77 research outputs found
Update on HER-2 as a target for cancer therapy: alternative strategies for targeting the epidermal growth factor system in cancer
No full textThe epidermal growth factor (EGF) family of ligands and receptors interact to influence cell division, differentiation and motility. Much evidence supports their importance in causing and sustaining cell transformation in model systems and in human cancer. The exact mechanism by which this is achieved varies in different tumour types and from case to case. The EGF system is a target for new types of targeted chemotherapy. The choice of strategy will depend on the mechanism involved, however, and several approaches are under development or evaluation in clinical trials. Each will have a different spectrum of side effects and the potential for development of drug resistance
Computational and Mathematical Modelling of the EGF Receptor System
No full textThis chapter gives an overview of computational and mathematical modelling of the EGF receptor system. It begins with a survey of motivations for producing such models, then describes the main approaches that are taken to carrying out such modelling, viz. differential equations and individual-based modelling. Finally, a number of projects that applying modelling and simulation techniques to various aspects of the EGF receptor system are described
A new model for ductal carcinoma in situ suggests strategies for treatment
No full textHuman ductal carcinoma in situ (DCIS) of the breast is now diagnosed quite frequently, due largely to the introduction of mammographic screening. It has been shown in a cell culture system that activation of c-erbB-2, but not the epidermal growth factor receptor, results in a DCIS-like phenotype. Since overexpression of c-erbB-2 occurs in 60% of DCIS, this suggests that it could be a target for treatment in this disease
Identification and biological characterization of an epidermal growth factor-related protein: cripto-1
No full textThe complete family of epidermal growth factor receptors and their ligands are co-ordinately expressed in breast cancer
No full textThe levels of expression of the four receptors and eleven ligands composing the Epidermal Growth Factor family were measured using immunohistochemical staining in one hundred cases of breast cancer. All of the family were expressed to some degree in some cases, however individual cases showed a very wide range of expression of the family from essentially none to all the factors at high levels. The highest aggregate level of expression of a receptor was HER2 followed by HER1, then HER3, then HER4. The ligands (including two splice variants of the NRG1 and NRG2 genes) broadly fell into three groups, those with the highest aggregate expression were Epigen, Epiregulin, Neuregulin 1?, Neuregulin 2?, Neuregulin 2?, Neuregulin 4 and TGF?, moderate expression was seen with EGF, Neuregulin 1? and Neuregulin 3, and relatively low levels of expression were seen of HB-EGF, Betacellulin and Amphiregulin. Statistical analysis using Spearman’s Rank Correlation showed a positive correlation of expression between each of the factors. Analysing the data using the Cox Proportional Hazards model showed that, in this data set, the most powerful predictors of relapse free interval and overall survival were the combined measurement of only Epigen and Neuregulin 4
Differential immunohistochemical detection of amphiregulin and cripto in human normal colon and colorectal tumors
No full textExpression of transforming growth factor alpha, amphiregulin and cripto-1 in human breast carcinomas
No full textEGFR signaling in invasion, angiogenesis and metastasis
No full textTumour invasion and metastasis are the hallmarks of advanced stage cancer and are associated with poor patient prognosis. EGFR is overexpressed in a variety of tumour types and this frequently correlates with a more aggressive tumour phenotype. In this chapter, we discuss the cellular and molecular mechanisms by which EGFR contributes to tumour progression and present evidence from experimental and clinical observations that reinforce the notion that EGFR actively contributes to the onset of metastatic disease. EGFR plays a key role in the regulation of processes central to tumour invasion including cell adhesion and motility through its interactions with molecules such as integrins, cadherins, phospholipase Cγ1 and phosphoinositide 3-kinase. In addition, EGFR signaling can contribute to both proteolysis and angiogenesis through up-regulated expression of matrix metalloproteinases (MMPs) and angiogenic cytokines e.g. VEGF-A and IL-8. The significance of these contributions to tumour invasion and metastasis is highlighted by the fact that a mutant, constitutively active receptor (EGFRvIII) associated with human cancers can induce these behaviours when transfected into fibroblasts. Finally, we discuss the use of EGFR antagonists to stem metastatic disease and their potential, in combination with additional novel agents, to improve treatment for cancer patients
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
A monoclonal antibody to the human c-erbB3 protein stimulates the anchorage-independent growth of breast cancer cell lines
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