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)

The melanoma-associated antigen P3.58 is rarely found on benign proliferating melanocytes but is consistently expressed on advanced malignant melanomas which have a high probability of metastasis. Previous studies have shown that its expression on normal tissues is limited to vascular endothelia and lymphoid follicle germinal centers and that it is also expressed by activated monocytes in vitro. In the studies reported here, anti-P3.58 monoclonal antibodies (mAb) were shown to partially inhibit antigen-specific and anti-CD3-induced T cell proliferation and to completely block a lymphocyte/monocyte clustering which occurs in the absence of added antigen. This inhibition is highly specific for P3.58 mAb and was not affected by mAb directed to major histocompatibility complex or T cell antigens. P3.58 therefore seems to be involved in an antigen-independent attraction or adhesion of lymphocytes. P3.58 is the second example (HLA-DR being the first) of an association between the expression of an immune function-associated molecule and the development of metastatic disease in melanoma.
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PMID:The tumor progression-associated human melanoma antigen P3.58 mediates monocyte-lymphocyte interactions in vitro. 322 Jan 5

The present study shows that the distribution of T lymphocytes in gastrointestinal carcinomas and their metastases mimic the distribution of T lymphocytes in normal intestine. The composition of the peritumoral reaction resembled that of normal lamina propria with a predominance of CD3 + CD4 + T cells. In contrast, lymphocytes located between carcinomatous cells showed phenotypical features similar to those of intraepithelial lymphocytes (IEL) in normal intestine; in particu(abstractlar they expressed the antigen defined by HML-1, a monoclonal antibody raised against normal human intestinal IEL which reveals 95% IEL but very few cells in lymphoid (abstractorgans and blood. As normal intestinal IEL, the majority of intratumoral lymphocytes had the CD3+ CD8+ phenotype. A panel of monoclonal antibodies and double immunostaining techniques permitted a better characterisation of minor subsets of IEL. Two subsets of HML1 + CD3 + CD4- CD8- and of HML1+ CD3- cells, representing 2% and 3% of normal intestinal IEL respectively, did not significantly increase in carcinomatous epithelium. In contrast, in carcinomatous epithelium, but not in normal intestinal epithelium, we observed the appearance of a few lymphocytes displaying the phenotype of activated T cells (CD25+) or of natural killer cells (NKHI+) or of suppressor cells (CD11+). Such cells may participate in antitumoral defence. Although a similar population of HML1+ lymphocytes is associated with normal and carcinomatous intestinal epithelium, some interactions between lymphocytes and epithelial cells may not be maintained in tumoral epithelium. It has previously been shown that HLA-DR expression by enterocytes is modulated by intraepithelial lymphocytes. In our study, no correlation could be shown between the degree of lymphocytic infiltration and the expression of HLA-DR antigens on carcinomatous cells.
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PMID:Same peculiar subset of HML1 + lymphocytes present within normal intestinal epithelium is associated with tumoral epithelium of gastrointestinal carcinomas. 326 3

Fifty-five primary and 33 metastatic surgically removed melanoma lesions were stained in indirect immunoperoxidase with anti HLA-DR, DQ, and DP monoclonal antibodies and with the monoclonal antibody CL203.4 to a 96-K melanoma associated antigen (MAA). The latter antigen may represent a marker to monitor susceptibility of melanoma cells to modulation by IFN-gamma, because it is highly susceptible to induction by IFN-gamma. In primary melanomas 44%, 29%, 10%, and 55% of the lesions tested were evidently stained by anti HLA-DR, DQ, DP, and 96-K MAA monoclonal antibodies, respectively. A statistically significant association (P less than 0.01) was demonstrated between the degree of intratumoral lymphocytic infiltrate and the expression of HLA-DR and HLA-DQ antigens. In addition, a high degree of concordance in the reactivity pattern of individual lesions stained for HLA-DR antigens and for the 96-K MAA was found. In metastases 64%, 33%, 47%, and 100% of the lesions tested were evidently stained by anti HLA-DR, DQ, DP, and 96-K MAA monoclonal antibodies, respectively. This study indicates that HLA-DR and HLA-DP antigens are expressed in a higher percentage of metastatic than of primary melanomas and that there is no marked difference in the expression of HLA-DQ antigens between primary and metastatic melanomas. The data suggest that the regulatory mechanisms which control the expression of HLA-DR and DP antigens in primary and metastatic melanoma lesions are different. Locally produced IFN-gamma may play a role in the regulation of HLA Class II antigens in primary melanomas.
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PMID:Differential expression of HLA-DR, DQ, and DP antigens in primary and metastatic melanoma. 328 52

To pursue the hypothesis that astrocytes may function as immunoregulatory cells, astrocytes within the reactive gliosis surrounding metastases and abscesses were examined for the expression of the class II major histocompatibility antigen HLA-DR. The tissue was analysed using single- and double-label avidin-biotin immunoperoxidase techniques employing monoclonal antibodies for HLA-DR (D1-12), macrophages (anti-Fc), T lymphocytes (2D3), glial fibrillary acidic protein (GFAP) and GFAP antiserum. Macrophages, astrocytes and T lymphocytes were present. The double label demonstrated HLA-DR on a large number of astrocytes. Taken together with evidence that astrocytes can release interleukin-1 and can present an antigen to lymphocytes, the finding of HLA-DR on these astrocytes supports their possible involvement in the cellular immune response.
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PMID:Expression of class II major histocompatibility antigens on reactive astrocytes and endothelial cells within the gliosis surrounding metastases and abscesses. 345 14

A new cell line having the ability to metastasize to the lungs in nude mice was established from GCH-1 (human choriocarcinoma cell line). Twenty CD-1 nude mice were injected with GCH-1 cells subcutaneously. A solitary metastatic pulmonary nodule appeared in only one of these mice. The pulmonary nodule was removed and minced, and the dissociated cells obtained were transplanted subcutaneously into new mice. By repeating this process, metastatic pulmonary nodules were seen clearly to have grown in size and number by the 4th transplantation. An in vitro cell line originating in the pulmonary lesion of the 5th transplantation was designated GCH-1 (m). Pulmonary metastasis occurred in all of the mice inoculated with GCH-1 (m) grown in vitro. The doubling time of the parent line GCH-1 and its subline GCH-1 (m) was 22.6 and 36.2 hours, respectively. GCH-1 (m) cells seemed to be heterogeneous in their size and shape compared with GCH-1 cells. GCH-1 (m) secreted more hCG and beta-hCG into the culture medium than GCH-1. By the immunoperoxidase technique using poly- or monoclonal antibodies, GCH-1 (m) showed a clear positive reaction but GCH-1 was only slightly positive for hCG and beta-hCG. Both GCH-1 and GCH-1 (m) were weakly positive for HLA-A, B,C and negative for HLA-DR, SP1 and hPL. Addition of the extracts from mouse lungs to the culture medium obviously promoted the growth of GCH-1 (m) but not of GCH-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Establishment and characterization of a cell line [GCH-1 (m)] highly metastasizing to the lung in nude mice]. 358 8

In order to gain insight into the role of macrophages in human melanoma, we studied fresh-frozen material from 15 dysplastic nevi, 199 primary melanomas, 107 melanoma metastases, and paraffin sections from 98 primary melanomas with the monoclonal antibody 25F9 which recognizes an 86 x 10(3) dalton protein present on a subset of mature human macrophages. Considerable infiltration of tumors with 25F9-positive macrophages was observed in 2 dysplastic nevi (13%), 87 primary melanomas (44%), and 45 metastases (42%). The degree of intratumoral macrophage infiltration correlated with expression of class II HLA-DR antigens on tumor cells, in primary melanoma with a tumor thickness above 0.75 mm, and with the occurrence of metastases within 2 years. In paraffin sections, intratumoral 25F9-positive macrophages also correlated with metastatic spread of primary tumors after longer follow-up. Metastases revealed a higher degree of macrophage infiltration following systemic or local immunotherapy, compared with untreated metastases, or metastases removed during chemotherapy. Of 38 patients who died within an observation period of 1 year, 19 (50%) had considerable infiltration of metastases with 25F9-positive macrophages, whereas this was found in only 4 of 12 patients (33%), who survived for longer than 2 years following metastases removal. A higher degree of 25F9-positive macrophages correlated with a shift towards the T8-positive subsets within the T cell compartment of the infiltrate. Our results suggest that accumulation of 25F9-positive macrophages in melanomas indicates more aggressive tumor properties.
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PMID:Infiltration of primary and metastatic melanomas with macrophages of the 25F9-positive phenotype. 366 32

It has been recently established that there is a correlation between the lack of MHC class I gene expression on murine tumour cells and their ability to grow and metastasize. We have studied the expression of HLA-ABC and HLA-DR products on human malignant tumours from the digestive tract using monoclonal antibodies, by indirect immunofluorescence on the cell suspensions obtained from 29 freshly explanted digestive tumours. Our results show that digestive tract cancers have an heterogeneous expression of HLA class I molecules on their surface. Whereas 50% have high levels of expression of these molecules (more than 60% positive cells), 25% have a moderate level of expression (20-60% positive cells) and 25% have weak expression (less than 20% positive cells). It has been found that there is a correlation between the level of HLA class I molecule expression and the degree of histological differentiation of a tumour. The absence of MHC class I antigens on human tumour cells, detected in this study, may play a relevant role in oncogenesis, as has been established in experimental models.
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PMID:Expression of HLA molecules on cells from fresh explants of human digestive tract cancer. 381 52

The phenotypic changes in human melanoma cells during the course of tumor progression were studied with monoclonal antibodies (MAbs) against the melanoma-associated antigens (MAA) M.2.2.4, H.2.8.10, K.1.2, A.1.43, and A.10.33, and HLA-(A,B,C and D). Cryostat sections of 172 primary melanomas of the skin, 157 melanoma metastases and 56 nevi were investigated with an indirect immunoperoxidase method. Phenotypic heterogeneity was observed within lesions at all stages, and also within different tumors of the same patients. Despite this heterogeneity, principles of antigen expression were found. From the reaction pattern of MAbs, the following classifications of antigens were derived: "constitutive" markers of nevomelanocytic cells (M.2.2.4 and H.2.8.10) were found expressed over a wide range of local and systemic tumors. One MAA, K.1.2 (Suter et al., 1985), that declines with progression of melanoma, was classified as an "early" antigen, whereas MAA that appear in primary melanoma in proportion to invasiveness, and which are expressed in metastases of lymph nodes and visceral organs (A.1.43, and A.10.33), were classified as "late" markers of tumor progression. HLA-antigens were classified as "intermediate" markers, HLA-A,B,C, as an "early-intermediate", and HLA-DR as a "late-intermediate" marker. The occurrence of class II HLA, A.1.43-, and A.10.33-positive tumor cells in primary melanoma indicates a high metastatic potential of tumors, independent of tumor thickness. The data show that local and systemic progression of melanoma is associated with qualitative changes in tumor cells which can be recognized by MAbs.
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PMID:Phenotypic dynamics of tumor progression in human malignant melanoma. 386 Apr 79

Tumor specimens were obtained from seven patients with large bowel carcinomas at operation of the primary neoplasm and by resection of local recurrences or metastases 2 1/2 to 36 months later. All specimens were evaluated with regard to nuclear DNA distribution as measured by flow cytometry and expression of carcinoembryonic antigen (CEA), secretory component, epithelial IgA, and HLA-DR antigens, as determined by immunofluorescence staining of tissue sections. Both the DNA distributions and the immunohistochemical staining patterns were similar in the primary and secondary tumors. These findings are in keeping with a monoclonal or oligoclonal tumor progression in advanced large bowel carcinoma.
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PMID:Preservation of cytometric DNA distribution and epithelial marker expression after tumor progression of human large bowel carcinomas. 386 Dec 31

Certain HLA antigens have been found to possess positive associations with a number of disease. Weak associations have been recognized for a number of malignancies. In our present study, we contemplated unraveling the relationship between HLA antigens and malignant bone and soft-tissue tumor. A homogeneous group of thirty Japanese patients underwent tissue-typing for the expression of HLA-A, B, DR and DQ antigens. Significant increases were noted in the frequencies of HLA-A 26, B 39 and DR blank antigens. When these subjects were subdivided into two groups according to their age of onset, the frequencies of HLA-A 26 and B 39 were noticed to be increased among the juvenile group only. Frequency of HLA-DR blank was increased in both groups. The frequency of HLA-B 12 was observed to be increased among those and especially in the juvenile group who developed pulmonary metastases within one year after initiation of treatment. Half of the ten poor prognosis cases carried this antigen. The etiological and prognostic significance of these findings remain to be determined.
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PMID:Malignant bone and soft-tissue tumor and HLA. 386 5


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