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)

Two types of gastric adenocarcinoma can be distinguished histopathologically: the diffuse and the intestinal type. Molecular pathology supports this theory by showing differences in the genetic pathways of both tumor types. In addition to known pathomorphological factors of prognosis, e.g., depth of tumor infiltration, number of lymph node metastases and resection margins, a few genes have been suggested to have prognostic impact in gastric carcinoma. Clinically relevant molecules whose expression or structure is altered include the plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1), the cell cycle regulator cyclin E, epidermal growth factor (EGF), the apoptosis inhibitor bcl-2, the cell adhesion molecule E-cadherin, and the multifunctional protein beta-catenin. Gene amplification and protein overexpression of the growth factor receptors c-erbB-2 and K-sam may be prognostic factors for intestinal-type and diffuse-type gastric cancer, respectively. In addition, genetic instability is commonly seen. There has long been evidence for a genetic predisposition to gastric cancer by epidemiological studies and case reports. Very recently, germ line mutations of E-cadherin have been identified that are responsible for a dominantly inherited form of diffuse-type gastric cancer and could be used to identify individuals that are at high risk.
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PMID:Gastric adenocarcinoma: pathomorphology and molecular pathology. 1131 54

In order to make optimal treatment recommendations for patients with early-stage breast cancer, it is essential to accurately determine the patient's underlying risk of disease recurrence and choose a therapy to which the individual is most likely to respond. Lymph node status, tumor size, histopathologic features including tumor type and grade, and hormone receptor status are well-accepted prognostic factors related to breast cancer. In addition, hormone receptor status is a very strong predictor of response to hormonal therapy. However, our currently accepted prognostic and predictive factors fall short and there is a critical need to more accurately identify those most likely to require or benefit from particular therapies. Attention has therefore focused on the determination of novel prognostic and predictive factors. The most promising new factor is the level of urokinase plasminogen activator and its inhibitor plasminogen activator inhibitor. Other putative factors include proliferative rate, the presence of lymphatic or vascular invasion, human epidermal growth factor receptor 2 (HER-2/neu or erbB-2) positivity, the presence of micrometastases in lymph nodes or bone marrow, and gene expression profile by microarray analysis, and by RNA-based methodology. Data regarding potential new prognostic factors are constantly emerging. These studies are frequently challenging to interpret as they are often retrospective, based on relatively small numbers of patients, include a mix of treated and untreated women, and often do not control for other known prognostic factors. Therefore, new data must be interpreted with caution.
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PMID:Utilizing prognostic and predictive factors in breast cancer. 1571 96

The phenotypic switching called epithelial-to-mesenchymal transition is frequently associated with epithelial tumor cell progression from a comparatively benign to an aggressive, invasive malignancy. Coincident with the emergence of such cellular plasticity is an altered response to transforming growth factor-beta (TGF-beta) as well as epidermal growth factor (EGF) receptor amplification. TGF-beta in the tumor microenvironment promotes invasive traits largely through reprogramming gene expression, which paradoxically supports matrix-disruptive as well as stabilizing processes. ras-transformed HaCaT II-4 keratinocytes undergo phenotypic changes typical of epithelial-to-mesenchymal transition, acquire a collagenolytic phenotype, and effectively invade collagen type 1 gels as a consequence of TGF-beta1 + EGF stimulation in a three-dimensional physiologically relevant model system that monitors collagen remodeling. Enhanced collagen degradation was coupled to a significant increase in matrix metalloproteinase (MMP)-10 expression and involved a proteolytic axis composed of plasmin, MMP-10, and MMP-1. Neutralization of any one component in this cascade inhibited collagen gel lysis. Similarly, addition of plasminogen activator inhibitor type 1 (SERPINE1) blocked collagen degradation as well as the conversion of both proMMP-10 and proMMP-1 to their catalytically active forms. This study therefore identifies an important mechanism in TGF-beta1 + EGF-initiated collagen remodeling by transformed human keratinocytes and proposes a crucial upstream role for plasminogen activator inhibitor type 1-dependent regulation in this event.
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PMID:TGF-beta1 + EGF-initiated invasive potential in transformed human keratinocytes is coupled to a plasmin/MMP-10/MMP-1-dependent collagen remodeling axis: role for PAI-1. 1938 99

Age-dependent angiogenesis intensity changes have been studied in transgenic HER-2/neu (FBV/N) mice characteristic of breast tumors' high incidence with hyperexpression of HER-2/neu. Concentration of vascular endothelial growth factor, insulin-dependent growth factor 1, nitrogen monoxide, tissue plasminogen activator and type 1 plasminogen activator inhibitor were assessed by means of immune-enzyme assay. The results testify to angiogenesis processes activation side by side with aging and growth of the tumors. Maximum manifestation of these disturbances (growth factors' blood concentrations increase and endotheliocytes' functional activity inhibition) has been revealed in 6-month-old mice during neoplasma maximum intensive and aggressive growth period.
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PMID:[Age dynamics of angiogenesis markers in transgenic HER-2/neu (FBV/N) mammary adenocarcinoma-prone mice]. 2657 37