Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre-synaptic dopamine, norepinephrine and serotonin transporters (DAT, NET and SERT) terminate synaptic catecholamine transmission through reuptake of released neurotransmitter. Common approaches for studying these transporters involve radiolabeled substrates or inhibitors which, however, have several limitations. In this study we have used a novel neurotransmitter transporter uptake assay kit. The assay employs a fluorescent substrate that mimics the biogenic amine neurotransmitters and is taken up by the cell through the specific transporters, resulting in increased fluorescence intensity. In order to validate the assay, a variety of reference and proprietary neurotransmitter transporter ligands from a number of chemical and pharmacological classes were tested. The ability of these compounds to inhibit the selective transporter-mediated uptake demonstrated a similar rank order of potency and IC(50) values close to those obtained in radiolabeled neurotransmitter uptake assays. The described assay enables monitoring of dynamic transport activity of DAT, NET and SERT and is amenable for high-throughput screening and compound characterization.
...
PMID:Validation of a fluorescence-based high-throughput assay for the measurement of neurotransmitter transporter uptake activity. 1822 6

EGFR represents a promising therapeutic target in urothelial cancer (UC). Our study aimed to investigate the clinicopathological significance of EGFR in upper urinary tract UC. EGFR was immunohistochemically assessed (EGFR pharmDX kit(TM)) in 268 consecutive tumours using a tissue microarray technique and correlated with other histopathological parameters as well as patient outcome. EGFR immunoreactivity was observed in 140/253 (55%) evaluable UCs and was associated with high tumour stage (47% pTa/pT1 vs 66% pT2-pT4; p=0.003) and high tumour grade (45% low grade vs 67% high grade; p<0.001). In addition, EGFR expression was associated with metaplastic squamous and/or glandular differentiation (p<0.001). EGFR staining intensity was 1+ in 49%, 2+ in 31%, and 3+ in 20% of cases. EGFR 3+ staining intensity was associated with the occurrence of metastatic disease by univariate analysis (p=0.016). Multivariate analysis, however, proved only pT stage >1 (p<0.001) and high tumour grade (p<0.001) to be independent predictors of patient outcome. In conclusion, EGFR was significantly associated with advanced disease and metaplastic squamous and/or glandular differentiation. Since UCs with metaplastic morphology have been shown to be more resistant to conventional radiotherapy or chemotherapy, the strikingly strong EGFR expression in these tumours may offer a new perspective for affected patients.
...
PMID:EGFR expression in urothelial carcinoma of the upper urinary tract is associated with disease progression and metaplastic morphology. 1825 77

Microglandular adenosis (MGA) of the breast is widely known as a benign lesion that can mimic invasive carcinoma. In situ and invasive carcinomas have been described as arising in MGA, but which cases of MGA will progress to carcinoma is unclear. Criteria for distinguishing uncomplicated MGA, MGA with atypia (AMGA), and carcinoma arising in MGA (MGACA) are not standardized. The primary objective of this study was to illustrate the clinical, histopathologic, and immunophenotypical characteristics of MGA, AMGA, and MGACA in an effort to provide criteria for distinguishing the 3 types. We retrospectively identified 108 cases seen at M.D. Anderson Cancer Center between 1983 and 2007 that had a diagnosis of MGA. Of the 108 cases, 65 cases had available material for review. Inclusion criteria were glands of MGA expressing S-100 protein and lacking myoepithelial layer (smooth muscle actin negative). Eleven out of 65 cases qualified to have an MGA component; myoepithelial layer was detected in the remaining 54 cases and were classified as adenosis. Out of the 11 MGA patients, there were 3 patients with uncomplicated MGA, 2 had AMGA, and 6 had MGACA. Staining indices for the cell cycle markers p53 and Ki-67 were used to compare the 3 tumor categories. Additional staining for other tumor markers [estrogen and progesterone receptors, HER2, epidermal growth factor receptor (EGFR), c-kit, CK5/6, and CK18] were performed. Patient demographics, tumor radiologic features, and clinical follow-up data were collected for all cases. Multiple invasive histologic components were identified in each of the MGACA cases. All invasive MGACAs had a duct-forming component. In addition, basal-like component was present in 2 cases, aciniclike in 2, matrix producing in 4, sarcomatoid in 1, and adenoid cystic in 1. All tumors had strong and diffuse CK8/18 and EGFR expression but no estrogen receptor, progesterone receptor, HER2 (ie, triple negative), or CK5/6 expression. C-kit was focally expressed in 2 of the MGACAs. Ki-67 and p53 labeling indices was < 3% in all MGAs, 5% to 10% in the AMGAs, and > 30% in MGACAs. In a follow-up ranging from 14 days to 8 years, none of the MGA cases recurred. One of the AMGA cases recurred as invasive carcinoma in a background of AMGA after 8 years following incomplete excision of the lesion. Three out of 6 MGACA cases (50%) required multiple consecutive resections ending up with mastectomy due to involved margins by invasive or in situ carcinoma. Two out of 6 MGACA cases (34%) developed metastasis and died of disease. Our data showed that Ki-67 and p53 expression, in conjunction with the morphologic features, could be a reliable marker to distinguish MGA from AMGA and MGACA. Although 11 tumors were only included in our study, 64% of the tumors were carcinomas arising in MGA. This high incidence of MGACA may not represent the actual frequency of MGAs progressing into carcinoma and is likely due to referral bias in our institution. Nonetheless, the high association of carcinoma with MGA necessitates complete excision of MGA to rule out invasion. Although all the MGACA cases were triple negative and express EGFR (basal-like features), all the cases in our study showed a luminal type of differentiation by CK8/18 expression, indicating that MGACA may not fit well into the current proposed molecular classification of breast cancer.
...
PMID:Clinical, histopathologic, and immunohistochemical features of microglandular adenosis and transition into in situ and invasive carcinoma. 1830 Jul 93

Merkel cell carcinoma is a rare but very aggressive tumor of the skin. With current treatment options, Merkel cell carcinoma is associated with a high incidence of recurrence and metastasis. Targeted anticancer therapies such as receptor tyrosine kinase inhibitors and antisense oligonucleotides have been found to be a promising new type of treatment for various types of cancer. To evaluate whether the use of targeted therapies is a possible treatment option in Merkel cell carcinoma, we determined the expression of the target molecules c-kit, Mcl-1, Bmi-1, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-receptor 2 (VEGF-R2), platelet-derived growth factor (PDGF)-alpha, PDGF-beta, epidermal growth factor receptor (EGFR) and Her-2/Neu in a tissue microarray of 32 samples of 29 patients with Merkel cell carcinoma. C-kit-positive samples were analyzed for mutations in exons 9 and 11. The tissue microarray was stained immunohistochemically with antibodies directed against the above-mentioned proteins, and an immunoreactivity score was calculated. DNA was extracted from c-kit-positive samples and was analyzed for exon 9 and 11 mutations using direct DNA sequencing. We found that c-kit (7%), Mcl-1 (88%), Bmi-1 (78%), VEGF-A (91%), VEGF-C (75%) VEGF-R2 (88%), PDGF-alpha (72%) and PDGF-beta (13%) were expressed in Merkel cell carcinomas. All samples showed a lack of EGFR and Her-2/Neu expression. Analysis of c-kit revealed no mutations. As VEGF-A, VEGF-C, VEGF-R2, PDGFs and c-kit are targets of new cytostatic agents used in the treatment of other cancers, inhibition by a multitargeted chemotherapy could be a very promising treatment option. High expression of Bmi-1 and Mcl-1 warrants further studies on the use of antisense oligonucleotides in Merkel cell carcinoma.
...
PMID:Expression of VEGF-A/C, VEGF-R2, PDGF-alpha/beta, c-kit, EGFR, Her-2/Neu, Mcl-1 and Bmi-1 in Merkel cell carcinoma. 1840 56

The thrombin/proteinase-activated receptors (PARs) have been shown to regulate smooth muscle cell proliferation, migration, and vascular maturation. Thrombin up-regulates expression of several proteins including cyclooxygenase (COX)-2 in vascular smooth muscle cells (VSMCs) and contributes to vascular diseases. However, the mechanisms underlying thrombin-regulated COX-2 expression in VSMCs remain unclear. Western blotting, RT-PCR, and EIA kit analyses showed that thrombin induced the expression of COX-2 mRNA and protein and PGE(2) release in a time-dependent manner, which was attenuated by inhibitors of PKC (GF109203X and rottlerin), c-Src (PP1), EGF receptor (EGFR; AG1478) and MEK1/2 (U0126), or transfection with dominant negative mutants of PKC-delta, c-Src or extracellular regulated kinase (ERK) and ERK1 short hairpin RNA interference (shRNA). These results suggest that transactivation of EGFR participates in COX-2 expression induced by thrombin in VSMCs. Accordingly, thrombin stimulated phosphorylation of ERK1/2 which was attenuated by GF109203X, rottlerin, PP1, GM6001, CRM197, AG1478, or U0126, respectively. Furthermore, this up-regulation of COX-2 mRNA and protein was blocked by selective inhibitors of AP-1 and NF-kappaB, curcumin and helenalin, respectively. Moreover, thrombin-stimulated activation of NF-kappaB, AP-1, and COX-2 promoter activity was blocked by the inhibitors of c-Src, PKC, EGFR, MEK1/2, AP-1 and NF-kappaB, suggesting that thrombin induces COX-2 promoter activity mediated through PKC(delta)/c-Src-dependent EGFR transactivation, MEK-ERK1/2, AP-1, and NF-kappaB. These results demonstrate that in VSMCs, activation of ERK1/2, AP-1 and NF-kappaB pathways was essential for thrombin-induced COX-2 gene expression. Understanding the regulation of COX-2 expression and PGE(2) release by thrombin/PARs system on VSMCs may provide potential therapeutic targets of vascular inflammatory disorders including arteriosclerosis.
...
PMID:PKC-delta/c-Src-mediated EGF receptor transactivation regulates thrombin-induced COX-2 expression and PGE(2) production in rat vascular smooth muscle cells. 1845 14

Amplification of the HER2 gene, mapping to 17q21.1, is present in about 20 % of breast carcinomas. Amplification leads to an overexpression of the protein that made it possible to develop a targeted therapy by the monoclonal antibody trastuzumab (Herceptin). A good response to the treatment requires a stringent assessment of the gene status in tumours; only patients whose tumour shows a high expression of the protein or an amplification of the gene are eligible. Cases with intermediate level expression are checked by in situ hybridization, mainly by FISH, to identify amplifications in this subset of tumours. Results are sometimes difficult to interpret due to the frequent aneuploidy of the tumours. Moreover, copy number cut-offs of the gene for defining an amplification are variable according to the studies. A tumour is considered now as amplified when showing more than six HER2 copies per nucleus, or a ratio HER2 to centromere 17 greater than 2.2. The phenomenon of HER2 amplification in breast cancers is discussed in this paper, and distinguished from gene overrepresentation. It is recommended that tumours showing six to seven copies of HER2 are assessed with a kit including the centromere 17. Clusters of signals are characteristic of amplifications. The process designed for the assessment of HER2 is a model of strategies that will be used for the evaluation of markers involved in future targeted therapies.
...
PMID:[Diagnosis of HER2 gene amplification in breast carcinoma]. 1845 24

To observe the effects of basic fibroblast growth factor (bFGF) on human adenoid cystic carcinoma ACC-2 cell line proliferation and ERK, cyclin D1/p21(waf/cip1) signaling pathways, human adenoid cystic carcinoma cells (ACC-2) were cultured and the influence of bFGF of different concentrations on cell proliferation was determined by MTT. Protein was detected by immuno-precipitation and ERK activity by using ERK agent kit. p-ERK(1/2) and down-stream cyclin D1, p21(waf/cip1) expression were detected by Western blotting and the interfering role of mitogen protein-activated kinase (MEK) suppressor U0126 in the afore-mentioned indicators was examined. MTT demonstrated ACC-2 cell proliferation was substantially enhanced by bFGF, immuno-precipitation displayed ERK activity was up-regulated by bFGF, and immuno-imprinting also showed p-ERK(1/2), cyclin D1 expression was greatly enhanced and p21(waf/cip1) expression was inhibited by bFGF. U0126 suppressed the effect of bFGF. It is concluded that bFGF can promote the proliferation of human adenoid cystic carcinoma ACC-2 cells, and its pathways are associated with the up-regulated activity and expression of p-ERK(1/2), inhibited p21waf/cip1 expression and enhanced cyclin D1 expression.
...
PMID:Effect of exogenous bFGF on the proliferation of human adenoid cystic carcinoma ACC-2 cells. 1848 Oct 5

The expression of c-kit, a protooncogene tyrosine kinase receptor (CD117), in phyllodes tumors of the breast has been the subject of recent investigations. We examined stromal c-kit expression by immunohistochemistry in 68 cases comprising fibroadenomas, fibroadenomas with cellular stroma, and benign, borderline, and malignant phyllodes tumors. Membrane staining was identified in the epithelium of 82% of cases, representing all diagnostic categories in the study. Membrane and cytoplasmic staining was detected in scant cells in the stroma in 74% of the cases in the study, again, across all diagnostic entities. However, when toluidine blue and tryptase staining was performed, the staining pattern matched that of c-kit in the number of cells and their distribution, thereby confirming the presence of mast cells and excluding any appreciable level of true stromal c-kit staining. One borderline and one malignant phyllodes tumor showed a diffuse weak stromal signal, which could not be accounted for by toluidine blue and tryptase. These cases were further tested for the presence of known activating mutations of c-kit and PDGFR-alpha, and yielded negative results. Our findings indicate that c-kit is an unlikely player in the pathogenesis of fibroepithelial lesions of the breast. The positive stromal staining suggested previously by other authors may be attributed to mast cells. C-kit, therefore, has neither a diagnostic nor a prognostic role in phyllodes tumors, and there is no rationale for the treatment of recurrent of malignant phyllodes tumor patients with tyrosine kinase inhibitors.
...
PMID:Expression of c-kit in fibroepithelial lesions of the breast is a mast cell phenomenon. 1850 Feb 66

Cutaneous mastocytosis (CM) in children is a usually benign skin disorder caused by mast cell proliferation. Progressive disease leading to systemic involvement and fatal outcomes has been described. C-kit receptor mutations have been identified as causative for CM, some of which potentially respond to imatinib treatment as described for patients with systemic mastocytosis. We report successful therapy of progressive CM with imatinib in a 23-month-old boy. KIT gene analysis revealed not only a somatic deletion of codon 419 in exon 8 (c.1255_1257delGAC) which responds to imatinib therapy, but also a novel germ line p. Ser840Asn substitution encoded by exon 18 in the c-kit kinase domain. Family history suggests this exchange does not affect receptor function or cause disease. Imatinib therapy was well tolerated, stopped symptoms and disease progression, and appeared to shorten the course of the disease. Imatinib could possibly represent a novel therapeutic option in patients with progressive CM.
...
PMID:Successful treatment of progressive cutaneous mastocytosis with imatinib in a 2-year-old boy carrying a somatic KIT mutation. 1856 37

The rules of diagnostic kit elaboration for genetic typing of microorganisms, designed for epidemiological studies, have been shown in this paper. PCR MP method has been used for diagnostic kit elaboration. Well defined epidemiologically Enterococcus faecium strains have been applied as a research model. The optimisation of the method has been carried out using different amount of reagents and time of the particular stages. Critical parameters, which have significant influence on the quality of obtained results, have been assigned. Optimalised procedure, named PCR MP unique, has been validated for genetic typing of different species of microorganisms and its potential application for routine epidemiological studies. The PCR MP method has been successfully used for elaboration of diagnostic PCR MP unique-KIT, which allows intra-species differentiation of bacterial strains. The PCR MP unique-KIT enables fast, easy and cheap analysis of strains, using elementary laboratory equipment--gradient thermocycler.
...
PMID:[Elaboration of PCR MP diagnostic kit for genetic typing of bacterial strains]. 1881 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---