Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptide growth factors are proteins that stimulate cellular proliferation by binding to specific cell membrane receptors. Evidence is accumulating that abnormal regulation of growth factors may contribute to carcinogenesis. The epithelial growth factors, EGF and TGF-alpha, which share the same receptor, EGFR, may play a pivotal role in the development and maintenance of head and neck cancer; preliminary studies concerning TGF-beta and IL-2 are inconclusive. There is increased production of TGF-alpha and EGFR mRNA in the majority of fresh tissues and cell lines from patients with SCCHN. This increase results from transcriptional activation of the gene(s). Therapies directed at the regulation of gene transcription may be useful in chemoprevention or modulation of disease. Nuclear studies that target up-regulated growth factor receptors may improve the ability to detect microscopic regional metastatic disease.
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PMID:The role of peptide growth factors in head and neck carcinoma. 140 94

Epidermal growth factor (EGF) stimulates the growth of several types of epithelial tissues and possesses a strong mitogenic activity that is mediated through its cell surface receptor (EGFR). The aim of this study was to characterize EGFR and measure its levels in head and neck tumors biopsies (70 patients); use of a simplified competition technique with a radiolabeled ligand allowed evaluation of functional EGFR. Five samples (4 tumors and 1 control) were used to characterize EGF binding. Graphic representation identified a single family of binding sites. Kd values revealed high affinity for EGF binding: mean Kd, 0.156 +/- 0.108 nM (0.095-0.347 nM). EGF-binding characteristics (Kd) were similar in nontumoral tissue samples (controls) and in tumor material. In 59 of 60 cases, EGFR levels were higher in the tumor than in the corresponding controls. A significant correlation was found between EGFR levels and tumor size and stage. Controls exhibited a trend toward higher EGFR levels in elevated sizes and stages. According to a cutoff EGFR value of 100 fmol/mg protein, which separated all controls from tumors, EGFR-positive tumors (greater than 100 fmol/mg protein) had a greater probability of complete response to chemotherapy than EGFR-negative tumors; other tumor characteristics, such as the degree of tumoral differentiation, tumor size, or stage, were unable to operate such a discrimination in the response to chemotherapy. EGFR may thus be an interesting biological marker for head and neck cancer.
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PMID:Characterization, quantification, and potential clinical value of the epidermal growth factor receptor in head and neck squamous cell carcinomas. 202 78

EGFR was determined, before treatment; in tumors biopsies obtained from 109 consecutive patients with head and neck cancer (100 men and nine women), using iodine labelled recombinant EGF. The median age of the study population was 60 years. EGFR levels varied from 2 to 2302 fmol/mg membrane protein (median 71). There was a significant difference of distribution for EGFR levels between stages I and II tumors and stages III and IV tumors (P = 0.03). The EGFR cut-off value for overall survival was 120 fmol/mg protein and the median follow-up was 18 months (3-35) EGFR overexpression was associated with shorter relapse-free (P = 0.0125) and overall survival (P = 0.028). By multivariate analysis the only significant variables were EGFR for relapse-free survival and tumor staging and EGFR for overall survival. Analyzed in 60 patients treated by first-line chemotherapy CDDP-5FU, the longest survival was achieved for patients who had a complete response to chemotherapy and the lowest EGFR levels (P = 0.018). EGFR expression in the primary tumor allows survival among first line chemotherapy responder categories to be discriminated.
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PMID:[EGF receptor, a prognostic factor in epidermoid cancers of the upper aerodigestive tracts]. 774 4

Cancer has been defined as a fundamental disorder of cellular growth control. Which arises in some cells through changes in genes (DNA-level: geneamplification, mutation and rearrangement) or their expression (RNA- and protein-level), and gives these cells a growth advantage in comparison to the surrounding cells. Since the last decade we know the identity of these genes and the nature of the changes they underwent in the cancer cell. Only a few of the known oncogenes play a role in head and neck cancer. These are the EGFR (epidermal growth factor receptor), c-myc, the ras gene family, int-2, hst- 1 and bcl- 1. In some clinical disorders, like childhood neuroblastoma and breast cancer, oncogenes play already an important role in tumor staging as well as a prognostic parameter. The aim for the future is the therapeutic application of oncogenes better known as gene therapy.
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PMID:Oncogenes related to head and neck cancer. 813 94

The significance of prognostic factors that may predict the clinical outcome of patients with head and neck cancer was discussed. Many indicators can be grouped into three categories, patient factors, tumor factors and treatment factors. The most significant indicator of prognosis seems to be pathological nodal stage. Factors such as clinical stage, resectability, and depth of invasion may also affect the patient outcome. Recent research development has revealed biological phenotypes of cancer cells to predict the effect of cancer treatment and the clinical course in head and neck cancer. Possible predictive indicators include DNA ploidy, Tpot, EGFR and cyclin D1. C erbB2 and p53 may not predict the survival of patients with head and neck cancer.
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PMID:[Clinico-pathological predictive indicators in squamous cell carcinoma of the head and neck]. 871 16

The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations) and tumor suppressor gene inactivation (loss of function mutations), leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC) development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.
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PMID:Genetic alterations in head and neck squamous cell carcinomas. 1045 50

