title: PPI-G4 Glycodendrimers Upregulate TRAIL-Induced Apoptosis in Chronic Lymphocytic Leukemia Cells.
abstract: Although chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western world, it remains incurable with conventional chemotherapeutic agents. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an antitumor candidate in cancer therapy. This study examines the proapoptotic effects of poly(propylene imine) (PPI) glycodendrimers modified with the maltotriose residues (PPI-G4-OS-Mal-III and PPI-G4-DS-Mal-III) on the TNF family in CLL cells. The combination of an understanding of the signaling pathways associated with CLL and the development of a molecular profiling is a key issue for the design of personalized approaches to therapy. Gene expression is determined with two-color microarray 8 × 60K. The findings indicate that PPI-G4-OS/DS-Mal-III affect gene expression from the TRAIL apoptotic pathway and exert a strong effect on CLL cells comparable with fludarabine. Dendrimer-targeted technology may well prove to bridge the gap between the ineffective treatment of today and the effective personalized therapy of the future.
authors.affiliation: Department of Clinical and Laboratory Genetics, Medical University of Lodz, 251 Pomorska Str., 92-213, Lodz, Poland.|Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, 2 Pabianicka Str., 90-513, Lodz, Poland.
authors.forename: Ida
authors.initials: I
authors.lastname: Franiak-Pietryga
authors.affiliation: Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, 2 Pabianicka Str., 90-513, Lodz, Poland.|Department of Immunobiology of Bacteria, University of Lodz, 12/16 Banacha Str., 90-231, Lodz, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Ostrowska
authors.affiliation: Department of Computer Engineering, Wroclaw University of Technology, 5 Łukasiewicza Str., 50-371, Wroclaw, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Maciejewski
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Hohe Straße 6, 01069, Dresden, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Appelhans
authors.affiliation: Department of Hematology, Medical University of Lodz, 251 Pomorska Str., 92-213, Lodz, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Misiewicz
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Str., 90-236, Lodz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ziemba
authors.affiliation: Genos, 9 Inowrocławska Str., 91-020, Lodz, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Bednarek
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Str., 90-236, Lodz, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Bryszewska
authors.affiliation: Department of Clinical and Laboratory Genetics, Medical University of Lodz, 251 Pomorska Str., 92-213, Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011126:Polypropylenes / Q000494:pharmacology*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects*; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D050091:Dendrimers; D011126:Polypropylenes; D053221:TNF-Related Apoptosis-Inducing Ligand; C443641:poly(propyleneimine); D014740:Vidarabine; C024352:fludarabine
keywords: TNF; chronic lymphocytic leukemia (CLL); gene expression; glycodendrimers; signaling pathway