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 expressions of c-erbB-2 oncogene and epidermal growth factor receptor (EGFR) were investigated immunohistochemically in specimens from 184 cases of hepatitis B, cirrhosis and hepatocellular carcinoma (HCC) and 29 normal liver specimens. EGFR was expressed in 36% (48/134) of the hepatocellular carcinoma and chronic liver disorder specimens and it was immunolocalized mainly in the sinusoidal endothelial cells. No significant difference was found between EGFR expression in HCC and in benign chronic liver disorders. These results indicate that EGFR may have some role in the proliferation of the sinusoidal epithelial cells in chronic liver disease. Low level c-erbB-2 expression was observed in 5/29 (17%) of normal liver specimens. In chronic hepatitis B and liver cirrhosis, its expression was found in all specimens. c-erbB-2 protein was immunolocalized mainly in small polygonal liver cells (SPLCs) and hepatocytes in small-cell dysplasia (SCD) and in ductular metaplasia (DM); c-erbB-2 expression in HCC cells was found to be weaker than in SPLCs, the hepatocytes in SCD and in DM. These results indicate that activated c-erbB-2 oncogene may have a role in human HCC genesis through promoting the development of SCD from SPLC proliferation and the progression of SCD. The close relation between the expression of c-erbB-2 and HBxAg imply that the activation of c-erbB-2 in human liver tissues may be related to HBV X gene.
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PMID:[Expression of c-erbB-2 protein and EGF receptor in hepatitis B, cirrhosis and hepatocellular carcinoma]. 778 35

The histology of 72 livers from 72 children who underwent liver transplantation was reviewed. Nine children (12.5%) had hepatocellular carcinoma (HCC) and/or liver cell dysplasia (LCD) in their native livers. Ages at the time of transplantation ranged from 2 months to 11 years. Primary liver diseases included tyrosinemia (3), biliary atresia (2), chronic active hepatitis B (1), chronic active non-A non-B non-C hepatitis (1), idiopathic neonatal hepatitis (1), and neonatal iron storage disease (1). Explanted livers showed large multifocal HCC in two cases, incidental HCC in three, and dysplastic nodules in four. LCD also was present in three cases in conjunction with HCC. All patients had cirrhosis. Alpha-fetoprotein was measured in six children and was elevated in all six (range, 300 to 1,770,000 ng/mL; normal, 0 to 15 ng/mL). Abdominal computed tomography, ultrasonography, and/or magnetic resonance imaging showed large masses in two cases, but did not detect the tumors of less than 2 cm or the dysplastic nodules in the other seven children. After a follow-up period of 2 months to 3 years (mean, 19.8 +/- 12.1 months), eight children are alive and have no evidence of recurrence. The patient with neonatal iron storage disease died 2 months after transplantation, without evidence of tumor recurrence. The authors conclude that children with end-stage liver disease of diverse causes referred for liver transplantation may have LCD and/or HCC. Serial determination of alpha-fetoprotein and images studies may detect early lesions curable by liver transplantation.
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PMID:Hepatocellular carcinoma and liver cell dysplasia in children with chronic liver disease. 784 22

Macroregenerative nodules (MRNs), probably representing a pathway for human hepatocarcinogenesis, are generally classified into type I MRNs (or ordinary adenomatous hyperplasia) and type II MRNs (or atypical adenomatous hyperplasia), on the basis of imprecise definitions of cytological and architectural atypia. It is currently believed that type II MRNs are probably true precursors of hepatocellular carcinoma (HCC), whereas type I lesions may simply represent large regenerative nodules. A series of 155 consecutive adult cirrhotic liver explants were examined for evidence of MRNs, HCC, and liver cell dysplasia (LCD) of large and small cell types, and their appearance, in terms of proposed classification schemes, was reviewed. There was evidence indicating that the presence of either type of MRN was associated with an increased incidence of HCC (all MRNs, P < .00019; type I MRNs, P < .067; type II MRNs, P < .012) compared with cirrhotic livers without MRNs. A subset of younger patients with a large (uncountable) number of MRNs in their livers, who did not show any increased incidence of carcinoma, was identified. Excluding these cases from statistical analysis, all associations were strengthened, implying either that malignant progression had not had time to occur in this younger population or that these nodules were simply large regenerative nodules without malignant potential. MRNs from these livers were histologically indistinguishable from MRNs occurring in more limited numbers, although atypical changes other than large cell type LCD were less frequent. No independent association between LCD of large cell type and HCC was found in the entire series.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Macroregenerative nodules in a series of adult cirrhotic liver explants: issues of classification and nomenclature. 787 67

