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)

Overexpression of epidermal growth factor (EGF) receptor and HER2 (p185neu) may both contribute to the growth of human cancers. A humanized anti-HER2 monoclonal antibody (mAb) 4D5 and a human-mouse chimeric anti-EGF receptor mAb C225 are currently being investigated in clinical trials for their anti-tumor activities. In the present study, we have examined the effect of concurrent treatment of OVCA 420 human ovarian cancer cells with mAb C225 and mAb 4D5. Exposure of OVCA420 cells to saturating concentrations of C225 (20 nM) for 7 days resulted in 40-50% growth inhibition, and exposure to 20 nM mAb 4D5 also resulted in 30-40% growth inhibition. The growth inhibition of OVCA420 cells by mAb C225 or 4D5 was associated with an increased G1 cell population; an increased level of a cyclin-dependent kinase (CDK) inhibitor p27Kip1 with increased association of p27kip1 with CDK2, CDK4 and CDK6; and decreased activities of these CDKs. Combination treatment with concurrent exposure to mAbs C225 and 4D5 resulted in additive anti-proliferative effects on these cells, which was accompanied by enhanced G1 cell distribution, a greater increase in the levels of p27Kip1 and a greater decrease in the activities of CDK kinases. The anti-proliferative effects and related changes in cell cycle regulators induced by mAb 4D5, mAb C225 or the combination of the two mAbs could be reversed by concurrent exposure to exogenous EGF. Our data suggest the potential fruitful cooperation of anti-EGF receptor mAb and anti-HER2 mAb in the treatment of human cancers stimulated by EGF receptor and HER2 signals.
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PMID:Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a human-mouse chimeric anti-EGF receptor mAb C225. 998 23

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for better prognostic markers to identify those subsets of patients who would benefit from more aggressive therapy because their tumors show an increased risk of poor clinical behavior. p27kip1 is an important inhibitor of the cell cycle that acts by binding and inactivating cyclin-dependent kinases (CDKs). The aim of this study was to determine the prognostic value of loss of p27 protein in invasive breast cancer. We performed an immunohistochemical study of 147 patients with T1 and T2 invasive breast cancers and compared survival in the high p27 expressing group with that of the low p27 expressing group. On univariate analysis comparing tumor size, nodal status, Ki-67, c-erbB-2, p53 and estrogen receptor, low or absent p27kip1 is a strong predictor of reduced disease-free survival. Importantly, on multivariate analysis, the combined effect of low p27 with high Ki-67 is a stronger predictor of reduced disease-free survival than either marker alone. This simple, reliable and inexpensive assay, particularly when used in combination with Ki-67, improves the ability to predict disease recurrence and could become a useful adjunct of breast cancer evaluation to better identify high risk patients.
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PMID:Low levels of cell cycle inhibitor p27kip1 combined with high levels of Ki-67 predict shortened disease-free survival in T1 and T2 invasive breast carcinomas. 1111 34

The predictivity of tumour size, oestrogen (ER) and progesterone (PgR) receptors, 3H-thymidine labelling index (TLI), c-erbB-2 and p27kip1 expression on clinical outcome was analysed on a consecutive series of 118 postmenopausal patients with ER-positive, node-positive tumours. All patients were treated with surgery +/- radiotherapy and adjuvant tamoxifen (30 mg/day) for at least 2 years. TLI, ER, c-erbB-2 and p27kip1 were generally unrelated to each other. PgR was directly related to ER and inversely to c-erbB-2. Tumour size was inversely related to both c-erbB-2 and p27kip1 expression. At a median follow-up of 75 months, 5-year relapse-free survival was significantly lower for patients with very rapidly proliferating (HR = 2.61, 95% CI = 1.34-5.08), PgR negative (HR = 2.76, 95% CI = 1.43-5.33) or relatively low ER content (HR = 2.20, 95% CI = 1.14-4.25) tumours than for patients with tumours expressing the opposite biological profiles. Overall survival was also significantly different as a function of TLI (HR = 3.47, 95% CI = 1.52-7.93) and PgR (HR = 2.27, 95% CI = 1.00-5.15). TLI and PgR maintained an independent relevance in multivariate analysis and together were capable of identifying subgroups of patients at significantly different risk of relapse and death.
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PMID:Biomarker prediction of clinical outcome in operable breast cancer patients treated with tamoxifen. 1168 13