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

Interferon alpha is the only available therapy for patients with chronic hepatitis B. With interferon alpha 3-15 MU thrice weekly or 5 MU daily during 3-6 months one-third of the patients achieve seroconversion of HBeAg and HBV-DNA together with normalization of aminotransferases and slight improvement of histology. Loss of HBsAg is reported in a minority of responders during treatment, but increases during follow-up. Patients with baseline alanine aminotransferase of at least twice the upper limit of normal and low HBV-DNA concentration achieve the best response rates. HIV-positive patients with low CD4 counts and Asians are poor responders. As side-effects influenza-like symptoms are experienced by almost all patients. Mild leukopenia, thrombocytopenia and decreased hairgrowth are frequently reported. Severe depression, depersonalization and psychosis are reported in a small number of patients but tend to be poorly recognized in some studies. The decision whether dose reduction is indicated seems strongly related to the opinion of the investigator. Although long-term effects on the occurrence of cirrhosis and the development of hepatocellular carcinoma are not available yet, the achieved results are promising.
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PMID:Current status of interferon alpha in the treatment of chronic hepatitis B. 143 94

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

It has recently been hypothesized that tumor cells with reduced levels of MHC class I antigens are more susceptible to NK-mediated lysis and are rejected by NK cells, whereas tumor cells with normal levels of class I are rejected by tumor-specific CTL. We have tested this hypothesis using a mouse hepatoma system. The Hepa-1 tumor is a spontaneous H-2Kb loss variant that arose from the BW7756 tumor, when BW7756 was adapted to growth in culture. Our studies have shown that despite the loss of H-2Kb antigen, Hepa-1 is not more susceptible to NK lysis than its H-2Kb-transfected variants. These studies also suggested that NK cells were not responsible for rejection of the Hepa-1 tumor. The Hepa-1 tumor, therefore, appears to contradict the hypothesized linkage of MHC levels and NK susceptibility. Because NK cells are not involved in immunity to this tumor, we have sought to identify the effector cell responsible for Hepa-1 rejection. Cytotoxic T lymphocyte assays demonstrate that in vitro, Hepa-1 cells are lysed by Hepa-1-specific H-2Db-restricted CD4-CD8+ T lymphocytes. Footpad assays demonstrate that in vivo, Hepa-1 rejection requires CD4+CD8- and CD4-CD8+ Hepa-1-primed splenocytes. These results indicate that immunity to Hepa-1 is T cell mediated. Hepa-1 is therefore an example of an unusual tumor in that down-regulation of MHC class I antigen expression is associated with increased CTL susceptibility.
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PMID:Mouse Hepa-1 tumor is rejected by H-2Db-restricted CTL despite decreased MHC class I antigen expression. 190 53

Five hepatoma cell lines, including CZHC/8571, PLC/PRF/5, Hep3B, HepG2, and HUH7, were inoculated with three diverse isolates of human immunodeficiency virus type 1 (HIV-1). Productive infection was noted in all hepatoma cell lines, and expression of viral p24 antigen lasted for over 3 months, but its level decreased in proportion to the number of viable cells. HIV-1 antigens were also found in the cells by immunohistochemical staining and radioimmunoprecipitation assay, as were viral RNA by in situ hybridization and HIV-1-like particles by electron microscopy. Virus yield assays were also positive on supernatant fluids collected from hepatoma cultures inoculated with HIV-1. Despite their susceptibility to infection, all five hepatoma cell lines were negative for CD4 by immunofluorescence and for CD4 mRNA by slot-blot hybridization. In addition, HIV-1 infection of hepatoma cell lines was not blocked by anti-CD4 monoclonal antibody or soluble CD4. Together, these findings clearly demonstrate that all five hepatoma cell lines were susceptible to productive infection by HIV-1 in vitro via a CD4-independent mechanism.
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PMID:CD4-independent, productive human immunodeficiency virus type 1 infection of hepatoma cell lines in vitro. 215 30

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

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

A cohort of haemophilic patients who seroconverted to HIV-1 between October 1979 and July 1985 has been followed to 1 January 1992. The median age at initial seropositivity was 24 years with a range of 2-77 years. By January 1992, 38/111 (34%) had developed AIDS and 39/111 (35%) had died (four of liver failure including one hepatoma). Using Kaplan-Meier plots, the calculated progression to AIDS at 12 years is 45% (95% CI 31, 58): for age > 25 years 63% (95% CI 45, 82), age < 25 years 32% (95% CI 15, 48) P = 0.0001; CMV positive 68% (95% CI 48, 87) CMV -ve 20% (95% CI 8, 32) P = 0.0009. The 12-year progression rate to CD4 + 0.2 or AIDS is 66% (95% CI 55, 76). 21/34 (63%) of patients who are p24 antigen positive have developed AIDS compared to 17/77 (22%) who are p24 antigen negative (= 0.0001). 19/34 (56%) and 20/77 (23%) of those p24 positive and negative respectively have died (P = 0.007). Before antiviral and prophylactic treatment for asymptomatic patients there were nine AIDS cases in 3.84 years experience with CD4+ < 0.05 (1/0.43 years) and since treatment, 10 AIDS cases in 18.22 years (1/1.8 years). Age, CMV status and p24 remain strongly predictive of disease progression. Treatment appears to reduce the incidence of AIDS.
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PMID:The progression of HIV disease in a haemophilic cohort followed for 12 years. 838 72


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