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)

In an attempt to construct bispecific monoclonal antibodies (bimAbs) able to target cytotoxic T lymphocytes against human hepatoma cells, an HGPRT-deficient mutant of the Hepama-6 hybridoma, which produces an antihuman-hepatoma mAb, was directly fused with splenocytes from Balb/C mice immunized by a polyclonal cytotoxic T-cell line. Hybrid hybridomas were selected in HAT medium, and their supernatants were directly screened for the ability to induce IL-2-cultured cytotoxic T lymphocytes to kill hepatoma cells in a 51Cr-release assay. The selected hybrid hybridoma, termed DQ-33, secretes a bimAb, which reacts with a CD3-associated determinant. When resting peripheral-blood lymphocytes were used as effector cells, virtually no cytolytic activity could be induced by DQ-33, whereas phytohemagglutinin-activated lymphocytes that had been expanded in vitro in IL-2-containing medium could be efficiently targeted against hepatoma cells. Targeting by DQ-33 bimAb was analyzed on different subsets of IL-2-cultured lymphocytes. It was evident that CD+4-8+ TCR alpha/beta+ and CD3+4-8-TCR gamma/delta+ lymphocytes were efficiently induced by bimAb to lyse human hepatoma cells, whereas no induction of cytolysis could be observed when CD3 + 4 + 8-TCR alpha/beta+ cells were used as effectors. DQ-33 bimAb was also able to induce lymphokine secretion (IL-2, GM-CSF and TNF-alpha) by all the different subsets of lymphocytes analyzed in the presence of target cells expressing the relevant antigen, independent of the expression of cytolytic activity.
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PMID:Targeting of "T" lymphocytes against human hepatoma cells by a bispecific monoclonal antibody: role of different lymphocyte subsets. 132 41

Interleukin-2 was entrapped in liposomes (Lip-IL-2) and injected into rats. The intraperitoneal injection of Lip-IL-2 into rats bearing an ascites-forming rat hepatoma (AH-66) significantly increased the survival time when compared with rats administered free IL-2 or saline-containing liposomes. The number of peritoneal exudate cells (PEC) increased markedly after intraperitoneal injection of Lip-IL-2 and consisted mainly of macrophages. The level of tumor necrosis factor alpha (TNF-alpha) and the intensity of free radicals increased in the ascites at 48 hrs after Lip-IL-2 administration, whereas TNF-alpha was not detected and the intensity of free radicals did not increase after free IL-2 administration. Our findings suggested that entrapment of IL-2 into liposomes enhanced its potential for cancer therapy, presumably by activating macrophages to produce TNF-alpha and free radicals.
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PMID:Effect of liposomal interleukin-2 on ascites-forming rat hepatoma. 151 92

Recombinant interleukin-2 (rIL-2) and adriamycin were administered systemically to treat nine patients (age 15.5-68 years, mean 48.9 years) with far advanced primary hepatocellular carcinoma. Three patients were newly diagnosed, and the remaining patients had received surgery, transcatheter arterial embolization, chemotherapy and other treatments but without improvement. RIL-2 was given at a dose of 10,000 to 30,000 units/kg every 8 hours for consecutive 9 days, and on the fifth day, a single dose of adriamycin 30 to 60 mg/M2 was administered. Four patients interrupted the immunotherapy because of severe intolerable side effects, 4 patients completed one course and the remaining one received 2 courses of treatment. Various adverse reactions were encountered, however, they subsided promptly after stop of therapy. All patients failed to respond to the regimen. Primary hepatic tumors continued to enlarge in 8 patients and remained unchanged in one, and pulmonary metastases also increased in size and number in 4 patients. Transient decrease in serum alpha-fetoprotein was found in 6 patients. These results suggests that systemic IL-2 immunotherapy, even in combination with chemotherapy, is not effective for the treatment of far advanced hepatocellular carcinoma. However, in viewing of its immune amplifying effect, rIL-2 in combination with other treatment modalities may still be worth trying in early stages of hepatocellular carcinoma.
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PMID:Immunochemotherapy with recombinant interleukin-2 and adriamycin in primary hepatocellular carcinoma. 164 35

More than 10(11) killer cells are needed for adoptive immunotherapy, but it is difficult to obtain so many from patients. Peripheral blood lymphocytes (PBL) treated with lectin and then with recombinant interleukin-2 (rIL-2) give many lectin-induced lymphokine-activated killer (LILAK) cells, studied here for proliferation, cytotoxicity, IL-2 receptors (IL-2R) and subsets. PBL obtained from hepatoma patients or healthy adults were incubated with phytohaemagglutinin (PHA) or concanavalin A (ConA) for 3 days and with rIL-2 for 4 days. Then the medium was replaced with fresh medium containing rIL-2 every 3 or 4 days, with the volume increased as cells proliferated. Cytotoxicity was expressed as the percentage lysis of target cells by 4 h 51Cr release. LILAK cells from healthy adults increased 120-fold in 2 weeks when incubated with ConA; the lymphokine-activated killer (LAK) cells increased 7-fold. The percentage of IL-2R+ cells increased more with ConA than with rIL-2 alone. ConA induced more suppressor T cells than PHA. LILAK cells obtained from patients by PHA treatment increased 180-fold in 2 weeks. Their cytotoxicity to Daudi cells was 1% before culture and 91% in 2 weeks; that of LAK cells was 60%. LILAK cells were cytotoxic to the tumour target cells, but not to allogeneic PBL. Adoptive immunotherapy may become more practical if many LILAK cells can be obtained at once by large-scale culture, such as by a hollow-fibre system.
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PMID:Proliferation and cytotoxicity of lectin-induced lymphokine-activated killer (LILAK) cells. 165 42

Thirty patients with hepatocellular carcinoma who underwent hepatic resection during the recent 2 years in our department were randomized. We derived LAK cells from the autologous spleen removed during operation. The cultivation of LAK cells were done with IL-2. Adriamycin 20mg/body was injected into hepatic artery via subcutaneous implanted reservoir on the 8th postoperative day. In group A, 1.0-7.6 x 10(9) LAK cells were injected i.a on day, 10, 14, and 21 after operation. IL-2 of 5 x 10(5) JU were also injected i.a. during 3 weeks. Group B patients were treated only by adriamycin. High fever was seen in all patients belonged to group A. Twelve patients in each group were evaluable. Recurrence rate 8.3% in group A was significantly lower than 50% in group B. In experimental study, accumulation of 111In-oxine labelled LAK cells in mouse 3LL lung cancer was augmented in splenectomized ones. Adopted immunotherapy by spleen LAK-cells may be effective and safe treatment to preventing recurrence of hepatocellular carcinoma after hepatectomy.
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PMID:[Adopted immunochemotherapy using IL-2 and spleen LAK cell--randomized study]. 165 91

Recombinant interleukin-2 (rIL-2) and adriamycin were administered systemically to treat nine patients (age 15.5-68 years, mean 48.9 +/- 15.5 years) with far advanced primary hepatocellular carcinoma. Three patients were newly diagnosed, and the remaining patients had received surgery, transcatheter arterial embolization, chemotherapy and other treatments but without improvement. rIL-2 was given at a dose of 10,000 to 30,000 units/kg every 8 hours for consecutive 9 days, and on the fifth day, a single dose of adriamycin 30 to 60 mg/m2 was administered. Four patients interrupted the immunotherapy because of severe intolerable side effects, 4 patients completed one course and the remaining one received 2 courses of treatment. Various adverse reactions were encountered, however, they subsided promptly after stopping therapy. All patients failed to respond to the regimen. Primary hepatic tumors continued to enlarge in 8 patients and remained unchanged in one, and pulmonary metastasis also increased in size and number in 4 patients. Transient decrease in serum alpha-fetoprotein was found in 6 patients. These results suggest that systemic IL-2 immunotherapy, even in combination with chemotherapy, is not effective for the treatment of far advanced hepatocellular carcinoma. However, in view of its immune amplifying effect, rIL-2 in combination with other treatment modalities may still be worth trying in early stages of hepatocellular carcinoma.
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PMID:Immunochemotherapy with recombinant interleukin-2 and adriamycin in primary hepatocellular carcinoma. 166 52

Tumor-infiltrating lymphocytes (TIL) were isolated from 22 human primary and metastatic liver tumors, and expanded in vitro in the presence of either interleukin-2 (IL-2, 100 U/ml) plus tumor necrosis factor alpha (TNF alpha, 1000 U/ml), IL-2 (1000 U/ml) plus IL-4 (1000 U/ml) or IL-2 (1000 U/ml) alone. TIL proliferated in culture in 20/22 cases. Among different cytoline combination, TNF alpha and IL-2 were most effective in promoting the outgrowth of CD3+CD8+T lymphocytes (mean +/- SEM: 90% +/- 5) in the cultures of TIL from primary liver tumors. Cytotoxicity against autologous tumor cells was demonstrated in all early cultures of TIL from primary liver cancers in the presence of IL-2 plus TNF alpha. In contrast, cultures of TIL derived from colon cancer metastatic to liver had significantly lower levels of autotumor cytotoxicity and proportions of CD3+CD8+ cells (40% +/- 13) than those of TIL from primary liver tumors. The addition on day 0 of interferons (alpha or gamma) to TIL cultured in the presence of TNF alpha and IL-2, significantly augmented cytotoxicity against autologous tumor. In contrast, incubation of TIL in the presence of IL-4 and IL-2 did not result in increased autotumor responses in the cultures of TIL from primary liver tumors. The expansion (-fold) of TIL (day 30) cultured in the presence of IL-2 alone compared to that in the presence of TNF alpha and IL-2 was significantly greater for hepatocellular carcinoma (median, 280 vs 260) than for autologous peripheral blood lymphocytes (36 vs 27), cholangiocarcinoma (42 vs 51) or TIL from metastatic colon cancer (39 vs 30). Outgrowth of TIL in IL-2 plus TNF alpha offers an opportunity for in vitro enrichment in cells with autotumor cytotoxicity in primary liver tumors. However, this cytokine combination was unable to promote and sustain growth of autotumor effectors from TIL in metastatic liver cancer.
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PMID:Effects of cytokines on in vitro growth of tumor-infiltrating lymphocytes obtained from human primary and metastatic liver tumors. 184 44

Bradykinin was found to induce production of IL-6 in human diploid fibroblasts, as well as in a hepatoma-derived cell line, but not in a human melanoma or an osteosarcoma cell line. With the exception of the melanoma cell line, these cells were also found to be responsive to IL-1 beta. The response to bradykinin was faster but less high than that induced by IL-1. Experiments in which IL-1 (-alpha or -beta) and bradykinin were applied simultaneously revealed a synergistic interaction. Of the other cytokines tested, TNF-alpha and IFN-gamma weakly induced IL-6. Neither IL-2, IFN-alpha, nor IFN-beta was able to induce IL-6, either in the absence or the presence of bradykinin. These observations constitute further evidence for the existence of interactions between cytokine and noncytokine peptides, thus linking the neuroendocrine and immune systems.
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PMID:Bradykinin induces interleukin-6 and synergizes with interleukin-1. 193 73

Fourteen days' culture of human spleen cells with recombinant interleukin-2 (rIL-2) or T-cell growth factor (TCGF) results in the generation of lymphokine-activated killer (LAK) effector cells that have the unique property of lysing natural killer (NK)-resistant human tumor cells, Daudi, and NK-sensitive K562 cells. LAK cells were generated from patients with advanced cancer or liver cirrhosis. The splenic LAK-effector cell types were analyzed by two-color flow cytometry. The rIL-2-induced LAK cells showed an increased proportion of CD8+CD11- and CD57+CD16- and a decreased proportion of CD4+Leu-8- cells. In contrast, TCGF-induced LAK cells revealed a significantly increased proportion of CD8+CD11- and CD4+Leu-8- cells and a decreased proportion of CD57+CD16- cells. Thus, splenic LAK cells with different surface phenotypes were induced by the cultivation with rIL-2 or TCGF. Furthermore, TCGF-induced LAK cell activities in patients with cancer were found to be lower than the rIL-2-induced LAK cell activities. It was noted that the TCGF-activated splenic lymphoid cells did not inhibit the effector process of tumor cell lysis by LAK cells that had been activated by rIL-2. Other mechanisms of lower LAK cell activities of TCGF-activated splenic lymphoid cells from patients with cancer were discussed. The findings suggest that spleens of examined patients with gastric or hepatocellular carcinoma do not seem to be responsible for suppression of cell-mediated antitumor immunity.
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PMID:Functional and phenotypic characteristics of recombinant interleukin-2 or T-cell growth factor-activated splenic lymphoid cells from patients with gastric or hepatocellular carcinoma. 216 47

Immunotherapy with interleukin (IL)-2 possesses great potential in the treatment of immune-mediated diseases and cancers. However, only a few reports on a small number of children have appeared in the literature. From March 1988 to March 1989, 11 children and adolescents were treated with IL-2. They included 1 patient with hepatocellular carcinoma, 1 with hepatoblastoma, 6 with childhood atopic dermatitis, and 3 with juvenile rheumatoid arthritis. The dosages ranged from 10,000 to 50,000 U/kg every 8 hours by intravenous drip. The following side effects were observed: anorexia, fever, and chillness (100%), general malaise (82%), irritability (64%), diarrhea (100%), nausea and vomiting (73%), weight gain (82%), edema (82%), abdominal distension (73%), oliguria (82%), cough (91%), dyspnea (27%), pleural effusion (40%), hypotension (82%), skin eruption (82%), oral ulcer (18%), enlarged liver (73%) liver function abnormalities (82%), renal function impairment (36%), electrolyte imbalance (73%), anemia (91%), thrombocytopenia (54%), leukopenia (18%), and eosinophilia (73%). Immunologically, numbers of natural killer cells were increased and natural killer and lymphokine-activated killer cell activities were augmented after IL-2 treatment. There was a tendency for serum levels of IL-2 and receptor IL-2 to decrease, especially in patients with atopic eczema. Ten patients (91%) completed one course (9 to 12 days) of therapy, and the remaining patient interrupted the treatment because of intolerable adverse effects. Clinically, complete remission for 3 months was obtained in 1 juvenile rheumatoid arthritis patient, transient improvement (2 to 6 weeks) in all atopic dermatitis patients, minor response in the hepatoblastoma patient, and no response in the patient with hepatocellular carcinoma.
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PMID:Interleukin-2 immunotherapy in children. 217 36


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