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

Ferromagnetic microembolization (FME) was applied to patients with hepatoma, using iron microspheres (30-50 mu), suspended in aqueous polysaccharide solution; dextran 40 (12%), sodium carboxymethyl-cellulose (2%) in saline solution. Hepatic arterial infusion of this agent was performed under external magnetic control to confine iron microspheres within the target organs. The therapeutic effect of this procedure on 44 patients with hepatoma was evaluated in relation to the stages of the disease, showing excellent, improved survival terms; survival rates calculated by Kaplan-Meier's method for patients with stage I to III hepatomas were 80% (1 year), 50% (2 years) and 30% (3 years). In order to extend the therapeutic effect of this procedure further, polysaccharide solution was also utilized as a carrier of anti-cancer agents. Serologic and histologic data in experimental animals showed evidence of prolonged release of Mitomycin from polysaccharide solution admixed, indicating its potential use as a method of chemo-embolization. In addition to this, we have also been developing the induction heating of the magnetic microspheres, introduced into the lesion by means of FME, to heat the lesion selectively. The procedure is still in the experimental phase. However, recent results strongly suggest the possibility of its clinical use. In conclusion, we consider FME to be one of the most reliable and potentially valuable methods for extending the capability of multidisciplinary treatment of hepatoma.
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PMID:[Embolotherapy of hepatomas using ferromagnetic microspheres, its clinical evaluation and the prospect of its use as a vehicle in chemoembolo-hyperthermic therapy]. 242 45

Effects of o-phenanthroline, 2,2'-dipyridyl and neocuproine, which form stable complexes preferentially with Fe(II), Fe(II) and specifically with Cu(I), respectively, on the inhibitory activity of bleomycin against DNA synthesis of rat ascites hepatoma AH66 cells were examined. The inhibitory activity of metal-free bleomycin was suppressed in the presence of o-phenanthroline or 2,2'-dipyridyl, but not by neocuproine, though these chelating agents also showed the inhibitory activity against the DNA synthesis of the cells by themselves alone. The activity of bleomycin-Cu(II) was also suppressed by o-phenanthroline, but bleomycin-Fe(II) and bleomycin-Fe(III) exhibited some activities in the presence of o-phenanthroline. The growth inhibitory activity of bleomycin against HeLa cells was also suppressed by o-phenanthroline. From these results, bleomycin-iron complexes were suggested to be responsible to the bleomycin action in cells.
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PMID:Effects of o-phenanthroline, 2,2'-dipyridyl and neocuproine on the activities of bleomycin to inhibit DNA synthesis and growth of cultured cells. 243 Sep 25

The occurrence of hepatocellular carcinoma in a 22-year-old man with thalassemia major is reported. As a result of transfusional hemochromatosis, this patient had already developed diabetes, hypogonadism, heart failure, and the sicca syndrome; he was serum and tissue HBsAg negative. Liver iron concentration measured postmortem was found to be 50 times normal. Multiply transfused patients are at risk of developing hepatocellular carcinoma. Serial measurements of serum alpha-fetoprotein should permit early detection of the tumor and reduce mortality. Preventive measures include early immunisation against hepatitis B virus and prevention of iron accumulation by intensive use of desferrioxamine. Treatment of hemochromatosis-associated hypogonadism with androgens should be considered with caution.
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PMID:Hepatocellular carcinoma in thalassemia major. 243 Dec 57

We here describe the morphologies of 9 macroregenerative nodules (MRNs) showing moderate to marked fatty change (fatty MRN) from 6 cases of non- or minimally-steatotic cirrhotic livers. In most of these cases, no obvious steatogenic factors of the liver were obtainable. These fatty MRNs showed more or less a sharp border. Seven of these fatty MRNs showed a variable degree of unusual morphological alterations suggestive of neoplasia: atypical and hyperchromatic nuclei, abnormal blood vessels, foci of clustering Mallory bodies, numerous hyaline globules, alpha-fetoprotein-positive hepatocytes, resistance to iron accumulation, infiltration into the portal tracts within MRN, and occurrence of hepatocellular carcinoma without fatty change. These observations suggest that at least some of the fatty MRNs are neoplastic or belong to a borderline lesion, and that the fatty change in the MRNs may be one of hepatocellular expressions related to human hepatocarcinogenesis.
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PMID:Fatty macroregenerative nodule in non-steatotic liver cirrhosis. A morphologic study. 250 Jul 68

