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Danuta Balicki

Publications and source records attributed to Danuta Balicki.

4 recordsLinked to original sources

SP analysis may be used to identify cancer stem cell populations.

Side populations (SP), as defined by Hoechst exclusion in flow cytometry, have been described a few years ago. While they represent only a small fraction of the whole cell population, their properties confer an important place in several investigations. SP cells express high levels of various members of ABC transporters family, such as MDR1 and BCRP, which are responsible for drug resistance. Targeting SP could improve cancer therapy by blocking these transporters. In addition, SP appear to be enriched in stem cells, cells that play a pivotal role in normal development and cancer biology. Thus, they could provide a useful tool and a readily accessible source for stem cell studies in both the normal and cancerous settings. However, these cells are poorly defined and pose challenges in their identification and isolation, particularly since they are few in number. Thus, better characterization of SP will advance our understanding of stem cells and will provide us an accessible target for drug resistance in cancer therapy.

ATP-Binding Cassette Transporters↗

Histonefection: Novel and potent non-viral gene delivery.

Protein/peptide-mediated gene delivery has recently emerged as a powerful approach in non-viral gene transfer. In previous studies, we and other groups found that histones efficiently mediate gene transfer (histonefection). Histonefection has been demonstrated to be effective with various members of the histone family. The DNA binding domains and natural nuclear localisation signal sequences make histones excellent candidates for effective gene transfer. In addition, their positive charge promotes binding to anionic molecules and helps them to overcome the negative charge of cells that is an important barrier to cellular penetration. Histonefection appears to have particular promise in cancer gene transfer and therapy.

Active Transport, Cell Nucleus↗

Structure and function correlation in histone H2A peptide-mediated gene transfer.

Histone H2A has been found to be efficient in DNA delivery into a number of cell lines. We have reasoned that this DNA-delivery activity is mediated by two mechanisms: (i) electrostatically driven DNA binding and condensation by histone and (ii) nuclear import of these histone H2A.DNA polyplexes via nuclear localization signals in the protein. We have identified a 37-aa N-terminal peptide of histone H2A that is active in in vitro gene transfer. This peptide can function as a nuclear localization signal and can bind DNA. Amino acid substitutions that replace positively charged residues and/or DNA-binding residues of this peptide obliterate transfection activity. The introduction of a proline in the first turn of an alpha-helix of this 37-mer obliterates transfection activity, suggesting that the integrity of the alpha-helical structure of the N-terminal region of histone H2A is related to its transfection activity.

Amino Acid Sequence↗