Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chondroid chordomas are cartilage-rich neoplasms, most often located in the spheno-occipital region, that have a better prognosis than classic chordomas. The immunohistochemical features of 19 classic and chondroid chordomas were studied retrospectively using avidin-biotin-complex (ABC) immunoperoxidase histochemistry on formalin-fixed, paraffin-embedded tissue. Of the 19 tumors, all located in the spheno-occipital region, 5 exhibited predominantly chondroid morphologic features. The 14 classic chordomas showed the following pattern of antigen expression (percent of tumors positive): epithelial membrane antigen (EMA) 100%, AE 1/3 (a "cocktail" of monoclonal antibodies directed against low and high molecular weight epidermal cytokeratins) 100%, DP keratin (DPK) 100%, vimentin 100%, S100 86%, neuron specific enolase (NSE) 100%, carcinoembryonic antigen (CEA) 57%, and HMB-45 (an anti-melanoma-associated antibody) 57%. The five chondroid chordomas exhibited the following pattern: EMA 0%, AE 1/3 0%, DPK 0%, vimentin 100%, S100 100%, NSE 100%, CEA 0%, and HMB-45 0%. The focal, weak HMB-45 positivity (performed on the index case because of a clinical concern of metastatic melanoma) seen in 57% of the classic chordomas is a previously unreported finding. This finding suggests either that classic chordomas are capable of HMB-45 expression or that this antibody has broader reactivity than previously recognized. The lack of cytokeratin, EMA, and CEA expression by the chondroid chordomas is similar to chondrosarcomas as reported in the literature and dissimilar to the classic chordoma group. These immunohistochemical findings suggest that chondroid chordomas may more validly be classified as low grade chondrosarcomas.
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PMID:Immunohistochemical distinction of classic and chondroid chordomas. 172 44

The authors have engineered a cell line that can be used in human studies as a universal donor cell for the formation of semiallogeneic cell hybrids after fusion with patient-derived tumor cells. These hybrids can be irradiated and injected as a patient-tailored therapeutic vaccine in patients affected by virtually any type of cancer. A crucial step in this research effort has been the derivation of an allogeneic cell line (FO1-12) that expresses both a dominant selectable marker (neomycin resistance) and a recessive selectable marker (sensitivity to hypoxanthine, aminopterin, and thymidine), which allows easy selection of semiallogeneic cell hybrids derived from the fusion of FO1-12 cells with patient-derived tumor cells. Tumor-infiltrating lymphocytes derived from select patients with melanoma and exposed to semiallogeneic cell hybrids from the same patient were better able to specifically lyse autologous tumor cells. Furthermore, FO1-12 cells express carcinoembryonic antigen, which is ubiquitous in adenocarcinomas, and fusion of FO1-12 cells with various patient-derived adenocarcinoma cells showed that the hybrid cells also express carcinoembryonic antigen. Because of the results of these preclinical studies, the authors were given permission to use semiallogeneic cell hybrids for immunotherapy of patients with metastatic melanoma or metastatic adenocarcinoma who had not responded to standard treatment regimens. Treatment with semiallogeneic vaccines is associated with minimal or no toxicity and can induce a specific anti-tumor immune response.
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PMID:Semiallogeneic cell hybrids as therapeutic vaccines for cancer. 1074 51

Melanoma can show a broad spectrum of immunoreactivity and exhibit aberrant expression of antigens or changes in immunophenotype, particularly at metastatic sites. We studied 70 primary melanomas and their metastases with a broad panel of immunohistochemical markers using a tissue microarray technique to determine possible antigenic shift between the primary lesions and their metastases. Representative tissue cores were taken and processed from each case, and the tissue microarrays were stained by standard methods using antibodies to vimentin, bcl-2, CD117, carcinoembryonic antigen, epithelial membrane antigen, S-100 protein, HMB-45, cytokeratin AE1/AE3, Melan-A, TTF-1, CD99, and tyrosinase. Histologically, all the melanomas were of the classic epithelioid type. A slight increase in the expression of Melan-A was noted in metastatic lesions as opposed to the primary tumors (63% vs. 48.4%). Expression of other melanoma-associated markers, including S-100 protein and tyrosinase was only slightly decreased at metastatic sites as opposed to the primary tumor. Increased aberrant expression of epithelial-associated markers, including epithelial membrane antigen and cytokeratin AE1/AE3 was also noted in the metastases. bcl-2, CD117, and TTF-1 also showed a modest increase in antigenic expression at metastatic sites over the primary lesions. The results of this study demonstrated minimal antigenic shift between primary and metastatic melanoma for some of the more conventional melanocytic markers, it showed increased expression of aberrant markers and oncogene expression at metastatic sites.
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PMID:Expression of immunohistochemical markers in primary and metastatic malignant melanoma: a comparative study in 70 patients using a tissue microarray technique. 1809 85

Genetic vaccines are emerging as a powerful modality to induce T-cell responses to target tumor associated antigens (TAA). Viral or plasmid DNA or RNA vectors harbor an expression cassette encoding the antigen of choice delivered in vivo by vaccination. In this context, immunizations with minigenes containing selected, highly antigenic, T-cell epitopes of TAAs may have several advantages relative to full-length proteins. The objective of this study was to identify an optimal scaffold for minigene construction. We generated a number of minigenes containing epitopes from the carcinoembryonic antigen (CEA) model TAA and utilized muscle DNA electro-gene-transfer (DNA-EGT) to vaccinate HLA-A*0201 (HHD) and CEA/HHD double transgenic mice. The components utilized to construct the minigenes included CD8+ T cell epitopes and (or) anchor modified analogs that were selected on the basis of their predicted binding to HLA-*A0201, their uniqueness in the human proteome, and the likelihood of cancer cell natural processing and presentation via MHC-I. Other candidate components comparatively tested included: helper CD4+ T-cell epitopes, flanking regions for optimal epitope processing (including both proteasome-dependent and furin-dependent polypeptide processing mechanisms), and immunoenhancing moieties. Through a series of comparative studies and iterations we have identified an optimal minigene scaffold comprising the following elements: human tissue plasminogen activator (TPA) signal peptide, T-cell epitopes connected by furin sensitive linkers, and the E. Coli enterotoxin B subunit. The selected epitope modified minigenes (EMM) delivered by DNA-EGT were able to break immune tolerance in CEA/HHD mice and induce a strong immune response against all epitopes tested, independently of their relative positions within the scaffold. Furthermore, the optimized EMMs delivered via DNA-EGT were more immunogenic and exerted more powerful antitumor effects in a B16-CEA/HHD metastatic melanoma model than a DNA vector encoding the full-length protein or a mixture of the same peptides injected subcutaneously. Our data may shed light on the optimal design of a universal vehicle for epitope-targeted, genetic cancer vaccines.
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PMID:A novel minigene scaffold for therapeutic cancer vaccines. 2479 Jul 91

The prognostic value of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in melanoma was demonstrated more than a decade ago as superior to Breslow score. We have previously shown that intercellular homophilic CEACAM1 interactions protect melanoma cells from lymphocyte-mediated elimination. Here, we study the direct effects of CEACAM1 on melanoma cell biology. By employing tissue microarrays and low-passage primary cultures of metastatic melanoma, we show that CEACAM1 expression gradually increases from nevi to metastatic specimens, with a strong dominance of the CEACAM1-Long tail splice variant. Using experimental systems of CEACAM1 knockdown and overexpression of selective variants or truncation mutants, we prove that only the full-length long tail variant enhances melanoma cell proliferation in vitro and in vivo. This effect is not reversed with a CEACAM1-blocking antibody, suggesting that it is not mediated by intercellular homophilic interactions. Downstream, CEACAM1-Long increases the expression of Sox-2, which we show to be responsible for the CEACAM1-mediated enhanced proliferation. Furthermore, analysis of the CEACAM1 promoter reveals two single-nucleotide polymorphisms (SNPs) that significantly enhance the promoter's activity compared with the consensus nucleotides. Importantly, case-control genetic SNP analysis of 134 patients with melanoma and matched healthy donors show that patients with melanoma do not exhibit the Hardy-Weinberg balance and that homozygous SNP genotype enhances the hazard ratio to develop melanoma by 35%. These observations shed new mechanistic light on the role of CEACAM1 in melanoma, forming the basis for development of novel therapeutic and diagnostic technologies.
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PMID:CEACAM1 promotes melanoma cell growth through Sox-2. 2493 67

Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination.
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PMID:CEACAM1: Expression and Role in Melanocyte Transformation. 2764 17