UMLS:C0025202 - FACTA Search

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

The combination of recombinant human fibroblast interferon (INF-delta) and the antileukemic compound mezerein (MEZ) results in a synergistic suppression in the growth of human melanoma cells and a concomitant increase in melanin synthesis. In the present study we have further analyzed this synergistic interaction and have also evaluated the effect of IFN-delta and MEZ, alone and in combination, on recombinant human gamma interferon (IFN-gamma) binding and Class I HLA and melanoma associated antigen (MAA) expression in the HO-1 human melanoma cell line. Single cell clones isolated from the HO-1 cell line varied in their sensitivity to the antiproliferative effects of IFN-delta and MEZ. With all twelve clones, however, the combination of IFN-delta plus MEZ was more growth inhibitory than either agent used alone, even in HO-1 subclones displaying relative resistance to IFN-delta. By continuous growth in gradually increasing concentrations of IFN-delta, a variant population of HO-1 cells, HO-1 delta R-D, was generated which was more resistant to the antigrowth effects of IFN-delta than the original HO-1 parental cell line. In the IFN delta R-D cell line the combination of IFN-delta plus MEZ synergistically suppressed growth. Exposure of HO-1 cells to 2500 units/ml IFN-delta or 50 ng/ml MEZ for 96 hr resulted in no change or an increase in the binding of labelled IFN-gamma to surface receptors, whereas the combination of IFN-delta plus MEZ increased IFN-gamma binding 2-to-4-fold in HO-1 cells. This increase was the result of an increase in the number of receptors on treated cells coupled with a protection against a decrease in receptors observed for confluent untreated cells. Changes in IFN-gamma binding resulting from treatment with IFN-delta plus MEZ were not associated with alterations in the binding affinity of INF-gamma to its receptor. Changes were also observed in the expression of HLA Class I antigens and MAAs following treatment of HO-1 cells with IFN-delta, MEZ or IFN-delta plus MEZ. IFN-delta and MEZ increased the expression of HLA Class I antigens a 96 kd MAA defined by MoAb CL203, a 100 kd MAA defined by MoAb 376.96 and a 115 kd MAA defined by MoAb 345.134 but decreased the expression of a high molecular weight-melanoma associated antigen (HMW-MAA) defined by MoAb 325.28S.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of recombinant human fibroblast interferon and mezerein on growth, differentiation, immune interferon binding and tumor associated antigen expression in human melanoma cells. 294 74

Melanoma patients were vaccinated with cell-free lysates prepared from vesicular stomatitis virus (VSV)-infected cultured autologous and allogeneic melanoma cells. Eleven patients received vaccines produced from the melanoma cell line SK-MEL-13. This cell line, derived from the melanoma of Patient AH, expresses a differentiation antigen (initially defined by autologous antibody) that is restricted to melanomas and other cells of neural crest origin (an example of a Class 2 melanoma antigen). Thirteen patients received vaccines prepared from autologous melanoma cells, the only known source of autologous unique (Class 1) melanoma antigens. VSV lysates were used for vaccination because VSV infection of tumor cells has been shown to augment the immunogenicity of tumor antigens. All patients but one vaccinated with VSV lysates of autologous melanoma cells developed antibodies against VSV, and all patients vaccinated with VSV lysates of SK-MEL-13 developed antibodies against HLA-related antigens. Antibodies against a Class 1 (unique) melanoma antigen were detected in only one case, and antibodies against Class 2 (shared) melanoma antigens were not found in any of the patients. The authors conclude that VSV lysates of melanoma cells are not effective in increasing the serologic response of melanoma patients to Class 1 or 2 melanoma antigens.
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PMID:Serological response of melanoma patients to vaccines prepared from VSV lysates of autologous and allogeneic cultured melanoma cells. 298 1

Using monoclonal antibodies, recombinant human gamma-interferon, and fluorescence-activated cell sorter, 2 human melanoma cell lines (KHm-1/4 and A101D) were examined quantitatively for HLA-DR and 97-kD melanoma-associated antigen (p97) expression throughout the cell cycle. Two-color flow cytometric analysis showed that the mean cell volume increased (KHm-1/4, 2.6 times; A101D, 3.6 times) during the progression of the cell cycle, and that fluorescence intensity of HLA-DR and p97 correlated well with cell volume, i.e., both antigens were maximally detected during the G2-M phase. The density of HLA-DR and p97 on the cell surface remained relatively constant throughout the cell cycle with the exception that cells in S phase showed a slightly lower density compared with those in G0/G1 and G2-M phases. gamma-Interferon treatment (500 IU/ml, 72 h) increased HLA-DR+ cells (KHm-1/4, 65% to 89%; A101D, 34% to 84%) and p97+ cells (KHm-1/4, 8% to 12%; A101D, 19% to 35%). Increased antigen densities were also relatively constant throughout the cell cycle as in nontreated cells. Cells treated with gamma-interferon tended to accumulate at G0/G1 phase (KHm-1/4, 21% to 37%; A101D, 17% to 53%), and had a reduced cell volume (0.82-0.95 times) throughout cell cycle. This study revealed that both melanoma cell lines showed heterogeneity in the expression of HLA-DR and p97, and that this heterogeneity was influenced, at least in part, by cell cycle and immunologic events such as gamma-interferon treatment.
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PMID:HLA-DR and melanoma-associated antigen (p97) expression during the cell cycle in human melanoma cell lines, and the effects of recombinant gamma-interferon: two-color flow cytometric analysis. 309 Jan 58