Transactivation of the epidermal growth factor receptor (EGFR) represents the paradigm for cross-talk between G protein-coupled receptors (GPCRs) and receptor tyrosine kinase signaling pathways. In a variety of squamous cell carcinoma cell lines of the head and neck (HNSCCs), we found that treatment with the GPCR agonists lysophosphatidic acid (LPA), bradykinin, thrombin, and carbachol results in rapid tyrosine phosphorylation of the EGFR. In these tumor cells, signal transactivation of the EGFR and the oncoprotein HER2/neu is critically dependent on metalloprotease activity. Using the metalloprotease inhibitor batimastat, the EGFR-specific tyrphostin AG1478, and a dominant-negative EGFR mutant, we show that in HNSCC cell lines, EGFR tyrosine phosphorylation, recruitment of the adaptor proteins SHC and Gab1, and activation of the ERK/mitogen-activated protein kinase pathway in response to LPA depend both on metalloprotease function and EGFR tyrosine kinase activity. Most importantly, critical characteristics of HNSCC cell lines such as DNA synthesis, cell cycle progression and tumor cell migration are stimulated by LPA and can be abrogated by interfering with EGFR signal transmission. Together, our results demonstrate the importance of a mechanism that promotes head and neck cancer cell proliferation and motility by GPCR ligands involving EGFR transactivation. Our findings suggest that highly abundant GPCR ligands such as LPA may function as tumor promoters and determinants of HNSCC progression.
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PMID:Lysophosphatidic acid-induced squamous cell carcinoma cell proliferation and motility involves epidermal growth factor receptor signal transactivation. 1241 65

Growing evidence suggests that epidermal growth factor family receptors (HERs) play a significant role in radiation response. EGFR expression levels and activation by ligand correlate with radioresistance, and exogenous HER2 expression alters radiation response. Preclinical studies of anti-EGFR anti-HER2 antibodies, and kinase inhibitors that inhibit EGFR, both EGFR and HER2, or all 4 family members show potential for clinical radiosensitization. Early-phase clinical trials of the anti-EGFR antibody, C225, prove the combination of C225 and radiotherapy to be well tolerated and promising. A phase 3 randomized trial in head and neck cancer is underway, and clinical investigation of other HER inhibitors is in progress. The mechanisms(s) of radiation response modulation by HERs appear complex and diverse. Signal transduction initiated by receptor activation promotes survival and proliferation after ionizing radiation, and HER inhibitors affect cellular responses to ionizing radiation (IR) in diverse ways, including inducing apoptosis, cell cycle arrest, and impeding DNA repair. HER signaling and inhibition also affect tumor-stroma interactions, particularly angiogenesis and endothelial survival after IR. Further investigation of the radiation response modulation by EGFR family members and their inhibitors will lead to optimization of this promising therapeutic approach.
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PMID:Epidermal growth factor family receptors and inhibitors: radiation response modulators. 1252 Apr 61

Mouse, chimeric, humanized and human monoclonal antibodies (MABs) are all in use for treatment of human cancer. Unconjugated antibodies have a complex mechanism of action, dependent on the nature of the target structure. Antibodies can activate the immune system (antibody-dependent cellular cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC], induction of tumor immunity [idiotype network]). ADCC appears to be one of the most important immune effector functions. Antibodies may also induce apoptosis, cell cycle arrest, inhibition of cell proliferation as well as angiogenesis and metastatic spread. For most antibodies there is no clear dose-response relationship in vivo. The effect of antibodies can be enhanced by combination with chemotherapy and/or by agents which activate the immune system. The best therapeutic effect may be obtained if MABs are used early in the course of the disease. Rituximab (anti-CD20) was the first registered MAB for the therapy of follicular lymphoma. Impressive results have been seen in combination with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) in follicular and high-grade lymphomas. In other non-Hodgkin's lymphoma subtypes, promising results are also seen in combination with chemotherapy. Trastuzumab (anti-Her2) is a breakthrough in the treatment of breast cancer in combination with chemotherapeutic agents. This antibody is also in clinical testing for adjuvant treatment. Alemtuzumab (anti-CD52) has shown impressive results both in refractory chronic lymphocytic leukemia and as up-front therapy. There are many other antibodies in late stages of testing for registration. Interesting MABs include cetuximab (anti-epidermal growth factor receptor [EGFR]), especially in combination with radiotherapy in head and neck cancer; ABX-EGF (anti-EGFR) in renal carcinoma; bevacizumab (anti-vascular endothelial growth factor) in several solid tumors. Antiepithelial cell adhesion molecule antibodies show promise in combination with chemotherapy in the adjuvant setting of colorectal carcinoma. It is estimated that about 20 antibodies will be in clinical use by the year 2010.
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PMID:Monoclonal antibodies in human cancer. 1498 43

Inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) activity have shown promise as novel anticancer agents in a variety of common solid tumors. In preclinical studies and phase I trials, tumor responses to EGFR-TK inhibitors (EGFR-TKIs), such as gefitinib (Iressa, AstraZeneca Pharmaceuticals LP, Wilmington, DE) and erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY, and Genentech, Inc., South San Francisco, CA) were observed in heavily pretreated patients with advanced non-small cell lung cancer (NSCLC), head and neck cancer, breast cancer, colorectal cancer, and other solid tumors. Subsequent phase II studies resulted in tumor responses, disease stabilization, symptom improvement, and improved quality of life in patients with advanced NSCLC who had received prior platinum-based chemotherapy or platinum and docetaxel chemotherapies. Side effects related to treatment with EGFR-TKIs were generally mild, reversible, and noncumulative. Severity and frequency of drug-related adverse events were related directly to dose. The potential role of EGFR-TKIs in treating other solid tumors currently is being studied. Furthermore, research is being conducted to explore the potential use of EGFR-TKIs in novel combinations with chemotherapy, radiation therapy, endocrine therapy, and other molecular targeted therapies.
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PMID:Epidermal growth factor receptor tyrosine kinase inhibitors: evolving role in the treatment of solid tumors. 1510 18


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