Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HER-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. The oncogenic potential of HER-2/neu, together with its elevated expression in tumors, cell surface localization, and immunogenicity in some patients, make this oncoprotein an ideal target for immunotherapeutic approaches. To test the efficacy of immune-based strategies in eliciting an antitumor response, we used the N#202 transgenic mouse model engineered to overexpress the rat neu proto-oncogene under the control of the mouse mammary tumor virus promoter; females of this line develop spontaneous focal mammary tumors by 6 months of age. Transgenic mice immunized intramuscularly with a HER-2 cDNA ligated into the VR1012 (VICAL) expression vector under the control of the cytomegalovirus promoter developed significantly fewer spontaneous tumors as compared with mice injected with the empty vector (P < 0.0001) or not injected (P = 0.0006). However, this protection was observed only when immunization was started in 3-month-old but not in 6-month-old mice. These data suggest that the xenogeneic HER-2 DNA sequence can break immune tolerance to rat neu in transgenic N#202 mice and induce protective immunity that impairs the neu oncogene-driven progression of mammary carcinogenesis. The preventive effect achieved by our immunological approach appeared not to be based on anti-neu specific B and T cell immune attacks but was more possibly based on different mechanisms including aspecific and inflammatory immunological responses.
 ...
PMID:Prevention of spontaneous neu-expressing mammary tumor development in mice transgenic for rat proto-neu by DNA vaccination. 1140 5

Tumor-targeted vectors with controllable expression of therapeutic genes and specific antitumor antibodies are promising tools for the reduction of malignant tumors. Here we describe a new plasmid for the eukaryotic expression of an anti-HER2/neu mini-antibody-barnase fusion protein (4D5 scFv-barnase-His(5)) with an NH(2)-terminal leader peptide. The 4D5 scFv-barnase-His(5) gene was placed downstream of the tetracycline responsive-element minimal promoter in the vector using the Tet-Off gene-expression system. The Bacillus amyloliquefaciens ribonuclease barnase is toxic for the host cells. To overcome this problem, barstar gene under its own minimal cytomegalovirus promoter was used in designed vector. Barstar inhibits the background level of barnase in the cells in the presence of tetracycline in culture medium. The HEK 293T cells were transfected with the designed vector, and the 4D5 scFv-barnase-His(5) fusion protein was identified by anti-barnase antibodies in cell culture medium and after purification from cell lysates using metal-affinity chromatography. The overexpression of the anti-HER2/neu mini-antibody-barnase fusion protein decreased the intensity of fluorescence of HEK 293T cells co-transfected with the generated plasmid and a plasmid containing the gene of enhanced green fluorescent protein (pEGFP-N1), in comparison with the intensity of fluorescence of HEK 293T cells transfected with pEGFP-N1, in the absence of tetracycline in the medium. The effect of the 4D5 scFv-barnase-His(5) on EGFP fluorescence indicates that the introduced barnase functions as a ribonuclease inside the cells. The anti-HER2/neu mini-antibody could be used to deliver barnase to HER2/neu-positive cells and provide its penetration into the target cells, as HER2/neu is a ligand-internalizing receptor. This expression vector has potential applications to both gene and antibody therapies of cancer.
 ...
PMID:A new vector for controllable expression of an anti-HER2/neu mini-antibody-barnase fusion protein in HEK 293T cells. 1630 Sep 8

The cytomegalovirus (CMV) promoter is considered to be one of the strongest promoters for driving the in vivo expression of genes encoded by DNA vaccines. However, the efficacy of DNA vaccines has so far been disappointing (particularly in humans), and this might be explained in part by histone deacetylase (HDAC)-mediated chromatin condensation. Hence, we sought to investigate whether increasing the expression of DNA vaccine antigens with the HDAC inhibitor OSU-HDAC42 would enhance the efficacy of DNA vaccines in vivo. A luciferase assay was used to determine the effects of OSU-HDAC42 on CMV promoter-driven DNA plasmids in vitro and in vivo. Three HDAC inhibitors were able to activate expression from the CMV promoter in NIH3T3 cells and MBT-2 bladder cancer cells. The expression of luciferase was significantly enhanced by co-administration of pCMV-luciferase and OSU-HDAC42 in mice. To explore whether OSU-HDAC42 could enhance the specific antitumor activity of a neu DNA vaccine driven by the CMV promoter, we evaluated therapeutic effects and immune responses in a mouse tumor natively overexpressing HER2/neu. Mice receiving OSU-HDAC42 in combination with the CMV-promoter neu DNA vaccine exhibited stronger antitumor effects than mice given the DNA vaccine only. In addition, a correlation between the antitumor effects and the specific cellular immune responses was observed in the mice receiving the DNA vaccine and OSU-HDAC42.
 ...
PMID:An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine. 1985 54

This report describes the clinicopathologic features of a primary lymphoepithelioma-like carcinoma of the endometrium, representing only the fourth reported case of this tumor at this location. In addition to its classic morphologic features, focal clear cells were also identified within the tumor, thereby expanding the morphologic spectrum of the neoplasm at this location. A comprehensive immunohistochemical characterization of the tumor was performed, as was microsatellite instability testing. The tumor was diagnosed in a 79-year-old woman and was surgically/pathologically staged as IB by the International Federation of Gynecology and Obstetrics (FIGO) criteria. The tumor displayed typical morphologic features (tumor cells with a syncytial appearance in an inflammatory background) with the exception of the aforementioned polygonal cells with well-defined cell membranes and cytoplasmic clarity in <1% of the tumor. The epithelial component showed strong and diffuse immunoreactivity for CAM 5.2, p53, p16, E-cadherin, cytokeratin (CK) 7, vimentin, CKAE1/3, and epithelial membrane antigen. The MIB-1 proliferative index in these regions was about 70%. Approximately 10% to 30% of lesional cells showed strong immunoreactivity for CK903, S100, MOC31, CD138, but the pattern of positivity was patchy and discontinuous. The epithelial cells were entirely negative for CK5/6, smooth muscle actin, p504S, CK20, synaptophysin, chromogranin, CD56, CD99, WT-1, thyroid transcription factor-1, p63, CD117 (c-kit), CD34, calretinin, desmin, estrogen receptor, progesterone receptor, FLI-1, ALK-1, D2-40, cytomegalovirus antigen, Epstein-Barr virus-encoded RNA-1, Epstein-Barr virus, monoclonal carcinoembryonic antigen, and HER2/neu. The foci with clear cells were not immunophenotypically distinct from the non-clear cell areas and had an approximately similar proliferative index. The inflammatory component was mixed (lymphocytes, histiocytes, plasma cells, neutrophils) but was composed predominantly of CD45/CD3/CD8 T lymphocytes, with a CD3 to CD20 ratio of approximately 10:1 and CD8 to CD4 T-cell ratio of approximately 3:1. Numerous (>100 positive cells per 10 high-power fields) S100-positive tumor-infiltrating Langerhans cells were present. The tumor DNA did not exhibit microsatellite instability at any of the loci analyzed. In summary, the limited data available suggest that lymphoepithelioma-like carcinoma is a distinct histotype of endometrial carcinoma that is typically seen in postmenopausal women, seems to be unrelated to the Epstein-Barr virus, and has an uncertain prognosis. Differential diagnostic and pathogenetic considerations are discussed within the context of the lesional morphologic and immunophenotypic profile as described herein and in previously reported cases.
...
PMID:Lymphoepithelioma-like carcinoma of the endometrium: immunophenotypic characterization of a rare tumor with microsatellite instability testing. 2430 May 38