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)

The gene regulatory functions of the human IL-2 receptor (IL-2R) were reconstituted in transiently transfected hepatoma cells. The combination of IL-2R beta and -gamma mediated a strong stimulation via the cytokine response element of the alpha 1-acid glycoprotein gene and the hematopoietin receptor response element, but none via the IL-6 response element or the sis-inducible element. IL-2R alpha enhanced 10-fold the sensitivity of the IL-2R beta.gamma complex to respond to IL-2 or IL-15, but did not modify the specificity or the magnitude of maximal gene regulation. A homodimerizing chimeric receptor G-CSFR-IL-2R beta could mimic the IL-2R action. The IL-2R-mediated gene regulation was similar to that seen with receptors for IL-4 and IL-7, but differed from that for IL-6 type cytokines, thrombopoietin, erythropoietin, and growth hormone. The activation of STAT proteins by the IL-2R was assessed in transfected L-cells and COS-1 cells. Although IL-2R subunits were highly expressed in these cells, no STAT protein activation was detectable. Transient overexpression of JAK3 was unable to change the signaling specificity of the hematopoietin receptors in rat hepatoma, L-, and COS cells, but established a prominent activation of the IL-6 response elements by the IL-2R and IL-4R in HepG2 cells. The data support the model that the IL-2R and related hematopoietin receptors produce at least two separate signals which control gene expression.
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PMID:The action of interleukin-2 receptor subunits defines a new type of signaling mechanism for hematopoietin receptors in hepatic cells and fibroblasts. 771 38

Transferrin (Tf) plays an important role during immunologic activation by donating iron to activated lymphocytes. Therefore, synthesis by lymphomyeloid cells has been investigated. Mouse macrophages and macrophage cell lines synthesized Tf, with levels being markedly increased by gamma-interferon (gamma-IFN) and, to a lesser extent, by interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF alpha). Tf was also produced by phytohemagglutinin-stimulated human T cells and two T-cell lines and was increased by IL-2. Even after appropriate activation, none was synthesized by human macrophages or monocytic cell lines or by mouse T cells, T-cell lines, or thymus cells. In both species, B-lineage cell lines were negative. Tf was also synthesised by macrophages from congenitally hypotransferrinemic mice and was responsive to gamma-IFN, but levels were lower than those from normal controls. Synthesis by human and murine hepatoma cells was increased by IL-6 but unaffected by IL-1, TNF alpha, or gamma-IFN. Iron decreased synthesis by hepatoma cells but had no effect on the lymphomyeloid cells. Tf mRNA levels paralleled protein synthesis, suggesting that regulation was pre-translational. Thus, Tf synthesis by lymphomyeloid cells is regulated differently from hepatic synthesis, which is consistent with the suggestion that Tf may act in a paracrine (mouse) or autocrine (human) manner on activated lymphocytes.
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PMID:Cytokine-mediated regulation of transferrin synthesis in mouse macrophages and human T lymphocytes. 784 92

Activated and expanded autologous peripheral blood lymphocytes by cultivation with immobilized anti-CD3 antibody and IL-2 have been infused to the patients with hepatocellular carcinoma after culative operation as a randomized clinical trial. This study is on-going and primary efficacy endpoints of this study were disease-free survival and overall survival, and the sample size for the study was designed as a minimum of 146 patients. From interim analysis at the second year from start of the study, Eligible cases were 101, 49 cases in treated group and 52 cases in control. Recurrences were confirmed 13 cases from treated group and 22 cases from control group. Minor adverse reaction were observed in 28 cases (57%).
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PMID:[Prevention of cancer recurrence by infusion of activated autologous lymphocytes]. 787 94

