184,406 research outputs found
c-erbB-2 expression in benign and malignant breast disease.
No full textAn antibody, 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein has been used immunocytochemically in a retrospective study of formalin fixed paraffin embedded breast biopsies. Fourteen out of 103 infiltrating ductal carcinomas exhibited positive membrane staining. Fifty-four of these tumours had lymph node involvement of which nine contained stained cells. These were all cases where the primary tumour was positive. In this series there was no correlation between c-erbB-2 overexpression and lymph node status. In five of the positive cases studied there was an associated in situ component which was also positively stained. Ten out of 24 pure intraduct carcinomas showed membrane staining, but none of the 149 benign conditions studied, which included 22 radial scars and 13 cases of atypical ductal proliferation, demonstrated the pattern of staining associated with overexpression. It is concluded that the c-erbB-2 protein is overexpressed in a minority (approximately 14%) of infiltrating ductal carcinomas and only in cells that are cytologically malignant. Overexpression of c-erbB-2 is considered in relation to pathogenesis
Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis
No full textBackground: P53, egfr and her-2/neu are the most frequently studied molecular biological parameters in epithelial ovarian cancer, but their prognostic impact is still unequivocal. We performed a meta-analysis to more precisely estimate their prognostic significance. Methods: Published studies that investigated the association between p53, egfr and her-2/neu status and survival were identified. Meta-analysis was performed using a dersimonian-laird model. Publication bias was investigated using funnel plots and sources of heterogeneity were identified using meta-regression analysis. Results: A total of 62 studies were included for p53, 15 for egfr and 20 for her-2/neu. P53, egfr and her-2/neu status had a modest effect on overall survival (Pooled hr 1.47, 95% Ci 1.33-1.61 For p53; Hr 1.65, 95% Ci 1.25-2.19 For egfr and hr 1.67, 95% Ci 1.34-2.08 For her-2/neu). Meta-regression analysis for p53 showed that figo stage distribution influenced study outcome. For egfr and her-2/neu, considerable publication bias was present. Conclusions: Although p53, egfr and her-2/neu status modestly influences survival, these markers are, by themselves, unlikely to be useful as prognostic markers in clinical practice. Our study highlights the need for well-defined, prospective clinical trials and more complete reporting of results of prognostic factor studies. British journal of cancer ( 2009) 101, 149-159. Doi: 10.1038/Sj.Bjc.6605112 Www.Bjcancer.Com published online 9 june 2009 (C) 2009 Cancer research uk
Trastuzumab (Herceptin (R)): Monoclonal antibody in the treatment of HER2/neu-overexpressing breast cancer in the metastatic and (neo)adjuvant situation
No full textTrastuzumab (Herceptin (R)) is a humanized monoclonal antibody that specifically targets HER2/neu (human epidermal growth factor receptor-2) breast cancer cells, which are overexpressed in about 25-30% of breast carcinomas. After phase I and II trials, several phase III studies of trastuzumab alone or in combination with various chemotherapies were conducted. Patients with HER2/neu overexpression levels of 3+ determined by immunohistochemical assay or gene amplification (fluorescence in situ hybridization) derive most clinical benefit from trastuzumab. Taking into consideration efficacy and side effect profile, the combination of trastuzumab and paclitaxel showed an improvement of all clinical parameters, including overall survival, for the first time in the history of palliative breast cancer therapy. The application of trastuzumab has meanwhile become an established part of systemic therapy of metastastic breast cancer, and excellent data of its application in the adjuvant setting now exist (NSABP-B31, NCCTG-N9831, HERA), with significantly better relapse-free survival in the treatment arms with trastuzumab. Ongoing trials investigate the role of trastuzumab in the neoadjuvant setting. Trastuzumab is generally well tolerated. Cardiotoxicity is the main concern, thus monitoring of cardiac function is recommended
Clinical relevance of soluble c-erbB-2 for patients with metastatic breast cancer predicting the response to second-line hormone or chemotherapy
