Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanoma cells freshly isolated from regional lymph node metastases of 59 stage II malignant melanoma patients were analyzed by indirect immunofluorescence staining with monoclonal antibody TAL 1B5, detecting the HLA-DR alpha chain. The expression of HLA-A,B,C antigens, using antibody W6/32, was also investigated in 45 of these cases. There were no substantial differences in the course of the disease with respect to the percentage of positive cells. In 13 malignant melanoma patients two to four simultaneous and/or successive metastases (both locoregional and distant-subcutaneous) were analysed for HLA-DR. With simultaneous metastases (7 cases) the percentage of HLA-DR-positive cells was mostly very similar, and in no case was there more than 25% variation. As to successive metastases (9 cases) the percentage of HLA-DR-positive cells remained practically unchanged or decreased during the course of the disease.
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PMID:HLA-DR antigen expression on melanoma metastases and the course of the disease. 259 88

The expression of HLA class I and II antigens was analysed in 30 primary gastric carcinomas, 27 autologous lymph node metastases and 25 autologous gastric mucosae. We used an immune alkaline phosphatase technique on cryostatic sections and mAbs directed against HLA class I monomorphic determinants, HLA-B locus-specific products and HLA-DR, -DP and -DQ molecules. In addition HLA class I genes were analysed in tumour tissue and compared by Southern blots with the RFLP from autologous mucosa using locus-specific HLA probes. Finally the infiltrating mononuclear cells were studied on gastric tumours and adjacent mucosa with mAbs defining CD4, CD8 and CD11b differentiation antigens. The results obtained showed that three out of 27 primary gastric carcinomas completely lack HLA-ABC antigens (10%). In addition, two primary tumours presented a variable expression. The remaining 22 tumours presented a homogeneous positive HLA class I expression. Interestingly, when the autologous mucosa was analysed, only 12 out 25 specimens were homogeneously stained with mAbs against HLA class I antigens, suggesting that this tissue may lack the expression of HLA antigens before becoming malignant. Indeed, the majority of the gastric carcinomas studied presented a higher HLA-ABC antigenic expression than autologous mucosa. Finally, the HLA expression observed in the primary tumour was similar to that observed in autologous metastases. As a second part of the study we have found a direct relationship between the expression of HLA-DR antigens in mucosa and the intensity of inflammatory infiltration. This relationship was not maintained in the tumour tissue. In the mucosa the CD4-positive T cell was the predominant lymphocyte, while it was CD8 in the HLA-DR-positive tumours. Finally the RFLP of class I genes did not show any differences in any of the cases when compared with autologous mucosa. We included in these studies DNAs from HLA class I-negative tumours, HLA positive and HLA-B-negative ones.
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PMID:MHC class I and II antigens on gastric carcinomas and autologous mucosa. 263 12

The authors have studied in detail human leukocyte antigen (HLA) association in 87 Hungarian patients with thyroid epithelial carcinoma. The authors also examined in a small group of patients, five parameters of cell-mediated immunity and related them to HLA as well as to lymphocytic infiltration of the tumor/normal tissue interface. HLA-DR1 was significantly associated with thyroid carcinoma; the strongest association was in patients with follicular histologic features and DR1 homozygotes were not at greater risk for thyroid cancer. The HLA-DR3 was nonsignificantly increased in patients with papillary or mixed histologic features. The HLA-DR1, 3 heterozygotes were highly associated with follicular carcinoma, carried no risk for papillary carcinoma, and an intermediate risk for tumors with mixed histologic features. Because of the small proportion of DR1, 3 heterozygotes in the follicular and mixed histologic group, its predictive value at the population level was low. Better predictive potential was shown for the phenotype DR1 and/or DR3. Neither metastatic disease nor age at diagnosis (less than 45 years) could be related to HLA phenotypes. Patients in all histologic variants showed some measure of cell-mediated immunity compared to controls. Patients with papillary carcinoma showed an overall better response than those with tumors with follicular or mixed histology. The HLA-DR could not be related to cell-mediated immune response. Patients with papillary carcinoma with a good cell-mediated immune response occurred with much lower infiltration of the tumor boundary with lymphocyte whereas the follicular carcinoma less cell-mediated immunity was associated with dense lymphocytic infiltration, suggesting the biological relevance of lymphocytic infiltration may be different for the two histologic variants.
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PMID:Immunogenetic and immunologic studies of differentiated thyroid cancer. 278 72

Class I and HLA-DR antigen expression were studied with histochemical techniques involving monomorphic monoclonal antibodies in 49 cases of human malignant melanomas, 20 primary and 29 metastatic. A large percentage (90%) of primary melanomas were positive for HLA class I, while those primary lesions showing lowest levels of class I antigen expression were at the upper end of the range of invasiveness and possessed a higher metastatic potential. Expression of HLA-DR molecules on primary melanomas was low (25% of all cases) and HLA-DR-positive melanomas were among the most aggressive. In metastatic melanomas, HLA class I expression was less common than in primary lesions. The lowest percentage of cases positive for HLA class I was found for cutaneous metastases. HLA-DR molecules were more frequently expressed by lymph node metastases than on primary melanomas. The comparison of the expression of HLA class I and HLA-DR molecules by primary melanomas and their autologous metastases revealed a high degree of heterogeneity. Class I genes were further studied by Southern blot assays. No differences were found in restriction fragments for class I genes among 4 melanomas and their autologous lymphocytes, 2 of which were positive and 2 negative for class I expression.
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PMID:Phenotypic and genetic analysis of HLA class I and HLA-DR antigen expression on human melanomas. 307 72

Human melanoma cells freshly isolated from 20 patients with primary and 73 patients with metastatic melanomas were analyzed by indirect immunofluorescence staining with monoclonal antibodies (MoAb) to class I (HLA-A, -B, and -C) and class II (HLA-DR and -DQ) antigens and to melanoma associated antigen (MAA). The latter included the GD3-MAA and the high molecular weight MAA. HLA class I antigens were present in 91 and 93% of primary and metastatic tumors, respectively. GD3-MAA was detected in 100% of primary and 80% of metastatic tumors. Whereas the high molecular weight MAA was expressed in 75% of tumors. Sixty % of primary and 50% of metastatic melanomas were stained by anti-HLA-DR MoAb, whereas 38 and 21% of cases, respectively, were stained by anti-HLA-DQ MoAb. Marked phenotypic heterogeneity was evident among primary and metastatic tumors, including different metastases from the same patient. Moreover, in vitro culture of melanoma cells isolated from metastases was associated with an increase from 50 to 75% of tumors stained by anti-HLA-DR MoAb but not of tumors positive for HLA class I antigens and MAA. In vitro incubation with partially purified or recombinant human gamma-interferon enhanced the expression of HLA-DR antigens on all short-term cultured melanoma cells tested but induced and/or augmented the expression of HLA-DQ antigens only in 5 of the 8 cases examined. The average increase in antigenic expression was higher for HLA-DQ than for HLA-DR antigens. Flow cytometric measurement of DNA content of melanoma cells treated with gamma-interferon revealed that the increase of HLA-DR and -DQ expression induced by gamma-interferon was independent from the cell cycle of the tumor cells.
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PMID:Classes I and II HLA and melanoma-associated antigen expression and modulation on melanoma cells isolated from primary and metastatic lesions. 307 89

Lymphocyte subset phenotypes in peripheral blood and axillary lymph node cell isolated from 28 patients undergoing surgery for breast cancer were determined by two-color immunofluorescence with monoclonal antibodies and flow cytometric analysis. Lymphocyte subpopulation proportions were determined with combinations of monoclonal antibodies directed against the Leu 2, Leu 3, Leu 7, Leu 8, Leu 11, Leu 12, Leu 15, Leu M3, and HLA-DR surface markers. Patients were staged according to the postsurgical-pathological modification of the Tumor-Node-Metastases staging system, for analysis of tissue source (lymph node versus peripheral blood) and stage of disease as factors influencing lymphocyte subset size. Activated Leu 2+DR+ and Leu 3+DR+T-cells were elevated in stage 2 carcinoma compared to Stage 1. Elevation of Leu 2+8+ circulating T-cells and a reciprocal depression of Leu 2+8- T-cells were also seen in Stage 2 patients when compared to Stage 1. Total T-cells, B-cells, Leu 2+, and Leu 3+ T-cell subsets and natural killer phenotypes defined by Leu 7 and Leu 11 were unchanged in the peripheral blood of Stages 1 and 2 breast cancer. Regional lymph nodes from Stage 1 were found to contain a high frequency of Leu 3+ cells which dropped significantly in Stage 2 patients; this was found to be numerically due to a sharp decrease in the Leu 3+8- subpopulation in Stage 2 patients. Elevated B-cells (Leu 12+), activated T-cells (Leu 2+DR+ and Leu 3+DR+), total Leu 2+ cells, and Leu 7-11+ natural killer cells were demonstrated in Stage 2 lymph nodes when compared to Stage 1. Generally, no differences in subpopulations were seen when level 1 (low axillary) lymph node cells were compared to level 3 (high axillary) lymph node cells at each stage of the disease. These findings demonstrate substantial differences in the profile of lymphocyte phenotypes between Stage 1 and Stage 2 breast carcinoma, especially in the ipsilateral regional nodes. The findings presented in this study suggest that changes in local-regional immunocompetent cell subsets may be related to metastasis of tumor to the regional nodes and progression of disease without being fully reflected in the systemic circulation.
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PMID:Monoclonal antibody-defined phenotypes of regional lymph node and peripheral blood lymphocyte subpopulations in early breast cancer. 308 Dec 62

Indirect immunofluorescence staining with monoclonal antibodies has shown a differential distribution of HLA-DR, DQ, and DP antigens in normal tissues of nonlymphoid origin. The distribution of HLA-DP antigens is similar to that of HLA-DR antigens, while that of HLA-DQ antigens is more restricted. Malignant transformation of cells of nonlymphoid origin may be associated with the appearance of the gene products of the HLA-D region. HLA-DR antigens appear more frequently than the other two types of HLA class II antigens and HLA-DP antigens more frequently than HLA-DQ antigens. Differential expression of the gene products of the HLA-D region was also found in autologous metastases removed from different anatomic sites from patients with melanoma. The HLA class II phenotype of surgically removed malignant lesions did not correlate with the degree of differentiation of tumor cells and/or with the expression and/or cellular distribution of HLA class I antigens. Furthermore, in melanoma lesions, no relationship was found between the HLA class II phenotype and the expression of 3 membrane bound and 1 cytoplasmic melanoma associated antigen recognized by monoclonal antibodies. The functional significance and the practical implications of the differential expression of the gene products of the HLA-D region by tumor cells are discussed.
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PMID:Gene products of the HLA-D region in normal and malignant tissues of nonlymphoid origin. 308 70

Progression of human melanoma is associated with changes in antigenic phenotypes of tumor cells. To establish whether inflammatory infiltrates in progressing melanoma also change, we studied 146 cutaneous melanomas at different stages of progression. Monoclonal antibodies (MAbs) against lymphocyte and macrophage subpopulations, interleukin-2 receptor (IL-2 R), immune interferon (IFN-gamma), and the IFN-gamma-inducible, progression-associated melanoma antigens HLA-DR and gp89 were applied in situ. During the course of melanoma progression, decreased amounts of peritumoral T cells, IL-2 R-expressing lymphocytes and dermal T6+ dendritic cells were found, while increased numbers of intratumoral T cells, inflammatory (27E10+) and mature (25F9+) macrophages were associated with local progression of primary melanomas. In metastases, most infiltrate components except 25F9+ macrophages were rare. Positive correlations were observed between: (1) dermal T6+ cells and IL-2 R+ lymphocytes, and (2) presence of IFN-gamma in the infiltrate and HLA-DR and gp89 antigens on tumor cells. In all stages, HLA-DR expression on tumor cells was correlated with: (1) a shift towards T8+ lymphocytes in the infiltrates and (2) a loss of IL-2 R expression. Our data suggest mutual influences between melanoma cells and mononuclear cell infiltrates in situ.
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PMID:Inflammatory cell infiltrates in human melanoma at different stages of tumor progression. 312 89

One hundred twenty-seven white European patients with differentiated thyroid cancer were typed for human lymphocyte antigen (HLA) DR specificities. There was no significant deviation from the HLA-DR distribution observed in 160 normal patient controls, neither in the entire group nor in the patient groups with nonmedullary types of thyroid cancer (61 with papillary and 44 with follicular, all nonradiation associated). Also, subdivision of patients with nonmedullary thyroid cancer according to age at diagnosis, presence of metastases, and presence of thyroglobulin antibodies in serum showed no significant deviation from the HLA-DR distribution. For the patients with medullary thyroid cancer (only sporadic [n = 20] or inherited isolated [n = 2] forms, no multiple endocrine neoplasias), there was a significant increase of HLA-DR2 (11 of 22 cases [50%]) in comparison with control patients (22%; P corrected to 0.02; relative risk, 3.6). These data suggest, in contrast to previous reports, that there is no genetic influence on the development of nonmedullary types of differentiated thyroid cancer. Medullary thyroid cancer without multiple endocrine neoplasia, however, may be associated with HLA-DR2.
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PMID:HLA-DR and differentiated thyroid cancer. Lack of association with the nonmedullary types and possible association with the medullary type. 319 50

To assess the clinical value of two comparatively new properties (DNA content and MHC class II antigen expression (HLA-DR, DP, DQ) of melanoma cells) which have been independently reported to reflect the outlook for patients with malignant melanoma, we investigated retrospectively 50 stage I nodular melanomas in two comparably homogeneous groups of 23 and 27 patients, the course of whose disease differed at five years. Flow cytometry and immunohistology were used on paraffin wax embedded archival material for the analysis of DNA ploidy and detection of class II antigens, respectively. A close association was found between class II antigen expression, detected by monoclonal antibody CR3/43 (antimonomorphic DR, DP, DQ) present in 23 of 50 (46%) melanomas and unfavourable clinical course (p less than 0.005, by log rank test), but no such association was found for DNA ploidy. It is suggested that immunohistology for MHC class II antigen expression may help to predict the behaviour of nodular melanomas whereas the prognostic value of DNA ploidy is more limited. The finding that class II positive cells are found predominantly in melanomas with a substantially increased risk of metastases has implications both for concepts of tumour heterogeneity and host immunity.
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PMID:DNA content and MHC class II antigen expression in malignant melanoma: clinical course. 319 29


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