| 1. |
- Aili, Ulrika, et al.
(författare)
-
Antiproliferative effects of peracetylated naphthoxylosides.
- 2009
-
Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X. ; 19, s. 1763-1766
-
Tidskriftsartikel (refereegranskat)abstract
- The antiproliferative activity, and the capability of priming of glycosaminoglycan chains, of two series of peracetylated mono- and bis-xylosylated dihydroxynaphthalenes have been investigated for normal HFL-1 cells, as well as transformed T24 cells, and compared to the unprotected analogs. Our data show increased antiproliferative activity upon peracetylation, but a loss of selectivity towards T24 cells.
|
|
| 2. |
- Aili, Ulrika, et al.
(författare)
-
Attenuation of tumor growth by formation of antiproliferative glycosaminoglycans correlates with low acetylation of histone H3.
- 2010
-
Ingår i: Cancer Research. - 1538-7445. ; 70:9, s. 3771-3779
-
Tidskriftsartikel (refereegranskat)abstract
- Glycosaminoglycan (GAG) chains anchored to core proteins form proteoglycans, widely distributed cell-surface macromolecules with multiple functions, such as regulation of growth factor and cytokine signaling, cell-cell interactions, and uptake of biomolecules. The biosynthesis of GAG can be manipulated by xylosides attached to various hydrophobic groups, and we have earlier reported that a naphthoxyloside, 2-(6-hydroxynaphthyl) beta-D-xylopyranoside (XylNapOH), which serves as a primer for GAG synthesis, reduces tumor load up to 97% in vivo, despite lower efficiency in vitro. Here we show, using radiolabeled xylosides and coculture experiments, that XylNapOH-treated bladder and breast carcinoma cells secrete antiproliferative GAG chains that are taken up by both normal and cancer cells and transported to the cell nuclei where they induce an antiproliferative effect, accompanied by apoptosis. We also show that XylNapOH treatment lowers the level of histone H3 acetylation selectively in bladder and breast carcinoma cells without affecting expression of histone H3. However, XylNapOH-primed GAG chains from normal cells are not internalized and do not cause growth retardation. Using in vitro and in vivo C6 glioma cell and tumor models, we show that XylNapOH is much more effective in vivo than in vitro. We propose that, in vivo, the antiproliferative XylNapOH-primed GAG chains produced by tumor cells inhibit tumor growth in an autocrine fashion by formation of antiproliferative GAG chains on the xyloside prodrug, whereas no antiproliferative GAG chains are produced by surrounding normal cells. This is a novel mechanism for targeting tumor cells, making these xylosides promising drug candidates for antitumor therapy.
|
|
| 3. |
- Aili, Ulrika
(författare)
-
Tumor Selective Antiproliferative Naphthoxylosides
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteoglycans (PG) are highly anionic macromolecules consisting of a core protein covalently substituted with long unbranched polysaccharide chains called glycosaminoglycans (GAGs). PGs are central components in multicellular organisms, and they may occur in the extracellular matrix (ECM), at the cell surface, or in the secretory pathway. At the tumor cell surface, PGs and GAGs are involved in the pathophysiological steps of tumor progression by regulation of tumor proliferation, invasion, metastasis, angiogenesis, and stem cell differentiation. Xylose is an unusual structural component of mammalian cells and it serves as the linker between the protein and the GAG chain in PG. β-D-xylosides attached to various hydrophobic aglycons can penetrate plasma membranes and act as artificial primers for GAG formation, independently of core protein synthesis. The overall purpose of this project was to investigate the antiproliferative activity of xyloside primed GAG chains and to study different aspects on how xylosides or xyloside primed GAG chains inhibit growth of cancer cells. This thesis demonstrates that the xyloside primed GAG chains produced by tumor cells inhibit growth in an autocrine fashion by formation of antiproliferative GAG chains on the xyloside pro-drug, while surrounding normal cells do not produce any antiproliferative GAG chains. We have also shown effects on histone acetylation, indicating epigenetic effects.
|
|
| 4. |
- Harris, Ulrika, et al.
(författare)
-
Parents’ Experiences of Direct and Indirect Implications of Sleep Quality on the Health of Children with ADHD : A Qualitative Study
- 2022
-
Ingår i: International Journal of Environmental Research and Public Health. - Basel : MDPI. - 1661-7827 .- 1660-4601. ; 19:22
-
Tidskriftsartikel (refereegranskat)abstract
- Sleep problems represent a significant challenge for children with ADHD. However, lack of knowledge about how sleep affects children with ADHD in terms of their health and everyday life prevents the development and implementation of interventions to promote sleep. The aim of this study was to explore parents’ experiences of direct and indirect implications of sleep quality onthe health of children with ADHD. The study used an abductive qualitative design, with Tengland’s two-dimensional theory of health as a deductive analysis framework. Semi-structured interviews were conducted with 21 parents of children aged 6–13 with ADHD and sleep problems. The parents experienced that sleep influenced their children’s abilities to control emotional behaviour relatedto ADHD and to manage everyday life. Sleep also had an impact on the children’s well-being,in relation to both vitality and self-esteem. In conclusion, the results show important direct and indirect implications of sleep quality on the health of children with ADHD. This implies a need forgreater focus on sleep, to target both abilities and well-being in promoting health among childrenwith ADHD. © 2022 by the authors
|
|
| 5. |
|
|
| 6. |
- Siegbahn, Anna, et al.
(författare)
-
Synthesis, conformation and biology of naphthoxylosides
- 2011
-
Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 19:13, s. 4114-4126
-
Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans (PG) are polyanionic proteins consisting of a core protein substituted with carbohydrate chains, that is, glycosaminoglycans (GAG). The biosynthesis of GAG can be manipulated by simple xylosides carrying hydrophobic aglycons, which can enter the cell and initiate the biosynthesis. While the importance of the aglycon is well investigated, there is far less information on the effect of modifications in the xylose residue. We have developed a new synthetic protocol, based on acetal protection and selective benzylation, for modification of the three hydroxyl groups in xylose. Thus we have synthesized twelve analogs of 2-naphthyl β-d-xylopyranoside (XylNap), where each hydroxyl group has been epimerized or replaced by methoxy, fluoro, or hydrogen. To gain more information about the properties of xylose, conformational studies were made on some of the analogs. It was found that the 4C1 conformation is highly predominant, accompanied by a nonnegligible population of the 2S0 conformation. However, deoxygenation at C3 results in a large portion of the 1C4 conformation. The GAG priming ability and proliferation activity of the twelve analogs, were investigated using a matched pair of human breast fibroblasts and human breast carcinoma cells. None of the analogs initiated the biosynthesis of GAG, but an inhibitory effect on endogenous PG production was observed for analogs fluorinated or deoxygenated at C4. From our data it seems reasonable that all three hydroxyl groups in XylNap are essential for the priming of GAG chains and for selective toxicity for tumor cells.
|
|
