Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of EGF receptors has been studied on luminal and basal cells of human breast in vitro. Primary cultures of normal adult human breast epithelium were prepared as single cell suspensions containing a mixture of luminal and basal cells. The cells were simultaneously immunolabelled with antibodies recognising EMA (luminal epithelial cells), CALLA/CD10 (basal cells) and the epidermal growth factor receptor (EGFR). Flow cytometric analysis of these triple labelled cells detected low levels of EGFR on both cell types, with proportionally more EGFR on basal cells compared with luminal cells. Separated populations of basal and luminal cells were prepared from single cell suspensions by flow sorting or by immunomagnetic methods and cultured with and without EGF. Increased proliferation was detected in both cell types in the presence of EGF. To determine the localisation of the EGF receptor, purified cell populations were immunolabelled with anti-EGFR antibody and an FITC-labelled second antibody for fluorescence light microscopy and colloidal gold-labelled antibody for scanning electron microscopy (SEM). Low levels of EGFR were detected by indirect immunofluorescence on both cell types with higher levels on basal cells compared with luminal cells. The detailed subcellular distribution of the receptor was examined by SEM, with gold-labelling of EGFR detected using a field emission scanning electron microscope with a YAG crystal backscattered electron detector. Both luminal and basal cells expressed EGFR over the upper surface of individual cells when these were growing in isolation, but when cells formed part of a confluent island, levels of EGFR on the upper surface of cells were obviously reduced. Observations made by SEM on cells at the edges of such confluent islands showed that cultured basal cells expressed much higher levels of EGFR on their basal, as compared with their upper surfaces.
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PMID:Epidermal growth factor receptor expression on human breast luminal and basal cells in vitro. 868 18

Cetuximab is a chimeric human-mouse anti-EGF receptor monoclonal antibody. In Phase I studies, no dose-limiting toxicities were observed with cetuximab as a single agent or combined with chemotherapy; pharmacokinetic and pharmacodynamic analyses supported 250 mg/m(2) weekly administration. Skin toxicity, diarrhea and fatigue were the most common toxicities. The positive results obtained in Phase II trials in patients with advanced non-small-cell lung cancer prompted two randomized Phase III trials evaluating cetuximab in addition to first-line chemotherapy. Both trials showed a small benefit in overall survival for the experimental treatment, which was considered insufficient by the EMA for marketing approval. However, a subgroup analysis of the FLEX Phase III trial recently demonstrated a larger survival benefit from the experimental treatment in patients with high immunohistochemical EGF receptor expression. This finding, if confirmed prospectively, could represent a new opportunity for positioning cetuximab into the standard treatment of advanced non-small-cell lung carcinoma.
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PMID:Cetuximab in non-small-cell lung cancer. 2231 64

Panitumumab is a fully human, monoclonal antibody targeting the EGF receptor with proven clinical activity in KRAS wild-type metastatic colorectal carcinoma. Treatment with panitumumab has been shown to significantly improve response rate and progression-free survival in this subgroup of patients, with a manageable toxicity profile. Panitumumab's first worldwide indication was as a single agent in chemorefractory patients. Recently, the EMA approved its use as part of a chemotherapy regimen in first- and second-line settings, following the encouraging results of large randomized Phase III trials. In order to identify patients with higher chances of benefiting from the treatment, additional molecular aberrations in the EGF receptor signaling pathway are being investigated as predictive biomarkers. In this article we review 10 years of drug development, focusing on the clinical evidence for panitumumab's indication in metastatic colorectal cancer and future strategies of investigation.
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PMID:Panitumumab: a summary of clinical development in colorectal cancer and future directions. 2251 40