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 efficacy of monoclonal antibody therapy depends in part on the expression of the relevant tumor-associated antigens by both primary tumors and their metastases. Antigen expression by paired primary and autologous metastases from surgically excised osteogenic and soft-tissue sarcomas from 15 patients was studied using a panel of murine hybridoma monoclonal antibodies and indirect immunoperoxidase staining of formalin-fixed tissue sections. The panel included three antibodies (B3619, 17-9H3, OST6) recognizing sarcoma-associated antigens and an antibody recognizing an HLA-DR framework determinant (OKla1). In most cases, antibody binding to both primary and metastatic tumors was observed. However, marked heterogeneity of binding intensity between primary and metastatic tumors and of cells expressing antigens within tumors was noted. This occurred even though primary and metastatic tumors demonstrated homogeneous histology and cellular morphology. Differences were noted among patients as well as among metastases taken from an individual. A significant number of both primary and metastatic tumors contained cells that did not bind a particular antibody even in the presence of other cells that demonstrated significant antibody binding. Thus, strategies for single monoclonal antibody therapy may be limited by heterogeneity of intertumor and intratumor antigenic expression.
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PMID:Analysis of antigenic expression by primary and autologous metastatic human sarcomas using murine monoclonal antibodies. 638 49

Monoclonal antibodies were raised against cultured melanoma cells and selected for their reactivity with melanoma-associated antigens expressed on various melanoma lines. Of 34 monoclonal antibodies, which were all reacting with melanoma lines only 19 antibodies bound to fresh melanoma tissue. Of the 19 antibodies 10 displayed a broad cross-reactivity with normal cells and structures, whereas 9 had a restricted reactivity. Of these antibodies five types were defined, which detected antigens (nevocellular I, nevocellular II, neural, endothelial, basal cell), which were found on certain normal tissues and structures and on certain tumor phenotypes. On the basis of an extensive study on melanoma biopsies of different stages it became evident, that the endothelial, the basal cell and also HLA-DR antigens were significantly more expressed in high risk melanomas. The basal cell antigen was preferentially expressed in locoregional metastases. By immunization with fresh melanoma biopsies different specificities of monoclonal antibodies were obtained as compared to immunization with established cell lines.
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PMID:The expression of tumor-associated antigens in primary and metastatic human malignant melanoma. 647 52

Three established lines of melanoma cells were derived from anatomically distinct metastases occurring in a single patient (DX). The lines, DX-1, DX-2, and DX-3, showed marked phenotypic diversity, as indicated by characteristic differences in growth rate, morphology, pigmentation, and the expression of surface antigens and glycoproteins. DX-1 and DX-3 expressed HLA-DR products, whereas DX-2 lacked HLA-DR expression. DX-1, DX-2, and DX-3 could also be distinguished on the basis of the profile of radiolabeled glycoproteins. Additional quantitative differences in the surface antigenic phenotype of the three cell lines were revealed by serological tests with a battery of monoclonal and conventional antibodies defining melanoma differentiation antigens. In tests for autologous humoral immunity to melanoma cells, sera from patient DX were found to have IgG antibody that reacted with surface antigens of DX-2 cells; no autologous reactivity was seen with DX-1 or DX-3 target cells or with three more recently established melanoma cell lines from patient DX. Absorption analysis indicated that the antigen detected by DX sera on DX-2 cells is a class 1 melanoma antigen, having been detected only on DX-2 cells and in much lower but demonstrable amounts on DX-1 and DX-3 cells. No other cell type, including DX normal fibroblasts, DX B cells, or 45 allogeneic melanoma cell lines expressed the class 1 antigen of DX melanoma. The fact that only one of the melanoma cell lines derived from patient DX was suitable target for the detection of autologous class 1 reactivity has implications for the study of human tumor antigens and may explain why antibody to class 1 antigens has been found so infrequently in past studies of melanoma patients.
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PMID:Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens. 697 7

The CD44 molecule and CD44 isoforms are expressed on some malignant tumours and it has been suggested that their expression may correlate with tumour spread. Human pancreatic carcinoma cell line (HPC-4) expressing CD44 was established from a patient with adenocarcinoma of pancreas. This line showed a rapid growth in vitro, several chromosome abnormalities and surface expression of some adhesion molecules (ICAM-1, LFA-3, beta 1-chain of VLA integrins, VNR). Xenotransplanted HPC-4 cells were able to grow rapidly in SCID mice as subcutaneous tumour, leading to 100% mortality within 3-5 weeks when 1 x 10(5)-1 x 10(7) cells were inoculated. Spontaneous metastases in the liver, lung, spleen and kidney of SCID mice were observed. Interestingly enough, HPC-4 cells in vivo and ex vivo also expressed HLA-DR molecules, but these were rapidly lost upon culture in vitro. It is suggested that the appearance of HLA-DR may be the result of interaction of the tumour with a local environment of the host, while CD44 expression may explain the rapid growth and occurrence of distant metastases in SCID mice. The ability of HPC-4 cells to form spontaneous metastases in SCID mice may prove to be a potentially interesting model of human carcinoma for testing new treatment modalities.
Invasion Metastasis 1995
PMID:Characterization of human pancreatic adenocarcinoma cell line with high metastatic potential in SCID mice. 754 54

Two human melanoma cell lines, derived from metastases of two patients with epithelioid malignant amelanotic melanomas, and designated IIB-MEL-LES and IIB-MEL-IAN, have been established. Both cell lines have been in continuous culture over 2 years and were propagated continuously for 85 and 75 serial passages, respectively. Morphologically, IIB-MEL-LES is composed predominantly of spindle shaped cells, whereas IIB-MEL-IAN grows as a monolayer of cuboid and stellate shaped cells with many rounded cells in suspension. Immunocytochemical studies revealed that both cell lines express S-100 protein, vimentin, and GD3 and GD2 gangliosides but are negative for keratin and collagen. Both cell lines express HLA class I and HLA-DR antigens in variable proportions. The MAGE-1 gene is expressed only by the IIB-MEL-IAN cell line, as revealed by PCR analysis. Cytogenetic analysis of both cell lines revealed abnormal karyotypes; the modal chromosome numbers of IIB-MEL-LES and IIB-MEL-IAN were 48 and 81, respectively. IIB-MEL-LES cells presented rearrangements in chromosomes 1, 14 and X, gains in chromosomes 10, 20, and 21 losses in chromosomes 15 and Y. The most frequent markers observed in IIB-MEL-IAN cells were 7q+, 10p+, 2p+, i(6p), 2q+, and 10q-. Clonal gains were observed in chromosomes 12 and 21, whereas losses were seen in chromosomes 1, 2, 3, 4, 6, 7, 11, and 17. Both cell lines were capable of forming colonies in soft agar and developed tumors when transplanted into nude mice, reproducing and maintaining the characteristics of the original tumors. These cell lines and their xenografts appear to provide useful systems for studying the biology, genetics and histogenesis of human malignant melanoma and could be utilized for the development of melanoma vaccines.
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PMID:Biologic, immunocytochemical, and cytogenetic characterization of two new human melanoma cell lines: IIB-MEL-LES and IIB-MEL-IAN. 756 87

A correlation between the lack of MHC class I gene expression on murine tumor cells and their ability to grow and metastasize has recently been established. This paper studies HLA-ABC and HLA-DR antigen expression in tumor cells and mononuclear infiltrate of 26 cutaneous squamous cell carcinomas (SCC). Our results showed a heterogeneous expression of HLA class I molecules in these tumors. No significant correlation between the degree of HLA class I molecule expression and anatomical-clinical parameters was found. Class II antigen expression was correlated to the histopathological type and to the degree of cell differentiation. Most mononuclear cells infiltrating the tumor were T-lymphocytes. No correlation with anatomical-clinical parameters was found.
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PMID:HLA molecule expression in cutaneous squamous cell carcinomas: an immunopathological study and clinical-immunohistopathological correlations. 768 37

Cryosections of 28 primary and metastatic midgut carcinoid tumors from 12 patients with carcinoid syndrome were investigated immunohistochemically with antibodies that recognize human MHC class I (HLA-ABC) and class II (HLA-DR) antigens. The tumor parenchyma of all six patients treated with interferon alpha (IFN-alpha) during a mean 8.6 months (3 x 10(6) to 5 x 10(6) U three times weekly) exhibited unequivocal HLA-ABC immunoreactivity, with only minor discrepancies between primary lesions and metastases in mesenteric lymph nodes and liver. Class I staining was absent on the tumor cells of all 14 specimens from the patients without IFN therapy but was induced by culturing freshly dispersed tumor cells in vitro for 48 hours in the presence of recombinant IFN-alpha. The stroma of all neoplasms displayed class I and II immunostaining, as did usually a few CD4-expressing cells. The carcinoid specimens lacked parenchymal HLA-DR immunoreactivity, which is interesting considering suggestions on improved prognosis for bowel carcinomas lacking the class II expression. The study supports the idea that induction of MHC class I antigens could contribute to the beneficial clinical effect of IFN-alpha treatment in patients with midgut carcinoid tumors.
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PMID:MHC class I and II antigen expression and interferon alpha treatment of human midgut carcinoid tumors. 772 32

T cells from mice bearing an experimental colon carcinoma, and from patients with colorectal and renal carcinomas, have atypical T-cell receptors (TCR). In the present study, further characterization of modulations in CD3- and CD16-associated zeta chain in peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from colorectal carcinomas was performed. Relative to PBL, the percentage of natural killer (NK) cells among fresh TIL was reduced, while a higher proportion of T cells expressing HLA-DR was found. As previously reported, we found significantly reduced levels of the CD3- and CD16-associated zeta chain in TIL and, to a lesser extent, also in patients' PBL. Levels of zeta chain in T and NK cells from non-cancerous colorectal tissue from patients were lower than in PBL but higher than in TIL, with a direct relationship between levels of this signal-transducing molecule and the distance from the tumor. In addition, zeta levels correlated with the Dukes' stage of the disease, since PBL from patients with lymph-node involvement or distant organ metastases (Dukes' stages C and D) had significantly less CD3 zeta than patients with localized disease (stages A and B). Patients' T cells also had decreased levels of cell-surface and cytoplasmic CD3 epsilon. We also observed reduced levels of the TCR accessory molecules CD4 and CD8, mainly on TIL but to a lesser extent also on patients' PBL. Biochemical analysis of anti-CD3 epsilon-immunoprecipitated TCR complexes demonstrated that the CD3 complex was not associated with the zeta chain, either on TIL or on PBL or on lymphocytes from non-cancerous colon tissue, suggesting a defect in the assembly of the TCR complex. Following several days of in vitro culture with recombinant interleukin-2 and phytohemagglutinin, anti-CD3 or anti-CD2 monoclonal antibodies (MAbs), levels of CD3 zeta chain as well as of cell surface CD3 epsilon were normalized. Our findings suggest an abnormal expression as well as assembly of several different signal-transducing molecules of T cells and NK cells, which correlate with the stage of the disease in patients with colorectal carcinomas.
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PMID:Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. 779 Jan 9

Treatment of metastatic melanoma patients with an autologous vaccine modified by the hapten, dinitrophenyl (DNP), produces a striking immunological effect: the induction of clinically evident inflammatory responses in metastatic tumors. Histological examination shows these tumors to be infiltrated with T lymphocytes. We studied the expression of activation markers on those cells and compared them with matched peripheral blood lymphocytes (PBL) and with lymphocytes extracted from metastases before treatment with DNP-conjugated vaccine. The median fraction of cells that were T cells in post-vaccine tumors was 41%, as compared with 9% in pre-treatment tumors, and those T cells were predominantly CD8+ (mean CD8/CD4 ratio = 5.0). A high proportion of both pre- and post-treatment infiltrating T cells expressed HLA-DR (mean +/- SE = 48% +/- 4%), CD69 (56% +/- 7%), and ganglioside GD3 (68% +/- 5%). This distinguished them from matched PBL in which expression of those markers was significantly lower (HLA-DR = 10% +/- 2%; CD69 = 2% +/- 0.4%; GD3 = 49% +/- 4%). These changes were not accompanied by increased cell-surface expression of interleukin-2 (IL-2) receptors, either CD25 or p75, which were expressed by 1%-2% and 12% of tumor-infiltrating lymphocytes (TIL), respectively. The pattern of activation marker expression that we identified appears to be characteristic of tissue T cells with the memory phenotype. The low expression of IL-2 receptors could indicate functional impairment of TIL in situ, perhaps because of inhibitory molecules produced by melanoma cells.
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PMID:Activation markers on T cells infiltrating melanoma metastases after therapy with dinitrophenyl-conjugated vaccine. 792 43

In order to investigate the effects of in vivo treatment with interferon-alpha (IFN-alpha) on melanoma antigens, a clinical EORTC trial (No. 18852) was accompanied by an immunohistological study. Twenty patients with melanoma metastases of skin and soft tissues, eventually also of the lung, who were treated with systemic IFN-alpha, were evaluated for a comparison of metastases before (40) and during (42) treatment. Representative cryostat sections were studied immunohistologically with a panel of monoclonal antibodies against differentiation antigens (HMW-MAA, K-1-2, NKI-beteb, M-2-10-15), progression markers (transferrin receptor, ICAM-1, VLA-2), histocompatibility antigens (HLA-A, B, C, HLA-DR) and the proliferation-associated nuclear antigen Ki67. We found an overall reduction of the proliferation-associated antigen Ki-67 (p < 0.01), and an increase in expression of HLA-DR (p < 0.05) and ICAM-1 (trend) during treatment. The intensity of expression of HLA-A, B and C antigens as well as pigmentation (p < 0.01) was found to be increased. Early progression (< or = 8 weeks after onset of treatment) was associated with a lack of phenotypic changes. The data suggest an independent modulation of proliferation, pigmentation, and antigen expression by systemic treatment of metastatic melanoma with IFN-alpha.
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PMID:Effects of systemic interferon-alpha (IFN-alpha) on the antigenic phenotype of melanoma metastases. EORTC melanoma group cooperative study No. 18852. 810 70


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