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)

The expression of different immunological markers by cultured human melanocytes (MC) in relation to immune phenomena, were investigated on ten different MC cell lines from early (1st) to late (22nd) passage. Four melanocyte lines (MC-a) which had undergone changes in growth behaviour during prolonged culture were included in the study, together with two melanoma lines. Cytospin preparations of the cells were stained for the presence of a set of different immunological markers and a melanoma-associated antigen (MAA). All MC lines, including the MC-a and the melanoma lines, showed expression of MHC class I, IL-1, IL-2, ICAM-1 and the MAA, NKI-Beteb, during all passages tested. Interestingly, four of the MC lines showed staining for the Fc receptor. A tendency towards a stronger expression of ICAM-1 on a higher percentage of cells was observed on MC with increasing passage number, the MC-a and the melanoma lines. Expression of the MAA was strongly reduced for the MC-a lines in comparison with the MC and the M14 melanoma lines. Positive staining for the HLA class II molecules was obtained on MC of intermediate and late passages, and on the MC-a and the melanoma lines in the decreasing order HLA-DR, DP and DQ. Additionally, we carried out a preliminary study showing that cultured MC also produce IL-1 and IL-6. However, we were not able to show the production of biologically active IL-2 testing several cultured MC lines. Nevertheless, the overall results taken together suggest that MC are immunologically important cells that are susceptible to changes during long-term culture.
 ...
PMID:Expression of different immunological markers by cultured human melanocytes. 821 85

The purpose of this study was to determine the influence of recombinant human interleukin-4 (IL-4) on the regulation of lymphokine-activated killer (LAK) and mixed lymphocyte culture cytotoxic activity. Lymphocytes from several lymphoid tissues were studied including human peripheral blood leukocytes (PBL), spleen cells, thymocytes, and thoracic duct lymphocytes. Cells were cultured with IL-4 in the presence or absence of recombinant human interleukin-2 (IL-2) in 4-day cultures. LAK and natural killer (NK) activities were measured in a standard chromium release cytotoxicity assay against LAK-sensitive, NK-resistant M14 melanoma targets and NK-sensitive K562 erythroleukemic cells. IL-4 alone does not increase NK or LAK activity under the conditions studied. However, IL-4 does inhibit the induction of cytotoxic activity by IL-2. IL-4 inhibits IL-2-induced thymidine incorporation in 3-day PBL cultures, suggesting that the inhibition of cytotoxicity is not a dilution effect due to the proliferation of noncytotoxic cell populations. IL-4 also inhibits the development of LAK and NK-like activities generated in mixed lymphocyte culture (MLC) while augmenting MLC-generated allospecific cytotoxic T lymphocyte activity. Thus, IL-4 appears to inhibit the induction of nonspecific cytotoxic effectors while augmenting the generation of MHC-specific responses. This confirms an important regulatory function for this lymphokine in the generation of cytotoxic effectors.
 ...
PMID:IL-4 inhibits IL-2 induction of LAK cytotoxicity in lymphocytes from a variety of lymphoid tissues. 823 Nov 67

The inhibitory effect of saporin 6, a single-chain ribosome-inactivating protein (sc-RIP) purified from the seeds of Saponaria officinalis, on the proliferation of human primary (MeWo, WM 164, SK MEL 28, MEM), cloned (MEM A9, A12, A13) and metastatic (M14) melanoma cells has been tested by protein synthesis and colony formation assays in vitro. Results indicate a marked difference in the sensitivity of primary and metastatic cells to the action of saporin 6, the latter being significantly more affected, both in treated and in pretreated cultures, with a high and specific response evident after 24 h of treatment and progressively increasing up to 72 h of culture with the drug (IC50 = 0.82 microgram/ml). This effect, which was dose-dependent in exponentially growing cells, was partially reversed upon removal of the inhibitor from the culture medium. No inhibitory effect was evident in the MeWo primary cells at the highest saporin 6 concentration used: the p170 glycoprotein-mediated mechanism is not involved in such a resistance pathway.
Melanoma Res 1993 Oct
PMID:Diverse activity of sc-RIP saporin 6 on primary and metastatic melanoma cells in vitro. 829 94

Flow cytometric analysis reveals that 5 human melanoma cell lines (M14, IGR3, ME1477, JUSO, GLL19) express both alpha and beta chain of the interleukin 2 receptor (IL-2R alpha and IL-2R beta). These chains are able to specifically bind IL-2 and to form high-affinity heterodimers (IL-2R alpha beta). Analysis of poly A+ RNAs by Northern blot reveals the presence of typical transcripts for both the IL-2R alpha gene (3.6 kb) and the IL-2R beta gene (4 kb). Reverse transcription/polymerase chain reaction analysis allowed transcripts for the IL2R gamma (p64) gene to be detected in 3 of these melanoma cell lines (M14, IGR3, ME 1477). Incubation with human recombinant IL-2 modifies in IL-2R alpha+beta+gamma+ (M14) the expression of several surface molecules: down-regulation of ICAM-1, HLA class I and HLA-DR and up-regulation of CD44. IL-2 is also active on IL-2 alpha+beta+gamma- cell lines since it decreases ICAM-1 and HLA class-II expression at the surface of JUSO cells. Down-regulation of ICAM-1, whose expression in melanoma cells is a marker of tumor progression, is detectable within 3 hr in M14 cells and is maximal after 48 hr incubation, at IL-2 concentrations corresponding to the high-affinity heterodimers. This feature is specific since it is partially inhibited by MAbs directed against the IL-2 binding site of the IL-2R alpha (MAR93, 10T14) and IL-2R beta (MiK beta 1, TU27) chains. Our data support the notion of a direct effect of IL-2 on human melanoma cells. Modulation of the expression of surface molecules which is important for the interaction with immunocompetent cells or for tumor progression, could have a role to play during in vivo IL-2 treatment of human melanomas.
 ...
PMID:Human melanoma cells express a functional interleukin-2 receptor. 834 47

A patient with renal cell cancer developed acute renal failure due to biopsy-proven acute tubulo-interstitial nephritis (AIN) in the 6th week of continuous infusion of 9 x 10(6) IU m-2 day-1 recombinant interleukin-2 (rIL-2). We investigated whether the AIN was the result of a cellular cytotoxic reaction induced by the rIL-2 treatment. The cytolytic activity of cryopreserved peripheral blood lymphocytes (PBL), isolated before and at the end of the rIL-2 treatment (at the time of AIN), was studied after 5 days of culture with or without rIL-2 or anti-CD28 and immobilized anti-CD3 antibodies. The PBL isolated before and at the end of the rIL-2 treatment showed cytolytic activity towards a number of allogeneic targets. However, only the PBL isolated at the end of the rIL-2 treatment showed, when stimulated with rIL-2 in vitro, significant cytolytic activity against an autologous renal cell line cultured from the AIN biopsy specimen and against an allogeneic renal cell cancer cell line. These PBL displayed no enhanced killing capacity towards autologous PBL and the melanoma cell line M14. These observations suggest that the AIN may be the result of a cytotoxic lymphocyte-mediated reaction induced by the rIL-2 treatment.
 ...
PMID:Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer. 843 83

Adoptive immunotherapy with interleukin-2 and tumor-infiltrating lymphocytes (TIL) is rarely effective in primary lung cancer. We hypothesize that pulmonary macrophages (PM), which are increased substantially in the lungs of smokers, might suppress TIL function. The addition of PM into the TIL cytotoxicity assay produced a concentration-dependent suppression of TIL cytotoxicity with up to 71% inhibition of autologous tumor killing at the 1:1 PM:TIL ratio. Inhibition was not target-specific, as killing of NK-sensitive (K562), NK-resistant (M14), and autologous tumor targets were equally suppressed. Nor was inhibition specific for lung TIL, as similar inhibition was observed with melanoma and renal TIL. Using a model system, we demonstrated that both CD3+ antigen-specific and CD56+ nonspecific lymphocytes are susceptible to the suppressive effects of the PM. Direct co-incubation of PM and TIL for 4 to 44 h resulted in progressive suppression of TIL proliferation and cytotoxicity. TIL cytotoxicity remained suppressed even if PM were removed from the co-culture after 24 h, but was restored if the separated TIL were re-incubated in interleukin-2. These results suggest that PM may locally regulate the proliferative and cytotoxic function of adoptively transferred TIL.
 ...
PMID:Pulmonary macrophages suppress the proliferation and cytotoxicity of tumor-infiltrating lymphocytes. 848 Dec 33

Peripheral mononuclear cells (PMNC) from 18 melanoma were monitored for vaccine-related changes in their immune responses by measuring functional activity and phenotypic expression of PMNC prior to- and following 4-6 vaccinations. Assays included: cytolytic responses directed against melanoma cell lines included in the vaccine (M20, M14, HM54 and SKMel28), control melanoma (SKMel23) and non-melanoma (SKCo1, K562 and Daudi) cell lines. Direct lytic responses were significantly enhanced following vaccine treatment, mainly against M20 cell line and was further augmented following In Vitro Stimulation (IVS) by Mit-C-treated M20 or M14 cells. No evidence was found of augmentation of NK or LAK activity by vaccine treatment. Significantly enhanced proliferative responses to of vaccine-treated patients' PMNC to melanoma cell lines were also observed. The human melanoma cell lines used for vaccine preparation (M14, M20 and SKMel28) are high expressors of HLA class I, while high expression of HLA-DR only on M20 cells. Cell surface markers' study indicate a shift in CD4/CD8 ratio from 1.1 to 2.1 and increase in CD25 and HLA-DR positive cells. In M20-stimulated cultures of post-vaccine patients' PMNC the predominant phenotype was CD3+/CD4+. In conclusion, we have demonstrated that treatment with polyvalent allogeneic melanoma vaccine significantly augments T-cell mediated CD3+/CD4+), anti-melanoma lytic and proliferative responses, non-MHC-restricted.
 ...
PMID:In vitro cell-mediated immune responses induced by a polyvalent allogeneic melanoma vaccine. 854 60

We have investigated the effect of mild hyperthermia (42 degrees C) on the cytotoxic activity of a 1 h melphalan exposure in human melanoma cell lines. Hyperthermia did not affect cell growth of any culture, but it increased, to a different extent, melphalan cytotoxicity in all cell lines, with a reduction in the IC50 of 1.7 to 2.6-fold. Flow cytometric analysis showed that in normal temperature conditions melphalan caused S phase cell accumulation, which was evident only at 24 h in JR8, M14 and 2/21 cell lines and was still persistent at 72 h in 2/60 cells. Moreover, in all cell lines, the delay in S phase was paralleled, or followed, by an accumulation of cells in G2+M, which was transient in JR8 and M14 cells and persisted until 72 h in 2/21 and 2/60 melanoma clones. Hyperthermia caused a stabilization and prolongation of melphalan induced G2+M accumulation in JR8 and M14 cells. Conversely, in 2/21 and 2/60 clones, cell cycle perturbations induced by the drug were similar under normothermic or hyperthermic conditions. Specifically, in JR8, for which the maximum enhancement by hyperthermia on melphalan cytotoxicity was observed, cell accumulation in G2+M was still present 120 h after treatment. The accumulation was accompanied by an inhibition in the G2-M transition, as demonstrated by the significant reduction in the mitotic index of cells exposed to combined treatment compared to controls. Moreover, a bivariate distribution of cells stained for DNA and cyclin B1 showed that, following melphalan and hyperthermia treatment, the fraction of cyclin B1-expressing cells paralleled the fraction of G2+M phase cells, thus indicating that the inability of cells to enter mitosis was not ascribable to a reduction of cyclin B1 expression. On the whole, our results indicate that hyperthermia can stabilize the G2 accumulation induced by melphalan in human melanoma cells. Such a stabilization could contribute to the enhancement of melphalan cytotoxicity by heat, even though a strict correlation was not observed between the magnitude and persistence of the cell cycle perturbations and the extent of melphalan activity.
 ...
PMID:Effect of melphalan and hyperthermia on cell cycle progression and cyclin B1 expression in human melanoma cells. 855 74

In the present study we investigated the effect of gamma-irradiation (2.5 and 10 Gy) on cell-cycle progression of a human melanoma cell line, M14, characterized by a moderate radiosensitivity (SF2 = O.5). Flow cytometric analysis showed a dose-dependent S-phase accumulation, which was detectable 8 hr after treatment with 2 and 5 Gy and was still persistent at 12 hr after 10 Gy exposure. Such a delay in S-phase was paralleled or followed by an accumulation of cells in G2M, which was transient at the lowest radiation doses and still persistent at 72 hr after 10 Gy. Such an accumulation was, at least in part, due to a block in G2-M transition, as demonstrated by mitotic index analysis. Bivariate flow cytometric analysis of DNA content and cyclin B1 expression showed that, following 2 and 5 Gy, the fraction of cyclin B1-expressing cells was superimposable upon that of G2M cells. Conversely, in cells treated with 10 Gy, the fraction of cyclin B1-expressing cells was half the G2M cell fraction. Northern-blot analysis indicated that the radiation-induced decrease in cyclin B1 protein expression was accompanied by a reduced cyclin B mRNA level. On the whole, our results indicate a direct inhibitory effect of 10 Gy irradiation on cyclin B1 expression as a possible cause for the persistent G2 block in irradiated M14 cells.
 ...
PMID:Effect of ionizing radiation on cell-cycle progression and cyclin B1 expression in human melanoma cells. 860 51

In vivo, melanocytes were detected in epidermis from human tissue of 6.5 weeks estimated gestinational age (EGA) and older. We have successfully established melanocyte monocultures from tissue of 9 to 10 weeks EGA. To our knowledge, this is the first report on physiology of human foetal melanocytes in monoculture. In culture, such melanocytes retained foetal characteristics. Proliferation rates noted were markedly higher (approximately 2.7-fold) when compared to those in cultures of neonatal melanocytes. Moreover, when analyzing cellular phenotypes by markers for cells of the melanocytic lineage, foetal cells isolated from tissue of 9 weeks EGA reproducibly showed expression of the high molecular weight (HMW) antigen and c-kit to an extent intermediate to that found in neonatal melanocytes and M14 melanoma cells. Such differential expression was not observed if cells were isolated from tissue of 10 weeks EGA, indicating that the foetal environment provides essential differentiation stimuli during the 10th week of gestation. Moreover, these results are supportive of the theory that malignant transformation involves a process of dedifferentiation. In all, human foetal melanocyte culture provides a useful model to investigate pigment cell differentiation.
 ...
PMID:Foetal human melanocytes: in situ detection, in vitro culture and differentiation characteristics at 6-11 weeks EGA. 888 11


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