Authors
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Franiak-Pietryga, I. ; Ziólkowska, E. ; Ziemba, B. ; Appelhans, D. ; Voit, B. ; Kaczmarek, A. ; Robak, T. ; Klajnert-Maculewicz, B. ; Cebula-Obrzut, B. ; Smolewski, P. ; Borowiec, M. ; Bryszewska, M.
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Title
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Glycodendrimer PPI as a potential drug in chronic lymphocytic leukemia. The influence of glycodendrimer on apoptosis in in vitro B-CLL cells defined by microarrays
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Date
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01.01.2017
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Number
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51964
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Abstract
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Chronic lymphocytic leukemia (CLL) cells are characterized by failures in the apoptosis pathway and increased proliferation, resulting in the progressive accumulation of B-lymphocytes in blood. Despite the wide range of antileukemic drugs, CLL remains an incurable disease. However, a breakthrough is expected which will allow more effective treatment. The study investigates the influence of poly(propylene)imine (PPI) dendrimer on peripheral amino groups, 30% of which were coated with maltotriose (PPI-G4-OS-Mal-III), on CLL cells, and demonstrates that it acts through the induction of the apoptotic mechanism. CLL and normal lymphocytes were treated with the dendrimer, either alone or in combination with fludarabine (FA). The results confirm that PPI-G4-OS-Mal-III influences the viability of CLL cells in vitro and does not exert any significant harmful effect on normal lymphocytes. It is important to note that the dendrimer was used as a drug itself and not as a drug carrier. The percentages of apoptotic and necrotic cells, and the protein expression, were checked using a flow cytometer. Gene expression was screened using a two-colour microarray with 60-mer probes. The dendrimer appears to significantly influence gene and protein expression in CLL cells. Since dendrimers can be specifically targeted, they may be very effective in CLL therapy, especially since in vitro PPI-G4-OS-Mal-III has been found to have stronger effect than fludarabine.
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Publisher
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Anti-Cancer Agents in Medicinal Chemistry
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Wikidata
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Citation
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Anti-Cancer Agents in Medicinal Chemistry 17 (2017) 102-114
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DOI
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http://www.ingentaconnect.com/content/ben/acamc/2017/00000017/00000001/art00015
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Tags
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apoptosis chronic lymphocytic leukemia (cll) dendrimers gene expression glycodendrimers poly(propylene imine) (ppi) protein expression toxicity.
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