Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokine levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6) and tumor-necrosis-factor alpha (TNF-alpha) were studied in 12 healthy volunteers at 11 different times of day. TNF-alpha levels were below the detection limit, and IL-6 levels were at baseline values of the respective assay used. Interindividual variations were found for the plasma levels of sIL-2R (179-524 U/ml). Shedded IL-2 receptors displayed a pronounced circadian phase-dependency (p less than 0.0001) with a peak value at 12:29 h and a trough at 4:14 h when a complex cosine function (period lengths: 24 h plus 12 h) was fitted to the data. These findings may be of importance when using sIL-2R as a diagnostic tool as well as in controlling efficacy of drug treatment.
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PMID:Circadian rhythm of soluble interleukin-2 receptor in healthy individuals. 149 63

Nongenetically restricted T cells may be important host effector cells in women with ovarian cancer receiving intraperitoneal (ip) IL-2 therapy. We developed an in vitro technique to produce murine lymphokine-activated killer T cells. Murine splenocytes were cultured in the presence of 1000 U/ml IL-2 for 10 to 15 days. Phenotypical analysis showed 95% of total cells to express the pan T phenotype Thy 1.2 and no NK cell phenotypes by Day 7 in culture. These cells were labeled with 51Cr and their trafficking pattern after ip administration into normal and M5067 tumor bearing mice was examined. Various organs and tissues were collected at different timepoints and monitored for radioactivity. Within 4 hr., about 60% of the counts were associated with the bowel, peritoneum, and omentum of both normal and tumor bearing mice. About 15% of counts were associated with the blood, lung, kidney, spleen, and liver of both normal and tumor bearing mice.
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PMID:Trafficking of syngeneic murine lymphokine activated killer T cells following intraperitoneal administration in normal and tumor bearing mice. 150 17

The study of specific immunity in human cancers has been hampered by the elusive distribution and heterogeneity of effector cells. In this study, we have investigated the distribution of autologous melanoma-specific cytotoxic T lymphocytes (CTLs) in 18 different distant metastases from melanomas (9 non-visceral and 9 visceral metastases). Uncultured cells from tumors were provided directly for the establishment of T-cell clones using limiting dilution analysis to avoid any possible effects of in vitro sensitization of T cells to coexisting tumor cells. Autologous tumor specific CTL clones were detected in 6 of 18 tumors (33%, 4 non-visceral and 2 visceral metastases). The majority of CTL clones (35 of 46 and 17 of 19) in 2 patients with HLA class-I A2 haplotype failed to lyse either A2+ or A2- allogeneic melanoma cells, although anti-class-I (monomorphic) MAb inhibited their cytotoxicity. The remaining 11 of 46 and 2 of 19 CTL clones showed A2-restricted cytotoxicity. Autologous tumor-specific cytotoxicity was also detected after polyclonal culture of these tumor-infiltrating lymphocytes (TILs) in 8 of 16 tumors (50%, 5 non-visceral and 3 visceral metastases). These results suggest that tumor-specific T cells exist at tumor sites in at least one-third of distant metastases of melanomas and could be induced by the addition of IL-2 in at least half of the tumors. Tumor-specific T cells were detectable more often in non-visceral than in visceral metastases.
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PMID:Distribution of autologous tumor-specific cytotoxic T lymphocytes in human metastatic melanoma. 150 Feb 28

The variable clinical response seen with most cancer immunotherapy suggests that there is a large interindividual variation in immunologic response to tumors. One of the key functional parameters of an immune response is the local production of cytokines. As a method to survey the immune status of tumor-infiltrating cells, we have investigated the constitutive expression of cytokine mRNA in biopsies from epithelial ovarian carcinomas by using a PCR-assisted mRNA amplification assay. Using a set of cytokine-specific primers for 10 different cytokines, we have found selective expression of interleukin 10 (IL-10), granulocyte-macrophage colony-stimulating factor, and interferon gamma mRNA in ovarian tumor tissue as compared to normal ovaries and ovarian tumor cell lines. Such differences could not be explained by the extent of T-cell infiltration, since comparing samples with the same intensity of T-cell receptor (TCR) constant region alpha-chain product from the tumor and normal biopsies demonstrated different cytokine patterns. No IL-2 gene expression was detected in the tumor biopsies. IL-2 mRNA, however, became expressed after stimulation of the tumor-derived cells via the CD3 molecule but not after growth in recombinant IL-2 alone. Using the same methodology, we also analyzed the TCR variable region beta-chain gene repertoire. No restriction or biased expression of these genes was observed.
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PMID:Selective expression of interleukin 10, interferon gamma, and granulocyte-macrophage colony-stimulating factor in ovarian cancer biopsies. 150 88

Published data indicate that when recombinant interleukin-2 (rIL-2) is administered to children as a 15-min i.v. bolus, doses of 18 x 10(6) IU/m2 are poorly tolerated, requiring intensive care unit (ICU) management of IL-2-induced hypotension. We administered rIL-2 as a 1- or 2-h i.v. infusion to 11 children with malignancies refractory to conventional therapy. IL-2 was given every Monday/Wednesday/Friday for 3 weeks. Four children received 12 x 10(6) IU/m2/dose, four received 18 x 10(6) IU/m2/dose, and three received 24 x 10(6) IU/m2/dose (1 Cetus Unit = 6 IU). Fever, chills, flushing, nausea, vomiting, transient weight gain, and oliguria were observed at all three dose levels (not dose-limiting toxicities). Cardiovascular toxicity was significantly reduced compared to the bolus regimen. Mild hypotension was observed at all three dose levels; however, there was no severe dose-limiting hypotension. Because of reduced cardiovascular toxicity, IL-2 was safely administered on an outpatient basis. This regimen induced marginal transient increases in natural killer cell activity and lymphokine-activated killer cell activity. No measurable clinical tumor response was observed in any of the 11 children. The maximum-tolerated dose has not been reached. This regimen allows for a considerable cost reduction (outpatient care instead of ICU care) and safety, making further clinical trials on the use of IL-2 in children more feasible.
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PMID:Phase I study of recombinant human interleukin-2 for pediatric malignancies: feasibility of outpatient therapy. A Pediatric Oncology Group Study. 150 55

Current methods of expanding tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma bulk cultures result in a heterogeneous population of cells with low tumor-killing specificity. To improve the yield of cells with higher autologous and lower nonspecific cytotoxicity, interleukin-4 (IL-4) was added to high (1,000 U/ml)- and low (20 U/ml)-dose IL-2 and compared to cultures grown without IL-4 for proliferation, phenotype, and cytotoxicity against targets including autologous and allogeneic tumors. When compared to culture in IL-2 alone, the addition of IL-4 improved overall expansion in both high-dose (mean fold expansion of 2,061 vs. 1,087) and low-dose (mean fold expansion of 1,904 vs. 262) IL-2. Enhancement of TIL proliferation was dependent on the timing of IL-4 addition to the culture; augmented growth occurred only when IL-4 was added with or following activation by IL-2. The phenotype consisted primarily of CD3+/CD4+ lymphocytes with a reciprocal reduction in CD56+/CD16+ cells. Finally, there was a significant reduction in nonspecific cytotoxicity against K-562, M-14, and allogeneic tumor targets, but no significant change against autologous tumor. We conclude that IL-4 has an important regulatory effect on the expansion of renal cell carcinoma TILs in IL-2 by the promoting growth of CD3+/CD4+ lymphocytes and inhibiting the growth and nonspecific cytotoxicity associated with LAK-like CD16+/CD56+ cells. These findings may be beneficial in extracting more potent effector cells from bulk TIL culture for use in clinical trials.
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PMID:Modulation of tumor-infiltrating lymphocytes derived from human renal cell carcinoma by interleukin-4. 150 57

We previously reported that human macrophages cultured with IL-2 for a long period (lymphokine-activated macrophages, LAMs) showed high tumoricidal activity against human and murine leukemic cell lines through a different mechanism from lymphokine-activated killer (LAK) cells. In this report, we investigated the effects of various cytokines on the tumoricidal activity of IL-2-induced LAMs against HeLa cells. CSF-1 and IL-1 were found to enhance the tumoricidal activity of LAM in a dose-dependent manner, whereas IFN-gamma and TNF had inhibitory effects. CSF-1 in combination with a low dose of IL-2 synergistically induced LAMs with highly tumoricidal activity. We also found that monocytes from some donors that did not respond to IL-2 were differentiated to tumoricidal macrophages by treatment with a combination of CSF-1 and IL-2. Furthermore, IL-2-induced LAMs were found to produce cytotoxic factors in the culture medium when they were cocultured with tumor cells, and the cytotoxic activity in the culture supernatant of LAMs was also increased by the incubation of LAMs with CSF-1. The cytotoxicity of the supernatants from macrophages with different tumoricidal activity correlated with their cell-mediated cytotoxicity. It is suggested from these results that the cytotoxicity of LAMs is regulated by CSF-1, IL-1, IFN-gamma, and TNF, and that the production of cytotoxic molecules is involved in cell-mediated killing by LAMs.
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PMID:Activation of human monocytes by interleukin-2 and various cytokines. 150 58

We have investigated the tumor-specific reactivity of different T-cell subsets from mice primed with clonal variants of L5178Y and P815 cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In both tumor systems, anti-parental tumor immunity and protection against non-immunogenic clones were only induced by vaccinating the hosts with highly immunogenic cell variants, and the effect correlated with the detection of TATA-specific delayed-type hypersensitivity (DTH) reactions. The footpad reaction was transferable with spleen cell populations from immunized mice, and enrichment of splenic lymphocytes in L3T4+ but not Lyt-2+ lymphocytes increased the footpad swelling. Unfractionated spleen cell populations from immunized mice released high amounts of IL-2 and IFN-gamma in vitro in response to parental antigens. Purified L3T4+ and Lyt-2+ lymphocytes also produced IFN-gamma when incubated in vitro with the parental tumors and accessory cells. It is suggested that the mechanisms of anti-parental tumor immunity induced by MNNG-treated variants may be similar to those described previously for triazene-xenogenized L5178Y/DTIC cells, and may involve induction of a tumor-specific DTH reaction and IFN-gamma-mediated stimulation of non-specific tumoricidal effects.
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PMID:Tumor-specific L3T4+ and Lyt-2+ lymphocytes in mice primed to mutagenized cell variants. 151 82

The production of tumor-binding antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated, cholesterol-treated, cell culture-derived autologous tumor cells injected by the intralymphatic route. Fifteen patients were analyzed: nine patients (four melanoma, one breast, one sarcoma, one colon, and one undifferentiated cancer) received three injections of 10 to 15 x 10(6) tumor cells, spaced 2 weeks apart, and six patients (two melanoma, two renal, one breast, and one colon cancer) received tumor cells admixed with 3 x 10(6) U recombinant interleukin-2 (IL-2) (Proleukin, Cetus, Emeryville, CA, USA) plus a 10-day intravenous infusion of 15 x 10(6) U/kg/day IL-2 after each immunization. Serum antibody binding to autologous tumor cells was measured at 2 and 4 weeks after initiation of therapy using an enzyme-linked immunosorbent assay with patient serum being added to adherent tumor cells bound to 96-well microtiter plates. After 4 weeks, we found a significant difference (0.02 less than P less than 0.04) in serum titer in the group receiving IL-2 (33% mean increase) compared with the non-IL-2 group (8% mean increase). Although neither group showed clinical improvement in response to the therapy, the results clearly demonstrated the efficacy of IL-2 in augmenting patient antibody response to autologous intralymphatic tumor cell immunization.
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PMID:Interleukin-2 increases the antibody response in patients receiving autologous intralymphatic tumor cell vaccine immunotherapy. 151 96

To determine if intensive chemotherapy consisting of cyclophosphamide (C), etoposide (E), and cisplatin (P) (CEP) may be usefully combined with recombinant human interleukin-2 (rhIL-2), we examined a murine tumor model designed to approximate a common clinical situation: macroscopic, drug-resistant cancer. Using C57BL/6 mice with extensive tumor burden 10 days after intravenous B16 melanoma cell injection, we observed (1) C, E, and P synergize to enhance survival but do not cure mice at the highest tolerable dose (C = 200 mg/kg, E = 60 mg/kg, and P = 3 mg/kg); (2) rhIL-2 at 3 x 10(5) U (subcutaneously) daily for 4 days administered 10-18 days after B16 injection significantly improves survival; (3) CEP plus rhIL-2 is more effective than CEP alone only when rhIL-2 is administered before CEP; (4) CEP suppresses IL-2-induced lymphokine-activated killer cell activity in the spleen; and (5) rhIL-2 protects mice incompletely from the immunologic and hematologic suppression of CEP. Our results suggest that intensive chemotherapy combined with rhIL-2 may be beneficial. The success of any such combination may be schedule dependent.
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PMID:Modulation of hematologic and immunologic effects of high dose chemotherapy by interleukin-2 in a murine tumor model. 151 98


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