liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Targeting malignant glioma cells in vitro using platelet-derived growth factor AA-based conjugates
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
2009 (English)In: Journal of drug targeting, ISSN 1029-2330, 1-10 p.Article in journal (Refereed) Published
Abstract [en]

Glioblastoma multiforme (GBM) is an unusually aggressive brain tumor; it is also highly heterogeneous. Poor prognosis and a median survival of less than 1 year, using conventional treatment, calls for development of new treatment strategies. Overexpression and/or amplification of platelet-derived growth factor alpha receptors (PDGFalphaRs) in GBM might act as potential targets for a novel therapeutic approach. In this study, conjugates based on PDGFAA-ligand and dextran, of different sizes (10 and 40 kDa dextran), were prepared and investigated regarding targeting properties in vitro. Three human malignant glioma cell lines, U343MGa31L, U343MGaCl2:6, and U563MG, were used because of their previously reported differences in receptor expression and behavior. PDGFAA-based 10 kDa dextran iodine-125 radiolabeled conjugates showed the most favorable properties according to results achieved in accumulation, retention, and localization of cell-associated radioactivity. In comparison with dextran-(125)I-tyrosine delivered radioactivity, the PDGFAA-based dextran conjugates confirm the potential of receptor targeting.

Place, publisher, year, edition, pages
2009. 1-10 p.
Keyword [en]
Conjugate, dextran, glioblastoma multiforme, PDGFAA, PDGF receptors, targeting
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-18470DOI: 10.1080/10611860902718698PubMedID: 19255898OAI: oai:DiVA.org:liu-18470DiVA: diva2:219696
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2009-05-28Bibliographically approved
In thesis
1. Aspects of Tumour Targeting: Preclinical Studies on Human Malignant Cells in vitro
Open this publication in new window or tab >>Aspects of Tumour Targeting: Preclinical Studies on Human Malignant Cells in vitro
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Exclusive eradication of tumour cells causing minimal damage to healthy tissue, a concept referred to as targeting, is an interesting approach to improve the outcome for patients afflicted with cancer.

The general aim of this thesis was to highlighten aspects that could be of importance in developing novel treatment regimens based on specific targeting of tumour cells. Two variants of targeting strategies, boron neutron capture therapy (BNCT) and platelet-derived growth factor receptor (PDGFR) tumour targeting were studied in vitro.

In BNCT, the ability of boron-10, 10B, to capture neutrons is utilized. The capture reaction initiate emission of high linear energy transfer (LET) particles which exerts potential damaging effects on exposed cells. A preferential accumulation of at least 10 μg 10B/g tumour tissue is suggested to be required for effective clinical outcome. Here, the accumulation of boronophenylalanine, BPA, was investigated in human glioma, synovial sarcoma, fibroblast and monocytoid cells in vitro. For the purpose of quick and effective separation of extracellular and cell-associated boron, a rapid cell filtration method was developed. Inductively coupled plasma atomic emission spectroscopy, ICP-AES, was used to analyse the amount of boron associated to the cells.

Over-expression of PDGFRs may render the possibility to target certain tumours using PDGF-based conjugates for a specific delivery of cytotoxic agents. PDGF-AA was conjugated to dextran of two different sizes, 10 and 40 kDa, and compared with 125I-radiolabelled PDGF-AA regarding accumulation, retention and localisation in human glioma cells in vitro.

A boron concentration of >10 μg 10B/g tumour tissue was found in all human cell lines studied. For the two glioma cell lines, the results extend differences between the two although originating from the same human tumour material. Since fibroblasts and monocytoid cells, here used to represent normal cells, accumulated boron at a clinically relevant amount one may have to consider the role of these cells in/at the tumour site during treatment. Regarding results for the human synovial sarcoma cells, further investigations may state the potential of BNCT as a treatment modality and explore the possibilities of a directed delivery of boron-containing substances to receptors specifically expressed in this malignancy.

PDGF-AA-based dextran conjugates, preferentially 10 kDa dextran conjugates, showed in vitro properties that were superior to radiolabelled unconjugated PDGF-AA. A prolonged retention time was observed for the conjugates. Radiolabelled PDGF-AA was mainly determined to be located intracellular but the localisation, internalised or membrane-associated, of radiolabelled conjugates seemed to be dependent on the composition of the conjugate. It is of interest to explore the potential of dextran conjugates carrying toxic substances for therapeutic purpose.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 80 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1118
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18471 (URN)978-91-7393-649-1 (ISBN)
Public defence
2009-06-04, Aulan, Hälsans Hus, Campus US, Linköpings Universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2009-06-22Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedLink to Ph.D. Thesis

Authority records BETA

Dahlström Wester, MariaWasteson, ÅkeLindström, Annelie

Search in DiVA

By author/editor
Dahlström Wester, MariaWasteson, ÅkeLindström, Annelie
By organisation
Cell BiologyFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 94 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf