Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.
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PMID:Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma. 131 67

To investigate the decrease in natural killer (NK) activity in chronic liver disease, interleukin-2 receptor beta chain (IL-2R beta) expression was assessed by peripheral blood lymphocytes (PBL) using flow cytometry and an IL-2R beta chain-specific mouse monoclonal antibody. The percentage of IL-2R beta chain-positive PBL was significantly decreased in patients with chronic viral hepatitis, liver cirrhosis and hepatocellular carcinoma in comparison with normal controls (P less than 0.01). Among chronic viral hepatitis patients, it was significantly less in those with chronic active hepatitis than in those with chronic persistent hepatitis (P less than 0.05). Two-colour flow cytometry revealed that the IL-2R beta chain was mainly expressed by CD8+ or CD16+ cells in both the controls and the liver disease patients. CD8dull+ cells (NK cells) constituted more than 60% of the CD8+ cells expressing the IL-2R beta chain. Expression of the IL-2R beta chain with CD8 or CD16 was also significantly decreased in chronic liver disease patients compared with controls. In chronic viral hepatitis, there was a significant correlation between NK activity and the percentage of IL-2R beta+ PBL (P less than 0.001, r = 0.916), as well as between NK activity and the percentage of PBL co-expressing both the IL-2R beta chain and CD16 (P less than 0.001, r = 0.850). These findings suggest that decreased expression of the IL-2R beta chain by PBL may result in diminished NK activity in chronic liver disease.
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PMID:Decreased interleukin-2 receptor beta chain expression by peripheral blood lymphocytes in chronic liver disease. 132 98

To generate autologous-tumor-specific cytotoxic T cells (CTL), peripheral blood mononuclear cells (PBMC) obtained from cancer patients were cultivated with autologous tumor cells for 5 days, and restimulated with interleukin-2 for another 5 days. Subsequently, their cytotoxic activity was examined by an in vitro cytotoxic test as well as by Winn's assay utilizing nude mouse transplanted autologous tumors. The present results demonstrated that these in vitro-stimulated cells were able to kill autologous tumor cells but not allogeneic tumors, and that they also inhibited the growth of transplanted autologous tumors in the nude mouse. Their cytotoxic activity was completely abrogated by pre-treatment with either anti-CD3 or anti-CD8, but not with anti-CD4, plus complement. Based on these studies, we injected these CTL via the hepatic artery into patients having either nonresected tumors or recurrent tumors in the liver. Among 15 treated patients (13 with hepatocellular carcinoma and 2 with metastatic liver cancer) 2 complete responses, 3 partial responses and 4 minor responses were observed. During the 6 to 25 months following injection of CTL, no definite signs of tumor recurrence or regrowth were demonstrated in these 5 responding patients (complete plus partial).
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PMID:Induction of autologous tumor-specific cytotoxic T cells in patients with liver cancer. Characterizations and clinical utilization. 167 33

The distribution and number of CD2 (Coulter T11)+ cells, CD16 (Leu 11b)+ cells, Leu 7+ cells, CD8 (OKT 8)+ cells, CD11 (Leu 15)+ cells, CD4 (Leu 3a + 3b)+ cells and Leu 10+ or Leu 14+ cells in the liver of patients with hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC) were investigated using monoclonal antibodies and immunohistological methods. In the majority of those with HCC and MLC, CD8 (OKT 8)+, Leu 7+ and CD16 (Leu 11b)+ cells were present both in the tumor and non-tumor tissues. The CD8 (OKT 8)+ cells were more numerous than Leu 7+ and CD16 (Leu 11b)+ cells. No significant difference was observed in the distribution and number of Leu 7+ and CD16 (Leu 11b)+ cells, in any area, in both groups. The number of CD8 (OKT 8)+ cells predominated in the non-tumor area, in both groups. CD11 (Leu 15)+ cells and CD8 (OKT 8)+ cells were present in the ratio of 1:3 or 1:4. The number of CD4 (Leu 3a + 3b)+ cells was less than that of CD8 (OKT 8)+ cells in both groups, especially in the tumor area. A few Leu 10+ or Leu 14+ cells were present in all areas, in both groups. In most cases of MLC, the CD8 (OKT 8)+ cells were absent in the tumor area. There was no correlation between the distribution and number of these cells and anti-tumor chemotherapy or non-specific immunotherapy.
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PMID:Immunological analysis and characterization of lymphocyte subsets in specimens of human hepatocellular carcinomas and metastatic liver cancers. 253 91

Autologous mixed lymphocyte reaction (AMLR) and phenotypical composition of circulating lymphocytes obtained from nine subjects with untreated hepatocellular carcinoma (HCC); three HCC patients locally treated by means of intraarterial chemoembolization; six subjects with gut-derived carcinoma (GDC); nine chronic active liver disease patients (CALD), and 14 normal controls have been evaluated, using monoclonal antibodies (MAB) against CD5, CD8, CD4 glycoproteins and anti-LAK-1 molecule, a novel 120-KD surface antigen that is present on the membrane of large granular lymphocytes, by means of classical indirect immunofluorescence technique. Autologous mixed lymphocyte reaction was significantly reduced in all patients, along with CD4-positive cells that are the responder cells in this reaction. A relative increase in the percentage of LAK cells was also observed in neoplastic patients with a normalization after local treatment of the HCC. In the light of promising results obtained by Rosenberg et al. by adoptive transfer of LAK cells activated with Interleukin-2 (IL2) in various cancers, our results support a similar therapeutic trial in HCC patients.
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PMID:Circulating LAK-1 cells and autologous mixed lymphocyte reaction in patients with hepatocellular carcinoma. 253 11

Because primary sclerosing cholangitis (PSC) frequently is associated with inflammatory bowel disease, the phenotypic and functional characteristics of lymphocytes isolated from colonic mucosa were studied in patients with primary sclerosing cholangitis (PSC), patients with ulcerative colitis and patients with other colonic and hepatic disorders. To accomplish this, lymphocytes isolated from colonic biopsies obtained at the time of colonoscopy were expanded in vitro in the presence of interleukin 2 (IL2). Cell propagation was similar in patients with PSC with or without associated inflammatory bowel disease but was diminished significantly when compared to results obtained in patients with ulcerative colitis not associated with PSC. The CD4:CD8 ratio of the propagated lymphocytes was increased in patients with PSC compared to controls. The Leu 19+ subset of cells was also increased in PSC patients. In patients with inflammatory bowel disease, increased cytotoxicity was noted at low effector to target cell ratios with SK-HEP (hepatocellular carcinoma) but not RPMI 7451 (cholangiocarcinoma) targets. No differences between PSC patients and controls were observed for NK sensitive and NK resistant targets. Based upon these studies it can be concluded that: 1) expansion of lymphocytes obtained from endoscopic colonic biopsies using recombinant IL2 represents an alternative method by which intestinal lymphocytes can be studied; 2) natural killer cells are increased in the colonic mucosa of patients with primary sclerosing cholangitis; 3) colonic cytotoxic T lymphocytes may be more active in patients with chronic liver disease and particularly those with associated inflammatory bowel disease.
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PMID:Phenotypic and functional characteristics of colonic lymphocytes isolated from patients with primary sclerosing cholangitis and inflammatory bowel disease. 759 May 74

The localization and distribution of gamma delta T cell receptor (TCR)-positive cells (gamma delta T cells) in hepatocellular carcinoma capsules was investigated immunohistochemically at both light and electron microscopic levels. Most of the mononuclear cells infiltrating the tumor capsules were CD3-positive. Together with gamma delta T cells, they were significantly increased in the tumor capsules compared to amounts in the fibrous septa in non-cancerous cirrhotic areas of the same liver, and compared to amounts in the liver of patients with cirrhosis. Phenotypic characterization by the two-color double-staining technique showed that CD8/gamma delta cells were significantly increased in the tumor capsule, and that more than one-third of gamma delta TCR-positive cells also expressed the CD56 antigen. Morphological observation revealed that large gamma delta T cells were increased in number in the tumor capsule and that the cytoplasm of these cells contained multivesicular bodies and dense granules. These morphological features were similar to those of large granular lymphocytes, and most of the gamma delta T cells were also positive for BB3. This suggests that extrathymic maturation of gamma delta T cells occurs in the tumor capsule, and that these gamma delta T cells may have a cytolytic effect on tumor cells, as shown in large granular lymphocytes; further, the results suggest that these cells may play a role in the defense against tumor expansion.
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PMID:Immunohistochemical study of gamma delta T cell receptor-positive cells in the capsular region of hepatocellular carcinoma: possible role in defense against expansion of carcinoma in the liver. 764

Fischer rats became resistant to syngeneic hepatocellular carcinoma (FAA-HTC1) cells on repeated sensitization with mitomycin C-treated FAA-HTC1 cells. In contrast, FAA-HTC1 cells injected into the liver killed normal control Fischer rats within 2 months. Histopathological studies revealed massive accumulation of mononuclear cells in the tumor tissues of sensitized rats that rejected syngeneic FAA-HTC1 cells, whereas very few mononuclear cells were found in the tumor tissues of control rats. Cell populations infiltrating the tumor tissues were identified by flow cytometric analysis. Mononuclear cells found within the regressing tumors of the sensitized rats were identified as mostly T cells, and two-thirds of these T cells were CD8-positive. Compared with the activity in control rats, the killer activity of mononuclear cells infiltrating tumors was significantly increased in the sensitized rats 7 days after tumor inoculation. Depletion of CD8(+) T cells significantly reduced the cytotoxicity of mononuclear cells infiltrating tumors obtained from sensitized rats. In contrast, depletion of CD16(+) cells reduced the cytotoxicity of mononuclear cells infiltrating tumors obtained from both control and sensitized rats. Furthermore, the CD16(+) cell-depleted fraction of mononuclear cells infiltrating tumors showed significant cytotoxicity against FAA-HTC1 cells, but failed to show cytotoxicity against other syngeneic tumor cells or allogeneic hepatoma cells.
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PMID:Importance of cytotoxic T lymphocytes in the rejection of transplanted hepatocellular carcinoma. 806 96

We performed a detailed analysis of immune responses in a hepatocellular carcinoma (HCC) cell line and effector cells obtained from a patient with HCC. We examined the cytotoxic activity of natural killer (NK) cells, lymphokine-activated killer (LAK) cells and cytotoxic T lymphocytes (CTL) against an autologous tumour cell line (SUHC-1) to investigate the immune mechanism of human lymphocytes against HCC cells. Cytotoxic T lymphocytes were induced by co-culturing of peripheral blood lymphocytes (PBL) and SUHC-1 cells, mixed lymphocyte and tumour cell culture (MLTC). The susceptibility of SUHC-1 to NK and LAK cells was similar to that of other allogeneic cell lines, such as K562, PLC/PRF/5 and Mahlavu. Effector cells induced in the primary MLTC had high cytotoxic activity but were not specific for SUHC-1. Cytotoxic T lymphocytes with specific activity against SUHC-1 were induced after PBL were stimulated five times at 7-10 day intervals with SUHC-1 and low-dose recombinant interleukin-2 (rIL-2), suggesting that as the culture progressed, broadly reactive effector cells disappeared and specific effector cells survived. The specific effector cells were identified as CD3+/CD4+ and CD3+/CD8+ T-lymphocyte subsets. The recognition mechanisms of CD3+/CD4+ CTL remain unresolved because the cytotoxicities were not inhibited by anti-CD4 and anti-major histocompatibility complex (MHC) class II monoclonal antibodies (MoAb). Treatment of cells with anti-CD3, anti-CD8 and anti-MHC class I MoAb partially inhibited lysis. These results demonstrated that the T-cell receptor (TCR)/CD3 complex appeared to be involved in SUHC-1 specific antigen recognition and antigen recognition of CD3+/CD8+ CTL was MHC class I restricted.
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PMID:Immunological responses against an autologous human hepatocellular carcinoma cell line. 828 Aug 38

The immune response in liver cirrhosis and hepatocellular carcinoma is receiving renewed attention in consideration of the possible treatment with biological response modifiers. The aim of this study was to evaluate whether cirrhosis and hepatocellular carcinoma induce any modification in peripheral lymphocyte subsets. Lymphocytes were evaluated (number/percentage) in 61 patients with hepatocellular carcinoma, 35 with cirrhosis and 24 healthy controls. Using flow cytometry, 10 lymphocyte subpopulations were assayed, plus the CD4/CD8 ratio. Results demonstrated no change in the number of lymphocytes; cirrhosis and hepatocellular carcinoma patients had significantly more HLA-DR+ (p = 0.001) and CD3+/HLA-DR+ (activated T) (p = 0.002) and fewer CD3+ (mature T) (p = 0.02) cell than controls; hepatocellular carcinoma patients had significantly more CD3+/CD56+/CD16- (cytotoxic non-MHC restricted T cells) and CD25+ (IL-2 receptor positive cells). If the percentages of all cells with cytotoxic-T activity were pooled, a significant increase (p = 0.03) was seen in hepatocellular carcinoma patients. In conclusion, in contrast to previous data, hepatocellular carcinoma patients reveal an increased number of cytotoxic non-MHC restricted T cells.
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PMID:Activation of cytotoxic and natural killer T-cell system in patients with hepatocellular carcinoma and cirrhosis. 913 93


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