No full textConcentrations of soluble c-erbB-2 were determined in the sera of 64 patients with distant metastasis from advanced breast cancer receiving second-line hormone or chemotherapy in comparison to 35 breast cancer patients without detectable recurrent disease and 17 healthy blood donors. The sera of non-metastatic breast cancer patients contained s-erbB-2 concentrations similar to those of healthy blood donors. Patients with distant metastasis from advanced breast cancer had significantly higher values of s-erbB-2 in comparison to patients with non-disseminated disease (mean: 59.6 vs. 11.6 U/ml; p = 0.022). A significant correlation was observed between s-erbB-2 serum levels and serum LDH concentrations (p < 0.001), levels of alkaline phosphatase (p < 0.001), and the presence of hepatic metastasis (p = 0.001). Time to tumor progression was significantly shorter in patients with s-erbB-2 levels above 40 U/ml (mean: 23.4 vs. 56.7 months; p = 0.002). Furthermore, breast cancer patients with hepatic metastasis and those with elevated s-erbB-2 serum levels above 40 U/ml had limited response to hormone or chemotherapy. Non-responders had significantly higher s-erbB-2 levels (mean: 270.3, range: 42-500 U/ml;) compared with the responder group (mean: 23.1, range: 0-149 U/ml; p < 0.001). Logistic regression analysis indicated that elevated s-erbB-2 serum levels above 40 U/ml independently predicted an unfavorable response to second-line hormone or chemotherapy in patients with advanced metastatic breast cancer. Copyright (C) 2002 S. KargerAG, Basel
Murine c-erbB2: an oncogene that could be a target for vaccination therapy? : and the effect of HER2/c-erbB2/NeuT expression on cell signaling and milk protein formation in mouse mammary epithelial cells
No full textErbB2 is an orphan receptor tyrosine kinase which can dimerize with other ligand-activated
members of the EGF receptor family to signal in pathways inducing cell proliferation.
Frequently overexpressed in breast cancer and other human cancers, homologs of ErbB2 are
oncogenes in different animal species which have been studied for their contribution to the
development of carcinomas.
The first part of this project was aimed at developing a method for vaccination of
mouse, so that a transplanted tumor expressing the endogenous mouse c-erbB2 would be
rejected. Initially, it was necessary to prepare a functional expression clone of mouse cerbB2.
Then the question of how to break the natural tolerance against an immune response
against the self-antigen, mouse c-erbB2, had to be approached. Several protocols were
attempted as described below, but I was unsuccessful in obtaining the intended protective
effect against transplanted tumor.
In the second part of this work, we have examined phenotypes induced by several
ErbB2 homologs in Line 31E mouse mammary epithelial cells which are capable of
differentiation in vitro to undergo dome formation and to produce milk protein in response to
lactogenic hormones. Included in this comparative study are the functional clone of the mouse
proto-oncogene c-erbB2, a human homolog overexpressed in breast cancer, HER2, and the
mutated rat homolog, NeuT, which is known to be oncogenic.
Line 31E mammary epithelial cells were infected with retroviral pBabepuro constructs
of the different ErbB2 homologs. Typical features of epithelial intercellular organization,
such as density of tight junctions and dome formation, were disturbed by ErbB2 expression.
While a dominant negative mutant of HER2 had no effect on the epithelial cells, both
transepithelial monolayer resistance and dome formation were reduced by all three of the
functional ErbB2 homologs, most dramatically by NeuT. While expression of both the mouse
proto-oncogene c-erbB2 and HER2 resulted in significant inhibition of β-casein mRNA and
protein levels after lactogenic hormone treatment, NeuT completely abrogated β-casein
production and caused oncogenic transformation as evidenced by large colonies in soft agar
and Matrigel suspension culture. While the cells expressing the homologs remain acutely
responsive to EGF ligand in terms of Akt/PKB, ERK 1/2 and PKCα phosphorylation, an
elevated basal phosphorylation in the absence of ligand was not apparent for PKCα
Umgebungen von Neu Bidsow und Königsgrätz / C. Steingruber scrip. C. Linzer sculp.
No full textUMGEBUNGEN VON NEU BIDSOW UND KÖNIGSGRÄTZ / C. STEINGRUBER SCRIP. C. LINZER SCULP.
Special-Karte des Koenigreiches Boehmen (-)
Umgebungen von Neu Bidsow und Königsgrätz / C. Steingruber scrip. C. Linzer sculp. (Nro. 15) ( -
Studies of the interaction of novel forms of the p185(c-neu) receptor ectodomain
No full textWe are exploring the roles of the extracellular domain (ECD) of the rat p185c-neu, one member of the erbB family transmembrane receptor tyrosine kinases, which features a signal diversifying mechanism. This mechanism involves the formation of various homo- and hetero-oligomers. One set of the rat c-neu extracellular subdomain individually-deleted constructs and their corresponding NR6 transfectants with or without the coexpression of other erbB family members were studied for inter-receptor interactions. A c-neu-IgG(human) immunoadhesin was also developed to search for the rat p185c-neu ECD specific interacting proteins and to generate a rabbit polyclonal antibody, Anti-NEX. We found that the rat c-neu extracellular subdomain deletions significantly limited cell surface targeting of these mutant receptors, especially in single transfectants. The deletions at the c-neu different extracellular subdomains resulted in distinct changes of the mutant c-neu receptors\u27 phosphotyrosine (PY) content. Extracellular treatment with Anti-NEX significantly down-modulated p185c-neu and increased the PY content of the remaining p185 c-neu. Rat E18 frozen sections stained by high concentrations of the c-neu-IgG(human) immunoadhesin showed a pattern parallel to p185c-neu tissue distribution pattern. Two lines of the c-neu-IgG(human) transgenic driven by the human cytomegalovirus promoter/enhancer were established. RT-PCR assay detected the transcripts of the c-neu-IgG(human) transgene and the mouse c-neu in all examined organs. The c-neu-IgG(human) protein was also detectable in the plasma. But the c-neu-IgG(human) transgenic mice lacked any obvious phenotype. These studies reveal novel regulatory roles of the p185 c-neu ECD. The results of this dissertation may provide new thoughts for cancer therapy and protein engineering
Distribution of neu (c-erbB-2) Protein in Human Skin
No full textThe neu (c-erbB-2) gene encodes a transmembrane protein with tyrosine kinase activity that appears to be a growth factor receptor. An antibody was generated by immunization of rabbits with a synthetic polypeptide that was based on an internal sequence at the carboxy terminus of the molecule. This antibody was used to survey the expression of neu in human skin by immunohistochemistry. Significant protein was found in the squamous cell layer of the surface epidermis, in squamous cell carcinomas, in the external root sheath of hair follicles, and in eccrine gland secretory cells; it was poorly expressed in the basal cell layer and in basal cell carcinomas. Increased neu expression appears to be associated with the differentiation of keratinocytes
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Immunogenicity of rat-neu(+) mouse mammary tumours determines the T cell-dependent therapeutic efficacy of anti-neu monoclonal antibody treatment
No full textThe use of Trastuzumab (Herceptin), a monoclonal antibody (mAb) targeting HER2/neu, results in an increased median survival in Her2(+) breast cancer patients. The tumour mutational burden and the presence of tumour infiltrating lymphocytes (TILs) clearly correlate with response to trastuzumab. Here, we investigated if the immunogenicity of the transplantable rat-neu(+) tumour cell line (TUBO) derived from a BALB/c-NeuT primary tumour is associated with the response to anti-neu mAb therapy. We compared the TUBO tumour outgrowth and tumour infiltrating T cells in isogenic (BALB/c-NeuT) and non-isogenic (WT BALB/c) recipient mice. Furthermore, therapeutic efficacy of anti-neu mAb and the contribution of T cells were examined in both mouse strains. The outgrowth of untreated tumours was significantly better in BALB/c-NeuT than WT BALB/c mice. Moreover, tumour infiltrating T cells were more abundantly present in WT BALB/c than BALB/c-NeuT mice, showing that the TUBO tumour was more immunogenic in WT BALB/c mice. In TUBO tumour bearing WT BALB/c mice, anti-neu mAb therapy resulted in an increase of tumour infiltrating T cells and long-term survival. When T cells were depleted, this strong anti-tumour effect was reduced to an outgrowth delay. In contrast, in TUBO tumour bearing BALB/c-NeuT mice, treatment with anti-neu mAb resulted only in tumour outgrowth delay, both in the presence and absence of T cells. We concluded that in immunogenic tumours the response to anti-neu mAb therapy is enhanced by additional T cell involvement compared to the response to anti-neu mAb in non-immunogenic tumours.Functional Genomics of Systemic Disorder
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