Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fourteen continuous human cell lines, including nine derived from tumors and five from non-neoplastic tissues, produced interferon in response to induction with bluetongue virus (BTV), Newcastle disease virus (NDV), and poly(I) . poly(C) complexed with DEAE-dextran. The seven best interferon-producing cell lines (one from a melanoma, five derived from carcinomas, and one SV40-virus-transformed kidney cell line) responded to at least one of the viral inducers with yields of interferon over 1000 units/ml. Because the HT-1376 bladder carcinoma cell line produced high yields of interferon in this survey, and is easily propagated, the optimal conditions for interferon production were investigated, using BTV as the inducer. Interferon yields in 59 inductions over a period of about two years consistently fell within a 6-fold range, and had a geometric mean titer of about 2700 reference units (RU)/ml, representing the production of about 3 RU/10(3) cells. This yield is comparable to mean titers of 1 to 10 RU/10(3) cells obtained by others with human leukocytes, foreskin cell strains, or the Namalva lymphoblastoid cell line. UV-inactivated BTV at a multiplicity corresponding to 10 PFU/cell was as effective an inducer in the HT-1376 cell line as the fully infectious virus at a multiplicity of 1 PFU/cell. The interferon produced by the HT-1376 epithelial cell line has characteristics similar to the interferon induced by poly(I) . poly(C) in human diploid fibroblasts. These studies clearly demonstrate that many different types of tumor-derived cells have the capacity to produce interferon, and that some equal or surpass the efficiency of diploid cells.
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PMID:Production of interferon by human tumor cell lines. 22 5

Tumour-necrosis factor (TNF) is growth-inhibitory or cytotoxic to certain tumour cell lines, and is present in the serum of rabbits injected i.v. with BCG and endotoxin 2 weeks apart (TNF serum). TNF serum also has interferon activity, and as TNF and interferons have a number of properties in common their relationship has been investigated further. TNF was assayed by cytotoxicity in vitro against L cells and interferon by a CPE-inhibition assay with Semliki Forest virus.TNF appears not to be an interferon, on the following bases:1. TNF activity could be separated from the Type I interferon of TNF serum by passage through a Cibacron blue-agarose column or by sequential salt precipitation, ion-exchange chromatography and gel filtration.2. Preparations of Type I interferon induced by poly I, poly C or virus lacked TNF activity.3. Though it was not possible to compare TNF with rabbit Type II interferon (as methods used to induce Type II interferon in other species were unsuccessful in the rabbit) rabbit TNF has a number of properties which distinguish it from the Type II interferons of other species.4. Rabbit TNF inhibited the growth of a human melanoma cell line, and also had effects on certain mouse and rabbit cell lines, whereas the anti-cellular effects of interferons are reported to be species-specific.
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PMID:Tumour-necrosis factor from the rabbit. III. Relationship to interferons. 38 59

Intravenous injection of pyran copolymer (divinyl ether-maleic anhydride) 24 h prior to intravenous injection of B16 melanoma in C57/BL6 mice greatly decreased the number of liver metastases. If the pyran copolymer was administered 3 days after injection of tumor cells, the number of metastases was not significantly decreased. Pyran copolymer has been reported to stimulate interferon production and increase clearance of particulate matter by the reticuloendothelial system. The results of this experiment suggests an important role played by the reticuloendothelial system in experimental liver metastasis.
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PMID:Decrease in experimental liver metastasis in mice after treatment with pyran copolymer. 105 13

The present data show that biological and synthetic inducers of interferon are able to reduce the growth of a transplantable malignant melanoma in the Syrian hamster. The advantage of the biological inducer H-MP are that it is not toxic for humans and that a high titer of interferon can be maintained over a long period of time.
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PMID:[Effect of active interferonization and anti-thymocyte globulin on the growth of virus-induced hamster melanoma A-Mel-S]. 108 56

Interferons produced by recombinant DNA technology began phase I trials little more than a decade ago. Today interferon alfa-2 is a mainstay in the treatment of hairy cell leukemia, and has demonstrated benefit in the more common chronic myelogenous leukemia. Interferon alfa-2 also has activity in other hematologic malignancies, including indolent non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, T-cell lymphoma, and multiple myeloma, and in solid tumors such as disseminated melanoma, renal cell carcinoma, Kaposi's sarcoma, endocrine pancreatic tumors, and malignant carcinoid tumors. Interferon alfa, beta, and gamma remain under investigation to define potential roles in ovarian, breast, bladder, and cervical carcinomas and gliomas. The greatest value of the interferons will be in prolonging the disease-free interval when used in combination with other treatment modalities, including surgery, radiation, chemotherapy, and other biologic agents.
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PMID:Current status of interferons in the treatment of cancer. 128 Jan 53

The effects of interferon (IFN) on the expression of ICAM-1 in human melanoma cell lines and the shedding of ICAM-1 into spent media were investigated using an indirect binding assay and a double determinant immunoassay (DDIA). While IFN increased the level of expression of ICAM-1 on melanoma cell lines, the susceptibility to IFN differed according to cell line. The enhancing effect of IFN-gamma was concentration-dependent, and it exceeded those of IFN-alpha and IFN-beta. Shedding of ICAM-1 into spent media was detected effectively, and the results agreed well with the expression of ICAM-1 on melanoma cells. Immunostaining of the surgically removed melanoma lesions was positively correlated with the thickness of the primary lesion. The expression of ICAM-1 in primary melanoma lesions was inversely correlated with the disease-free interval. The circulating ICAM-1 with stage 4 melanoma patients significantly exceeded that of stage 1-3 melanoma patients. These observations suggest that ICAM-1 in its soluble form may play an important role in host immunities and may be useful in evaluating the prognosis of patients with melanoma.
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PMID:Analysis of expression and soluble form of intercellular adhesion molecule-1 in malignant melanoma. 128 75

The effect of gamma-interferon (IFN-gamma) on the induction of interleukin-2 (IL-2) activated killer cell activity was studied: (I) in peripheral blood lymphocytes (LAK cells) from cancer patients and healthy donors, (II) in lymphocytes infiltrating solid tumors (TIL) from melanoma and breast cancer patients, and (III) in pleural effusion associated lymphocytes (EAL) from patients with lung adenocarcinoma. The coculture of LAK, TIL and pleural effusion mononuclear cells (MNC) with several doses of IFN-gamma (10, 50, 250, and 1250 U/ml) and a low dose of IL-2 (10 U/ml) for 5 days resulted in a synergistic effect on the cytotoxicity of these cells against several tumor cell lines. Furthermore there was a potentiation in the proliferation of MNC after a 5-day culture. The induction of lymphocyte cytotoxicity by a combination of IFN-gamma with low doses of IL-2 may be helpful in designing more effective cancer immunotherapeutic protocols with LAK, TIL or EAL.
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PMID:Gamma-interferon enhances the cytotoxic activity of interleukin-2-induced peripheral blood lymphocyte (LAK) cells, tumor infiltrating lymphocytes (TIL), and effusion associated lymphocytes. 128 41

After the promising results achieved with immunotherapy in disseminated malignant melanoma, a disease reported to show little response to chemotherapy, use of combination chemotherapy regimens with interferon or interleukin and interferon has been shown to provide higher response rates and responses of longer duration. A few phase I-II trials on monoclonal antibodies have also been reported. However, toxicity is substantial with these complex combination regimens.
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PMID:[Treatment of disseminated malignant melanoma. Results are promising, but toxicity is high]. 130 93

A total of 22 patients with metastatic renal cell carcinoma or malignant melanoma were treated in a phase II study to assess the safety and efficacy of combination therapy of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). 3 x 10(6) U/m2/day recombinant human (rh)IL-2 was given in repetitive cycles by continuous 24-h infusion from day 1 to day 4; 6 x 10(6) U/m2/day rhIFN-alpha was given subcutaneously on days 1 and 4. There was one complete remission and two partial remissions in the renal cell carcinoma group and two partial remissions in the malignant melanoma group, giving an overall response rate of 24% in 21 evaluable patients with a median response duration of 5+ months. Toxicity was moderate, with hypotension, fever, chills, nausea, neurotoxicity, and dermatitis as prominent side effects. Measurement of circulating cytokine levels showed increased serum tumor necrosis factor-alpha (TNF), interferon-tau, and soluble interleukin-2 receptor levels during each cycle with a tendency to higher concentrations of TNF in responders as compared to nonresponders. With regard to therapeutic efficacy and tolerance, our approach might represent an alternative to the high-dose protocols and the labor- and cost-intensive strategies of adoptive immunotherapy.
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PMID:Combination of interleukin-2 and interferon-alpha in renal cell carcinoma and malignant melanoma: a phase II clinical trial. 130 89

The ability of interleukin-3 (IL-3) to induce antimicrobial and tumoricidal activity was evaluated. Macrophages infected with two intracellular protozoa, Leishmania amazonensis or Trypanosoma cruzi, were treated with cytokines. IL-3 induced a dose-dependent enhancement of microbistasis against leishmanias, and the activity of IL-3 (100 ng/ml) was comparable to that of gamma interferon (IFN-gamma) (1,000 U/ml). In addition, IL-3 in combination with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage CSF (M-CSF) or with IFN-gamma reduced infection and lowered the required dose. IL-3 similarly activated macrophages to inhibit intracellular replication of T. cruzi. Furthermore, IL-3 induced antibody-independent tumoricidal activity against melanoma cells that was dose dependent and comparable to that of lipopolysaccharide and GM-CSF. The mechanisms by which IL-3 induced antimicrobial activity may involve at least the augmentation of oxidative capacity. IL-3, at concentrations of 0.5 ng/ml or greater, led to a significantly increased oxidative burst which paralleled the inhibition of protozoan replication. The enhancement of oxidative capacity by IL-3 (5 ng/ml or higher) was comparable to that of IFN-gamma. The induction of tumoricidal activity was associated with the production of tumor necrosis factor alpha (TNF-alpha), which in this system may feed back to enhance the macrophage inhibition of leishmanias, as demonstrated by neutralization of IL-3 activation by anti-TNF-alpha antibody. Thus, peripheral blood macrophages remain responsive to IL-3, as demonstrated by enhanced antimicrobial and tumoricidal activity. IL-3 may have potential clinical applications because of these properties and its effect on myelopoiesis.
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PMID:Interleukin-3 induces antimicrobial activity against Leishmania amazonensis and Trypanosoma cruzi and tumoricidal activity in human peripheral blood-derived macrophages. 131 23


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