2011

Verissimo, C.S., Molenaar, J.J., Fitzsimons, C.P., Vreugdenhil, E. , Neuroblastoma therapy: what's in the pipeline?, Endocr Relat Cancer.

de Vrij, J., Dautzenberg, I.J., van den Hengel, S.K., Magnusson, M.K., Uil, T.G., Cramer, S.J., Vellinga, J., Verissimo, C.S., Lindholm, L., Koppers-Lalic, D., Hoeben, R.C. , A cathepsin-cleavage site between the adenovirus capsid protein IX and a tumor-targeting ligand improves targeted transduction, Gene Ther.

2010

Verissimo, C.S., Molenaar, J.J., Meerman, J., Puigvert, J.C., Lamers, F., van Kuik-Romeijn, P., Danen, E.H.J., van de Water, B., Versteeg, R., Fitzsimons, C.P., Vreugdenhil, E. , Exploring a new therapy for Neuroblastoma: silencing of DoubleCortin-Like Kinase using RNA-interference, Neuro-Oncology, vol. 12, no. suppl 3, Maastricht, The Netherlands, pp. 64-64.

Verissimo, C.S., Molenaar, J.J., Puigvert, J.C., Lamers, F., van Kuik-Romeijn, P., Danen, E.H.J., van de Water, B., Versteeg, R., Fitzsimons, C.P., Vreugdenhil, E. , Exploring a new therapy for Neuroblastoma: silencing of DoubleCortin-Like Kinase using RNA-interference, EJC Supplements, vol. 8, no. 5, Maastricht, The Netherlands, pp. 52-52.

Verissimo, C.S., Molenaar, J.J., Meerman, J., Puigvert, J.C., Lamers, F., Koster, J., Danen, E.H., van de Water, B., Versteeg, R., Fitzsimons, C.P., Vreugdenhil, E. , Silencing of the microtubule-associated proteins doublecortin-like and doublecortin-like kinase-long induces apoptosis in neuroblastoma cells, Endocr Relat Cancer, vol. 17, no. 2, pp. 399-414.

2009

Vreugdenhil, E., Verissimo, C.S., Mariman, R., Kamphorst, J.T., Barbosa, J.S., Zweers, T., Champagne, D.L., Schouten, T., Meijer, O.C., de Kloet, E.R., Fitzsimons, C.P. , MicroRNA 18 and 124a down-regulate the glucocorticoid receptor: implications for glucocorticoid responsiveness in the brain, Endocrinology, vol. 150, no. 5, pp. 2220-2228.

2006

Gabor, K., Verissimo, C.S., Cyran, B.C., Ter Horst, P., Meijer, N.P., Smidt, H., de Vos, W.M., van der Oost, J. , Characterization of CprK1, a CRP/FNR-type transcriptional regulator of halorespiration from Desulfitobacterium hafniense, Journal of Bacteriology, vol. 188, no. 7, pp. 2604-2613.

Exploring a new therapy for neuroblastoma: silencing of Doublecortin-like kinase, a microtubule-binding protein

Neuroblastoma is one of the most common childhood cancers.
Microtubule-destabilizing agents are used in the treatment of these
tumors in human patients. However, resistance to chemotherapeutic
agents and systemic toxicity make neuroblastoma a difficult drug target.
In our previous work, we found that doublecortin-like kinase (DCLK)
gene transcripts are crucial microtubule-associated proteins for
correct proliferation and differentiation of neuroprogenitor cells.
Gene expression profiling revealed a high expression of these
transcripts in neuroblastoma patients. Furthermore, these transcripts
are endogenously expressed specifically in neuroblasts but are not
found in other cell types. Suppression of DCLK by short interfering RNA
(siRNA) disrupted the mitotic spindles in neuroblastoma cells and gene
expression profiling showed that several affected pathways are linked
to cell cycle, differentiation and apoptosis. Apoptotic cell death of
neuroblastoma cells by DCLK knockdown was further confirmed by a
variety of assays. Furthermore, we showed a successful delivery of
siRNA targeting DCLK to neuroblastoma cells by using specific
peptide-siRNA conjugates.
In conclusion, silencing of the DCLK gene by siRNA interference is a
novel potential therapeutic approach for neuroblastoma with the promise
of combining high specificity with fewer side effects. Peptide-siRNA
conjugates might be the tool needed for specific neuroblastoma
delivery.