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

Hepatocellular carcinoma is one of the leading causes of cancer death in the world. To understand the cellular changes associated with transformation of hepatocytes to the malignant state, we have made several libraries of monoclonal antibodies against the hepatocellular carcinoma cell line FOCUS and have found six antibodies (AF-20, SF-25, SF-31, SF-90, XF-4, and XF-8) that recognize antigens expressed at consistently higher levels on hepatoma cells. We have studied malignant and nontransformed liver tissue from the same individual by using direct 125I-labeled antibody binding and immunoperoxidase staining techniques. For each of these antibodies, we found striking increases in antigen expression on the transformed tissues. These antigens were found to be expressed throughout the tumor and on distant metastases, with little, if any, expression on the nontransformed adjacent liver. These antibodies demonstrate that hepatic transformation may be accompanied by stereotyped and predictable antigenic changes. The uniformity of such antigenic changes suggests an association between these cell-surface alterations and the malignant transformation process.
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PMID:Cell-surface changes associated with transformation of human hepatocytes to the malignant phenotype. 283 34

The major risk factors for HCC are outlined in Table 2. Each factor may contribute to the multistep process of hepatocarcinogenesis. Hepatitis B virus and aflatoxins are the principal aetiological candidates and may be considered as initiators of the malignant state (see Figure 1). The majority of HCC arises via the cirrhotic pathway; the associated changes in the hormonal milieu may alter the handling of environmental carcinogens and the rounds of cell proliferation may increase sensitivity to sub-threshold doses of carcinogens. Exogenous androgens and oestrogens may operate through a similar mechanism to promote clonal expansion of preneoplastic cells. The importance of identifying the major aetiological factors lies in the possibility of prevention. The prognosis of HCC is dismal and it represents a major scourge in developing Third World countries. It is encouraging to think that the majority of cases could be prevented by the widespread use of hepatitis B vaccines and the development of intervention programmes against aflatoxin contamination of foodstuffs.
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PMID:Aetiological factors in hepatocellular cancer. 303 54

The relationshio between Con A-receptor mobility and Con A-induced agglutination of Novikoff hepatoma and normal rat liver cells was investigated. Novikoff cells, incubated with fluorescein-labelled Con A at 3 degrees C displayed uniform, ring-like surface fluorescence. Increasing the temperature of the cells to 37 degrees C caused capping of Con A receptors in approximately 65% of the cells, a phenomenon that could be prevented by prefixing the cells with glutaraldehyde. In spite of these variations in Con A-receptor distribution, Con A-induced agglutination was remarkably constant over a temperature range from 3 to 37 degrees C. In contrast to Novikoff cells, normal hepatocytes displayed a uniform, ringlike surface fluorescence at both 3 and 37 degrees C. No capping was observed. However, hepatocytes, similar to Novikoff cells, were agglutinable by low concentrations of Con A. These findings indicate that, in this model system, Con A-induced cytoagglutination is not dependent upon long-range lateral mobility of Con A receptors. The qualitative differences in the lateral mobility of cell-surface Con A receptors of normal and malignant rat liver cells may represent a marker for neoplastioc transformation during hepatocarcinogenesis, adaptation to growth in ascitic form, or progression of a tumour to a more malignant state.
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PMID:Role of cell surface receptor mobility in concanavalin A-induced agglutination of Novikoff hepatoma and normal rat liver cells. 740 Feb 30

In poorly differentiated hepatoma cells, a glycoprotein carrying lactosaminoglycans is identified, and the structure of its glycan moiety is proposed. After membrane solubilization, protein fractionation by gel filtration, and electroelution, this glycoprotein (GPIII) was identified by its affinity for Datura stramonium lectin and its content in large glycopeptides. As shown by PAGE, GPIII has an apparent molecular mass of 100 kDa and is highly glycosylated (36%). It appears as an integral membrane glycoprotein. It is absent from normal hepatocytes, in that no heavy glycopeptides could be detected that bound to Datura lectin or to specific antiserum. The glycan moiety of GPIII has been analyzed according to carbohydrate composition, glycosidase treatment, affinity chromatography on immobilized pokeweed, Datura and Griffonia lectins, and by NMR and methylation analyses. The glycan is a N-linked tetraantennary lactosaminoglycan of 6.6 kDa, containing Gal, GlcNAc, Man, and NeuNAc in a 16:14:3:4 molar ratio, with an average of three repeating units/branch. Its beta-Gal residues are in the penultimate position and are linked in beta1-4 at least in four structural elements (three peripheral and one internal). It contains a very branched structure with Gal alpha1-3Gal beta1-4GlcNAc side chains linked in the C6 position to an inner Gal residue in a main branch. Alpha-Gal and NeuNAc residues [mainly NeuNAc alpha(2-3) linkage] are expressed as the nonreducing terminal groups. A possible structural model is proposed for this heterogeneous lactosaminoglycan, although no definitive structure can be established. That this lactosaminoglycan-carrying glycoprotein GPIII is not expressed in hepatocytes suggests its expression to be linked to the undifferentiated and/or malignant state of this hepatoma.
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PMID:Expression and characterization of a lactosaminoglycan-carrying glycoprotein of Zajdela hepatoma cell surface--structural analysis of the carbohydrate moiety. 928 35

Hepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically validated biomarkers that can predict natural history of malignant progression are lacking. The present study explored the proteome-wide patterns of HCC to identify biomarker signature that could distinguish cancerous and nonmalignant liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and both the tumor and adjacent nontumor tissues were subjected to proteome-wide expression profiling by 2-DE method. The subjects were randomly divided into the training (n = 55) and validation (n = 25) subsets, and the data analyzed by classification-and-regression tree algorithm. Protein markers were characterized by MALDI-ToF/MS and confirmed by immunohistochemistry, Western blotting and qPCR assays. Proteomic expression signature composed of six biomarkers (haptoglobin, cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa protein 1, lysosomal proteinase cathepsin B, keratin I) was developed as a classifier model for predicting HCC. We further evaluated the model using both leave-one-out procedure and independent validation, and the overall sensitivity and specificity for HCC both are 92.5%, respectively. Clinical correlation analysis revealed that these biomarkers were significantly associated with serum AFP, total protein levels and the Ishak's score. The described model using biomarker signatures could accurately distinguish HCC from nonmalignant tissues, which may also provide hints on how normal hepatocytes are transformed to malignant state during tumor progression.
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PMID:Proteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma. 1916 26

Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the "gold standard" in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.
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PMID:The nanomechanical signature of liver cancer tissues and its molecular origin. 2616 46