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)

Soluble transferrin receptor (sTfR) in serum of cancer patients was measured by a sandwich enzyme-linked immunosorbent assay, and the effect of sTfR for natural killer cytotoxicity was also studied. The statistical values of sTfR levels in sera were found to be 250 +/- 77 U (Mean +/- SD) in healthy individuals, while 288 +/- 162 U in chronic liver disease, 402 +/- 290 U in hepatocellular carcinoma, 429 +/- 261 U in gastric cancer, 347 +/- 207 U in acute leukemia and malignant lymphoma, and 251 +/- 100 U in other cancer. No significant difference in the sTfR levels among the patients was observed, although the difference between the healthy individuals and the patient groups was shown to be statistically significant at p less than 0.01 level. The effect of sTfR isolated from serum of a patient with iron-deficiency anemia by means of Sephadex G-200 column for natural killer activity was carried out. Cytotoxicity of natural killer cell in healthy individuals was inhibited by sTfR as the dose dependent manner, and the inhibitory rate was found to be 23.1 +/- 12.8% (Mean +/- SD) when the concentration of the sTfR was 1,250 U added in the cytotoxicity test. Furthermore, the inhibitory activity of serum in cancer patients was correlated with the sTfR level. These results suggest that sTfR is one of the inhibitory factors for the natural killer cell activity in vivo, and the factor could be facilitated for tumor growth and metastasis. Therefore, the measurement of sTfR in serum may be useful for monitoring immunological competency in cancer patients.
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PMID:[Elevation of soluble transferrin receptor substance in serum of cancer patients with suppressed natural killer activity]. 261 80

Transferrin (Tf), the iron transport protein of vertebrate serum, is mainly synthesized in the liver. cis-Acting DNA elements required for liver-specific expression of the human Tf gene were identified by transient and stable expression assays in human hepatoma (HepG2 and Hep3B) and epithelial carcinoma (HeLa) cell lines. Deletion analysis of the 5' DNA sequences of the gene have defined four functionally different regions: (a) A cell type-specific promoter located between positions -125 and -45 which interacts with two nuclear factors and is sufficient for liver-specific expression. (b) A distal promoter region from -620 to -125 base pairs containing positive and negative cis-acting elements which regulate the promoter activity. (c) A negative-acting region between -1.0 and -0.6 kilobase pairs which down-regulates transcription from the Tf promoter. (d) An enhancer located between -4.0 and -3.3 kilobase pairs which is more active in hepatoma than in HeLa cells. Thus, Tf gene expression is modulated by a combination of multiple positive and negative cis-acting elements. The expression results are discussed with respect to our previous description of the trans-acting factors interacting with the proximal and distal promoter regions.
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PMID:Cell type-specific expression of the human transferrin gene. Role of promoter, negative, and enhancer elements. 270 61

Iron deposits in the human labial minor salivary glands were examined in a series of 195 postmortem subjects. Iron deposits (hemosiderin granules) were found in 7 subjects (3.6%), and the major types of illness in these cases were liver cirrhosis with or without hepatoma, aplastic anemia and acute myelogenous leukemia. Three out of 7 subjects had a history of blood transfusion. Considerable quantities of hemosiderin granules were deposited within the cytoplasm of the acinar and ductal epithelial cells, and hemosiderin-laden cells were scattered in the interstitial connective tissue.
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PMID:Iron deposits in the human labial minor salivary glands: a postmortem study. 273 86

Resistance to iron accumulation is known as a phenotypic marker of neoplasia and preneoplasia in experimental hepatocarcinogenesis in rodents overloaded by iron. This study was aimed to evaluate whether such iron-free foci are present and valuable for identification of preneoplastic and incipient neoplastic lesions in human cirrhotic livers, especially within macroregenerative nodules in which hepatocellular carcinoma is known to arise. Iron-free foci were found in siderotic macroregenerative nodules in liver cirrhosis. These foci were classic and overt carcinoma or borderline lesions showing an expansive growth pattern. Borderline lesions were composed of hyperplastic or small basophilic hepatocytes with hyperchromasia and distinct nuclear membrane showing pseudoglandular, trabecular, compact, and scirrhous patterns. These data suggest that iron stain is valuable for identification of neoplastic or borderline lesions representing a transition from hyperplastic nodule to carcinoma in human liver cirrhosis.
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PMID:Iron-negative foci in siderotic macroregenerative nodules in human cirrhotic liver. A marker of incipient neoplastic lesions. 275 93

Recently, macroregenerative nodules in cirrhotic livers have been suspected to be among the putative precancerous lesions in human hepatocarcinogenesis. We examined the morphologies of 99 macroregenerative nodules in 44 cirrhotic livers with special emphasis on stainable iron. In 26 macroregenerative nodules (26%), stainable iron selectively accumulated within the macroregenerative nodules themselves, and little or no iron was found in the surrounding regenerative nodules. In nine macroregenerative nodules (9%), an appreciable amount of stainable iron was present in both the macroregenerative nodules and the surrounding regenerative nodules. In the remaining 64 macroregenerative nodules (65%), stainable iron was absent in both the macroregenerative nodules and the surrounding regenerative nodules. Hyperplastic hepatocellular foci were present within 19 (73%) of the 26 iron-accumulative macroregenerative nodules, one (11%) of the nine iron-positive macroregenerative nodules and 20 (31%) of the 64 iron-negative macroregenerative nodules. These findings suggest that iron-accumulative macroregenerative nodules are frequently associated with hyperplastic hepatocellular foci and should be included among the precancerous lesions in human hepatocellular carcinoma.
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PMID:Survey of iron-accumulative macroregenerative nodules in cirrhotic livers. 280 65

