Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic antigen-presenting cells are considered to be the most effective stimulators of T cell immunity. The use of dendritic cells has been proposed to generate therapeutic T cell responses to tumor antigens in cancer patients. One limitation is that the number of dendritic cells in peripheral blood is exceedingly low. Dendritic cells originate from CD34+ hematopoietic progenitor cells (HPC) which are present in the bone marrow and in small numbers in peripheral blood. CD34+ HPC can be mobilized into the peripheral blood by in vivo administration of granulocyte-colony-stimulating factor. The aim of the current study was to determine whether functional dendritic cells could be elicited and grown in vitro from CD34+ HPC derived from bone marrow or granulocyte-colony-stimulating factor-mobilized peripheral blood. Culture of CD34+ HPC with granulocyte-macrophage-colony-stimulating factor and tumor necrosis factor alpha yielded a heterogeneous cell population containing cells with typical dendritic morphology. Phenotypic studies demonstrated a loss of the CD34 molecule over 1 week and an increase in cells expressing surface markers associated with dendritic cells, CD1a, CD80 (B7/BB1), CD4, CD14, HLA-DR, and CD64 (Fc gamma RI). Function was validated in experiments showing that cultured cells could stimulate proliferation of allogeneic CD4+ and CD8+ T lymphocytes. Antigen-presenting capacity was further confirmed in experiments showing that cultured cells could effectively stimulate tetanus toxoid-specific responses and HER-2/neu peptide-specific responses. The derivation and expansion of dendritic cells from cultured bone marrow or granulocyte-colony-stimulating factor-mobilized CD34+ HPC may provide adequate numbers for testing of dendritic cells in clinical studies, such as vaccine and T cell therapy trials.
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PMID:Generation of immunostimulatory dendritic cells from human CD34+ hematopoietic progenitor cells of the bone marrow and peripheral blood. 753 43

This report describes the characterization of an estrogen receptor-positive breast cancer cell line, HMA-1, established from a breast cancer patient, based on the expression of tumor-associated antigens (TAAs), the HLA-DR antigen, and the c-erbB-2 proto-oncogene product. In flow cytometric and immunohistochemical analyses, HMA-1 was found to express increased levels of several TAAs including MUC1, TAG-72 (sialyl Tn), Tn, T, sialyl Le(a), Le(x), and Le(y). HMA-1 also expressed enhanced levels of the HLA-DR antigen and c-erbB-2 protein. These results indicate that HMA-1 is a unique cell line with abundant TAAs which may serve as an appropriate breast cancer cell line for application in the multidisciplinary research of breast cancer.
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PMID:Characterization of cell surface antigens expressed in the HMA-1 breast cancer cell line. 764 Apr 54

We have examined the character and carcinogenic properties of the normal-appearing epidermis overlying basal cell carcinomas by immunohistochemical methods, employing a series of monoclonal antibodies. The labelling index was significantly increased in the atrophic epidermis overlying basal cell carcinomas (solid type, n = 20), compared with the epidermis overlying or adjacent to squamous cell carcinoma (n = 20), keratoacanthoma (n = 10), dermatofibroma (n = 10), neurofibroma (n = 10), soft fibroma (n = 10), pyogenic granuloma (n = 10) and cutaneous leiomyoma (n = 5). Cells which expressed epidermal growth factor (EGF) receptor were detected in all layers of the epidermis over the basal cell carcinomas, but not the other tumours. Basement membrane-related antigens, including bullous pemphigoid antigen and GB3 antigen, were decreased in the epidermis. AE1, the monoclonal antibody against basal cell keratin, reacted with the uppermost layers of the normal-appearing epidermis overlying the basal cell carcinomas. ICAM-1 expression was very weak in the overlying epidermis. The dermis subjacent to the proliferating epidermis showed staining for transforming growth factor-alpha (TGF-alpha), strong positive PECAM-1 staining of endothelium, and numerous HLA-DR-positive cells. From these results, we suggest that the proliferative activity in the epidermis overlying basal cell carcinomas is not a state induced by the dermal infiltrate, but represents carcinogenic activity of the epidermis.
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PMID:Immunohistochemical evaluation of epidermis overlying basal cell carcinomas. 768 54

We characterized the changes induced by treatment for 48 h with 100 U/ ml interferon gamma (IFN-gamma) on HeLa and CaSki cells, derived from human uterine carcinomas and containing human papillomavirus (HPV) type 16 and HPV type 18 respectively, by studying cell growth, cell morphology, the cell cycle and expression of epidermal growth factor (EGF) receptor, filaggrin-profilaggrin and MHC class II antigen, HLA-DR. The response of the two cell lines to IFN gamma differed in some cases. In both cell lines, the cells remained viable; cell growth was similarly inhibited as shown by cell counts. Signs of morphological changes were essentially observed in HeLa cells. The cell cycle phases, analyzed by flow cytometry were more disturbed in CaSki than in HeLa cells; the proportion of CaSki cells in S phase increased and those in G2 + M decreased. Expression of EGF receptors related to proliferation increased only in CaSki cells while expression of filaggrin-profilaggrin, a marker of differentiation, and HLA-DR, a marker of epithelial cell immune response, was enhanced in both cell lines. The presence of filaggrin-profilaggrin being unexpected in these cells, the specificity of the reaction with the monoclonal antibody AKH1 was confirmed by immunoblotting. In conclusion, our results show that the two cell lines reacted differently to IFN gamma although they are of similar origin and the different antigens studied may be useful to predict the progression of lesions infected with HPV towards malignancy or the reactivity to IFN gamma of such lesions. However, enhanced synthesis of EGF receptors is probably independent of the antiproliferative effect of IFN gamma but an increase in HLA-DR antigen expression by epithelial cells, which corresponds to an immune response favored by IFN gamma, could act synergistically with cell growth inhibition and differentiation to exclude tumoral and/or HPV-infected cells.
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PMID:Differences of reactivity to interferon gamma in HeLa and CaSki cells: a combined immunocytochemical and flow-cytometric study. 860 75

Archival biopsy specimens from transitional cell bladder cancers (n=88) were analysed immunohistochemically for the expression of the retinoblastoma (Rb) gene protein, p53, mdm2, c-erbB-2, HLA-DR antigen and proliferation indices. An altered nuclear expression of Rb, p53 and mdm2 was observed in 55.2%, 33.3% and 18.2% of tumors respectively. Cytoplasmic membrane immunoreactivity (>25% tumor cells) for c-erbB-2 was detected in 14.1% of tumors and aberrant HLA-DR antigen cytoplasmic staining (>5% of tumor cells) in 22.2% of the cases. P53 overexpression was associated with higher tumor grade and stage. Aberrant HLA-DR antigen expression and PCNA were also correlated with the grade of differentiation and tumor stage. MIB1 was statistically correlated with stage. pRb scores and HLA-DR antigen expression were correlated with proliferation activity as determined by PCNA and MIB1 immunostaining. p53 protein was also strongly correlated with the proliferation index PCNA. A strong correlation between PCNA and MIB1 (p<0.0001) was also found. In addition a statistically positive correlation between p53 and HLA-DR antigen expression was observed. Our data show that, although pRb and p53 protein expressions are not associated between them, they may contribute to the growth fraction of the bladder cancer. In addition, p53 and HLA-DR antigen expression could be indicators of aggressive behavior of bladder cancer.
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PMID:Immunohistochemical expression of retinoblastoma gene product (Rb), p53 protein, MDM2, c-erbB-2, HLA-DR and proliferation indices in human urinary bladder carcinoma. 1096 16

HER2/neu-derived peptides inducing MHC class II-restricted CD4+ T helper lymphocyte (Th) responses, although critical for tumour rejection, are not thoroughly characterized. Here, we report the generation and characterization of CD4+ T cell clones specifically recognizing a HER-2/neu-derived peptide (776-788) [designated HER2(776-788)]. Such clones yielded specific proliferative and cytokine [gamma-interferon(IFN)-gamma] responses when challenged with autologous dendritic cells (DCs) loaded with HER2(776-788). By performing blocking studies with monoclonal antibodies (MAbs) and by using DCs from allogeneic donors sharing certain HLA-DR alleles, we found that HER2(776-788) is a promiscuous peptide presented, at least, by DRB5*0101, DRB1*0701 and DRB1*0405 alleles. One TCRV beta 6.7+ clone recognized the HLA-DRB5*0101+ FM3 melanoma cell line transfected with a full length HER-2/neu cDNA. Moreover, this clone recognized the HER-2/neu+ SKBR3 breast cancer cell line induced to express HLA-DR, thus demonstrating that HER2(776-788) represents a naturally processed and presented epitope. Our data demonstrate that helper peptide HER2(776-788) represents a promiscuous epitope binding to at least three HLA-DR alleles, thus offering a broad population coverage. The use of antigenic peptides presented by major histocompatibility complex (MHC) class II in addition to those presented by class I may improve the therapeutic efficacy of active immunization.
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PMID:Peptide HER2(776-788) represents a naturally processed broad MHC class II-restricted T cell epitope. 1172 Apr 40

HER-2/neu peptides recognized in the context of HLA-DR molecules by CD4(+) Th lymphocytes on antigen-presenting cells have been identified. In this report, we demonstrate for the first time that HER-2/neu helper epitopes are also expressed on the surface of metastatic breast, colorectal and pancreatic carcinomas. Peripheral blood mononuclear cells from an HLA-DR4 healthy donor were used to induce HER-2/neu peptide-specific CD4(+) T cell clones by in vitro immunization with HER-2/neu peptide (884-899)-pulsed autologous dendritic cells (DCs). Strong proliferation and significant levels of IFN-gamma were induced by the CD4(+) T cell clones in response to specific stimulation with autologous DCs loaded with HER-2(884-899). Furthermore, these clones also recognized HER-2/neu(+) tumor cell lines, and tumor cells from breast, colorectal and pancreatic adenocarcinomas induced to express HLA-DR4, but also the HLA-DR4(+) melanoma cell line FM3 transfected to express HER-2/neu. The recognition of tumor cells was strongly inhibited by an anti-HLA-DR mAb. Taken altogether, we provide novel information for the role of HER-2(884-899) as a naturally processed epitope expressed by breast, colorectal and pancreatic carcinomas and the capacity of HER-2/neu protein to follow the endogenous class II processing pathway. Our results suggest that HER-2(884-899) might be attractive for broadly applicable vaccines and may prove useful for adoptive immunotherapy designed for breast, colorectal and pancreatic carcinomas.
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PMID:HER-2/neu-derived peptide 884-899 is expressed by human breast, colorectal and pancreatic adenocarcinomas and is recognized by in-vitro-induced specific CD4(+) T cell clones. 1180 25

The specificity and potency of the immune system make immunotherapy a potential strategy for the treatment of cancer. To exploit this potential, we have developed cell-based cancer vaccines consisting of tumor cells expressing syngeneic MHC class II and costimulatory molecules. The vaccines mediate tumor regression in mice and activate human CD4+ T cells in vitro. Previous vaccines were generated by transducing MHC II negative tumor cells with a single HLA-DR allele. Because expression of multiple MHC II alleles would facilitate presentation of a broader repertoire of tumor antigens, we have now transduced tumor cells with the MHC class II transactivator (CIITA), a regulatory gene that coordinately increases expression of all MHC II alleles. Previous studies in mice indicated that coexpression of the MHC II accessory molecule invariant chain (Ii) inhibited presentation of endogenously synthesized tumor antigens and reduced vaccine efficacy. To determine if Ii expression affects presentation of MHC class II-restricted endogenously synthesized tumor antigens in human tumor cells, HLA-DR-MCF10 breast cancer cells were transduced with the CIITA, CD80 costimulatory molecule gene, and with or without small interfering RNAs (siRNA) specific for Ii. Ii expression is silenced >95% in CIITA/CD80/siRNA transductants; down-regulation of Ii does not affect HLA-DR expression or stability; and Ii(+) and Ii(-) transductants activate human CD4+ T cells to DRB1*0701-restricted HER-2/neu epitopes. Therefore, tumor cells transduced with the CIITA, CD80, and with or without Ii siRNA present endogenously synthesized tumor antigens and are potential vaccines for activating tumor-specific CD4+ T cells.
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PMID:Tumor cells transduced with the MHC class II Transactivator and CD80 activate tumor-specific CD4+ T cells whether or not they are silenced for invariant chain. 1642 52

We describe here a case of malignant lymphoma (ML) which coexpressed common acute lymphoblastic leukemia antigen (CALLA:CD10) and NRAS p21 and c-erbB-2 (neu) oncogene products. The patient, an 83 year-old man, had massive generalized lymphadenopathy and pleural effusions. Serum LDH levels were elevated to 801 IU/L. Surface phenotypes were analysed by a fluorescent-activated cell sorter with a panel of monoclonal antibodies (MAbs). The ML cells coexpressed antigens detected by MAbs CD10, CD19, CD20, CD22, CD24, CD38, Ia (HLA-DR), c-neu and surface immunoglobulin (Ig) G, Kappa. Gene rearrangements for the Ig JH and JK were found. Overexpression of NRAS p21 was shown by gene amplification using Southern blot analysis, while gene amplification of c-erbB-2 oncogene was also demonstrated. To our knowledge, this is the first report to demonstrate an overexpression of p185 c-neu on ML cells. These findings suggest that the p185 neu may be a prognostic indicator not only for breast adenocarcinomas but also for lymphoproliferative disorders, and that the transforming p185 protein may be involved in the mechanisms of aggressive expansion of lymphoid neoplasias.
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PMID:Aggressive Diffuse Lymphoma Coexpressing NRAS p21 and C-erbB-2 (neu) Oncogene Products, and CALL A (CD 10). 2746 77