The author reviews the problem of the pattern of lipid peroxidation in cancer cells with special reference to a comparison between normal liver cells and hepatomas both transplanted and induced by diethylnitrosamine. It is stated that the loss of lipid peroxidation is proportional to the degree of de-differentiation of hepatoma cells. During carcinogenesis, however, the loss is already evident at the stage of preneoplastic nodules. A common feature of all tumors, independently of the extent of the loss of peroxidation in basal conditions, is the lack of further stimulation by ADP/iron or by ascorbate/iron. As regards the reasons for the decline in lipid peroxidation, they are certainly not unique. An important cause is the low activity of the enzymes of the monooxygenase microsomal chain. Another very important one is the change in lipid composition of membranes, with a marked decrease in polyunsaturated fatty acids, which are the main substrate for lipid peroxidation. It has been shown that enrichment of membranes of hepatomas with arachidonic acid results in restoration of stimulation of peroxidation by ascorbate/iron, but not with ADP/iron. The last type of stimulation mostly reflects the behaviour of the monooxygenase chain, whereas ascorbate/iron-induced stimulation does not require the presence of an efficient cytochrome P450-chain. Another cause for decreased lipid peroxidation in tumors is the increased rigidity of membranes, due to the large increase in cholesterol content: this prevents to some extent the influx of oxygen inside the membranes. Yet another cause is the presence of increased amounts of antioxidants in both cytosol and membranes. The main toxic product of lipid peroxidation, 4-hydroxynonenal, has been found to elicit several actions at extremely low concentrations. In fact, 4-hydroxynonenal stimulates chemotaxis of polymorphonuclear leukocytes, stimulates plasma membrane adenylate cyclase, stimulates plasma membrane guanylate cyclase, and stimulates phospholipase C. The last three enzymes involve the action of G-proteins. The effect of the aldehyde is present at less than micromolar concentrations, which may occur inside the cells in certain conditions. Moreover, at concentrations from 10(-6) to 10(-7) M, the aldehyde is able to block oncogene c-myc expression in the human erythroleukemic K562 cell line, which at the same time becomes able to express the gamma-globin gene. These facts are discussed with reference to a possible biological meaning of the loss of lipid peroxidation in tumors.
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PMID:Lipid peroxidation and cancer: a critical reconsideration. 251 Mar 83

Using an indirect immunoperoxidase technique on frozen sections with the monoclonal antibody 96.5, we investigated the in situ distribution of melanotransferrin, a transferrin (Tf) and transferrin receptor (TfR) related glycoprotein, in human liver. Specimens included normal liver, liver in iron overload, hepatocellular carcinoma, angioma and foetal liver. On light microscopy, immunoreactivity was almost exclusively present on sinusoidal lining cells, apparently endothelial cells; the pattern was similar in normal and in iron-loaded liver. A gradient of more enhanced staining in acinar zone II and III was observed. The endothelial localization of the staining was supported by the positivity of the central vein endothelium and of the angiomas. Immunoelectron microscopy on three liver specimens showed positivity on sinusoidal endothelial cells but not on Ito and Kupffer cells. In addition, positivity on rough endoplasmic reticulum vesicles of some hepatocytes was also present. Four hepatocellular carcinomas showed an intense staining in tumour cells, 3 were weakly positive and 3 were negative. In the foetal livers, the central vein endothelium was positive from 21 weeks of gestation onward and additional positivity of zone III sinusoidal endothelial cells was present from 27 weeks on. The present results show that in the liver melanotransferrin has a localization different from Tf and the TfR. These latter molecules are predominantly localized in parenchymal cells. In addition, there does not appear to be a coordinate regulation secondary to iron storage, between melanotransferrin, Tf and the TfR. The observed gradient in the staining pattern in foetal and adult liver specimens further supports the heterogeneity of the endothelial cell population in the liver and suggests a developmental relationship between endothelial cells of sinusoids and central vein.
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PMID:In situ localization of melanotransferrin (melanoma-associated antigen P97) in human liver. A light- and electronmicroscopic immunohistochemical study. 254 Mar 89

