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)

The extracellular matrix adhesion molecule fibronectin exhibits different isoforms derived by alternative splicing as well as recently demonstrated variation in O-glycosylation. Although fibronectin is widely distributed in normal tissues, the individual isoforms have been found to show restricted tissue distribution and association with malignancies. The monoclonal antibody FDC-6 defines a cancer-associated de novo glycosylation of a specific threonine residue in the C-terminal region of the fibronectin molecule termed oncofetal fibronectin. Here we report an immunohistological study of oral squamous cell carcinomas (n = 33), premalignant lesions (n = 15), and normal oral mucosa (n = 10) using the FDC-6 antibody. A selective expression of the oncofetal fibronectin epitope was demonstrated in close relation to the invading carcinoma, whereas no staining was observed in premalignant lesions without epithelial dysplasia, or in normal epithelium. Furthermore, we attempted to identify additional carbohydrate-related epitopes distinguishing fibronectin of human hepatoma cell line HUH-7 from plasma fibronectin. No novel epitopes were identified, as all generated monoclonal antibodies lacking reactivity with plasma fibronectin showed the same specificity as FDC-6. Previous studies have indicated that the de novo glycosylation is induced by a novel transferase activity only found in fetal and carcinoma cell lines, placenta and hepatoma tissues. Here we provide further evidence that a purified UDP-GalNAc:peptide N-acetylgalactosaminyltransferase from normal bovine thymus and human placentae is incapable of utilizing the hexapeptide VTHPGY as a substrate. The results demonstrate that oncofetal fibronectin is highly associated with malignancy, and appears to be induced by expression of a unique glycosyltransferase or modification of the specificity of the normally expressed transferase.
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PMID:Cancer-associated changes in glycosylation of fibronectin. Immunohistological localization of oncofetal fibronectin defined by monoclonal antibodies. 138

We evaluated the applicability of limited hepatic resection in cases of hepatocellular carcinoma (HCC) in cirrhotic patients. According to the severity of impaired hepatocellular function, 37 patients underwent limited resection, and for 13, standard major hepatic resection was done. There were no significant differences in the mortality and survival rates between the two groups. This limited resection can be selectively used to treat cancer associated with cirrhosis and encapsulated tumors. For further evaluation of this limited procedure, an attempt was made to elucidate the manner in which the surgical margin is linked to a recurrence after curative resection for hepatocellular carcinoma in patients with cirrhosis. Forty patients were divided into two groups; those in whom the margin from the cut surface to HCC in the fresh specimen was less than 10 mm wide [TW(+)] and patients in whom the surgical margin was equal to or exceeded 10 mm [TW(-)]. There were 24 and 16 patients in the TW(+) and TW(-) groups, respectively. There was no statistically significant difference in the rate of recurrence between the two groups. In patients with a tumor less than 4 cm in diameter, the extent of TW is not linked to an early recurrence. However, when the tumor size exceeds 4 cm, 10 mm of TW is inadequate to achieve curability. When a wide resection is not feasible, then adjuvant therapy should be aggressive.
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PMID:Surgical strategy for primary hepatocellular carcinoma associated with cirrhosis. 215 25

Cathepsin D was purified to apparently homogeneous form from normal human liver and hepatoma. The purified enzyme could not be distinguished between normal liver and hepatoma in terms of specific activity, subunit composition, antigenicity, amino acid composition and tryptic peptides. However, the hepatoma enzyme exhibited more charge heterogeneity to give multiple acidic variant forms which were devoid or much less in the normal liver enzyme. When the hepatoma enzyme was treated with endo-beta-N-acetylglucosaminidase H, the acidic variant forms disappeared and were converted into forms identical to those of normal liver. The content of mannose-6-phosphate in the hepatoma enzyme was twice as much as that in the normal liver enzyme. Thus, charge heterogeneity found in hepatoma cathepsin D is ascribed to increased phosphorylation on oligosaccharides bound to the enzyme, most probably due to cancer-associated, impaired processing in carbohydrate moiety. A significant elevation of cathepsin D activity per tissue proteins was observed in hepatoma as compared to normal liver. In contrast, true specific activity per cathepsin D protein in hepatoma was significantly lowered than that of normal liver. The lower true specific activity in hepatoma tissue may be attributed to an increased content in an inactive, large-molecular precursor form of the enzyme.
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PMID:[Tumor-associated impairment of the processing of hepatoma cathepsin D]. 283 81

