Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Acquired inherited and/or somatic mutations drive its development. In order to prevent the formation of these mutations, precise and immediate repair of any DNA damage is indispensable. Non-homologous end-joining (NHEJ) is the key mechanism of DNA double-strand break repair. Here, we report that miR-502 targets two components in pancreatic cell lines, Ku70 and XLF of the C-NHEJ. Interestingly, we also observed an attenuated cell cycle response to gamma ionizing radiation (γ-IR) via diminished phosphorylation of checkpoint kinase 1 (Chk1) on serine 345 in these cell lines. Altogether, pancreatic cells showed increased susceptibility to γ-IR via direct inhibition of DNA double-strand break repair and attenuation of the cell cycle response.
Abstract. The article presents the effects of research on models of high density housing. The authors present urban projects for experimental high density housing estates. The design was based on research performed on 38 examples of similar housing in Poland that have been built after 2003. Some of the case studies show extreme density and that inspired the researchers to test individual virtual solutions that would answer the question: How far can we push the limits? The experimental housing projects show strengths and weaknesses of design driven only by such indexes as FAR (floor attenuation ratio -housing density) and DPH (dwellings per hectare). Although such projects are implemented, the authors believe that there are reasons for limits since high index values may be in contradiction to the optimum character of housing environment. Virtual models on virtual plots presented by the authors were oriented toward maximising the DPH index and DAI (dwellings area index) which is very often the main driver for developers. The authors also raise the question of sustainability of such solutions. The research was carried out in the URBAN model research group (Gliwice, Poland) that consists of academic researchers and architecture students. The models reflect architectural and urban regulations that are valid in Poland. Conclusions might be helpful for urban planners, urban designers, developers, architects and architecture students.
Adult stem cells are necessary for self-renewal tissues and regeneration after damage. Especially in the intestine, which self-renews every few days, they play a key role in tissue homeostasis. Therefore, complex regulatory mechanisms are needed to prevent hyperproliferation, which can lead in the worst case to carcinogenesis or under-activation of stem cells, which can result in dysfunctional epithelial. One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway. It is a highly conserved pathway, with β-catenin, a transcription factor, as target protein. Translocation of β-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripo-tency, proliferation, cell differentiation and regulation of cell death. This review presents a brief overview of the Wnt/β-catenin signaling pathway, the regulatory mechanism of this pathway and its role in intestinal homeostasis. Additionally, this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation. Furthermore, the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.
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