129 research outputs found
Molecular Studies in Myelodysplastic Syndromes.
No full textItem does not contain fulltextkun, 18 september 2003Promotor : Witte, T.J.M. de Co-promotores : Raymakers, R.A.P., Jansen, J.H
Biology of stem cells and myeloid progenitor cells in myelodysplastic syndromes.
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52863.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit Nijmegen, 07 februari 2007Promotor : Witte, T.J.M. de Co-promotor : Raymakers, R.A.P.149 p
ABC transporter modulation in acute myeloid leukemia. Studies from the leukemic stem cell perspective.
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27392.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit Nijmegen, 17 februari 2006Promotor : Witte, T.J.M. de Co-promotores : Raymakers, R.A.P., Jansen, J.H.189 p
Allogeneic stem cell transplantation: exploration of new indications and strategies to exploit graft-versus-tumor immunity for cancer treatment
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83230.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 01 december 2010Promotores : Witte, T.J.M. de, Punt, C.J.A. Co-promotores : Dolstra, H., Raymakers, R.A.P., Schaap, N.P.M.216 p
Dynamic interactions of dendritic cells - adhesive and migratory properties.
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59090.pdf (Publisher’s version ) (Open Access)Dendritic cells (DCs) are professional antigen presenting cells. They patrol in an immature state for antigen and upon antigen encounter they mature. Mature DCs migrate from the periphery to secondary lymphoid organs, where they interact with naïve T cells to initiate an effective immune response. DCs have the potential to be used as vaccine adjuvants in immunotherapy against cancer. A better understanding of regulation of DC migration is of major importance to improve clinical efficiency of DCs when used as vaccine adjuvant to fight cancer. In this thesis, we investigated the role of (novel) adhesion molecules in DC adhesion and migration in vitro as well as after injection into cancer patients. We developed an automated cell track system to monitor the migratory behavior of individual DCs. Strikingly, immature DCs firmly adhere, whereas mature DCs are highly motile and efficiently migrate to T cell areas of lymph nodes in vivo. The differences in adhesion in vitro can be attributed to a difference in activation status of the ß1 integrin. We also demonstrate that the DC-specific molecule DC-SIGN binds to endothelial ICAM-2 and mediates rolling interactions. Our data indicate a central role for endothelial ICAM-2 in DC-specific migration from blood into the periphery and subsequently of immature DCs via lymph into lymphatics. Mature DCs are very well equipped to stimulate T cells. MHC class I and II, as well as the costimulatory molecules CD80 and CD86 are highly expressed on mature DCs. Moreover mature DCs are characterized by the expression of the maturation marker CD83. Interestingly, we show that the protein CD83 binds both immature and mature DCs and has a functional role in DC biology by regulating DC-mediated immune responses. The data presented in this thesis provide insight into DC migration and thereby give the opportunity to improve cancer vaccine effectiveness.KUN, 30 januari 2004Promotor : Figdor, C.G. Co-promotor : Raymakers, R.A.P.159 p
ABC transporters in normal and malignant stem cells.
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71528.pdf (Publisher’s version ) (Open Access)Acute myelogenous leukemia is a disease originating from normal hematopoietic CD34+CD38- progenitor cells. Incomplete eradication of these primitive cells may eventually lead to disease relapse. Drug efflux by ABC-transporters is a well-established mechanism by which leukemic cells escape chemotherapeutical eradication. We confirmed that ABCB1 and ABCG2 are involved in transport of chemotherapeutical drugs from normal and leukemic CD34+CD38- primitive cells, but it became clear that additional drug efflux mechanisms must be active in leukemic primitive cells. To identify additional drug efflux mechanisms we studied the expression of all ABC-transporters in CD34+CD38- cells. In normal CD34+CD38- cells 36/45 ABC-transporters were expressed. Among these expressed genes the known multidrug resistance ABC-transporters were found but in addition we found many members not described to be expressed on stem cells. In leukemic CD34+CD38- cells the ABC-transporter profile was largely conserved. Furthermore, we determined the expression pattern of ABC-transporters during exposure to antileukemic drugs. Short-term exposure to anthracyclines rapidly induced a large range of ABC-transporters in leukemic progenitor cells. These induced transporters included both known drug transporters as well as transporters not previously associated with drug-transport or -resistance. These findings challenge the rationale of inhibition of single transporters to circumvent drug resistance of leukemic progenitors. Next to anthracyclines, Ara-C is one of the most important antileukemic drugs currently available for the treatment of AML. Many mechanisms for resistance to Ara-C have been identified, but an effect on ABC-transporters has never been described. A number of ABC-transporters were induced after exposure to Ara-C, ABCC6 showed the strongest induction. Further studies are warranted to unravel the mechanism behind the Ara-C resistance in ABCC6 expressing cells. The identification of previously unrecognized ABC-transporters in leukemic primitive cells offers the basis for future studies investigating the functional role of these ABC-transporters in resistance and their usefulness as therapeutically targets.RU Radboud Universiteit Nijmegen, 27 augustus 2008Promotor : Witte, T.J.M. de Co-promotores : Raymakers, R.A.P., Reijden, B.A. van der160 p
Molecular studies in myelodysplastic syndromes
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19322_molestinm.pdf (Publisher’s version ) (Open Access)This thesis describes molecular studies of myelodysplastic syndromes (MDS). The first question was if high-dose chemotherapy could induce polyclonal remission. Disease clonality was investigated with karyotyping in patients with large chromosomal aberrations and determination of X-chromosome inactivation patterns (XCIP) in female patients. These investigations were performed at diagnosis and in clinical complete remission. The biological background of non-random XCIPs in healthy female donors was investigated and improved methods for determination of XCIPs were developed. A second question was the involvement of the WT1 gene in MDS. This gene is highly expressed in acute myeloid leukemia (AML) but not in normal bone marrow (BM). The involvement of WT1 in MDS was investigated by looking at the expression patterns in various cell lineages in MDS bone marrow (BM)91 p
Functional and stochastic modelling of satellite gravity data
No full textPhysical and Space GeodesyAerospace Engineerin
Regional gravity field modelling with radial basis functions
No full textPhysical and Space GeodesyAerospace Engineerin
Regional gravity field modeling using airborne gravity data
No full textEarth Observation and Space SystemsAerospace Engineerin
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