UMLS:C0019204 - FACTA Search

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

Experiments were carried out on Buffalo rats with implantable Morris hepatoma 5123 growing in the skeletal muscles of the limbs. Mutein VI (a protein which differs from the native TNF-alpha molecule in its N-terminal amino acid composition) was administered at a dose of 10 micrograms per rat once a day in a cycle of 8 days. Control animals were given saline (PBS). Ultrastructural changes within the pulmonary tissue were evaluated with an electron transmission microscope (TEM), with special attention paid to endothelial cells and alveolar epithelial cells. Quantitative analysis of neoplastic metastases to the lungs was carried out. The animals given mutein VI compared to those injected with PBS demonstrated a decrease in the number of metastases. TEM pictures showed accumulations of eosinophilic granulocytes and monocytes in the lumen of the blood vessels. Enhanced activity of endothelial cells was observed. In pulmonary alveoli conglomerates of fibrin, and fragments of damaged cells were found, with erythrocytes, granulocytes and macrophages in their vicinity. The epithelium of pulmonary alveoli showed signs of considerable damage, including necrosis. The mutein VI-hrec TNF-alpha was found to block the neoplastic process, illustrated by a reduction in the volume of lung parenchyma occupied by neoplastic metastases. Also, the ultrastructural changes observed in the pulmonary tissue indicate the possibility of peripheral action of mutein VI after its administration to rats carrying the Morris hepatoma.
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PMID:Studies on pulmonary tissue after administration of mutein VI-HREC TNF-alpha into implantable experimental Morris hepatoma. 906 67

ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. We have examined the therapeutic effects of ONO-4007 on rat hepatocellular carcinoma KDH-8 cells, rat fibrosarcoma KMT-17 cells and rat mammary adenocarcinoma SST-2 cells in vivo. Multiple systemic i.v. administration of ONO-4007 was performed on days 7, 14 and 21 after tumor implantation of KDH-8 and SST-2 cells, and on days 5, 10 and 15 after tumor implantation of KMT-17 cells. ONO-4007 showed significant therapeutic effects on KDH-8 cells; by the administration of ONO-4007 (2.5 mg/kg) 70% of rats were cured and by the administration of ONO-4007 (5 mg/kg) 50% of rats were cured. Furthermore, the ONO-4007 treatment prolonged the mean survival time of KDH-8-bearing rats. However, ONO-4007 had no effect on KMT-17 and SST-2 cells, and it had no direct effect on the growth of KDH-8 cells in vivo. Albeit the stimulation with ONO-4007 induced mRNA expressions of interleukin (IL)-1alpha, IL-6 and tumor necrosis factor (TNF)-a, those of IL-2, IL-4, IL-10 and interferon (IFN)-gamma were not induced. Using a bioassay, we found that the production of TNF-alpha in the tumor tissues was induced by ONO-4007 in a dose-dependent manner. KDH-8 cells were sensitive to human natural TNF-alpha in vitro. However, KMT-17 and SST-2 cells were resistant against TNF-alpha in vitro. These results suggest that ONO-4007 is therapeutically useful for the treatment of TNF-alpha-sensitive tumors.
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PMID:A new synthetic lipid A analog, ONO-4007, stimulates the production of tumor necrosis factor-alpha in tumor tissues, resulting in the rejection of transplanted rat hepatoma cells. 921 14

We previously reported that the number of TNF-alpha-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-alphaRI (p55) and -alphaRII (p75), and IL-10, all of which act as TNF-alpha buffer, and IL-15, a novel cytokine sharing many immunological activities with IL-2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-alphaR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-alphaRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating IL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-alphaRs. These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC.
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PMID:Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-alpha) receptors in type C chronic liver disease. 932 22

The aim of this study was to explore the effect of intratumour mutein VI-Hrec TNF-alpha administration upon the ultrastructural changes within the pulmonary tissue, with special attention paid to type II alveolar epithelial cells. The experiment was carried out on Buffalo rats with implantable Morris hepatoma series 5123 in the skeletal muscles of the limb. Mutein VI-Hrec TNF-alpha was administered in a dose of 10 micrograms once a day in a cycle of eight days. Control animals were given saline (PBS). Ultrastructural changes within the pulmonary tissue were evaluated in the electron transmission microscope (TEM), with special attention paid to alveolar epithelial cells. In the animals receiving hrec TNF-alpha mutein VI, damage to the alveolar epithelial cells was found. In the later period (14 days after the mutein treatment), repairing processes were observed, accompanied by intensified fibrotic processes in the interalveolar septal interstitium, with the subsequent pulmonary tissue rebuilding. The study confirmed the possibility of a peripheral action of hrec TNF-alpha mutein VI after its administration to the experimental Morris hepatoma and found the alveolar epithelial cells to be a key element of the pulmonary tissue subjected to the cytokine effect.
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PMID:Alveolar epithelial cells after intratumour administration of HREC TNF-alpha mutein VI. 933 53

The aim of this study was to explore the effect of intratumor TNF-alpha administration upon the composition and adherence degree of cells isolated from the lungs through multiple bronchoalveolar lavages (BAL). Ultrastructural evaluation of BAL-isolated cells was performed in the scanning electron microscope (SEM). The experiment used Buffalo rats. A suspension of 3 x 10(6) cells of Morris hepatoma (5123 series) was injected to the right hind leg of the animals. After fourteen days, TNF-alpha was administered into the tumor in a dose of 1.5 x 10(4) U in 0.5 ml PBS solution. The animals of group I were given 4 doses of TNF-alpha and group II-8 doses of TNF-alpha every 24 hours. Control groups consisted of rats with injected Morris hepatoma which were given PBS solution instead of TNF-alpha (group III A, B) and animals without the hepatoma, given intramuscullary 4 or 8 TNF-alpha, respectively (groups IV A, B). No statistically significant differences were noticed between groups I and II with regard to the number of macrophages and neutrophils isolated from the rat lungs compared with control group IV. However, such differences were observed compared with group III. In group II and IV B, an increase in the adherence of isolated cells was found compared with group III, as well as arise in the number of macrophages with the largest diameters. We found a correlation between the increase in cell adherence and ultrastructural changes (in SEM) suggesting an increased activity of BAL-isolated cells.
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PMID:Quantitative and morphological changes in BAL-isolated cells after the administration of TNF-alpha into Morris hepatoma. 933 55

There is now good evidence that cytokines contribute to the regulation of tumor growth. The cytokine-driven modulation of tumor growth was investigated during the progression of a hepatocellular carcinoma (HCC) in SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of liver growth correlated with increased transforming growth factor (TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis factor (TNF)-alpha mRNA were detected earlier during tumor development. Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2, IL-4 and IFN-gamma mRNA production could be reported. In vitro, hepatocyte-like tumor cell lines established at two stages, either before or after HCC differentiation, were characterized. The early-stage-derived cell line produced TNF-alpha mRNA, but had barely detectable expression of TGF-beta 1 mRNA, while later-stage-derived cell lines showed the reciprocal pattern. All cell lines displayed a lack of sensitivity to TNF-alpha, although some degree of sensitivity to TNF-alpha could be observed in the presence of actinomycin-D or after treatment with IFN-gamma. The early-stage-derived cell line was sensitive to the growth inhibitory effects of TGF-beta 1, but late-stage-derived tumor cell lines displayed a loss of sensitivity to TGF-beta 1 which correlated with the increased expression of TGF-beta 1 mRNA. Altogether, this suggests that tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression patterns during HCC progression. This model of HCC could be of valuable interest to assess the impact of various immunotherapeutic strategies on modulation of tumor growth.
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PMID:Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor-alpha and transforming growth factor-beta mRNA production. 935 45

ONO-4007 is a new synthetic lipid A analog with low endotoxic activities. We previously found that ONO-4007 induced the production of tumor necrosis factor (TNF)-alpha in rat hepatoma KDH-8 tumor tissues and brought about the regression of transplanted KDH-8 cells. By contrast, ONO-4007 did not induce TNF-alpha production in spleens and sera 90 min after treatment. In the present study we attempted to elucidate how ONO-4007 induces TNF-alpha production in tumor tissues locally. We found that extracellular matrix including gelatin, fibronectin and Matrigel did not induce TNF-alpha production in splenocytes treated with ONO-4007 in vitro. However, splenocytes co-cultured with cKDH-8/11 tumor cells in the presence of ONO-4007 produced more TNF-alpha than splenocytes cultured by themselves in the presence of ONO-4007. The stimulation of cKDH-8/11 cells in the presence of ONO-4007 for splenocytes to produce TNF-alpha depended on the type of contact between the cells. The cKDH-8/11 cells fixed in formalin were not able to induce TNF-alpha production of splenocytes even in the presence of ONO-4007. However, syngeneic fibrosarcoma cell line KMT-17/A3, allogeneic hepatocellular carcinoma cell line LDH and rat lung endotherial cell line RLE induced TNF-alpha production in splenocytes, but their stimulation was weaker than that of cKDH-8/11. The soluble form of the cKDH-8/11 cell membrane did not stimulate splenocytes to produce TNF-alpha in the presence of ONO-4007. cKDH-8/11 cells did not stimulate the splenocytes devoid of macrophages to produce TNF-alpha in the presence of ONO-4007.
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PMID:The mechanism of locally enhanced production of tumor necrosis factor-alpha in tumor tissues by the administration of a new synthetic lipid A analog, ONO-4007, in hepatoma-bearing rats. 940 16

ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. ONO-4007 was effective against KDH-8, a tumor necrosis factor (TNF)-sensitive rat hepatoma cell line, but neither effective against KMT-17, a TNF-resistant rat fibrosarcoma cell line, nor SST-2, a TNF-resistant rat mammary adenocarcinoma cell line. We have established two sublines from KDH-8 to further examine the therapeutic mechanisms of ONO-4007 in vivo: TNF-sensitive KDH-8/YK and TNF-resistant cKDH-8/11. The two sublines equally proliferated in vitro. Multiple systemic i.v. administration of ONO-4007 was performed on days 7, 14 and 21 after tumor implantation. Although treatment with ONO-4007 had no effect on the growth of cKDH-8/11 in WKAH rats in vivo, 60% of KDH-8/YK-bearing rats treated with ONO-4007 survived. The administration of ONO-4007 brought about significant therapeutic effects on KDH-8/YK-bearing rats but not on cKDH-8/11-bearing rats. These results suggest that ONO-4007 is therapeutically useful for the treatment of TNF-alpha-sensitive tumors.
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PMID:Therapeutic effects of a new synthetic lipid A analog, ONO-4007, on rat hepatoma KDH-8 depend on tumor necrosis factor-sensitivity of the tumor cells. 940 18

Characteristics of human hepatoma cell lines with the wild-type p53 were compared with those of human hepatoma cell lines with the mutant-type p53. The p21 protein located downstream of p53 was expressed in cell lines with the wild-type p53 but was not expressed in cell lines with the mutant-type p53. As to other tumor suppressor genes such as p16 and p27, there was no difference in their expression between both types of cell lines. In addition, no marked difference was observed in the activities of CDK2 and CDK4 between cell lines with the wild-type and the mutant-type p53. Phosphorylated Rb protein was detected in all cell lines except the HLE line, indicating that this cell line may have a deletion of and/or a mutation of the Rb gene. These results indicate that abnormalities of tumor suppressor genes other than p53, p16, p27, and Rb may be involved in hepatocarcinogenesis. The population doubling time of the wild-type p53 cells was significantly longer than that of the mutant p53 cells. Neither type of cell line showed a specific chromosome distribution which would indicate karyotype instability. The cell lines expressing the wild-type p53 produced tumors at lower frequency than those with the mutant p53 gene. Although there was no significant difference in effects of TGF-beta 1, EGF, cholera toxin, and db-cAMP on cell growth between the two types of cells, all three cell lines with the wild-type p53 were resistant to cytotoxicity of TNF-alpha, while two of the three with the mutant p53 were very sensitive to its cytotoxic effects.
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PMID:Comparison of cellular characteristics between human hepatoma cell lines with wild-type p53 and those with mutant-type p53 gene. 943 73

Lipopolysaccharide (LPS) Binding Protein (LBP) is an acute phase protein with the ability to recognize bacterial LPS and transport it to the CD14 molecule or into HDL particles. It is synthesized in hepatocytes and secreted into the blood stream. LBP levels significantly rise during the acute phase response and levels of LBP may be important for an appropriate host reaction to bacterial challenge and for developing the sepsis syndrome. In order to elucidate the mechanisms of LBP regulation we investigated its transcription pattern and performed promoter studies under experimental conditions mimicking an acute phase scenario. In human hepatoma cell lines stimulation with IL-1 beta, IL-6, TNF-alpha and dexamethasone leads to strong transcriptional activation of the LBP gene in a dose- and time-dependent manner. IL-6 alone induces LBP significantly, whereas IL-1 beta mainly increases the IL-6 effect when applied in combination. Our results furthermore show that AP-1 and C/EBP beta are transcription factors involved in the activation of the LBP gene, as revealed by Luciferase reporter gene analysis and electromobility shift assays. Elucidating the mechanism of transcriptional activation of LBP potentially may help in understanding host-pathogen response patterns and mechanisms involved in the acute phase reaction and in the pathophysiology of sepsis.
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PMID:The transcriptional activation pattern of lipopolysaccharide binding protein (LBP) involving transcription factors AP-1 and C/EBP beta. 944 84

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