UMLS:C0025202 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0025202 (melanoma)
69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recombinant vaccinia virus containing and expressing the gene of murine granulocyte-macrophage colony-stimulating factor (VVGM-CSF) was tested for its antitumor activity. Murine pulmonary metastasis was established by injecting 2 x 10(5) B16F10 melanoma cells into tail vein of C57BL/6 mouse. Three days after B16F10 inoculation, VVGM-CSF or VVTK, a thymidine kinase gene deficient vaccinia virus, was injected intraperitoneally twice weekly for 2 weeks. Two weeks later mice were sacrificed and pulmonary metastasis foci counted. The results showed that VVGM-CSF treatment significantly decreased the number of pulmonary metastasis and prolonged the survival time of tumor-bearing mice (P < 0.01). Cytotoxic and phagocytic activities of peritoneal macrophages were found to be markedly elevated in mice treated with VVGM-CSF. Nitric oxide released from macrophages was also found to be increased. Based on these data, together with our previous results, we may speculate that continuous secretion of GM-CSF and activation of macrophages might partially explain the antitumor effects of VVGM-CSF.
...
PMID:[Therapeutic effect of vaccinia virus secreting granulocyte-macrophage colony-stimulating factor on pulmonary metastatic melanoma]. 938 45

The recipient of a cadaveric kidney was found to have donor melanoma within the graft together with metastatic spread. After cessation of immunosuppression, the kidney rejected and was removed. One month later there was both clinical and radiological evidence of remission and at autopsy 5 months later there was no histological evidence of melanoma. The outcome for recipients of other organs from the same donor was varied. Tumour cells expressed HLA class 1 antigens mismatched in the recipient and mRNA for the costimulator B7, and the cytokines GM-CSF, IL-1 alpha and beta. These characteristics may have been important in the host immunological response.
...
PMID:Remission of transplanted melanoma--clinical course and tumour cell characterisation. 940 85

We compared the immunogenic activity of irradiated vaccines prepared from B16 F10 melanoma cells with one made from B16 F10 melanoma cells transfected with genes encoding murine IL-2 or GM-CSF. Vaccines were studied in the conditions of treatment of C57BL/6 mice with or without the corresponding lymphokines. Control and prevaccinated mice were challenged with parental B16 F10 murine melanoma cells (5 x 10(5)) subcutaneously in the midtail to examine growth of the primary (local) tumor in the middle of the tall and metastases to the lungs. This experimental model is very close to the clinical stages of metastatic melanoma. The effectiveness of preimmunization of mice was determined by the levels of antibody production to a melanoma-associated antigen termed B700. The comparison of antibody production, growth of primary melanoma tumors, number of mice surviving at the end of the observation period, mean survival time and per cent mice with metastases in the lungs showed that the best course of immunotherapy was prevaccination of mice with a vaccine of irradiated B16 F10 melanoma cells transfected to secrete GM-CSF, coupled with GM-CSF therapy.
...
PMID:Immunization of mice with irradiated melanoma tumor cells transfected to secrete lymphokines and coupled with IL-2 or GM-CSF therapy. 941 96

The effect of granulocyte/macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicity and immunogenicity of 2 different murine tumor lines was determined. Transduction of B16 melanoma cells with the GM-CSF gene rendered the cells more immunogenic. In contrast, transduction of NG4TL4 fibrosarcoma in FVB/N mice (NG) with the GM-CSF gene showed increased tumorigenicity in a high producer line (NG-MGh). The parent NG or NG-MG cells induced the same level of cytotoxic T-lymphocyte (CTL) response and the same magnitude of tumor transplantation immunity. However, the proliferation of the NG-MGh cells was increased 2- to 10-fold. There was no increase in apoptosis in the NG cells and there was no increase of NG-MGh cells in S-phase, hence the increase of the proliferative activity appeared to be indeed inherent to the cells. Mixing the splenocytes from the NG-MGh tumor bearers with the NG tumor cells did not increase tumorigenicity but totally inhibited the growth of the NG tumor, indicating that suppressor cells were not present. Mixing 10,000 rad X-irradiated NG-MGh cells with viable NG tumor cells resulted in 3- to 10-fold increased NG tumor growth rate. The in vitro proliferation of NG cells was increased by adding both GM-CSFs and macrophages and not by either one alone, suggesting that interaction between macrophages and GM-CSFs resulted in the production of tumor growth enhancing factor(s). Our findings suggest that transduction of NG tumor cells with the GM-CSF gene increases tumorigenicity, which is attributed both to an increased inherent proliferative ability of the tumor cells and to the in vivo production of a tumor growth enhancing factor(s) at the tumor site.
...
PMID:Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors. 945 9

An sIL-6R/IL-6 chimera, directly fusing the natural forms of soluble IL-6 receptor and IL-6, as found in human body fluids, was produced in transfected human cells. The secreted p85 glycoprotein was active at a concentration of 120 pM to produce growth-arrest and spindleoid differentiation of murine melanoma F10.9 cells, which do not respond to IL-6 alone. This fusion protein was as active as the yeast-produced p56 fusion protein containing a shortened sIL-6R, linked through a flexible peptide chain to IL-6 (Hyper IL-6). The concentration of Hyper IL-6 needed to arrest the growth of F10.9 cells was much lower than that needed of a combination of IL-6 and sIL-6R, added separately. Hyper IL-6 was also more active than IL-6 in stimulating growth of murine plasmacytoma T1165 cells, the half maximal stimulation being obtained at 2 pM Hyper IL-6 versus 23 pM for IL-6. In order to evaluate the effect of the fused sIL-6R/IL-6 proteins on human hematopoietic primitive progenitor cells, they were added to suspension cultures of CD34+ cells from human cord blood in addition to both flt3/flk2 ligand (FL) and stem cell factor (SCF). Fused sIL-6R/IL-6 produced a marked stimulation of cell expansion and a marked increase in the number of colony forming units when subsequently plated in semi-solid medium with IL-3, GM-CSF, SCF and erythropoietin. Ex-vivo maintenance and expansion of early progenitor cells in bone marrow transplantation protocols may be a potential application for the sIL-6R/IL-6 chimeric glycoproteins.
...
PMID:Interleukin-6 receptor-interleukin-6 fusion proteins with enhanced interleukin-6 type pleiotropic activities. 945 15

We previously reported that an acidic polysaccharide from Panax ginseng named ginsan inhibits the incidence of benzo[a]pyrene-induced autochthonous lung tumors in mice. To elucidate the mechanism of antineoplastic activity, ginsan was tested for its ability to generate LAK cells and to produce cytokines. Spleen cells became cytotoxic to a wide range of tumor cells after 5 days of culture with ginsan in a non-major histocompatibility restricted manner and the activity of ginsan was 12 times higher than that of lentinan. The generation of killer cells by rIL-2 was neutralized only in the presence of anti-IL-2, whereas by ginsan it was neutralized in the presence of anti-IL-2 as well as anti-IFN gamma, or anti-IL-1 alpha. It was confirmed that ginsan induces the expression of mRNA for IL-2, IFN gamma, IL-1 alpha, and GM-CSF. Depletion of AsGM1+ cells from spleen cells reduced the generation of LAK by rIL-2. In contrast, depletion of AsGM1+ as well as Thy1+ cells, CD4+ cells, or DC8+ cells reduced the generation of LAK cells by ginsan. The serologic phenotype of rIL-2 induced LAK cells was CD8- cells, whereas the ginsan induced LAK cells, were CD8+ cells. Ginsan synergized with rIL-2 to generate LAK cells (2.0-15 fold) and the most dramatic synergy was seen at rIL-2 concentrations below 3 U/ml. Ginsan alone inhibited pulmonary metastasis of B16-F10 melanoma cells and enhanced the inhibition of lung colonies by rIL-2. These findings demonstrate that ginsan generates LAK cells from both NK and T cells through endogeneously produced multiple cytokines. This property may contribute to its effectiveness in the immunoprevention and immunotherapy of cancer.
...
PMID:Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage cytokines and generates LAK cells in synergy with rIL-2. 952 1

