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)

Precultured mouse peritoneal macrophages were incubated with a microbial growth inhibitory lymphokine prepared from cell-free ascites of rat Zajdela hepatoma. Cyclic nucleotide metabolism was followed in parallel to experiments demonstrating inhibition of intracellular growth of Corynebacterium murium kutscheri. Maximum increase of cAMP, adenylate cyclase and cAMP-phosphodiesterase activities was found after 60 to 90 min, while inhibition of microbial growth was evident only after 2-3 h. Both effects showed concordant dose dependence. It is concluded that cAMP induces cellular metabolic changes which lead to inhibition of bacterial growth by macrophages.
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PMID:Effect of a microbial growth inhibitory factor on the cyclic nucleotide metabolism of peritoneal macrophages. 626 1

As previously described, a cell surface-associated adhesive glycoprotein capable of inducing not only aggregation of hepatoma cells but also adhesiveness was separated from differentiated rat ascites hepatoma AH136B cells (forming cell islands in vivo) and highly purified by chromatography. The factor functioned as a mitogenic lectin on rat T lymphocytes. Undifferentiated rat ascites hepatoma AH109A cells (present as single cells in vivo) were unable to synthesize the factor. Distinct macrophage chemotactic activity was released in vitro from rat lymphocytes stimulated by this factor; it was detected in culture supernatant stimulated by 1 microgram/ml of the factor, becoming maximal by 10 micrograms/ml. The activity became detectable in 6 hr after stimulation, reaching its peak in 24 hr. Production of this type of chemotactic lymphokine was suppressed by puromycin (2.0 micrograms/ml). It was heat-stable, nondialysable, stable for freeze-thawing and had an approximate molecular weight of 12,500 on gel filtration; it was derived from nylon wool-non-adherent cells (T lymphocytes). AH136B tumour after subcutaneous transplantation was clearly small in size but the skin site was characterized by marked macrophage and lymphocyte reactions; AH109A tumour after similar transplantation was much larger in size but the cell reaction in the skin site was apparently less marked, suggesting an involvement of the lymphokine in the mediation of macrophage reaction in the tumour site.
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PMID:Immunological function of adhesive glycoprotein from rat ascites hepatoma cells: production of macrophage chemotactic lymphokine. 660 88

CTLs- and lymphokine-induced apoptosis of infected hepatocytes during the course of chronic viral hepatitis is thought to be important for both disease termination and prevention of hepatocellular transformation. We therefore studied apoptosis induced by Fas (APO-1 or CD95)-a widely expressed cell surface receptor whose ligand is involved in lymphocyte cytotoxicity-in a set of human hepatoma cell lines. As normal hepatocytes, all of the human hepatoma cell lines tested do express detectable amounts of Fas on their surface. Nevertheless, only PLC/PRF/5 cells undergo apoptosis following treatment with anti-Fas. Systematic cloning and sequence analysis of the Fas cDNA did not show mutations in the Fas gene in any of the cells lines tested. However, due to alternative splicing, 5 to 10% of the Fas cDNAs are deleted of 63 internal nucleotides corresponding to the transmembrane domain, thus encoding for a soluble and secreted form of Fas (Fas delta TM), potentially able to neutralize anti-Fas or Fas-Ligand. Although we could not demonstrate a direct correlation between resistance of different hepatoma cell lines to Fas mediated death and endogenous expression of this transcript, we show that PLC/PRF 5 stable transfectants overexpressing Fas delta TM are less sensitive to anti-Fas than control cells. In three different cell lines, resistance to anti-Fas was overcome by treatment with the protein synthesis inhibitor cycloheximide. Although this could suggest the existence of short-lived repressors of the Fas-activated apoptotic signalling pathway(s), we show that translational inhibition is not required for the synergistic effect of cycloheximide to take place, and that resistant hepatoma cells can be sensitized to anti-Fas by subinhibitory concentrations of this protein synthesis inhibitor. Since cycloheximide is able to activate intracellular signalling independently on its effects on protein synthesis, we suggest that it might provide a costimulatory signal that cooperates with Fas in the induction of cell death and that, at least in the cells we tested, resistance to Fas is not an active process involving gene transcription and translation but only the consequence of an inadequate apoptotic stimulation.
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PMID:Resistance to Fas-mediated apoptosis in human hepatoma cells. 756 76

