Umeå universitets logga

umu.sePublikationer
Ändra sökning
Avgränsa sökresultatet
1 - 14 av 14
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1. Geh, Katharina J.
    et al.
    Hubert, Madlen
    Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians Universität München, Munich, Germany.
    Winter, Gerhard
    Optimisation of one-step desolvation and scale-up of gelatine nanoparticle production2016Ingår i: Journal of Microencapsulation, ISSN 0265-2048, E-ISSN 1464-5246, Vol. 33, nr 7, s. 595-604Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gelatine nanoparticles (GNPs) are biodegradable and biocompatible drug delivery systems with excellent clinical performances. A two-step desolvation is commonly used for their preparation, although this methodology has several shortcomings: lack of reproducibility, small scales and low yields. A straightforward and more consistent GNP preparation approach is presented here focusing on the development of a one-step desolvation with the use of a commercially available gelatine type. Controlled stirring conditions and ultrafiltration are used to achieve large-scale production of nanoparticles of up to 2.6g per batch. Particle size distributions are conserved and comparable to those determined for two-step desolvation on small scale. Additionally, a range of cross-linking agents is examined for their effectiveness in stabilising GNPs as an alternative to glutaraldehyde. Glyceraldehyde demonstrated outstanding properties, which led to high colloidal stability. This approach optimises the manufacturing process and the scale-up of the production capacity, providing a clear potential for future applications.

  • 2. Geh, Katharina J.
    et al.
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Winter, Gerhard
    Progress in formulation development and sterilisation of freeze-dried oligodeoxynucleotide-loaded gelatine nanoparticles2018Ingår i: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 129, s. 10-20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Oligodeoxynucleotide (ODN)-loaded gelatine nanoparticles (GNPs) have proven their outstanding potential in the treatment of allergic diseases such as equine asthma and canine atopic dermatitis, which are appropriate models for the corresponding human diseases. To encourage the development of a marketable product, long term stability and sterility needs to be ensured. In this work, we aimed to advance freeze-drying options to stabilise ODN-loaded GNPs. Matrix-assisted laser desorption/ionisation mass spectrometry time-of-flight was implemented as a versatile tool to assess ODN stability. With this method long-term storage stability of lyophilised ODN-loaded GNPs formulated in sucrose or trehalose was achieved. Controlled nucleation was further introduced to optimise the lyophilisation approach. This allowed shortening of the process in comparison to standard freeze-drying procedures. Particle sizes, polydispersity indices, ODN stability, residual moisture and glass transition temperature were maintained upon storage. Excipient portfolio was enlarged by novel amino acid containing formulations for lyophilisates. His emerged as an excellent excipient in stabilising lyophilised ODN-loaded GNPs, whereas addition of Arg and Gly revealed to be inadequate at accelerated conditions. Lastly, gamma irradiation was evaluated as a suitable sterilisation method of ODN-loaded GNPs.

  • 3.
    Holst, Mikkel Roland
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Vidal-Quadras, Maite
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Song, Jie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Blomberg, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Lundborg, Magnus
    Landström, Maréne
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion2017Ingår i: Cell Reports, E-ISSN 2211-1247, Vol. 20, nr 8, s. 1893-1905Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cellular blebbing, caused by local alterations in cellsurface tension, has been shown to increase the invasiveness of cancer cells. However, the regulatory mechanisms balancing cell-surface dynamics and bleb formation remain elusive. Here, we show that an acute reduction in cell volume activates clathrinindependent endocytosis. Hence, a decrease in surface tension is buffered by the internalization of the plasma membrane (PM) lipid bilayer. Membrane invagination and endocytosis are driven by the tension- mediated recruitment of the membrane sculpting and GTPase-activating protein GRAF1 (GTPase regulator associated with focal adhesion kinase-1) to the PM. Disruption of this regulation by depleting cells of GRAF1 or mutating key phosphatidylinositol- interacting amino acids in the protein results in increased cellular blebbing and promotes the 3D motility of cancer cells. Our data support a role for clathrin-independent endocytic machinery in balancing membrane tension, which clarifies the previously reported role of GRAF1 as a tumor suppressor.

    Ladda ner fulltext (pdf)
    fulltext
  • 4.
    Hubert, Madlen
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Caveolae dynamics is strongly influenced by the lipid composition of the plasma membrane2017Ingår i: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 46, s. S121-S121Artikel i tidskrift (Övrigt vetenskapligt)
  • 5.
    Hubert, Madlen
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23 Uppsala, Sweden.
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Keeping in touch with the membrane; protein- and lipid-mediated confinement of caveolae to the cell surface2020Ingår i: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 48, s. 155-163Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Caveolae are small Omega-shaped invaginations of the plasma membrane that play important roles in mechanosensing, lipid homeostasis and signaling. Their typical morphology is characterized by a membrane funnel connecting a spherical bulb to the membrane. Membrane funnels (commonly known as necks and pores) are frequently observed as transient states during fusion and fission of membrane vesicles in cells. However, caveolae display atypical dynamics where the membrane funnel can be stabilized over an extended period of time, resulting in cell surface constrained caveolae. In addition, caveolae are also known to undergo flattening as well as short-range cycles of fission and fusion with the membrane, requiring that the membrane funnel closes or opens up, respectively. This mini-review considers the transition between these different states and highlights the role of the protein and lipid components that have been identified to control the balance between surface association and release of caveolae.

    Ladda ner fulltext (pdf)
    fulltext
  • 6.
    Hubert, Madlen
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Vegesna, Naga Venkata Gayathri
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Ahnlund, Maria
    Johansson, Annika I.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Moodie, Lindon W. K.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lipid accumulation controls the balance between surface connection and scission of caveolae2020Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 9, artikel-id e55038Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Caveolae are bulb-shaped invaginations of the plasma membrane (PM) that undergo scission and fusion at the cell surface and are enriched in specific lipids. However, the influence of lipid composition on caveolae surface stability is not well described or understood. Accordingly, we inserted specific lipids into the cell PM via membrane fusion and studied their acute effects on caveolae dynamics. We demonstrate that sphingomyelin stabilizes caveolae to the cell surface, whereas cholesterol and glycosphingolipids drive caveolae scission from the PM. Although all three lipids accumulated specifically in caveolae, cholesterol and sphingomyelin were actively sequestered, whereas glycosphingolipids diffused freely. The ATPase EHD2 restricts lipid diffusion and counteracts lipid-induced scission. We propose that specific lipid accumulation in caveolae generates an intrinsically unstable domain prone to scission if not restrained by EHD2 at the caveolae neck. This work provides a mechanistic link between caveolae and their ability to sense the PM lipid composition.

    Ladda ner fulltext (pdf)
    fulltext
  • 7.
    Larsson, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Analysis of protein and lipid interactions using liposome co-sedimentation assays2020Ingår i: Caveolae: methods and protocols / [ed] Cedric M. Blouin, Humana Press, 2020, , s. 9s. 119-127Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    The dynamic assembly of proteins at the membrane interphase is key to many cell biological processes such as the generation and stabilization of caveolae at the cell surface via coat proteins. The liposome co-sedimentation assay has been widely used for studies of protein and lipid interactions and has provided important information about binding mechanisms, lipid-binding specificity, and curvature preference of proteins. Here, we describe this technique in detail and how it can be used as a tool to address the membrane-binding ability and lipid specificity of caveolae-associated proteins.

  • 8.
    Liu, Kang-Cheng
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Pace, Hudson
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Hossain, Shakhawath
    Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden.
    Kabedev, Aleksei
    Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden.
    Shukla, Ankita
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Jerschabek, Vanessa
    Institute of Physical Chemistry, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
    Mohan, Jagan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Bergström, Christel A.S.
    Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden.
    Bally, Marta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Schwieger, Christian
    Institute of Physical Chemistry, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden.
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Membrane insertion mechanism of the caveola coat protein Cavin12022Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 119, nr 25, artikel-id 2202295119Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Caveolae are small plasma membrane invaginations, important for control of membrane tension, signaling cascades, and lipid sorting. The caveola coat protein Cavin1 is essential for shaping such high curvature membrane structures. Yet, a mechanistic understanding of how Cavin1 assembles at the membrane interface is lacking. Here, we used model membranes combined with biophysical dissection and computational modeling to show that Cavin1 inserts into membranes. We establish that initial phosphatidylinositol (4, 5) bisphosphate [PI(4,5)P2]-dependent membrane adsorption of the trimeric helical region 1 (HR1) of Cavin1 mediates the subsequent partial separation and membrane insertion of the individual helices. Insertion kinetics of HR1 is further enhanced by the presence of flanking negatively charged disordered regions, which was found important for the coassembly of Cavin1 with Caveolin1 in living cells. We propose that this intricate mechanism potentiates membrane curvature generation and facilitates dynamic rounds of assembly and disassembly of Cavin1 at the membrane.

  • 9.
    Mohan, Jagan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Schweiger, C
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Structural arrangement of membrane-bound cavinManuskript (preprint) (Övrigt vetenskapligt)
  • 10.
    Moodie, Lindon W. K.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Zhou, Xin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Albers, Michael Franz
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Wanrooij, Sjoerd
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Hedberg, Christian
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Photoactivated Colibactin Probes Induce Cellular DNA Damage2019Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 58, nr 5, s. 1417-1421Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colibactin is a small molecule produced by certain bacterial species of the human microbiota that harbour the pks genomic island. Pks(+) bacteria induce a genotoxic phenotype in eukaryotic cells and have been linked with colorectal cancer progression. Colibactin is produced in a benign, prodrug form which, prior to export, is enzymatically matured by the producing bacteria to its active form. Although the complete structure of colibactin has not been determined, key structural features have been described including an electrophilic cyclopropane motif, which is believed to alkylate DNA. To investigate the influence of the putative "warhead" and the prodrug strategy on genotoxicity, a series of photolabile colibactin probes were prepared that upon irradiation induced a pks(+) like phenotype in HeLa cells. Furthermore, results from DNA cross-linking and imaging studies of clickable analogues enforce the hypothesis that colibactin effects its genotoxicity by directly targeting DNA.

  • 11.
    Nilsson, Lars
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Rahmani, Shapour
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Williams, Chloe
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Gilthorpe, Jonathan D.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Tuck, Simon
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    TAT-5 and TAT-6 P4-family ATPases regulate the release of extracellular vesicles containing polycystins from Caenorhabditis elegans sensillaManuskript (preprint) (Övrigt vetenskapligt)
  • 12. Rodrigues, Leticia
    et al.
    Kyriakos, Konstantinos
    Schneider, Fabian
    Dietz, Hendrik
    Winter, Gerhard
    Papadakis, Christine M.
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Ludwig Maximilians Univ Munchen, Dept Pharm Pharmaceut Technol & Biopharm, Munich, Germany.
    Characterization of Lipid-Based Hexosomes as Versatile Vaccine Carriers2016Ingår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 13, nr 11, s. 3945-3954Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Subunit vaccines typically show insufficient immunogenicity. To address this issue, we developed a novel self-adjuvanting particulate carrier system based upon the lipids phytantriol (Phy) and mannide monooleate (MaMo). Phy is a lipid known to form nonlamellar phases in fully hydrated systems, whereas MaMo has been found to promote immune responses in emulsion form. A bulk phase composition of Phy/MaMo (14 wt %) showed hexagonal (HII) phase behavior over a practical temperature range (including room and body temperature), and was therefore used for particle development. Hexosomes stabilized with different concentrations of either poloxamer 407, Myrj 59, or Pluronic F108 were successfully prepared. To demonstrate the versatile nature of these systems, the particles were further modified with either positively or negatively charged lipids and loaded with model antigens, while maintaining the HII structure. These hexosomes are structurally robust and amenable to customization, rendering them suitable as antigen delivery carriers.

  • 13. Rodrigues, Leticia
    et al.
    Schneider, Fabian
    Zhang, Xiaohan
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Moodie, Lindon W. K.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Dietz, Hendrik
    Papadakis, Christine M.
    Winter, Gerhard
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Cellular uptake of self-assembled phytantriol-based hexosomes is independent of major endocytic machineries2019Ingår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 553, s. 820-833Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite increasing interests in non-lamellar liquid crystalline dispersions, such as hexosomes, for drug delivery, little is known about their interactions with cells and mechanism of cell entry. Here we examine the cellular uptake of hexosomes based on phytantriol and mannide monooleate by HeLa cells using live cell microscopy in comparison to conventional liposomes. To investigate the importance of specific endocytosis pathways upon particle internalization, we silenced regulatory proteins of major endocytosis pathways using short interfering RNA. While endocytosis plays a significant role in liposome internalization, hexosomes are not taken up via endocytosis but through a mechanism that is dependent on cell membrane tension. Biophysical studies using biomembrane models highlighted that hexosomes have a high affinity for membranes and an ability to disrupt lipid layers. Our data suggest that direct biomechanical interactions of hexosomes with membrane lipids play a crucial role and that the unique morphology of hexosomes is vital for their membrane activity. Based on these results, we propose a mechanism, where hexosomes destabilize the bilayer, allowing them to "phase through" the membrane. Understanding parameters that influence the uptake of hexosomes is critical to establish them as carrier systems that can potentially deliver therapeutics efficiently to intracellular sites of action.

  • 14.
    Wang, Tianyan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Sarwar, Martuza
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Whitchurch, Jonathan B.
    School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
    Collins, Hilary M.
    School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
    Green, Tami
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Semenas, Julius
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Amjad, Ali
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Roberts, Christopher J.
    School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
    Morris, Ryan D.
    School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
    Hubert, Madlen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Department of Pharmacy, Uppsala University, Uppsala, Sweden.
    Chen, Sa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    El-Schich, Zahra
    Department of Biomedical Science, Malmö University, Malmö, Sweden.
    Wingren, Anette G.
    Department of Biomedical Science, Malmö University, Malmö, Sweden.
    Grundström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Lundmark, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Mongan, Nigel P.
    School of Veterinary Medicine and Science, University of Nottingham, Nottingham, United Kingdom; Department of Pharmacology, Weill Cornell Medicine, New York, NY, United States.
    Gunhaga, Lena
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Heery, David M.
    School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
    Persson, Jenny L.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Biomedical Science, Malmö University, Malmö, Sweden; Department of Translational Medicine, Lund University, Clinical Research Centre in Malmö, Malmö, Sweden.
    PIP5K1α is Required for Promoting Tumor Progression in Castration-Resistant Prostate Cancer2022Ingår i: Frontiers in Cell and Developmental Biology, E-ISSN 2296-634X, Vol. 10, artikel-id 798590Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PIP5K1α has emerged as a promising drug target for the treatment of castration-resistant prostate cancer (CRPC), as it acts upstream of the PI3K/AKT signaling pathway to promote prostate cancer (PCa) growth, survival and invasion. However, little is known of the molecular actions of PIP5K1α in this process. Here, we show that siRNA-mediated knockdown of PIP5K1α and blockade of PIP5K1α action using its small molecule inhibitor ISA-2011B suppress growth and invasion of CRPC cells. We demonstrate that targeted deletion of the N-terminal domain of PIP5K1α in CRPC cells results in reduced growth and migratory ability of cancer cells. Further, the xenograft tumors lacking the N-terminal domain of PIP5K1α exhibited reduced tumor growth and aggressiveness in xenograft mice as compared to that of controls. The N-terminal domain of PIP5K1α is required for regulation of mRNA expression and protein stability of PIP5K1α. This suggests that the expression and oncogenic activity of PIP5K1α are in part dependent on its N-terminal domain. We further show that PIP5K1α acts as an upstream regulator of the androgen receptor (AR) and AR target genes including CDK1 and MMP9 that are key factors promoting growth, survival and invasion of PCa cells. ISA-2011B exhibited a significant inhibitory effect on AR target genes including CDK1 and MMP9 in CRPC cells with wild-type PIP5K1α and in CRPC cells lacking the N-terminal domain of PIP5K1α. These results indicate that the growth of PIP5K1α-dependent tumors is in part dependent on the integrity of the N-terminal sequence of this kinase. Our study identifies a novel functional mechanism involving PIP5K1α, confirming that PIP5K1α is an intriguing target for cancer treatment, especially for treatment of CRPC.

    Ladda ner fulltext (pdf)
    fulltext
1 - 14 av 14
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf