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)

We analyzed the antigenic phenotype of lymphokine-activated killer (LAK) effector cells. Human blood lymphocytes were cultured for 3 days with 100 U/ml recombinant interleukin 2 (rIL 2), subpopulations isolated with monoclonal antibodies and a fluorescence-activated cell sorter (FACS) and assayed for cytotoxic activity against 51chromium labeled noncultured melanoma tumor cells. Initial experiments compared the LAK effector function of CD5+ T lymphocytes vs CD5- cells (predominantly CD16+ NK cells). The mean percent specific release at a 10:1 effector:target (E:T) ratio was 25% +/- 16 for CD5- cells, 10% +/- 6 for CD5+ cells, and 22% +/- 9 for unsorted cells. In contrast, when lymphocyte subpopulations were isolated before rIL 2 culture (LAK precursors), CD5- cells but not CD5+ cells developed LAK activity (28% +/- 12 vs 1% +/- 1, mean percent specific release, 10:1 E:T ratio), confirming our previous results showing that only CD16+ cells were LAK precursors. The discrepancy between LAK effector and precursor phenotypes suggested that LAK precursors acquired CD5 determinants during rIL 2 culture; however, double label immunofluorescence of rIL 2 cultured CD16+ cells showed that this was not the case. The data suggested that in the presence of other cell types, some T lymphocytes may develop LAK activity, but purified blood T lymphocytes do not develop LAK function when cultured with rIL 2 alone. We also analyzed LAK effector function in lymphocyte subpopulations defined by CD4 and CD8 antigens. The data showed that lymphocytes with a low density expression of CD8 and no expression of CD4 were enriched for LAK effector cells, whereas CD4+ and CD8- had less activity than unsorted cells. Lymphocytes with a high density expression of CD8 had activity similar to unsorted cells. We also assessed the contribution of Leu-7 (HNK-1) granular lymphocytes to LAK effector function. After culture with IL 2, lymphocytes were depleted of Leu-7+ cells by antibody and complement treatment and then were sorted into CD5+ and CD5- fractions. The cytotoxic activity of Leu-7-CD5+ cells was a mean 5% +/- 5 vs a mean 14% +/- 8 for the total CD5+ population (20:1 E:T ratio). The activity of Leu-7- CD5- was slightly less than the total CD5- fraction (21% +/- 9 vs 28% +/- 14, 10:1 E:T ratio). In conclusion, LAK effector function was highest in non-T cell (CD5- CD16+) populations and some activity was also present in T cell populations (CD5+ and predominantly Leu-7+).
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PMID:Human lymphokine-activated killer (LAK) cells: identification of two types of effector cells. 310 Jun 27

In these studies we investigated the phenotypic and functional characteristics of human rIL 2-activated killer cells (LAK). By FACS sorting we separated PBL into Leu-11- and Leu-11+ cell fractions and cultured them for 4 days in 100 U/ml rIL 2. Under these culture conditions, cells of the Leu-11+ fraction acquired a stronger LAK activity against fresh autologous or allogeneic melanoma cells as compared with Leu-11- cells or unfractionated PBL. To better characterize the cells responsible for this cytolytic activity, we directly cloned Leu-11+ and Leu-11- FACS-sorted cells in the presence of 1% PHA, irradiated spleen feeder cells, and rIL 2. From 6 to 10% of the Leu-11+ cells and from 42 to 66% of the Leu-11- cells plated gave rise to clonal progenies that were tested simultaneously for cytolytic activity against fresh melanoma cells and NK-sensitive K562 target cells in a 4-hr 51Cr-release assay. Most of the Leu-11+ microcultures lysed fresh melanoma target cells (35 out of 38 and 26 out of 34 in two separate experiments), whereas only a few clones derived from the Leu-11- cell fraction had this capability (four out of 45 and one out of 41). All the clones lysing fresh melanoma cells also efficiently killed K562 target cells, whereas other clones lysing only K562 could be found among Leu-11+ and Leu-11- clones. Nine clones expressing LAK activity were tested for their reactivity against a panel of different tumor target cells. All clones were able to lyse a broad panel of target cells including NK-sensitive and NK-resistant cultured or noncultured human tumor target cells, as well as mouse tumor cell lines. Surface marker analysis of 14 clones displaying LAK activity, all derived from Leu-11+ cells, showed that they were all T3 (CD3)-, whereas 10 out of 14 expressed the T11 (CD2) antigen and only four were weakly stained by an anti-T8 (CD8) mAb. All 14 clones expressed the T40 (CD7) T cell marker and DR and LFA-1 antigens. Cytolysis inhibition experiments performed on a rIL 2-activated Leu-11+ population and on two LAK cell clones, both expressing T11 antigen, showed that anti-LFA-1 but not anti-T11 mAb could inhibit cytolysis of freshly derived tumor target cells.
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PMID:Phenotypic and functional characterization of recombinant interleukin 2 (rIL 2)-induced activated killer cells: analysis at the population and clonal levels. 310 Jun 33

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

Thirty-two melanoma patients treated with lymphoblastoid alpha interferon (Wellferon) were studied for augmentation of five putative parameters of natural immunity including natural killing (NK), antibody-dependent cellular cytotoxicity (ADCC), cell-mediated inhibition of growth in culture of a murine tumor (GIA), and the size of the OKTIO+ and Leu 7+ subpopulations of peripheral blood mononuclear cells (OKTIO and Leu7). This study confirms and extends our previous conclusions that interferon increases GIA and OKTIO. The increases occurred at 24 hr after interferon, both early and late in the course of treatment, and were dose dependent. NK, ADCC, and Leu7 were activated in many patients individually and mean values for NK and Leu7 were increased in the population as a whole. Two patients with complete remission showed dramatically increased natural immunity by the parameters studied, but the pattern of increase was very different for each patient. The current study of lymphoblastoid alpha interferon demonstrates the immunomodulatory potential of interferon given to melanoma patients, but it fails to support the hypothesis that augmentation of these parameters of natural immunity by interferon may result in tumor responses.
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PMID:Augmentation of natural immunity and correlation with tumor response in melanoma patients treated with human lymphoblastoid interferon. 310 49

Unstimulated human peripheral blood mononuclear cells from healthy donors exhibited spontaneous cytotoxicity against noncultured solid tumor targets in a 12- to 24-hr 51Cr release or 111In release assay. Both purified monocytes (greater than 99% monocytes) and natural killer (NK)-enriched lymphocytes exhibited comparable levels of spontaneous cytotoxicity against fresh melanoma tumor targets. This cytotoxicity was observed under endotoxin-free conditions. NK-depleted lymphocytes did not lyse the melanoma targets. Culture supernatants of monocytes incubated with the melanoma tumor cells did not exhibit cytotoxic activity against these targets. Purified monocytes lacked NK activity against the K562 targets in a 4-hr 51Cr release assay. Treatment of the monocytes with anti-Leu 1 1b and anti-Leu7 monoclonal antibodies plus complement did not reduce monocyte-mediated lysis of the melanoma targets, demonstrating that contaminating NK cells, if any, were not responsible for the lysis of noncultured melanoma targets by monocytes. In contrast, Leu 1 1b+ NK cells were responsible for the lysis of the melanoma targets by NK-enriched lymphocytes. The addition of recombinant interferon-gamma (rIFN-gamma), but not lipopolysaccharide, into the 51Cr release assay or pretreatment of monocytes with rIFN-gamma significantly increased their cytotoxicity against noncultured solid tumor cells. Monocytes cultured for 3 days with medium alone lost their cytotoxic activity. The addition of rIFN-gamma from the beginning of these cultures prevented the loss of the cytotoxic activity of monocytes. In summary, both unstimulated monocytes and NK-enriched lymphocytes exhibit comparable levels of spontaneous cytotoxicity against fresh solid tumor targets.
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PMID:Monocyte- and natural killer cell-mediated spontaneous cytotoxicity against human noncultured solid tumor cells. 311 44

Parent B16 melanoma and B16-F1 cell lines express a third actin (Ax) in addition to beta- and gamma-actin. It has the same molecular mass (43,000 daltons) and a more acidic isoelectric point (pI = 5.2) than the latter two actins (pI = 5.3) (Taniguchi, S., Kawano, T., Kakunaga, T., and Baba, T. (1986) J. Biol. Chem. 261, 6100-6106). We constructed a cDNA library from poly(A)+ RNA of B16-F1 and then isolated Ax actin candidate clones. According to the nucleotide sequencing analysis for one of the candidate clones, pMA 30, the predicted amino acid sequence was composed of 375 amino acids and was similar to that of beta-actin, but differed at the 28th amino acid in that leucine replaced the arginine of beta-actin. When RNA synthesized from the clone pMA 30 with the SP6 transcription system was translated in vitro using reticulocyte lysate, we identified a polypeptide which had the same isoelectric point and molecular weight as Ax actin; the polypeptide had binding activity to DNase I, a common characteristic of native actin. These observations provide evidence that the clone pMA 30 encodes the mRNA for Ax actin. In the nucleotide sequence of the Ax cDNA, there are: 1) one base change in the coding region which causes a loss of the SmaI site and an amino acid exchange, as mentioned above; 2) four deletion sites in the 3'-noncoding region; 3) one insertion site in the 3'-noncoding region; and 4) one base change in the 5'-noncoding region, as compared with hitherto known mouse beta-actin cDNA. These differences between Ax and beta-actin cDNA indicate that the Ax actin is encoded by an unique gene set, independent of beta-actin.
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PMID:cDNA cloning and sequence of a new type of actin in mouse B16 melanoma. 318 74

Melanomas are associated with a T-cell predominant infiltrate that may cause their regression. Langerhans cells (LC) are essential for initiation and maintenance of specific T-cell-mediate responses in the skin. Therefore, a change in this antigen-presenting LC population may alter the host response. To determine whether the LC population varies during the evolution of primary cutaneous melanoma 32 melanocytic lesions, nevi, and cutaneous melanomas were studied by quantitative immunohistology. The monoclonal antibody, Leu-6, and the avidin biotin complex immunoperoxidase method were used to identify LC. Compared with histologically normal melanoma-adjacent skin, epidermal LC were depleted above "deeply invasive" melanomas but were relatively unchanged above nevi, "early invasive" melanomas, and cutaneous metastatic melanoma nodules. Dermal LC were significantly increased around in situ and "early invasive" melanomas but not around "deeply invasive" melanomas or cutaneous metastatic nodules. Dermal LC are thus associated with early transformed melanocytes and may present neoantigens to T lymphocytes in situ or after LC maturation in the draining lymph node. Melanoma-associated LC decline in number as melanoma progresses.
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PMID:Quantitative alterations in cutaneous Langerhans cells during the evolution of malignant melanoma of the skin. 326 Sep 30

Intratumor macrophage numbers are enhanced by the administration of chemotactic f-MET-LEU-PHE - antitumor antibody - conjugates. The four f-MET-peptides f-MET-LEU-PHE, f-MET-LEU-PHE-o-methylester, formyl-norleucyl-phenylalanine and formyl-methionyl-phenylalanine, all chemotactic for human monocytes, where evaluated alone and conjugated to the melanoma directed monoclonal antibody ZME 018. f-MET-LEU-PHE-o-methyl-ester is the most active peptide, whereas f-MET-LEU-PHE - ZME 018 is the most active conjugate, not only inducing a response at the lowest concentration, but also the highest migrating cell numbers.
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PMID:Chemotactic monoclonal antibody conjugates: a comparison of four different f-Met-peptide-conjugates. 326 21

A rare case of hemorrhagic malignant melanoma from an unknown primary origin to the right sphenoid bone in a 37-year-old woman is presented. The tumor occupied an extensive intracranial extradural space with a mild orbital infiltration, but little involvement of the leptomeninges and parenchymal tissues. Immunohistochemical analysis of the tumor-infiltrating lymphocytes showed that the majority expressed pan-T or Leu-1 surface antigens and that the lymphocytes bearing the Leu-3 antigen, or helper phenotype, were predominant compared to the Leu-2 population representing both suppressor and cytotoxic T cells. Furthermore, most of the T lymphocytes stained with HLA-DR antigens. Because few B cells were seen, this observation indicates the presence of T cells in an activated state. The literature pertinent to associated organ involvement of metastatic melanomas and the correlations between the tumor and immunological cellular responses are discussed.
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PMID:Malignant melanoma metastatic to sphenoid bone with an unknown primary origin: report of a case with an immunohistochemical analysis of the infiltrating lymphocytes. 330 55

Monoclonal antibodies were produced by immunization of the human glioma cell line SK-MG-4. One of the antibodies, designated G-22, reacted with 18 of 20 glioma cell lines, two melanoma cell lines, and three lung cancer cell lines, but not with 39 cell lines derived from sarcoma, carcinoma, or hematopoietic tumors. The antigen was expressed in the brain of human fetuses in early gestation (9 weeks) but not in late gestation (8 months) or in normal adult brain, suggesting that the antibody recognizes neural differentiation antigens expressed by neuroectodermal origin. A high incidence of positive antigens has been observed in gliomas but not in the other neural tumors, such as ependymomas, meningiomas, and neuroblastomas. Thus, the antigen defined by the G-22 monoclonal antibody could be defined as glioma-associated antigen. Pulse-labeling with tritiated leucine and subsequent immunoprecipitation of the solubilized cell membrane revealed that the antigen recognized by this antibody had a molecular weight of 67 kD on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It was shown by dot-blot enzyme-linked immunospecific assay (ELISA) that the antigen could be detected in the cerebrospinal fluid (CSF) from patients with gliomas. From analysis of affinity chromatography and SDS-PAGE, the antigen present in the CSF had a molecular weight similar to that of a 1% Nonidet P-40 (NP-40) extract from a glioma cell line. When the antigen in CSF was quantitatively assayed by ELISA, the mean antigen level (expressed as optical density at 450 nm) in the CSF of seven patients was 0.8 +/- 0.28 (mean +/- standard deviation), which was significantly higher than the 0.38 +/- 0.14 level observed in the CSF of 15 patients with nonglioma brain tumors and the 0.23 +/- 0.09 level in the CSF of four patients without brain tumors. These results indicate that the monoclonal antibody G-22 is useful for the diagnosis of glioma.
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PMID:Characterization of neuroectodermal antigen by a monoclonal antibody and its application in CSF diagnosis of human glioma. 334 15


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