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)

Recent progress in biotechnology has uncovered the presence of trace substances which participate in the immunological response between cancer and host; They are cytokines, monoclonal antibodies, and immunomodulating agents produced by effector cells which are called macrophage, NK cells and lymphocytes of cancer patients. Recent genetic engineering enables mass production of these substances, and their clinical application in treating human cancers is expected to take place in the near future. In this paper, the recent trend of cancer treatment, using various cytokines are briefly introduced, namely interferon, interleukin-2, tumor necrosis factor and colony stimulating factor. Although IL-2 is effective for the activation of T-lymphocyte, intravenous injection of IL-2 is not so effective for treatment of cancer-patients. On the other hand, IL-2-activated killer cells (LAK cells) are potent effectors of adoptive immunotherapy in advanced cancer patients. The clinical study was conducted in 25 patients with advanced carcinomas. Therapeutic efficacy was obtained in patients for whom local transfer was undertaken rather than systemic administration. Tumor necrosis factor, a cytotoxin derived from macrophages shows much promise for application in cancer therapy because of its marked antitumor effects and its high specificity to tumors. Clinical study was performed on leukemia patients who showed marked decreases of percentage of leukemic cells in peripheral blood. Moreover, local injection of TNF was very effective for the decrease of tumor size in patients with hepatoma and subcutaneous tumor. In addition, to clinical results using CSF and interferon are reported.
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PMID:[Recent trends in cancer treatment using cytokines]. 247 55

We assessed the feasibility of using lymphokine-activated killer cells (adoptive immunotherapy) with infusions of interleukin-2 when given regionally in three patients with unresectable primary hepatocellular carcinoma (PHC). In 2 patients, 2 cycles, which included a bolus of LAK (10(7) to 10(8) cells followed by a 4-hourly infusion of IL-2 were administered via selective arterial catheterization of the hepatic artery. One further patient received 3 cycles of IL-2 alone by direct intralesional and perilesional injections. Minimal toxicity was observed and side effects such as fever were comparable to those observed with systemic infusions of IL-2 alone. Serial alpha-fetoprotein (AFP) levels initially fell but subsequently rose within 2 to 4 weeks of therapy. AFP levels had not reached pre-treatment values at 4 months in 2 patients, 1 of whom was alive and well at 15 months follow-up.
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PMID:Adoptive immunotherapy administered via the hepatic artery and intralesional interleukin-2 in hepatocellular carcinoma. 247 51

Peripheral blood and tumor-infiltrating T lymphocyte subsets in BERH-2 hepatoma-bearing rats were investigated by indirect immunofluorescence stain and flow cytometry. Based on the above study, comparison of immunoregulatory action and inhibitory effect on the tumor were also done in vivo among several groups which received IFN, IL-2, 5-FU, combined immunotherapy (CI) or immunochemotherapy (IC), respectively. The results indicated that T lymphocyte subsets in hepatoma-bearing rats would undergo changes which were closely related with tumor growth and metastasis. IC had multiple phased advantages against the tumor, such as improving immunity, eliminating immunosuppression and directly killing the tumor cells. It is a valuable therapeutic regime in hepatoma.
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PMID:[Changes of T lymphocyte subsets in BERH-2 hepatoma-bearing rats and effect of different immunotherapies on the tumor]. 248 58

To clarify the immunological effects of transcatheter arterial embolization (TAE) therapy for hepatocellular carcinoma (HCC), various immunological parameters were measured before and after TAE respectively. In most effective group of which AFP levels at first week after TAE therapy had decreased more than 50% compared with those before TAE, the percentage of OKT-4 and IL-2R positive cells in the peripheral blood lymphocytes (PBL) had significantly increased in number. In addition, IL-1, TNF, IL-2 and LAK activity were also enhanced by it. These immunological enhancement after TAE therapy was suggested to be a favourite condition for transferring LAK cells to the patients with HCC. Therefore the combination therapy with TAE and LAK-adoptive immunotherapy was conducted in 12 patients with HCC. Partial response to it was obtained in one case and minor response in three. However, no effectiveness was also found in eight (Progressive Disease: 1 case, No Change: 7 cases). Immunological response after combined TAE-LAK adoptive immunotherapy revealed that NK activity and LAK activity were markedly enhanced. Furthermore, the percentage of OKT-11+, IL-2R+ and Leu-7- 11c+ cells in the PBL had increased in number with statistically significant differences and OKT-8+ cells had increased in relative number. In conclusion, this study suggested that this combination therapy might be a well designed immunological and clinical therapy for HCC because it was done under the condition of well enhanced immunological parameters against tumors.
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PMID:[An immunological and clinical evaluation of combined TAE-LAK adoptive immunotherapy]. 255 34

Interleukin-2 has proved to be effective for the intralesional treatment of tumors of the bladder. There are examples in literature of hepatocellular carcinoma (HCC) treatment with lymphokine-activated killer (LAK) cells infused in the hepatic artery. We decided to check the effects of echo-guided intralesional injection of these cells in this disease. We treated 5 patients with inoperable hepatocellular carcinoma, following cirrhosis; in 4 cases the mass had a diameter less than 3 cm (small HCC) while in the remaining case it measured 7 cm. Tumor size remained unchanged in 3 of the 4 small HCC, and increased only slightly in the other (over a period of 10 months). This would appear to indicate that treatment halted neoplasm growth or at least slowed it down. The echo pattern of the lesions changed, with a constant reduction in echogenicity. Finally, in multiple control biopsies, fibrosis, present in only one case before treatment, was found fairly constantly after treatment. There were no significant side effects, apart from slight water retention in one patient. On the basis of our preliminary results, we consider it worthwhile continuing this study to establish the most suitable IL-2 doses and analyze in more detail the modifications induced in the neoplasm.
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PMID:Intratumoral echo-guided injection of interleukin-2 and lymphokine-activated killer cells in hepatocellular carcinoma. 255 85

Tumor-infiltrating lymphocytes (TIL) were isolated from 40 of 51 consecutive human liver tumor samples (primary hepatocellular carcinoma, 16 of 18; metastatic, 23 of 29; benign, one of four). Functional and phenotypic characteristics of fresh and recombinant interleukin-2 (rIL-2)-expanded TIL were evaluated. The expansion of TIL from hepatic tumors in the presence of 1000 units/ml of rIL-2 was possible in 60% of cases. In comparison to TIL from metastatic liver tumors, TIL obtained from primary liver tumors expanded faster and better in rIL-2 cultures. Expanded TIL from primary tumors had significantly higher cytotoxicity against K562 targets, but not Raji targets, than those from metastatic tumors. Cytotoxicity against fresh autologous tumor targets was detected in seven of eight cultures tested. TIL from primary tumors retained antitumor reactivity significantly longer in culture. The optimal in vitro cytotoxicity was achieved between days 20 and 60 of culture in the presence of rIL-2. Antitumor activity was associated with the increase in these TIL cultures of a cell population expressing the Leu19 antigen with or without the CD3 antigen. The frequency of the CD3+Leu19+ population showed a bimodal distribution during culture: the first peak of CD3+Leu19+ cells occurred between days 30 and 60 and was associated with the increased antitumor activity; the second peak occurred after day 60 and was not associated with activity. These findings demonstrate that TIL from most human hepatic tumors can be successfully isolated, cultured in rIL-2, and enriched in Leu19+ effectors. In addition, these TIL upon IL-2 activation in vitro are capable of lysing fresh autologous and/or allogeneic tumor targets.
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PMID:Functional and phenotypic analysis of tumor-infiltrating lymphocytes isolated from human primary and metastatic liver tumors and cultured in recombinant interleukin-2. 264 28

Recently, we developed an intrahepatic artery catheter and a device attached with an implantable double lumen reservoir. In this paper, we present clinical experience with this device in 15 cases of hepatocellular carcinoma and the results of an experimental study using canine regarding the significance of arterial infusion therapy with occlusion of hepatic arterial flow. Adriamycin and CDDP were used as anticancer agents, and in 3 out of 15 cases IL-2 and LAK cell were used as chemoimmunotherapy. Twenty-one infusions were possible without any severe side effects. This treatment was also safely done even in the out-patient clinic. In one case extravasation of drug and another case of fever caused by catheter were seen, which was easily diminished by conservative treatment. Ten cases were estimated for antitumor effects and 5 showed partial remission. In experimental study, augmentation of the intrahepatic tissue level of adriamycin was found with occlusion of arterial flow. Intra-arterial infusion therapy using this device promises to be a most useful routine method for cancer control in the outpatient clinic.
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PMID:[Intra-arterial infusion chemotherapy under flow occlusion using a double lumen reservoir]. 278 9