Liver catalase activity, one of the free-radical scavenger enzymes, has been measured in 22 normal subjects and compared with that of 13 patients suffering from hepatocellular carcinoma. The activity was estimated both in tumor tissue and in tumor-free tissue. A significant reduction of catalase activity was noted in tumor tissue (p less than 0.001) as well as in the adjacent tumor-free tissue (p less than 0.02). In patients with hepatoma, the serum iron level was lower than in normal (p less than 0.01) and was correlated with enzyme activity (r = 0.958). These findings suggest that in hepatocarcinoma the free radical scavenger system is impaired.
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PMID:Catalase activity in human hepatocellular carcinoma (HCC). 283 48

Hemopexin alters conformation upon binding heme as shown by circular dichroism (CD), but hemopexin binds the heme analog, iron-meso-tetra-(4-sulfonatophenyl)-porphine (FeTPPS), without undergoing concomitant changes in its CD spectrum. Moreover, FeTPPS, unlike heme, does not increase the compactness of the heme-binding domain (I) of hemopexin shown by an increased sedimentation rate in sucrose gradients. On the other hand, like heme, FeTPPS forms a bishistidyl coordination complex with hemopexin and upon binding protects hemopexin from cleavage by plasmin. Competitive inhibition and saturation studies demonstrate that FeTPPS-hemopexin binds to the hemopexin receptor on mouse hepatoma cells but with a lower affinity (Kd 125 nM) more characteristic of apo-hemopexin than heme-hemopexin (Kd 65 nM). This provides evidence that conformational changes produced in hemopexin upon binding heme, but not upon binding FeTPPS, are important for increasing the affinity of hemopexin for its receptor. The amount of cell-associated radiolabel from 55FeTPPS-hemopexin increases linearly for up to 90 min but at a rate only about a third of that of the mesoheme-complex. As expected from the recycling of hemopexin, more iron-tetrapyrrole than protein is associated with the Hepa cells, but the ratio of 55Fe-ligand to 125I-hemopexin is only 2:1 for FeTPPS-hemopexin compared to 4:1 for mesoheme complexes. [55Fe]Mesoheme was associated at 5 min with lower density fractions containing plasma membranes and at 30 min with fractions containing higher density intracellular compartments. In contrast, 55FeTPPS was found associated with plasma membrane fractions at both times and was not transported into the cell. Although FeTPPS-hemopexin binds to the receptor, subsequent events of heme transport are impaired. The results indicate that upon binding heme at least three types of conformational changes occur in hemopexin which have important roles in receptor recognition and that the nature of the ligand influences subsequent heme transport.
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PMID:Importance of ligand-induced conformational changes in hemopexin for receptor-mediated heme transport. 283

Previous reports have emphasized the association of primary hepatocellular carcinoma in patients with idiopathic hemochromatosis with cirrhosis. In contrast, patients with idiopathic hemochromatosis without cirrhosis have no increased risk of hepatocellular carcinoma. Phlebotomy therapy, by preventing the accumulation of parenchymal iron and subsequent cirrhosis, is believed to prevent hepatocellular carcinoma in the precirrhotic stage of the disease. We report the case of a 67-yr-old man with a 32-yr history of idiopathic hemochromatosis complicated by cirrhosis, who had reversal of cirrhosis with phlebotomy therapy, yet developed hepatocellular carcinoma. There was no serologic or tissue evidence of hepatitis B infection.
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PMID:Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. 284 22

Intracellular movement of cell surface 5'-nucleotidase was studied in H4S cells, a rat hepatoma cell line. Surface labelled cells were incubated for various periods at 37 degrees C and treated with neuraminidase at 0 degrees C. Removal of sialic acid residues from glycoproteins results in a change of their isoelectric points. Analysis with isoelectric focusing was then used to distinguish between cell surface and intracellular 5'-nucleotidase. Incubation of 125I-surface-labelled cells at 37 degrees C resulted in a gradual decrease of labelled 5'-nucleotidase at the plasma membrane until, at 60 to 90 min, a steady state was reached with 52% of the label on the cell surface and 48% intracellular. Pretreatment of the cells with the weak base primaquine had no influence on this distribution while at the same time uptake of iron via the transferrin receptor was inhibited. Using immunoelectron microscopy 5'-nucleotidase was found on the cell surface, in multivesicular endosomes and the Golgi complex. Preincubation of the cells in the presence of cycloheximide caused a reduction of labelling in the Golgi complex, whereas the label in the other compartments was retained. These results lead to the conclusion that 5'-nucleotidase does not recycle through the Golgi complex and that in contrast to the transferrin receptor the recycling of 5'-nucleotidase is not inhibited by primaquine.
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PMID:Recycling of 5'-nucleotidase in a rat hepatoma cell line. 285 Jan 62

Two patients with primary haemochromatosis are reported in whom hepatocellular carcinoma supervened despite removal of excess iron after venesection therapy. These are the first patients described in whom hepatocellular carcinoma has complicated primary haemochromatosis in the absence of concomitant cirrhosis.
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PMID:Hepatocellular carcinoma in primary haemochromatosis in the absence of cirrhosis. 285 Feb 72


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