Ricinus communis agglutinin II-reactive glycoproteins from the ascites of patients with hepatocellular carcinoma were prepared using lectin affinity chromatography. Normal serum- and cirrhotic ascites-components were removed by columns with immobilized antibodies against them. Ricinus communis agglutinin II-reactive glycoproteins thus obtained were supposed to be hepatocellular carcinoma-associated and less than 0.1% of the protein in the starting material. Polyacrylamide gel electrophoresis of these glycoproteins revealed more than 10 major polypeptides with molecular weights ranging from 20K to 200K daltons. The rabbit antiserum raised against them reacted with at least three components of 45, 52 and 55K daltons. The serum level of this antibody-reactive glycoproteins was assessed by an enzyme-linked immunosorbent assay. It was elevated in 91% of cases of hepatocellular carcinoma, 70% of cases of other gastrointestinal carcinoma, 88% of cases of liver cirrhosis, 55% of cases of chronic hepatitis, and 25% of cases of acute hepatitis. The mean value of hepatocellular carcinoma was significantly greater than those of other groups. These results suggest that some of Ricinus communis agglutinin II-reactive glycoproteins in hepatocellular carcinoma patients may be cancer-associated glycoproteins and that their serum levels are increased in hepatocellular carcinoma patients.
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PMID:Ricinus communis agglutinin II-reactive glycoproteins from the ascites of patients with hepatocellular carcinoma and their use in enzyme-linked immunosorbent assay. 303 39

1. Rats were fed various diets ranging from the normal chow, pure flour containing large amounts of phytic acid, Ca-enriched flour and mixtures of flour and normal food with various levels of calcium. 2. It was found that the animals eating the pure flour grew less and were smaller. 3. They suffered from hypocalcemia and had low plasma alkaline phosphatase and 25-HCC-vitamin D3 levels. 4. These animals had rib-cage deformities. 5. Additional calcium in the flour improved the animals' growth and calcification. 6. The mixed food did not greatly affect the animals and additional calcium did not improve growth or bone mineralisation. 7. The Bedouin eat large amounts of unleavened bread containing large amounts of phytates. 8. It is concluded that uptake of large amounts of phytates by the Bedouin eating unleavened bread is due to the flour and that the clinical manifestations are a direct result of the flour and not the lack of vitamin D due to covering the skin from sunlight.
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PMID:Growth and bone mineralisation as affected by dietary calcium, phytic acid and vitamin D. 612 64

Thoracic cage tumors are infrequently encountered and may present a dilemma in diagnosis and treatment. A case of hepatocellular carcinoma metastatic to rib, an unusual chest wall tumor, is presented here, and an orderly and effective approach to chest wall lesions is described. Computerized tomography and biopsy are the most efficacious diagnostic modalities.
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PMID:Hepatocellular carcinoma metastatic to rib: an approach to an unusual chest wall tumor. 631 51

A 67-year-old man, diagnosed as hepatocellular carcinoma by percutaneous needle aspiration biopsy of liver mass, presented microangiopathic hemolytic anemia, thrombocytopenia and renal failure from the early phase of the illness. We could establish the diagnosis of cancer-associated hemolytic uremic syndrome which was unrelated to chemotherapy clinically. This is a rare case reported in adult hepatoma patients.
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PMID:Hepatocellular carcinoma associated hemolytic uremic syndrome unrelated to chemotherapy. 799 94