We have studied the occurrence and specific features of liver cell dysplasia (LCD) in Chinese patients showing liver cirrhosis with or without hepatocellular carcinoma (HCC). Three types of LCD (SLCD, LLCDo, LLCDe) were morphologically defined, and these types were further analyzed using karyometry, estimation of nucleic acid content and density, and PCNA immunostaining. Features found for three types of LCD were compared with those of normal hepatocytes (NLC), simple regenerating hepatocytes (SRLC), and cells of HCCs covering different grades. The results show that 1) karyometry and nucleic acid parameters allow an objective separation of LCD types both from NLC and SRLC; 2) karyometric features of LLCDe are most close to those of highly differentiated HCCs, whereas nuclear size and chromatin composition of SLCD closely reflect those of poorly differentiated HCCs; 3) the frequency of LCD clusters was higher in cirrhotic livers carrying HCC, being about double for all three LCD types; 4) the highest PCNA labelling occurred in the small cell group of LCD (SLCD), still, however, being smaller than that of simple regenerating hepatocytes. Based on these findings it is suggested that, similar to atypical adenomatous hyperplasia, LCDs of distinct morphotypes may represent precursor lesions for HCC, and some cellular forms may mimick cell types known to occur in experimental carcinogenesis.
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PMID:Three types of liver cell dysplasia (LCD) in small cirrhotic nodules are distinguishable by karyometry and PCNA labelling, and their features resemble distinct grades of hepatocellular carcinoma. 791 90

The immunohistochemical determination of the accessory protein of DNA-polymerase delta (PCNA), a marker of an early S-phase of the cell cycle, was used to evaluate cell proliferation retrospectively in formalin-fixed, paraffin-embedded liver biopsy sections in a group of patients with cirrhosis of similar age and duration of follow up, and with no evidence of hepatocellular carcinoma (41), including 17 patients with and 24 without hepatocellular carcinoma appearance during follow up. Proliferation was expressed as total (PCNA-TOT) and strongly (PCNA-STRO) positive nuclei per 1000 hepatocytes. The presence of dysplasia was also recorded. Histological findings and biochemical data, at the time of liver biopsy, were compared in the two groups. While total PCNA positivities were not significantly different in the two groups, strong reactivity was significantly higher in patients who eventually developed hepato-cellular carcinoma (median 0.7 vs 2.6). Univariate analysis of histological and biochemical data at the time of biopsy, followed by a stepwise regression study, showed that the significant parameters for a time-dependent disease-free state were, in decreasing order: cholesterol, PCNA-STRO, PCNA-TOT and alpha foeto-protein. Other clinical, biochemical and histological parameters, including dysplasia, provided no further information. From these data, hepatocellular proliferation can be evaluated in patients with cirrhosis with a currently available technique. Patients with high cell proliferation are at increased risk of developing hepatocellular carcinoma and may require differentiated follow up.
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PMID:Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation. 791 17

Large-cell liver cell dysplasia (LCD), suggested to be a preneoplastic change that progresses to hepatocellular carcinoma (HCC), has a reported frequency of DNA aneuploidy by flow cytometry intermediate between that of nonneoplastic liver (0%) and HCC (80%). We assessed DNA ploidy by image cytometry of Feulgen-stained 5-microns sections of 30 livers with LCD and of 60 HCCs (29 with LCD in adjacent nonmalignant liver). All 30 LCDs were aneuploid, 27 (90%) of which were multiploid--11 (41%) with hyperdiploid and hypertetraploid peaks. Forty-eight (80%) HCCs were aneuploid; in nine of 20 (42%) with a hyperdiploid peak, a hyperdiploid peak was also present in the LCDs, but in none was there less than 0.24 between DNA indices. Besides the 12 (20%) diploid HCCs, a diploid peak was present in four heterogenous, three multiploid, and six HCCs with two phenotypes and two genotypes, one of which was diploid. One aneuploid/hyperdiploid peak in each of 22 nonneoplastic and 24 cirrhotic livers did not have a corresponding LCD or HCC aneuploid peak. These data do not suggest that dysplastic hepatocytes form a single mutant clone that progresses to HCC.
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PMID:Comparative image cytometric DNA ploidy of liver cell dysplasia and hepatocellular carcinoma. 799 27

We analysed p53 protein immunoreactivity in hepatocellular carcinomas (HCCs) and in liver cell dysplasia (LCD) of patients from an area in Northern China, using five anti-p53 protein antibodies recognizing different epitopes of the protein. In HCCs, the overall prevalence of p53 protein immunoreactivity was 78.3%. However, prevalence was strongly influenced by the type of antibody used, ranging from 67.5% for antibody PAb-1801 to only 10.8% for antibodies PAb-421 and DO-7. p53 protein immunoreactivity was not related to type or grade of HCC. In contrast to former reports, p53 protein staining was restricted to nuclei only when using the CM-1 antibody, whereas two other antibodies yielded both, nuclear and cytoplasmic or membrane staining, and no nuclear staining was observed with antibodies PAb-421 and DO-7, the latter two, however, demonstrating cytoplasmic and membrane staining. For LCD, three subtypes were morphologically and karyometrically defined. Nuclei of some LCD cells were p53 immunoreactive, but positivity was restricted to the small cell variant of LCD. Positivity was different for cirrhosis with or without associated HCC, amounting to 18.9% in the former and 39.4% in the latter. Interestingly, p53 protein immunoreactivity also occurred in a set of small hepatocytes not showing the typical feature of LCD and therefore classified as simple regenerating liver cells.
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PMID:Immunohistochemical analysis of p53 protein overexpression in liver cell dysplasia and in hepatocellular carcinoma. 805 55