The efficacy of tumor therapy using polyethylene-glycol-modified interleukin-2 (PEG-IL-2), alone or in combination with cyclophosphamide, was studied in advanced metastatic disease in the guinea pig. Line 10 (L10) tumor cells appeared in the axillary lymph node only 7 days after intradermal tumor-cell inoculation, and lymph-node leukocytes were almost completely replaced by tumor cells on day 28. Local treatment of the intradermally growing L10 hepatocarcinoma in the guinea pig with a relatively low dose of PEG-IL-2 resulted in regression of the primary tumor and prevention of lymph-node metastases. Therapy was completely curative (4 out of 5 animals) when started on day 7 or 14 after tumor-cell inoculation. When started on day 21, therapy was effective in only some (2 out of 5 cured) of the treated animals. Anti-tumor effects against the primary tumor and against lymph-node metastases were observed only after intratumoral (i.t.) administration of PEG-IL-2. Injection of the agent into or near lymph-node metastases in the absence of the primary tumor had no curative effect. In PBS/BSA-treated control animals the primary tumor and metastases grew progressively. In the treatment of far advanced metastatic disease, the combination of i.t. administration of PEG-IL-2 and i.p. injection of cyclophosphamide (Cy) resulted in improved anti-tumoral effects (5/5 guinea pigs were cured) when compared with monotherapy using either agent (one and none out of 5 animals cured, respectively). PBS/BSA heated controls showed progressive tumor-growth. We conclude that large primary tumors and lymph-node metastases can be treated effectively with PEG-IL-2. The i.t. route of administration is of major importance in the treatment of metastases, since administration of PEG-IL-2 near or into the lymph node had no therapeutic effect. Combination of PEG-IL-2 therapy with systemic injections of Cy significantly improved the curative effects of the treatment of advanced metastatic cancer.
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PMID:PEG-IL-2 therapy of advanced cancer in the guinea pig. Impact of the primary tumor and beneficial effect of cyclophosphamide. 792 81

The antitumor efficacy of IL-2 is limited to renal cancer and melanoma. Several cytokines have been associated with IL-2 in an attempt to improve its activity, without, however, any clear benefit. Recent experimental and clinical studies have suggested the possibility to manipulate the host biological response by immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). On the bases of these considerations, we have designed a neuroimmunotherapeutic protocol with low-dose IL-2 subcutaneous therapy (3 million IU/day for 6 days/week for 4 weeks) plus MLT (40 mg/day orally, starting 7 days before IL-2) in advanced solid neoplasms other than renal cancer and melanoma, which are generally resistant to IL-2 alone. The study included 82 patients, 72 of whom showed distant organ metastases. Tumor histotypes were, as follows: non-small cell lung cancer: 19; hepatocarcinoma: 16; colon cancer: 15; gastric cancer: 11; cancer of pancreas: 11; breast cancer: 6; miscellaneous: 4. Objective tumor regression were achieved in 17/82 (21%) patients, consisting of CR in 4 (liver: 2; pancreas: 1; stomach: 1) and PR in 13 (lung: 4; liver: 4; stomach: 2; pancreas: 1; breast: 1; colon: 1). The median duration of response was 8+ months. A stabilization of disease was obtained in 30 patients, while the other 35 patients progressed. The lack of progression was associated with a significantly higher increase in lymphocyte and eosinophil mean number and with a significantly lower increase in neopterin mean levels. The treatment was well tolerated in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cancer immunotherapy with low-dose interleukin-2 subcutaneous administration: potential efficacy in most solid tumor histotypes by a concomitant treatment with the pineal hormone melatonin. 802 99

Experimental studies have showed that hepatocellular carcinoma (HCC) cells are susceptible to cytolysis of interleukin (IL)-2-activated lymphocytes. Moreover, our previous studies demonstrated that the pineal neurohormone melatonin (MLT) may enhance IL-2 efficacy. On this basis, a study was started with low-dose IL-2 (3 million U/day subcutaneously for 6 days/week for 4 weeks) plus MLT (50 mg/day orally every day given in the evening) as a first-line therapy of unresectable HCC. The study included 14 patients. Objective tumour regressions were obtained in 5/14 (36%) patients (one complete response, four partial responses), with a median duration of 7+ months. 6 patients had stable disease, while the other 3 progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapy with low-dose IL-2 plus MLT is a new well-tolerated and effective therapy of advanced HCC.
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PMID:Low-dose interleukin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma. 815 91

HCC specific transfer factor (S-TF) was extracted from lymphoid tissues of goats immunized with HCC cell suspension. The effect of the S-TF on IL-2 activity and IL-2R expression was observed in vitro. The results showed that IL-2 activity and IL-2R expression in HCC patients but not in normal subjects could be increased by the S-TF. The IL-2 activities and IL-2R expressions in both normal subjects and patients with HCC could not be increased by normal transfer factor (N-TF). This may be one of the anti-tumor mechanisms of S-TF. It suggests that S-TF may be better than N-TF in immunotherapy of human tumors.
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PMID:[Effect of hepatocellular carcinoma-specific transfer factor (HCC-S-TF) on IL-2 activity and IL-2R expression]. 820 Feb 81

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

We examined the role of two T cell-growth factors, interleukin (IL)-2 and IL-4, in expansion of tumor-infiltrating lymphocytes (TILs) from human tumors. In sarcoma, IL-4 (1,000 U/ml) with IL-2 (10 or 1,000 U/ml) grew TILs better than did IL-2 alone in six of 10 cases during 6 weeks of culture. IL-4 decreased the relative number of CD56+ cells, which correlated with a decrease in cytolysis against Daudi in six of 10 cases. The addition of IL-4 with 1,000 U of IL-2 maintained or increased cytolysis against autologous sarcoma, while decreasing nonspecific cytolysis against Daudi or allogeneic sarcoma in three of eight cases. IL-4 decreased cytolysis against both autologous sarcoma and Daudi in four of 10 cases, suggesting nonspecific activity in these instances. In renal cell cancer (RCC), IL-4 with IL-2 (10 or 1,000 U/ml) augmented TIL growth in six of eight cases, especially during the first 2-3 weeks of culture. IL-4 with 10 U of IL-2 increased cytolysis against both autologous RCC and Daudi in six of eight cases, suggesting possible prior cell activation. In contrast, IL-4 addition with 1,000 U of IL-2 maintained or increased cytolysis against autologous RCC, while decreasing cytolysis against Daudi or allogeneic RCC in four of eight cases. In cases of bladder and of prostate cancer, IL-4 with 1,000 U of IL-2 grew TILs slightly better in five of seven cases for the first 2-3 weeks. Bladder TILs grown with IL-2 and/or IL-4 were CD+ T cell predominant (three of five) and rarely lytic for autologous tumor. In colon cancer and hepatoma, TILs grown with IL-2 and/or IL-4 were nonlytic for the autologous tumor. IL-4 in conjunction with IL-2 could therefore augment growth of some TILs especially for the first 2-3 weeks from various human tumors.
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PMID:Expansion of tumor-infiltrating lymphocytes from human tumors using the T-cell growth factors interleukin-2 and interleukin-4. 828 Jul 17

We studied clinical and immunological changes of the post-transfusional syndrome like graft versus host disease (GVDH) in six patients after open heart surgery and in one patient after hepatectomy. In the patient with hepatocellular carcinoma, transcatheter arterial embolization had been previously done. All patients received homologous blood transfusion during and after surgery and erythroderma associated hyperthermia occurred approximately 10 days after operation. Patients receiving open heart surgery died on between postoperative 17th and 21st day. One patient with hepatectomy died on the 29th day after operation. Skin biopsies in all patients showed the findings of acute GVHD. The number of CD3+ and CD4+ T lymphocytes decreased at postoperative day 1, however, the number of CD3+ T lymphocyte increased in three patients after postoperative day 14. The postoperative value of interleukin-2 production was low in patients in whom the value was measured. The immunological status in host has not been clearly resolved. However, the postoperative changes of lymphocytes subsets were abnormal and IL-2 production in two patients showed low level. Therefore, it was considered that pre and postoperative measurement of cell-modiated immunity might predict the occurrence of the post-transfusional GVHD and might be one of useful examinations to prevent the disease.
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PMID:[Post-transfusional syndrome like graft versus host disease]. 839 30


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