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)

An 83-year-old male was admitted with a right pleural effusion and generalized lymphadenopathy. Serum LDH level was elevated to 801 IU/L, and the pathological diagnosis from inguinal lymph node needle biopsy was malignant lymphoma (ML) of diffuse, large cell, non-cleaved type, according to the working formulation. The surface phenotypes of the malignant cells from the pleural effusion were analyzed by a fluorescent-activated cell sorter with a panel of monoclonal antibodies (MAbs). The ML cells coexpressed antigens detected by MAbs CD10 (CALLA), CD19, CD20, CD22, CD24, CD38, Ia, c-neu and surface immunoglobulin G kappa. A high expression of NRAS p21 was also detected by cytoplasmic immunofluorescence technique. The patient died 19 days later despite a combination of chemotherapy and intensive supportive therapy. From these findings it seems that c-neu may be a prognostic indicator not only for breast cancers but also for lymphoproliferative disorders. Further accumulation of such cases is needed.
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PMID:[Aggressive diffuse lymphoma with malignant pleural effusion expressing c-erbB-2 (neu) oncogene products]. 810 89

Peptides presented by class I major histocompatibility complex (MHC) molecules and derived from normal self-proteins that are expressed at elevated levels by cells from a variety of human (Hu) malignancies provide, in theory, potential target antigens for a broad-spectrum, cytotoxic T lymphocyte (CTL)-based immunotherapy of cancer and hematologic malignancies. However, as such tumor- and leukemia-associated self-proteins are also expressed at low levels in some types of normal tissues, such as thymus, spleen and lymphohemopoietic cells, these self-MHC-self-peptide complexes may also represent thymic and/or peripheral tolerogens, thereby preventing immune responses. This is particularly true for class I MHC-peptide complexes expressed by bone marrow-derived cells in the thymus, as such expression would cause negative selection of immature thymic T cells with high avidity for self-MHC-self-peptide complexes. This intrathymic deletion of potentially self-reactive T cells could result in a peripheral T cell repertoire purged of CTL precursors with sufficient avidity to recognize natural tumor associated self-epitopes presented by class I MHC molecules on tumor cells. HLA-transgenic (Tg) mice provide the basis of an experimental strategy that exploits species differences between Hu and murine (Mu) protein sequences in order to circumvent self-tolerance and obtain HLA-restricted CTL specific for epitopes derived from tumor- and leukemia-associated Hu self proteins, such as p53, Her-2/neu, hdm2 and CD19.
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PMID:Targeting p53, hdm2, and CD19: vaccination and immunologic strategies. 1093 87

Ab therapy against surface Ags on tumor cells has demonstrated significant efficacy for some cancers. However, it is costly and patients frequently develop acquired resistance over time. In cases of Ab therapy resistance, T cell responses have been shown to be essential in controlling disease progression. Thus, vaccination that generates a sustained Ab response as well as a T cell response may be more effective and economical. In this article, we have developed a vaccination strategy by targeting protein Ags to B cells via a CD19 single-chain variable fragment miniAb. Using the tumor-associated Ag her-2/neu extracellular domain, we showed that the coengagement of CD19 and BCR induced full B cell activation to produce a high titer of Abs and enhanced CD4 Th2 response and CD8 T cell activation and differentiation. These Abs competitively inhibited humanized her-2/neu Ab binding and were capable of activating the complement and inhibiting human breast cancer growth in vitro. Therapeutic efficacy was demonstrated in vivo using murine mammary carcinoma models. Furthermore, four different extracellular domains of her-2/neu could be targeted to B cells to generate Abs against particular domains with different antitumor properties. This approach may offer a new avenue for vaccine development with significantly lower cost, which may be of use not only for cancer therapy but also for infectious agents.
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PMID:Targeting of antigens to B lymphocytes via CD19 as a means for tumor vaccine development. 2718 54

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