Fifty-six tumor clones isolated by cloning in soft agar from early cultures (before the 10th in vitro passage) of two different human metastatic melanomas (Me9229 and Me28) were characterized by FACS analysis for surface expression of class-I and class-II HLA antigens and of melanoma-associated antigens (MAA) with a panel of 15 monoclonal antibodies (MAbs). A marked phenotypic heterogeneity involving MAA and/or HLA markers was observed among the clones derived from both tumors. The differences among the tumor clones and between them and the uncloned melanoma were qualitative and quantitative for each antigen considered. Clones derived from Me9229 expressed the same HLA profile as the parental culture (class I+, class II-) while strong heterogeneity was observed for MAA expression. Clones from Me28 presented a marked heterogeneity for class-I and class-II HLA antigens but were more homogeneous for MAA. The phenotype of the clones was repeatedly checked over the first month in culture and found to remain generally unchanged and not linked to the cell cycle. However, major changes in antigenic expression of the clones could be observed upon treatment with recombinant interferon-gamma (rIFN-gamma): class-I and -II HLA antigens could be induced or augmented while a moderate inhibition was seen on MAA expression. Furthermore, an apparent hierarchy in expression and/or induction of class-II antigens by rIFN-gamma was observed among the tumor clones. DR antigens were more frequently expressed (Me28 clones) and upon treatment with rIFN-gamma reached higher levels than DP and DQ products. Taken together these results indicate that antigenic heterogeneity for MAA and HLA antigens can be detected in cells isolated from early cultures of human metastatic melanomas and suggest that the original uncloned tumor might be considered as a complex mixed population made up of a number of neoplastic cells each expressing a distinct phenotype which can be modulated by lymphokines such as IFN-gamma.
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PMID:Phenotypic profile of clones from early cultures of human metastatic melanomas and its modulation by recombinant interferon gamma. 309 92

The effect of recombinant immune interferon (IFN-gamma) on the expression and shedding of HLA antigens and of melanoma-associated antigens (MAA) by epidermal melanocytes was investigated by using serologic and immunochemical techniques. IFN-gamma enhances the expression and/or shedding of HLA class I antigens and of the cytoplasmic MAA defined by monoclonal antibody (MoAb) 465.12S and induces a slight reduction in the expression of the high m.w. melanoma-associated antigen (HMW-MAA). In agreement with the data in the literature, melanocytes incubated with IFN-gamma acquire HLA-DR, -DQ, and -DP antigens. Contrary to previous information in the literature, the effect is not restricted to HLA class II antigens, since IFN-gamma also induces the expression of the 96-kDa MAA recognized by MoAb CL203. The effect of IFN-gamma on HLA class II antigens and 96-kDa MAA is dose and time dependent and is specific, because recombinant leukocyte interferon affects the expression of neither type of antigen. In spite of the expression of HLA class II antigens, IFN-gamma-treated melanocytes do not acquire the ability to stimulate the proliferation of allogeneic lymphocytes. HLA-DR antigens are more susceptible to induction by IFN-gamma than HLA-DQ and -DP antigens, since the percentage of melanocytes acquiring HLA-DQ and -DP antigens is lower than that acquiring HLA-DR antigens. Furthermore, the dose of IFN-gamma is higher and the time of incubation is longer to induce HLA-DQ and -DP antigens than to induce HLA-DR antigens. The differential susceptibility of HLA-DR, -DQ, and -DP antigens as well as of melanocytes from various donors to the modulating effect of IFN-gamma may provide an explanation for the more frequent detection of HLA-DR than of HLA-DQ and -DP antigens in melanoma lesions and for the expression of HLA class II antigens by some, but not all, melanoma lesions.
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PMID:Immunochemical and functional analysis of HLA class II antigens induced by recombinant immune interferon on normal epidermal melanocytes. 310 Jun 35

Class I and II histocompatibility antigen expression was studied in cryostat sections of biopsy tissues from 15 patients diagnosed as suffering from malignant melanoma, using monoclonal antibodies against HLA class I and II monomorphic determinants and an indirect immunofluorescence technique. Class I antigens were detected in three of the four primary melanomas and in five of the eleven metastatic melanomas. Class II antigens were expressed only in metastatic melanomas, in three out of eleven cases. Some tumour cell suspensions were obtained and short-term cultures were established. Radiobinding and immunoprecipitation studies were carried out in two cases, named M6 and M8. The results were comparable to those obtained with direct immunofluorescence. We modulated the expression of class I and II HLA antigens with interferon in M6 when adapted to tissue culture. This melanoma was class I and II negative; after IFN gamma treatment it became strongly positive for class I and II antigens. In addition we have demonstrated, using Southern blot analysis with the restriction enzymes PvuII and EcoRI, that the M6 melanoma does not have any detectable alterations in its class II beta genes.
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PMID:Differential expression of HLA class I and II antigens in primary and metastatic melanomas. 310 17