In order to determine if iron was able to stimulate specifically ferritin synthesis and secretion in transformed human hepatocytes in culture, human hepatoma cell (HepG2) cultures were submitted to increasing doses of ferric nitrilotriacetate. Iron uptake by the cells was demonstrated by incorporation of 59 Fe and the staining method of Perls. The following results were obtained: 1. iron incorporation within the hepatocytes increased as a function of culture time; 2. during the first 24 h of treatment, ferritin synthesis increased progressively, in parallel to the iron uptake; 3. a dose-dependent significant stimulation of ferritin synthesis and secretion were observed when the medium iron concentration increased from 5 to 20 mumol/l; 4. albumin, transthyretin and transferrin secretions were unaffected. These data demonstrated that, in our hepatocyte culture model, iron load increased the expression of ferritin in a highly specific manner.
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PMID:Iron induction of ferritin synthesis and secretion in human hepatoma cell (Hep G2) cultures. 254 99

It has been pointed out that hepatocellular carcinoma (HCC) develops more frequently in cirrhotic liver with siderosis than in liver without iron deposition, that excess copper in hepatocytes inhibits hepatocarcinogenesis, and that an increase in copper and a decrease in zinc are seen in the sera of patients with various malignant tumors. Iron, copper and zinc concentrations in the serum and liver were estimated in normal subjects and cirrhotic patients with and without HCC. Serum copper level was significantly higher in cirrhotic patients with or without HCC than in normal subjects. No significant differences were observed in the levels of these trace elements in the serum and liver of cirrhotic patients with and without HCC. The current study seems to indicate that iron, copper and zinc do not play an important role in the development of HCC in cirrhotic patients in Japan.
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PMID:Iron, copper and zinc levels in serum and cirrhotic liver of patients with and without hepatocellular carcinoma. 255 Aug 61

Histochemical markers are important for the early detection of chemically initiated neoplasia in experimental animal studies. The marker, iron resistance, was evaluated in the Shasta strain of rainbow trout (Salmo gairdneri). Twenty-one-day-old trout embryos were exposed to 100 ppm aqueous N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 30 min in a static water bath. Fish were fed a semipurified diet, and sampled monthly from the 4th to the 9th month. Two days before sampling, fish were iron-loaded with a single ip dose of 0.30 mg iron dextran/100 g body weight. Livers and kidneys were conventionally processed to paraffin sections for iron, or hematoxylin and eosin (H&E) staining. Normal hepatocytes accumulated iron in pericanalicular locations, but in hepatocytes from carcinogen-altered foci and tumors, iron staining was clearly reduced or absent. Normal renal tubule cells exhibited slight to moderate iron staining, while those from nephroblastoma were iron resistant. These results establish iron resistance as a property of preneoplastic and neoplastic trout hepatocytes and nephroblastoma cells for the first time. Iron resistance may offer a practical histochemical marker in experimental fish models of hepatocellular carcinoma and nephroblastoma.
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PMID:Iron resistance of hepatic lesions and nephroblastoma in rainbow trout (Salmo gairdneri) exposed to MNNG. 255 78

The cellular uptake and lysosomal accumulation of 67Ga-labelled transferrin within tumors of different malignancy were examined using tissue fractionation and immunological techniques. As tumor models the slowly growing Morris hepatoma 5123 C, the moderately growing Novikoff hepatoma and the fast and aggressive Yoshida hepatoma AH130 were investigated. Isolation of subcellular fractions of tumor homogenates was performed by differential centrifugation and density-gradient centrifugation. The intracellular 67Ga-transferrin was found to be highly concentrated within the purified lysosomes. The transferrin within the lysosomal fraction was identified by radial immunodiffusion technique using monospecific antiserum. The accumulation of 67Ga-transferrin by the tumors resulted in a faster disappearance of 67Ga-transferrin from the blood. This loss of circulating 67Ga-transferrin correlated with the proliferation activity and the spread of the tumors. Since transferrin is indispensible for the utilization of iron by the heme-synthesizing red cell precursors, transferrin concentration in the blood is the limiting factor for the utilization of iron in hemoglobin synthesis. Thus, in a further series of experiments we investigated the development of anemia in tumor-bearing rats. With increasing tumor mass a progressive fall of hemoglobin concentration was found. The anemia was more severe in the faster growing Novikoff hepatoma than in the slowly growing Morris hepatoma. The most significant reduction of hemoglobin concentration was found in the very fast growing Yoshida hepatoma. After total tumor resection hemoglobin concentration and red blood cell count normalized completely within 6-8 weeks. We conclude from these data that the uptake of transferrin by the tumor cells results in a faster disappearance of transferrin from the blood.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Anemia in malignant tumor diseases. II. Tumor-induced loss of transferrin as a cause of the development of anemia based on a rat model]. 260 49


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