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 cells derived from the human embryo liver tissue were transfected with a plasmid pSV3neo containing both the large and small T-antigen gene of the early region of simian virus 40 (SV40), and two cell strains, OUMS-21 and -22, were obtained. OUMS-22 cells, to date, have reached over 100 population doublings through a culture crisis and are considered to have become an immortal cell line. However, OUMS-21 cells failed to become an immortal cell line. Both OUMS-21 and -22 cells were SV40 T-antigen-positive, epithelial-like, and immunoreactive against an anti-keratin 18 monoclonal antibody but against neither an anti-vimentin nor an anti-von Willebrandt factor VIII monoclonal antibody. The staining pattern of cytokeratin in these cells was similar to that in the differentiated human hepatoblastoma and hepatocellular carcinoma cell lines but not to that in the human cholangiocellular carcinoma cell lines. OUMS-21 and -22 cells expressed neither alpha-fetoprotein nor albumin mRNAs. These cells showed no tyrosine aminotransferase activity. However, both OUMS-21 and -22 cells were sensitive to cytotoxicity of aflatoxin B1, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, and benzo[a]pyrene, whereas human embryo lung fibroblasts were insensitive to the cytotoxicity of these carcinogens. These findings suggest that OUMS-21 and -22 cells may arise from undifferentiated liver stem cells or from hepatocytes that lost their ability to express the liver-specific functions prior to immortalization. Both OUMS-21 and -22 cells expressed glutathione S-transferase pi (GST-pi) mRNA. The expression of GST-pi mRNA highly increased in OUMS-22 cells with their immortalization. Karyotypic analysis showed that numerical and structural aberrations of the chromosomes were profound, but neither specific events nor marker chromosomes were found in OUMS-21 and -22 cells. Both OUMS-21 and -22 cells could grow in soft agar, but they were not tumorigenic when transplanted into nude mice.
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PMID:Immortalization of epithelial-like cells from human liver tissue with SV40 T-antigen gene. 768 77

We describe successful partial hepatectomy for hepatocellular carcinoma (HCC) in a 43-year-old man with severe factor VIII deficiency (hemophilia A). Tumor size and plasma alpha-fetoprotein (AFP) decreased spontaneously prior to surgery. HCC was found in the anterior superior segment of the liver, with invasion of the diaphragm. A limited partial resection of the liver and diaphragm was performed. The administration of factor VIII during and immediately after surgery resulted in no postoperative bleeding complications. Macroscopic findings revealed hemorrhage and necrosis throughout the intrahepatic portion of the tumor. Viable HCC cells were recognized histologically in the intrahepatic tumor and infiltrating the diaphragm. In patients with hemophilia there is a tendency for HCC to hemorrhage, which may obscure the diagnosis. Appropriate administration of factor VIII permits the safe resection of HCC in hemophilia A.
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PMID:Partial hepatectomy for hepatocellular carcinoma in a patient with hemophilia: a case report. 795 55

The sinusoidal structure and blood supply of 38 liver nodules less than 2 cm in diameter were investigated. There were 18 cases of adenomatous hyperplasia (AH) and 20 cases of hepatocellular carcinoma (HCC). Growth pattern, encapsulation and vascularity were examined, and immunohistochemistry performed for factor VIII related antigen (factor VIII), type IV collagen (collagen IV), laminin and CD68. There were significant differences between AH and small HCC, except for the expression of CD68. There were differences in tumor size, vascularity and the components of the basement membrane between AH and small, well differentiated HCC. The cases of AH were supplied by the portal system and maintained the sinusoidal structure, but small well-differentiated' HCC were supplied by a mixture of portal and arterial vessels. In spite of their small size, moderately and poorly differentiated HCC had capillary and were supplied by branches of the hepatic artery.
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PMID:Immunohistochemistry and angiography in adenomatous hyperplasia and small hepatocellular carcinomas. 880 83

To examine the phenotype of the sinusoidal endothelial cells (SECs) surrounding tumor cells and the process of capillarization in hepatocellular carcinoma (HCC), 51 primary HCCs, 4 adrenal metastases, and 3 portal tumor thrombi were immunohistochemically stained with monoclonal antibodies (MAbs) for CD4, CD14 (lipopolysaccharide-binding protein complex receptors), and CD32 (Fc gamma receptor II), which are specifically found on the SECs in normal liver, but not on ordinary vascular endothelial cells (ECs). Immunostaining was also performed for CD36 (thrombospondin receptors), EN4 antigen (Ag) (a pan-vascular endothelial cell Ag), PAL-E Ag (a venous and capillary EC Ag), factor VIII-related Ag (FVIIIRAg), and laminin. MAb 25F9, which identifies macrophages, was simultaneously used with the other MAbs to distinguish macrophages from SECs in HCCs (HCC SECs). CD4, CD14, and/or CD32 were found on HCC SECs only in 12 well-differentiated primary HCCs showing a thin trabecular or pseudoglandular tumor cell arrangement. These 12 tumors were smaller than those without CD4-, CD14-, and/or CD32-positive SECs (P < .05). Among them, 7, 5, and 11 tumors were negative or only partially positive for laminin, PAL-E Ag, and FVIIIRAg, respectively. Staining for laminin and PAL-E Ag showed an inverse relationship to the expression of CD4, CD14, and CD32 on HCC SECs and the tumor differentiation. In conclusion, the phenotypes of the SECs in early and well-differentiated HCC are thought to be similar to those of the SECs in normal liver. With progressing tumor dedifferentiation the HCC SECs lose the phenotypes peculiar to liver SECs and acquire the characteristics of capillary ECs, though both types of phenotypical change occur independently of each other.
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PMID:Immunohistochemical studies on endothelial cell phenotype in hepatocellular carcinoma. 925 52

Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP-470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2-acetylaminofluorene to hepatectomized rats during 8-14 weeks of age. Predominantly arterial-to-portal circulation and sinusoidal capillarization were determined by the staining of nodules with arterially infused ink and immunostaining for factor VIII-related antigen, respectively. Intraperitoneal administration of 30 mg/kg b.w. of TNP-470 twice a week significantly reduced the number of hepatic nodules. Among the nodules, hyperplastic nodules stained with ink, atypical hyperplastic nodules and hepatocellular carcinoma, all of which possess structurally altered sinusoidal endothelial cells or capillary-type endothelial cells, were dramatically decreased in number. Suppression was observed equally in nodules of all sizes. TNP-470 was more effective when administered during 8-20 weeks than during 14-26 weeks. In contrast, ink-non-stained hyperplastic nodules, which have normal sinusoidal endothelial cells, were not affected at all. The present results indicate that TNP-470 suppresses the development of primary hepatic nodules whose microvessels are capillaries or transitional forms from sinusoids to capillaries.
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PMID:Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of carcinogen-induced hepatic nodules in rats. 954 41

In HCC specimens from 25 patients, the levels of nm23-H1 and H-ras mRNA were analyzed by quantitative reverse transcription-polymerase-chain reaction (RT-PCR). Tumor microvessel density (MDV), the essential factor of microenvironment and proliferating cell nucleus antigen (PCNA), indexes as tumor cell proliferating in its microenvironment are also analyzed by immunohistochemical methods using antibodies against endothelial protein factor VIII related antigen (F8RA) and antibody PC-10. Results show that The MDV and PCNA index in the group with intrahepatic metastasis is remarkably higher than that in without one (p<0.01), but the abundance of nm23-H mRNA is opposite (p<0.01). The abundance of H-ras mRNA shows little difference (p>0.05). MDV index shows directly relationship with PCNA index (p<0.01), the abundance of nm23-H1 mRNA show an inverse one with PCNA index (p<0.05). We conclude that in HCC, tumor in situ microenvironment, especially a deteriorative one, plays an important selective role. The decline of nm23-H1 mRNA abundance implies the increase of highly potential metastatic cancer cells which adapt to their microenvironment.
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PMID:The abundance of NM23-H1 mRNA is related with in situ microenvironment and intrahepatic metastasis in hepato-cellular carcinoma. 989 72

Both the full-length and B domain-deleted cDNA of factor VIII were constructed in plasmid pcDNA3, respectively, and successfully expressed in Cos-7 cells. The yield of recombinant factor VIII-deltaB (0.4 U/mL/10(6) cells/day) was approximately four times higher than that of the recombinant factor VIII. In addition, it was indicated that the gene expression of factor VIII is specific for cells from different tissues. The highest expression level was found in the hepatocellular carcinoma line SMMC-7721, followed by kidney, ovary, and lung cell lines. To compare the efficiency of gene expression of recombinant factor VIII, the factor VIII-deltaB gene was further reconstructed in different forms in the expression plasmid pCMV-dhfr for transient gene expression in Chinese hamster ovary cells. The redundant 5'- and 3'-untranslated sequences of factor VIII-deltaB were deleted. The cDNA encoding the heavy and light chains of factor VIII were constructed, respectively. Among them the high yield of the recombinant factor VIII was found in the coexpression of the heavy and light chain cDNA fragments of factor VIII. The deletion of the redundant 5'-untranslated sequence of factor VIII-deltaB was also beneficial for gene expression. As expected, the gene coexpression of factor VIII-deltaB and von Willibrand Factor cloned by the long-polymerase chain reaction method was also helpful for enhancing the expression level of recombinant factor VIII. A monoclonal antibody raised against factor VIII was prepared and used for the specific assay of recombinant factor VIII by the competitive ELISA method, the assay results were consistent with those determined by the one-stage bioassay.
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PMID:The gene expression of coagulation factor VIII in mammalian cell lines. 1041 99

