Science.gov (United States)

We have constructed a 27-kDa hTERT C-terminal polypeptide (hTERTC27) devoid of domains required for telomerase activity and demonstrated that it is capable of nuclear translocation/telomere-end targeting. Here we showed that expression of a low level of hTERTC27 renders hTERT positive HeLa cells sensitive to H(2)O(2)-induced oxidative stress and subsequent cell senescence. The senescence-associated gene, the cyclin/cdk inhibitor p21(Waf1), was up-regulated. This occurs without changing the expression of endogenous hTERT, causing significant telomere shortening or inhibiting telomerase activity. Results from this study suggest for the first time that in addition to telomerase activity, the C-terminus of hTERT also plays a role in hTERT-mediated cellular resistance to oxidative stress. PMID:12565825

UK PubMed Central (United Kingdom)

Binding of epidermal growth factor (EGF) to the EGF receptor (EGFR) initiates signal transduction, ultimately leading to altered gene expression. Ligand-activated EGFR is also rapidly internalized...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundPolymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung...Full Text Available

International Nuclear Information System (INIS)

Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, ...

British Library Electronic Table of Contents (United Kingdom)

A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.

UK PubMed Central (United Kingdom)

Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand...Full Text Available

International Nuclear Information System (INIS)

Differentiated thyroid cancer (DTC) has variable degree of F-18 FDG avidity. The purpose of this study was to evaluate the relationship between F-18 FDG uptake and pathological or immunohistochemical features of DTC. DTC patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included in the study. Maximum standardized uptake values (SUVmax) of primary tumor were calculated. If the primary tumor showed no perceptibly increased F-18 FDG uptake, region of interest was drawn based on finding of CT portion of the PET/CT images. Pathological and immunohistochemical markers such as presence of lymph node (LN) metastasis and underlying thyroiditis, tumor size, Ki-67 labeling index, expressions of EGFR, COX-2, and Galectin-3 were evaluated. Total of 106 patients was included (102 papillary carcinomas, 4 follicular carcinomas). The mean SUVmax of the large tumors (above 1 cm) was significantly higher than the mean SUVmax of small (equal to or less ...

British Library Electronic Table of Contents (United Kingdom)

Sphere-forming abilities in culture condition are considered a hallmark of cancer stem-like cells, which represents tumor cell invasiveness and stem-like characteristics. We aimed to show that the sphere-forming subpopulation of human malignant melanoma cell line WM-266-4 acts differently to zebrafish embryo extracts compared with their bulk counterpart. Spheres were maintained in neural stem cell culture conditions. The embryos of zebrafish at specific developmental stages were collected and the extracts were purified under 100 kDa. Spheres were treated with embyo extracts and proliferation assay and immunocytochemistry were conducted. Spheroid cells expressed nestin and epidermal growth factor receptor (EGFR) but not melanoma antigen recognized by T-cells (MART)1, indicating their stem-l...

British Library Electronic Table of Contents (United Kingdom)

Zusammenfassung Das Lungenkarzinom ist eine der h?ufigsten Krebserkrankungen und die h?ufigste Krebstodesursache. Mit der Einf?hrung innovativer Substanzen ist die M?glichkeit einer individualisierten Therapie gegeben, die eine Verbesserung von Prognose und Lebensqualit?t verspricht. Die Wirksamkeit dieser Therapeutika basiert auf spezifischen molekularen Eigenschaften des Lungenkarzinoms und stellt neue Anforderungen an die pathohistologische Diagnostik. Neben dem Histotyp haben sich molekulare Alterationen, insbesondere EGFR-Mutationen, als pr?diktive Marker erwiesen. Die histologische Typisierung umfasst daher nicht nur die Unterscheidung von SCLC und NSCLC, sondern die Subtypisierung der NSCLC unter Einbezug immunhistologischer und molekularer Untersuchungen. Zusammenfassend werden Kri...

Energy Technology Data Exchange (ETDEWEB)

Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic ...

International Nuclear Information System (INIS)

Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly ...