Search results for "kinase inhibitor"
showing 10 items of 414 documents
Restoration of Raf-1 Kinase Inhibitor Protein levels as a possible therapeutic approach in hepatocellular carcinoma.
2011
p27Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells
2015
Nuclear DNA duplication in the absence of cell division (i.e. endoreplication) leads to somatic polyploidy in eukaryotic cells. In contrast to some invertebrate neurons, whose nuclei may contain up to 200,000-fold the normal haploid DNA amount (C), polyploid neurons in higher vertebrates show only 4C DNA content. To explore the mechanism that prevents extra rounds of DNA synthesis in these latter cells we focused on the chick retina, where a population of tetraploid retinal ganglion cells (RGCs) has been described. We show that differentiating chick RGCs that express the neurotrophic receptors p75 and TrkB while lacking retinoblastoma protein, a feature of tetraploid RGCs, also express p27K…
Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study
2022
[Purpose] The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9–mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort.
Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study
2021
<b><i>Introduction:</i></b> In the REFLECT trial, lenvatinib was found to be noninferior compared to sorafenib in terms of overall survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world and identify clinical factors that could be significantly associated with survival outcomes. <b><i>Methods:</i></b> The study population was derived from retrospectively collected data of HCC patients treated with lenvatinib. The overall cohort included western and eastern populations from 23 center in five countries. <b><i>Results:</i></b> We included 1,325 patients with HCC …
Raloxifene increases proliferation of human endothelial cells in association with increased gene expression of cyclins A and B1.
2006
Objective To examine the proliferative effect of of raloxifene on human umbilical-vein endothelial cells (HUVECs), and to investigate whether there is an associated increased expression of some key regulators of the cell cycle. Design Cell culture for different incubation times. Setting University research laboratory. Patient(s) Sources of HUVECs. Intervention(s) Measurement of cell proliferation, of protein levels of cyclin A, cyclin B1, cyclin D1, cyclin-dependent protein kinase (CDK) 2, CDK4, and p27 Kip1 , and of messenger RNA expression of cyclin A, cyclin B1, and p27 Kip1 . Main Outcome Measure(s) Cell proliferation was measured by the 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazol…
DNA damage causes TP53-dependent coupling of self-renewal and senescence pathways in embryonal carcinoma cells.
2013
Recent studies have highlighted an apparently paradoxical link between self-renewal and senescence triggered by DNA damage in certain cell types. In addition, the finding that TP53 can suppress senescence has caused a re-evaluation of its functional role in regulating these outcomes. To investigate these phenomena and their relationship to pluripotency and senescence, we examined the response of the TP53-competent embryonal carcinoma (EC) cell line PA-1 to etoposide-induced DNA damage. Nuclear POU5F1/OCT4A and P21CIP1 were upregulated in the same cells following etoposide-induced G 2M arrest. However, while accumulating in the karyosol, the amount of OCT4A was reduced in the chromatin fract…
Regulation of the p19(Arf)/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice.
2015
Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1-NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age-related changes in B1-NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence-accelerated-prone mice (SAMP8) relative to senescence-accelerated-resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the stud…
Attenuation of NF-κB Signaling Response to UVB Light during Cellular Senescence
1999
The ability of cells to adapt to environmental stresses undergoes a progressive reduction during aging. NF-kappaB-mediated signaling is a major defensive system against various environmental challenges. The aim of this study was to find out whether replicative senescence affects the response of the NF-kappaB signaling pathway to UVB light in human WI-38 and IMR-90 fibroblasts. The exposure of early passage fibroblasts to UVB light inhibited the proliferation and induced a flat phenotype similar to that observed in replicatively senescent fibroblasts not exposed to UVB light. The UVB radiation dose used (153 mJ/cm2) did not induce apoptosis in either early or late passage WI-38 fibroblasts. …
An immunohistochemical study of the distribution of p 16 protein in oral mucosa in smokers, non-smokers and in frictional keratosis
2009
Objective: Our study aimed to characterize alteration in the immunohistochemical p16 expression in normal oral mucosa and non-neoplastic hyperproliferative disorders (i.e. frictional keratosis and mucosa from smokers). Study design: 43 specimen of oral mucosa were examined using immunohistochemistry. Results: In normal mucosa, there was strong positive nuclear staining in a proportion of fibroblasts and endothelial cells in the lamina propria, with variable expression in nuclei of the epithelial layer. However, when the patient?s tobacco smoking was examined, p16 nuclear staining in oral epithelium was seen in 4/20 (20%) of smokers and 0/23 (0%) of non-smokers. In every case of frictional k…
The development of benzimidazoles as selective rho kinase inhibitors
2010
Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC(50)<10nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA).