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)

We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 mini-pellet, in two murine solid tumor models, and also investigated the enhancement of its therapeutic effect by serial administration. The IL-2 mini-pellet contains 1 x 10(6) units of IL-2 and releases it slowly in vivo. In our experiment, the IL-2 mini-pellet was administered subcutaneously near the tumor site in combination with the intravenous injection of lymphokine-activated killer (LAK) cells. When this regimen was given on days 8 and 11 after the subcutaneous inoculation of Meth A fibrosarcoma into BALB/c mice, tumor growth was significantly inhibited (p less than 0.05) compared to tumor growth in untreated controls. Moreover, the IL-2 mini-pellet alone was also effective in inhibiting tumor growth. In another experiment, MH134 hepatoma was inoculated into C3H/He mice. Both administration of the IL-2 mini-pellet alone and in combination with LAK cells resulted in complete tumor regression in four of five mice. In a third experiment, serial administration of the IL-2 mini-pellet at 3- or 5-day intervals prolonged the suppression of Meth A fibrosarcoma growth in BALB/c mice. These results suggested that the IL-2 mini-pellet could be applied to cancer immunotherapy and that its antitumor effect could be prolonged by serial administration.
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PMID:Augmentation of antitumor effect on syngeneic murine solid tumors by an interleukin 2 slow delivery system, the IL-2 mini-pellet. 185 89

Liver-derived lymphocytes were isolated from 40 human livers with end-stage liver disease that were removed at the time of orthotopic liver transplantation. In addition, 10 resection specimens or whole livers removed from patients with liver cancer and seven normal livers (unused donor organs) were studied as controls. Liver-derived lymphocytes were isolated from enzymatically digested tissue by gradient centrifugation and adherence to plastic. Their phenotypical characteristics were studied by two-color flow cytometry, and effector cell function was determined in 4-hr 51Cr-release assays against a natural killer-sensitive target, K562 (natural killer activity), natural killer-resistant Daudi line (lymphokine-activated killer activity) and by P815 line with or without phytohemagglutinin to assess lectin-dependent cellular cytotoxicity. Liver-derived lymphocytes isolated from normal liver contained equal proportions of T and natural killer lymphocytes (mean natural killer/T ratio = 0.7). CD3-CD56+CD16- natural killer cells were the main natural killer subset present in liver-derived lymphocytes, in contrast to the predominant natural killer phenotype in the circulation (CD56+CD16+). Control liver-derived lymphocytes had levels of cytotoxicity significantly greater than those of the normal peripheral-blood lymphocytes against all three targets. In contrast, liver-derived lymphocytes isolated from organs with advanced liver disease differed markedly in the natural killer/T cell ratio and levels of liver-derived lymphocyte cytotoxicity. Liver-derived lymphocytes obtained from hepatocellular carcinoma or rejecting allografts treated by immunosuppressive therapy had virtually no cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Natural killer activity of human liver-derived lymphocytes in various liver diseases. 187 94

The in vitro lymphokine-activated killer (LAK) activity of peripheral blood mononuclear cells (PBMC) from 36 patients with hepatocellular carcinoma was investigated. The activity was greatly diminished in 13 patients and enhanced in seven patients. A flow cytometric study showed that the percentage of OKM1+, Leu-7+-11b+, and Leu-7-11b+ fractions in PBMC was decreased and the percentage of OKT8+ and Leu7+11- fractions was increased significantly in the 13 patients with lower LAK activity, compared with the values of the seven higher LAK activity patients. Furthermore, the response of PBMC to interleukin-2 (IL-2) was deficient in the lower activity group. However, there was no significant difference in IL-2 production by PBMC, IL-2 receptor (p55) expression of PBMC and mitogen (Con-A, PHA) response of PBMC between the two groups. These findings indicate the possibility that diminished LAK activity in hepatoma patients is due to a decreased number of LAK precursor cells and a defective response of LAK precursor cells to IL-2.
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PMID:Defective immunological functions associated with abnormal lymphokine-activated killer activity in patients with hepatocellular carcinoma. 196 92

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

Hepatocellular carcinoma (HCC) patients can be divided into two groups according to the degree of lymphokine activated killer (LAK) cell activity; a high LAK activity group (H-LAK-HCC) and a low LAK activity group (L-LAK-HCC). Interferon-gamma (IFN-gamma) production is severely defective in L-LAK-HCC but not defective in H-LAH-HCC. IFN-gamma production is suppressed with the addition of anti-Tac in dose dependent manner, though LAK activity is suppressed only in the presence of high concentration of anti-Tac. LAK activity is suppressed with the addition of anti-IFN-gamma, which is most prominent when the antibody is present during the first 12 hr of incubation. LAK generation is enhanced with the addition of recombinant IFN-gamma, which is most prominent when it is present during the first 12 hr of incubation. However, this enhancing effect is less prominent in L-LAK-HCC as compared to normals, liver cirrhosis, and H-LAK-HCC. This enhancement is regarded to depend on the presence of Leu7+ and Leu11+ subset, as this enhancement is abandoned and IFN-gamma production is inhibited when either of these subsets is deleted. These data suggest that IFN-gamma production and the participation of Leu7+ and Leu11+ subsets is important in sufficient LAK generation, and that poor IFN-gamma production and insufficient response to IFN-gamma may be the cause of severely defective LAK generation in L-LAK-HCC.
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PMID:Enhancement of depressed lymphokine activated killer cell activity in patients with hepatocellular carcinoma. 216 82

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

The in vitro lymphokine-activated killer activity and natural killer activity of peripheral blood mononuclear cells from 33 patients with hepatocellular carcinoma were investigated. Lymphokine-activated killer and natural killer activities of patients were significantly decreased compared with those of healthy volunteers. Peripheral blood mononuclear cells showed significantly lower lymphokine-activated killer and natural killer activities in patients with larger tumors (greater than or equal to 5 cm in diameter) than in patients with smaller tumors (less than 5 cm in diameter). Of 20 patients with larger tumors, 8 and 6 generated very little or no lymphokine-activated killer and natural killer activities. respectively. Lymphokine-activated killer precursors and natural killer cells were present mainly in the Leu-11+ fraction and partially in the Leu-7+ fraction in patients and normal volunteers. A flow cytometric study showed that the percentage of Leu-7+ 11+ and Leu-7-11+ fractions in peripheral blood mononuclear cells was lower in patients than in normal volunteers. The percentages of Leu-7-11+ and Leu-7+ 11+ fractions were diminished in the peripheral blood mononuclear cells of the patients with little or no lymphokine-activated killer activity. It is suggested that deficient lymphokine-activated killer and natural killer activities partially results from a reduction in the number of their precursor cells in patients with hepatocellular carcinoma.
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PMID:Depressed lymphokine-activated killer activity and analysis of the precursor cells in peripheral blood of patients with hepatocellular carcinoma. 217 25

Nonspecific tumoricidal effectors, called lymphokine-activated killer (LAK) cells, can be induced from the tumor-bearer's spleen in vitro. The adoptive transfer of such LAK cells to a patient with unresectable hepatoma was performed in this study. About 2.4 X 10(9) LAK cells generated from the autologous spleen were adoptively transferred to the patient via hepatic arterial catheter. Signs of toxicity encountered with LAK cell infusions comprised chills and fever only. Chemical studies of hepatic, renal, and hematologic parameters were normal; pulmonary function studies revealed no changes after infusion. With the transfer of LAK cells, serum alpha-fetoprotein (AFP) levels were markedly decreased and ascitic fluid retention was transiently reduced. Though the therapeutic effect was transient, these trials offered hope for a new therapeutic approach to unresectable hepatoma. Further, the availability of large amounts of recombinant interleukin-2 (rIL-2) may now make widespread use of this approach possible.
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PMID:Treatment for unresectable hepatoma via selective hepatic arterial infusion of lymphokine-activated killer cells generated from autologous spleen cells. 242 26

Ten patients with hepatocellular carcinoma, three of whom had pulmonary metastasis, were treated with adoptive immunotherapy using autologous lymphokine-activated killer cells plus recombinant interleukin 2. Patients received 15 micrograms per day of recombinant interleukin 2 consecutively (for 14 to 64 days), from Day 7 prior to the first leukapheresis, and received 10(9) to 10(10) lymphokine-activated killer cells once or twice per week intravenously; the lymphokine-activated killer cells had been generated from mononuclear cells obtained through leukapheresis. Preadministration of recombinant interleukin 2 prior to the first leukapheresis resulted in a remarkable increase of lymphokine-activated killer activity in seven of nine cases in whom lymphokine-activated killer activity had been poorly inducible even at high concentrations of recombinant interleukin 2. At the end of the treatment, liver tumor regression (34 and 63%, respectively, of two-dimensional size) was observed in two of two patients with a solitary tumor; no increase of liver tumor size was observed in seven patients with massive or multiple tumors, and no changes in the size or number of pulmonary metastatic tumors in any patients were observed. More than a 35% decrease in serum alpha-fetoprotein level was noted in four of nine alpha-fetoprotein-positive patients. However, Child's grades, performance status and lymphokine-activated killer activity on entry into the study could not be used as parameters to predict therapy responsiveness. Neither serious side effects nor significant changes of serum bilirubin, ALT and creatinine were noted. Thus, this treatment seems to be well tolerated even in advanced hepatocellular carcinoma with poor liver function reserve, and tumor regression could be expected in small-burden hepatocellular carcinoma. The assessment of the therapeutic effects and application in hepatocellular carcinoma awaits the development of this trial.
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PMID:Adoptive immunotherapy with lymphokine-activated killer cells plus recombinant interleukin 2 in patients with unresectable hepatocellular carcinoma. 247 81

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


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