Large cell liver cell dysplasia (LCD), a suggested preneoplastic change progressing to hepatocellular carcinoma, has been reported associated with alpha-1-antitrypsin deficiency which in some countries has an increased frequency of hepatocellular carcinoma. We examined the nonneoplastic liver from 13 alpha-1-antitrypsin deficiency patients for LCD and, using a labeled streptavidin-biotin technique, for immunohistochemical markers: AAT (1/200), hepatitis B surface (HBsAg, prediluted) and core (HBcAg, 1/400) antigens, and monoclonal (1/20) and polyclonal (1/40) mutant p53, a tumor suppressor gene. There were eight males and five females ranging from 2 mo to 76 yr (mean 40 yr). Nine livers showed cirrhosis, one chronic persistent hepatitis, one portal fibrosis, and two cholestatic hepatitis (in the two infants). The nine cases with LCD included five males and four females of mean age 46 yr (range, 17-71), eight with cirrhosis and one with portal fibrosis. Only one liver with LCD and cirrhosis had HBcAg in cirrhotic and dysplastic cells. No patient had developed hepatocellular carcinoma. All 13 livers were immunonegative for HBsAg and mutant p53, and immunopositive for AAT present in normal, cirrhotic, and dysplastic liver cells. Thus, LCD was identified in 82% of adult alpha-1-antitrypsin deficiency livers (69% including infantile patients), 89% with cirrhosis, and none with malignancy. HB expression was rarely present; serology for HB and/or hepatitis C was positive in 46% adults. Immunoreactive AAT was present in dysplastic cells. p53 gene mutations do not appear to have a role in the pathogenesis of LCD in alpha-1-antitrypsin deficiency.
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PMID:Liver cell dysplasia in alpha-1-antitrypsin deficiency. 815 50

The human immunodeficiency virus tat protein, a transactivator of viral and cellular genes, is suspected to be involved in the pathogenesis of acquired immunodeficiency syndrome-associated tumors. We report that transgenic mice carrying a recombinant DNA containing BK virus early region and the human immunodeficiency virus tat gene develop skin leiomyosarcomas, squamous cell papillomas and carcinomas, adenocarcinomas of skin adnexa, glands, and B-cell lymphomas. Although the incidence of hepatocellular carcinoma is low, most animals show a liver cell dysplasia of variable degree. These mice are also affected by skin lesions resembling the early stages of Kaposi's sarcoma. The transgene was detected intact in all the organs of transgenic mice, generally as multiple tandemly integrated copies. BK virus early region and tat were expressed in essentially all tissues and organs of BK virus/tat transgenic mice. This transgenic mouse model is representative of the systemic involvement of tat in human immunodeficiency virus natural infection and may be applied to investigate the role of tat in malignancies associated to acquired immunodeficiency syndrome, to study Kaposi's sarcoma pathogenesis and cell of origin, to characterize preneoplastic conditions established by tat in the skin and liver, and to assess in vivo the efficacy of antiangiogenic and anti-tat-specific drugs.
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PMID:Systemic expression of HIV-1 tat gene in transgenic mice induces endothelial proliferation and tumors of different histotypes. 822 99

New retinoids have been synthesized and screened in the search for chemopreventive agents of cancer. N-4-(Carboxyphenyl) retinamide showed a significant inhibitiory effect on carcinogenesis of cancers in the buccal pouch of hamsters and in the forestomach of mice. Clinical studies have demonstrated that N-4-(carboxyphenyl) retinamide is effective against oral leukoplakia, vulvar leukoplakia, and dysplasia of the uterine cervix and stomach. Field studies among a population at high risk for esophageal cancer in Linxian County, Henan Province, revealed that N-4-(ethoxycarbophenyl) retinamide decreased the incidence of this cancer. Qidong County is a high-risk area for hepatoma in China. This has been correlated to the low levels of selenium in the blood of the residents as well as in grain grown in the area. S. Y. Yu, W. G. Li, Y. J. Zhu, et al. (Biol. Trace Element Res. 1985; 7:22-26) reported that the administration of selenium inhibited the incidence of hepatoma induced by aflatoxin B in rats and in ducks. Experimental studies demonstrated that green tea extract inhibited 12-O-tetradecanoylphorbol-3-acetate-induced epidermal ornithine decarboxylase activity and counteracted 12-O-tetradecanoylphorbol-3-acetate-induced ear edema in mice. It is interesting that green tea extract inhibited the transformation of Balb/c 3T3 cells induced by methylcholanthrene and 12-O-tetradenanoylphorbol-3-acetate. Garlic has been used for thousands of years in Chinese cooking and folk medicine. Epidemiological studies show that the dietary intake of garlic is inversely related to gastric cancer incidence in Shandong Province.
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PMID:Highlights of the cancer chemoprevention studies in China. 823 11


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