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

Staphylococcal enterotoxin A (SEA), a protein isolated from culture supernatants of Staphylococcus aureus, is a potent T-cell mitogen and an inducer of interferon-gamma (IFN-gamma). We report here that SEA exhibits a number of significant in vitro immunomodulatory functions. In vitro treatment of human peripheral blood monocyte-depleted lymphocytes with SEA resulted in significant augmentation of their natural killer cytotoxicity against target cells from hemopoietic (K562, Daudi) or solid (melanoma, lung, colon) human tumor cell lines. SEA was found to be more effective than interferons-alpha (natural or Escherichia coli-derived) in augmenting natural killer (NK) cytotoxicity of peripheral blood lymphocytes. Studies on the kinetics of the augmentation revealed a significant increase of NK within 3 hr of in vitro treatment with SEA at 37 degrees C. A neutralizing monoclonal antibody specific for human IFN-gamma did not affect the augmentation of natural killer cytotoxicity by SEA, suggesting that SEA augmented natural killer cytotoxicity primarily by a mechanism not involving induction of interferon-gamma. Furthermore, in vitro treatment with SEA resulted in significant augmentation of antibody-dependent cell-mediated cytotoxicity and of natural killer-like cytotoxicity, generated in mixed lymphocyte culture, against the K562 targets. Induction of suppressor cells to proliferative responses of autologous or allogeneic mononuclear cells to phytohemagglutinin (PHA) or to allogeneic cells in mixed lymphocyte culture was observed after in vitro treatment of peripheral blood mononuclear leukocytes with SEA for 24 or 48 hr at 37 degrees C. In addition, the presence of SEA in mixed lymphocyte cultures (MLC) resulted in significant inhibition of the generation of specific T-cell-mediated cytotoxicity in MLC. These results suggest that SEA, which may be involved in S. aureus infections and in treatment with extracorporeal perfusion systems over S. aureus columns, can regulate a number of significant lymphoid functions.
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PMID:Immunomodulation of human leukocytes by staphylococcal enterotoxin A: augmentation of natural killer cells and induction of suppressor cells. 294 28

The relationship between metastatic cells in the spleen and bone marrow of tumor-bearing mice and the NK activity generated in vitro by cells obtained from these organs was investigated. EL-4 lymphoma and B16 melanoma cells injected intraperitoneally into syngeneic mice (10(6) cells/animal) killed the recipients in 16 days. These tumors had a different metastatic profile: EL-4 metastasized to the spleen and bone marrow while B16 did not. The number of metastatic cells was evaluated by plating spleen or bone-marrow cells of tumor-bearing mice in agarose cultures; in parallel, the ability of spleen and bone-marrow cells to generate NK activity in vitro was assessed. The presence of 10(5) EL-4 cells/10(6) spleen or bone-marrow cells correlated with a total lack of NK activity in these organs; in contrast, no decrease in NK activity was evident in the spleen or bone marrow of B16-bearing mice. The removal of metastatic EL-4 cells (by antibody and complement) from the spleen or bone marrow did not rescue the NK activity. The lack of NK activity in spleen and bone marrow colonized by metastatic cells was not due to induction of a suppressor cell in the host. Metastatic EL-4 cells appeared to have a direct and irreversible suppressive effect on the generation of NK activity by spleen or bone marrow. A possible cause-effect relationship between metastatic colonization of lymphoid organs and suppression of local NK activity is considered.
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PMID:EL-4 metastases in spleen and bone marrow suppress the NK activity generated in these organs. 294 65

The majority of melanocytic tumours are easily diagnosed but they become a problem when they are amelanotic and the tumour cells resemble those of other tumours. This applies particularly to secondary melanoma. Detection of S100 protein is a useful identifying marker. S100 protein, so named for its solubility in saturated ammonium sulphate, is derived from brain tissue. It is a dimer and belongs to a calcium binding group of proteins. The protein was first thought to be in neural or neural crest derived tissues but has been found in chondrocytes, adipocytes, myoepithelial cells, dendritic cells of lymphoid tissue, Langerhans cells and T lymphocytes. The protein is present in a high proportion of malignant melanomas and nevocytic nevi of skin, but is less positive in eye melanomas. It is present in gliomas, Schwannomas and neurofibromas but not in neurone derived tumours such as neuroblastomas. Chondromas, chondrosarcomas, liposarcomas, some osteogenic sarcomas and some histiocytic tumours are positive. The tumours that do not contain S100 protein are listed. Pending development of melanoma-directed monoclonal antibodies, the use of anti-serum to S100 protein plus anti-keratin and anti-leukocyte reagents is useful in the identification of tumours of doubtful histogenesis.
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PMID:S-100 protein as a marker for melanocytic and other tumours. 299 6

The mouse immunoglobulin heavy-chain (IgH) B-lymphocyte enhancer stimulates transcription from heterologous promoters 20- to 40-fold when transfected into several non-lymphoid cell lines. Stimulation in B-lymphocyte melanoma cell-lines is only about 5--10 times better. A central sequence is equally active in both cell types, whilst flanking sequences, on either side of the common enhancer sequences, specifically stimulate transcription in myeloma cells. These results suggest that there are factors in non-lymphoid cells that can interact with the IgH enhancer to stimulate transcription.
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PMID:The immunoglobulin heavy-chain B-lymphocyte enhancer efficiently stimulates transcription in non-lymphoid cells. 301 12

Eleven murine monoclonal antibodies (MoAbs) were isolated that defined unique membrane antigens expressed on human melanoma cells but not detectable on human lymphoid cells by radioimmunometric assays. Five of these MoAbs each identified a separate melanoma cell surface antigen as shown by distinctly different in vitro MoAb binding patterns to a diverse panel of tumor cell lines. One of these 5 monoclonals, MoAb 34.1, reacted specifically with 9/11 melanoma lines and 0/28 other human tumor or lymphoid cell lines. The other 4 MoAbs reacted strongly with melanomas, but also bound to 1 or more non-melanoma lines. The remaining 6 MoAbs defined three distinct regions of a single melanoma cell membrane protein with a molecular weight of 125 kiloDaltons (kD) as shown by antibody crossblocking and gel electrophoresis. A sensitive radioimmunoassay developed with MoAbs to 2 epitopes of this 125 kD protein detected up to 500-fold higher levels of this antigen in extracts of melanoma cells compared to autologous lymphoid cells. The 125 kD antigen also was detected by indirect immunoperoxidase assays with the MoAbs on biopsied tumors in histologic tissue sections of 5/11 metastatic melanomas and 1/11 carcinomas but was found on some normal endothelium and smooth muscle. Another monoclonal, MoAb 705, reacted more broadly with tumor cells in 10/14 biopsied melanomas and 10/11 carcinomas, but also was reactive with basal epidermis and normal fibroblasts. By contrast, MoAb 34.1 bound specifically to tumor cells of 7/11 biopsied metastatic melanomas, but bound 0/10 carcinomas and few normal tissues except for some macrophages. Thus, MoAb 34.1 was the most specific diagnostic reagent for immunohistologic detection of melanoma. The 250 kD antigen defined by MoAb 34.1 is similar to a high molecular weight proteoglycan reported to be an excellent tumor marker for human melanomas. The results of these studies show that murine monoclonal antibodies can be used as sensitive reagents for radioimmunoassays and immunohistology of malignant melanoma.
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PMID:Detection of malignant melanoma with monoclonal antibodies. 304 64

An immunohistological analysis of tumor tissue obtained from seven patients with malignant gliomas demonstrated varying levels of lymphoid cell infiltration. The tumor infiltrating lymphocytes obtained from each sample were cultured in vitro by a limiting dilution technique. In three of the cases studied many tumor infiltrating lymphocyte microcultures selectively lysed autologous glioblastoma cells but did not lyse allogeneic gliomas, natural killer-resistant fresh melanoma cells or K562 target cells. These cultures were found to consist of CD 3+ cells. In six cases studied a variable number of microcultures lysed both autologous tumor and K562 target cells only. A minority of the microcultures studied were cytolytic for allogeneic glioma cells and fresh melanoma target cells. The cytolytic activity expressed by tumor infiltrating lymphocytes against autologous tumor cells was significantly greater (P less than 0.001) than that obtained by the corresponding peripheral blood lymphocytes cultured in a similar manner. The present immunohistological and functional studies suggest that there is an immune response to human glioblastomas in vivo with an accumulation of cells with antitumor activity at the tumor site.
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PMID:Immunohistological and functional analyses of lymphoid infiltrates in human glioblastomas. 305 9

Increased sialylation and branching of asparagine-linked oligosaccharides have recently been associated with both neoplastic transformation and the metastatic phenotype. Swainsonine, an inhibitor of Golgi alpha-mannosidase II blocks the synthesis of sialylated tri- and tetraantennary asparagine-linked oligosaccharides and results in the expression of hybrid-type oligosaccharides at the cell surface. Both the lymphoid tumor line MDAY-D2 and B16F10 melanoma cells were less metastatic when grown in swainsonine (0.3 micrograms/ml) for 48 h prior to injection of the cells into the lateral tail veins of mice. The addition of swainsonine (2.5 micrograms/ml) to the drinking water of the mice further reduced the incidence of lung colonization by B16F10 melanoma cells. MDAY-D2 tumors removed from mice on swainsonine-supplemented drinking water showed a loss of leukoagglutinin-binding complex-type oligosaccharides similar to that of tumor cells cultured in medium containing swainsonine. The growth rate of s.c. MDAY-D2 tumors was not reduced by the addition of swainsonine to the drinking water of the host; however, when mice were given two i.p. injections of the interferon-inducing agent polyinosinic:polycytidylic acid in addition to swainsonine, the primary tumor grew at a reduced rate compared to either treatment alone. Swainsonine alone did not inhibit tumor cell growth in vitro; however, the drug enhanced the antiproliferative effect of interferon. The survival time of mice bearing established MDAY-D2 metastases was extended by treating the animals with swainsonine and polyinosinic:polycytidylic acid; however, the number of long-term survival was unchanged. Swainsonine-treated tumor cells appeared to be compromised in two ways: reduced organ colonization potential; and drug-treated MDAY-D2 cells were more sensitive to the antiproliferative effects of interferon in vitro and in vivo.
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PMID:Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis. 309 60

Cross reactions between monoclonal T-cell antibodies and non-lymphoid tissues have rarely been reported. In this study 28 samples of prostatic tissue obtained at the time of autopsy or surgery, two samples of metastatic prostatic carcinoma and a series of other tumours were snap frozen and sections reacted with a series of monoclonal antibodies directed against the following antigens: Leu 1, Leu 4, T3, T8, T4, T11 and B4. Reactions were detected with an indirect immunofluorescent method. In 10 of 11 normal prostates, 15 of 15 with nodular hyperplasia and 3 of 4 prostatic adenocarcinomas a strong positive reaction occurred with anti-Leu 4. All other antibodies tested were negative. Other tumours tested, including primary carcinomas of lung (2), kidney (3), stomach (1), colon (1), pancreas (1), breast (2), urinary bladder (1), esophagus (1), larynx (1) and malignant melanoma (2), were negative with all antibodies. This is, to our knowledge, the first report of cross reactivity between a monoclonal pan T-cell antibody and epithelium. This cross reaction may be related to a shared antigen between T-cells and prostate epithelial cells or, more likely, it represents reactivity with a shared epitope. Knowledge of this reaction will prevent possible misinterpretations in the evaluation of undifferentiated neoplasms.
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PMID:Cross reactivity of a monoclonal pan T-cell antibody (anti-Leu 4) with prostate epithelium. 310 Aug 24

The immunological phenotypes of the lymphoid cells in 39 cutaneous malignant melanomas have been investigated by staining cryostat sections with a panel of 20 monoclonal antibodies against lymphoid cells and their subsets. Staining was performed by the alkaline phosphatase: anti-alkaline phosphatase (APAAP) method in which the substrate label (red) is easily distinguishable from melanin. The lymphoid infiltrates had an essentially identical composition in all cases, consisting of T-lymphocytes associated with both Langerhans cells and HLA-DR-positive tissue macrophages. B-lymphocytes and natural killer cells were either absent or only present in low numbers. The ratio between T8 (suppressor/cytotoxic) and T4 (helper/inducer) lymphocytes varied and showed no correlation with melanoma subtype, level of invasion or magnitude of lymphocytic response. Examination for markers associated with T-cell activation and/or with cell proliferation revealed that all lesions contained HLA-DR-positive T-lymphocytes, whereas expression of the transferrin receptor and the interleukin-2 receptor (Tac-antigen) occurred mainly in melanomas with a significant inflammatory infiltrate. These data support the concept that malignant melanomas are capable of evoking autologous T-cell immune reactions.
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PMID:Immunohistological analysis of the lymphoid infiltrate in cutaneous malignant melanomas. 310 Dec 84

Two Lyt-1+, L3T4a+ autoreactive T cell clones specific for self-class II major histocompatibility complex (MHC) gene products were established from lymph node cells and spleen cells of C57BL/6J mice, respectively, by different methods. They were stimulated to proliferate in culture in response to I-Ab antigen-bearing syngeneic spleen cells in a class II MHC-restricted manner. This stimulation was inhibited completely by the addition of anti-L3T4a (GK1.5) or anti-I-Ab (3JP) monoclonal antibodies. The autoreactive T cell clones lysed syngeneic I-Ab+ target cells such as lipopolysaccharide (LPS) blasts. They also lysed I-A- bystander cells such as Cloudman and B16 melanoma and lymphoid tumor cells in the presence of I-Ab+ stimulator cells but not I-Ad+ cells. This bystander killing was most likely mediated by soluble factors released from the autoreactive T cells in response to I-Ab antigens, because culture supernatants from activated autoreactive T cells inhibited the proliferation of B16 melanoma cells in vitro and also had significant cytolytic activity. Both lymphotoxin and interferon-gamma were released from activated autoreactive T cells, suggesting that these cytotoxic lymphokines were responsible for autoreactive T cell-mediated cytolysis. The finding that the two clones, established independently and by different methods, show self-class II MHC antigen-restricted cytolysis, and bystander cytolysis suggests that these properties are not restricted to a unique population of autoreactive T cells. These results favor the concept that in vivo, autoreactive T cells may express not only regulatory activity in regard to antibody responses, but also anti-tumor activity via bystander cytolysis.
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PMID:Anti-tumor activity of class II MHC antigen-restricted cloned autoreactive T cells. I. Destruction of B16 melanoma cells mediated by bystander cytolysis in vitro. 310 9


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