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Frequent Expression (frequent + expression)
Selected AbstractsDifferential modulation of CD8, by rat ,, and ,, T cells after activationIMMUNOLOGY, Issue 3 2001Frank Straube Summary Major histocompatibility complex (MHC) class I-restricted ,, T cells express the CD8,, heterodimer, which acts as a MHC class I-specific co-receptor. Rats are so far the only species with frequent expression of the CD8,, by MHC-unrestricted ,, T cells. This study compares CD8,, expression by splenic rat ,, and ,, T cells and reveals a lineage-specific difference in the control of CD8, expression. After activation in vitro, many ,, T cells, but not ,, T cells, persistently down-modulate the expression of CD8,, but not CD8,, at the RNA level. Down-regulation occurred after stimulation with T-cell receptor (TCR)-specific monoclonal antibody (mAb) and interleukin-2 (IL-2) or CD28-mediated costimulation, and after activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Functional differences between modulating and non-modulating cells were not found with respect to interferon-, (IFN-,) production and cytolytic activity. The modulation could be indicative for a fundamental difference between ,, and ,, T cells and also limits the use of CD8, as a stable marker of ,, T-cell subsets. Possibly, CD8, modulation provides a mechanism to escape over-stimulation by (auto-)antigens by increasing the threshold of TCR-mediated activation in ,, T cells. [source] Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Axel Mischo Abstract To determine the expression of cancer testis (CT) genes and antibody responses in a nonselected population of patients with primary breast cancer, we investigated the composite expression of 11 CT genes by RT-PCR in fresh biopsies of 100 consecutive cases of primary breast carcinoma and by immunohistology in selected RT-PCR-positive cases. Antibody responses against 7 CT antigens were analyzed using recombinant antigen expression on yeast surface. In 98 evaluable cases, SCP-1 and SSX-4 were expressed most frequently (both 65%), followed by HOM-TES-85/CT-8 (47%), GAGE (26%), SSX-1 (20%), NY-ESO-1 (13%), MAGE-3 (11%), SSX-2 (8%), CT-10 (7%), MAGE-4 (4%) and CT-7 (1%). One CT gene was expressed by 90% of the cases; 79% expressed ,2, 48% ,3, 29% ,4, 12% ,5, 6% ,6, 3% ,7, 2% ,8 and one case coexpressed 9 antigens. Of 100 serum samples screened for CT antigen-specific antibodies, antibodies against NY-ESO-1 were detected in 4 patients, against SCP-1 in 6 patients and against SSX-2 in 1 patient, while no antibodies were detected against MAGE-3, CT-7 and CT-10. Expression of CT genes or antibody responses was not correlated with clinical parameters (menopausal status, tumor size, nodal involvement, grading, histology and estrogen receptor status) or the demonstration of CT gene expression at the protein level, by immunohistology. Our results show that breast carcinomas are among the tumors with the most frequent expression of CT antigens, rendering many patients potential candidates for vaccine trials. © 2005 Wiley-Liss, Inc. [source] Melanoma patients respond to a new HLA-A*01-presented antigenic ligand derived from a multi-epitope region of melanoma antigen TRP-2INTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Annette Paschen Abstract Tyrosinase-related protein-2 (TRP-2) is a known target antigen of spontaneous cytotoxic T cell responses in melanoma patients. Its frequent expression in metastatic tumors suggests that it might be an ideal candidate antigen for T cell-based immunotherapy. To provide knowledge about TRP-2-derived T cell epitopes useful for immunotherapy we applied a "reverse immunology strategy" based on repeated in vitro peptide stimulation of peripheral blood lymphocytes (PBL) from normal donors with predicted HLA-A*01 ligands. This led to the identification of TRP-2181,190 as the first HLA-A*01-presented TRP-2-derived epitope. T-cell lines specific for peptide TRP-2181,190 could be established from PBL of 50% of the normal HLA-A*01+ donors tested. Such T cells responded specifically to autologous dendritic cells transduced virally with TRP-2, as well as to HLA-A*01+, TRP-2+ melanoma cells, although tumor cells had to be pretreated with IFN-, to become susceptible to T cell recognition. Interestingly, short-term in vitro peptide stimulation of PBL from HLA-A*01+ melanoma patients showed the presence of TRP-2181,190 -reactive CD8+ T cells in some donors, suggesting their in vivo sensitization. Because TRP-2181,190 overlaps with the known HLA-A*0201-presented epitope TRP-2180,188, an 11mer peptide encompassing both epitopes might be of specific value for vaccination of a broad population of melanoma patients. © 2005 Wiley-Liss, Inc. [source] The Chemokine Receptor CXCR4 is More Frequently Expressed in Breast Compared to Other Metastatic Adenocarcinomas in EffusionsTHE BREAST JOURNAL, Issue 5 2008Ben Davidson MD Abstract:, This objective of this study was to investigate the expression of chemokine receptors in tumor cells and leukocytes in breast carcinoma effusions. The expression of leukocyte markers (CD3/4/8/14/16/19) and chemokine receptors (CXCR1/4, CCR2/5/7) was studied in 21 breast carcinoma effusions using flow cytometry. Breast carcinoma cells expressed CXCR4 in 7/21 (33%) effusions, with less frequent expression of CXCR1, CCR5, and CCR7. CXCR2 and CCR2 were absent. Lymphocytes showed frequent CXCR4, CCR5, and CCR7 expression, while CXCR1, CXCR2, CCR2 were rarely or never detected. Macrophages expressed all six receptors except for CXCR2. Comparative analysis of breast carcinoma effusions with previously studied ovarian and cervical/endometrial adenocarcinomas (ACs) showed significantly higher CXCR4 expression in breast carcinoma cells compared to the other gynecological ACs (p = 0.001). Breast and cervical/endometrial carcinoma effusions showed different expression of chemokine receptors in lymphocytes (lower CXCR1, higher CXCR4 and CCR7 levels; p = 0.012, p = 0.005, p < 0.001, respectively) and macrophages (higher CCR7 levels; p < 0.001), as well as lower CD8 counts (p < 0.001) and higher CD19 counts (p = 0.001) compared to ovarian carcinoma effusions. Higher numbers of CD8-positive lymphocytes (p = 0.080) and higher CCR7 monocyte expression (p = 0.087) were associated with a trend for shorter disease-free survival. In conclusion, breast carcinoma cells express CXCR4, a unique feature among metastatic ACs in effusions, with rare expression of other chemokine receptors. Chemokine receptor expression in leukocytes and lymphocyte counts significantly differ from those of ovarian carcinoma effusions. The prognostic role of CCR7 expression in monocytes and CD8 counts in breast carcinoma effusions merits further research. [source] SEREX identification of new tumour-associated antigens in cutaneous T-cell lymphomaBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2004T.B. Hartmann Summary Background Cutaneous T-cell lymphoma (CTCL) is a clonal lymphoproliferative disorder of mainly CD4+ T cells, with primary manifestation in the skin. Objectives To detect new CTCL-associated antigens for immunological therapies and to define their specificity in terms of RNA expression and seroreactivity. Methods A newly constructed CTCL cDNA phage library was screened and cross-reactivities against the detected clones were tested using 15 mycosis fungoides and six Sézary syndrome sera. The mRNA expression of the identified genes was analysed by reverse transcription,polymerase chain reaction (RT,PCR) using 22 tumour tissues, nine cell lines and up to 29 different types of normal tissue. Results We identified nine different tumour antigens (HD-CL-01 to HD-CL-09) of which seven clones had high homology to genes with known functions. Several of these genes had previously been associated with cancer, namely inositol 1,4,5-triphosphate 5-phosphatase, vimentin, aldose reductase and elongation factor-1,. Variations in the deduced protein sequences were observed in three cases, mostly due to variations in protein length. The individual clones were recognized by up to 56% of patients' sera, while control sera were negative except in one case. Using RT,PCR, we found a frequent expression of these new tumour antigens in tumour specimens (26,100%). In contrast to humoral specificity, specific mRNA was also detected in selected normal tissues (29,89%). Conclusions SEREX (serological identification of antigens by recombinant expression cloning) identified multiple tumour-associated antigens in CTCL. The serological specificity and the high percentage of reactive sera of CTCL patients against several clones suggest these genes as potential targets for diagnostic and prognostic purposes. [source] Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2, expression levels correlate with basal phenotype in breast cancerCANCER, Issue 4 2009Gulnur Guler MD Abstract BACKGROUND: The expression of fragile histidine triad protein (Fhit) and WW domain-containing oxidoreductase protein (Wwox), tumor suppressors that are encoded by fragile (FRA) loci FRA3B and FRA16D, are lost concordantly in breast cancers. In the current study, the authors examined correlations among Fhit, Wwox, the activator protein 2 transcription factors AP2, and AP2,, cytokeratins 5 and 6 (CK5/6), epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) and their associations with breast cancer phenotypes. METHODS: Tissue microarrays constructed from 837 breast cancer blocks were immunostained. Expression in >10% of tumor cells was considered positive for cytoplasmic CK5/6, membranous EGFR, and nuclear AP2, and AP2,. Cytoplasmic Fhit and Wwox staining was scored according to staining intensity. ER, PR, and HER-2 status of tumors was derived from records. Correlations among immunohistochemical markers and tumor subtypes were assessed by univariate and multivariate statistical methods. RESULTS: Triple-negative tumors had more frequent expression of EGFR, CK5/6 (P < .001), and AP2, (P = .003) and more frequent loss of Fhit and Wwox (P < .001), and an inverse correlation was observed between Fhit, Wwox expression and EGFR, ER, and PR expression (P < .001). Reduced Fhit expression was more common in HER-2-positive and AP2,-positive cases (P < .001 and P = .002, respectively). There was a direct correlation noted between Fhit and Wwox (P < .001) and a borderline positive relation between AP2, and AP2, (P = .054). CONCLUSIONS: The results from this investigation suggested that reduced expression levels of Fhit, Wwox, and nuclear AP2, have roles in the pathogenesis of basal-like differentiation in breast cancer. Alteration in the expression of fragile site genes occurs in most of these cancers and may contribute to defects in DNA repair, as observed in breast cancer 1 (BRCA1)-deficient cancers. Thus, DNA damage response checkpoint proteins may be targets for treatment. Cancer 2009. © 2009 American Cancer Society. [source] Angiogenic growth factors in tissue homogenates of HNSCC: expression pattern, prognostic relevance, and interrelationshipsCANCER SCIENCE, Issue 7 2009Michael Montag Head and neck squamous cell carcinoma has still a poor prognosis. Since angiogenesis is crucial for tumor growth, a better understanding of the potential clinical relevance as well as the interactions between the numerous proangiogenic growth factors is essential to develop improved therapeutic strategies in these tumors. Expression levels of eight growth factors known to induce angiogenesis (HGF, bFGF, VEGF-A, VEGF-D, PDGF-AB, PDGF-BB, G-CSF, and GM-CSF) were quantitatively measured by ELISA in homogenates of 41 head and neck squamous cell carcinomas. In addition, microvessel density and protein localization of growth factors were assessed by immunohistochemistry. Statistical analysis was performed to assess interrelationships between growth factors analyzed and to correlate protein levels with patient outcome. In 90% of the tissues at least 4/8 growth factors analyzed were detectable. Highest amounts and most frequent expression were found for HGF, bFGF and VEGF-A while PDGF-AB and PDGF-BB were present in two-thirds and G-CSF and GM-CSF in approximately half of the cases. Although there was no significant relation to microvessel density, we identified significant associations for bFGF with HGF and G-CSF as well as of PDGF-AB with those of VEGF-A and PDGF-BB. For the first time we demonstrate that expression levels of HGF as well as that of bFGF and G-CSF in head and neck squamous tumors are negative prognostic factors for patient survival. Our data indicate a network of interrelated and prognostically relevant growth factors in these tumors that have to be taken into consideration when planning an antiangiogenic and antitumor therapy. (Cancer Sci 2009; 100: 1210,1218) [source] | ||||||||||