We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in patients with relatively large hepatocellular carcinomas. These parameters were normal in cirrhosis. Some evidence had suggested a gamma-interferon production defect as the main cause of depressed lymphokine-activated killer activity in hepatocellular carcinoma, (i.e., gamma-interferon enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer induction). However, we were unable to clinically define the precise mechanism operating here because gamma-interferon production and lymphokine-activated killer activity were both defective in advanced hepatocellular carcinoma. In recent years, it has become possible to detect even small hepatocellular carcinomas on ultrasonography and to confirm them by fine-needle biopsy. In this study, we assessed those immune parameters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mechanism of these defects. Lymphokine-activated killer activity was defective in 31 patients (64.6%), whereas gamma-interferon production was defective in only 1 of these patients (2.1%). This observation argues against the hypothesis that defective gamma-interferon production is the primary defect and provides new insight into the mechanism of progression of defective immune function in hepatocellular carcinoma. Thirty-one of the 48 hepatocellular carcinoma patients were treated surgically, and these immune parameters were followed for 6 mo. The recovery of lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the tumor burden as the cause of defective lymphokine-activated killer activity.
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PMID:Assessment of lymphokine-activated killer activity and gamma-interferon production in patients with small hepatocellular carcinomas. 768 18

Hepatocellular carcinomas 1 cm in diameter with high or low echogenicity can be detected on ultrasonography and confirmed on fine-needle biopsy, but it is still very difficult to detect small hepatocellular carcinomas with isoechogenicity. In this study, we assessed lymphokine-activated killer cell activity and interferon-gamma production prospectively every 1 to 3 mo for 23 +/- 4 mo (mean +/- 1 S.D.) in 227 patients with cirrhosis. Transient depression of lymphokine-activated killer activity was detected in 43 patients (defective lymphokine-activated killer group), and hepatocellular carcinoma was detected in 24 cases before the end of the 18-mo follow-up. Twenty-one (87.5%) of the 24 hepatocellular carcinoma patients were included in the defective lymphokine-activated killer group. Defective lymphokine-activated killer activity was detected more than 6 mo before detection of a space occupying lesion in the liver or elevation of alpha-fetoprotein level above 400 ng/ml. Serum alpha-fetoprotein level was elevated above 400 ng/ml in only five cases in which hepatocellular carcinoma was detected as a space-occupying lesion. Our results indicate that sequential assessment of lymphokine-activated killer activity may be a predictor of hepatocellular carcinoma and that the depression of immune function in cirrhotic patients is a serious risk factor for hepatocellular carcinoma emergence.
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PMID:Depressed immune function in patients with cirrhosis before emergence of hepatocellular carcinoma. 768 81

To determine improved postresection survival in patients with hepatocellular carcinoma, two postoperative protocols were compared: adoptive chemoimmunotherapy versus chemotherapy. Following resection, 24 patients were allocated at random to receive (1) arterial infusion of Adriamycin, recombinant interleukin-2 and lymphokine-activated killer cells or (2) arterial infusion of Adriamycin alone. The spleen was removed at operation and used to prepare lymphokine-activated killer cells. Each group had 12 patients. They were followed until signs of recurrence appeared. The overall survival rates of the patients were 91.7%, 82.9%, and 72.5% at 1, 2, and 3 years, respectively, and slightly higher than would be expected with surgery alone. No statistically significant difference was found between the two groups either in the survival rate (generalized Wilcoxon test, P = .936) or in the cumulative disease free rate (P = .182). However, when patients who had had hepatic resection with negative margin (> or = 1 cm) were separated, the 2-year cumulative disease-free rate in the adoptive chemoimmunotherapy was higher (83.3%, n = 6) than that in chemotherapy (37.5%, n = 8). Toxicity to adoptive chemoimmunotherapy was moderate; no severe side effects were observed. Totally no statistical difference between the two groups was found. Although only one of six patients in adoptive chemoimmunotherapy experienced recurrence after hepatic resection with negative margin, it was not feasible to determine the role of interleukin-2 and lymphokine-activated killer cells. We conclude that the adoptive chemoimmunotherapy in this study is not an ideal adjuvant protocol after hepatic resection.
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PMID:Adjuvant chemoimmunotherapy for hepatocellular carcinoma patients. Adriamycin, interleukin-2, and lymphokine-activated killer cells versus adriamycin alone. 774 15

