.5%), miscellaneous—23 patients (4.0%).

Primary hepatoma and hepatitis-associated antigen in a young white woman.

A young woman whose serum was positive for hepatitis-associated antigen (H.A.A.) and alpha-fetoprotein developed a malignant hepatoma. Though the light-microscopical appearances of the surrounding liver tissue were normal, electronmicroscope examination of the tumour tissue disclosed both C-virus-like particles and H.A.A. particles. Possibly there was a causal connexion between one of these particles and the hepatoma.

Primary cancer of the liver following treatment of polycythaemia vera with radioactive phosphorus.

There are two types of primary cancer of the liver: carcinoma of the liver-cells (hepato-cellular carcinoma, malignant hepatoma) and carcinoma of the bileducts (cholangio-cellular carcinoma, cholangiocarcinoma). While many tumours fall into one of these two types, tumours of mixed structure also occur (Willis, 1960). Primary cancer of the liver is rare in whiteskinned peoples, in whom it is found in 0·1 to 0·3 per cent of all necropsies (Stewart, 1931), or in about 1 per cent of necropsies on cases of malignant disease. It is much commoner in the Bantu, Javanese, Chinese and Japanese. It occurs more frequently in males than in females, the ratio ranging between 2:1 and 12:1 in various reported series. In recently published series by Kew, Dos Santos and Sherlock (1971) there were 66 males and nine females. A great number of cases of primary cancer of the liver are associated with cirrhosis of the liver. The incidence of pre-existing cirrhosis in hepatocellular carcinoma varies from 39 per cent to 89 per ce...

The electrophoretic changes of mammalian cells associated with malignant transformation.

The significance of electro kinetic properties of tumor cells can not be accurately assessed without also considering cytogenetic variations between cells and differences In their rates of proliferation. The original assumption that elevated charge densities and increased susceptibility to neuraminidase characterizing tumor cells in general, was confirmed mainly by observations of malignant hepatoma cells in the present study. It was also found that the only property common to both leukemic cells and other malignant cells was an increased susceptibility to neuraminidase. The immunological effects of host animals to the electrophoretic mobility in the transplantable tumor cells were also analysed.