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  • 1
    Keywords: CELLS ; EXPRESSION ; GROWTH ; tumor ; IN-VIVO ; KINASE ; PATHWAYS ; GENE ; GENES ; PROTEIN ; MICE ; CARCINOGENESIS ; KERATINOCYTES ; SKIN ; PROTEIN-KINASE ; MAP KINASE ; LESIONS ; resistance ; INDUCED APOPTOSIS ; NUMBER ; epidermis ; GROWTH ARREST ; signaling ; RE ; TUMOR-SUPPRESSOR ; TUMORIGENESIS ; SIZE ; ERK ; function ; INVASIVENESS
    Abstract: Extracellular signal-regulated kinases (ERK) regulate cellular functions in response to a variety of external signals. However, the specific functions of individual ERK isoforms are largely unknown. Hence, we have investigated the specific function of ERK1 in skin homeostasis and tumorigenesis in ERK1 knockout mice. They spontaneously develop cutaneous lesions and hyperkeratosis with epidermis thickness. Skin hyperproliferation and inflammation induced by application of 12-O-tetradecanoylphorbol-13-acetate (TPA) is strongly reduced in mutant mice. ERKI-/- mice are resistant to development of skin papillomas induced by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by TPA. Tumor appearance was delayed, their formation was less frequent, and their number and size were reduced. Keratinocytes obtained from knockout mice showed reduced growth and resistance to apoptotic signals, accompanied by an impaired expression of genes implicated in growth control and invasiveness. These results highlight the importance of ERK1 in skin homeostasis and in the process of skin tumor development
    Type of Publication: Journal article published
    PubMed ID: 16510590
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  • 2
    Keywords: CANCER ; MONOCLONAL-ANTIBODY ; ACTIVATION ; IMPACT ; ASSOCIATION ; METASTATIC MELANOMA ; RECURRENCE ; CLINICAL-IMPLICATIONS ; TARGETED THERAPY ; BRAF V600E MUTATION
    Abstract: BACKGROUND: The aim of this study was to compare the detection of BRAF(V600E) by immunohistochemistry (IHC) using a mutation-specific antibody with molecular biology methods for evaluation of papillary thyroid carcinoma (PTC) patients. PATIENTS AND METHODS: This study concerned 198 consecutive conventional PTC patients, of which the majority were women (133/198; 67%), with a mean age of 56 years (range 19-79 years). BRAF mutation analysis was performed using DNA-based (direct sequencing, pyrosequencing, and SNaPshot) and IHC (VE1 antibody) methods. The sensitivity and specificity of IHC for BRAF(V600E) was compared with the molecular biology data. RESULTS: A BRAF mutational result was obtained in 194 cases. A BRAF(V600E) mutation was detected in 153/194 (79%) cases of PTC when using at least one molecular method, and in 151/194 (78%) cases with IHC. No false positive results were noted using IHC to detect the BRAF(V600E) mutation. Besides this mutation, other rare BRAF mutations (BRAF(V600K) and BRAF(K601E)), used as negative controls, were consistently negative with IHC. The sensitivity and specificity of IHC for the detection of this mutation were 98.7% and 100% respectively. The IHC test demonstrated excellent performance at a level equivalent to two DNA-based counterparts (pyrosequencing and SNaPshot). Failure to achieve a result was more frequent with the direct sequencing method than with the three other methods. CONCLUSION: IHC using the VE1 antibody is a specific and sensitive method for the detection of the BRAF(V600E) mutation in PTC. IHC may be an alternative to molecular biology approaches for the routine detection of this mutation in PTC patients.
    Type of Publication: Journal article published
    PubMed ID: 24417277
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  • 3
    ISSN: 1569-8041
    Keywords: breast cancer ; p53 ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There is heterogeneity of methods and conflictingresults concerning the prognostic value of p53 in node-negativebreast cancer. The clinical value of a quantitative method for measuringtumoral p53 content still needs to be evaluated. Patients and methods: A long-term retrospective study wasconducted on 297 node-negative patients with a median follow-up greater than10 years (11 years, 101–172 months). Classic prognostic factors wereconsidered including age, tumor size, histoprognostic grade and estradiol (ER)and progesterone receptors (PR). In addition, the value of p53 determination (immunoluminometric assay in tumor cytosol) was assessed forthis long follow-up period. Results: p53 concentrations were significantly linked tothe histological grade (P = 0.001), to tumor size (P = 0.02)and ER status (P = 0.01). Higher p53 tumoral concentrationswere found in tumors with large size, pejorative histological grade andnegative ER status. In contrast, p53 tumoral concentrations were notinfluenced by menopausal or PR status. Multivariate Cox analysis demonstratesthat tumor size was the only significant predictor of disease-free survival(P = 0.049) with a risk factor at 1.38. As regards specific survival,univariate Cox analysis indicates that p53 taken as a continuousvariable is a significant predictor (P = 0.024) together withhistological grade, tumor size and ER status. In a multivariate Cox analysisthere were two significant and independent variables for predicting overallsurvival: tumor size (P = 0.031) and ER status (P = 0.015)with the highest risk factor (RR = 2.14). Conclusions:The present investigation points out that theprognostic power of p53 tumor determination evaluated at more than10 years median survival is not higher than the well-recognized classicprognostic factors in node-negative breast cancer. The present data highlightthe need to assess the prognostic value of potentially new biological factorsin node-negative breast cancer on cohorts of patients followed over periodsin excess of 10 years.
    Type of Medium: Electronic Resource
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