We examined whether anti-cancer cells are induced in vivo in hepatocellular carcinoma (HCC) by OK-432. Ten patients with HCC were randomly divided into two groups. The group I patient (n = 5) served as the control. In group II (n = 5), OK-432 was preoperatively administered via the hepatic artery. Tumor infiltrating lymphocytes (TILs) were collected from resected tumors. Cytotoxicity of TILs against K562 cells and Raji cells was studied with phenotypic analysis by flow cytometry. Freshly isolated TILs, whether or not treated with OK-432, showed low cytotoxicity. When TILs were co-cultured with recombinant interleukin-2 (rIL-2), the cytotoxicity was significantly activated in the OK-432 treated group, whereas untreated TILs showed no activation. The natural killer (NK) activity and the lymphokine-activated killer (LAK) activity were depressed in group I after hepatic resection, but patients in group II had no depression. Our data indicate that LAK precursor cells are induced in TILs and the prevention of post-operative immune suppression is made possible by OK-432.
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PMID:[Induction of anti-cancer cells and systemic immune response in hepatocellular carcinoma by OK-432]. 794 16

We investigated the question whether lymphokine-activated killer precursor (pre-LAK) cells are induced by OK-432 in vivo, in hepatocellular carcinoma (HCC). Ten patients with HCC were randomly divided into two groups. In group A (n = 5), OK-432 was pre-operatively administered via the hepatic artery. The group B patients (n = 5) served as controls. Tumor-infiltrating lymphocytes (TILs) were collected from the resected tumors. The cytotoxicity of TILs against natural killer (NK)-sensitive K562 cells and NK-insensitive Raji cells was examined by phenotypic analysis with flow cytometry. Freshly isolated TILs, whether treated with OK-432 or not, showed low cytotoxicity against both tumor cells. However, OK-432 pretreatment increased the T-lymphocyte population of TILs, particularly with interleukin-2 (IL-2) receptor positive cells. When TILs were co-cultured with recombinant interleukin-2 (rIL-2), the cytotoxicity was significantly activated in the OK-432 treated group, while untreated TILs showed no activation (P < 0.05). We postulate that pre-LAK cells are induced by OK-432 in TILs, mainly from the T-lymphocyte population. The possibility that LAK cells can be endogenously induced in HCC if OK-432 and rIL-2 are concomitantly administered needs to be considered for immunotherapy to HCC.
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PMID:Induction by OK-432 of lymphokine activated killer precursor cells in hepatocellular carcinoma. 795 72

Immunotherapy with lymphokine-activated killer (LAK) cells and interleukin 2 is one of the newer treatment modalities for cancer. This raises important questions concerning synergism or suppressive effects of other existing treatment modalities on adoptive immunotherapy with LAK cells. A tumor model with H4IIe hepatoma cells grown on each flank of ACI rats was developed to evaluate the effect of external beam irradiation of tumors on the subsequent concentration of LAK cells in these tumors. Tumors on one side were irradiated at 6, 12, or 16 Gy prior to injection of [3H]thymidine-labeled LAK cells. The effect of irradiation was measured as the ratio of 3H recovered in the unirradiated tumor compared to that in the irradiated tumor in the same animal as a function of dose and time after irradiation. This ratio was significantly greater than 1.0 for a radiation dose of 12 Gy (2.35 +/- 0.51) measured 2 days after irradiation, indicating a reduction in LAK cell numbers in the irradiated tumor. This reduction in LAK cell number persists up to at least 4 days following radiation exposure. A similar experiment using 125I-labeled interleukin 2 showed equal distribution in the irradiated and unirradiated tumors. Our data demonstrates that the concentration of LAK cells is markedly reduced by prior radiation, in contradistinction to increased uptake of immunoglobulins in irradiated tumors, as shown by others. If a similar reduction is observed for longer duration after radiation exposure, it might suggest a clinically important interaction between prior radiation exposure and adoptive immunotherapy.
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PMID:Effect of tumor irradiation on the uptake of lymphokine-activated killer cells in a murine tumor model. 813 77

A randomized study using spleen-derived lymphokine-activated killer (LAK) cells in hepatocellular carcinoma (HCC) is reported. We induced cytotoxic lymphocytes from resected spleen of HCC. The effect of recombinant interleukin-2 (rIL-2)-activated spleen cells for prevention of recurrence of HCC after hepatic resection was studied. Enough mononuclear cells could be harvested from the resected spleens. The induction of activated spleen cells was carried out by culture in fresh medium containing 1,500 JU/ml of IL-2. The cytotoxicity of the activated spleen cells maintained high levels during the culture period ranging from 3-30 days. These autologous activated spleen cells were administered to patients 2 days after the intra-arterial infusion of Adriamycin. A randomized study using these spleen LAK cells resulted in lower recurrence rates in the LAK IL-2-treated group. No severe side effects were observed. The lymphocytes derived from resected spleens were useful as the source of effector cells in clinical adoptive immunochemotherapy for HCC, because of their higher cytotoxicity and the simplicity of gaining a large amount of cells.
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PMID:Postoperative chemoimmunotherapy for the treatment of liver cancer. 821 Sep 15


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