The hepatic sinusoids are preferentially supplied with portal venous blood and equipped with fenestrated endothelial cells that are distinct from capillary endothelial cells. We previously observed in rats that sinusoidal capillarization proceeded concurrently with arterial blood supply during hepatocarcinogenesis. This study aimed to clarify the inducing role of arterialization in sinusoidal capillarization by investigating phenotypical, morphological and functional alterations to sinusoidal endothelial cells (SECs) in arterialized rat livers induced by portal branch ligation. At one week, after massive hepatic necrosis following ligation, the livers were restored to their normal architecture without causing post-necrotic fibrosis. At 12-21 weeks, they exhibited a normal histology except for mild pericellular fibrosis which developed along sinusoids or between adjacent hepatocytes. SECs expressed factor VIII-related antigen and showed a decrease in the number of fenestrae and porosity, still lacking any basement membrane but further retaining the functional capacity for carmine dye uptake. Stellate cells, while occasionally associated with large amounts of collagen bundles, contained many lipid droplets and expressed no alpha-smooth muscle actin, indicating a quiescent property. Kupffer cells were commonly found within the sinusoids. The present results indicate that arterialization of the liver induces a partial (but not complete) transition of SECs into capillary-type endothelial cells, suggesting that arterialization might be one of the factors which induce sinusoidal capillarization in the development of hepatocellular carcinoma.
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PMID:Phenotypical and morphological alterations to rat sinusoidal endothelial cells in arterialized livers after portal branch ligation. 1067 69

The cytokine interleukin-12 (IL-12) has shown potent antitumor activity in several tumor models. Recently, natural killer (NK) T cells have been proposed to mediate the antitumor effects of IL-12. In this study, the antitumor response of IL-12 was investigated in a gene therapeutic model against s.c. growing mouse hepatocellular carcinomas using an adenoviral vector expressing murine IL-12 (AdVmIL-12). An adenoviral-based system was chosen because of the ability of adenoviruses to transduce dividing and nondividing cells and because of their high transduction efficiencies. Our goals were to examine the efficacy of AdVmIL-12 in a hepatocellular carcinoma model and to investigate the mechanism of the AdVmIL-12-mediated antitumor response with specific interest in the role of NK T cells. Our studies demonstrate that intratumoral AdVmIL-12-mediated regression of s.c. hepatocellular tumors is associated with rapid antitumor responses. AdVmIL-12 treatment was associated with an immune cellular infiltrate consisting of CD4 and CD8 T lymphocytes, macrophages, NK cells, and NK T cells. Antibody ablation of CD4 and CD8 T cells and use of NK cell-defective beige mice failed to abrogate the response to AdVmIL-12. Studies in T-cell- and B-cell-deficient severe combined immunodeficient and recombinase activating gene-2-deficient mice and T-cell-, B-cell-, and NK cell-defective severe combined immunodeficient/beige mice also failed to abrogate this response. AdVmIL-12 retained potent antitumor activity in mice with specific genetic defects in immune cellular cytotoxicity (perforin knockout mice) and costimulation (CD28 knockout mice). Use of mice with specific NK T cell deficiencies, Valpha14 T-cell receptor and CD1 knockout mice, also failed to abrogate the response to AdVmIL-12. Histological and immunohistochemical studies of AdVmIL-12-treated tumors showed extensive inhibition of neovascularization and a marked decrease in factor VIII-stained endothelial cells. Our studies indicate that the antitumor response of AdVmIL-12 is independent of direct cytotoxic cellular immunity (specifically, the function of NK T cells) and suggest that the initial mechanisms of AdVmIL-12-mediated tumor regression involve inhibition of angiogenesis.
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PMID:Adenovirus-interleukin-12-mediated tumor regression in a murine hepatocellular carcinoma model is not dependent on CD1-restricted natural killer T cells. 1110 13

Heparan sulfate plays an essential role for insolubility of the components of extracellular matrix and represents a storage depot for various growth factors. Therefore, heparanase produced by a given tumor may facilitate tumor invasiveness and angiogenesis through the release of heparan sulfate-bound growth factors. Although the growth factors responsible for angiogenesis in hepatocellular carcinoma (HCC) have recently been investigated, the clinicopathological significance of heparanase in connection with basic fibroblast growth factor (bFGF) expression in HCC has not been evaluated so far. Fifty-five patients who had undergone hepatic resection for HCC without preoperative treatment were included in the present study. Expression of heparanase mRNA was evaluated by reverse transcription-PCR, and bFGF was examined by Western blotting using a monoclonal antibody. Tumor angiogenesis was evaluated by immunostaining with a factor VIII-related monoclonal antibody. Expression of heparanase mRNA was detected in 47% of HCCs and was significantly correlated with larger tumor size (P = 0.01), presence of portal vein invasion (P = 0.01), and higher overall tumor invasiveness (P = 0.02). Moreover, its expression was correlated with tumor microvessel density (MVD; P = 0.02). There was a direct correlation between the levels of bFGF proteins and MVD in HCCs (P = 0.0001), and, furthermore, concomitant expression of bFGF and heparanase was associated with higher tumor MVD as compared with expression of either factor alone (P = 0.01). In conclusion, the expression of heparanase in HCC enhances growth, invasion, and angiogenesis of the tumor, and bFGF seems to be a potent angiogenic factor for HCC.
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PMID:The clinicopathological significance of heparanase and basic fibroblast growth factor expressions in hepatocellular carcinoma. 1135 Aug 98


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