A cancer-associated, high-molecular-weight glycoprotein antigen (6B3.Ag) recognized by monoclonal antibody 6B3 was purified from culture medium of human large cell lung carcinoma cell line (HLC-2) and characterized biochemically and immunochemically. The 6B3.Ag was purified more than 1,200-fold with a yield of 30% by salting out, precipitation by acidification at pH 4.5, and chromatographies on Sepharose 4B and concanavalin A-Sepharose. The molecular weight of 6B3.Ag is approximately 1,000,000 and the molecule is a homodecamer of 94,000 subunits. The 6B3.Ag is a glycoprotein containing 22.9% sugars, consisting of both N- and O-glycoside chains. The N-terminal 19 amino acids were determined and only 4 out of 19 amino acid residues were different from those of an antigen, L3, secreted by lung carcinoma cell line Calu-1. The serum level of 6B3.Ag was determined in normal adults as well as patients with various diseases by enzyme-linked immunosorbent assay. The mean serum level of 6B3.Ag was 3.1 micrograms/ml, ranging from 1.6 to 6.2 micrograms/ml in 131 healthy adults. When the cut-off value was set at 6.2 micrograms/ml, the incidence of positive values in the sera was elevated not only in malignant diseases such as hepatoma (73%) and leukemia (62%), but also in benign diseases such as chronic hepatitis (42%) and liver cirrhosis (63%). While the incidence of positive values was elevated in advanced liver diseases, namely, chronic hepatitis, liver cirrhosis and hepatoma, the cancer specificity of 6B3.Ag did not appear to be high.
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PMID:Detailed characterization of a high-molecular-weight glycoprotein secreted by lung cancer cells. 840 67

Helicobacter hepaticus has been associated with naturally occurring hepatitis in certain inbred strains of mice, and in A/JCr mice it has been linked to the development of hepatic adenomas and adenocarcinomas. H. hepaticus was orally inoculated into 30 axenic, outbred female mice, and the mice were studied longitudinally to fulfill Koch's postulates and to ascertain the pathogenic potential of the organism under defined germfree conditions. Ten cage contact mice were also housed in the same germfree isolator to study transmission patterns, and 10 germfree mice were maintained in separate isolators as controls. Mice serially euthanized from 3 weeks through 24 months postinoculation (p.i.) were surveyed by culture and PCR for H. hepaticus in liver and intestinal tissues. Tissues were analyzed for histopathological changes, and sera were assayed for the presence of immunoglobulin G antibody to H. hepaticus and changes in the liver enzyme alanine aminotransferase. Inoculated mice and cage contact mice were persistently infected with H. hepaticus as identified by culture and PCR, in both the intestine and, less frequently, the liver, for the duration of the 2-year study. Animals developed persistent chronic hepatitis, and in some animals enterocolitis was noted. Hepatocellular carcinoma was diagnosed in one H. hepaticus-infected mouse. The level of H. hepaticus serum antibody was highest in experimentally infected mice at 12 to 18 months p.i.; this corresponded in general to the time interval when the highest levels of alanine aminotransferase were recorded. Although cage contact mice became persistently infected with H. hepaticus, lesions were less severe and the levels of serological biomarkers utilized in the study were lower. The H. hepaticus-infected mouse will provide an ideal model to study putative bacterial virulence determinants and how they interact with the host to induce chronic inflammation and tumorigenesis.
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PMID:Persistent hepatitis and enterocolitis in germfree mice infected with Helicobacter hepaticus. 875 16

In conjunction with strategies introduced in recent years to identify cancer micrometastasis through amplification of cancer-associated mRNA, we developed a highly sensitive system to detect alpha-fetoprotein mRNA in circulating peripheral blood of hepatocellular carcinoma patients. The aim of the present study was to make our original system quantitative. Peripheral venous blood from patients with hepatocellular carcinoma and alpha-fetoprotein-producing gastric carcinoma was subjected to reverse transcription followed by our original three-step polymerase chain reaction co-amplifying both the original sequence and our synthetic competitor. We succeeded in modifying our system for quantitative analysis, and investigated the perioperative change, the postoperative change and the change after chemotherapy in order to illustrate the possible application of this method. The quantitative analysis of alpha-fetoprotein mRNA present in the peripheral blood represents a useful tool for analyzing the relationship of surgery to recurrence, the effect of chemotherapy, and to predict impending recurrence in patients with hepatocellular and alpha-fetoprotein-producing gastric carcinomas.
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PMID:Quantitative analysis of alpha-fetoprotein mRNA in circulating peripheral blood of patients with hepatocellular and alpha-fetoprotein-producing gastric carcinomas. 961 47


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