Three lymphocyte clones, derived by micromanipulation from peripheral blood lymphocytes (PBL) of a melanoma patient and expressing a broad pattern of reactivity against different target cells, were analyzed for the involvement of T-cell markers and HLA antigens in the lysis of target cells by blocking experiments with a panel of monoclonal antibodies (MAbs). The clones lysed autologous melanoma cells (Me 28) and 18 out of 22 allogeneic targets including neoplastic and normal cells of different histological origin. Anti-T3 and anti-T8 MAbs strongly inhibited the cytotoxicity of the lymphocyte clones against Me 28, 3 allogeneic melanomas and 3 carcinomas, but failed to affect the lysis of K562. Anti-HLA class-I MAb (w6/32) produced a significant enhancement of the lysis of Me 28 by the 3 clones without modifying cytotoxicity against one allogeneic melanoma or against K562 cells. Anti-HLA class-II MAb (D1.12) did not affect the lysis of the same targets by the 3 clones. These results thus indicate that some anti-melanoma CTL clones may interact with autologous tumor cells by the T3 and T8 structures in an HLA class-I unrestricted manner.
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PMID:Melanoma cell lysis by human CTL clones: differential involvement of T3, T8 and HLA antigens. 310 67

Vaccinia melanoma oncolysates (VMO) were tested in a Southeastern Cancer Study Group (SECSG)-sponsored phase I/II multiinstitutional trial. Forty-eight patients with stage I or II disease were placed on study at six different dose levels of VMO and two different dose schedules, immediate or delayed. Patients' sera, obtained before treatment and every 3 months following initiation of treatment, were tested for antimelanoma antibodies using a Staphylococcus protein A (SpA) assay. Pretreatment sera were negative in 46 of 47 patients, and only two of 19 patients on delayed treatment developed reactivity by 6 months. However, 13 of 23 on immediate treatment developed reactivity, including eight of eight at the higher doses (1.5 and 2.0 mg). Neither anti-HLA antibody tested by a standard microcytotoxicity assay nor circulating immune complexes measured by both Clq and conglutinin binding assays were produced as a result of the immunization. The demonstration of immunogenicity of VMO at the 2 mg dose and immediate schedule supported the rationale for the use of this dose and schedule for the ongoing second phase Ia/Ib trial and for the future phase III randomized prospective study.
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PMID:Serological evaluation of melanoma patients in a phase I/II trial of vaccinia melanoma oncolysate (VMO) immunotherapy. 315 79

Indirect immunofluorescence staining with a large battery of monoclonal antibodies of primary and autologous metastatic lesions removed from seven patients with melanoma has detected heterogeneity in the expression of various types of melanoma-associated antigens (MAAs), of distinct determinants of the high molecular weight melanoma-associated antigen (HMW-MAA), of the two subunits of Class I HLA antigens, and of the gene products of the HLA-D region. Among the 10 MAAs tested, the HMW-MAA had the highest frequency and the Mr 87,000 MAA the lowest. Furthermore, the HMW-MAA displayed the lowest heterogeneity. These findings, in conjunction with the restricted tissue distribution of the HMW-MAA, its lack of susceptibility to antibody-mediated modulation, and the high affinity of the available anti-HMW-MAA monoclonal antibodies, indicate that this antigen may be a useful marker for radioimaging and immunotherapy in patients with melanoma. The common acute lymphoblastic leukemia antigen was detected only in five lesions. Class I HLA antigens were detected in a larger number of lesions than HLA-DR antigens, which had a significantly higher frequency than HLA-DQ antigens. The degree of antigenic heterogeneity did not appear to correlate with the histopathological features of the lesions and/or with the clinical course of the disease. The results of the present study indicate that immunodiagnostic and immunotherapeutic approaches to melanoma should rely on the use of combinations of monoclonal antibodies to distinct MAAs.
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PMID:Heterogeneous expression of melanoma-associated antigens and HLA antigens by primary and multiple metastatic lesions removed from patients with melanoma. 315 50

Investigations have been performed to identify genetic markers in uveal melanoma (UM) patients. The immunogenetic heterogeneity of the histologically different forms of UM until now has been little analyzed. We subdivided our UM patients, all typed for class I and II HLA antigens and for Bf polymorphism, into two groups: 1) those with a high degree of malignancy (with nonspindle cells) and 2) those with a low degree of malignancy (with spindle cells). The deviated frequencies of class I HLA antigens (A32, B27) seem to be involved in the predisposition to spindle cell melanoma, while HLA class II (DR3, DR7) and class III (Bf F) strongly mark the worst form of UM. Different Gm allotype distributions between the two histological types of UM were also found.
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PMID:Immunogenetic heterogeneity of uveal melanoma. 318 Jan 22

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