Lymphokine activated killer cell is a newly described lytic system against a variety of solid tumours and is distinct in several respects from the classic cytolytic T cell and the natural killer systems. This study was conducted to evaluate the lytic activity of lymphokine activated killer cells against fresh autologous and allogeneic, as well as cultured hepatocellular carcinoma cells. Lymphokine activated killer cell was generated by incubating peripheral blood mononuclear cells with various concentrations of recombinant IL-2 (rIL-2, Cetus, USA) for various periods of time. A four hour 51Cr release assay was used to measure cytotoxicity. The results show that fresh and cultured hepatocellular carcinoma cells were only slightly susceptible to natural killer cells. Normal hepatocytes were resistant to lymphokine activated killer-mediated lysis. Lymphokine activated killer cells could be generated from mononuclear cells of hepatocellular carcinoma patients and normal subjects with lytic activity against fresh autologous and allogeneic and cultured hepatocellular carcinoma cells, but lymphokine activated killer cells from the former was less efficient than that from the latter. It is concluded that the adoptive immunotherapy with combined rIL-2 and lymphokine activated killer may be worth trying in early cases of primary hepatocellular carcinoma.
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PMID:Lysis of primary hepatic tumours by lymphokine activated killer cells. 303 Aug 99

Numatrin is a tightly bound nuclear matrix protein (40 kD/pI-5) whose synthesis is markedly and promptly increased in association with cellular commitment for mitogenesis in B lymphocytes. (Feuerstein, N., and J.J. Mond. 1987. J. Biol. Chem. 262:11389-11397). To study whether this event is exclusively associated with proliferation of B lymphocytes, we examined the synthesis of numatrin in T lymphocytes (murine and human) activated by lectins or by anti-T cell antigen receptor monoclonal antibody and in Swiss 3T3 fibroblasts stimulated by growth factors. We showed a close correlation between induction of DNA synthesis and induction of numatrin synthesis in T lymphocytes stimulated by concanavalin A, anti-T cell antigen receptor monoclonal antibody, and IL-2 in murine T cells. Similar results were observed in Swiss 3T3 fibroblasts, thus only combinations of growth factors (insulin/EGF or insulin/B subunit of cholera toxin) or serum, which induced a significant increase in DNA synthesis, were also associated with a significant increase in synthesis of numatrin. Similar to B cells, the increase in numatrin synthesis in fibroblasts was found to occur at early G1 phase. The calcium ionophores, A23187 and ionomycin, previously shown to induce an increase in c-myc and c-fos mRNA levels in fibroblasts, induced a marked increase in the synthesis of a nuclear protein at 80 kD/pI-5 but failed to induce an increase in the synthesis of numatrin indicating that an increase in intracellular Ca++ level is not sufficient for induction of the synthesis of numatrin. This further indicates that the increase in synthesis of numatrin may be more closely correlated with cellular commitment for mitogenesis as compared with other biochemical parameters. Using a polyclonal numatrin antibody we demonstrated that mitogen stimulation is also associated with a marked increase in numatrin abundance, which reached a peak at the onset of S phase and declined at the end of S phase. Evidence is presented to show that numatrin synthesis and abundance is elevated in various lymphoma cell lines. Using indirect immunofluorescence assays we showed that numatrin is abundant in other malignant cells: KB, epidermoid carcinoma, and Hep2 human hepatoma. Immunofluorescence studies further showed that mitogen stimulation of B lymphocytes induced a marked accumulation of numatrin in the nucleoli. This observation is in accord with the recent finding of identity of numatrin with the nucleolar protein B23 (Feuerstein et al. 1988. J. Biol. Chem. 263:10608-10612).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The nuclear matrix protein, numatrin (B23), is associated with growth factor-induced mitogenesis in Swiss 3T3 fibroblasts and with T lymphocyte proliferation stimulated by lectins and anti-T cell antigen receptor antibody. 314 28

In the present study, we observed the therapeutic effect of the fibroblast-mediated human IFN alpha gene therapy in combination with IL-2/AK/DOX adoptive chemoimmunotherapy on human hepatocellular carcinoma-bearing nude mice. Activated killer cells (AK) were prepared from human peripheral mononuclear cells co-stimulated in vitro with IL-2 and inactivated human hepatocellular carcinoma SMMC 7721 cells. The results demonstrated that (1) When the NIH3T3-IFN-alpha+ cells were implanted i.p. to the tumor-bearing nude mice, the growth of tumor was inhibited and the survival time of the mice was prolonged; (2) The growth of tumor was significantly inhibited when AK was injected i.v. and IL-2 was injected i.p. after the NIH3T3-IFN-alpha+ cells had been implanted; (3) The best therapeutic results could be achieved when NIH3T3-IFN-alpha+ cells were used in combination with IL-2/AK/DOX. All these results suggeste that the fibroblast-mediated human IFN-alpha gene therapy could be used to treat human hepatocellular carcinoma but better results can be obtained when used in combination with IL-2-based immunotherapy.
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PMID:[Experimental study on the treatment of human hepatocellular carcinoma by fibroblast-mediated human IFN-alpha gene therapy in combination with adoptive chemoimmunotherapy]. 758 92


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