Dendritic cells (DC) are antigen-presenting cells initiating primary and secondary immune responses. Since malignant tumors are able to escape immunologic control, DC might be prime candidates to activate the immune system against tumor cells. In an autologous system, a dynamic interaction among monocyte-derived DC (MoDC), T lymphocytes, and tumor cells obtained from melanoma patients could be noted. MoDC were generated from blood monocytes in the presence of GM-CSF, IL-4, and IFN-gamma. T cells were isolated either from peripheral blood or from lymph nodes. Melanoma cells were harvested from surgically removed tumor metastases. They were then gamma-irradiated and co-cultured with autologous MoDC and T lymphocytes. After 5 days, the lymphocytes showed a high proliferative activity and the majority of them were CD8-positive. In five cases tested, they revealed a high cytotoxic activity resulting in apoptosis of tumor cells. These findings suggest that MoDC are capable of initiating an effective specific anti-tumor response in a strictly autologous mixed lymphocyte tumor culture (MLTC), even though tumor-specific antigens had not been individually defined. Therefore (I) whole melanoma cells can serve as a source of antigen, (II) monocyte-derived dendritic cells may process and present melanoma-specific antigens resulting in a strong lymphocyte proliferation, (III) the majority of responding T lymphocytes are CD8-positive, and (IV) an acquired cytotoxic response eventually leads to apoptosis of the melanoma cells. The reaction demonstrated here permits to in vitro and quantitatively monitoring the effect of T cell directed immunotherapies such as the adoptive immunotherapy of tumors.
...
PMID:Specific autologous anti-melanoma T cell response in vitro using monocyte-derived dendritic cells. 956 71

Spontaneous regression of melanoma lesions is thought to be the result of an efficient immune response against melanoma cells in vivo. The outcome of immune responses is critically influenced by a complex network of interacting cytokines present in the local microenvironment. Analysis of cytokine gene transcription in melanoma lesions exhibiting or lacking a sufficient anti-tumor immune response thus may help to define cytokines or cytokine combinations critical to the development of this immune response. In the present study, we have investigated an extended panel of cytokine and cytokine receptor genes by reverse transcription-PCR and in situ hybridization in regressive and progressive primary human cutaneous melanoma samples. Whereas the presence of a lymphocyte infiltrate in tissue samples was associated with a TH1 cytokine mRNA profile (TNF-alpha, INF-gamma, IL12p35, IL12p40, IL2Rbeta, and IL2Rgamma), clinically and histologically regressive samples exhibited additionally increased transcript levels for GM-CSF, IL2, and IL15. mRNAs of TH2 cytokines IL4 and IL5 were detected only in a minor portion of progressive melanoma samples and regressive melanoma lesions. These results were further supported by comparison of progressive with regressive regions in three melanoma samples. Again, regressive regions contained higher transcript levels for GM-CSF, IL2, and IL15. In comparison to cutaneous metastatic melanoma lesions, regressive melanomas also overexpressed the same cytokine mRNA profile. These results provide evidence for an association of spontaneous regression with increased transcript levels for the cytokine combination GM-CSF, IL2, and IL15 in malignant melanoma. This cytokine combination could be relevant for experimental anti-tumor immune response studies and for immunotherapeutic and gene transfer studies in the treatment of melanoma patients.
...
PMID:Immune response against human primary malignant melanoma: a distinct cytokine mRNA profile associated with spontaneous regression. 960 79

Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2 of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by coadministration with IL-2. Whole-blood functional assays indicated that sufficient s(CHO) IL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis factor production, was observed. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R produced no apparent reduction in IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2. Therefore, no effective biological dose could be identified for the s(CHO) IL-1R.
...
PMID:A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor. 960 78

In vivo transfection of established tumors with immunostimulatory genes can elicit antitumor immunity. Therefore, we evaluated the safety and efficacy of intratumoral injections of a bacterial superantigen with a cytokine gene in dogs with malignant melanoma, a spontaneous and highly malignant canine tumor. 26 dogs with melanoma were treated with lipid-complexed plasmid DNA encoding staphylococcal enterotoxin B and either GM-CSF or IL-2. Dogs were evaluated for treatment-associated toxicity, tumor responses, immunologic responses, and survival times. The overall response rate (complete or partial remissions) for all 26 dogs was 46% (12 of 26), and was highest in patients with smaller tumors. Toxicity was minimal or absent in all dogs. Injected tumors developed marked infiltrates of CD4+ and CD8+ T cells and macrophages, and tumor regression was associated with development of high levels of antitumor cytotoxic T lymphocyte activity in peripheral blood lymphocytes. Survival times for animals with stage III melanomas treated by intratumoral gene therapy were prolonged significantly compared with animals treated with surgical tumor excision only. Thus, local tumor transfection with superantigen and cytokine genes was capable of inducing both local and systemic antitumor immunity in an outbred animal with a spontaneously developing malignant tumor.
...
PMID:In vivo tumor transfection with superantigen plus cytokine genes induces tumor regression and prolongs survival in dogs with malignant melanoma. 961 12

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>