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

Immunocytochemical assays were performed on frozen sections of inflammatory breast carcinomas (n = 22) using the following monoclonal antibodies (MoAb): anti-pHER2/neu, cathepsin, pS2, ER, PR and MoAb Ki67. The distribution of these proteins, known as prognostic indicators, was evaluated with an image analysis system (SAMBA, Alcatel TITN, France). On standard HE stained paraffin sections, only about 50% of inflammatory breast tumors exhibited intradermal tumor cell emboli. All tumors were strongly pHER/2neu positive. All tumors also, but to a lesser degree, were cathepsin and ki67 positive. Conversely, less than 40% were faintly ER, PR and pS2 immunoreactive. The results correlated with the high degree of malignancy of inflammatory breast carcinomas. Therefore the immuno-detection of these markers in addition to standard histological techniques appears to be a useful tool to evaluate the degree of malignancy of breast carcinomas.
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PMID:Inflammatory breast carcinoma: an immunohistochemical study using monoclonal anti-pHER-2/neu, pS2, cathepsin, ER and PR. 135 40

The monoclonal antibody (MAb) 1BE12 has recently been reported to react with several human normal and abnormal tissues. In human endometrium, it reacts more strongly with carcinomas than with normal tissue. To investigate the effectiveness of MAb 1BE12 in identifying cell proliferation in human endometrial cancers, 1BE12 immunocytochemical assays (ICAs) were performed on frozen (n = 47) and paraffin (n = 100) sections with subsequent computer-assisted microcytophotometric (SAMBA) evaluation of immunoprecipitate distribution. MAb 1BE12 immunoreactivity was not impaired by tissue fixation and paraffin embedding. It reacted with normal proliferative endometrium but not with normal secretory endometrium, and immunoreactivity increased with the degree of cell proliferation and malignancy, the amount of immunostaining being greater in invasive carcinomas than in normal proliferative endometrium and endometrial hyperplasia. ICAs showed no correlation between MAb 1BE12 immunoreactivity and estrogen and progesterone receptor antigenic sites. On the other hand, MAb 1BE12 staining in frozen sections increased with Ki67, EGFR, pHER-2/neu, and cathepsin immunostaining. These findings suggest that ICAs on frozen and paraffin-embedded biopsy specimens using MAb 1BE12 along with other markers can be useful for early detection and grading of endometrial carcinoma. The relevance of MAb 1BE12 to the selection of patients for laser ablation of the endometrium rather than hysterectomy is also discussed.
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PMID:Monoclonal antibody 1BE12 immunoreactivity with human endometrium. Correlations with hormone receptors and proliferation cell markers. 177 9

Patients with invasive breast cancer and pathologically negative lymph nodes (NO) have a favorable 10-year survival rate, particularly with small (less than 1 cm) primary tumors. Overall, however, 20% to 35% will experience recurrence with local therapy only. Adjuvant chemotherapy or tamoxifen have prolonged disease-free survival (DFS), but not overall survival (OS). Unanswered questions of optimal end point (DFS or OS) and the risk of treating many to benefit few have prompted clinicians to use prognostic indicators to facilitate treatment recommendations. Currently, the most readily available and accurate information comes from TNM staging, pathologic features, and hormone receptors. Ploidy, S-phase fraction, HER-2-neu amplification or over-expression, and cathepsin-D may be useful prognostic indices. Until a more precise system of weighing several prognostic variables is developed, the decision to recommend adjuvant systemic therapy in this generally good prognosis group will have to be thoughtfully considered by patient and physician. Whenever possible, patients should be encouraged to enter clinical trials.
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PMID:Adjuvant therapy for node-negative breast cancer. The use of prognostic factors in selecting patients. 200 69

Immunocytochemical assays of cathepsin D were assessed in a series of breast carcinomas (n = 257) using monoclonal M1G8 anti-total cathepsin D and the avidin-biotin-peroxidase complex. Cathepsin immunoreactivity was compared in frozen and paraffin sections. All tumours were anti-cathepsin-positive. Positive staining was observed in carcinoma and stromal cells and in the extracellular matrix. The amount of immunodetectable cathepsin in tissue was measured by computer-assisted image analysis (SAMBA 2005). Both the percentage of immunostained tumour surface and the mean optical densities were processed as continuous variables for statistical analysis and correlated with prognostic factors. It was shown that cathepsin D was independent of the tumour size, the lymph node status, hormone receptors, and pHER-2/neu overexpression. Cathepsin was significantly correlated with anti-EGFR (P = 0.012) and Ki67 (P = 0.002) immunoreactivity, tumour grade (P = 0.032), vascular invasion (P = 0.0081), proliferation index (P = 0.0045), and, to a lesser extent with AgNORs (P = 0.0504) and the degree of hyperploidy (P = 0.057). Tissue fixation and paraffin embedding significantly decreased cathepsin immunoreactivity. These results show that cathepsin D is not a totally independent prognostic factor in breast carcinomas.
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PMID:Cathepsin D immunocytochemical assays in breast carcinomas: image analysis and correlation to prognostic factors. 841 Apr 96

Recent studies have suggested that insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) may be implicated in the development and progression of breast cancer. Prostate-specific antigen (PSA), a serine protease, may play a role in the regulation of IGFs' function through cleavage of IGFBP-3, resulting in release of active IGFs from IGFBP-3. As IGFs, IGFBPs and PSA are all present in breast cancer, possible associations among these proteins were speculated. In this study, we have measured PSA, IGF-I, IGF-II, IGFBP-1 and IGFBP-3 in tumour tissue cytosols from 200 women with primary breast cancer, and have examined relationships between IGFs or IGFBPs and PSA along with other markers, including p53 protein, steroid hormone receptors (oestrogen and progesterone), cathepsin-D, epidermal growth factor receptor, Her-2/neu protein, S-phase fraction and DNA ploidy. Correlations or associations between PSA and IGF-I, IGF-II, IGFBP-1 or IGFBP-3 were not observed. IGF-II was positively correlated with both IGFBP-3 and IGFBP-1. IGF-I was not associated with either of the two binding proteins, nor with IGF-II. Both IGF-II and IGFBP-3 were inversely associated with the oestrogen receptor, and IGFBP-3 was also positively associated with S-phase fraction. Our finding of IGF-II and IGFBP-3 in association with unfavourable prognostic indicators of breast cancer suggests that IGFs may be involved in the progression of breast cancer.
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PMID:Associations between insulin-like growth factors and their binding proteins and other prognostic indicators in breast cancer. 888 11

We assessed distributions of breast cancer prognostic biomarkers by race/ethnicity and socioeconomic position among paraffin-embedded tumor biopsy specimens from 135 US women (48 white women, 44 black women, 43 Asian women) diagnosed with breast cancer between 1966 and 1990. No racial/ethnic or socioeconomic differences in distributions were observed for tumor stage, lymph node involvement, estrogen, progesterone, and epidermal growth factor receptors, oncogenes such as Her2/neu and p53, cytoplasmic proteins cathepsin-D and ps2, and two indices of cell growth, Ki67 and DNA ploidy, adjusting for age at diagnosis, menopausal status, place of birth and, for racial/ethnic comparisons, working class composition of census block-group at diagnosis. Black and Asian women, however, were 3.5 times (95% confidence interval [CI] = 1.2, 10.1) and 3.7 times (95% CI = 1.3, 10.6), respectively more likely than white women to have a tumor size of > or = 20 mm, and Asian women were 3.4 times (95% CI = 1.1, 10.4) more likely than black women to be positive for androgen receptor, adjusting for these same factors. No differences in distributions by socioeconomic position were observed for these latter two tumor characteristics. These data suggest that racial/ethnic and socioeconomic disparities in breast cancer survival are unlikely to be explained solely by differential distributions of molecular breast cancer prognostic biomarkers.
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PMID:Race/ethnicity, social class, and prevalence of breast cancer prognostic biomarkers: a study of white, black, and Asian women in the San Francisco bay area. 938 54

pS2 expression was studied in 212 breast carcinomas. Immunocytochemical assays (ICAs) were performed on frozen sections and evaluated by digital image analysis. pS2 immunostaining was compared in frozen sections and paraffin sections. The pS2 positivity was observed in 45% of the cases on frozen sections. But in pS2 positive tumors, the tumor surface which was immunostained was small (m=14.3%). In 22% of immunoreactive tumors the positive surface was 5% or less. In contrast to frozen sections, the pS2 positivity on paraffin sections could not be evaluated by image analysis system because of the background. No significant correlation was observed between pS2 expression and patient age, tumor size, histological type and grade, nor with lymph node status. The pS2 positivity was significantly correlated to ER and PR positive immunodetection on frozen sections. But pS2 was independent from pHER-2/neu and cathepsin expression whereas there was a significant inverse relationship between pS2 and Ki67. This study shows that pS2-ICAs on frozen sections and image analysis are optimal and standardized conditions for the evaluation of pS2 expression in breast carcinomas, and suitable for selecting patients for hormone therapy.
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PMID:Quantitative imaging of ps2 immunocytochemical assays in breast carcinomas. 2157 75

Human adenoviruses have a great potential as anticancer agents. One strategy to improve their tumor-cell specificity and anti-tumor efficacy is to include tumor-specific targeting ligands in the viral capsid. This can be achieved by fusion of polypeptide-targeting ligands with the minor capsid protein IX. Previous research suggested that protein IX-mediated targeting is limited by inefficient release of protein IX-fused ligands from their cognate receptors in the endosome. This thwarts endosomal escape of the virus particles. Here we describe that the targeted transduction of tumor cells is augmented by a cathepsin-cleavage site between the protein IX anchor and the HER2/neu-binding ZH Affibody molecule as ligand. The cathepsin-cleavage site did not interfere with virus production and incorporation of the Affibody molecules in the virus capsid. Virus particles harboring the cleavable protein IX-ligand fusion in their capsid transduced the HER2/neu-positive SKOV-3 ovarian carcinoma cells with increased efficiency in monolayer cultures, three-dimensional spheroid cultures and in SKOV-3 tumors grown on the chorioallantoic membrane of embryonated chicken eggs. These data show that inclusion of a cathepsin-cleavage sequence between protein IX and a high-affinity targeting ligand enhances targeted transduction. This modification further augments the applicability of protein IX as an anchor for coupling tumor-targeting ligands.
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PMID:A cathepsin-cleavage site between the adenovirus capsid protein IX and a tumor-targeting ligand improves targeted transduction. 2201 43

Cross-presentation is the process by which professional antigen presenting cells (APCs) (B cells, dendritic cells (DCs) and macrophages) present endocytosed antigens (Ags) via MHC-I to CD8+ T cells. This process is crucial for induction of adaptive immune responses against tumors and infected cells. The pathways and cellular compartments involved in cross-presentation are unresolved and controversial. Among the cells with cross-presenting capacity, DCs are the most efficient, which was proposed to depend on prevention of endosomal acidification to block degradation of the epitopes. Contrary to this view, we show in this report that some cargoes induce strong endosomal acidification following uptake by human DCs, while others not. Moreover, processing of the tumor-associated antigen HER2/neu delivered in nanoparticles (NP) for cross-presentation of the epitope HER2/neu369-377 on HLA-A2 depended on endosomal acidification and cathepsin activity as well as proteasomes, and newly synthesized HLA class I. However, the HLA-A*0201/HER2/neu369-377 complexes were not found in the endoplasmic reticulum (ER) nor in endolysosomes but in hitherto not described vesicles. The data thus indicate spatial separation of antigen processing and loading of MHC-I for cross-presentation: antigen processing occurs in the uptake compartment and the cytosol whereas MHC-I loading with peptide takes place in a distinct subcellular compartment. The findings further elucidate the cellular pathways involved in the cross-presentation of a full-length, clinically relevant tumor-associated antigen by human DCs, and the impact of the vaccine formulation on antigen processing and CD8+ T cell induction.
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PMID:Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neu by human dendritic cells. 2698 98