Publications
Below you can find a list of our published research.
Below you can find a list of our published research.
239 results
Cited 62 times since 2005 (3.3 per year) source: EuropePMC
Cardiovascular research, Volume 67, Issue 2, 1 1 2005, Pages 245-255 Activation of cardiac and smooth muscle-specific genes in primary human cells after forced expression of human myocardin. van Tuyn J, Knaän-Shanzer S, van de Watering MJ, de Graaf M, van der Laarse A, Schalij MJ, van der Wall EE, de Vries AA, Atsma DE
Objective: Myocardin is a recently discovered transcriptional regulator of cardiac and smooth muscle development. Its ability to transactivate smooth muscle-specific genes has been firmly established in animal cells but its effect on heart muscle genes has been investigated less extensively and the consequences of ectopic myocardin expression in human cells are unknown. Methods: In this study, primary human mesenchymal stem cells and foreskin fibroblasts were transduced with human adenovirus vec... Abstract
Cited 15 times since 2005 (0.8 per year) source: EuropePMC
British journal of cancer, Volume 92, Issue 5, 1 1 2005, Pages 882-887 Adenoviral vector-mediated expression of a gene encoding secreted, EpCAM-targeted carboxylesterase-2 sensitises colon cancer spheroids to CPT-11. Oosterhoff D, Overmeer RM, de Graaf M, van der Meulen IH, Giaccone G, van Beusechem VW, Haisma HJ, Pinedo HM, Gerritsen WR
CPT-11 (irinotecan or 7-ethyl-10[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) is an anticancer agent in use for the treatment of colon cancer. In order to be fully active, CPT-11 needs to be converted into SN-38 (7-ethyl-10-hydroxycamptothecin) by the enzyme carboxylesterase (CE). In humans, only a minority of CPT-11 is converted to SN-38. To increase the antitumour effect of CPT-11 by gene-directed enzyme prodrug therapy, we constructed a replication-deficient adenoviral vector Ad.C2... Abstract
Cited 14 times since 2004 (0.7 per year) source: EuropePMC
Biochemical pharmacology, Volume 68, Issue 11, 1 1 2004, Pages 2273-2281 A methylester of the glucuronide prodrug DOX-GA3 for improvement of tumor-selective chemotherapy. de Graaf M, Nevalainen TJ, Scheeren HW, Pinedo HM, Haisma HJ, Boven E
The glucuronide prodrug of doxorubicin, DOX-GA3, can be selectively activated in tumors by extracellular human beta-glucuronidase, resulting in a better therapeutic index than doxorubicin. DOX-GA3, however, is rapidly excreted by the kidney. We hypothesized that slow release of DOX-GA3 from its methylester, DOX-mGA3, by esterase activity in blood would result in improved circulation half-life (t(1/2)) of DOX-GA3. DOX-mGA3 was synthesized more efficiently with an overall yield of 60% as compared... Abstract
Cited 68 times since 2004 (3.4 per year) source: EuropePMC
Journal of virology, Volume 78, Issue 15, 1 1 2004, Pages 8264-8270 Recovery of human metapneumovirus genetic lineages a and B from cloned cDNA. Herfst S, de Graaf M, Schickli JH, Tang RS, Kaur J, Yang CF, Spaete RR, Haller AA, van den Hoogen BG, Osterhaus AD, Fouchier RA
Human metapneumovirus (hMPV) is a newly discovered pathogen associated with respiratory tract illness, primarily in young children, immunocompromised individuals, and the elderly. The genomic sequence of the prototype hMPV isolate NL/1/00 without the terminal leader and trailer sequences has been reported previously. Here we describe the leader and trailer sequences of two hMPV isolates, NL/1/00 and NL/1/99, representing the two main genetic lineages of hMPV. Minigenome constructs in which the g... Abstract
Cited 8 times since 2004 (0.4 per year) source: EuropePMC
Human gene therapy, Volume 15, Issue 3, 1 1 2004, Pages 229-238 Pronounced antitumor efficacy by extracellular activation of a doxorubicin-glucuronide prodrug after adenoviral vector-mediated expression of a human antibody-enzyme fusion protein. de Graaf M, Pinedo HM, Oosterhoff D, van der Meulen-Muileman IH, Gerritsen WR, Haisma HJ, Boven E
Tumor-specific activation of the glucuronide prodrug of doxorubicin, N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-beta-glucuronyl carbamate (DOX-GA3), by beta-glucuronidase present in necrotic tumor areas might be improved after transduction of tumor cells to secrete a targeted form of beta-glucuronidase. To that end, we constructed an adenovirus vector, designated Ad/C28-GUSh, encoding human beta-glucuronidase fused to a human single-chain Fv (scFv) against the epithelial cell adhesion molec... Abstract
Cited 214 times since 2004 (10.6 per year) source: EuropePMC
Journal of clinical microbiology, Volume 42, Issue 3, 1 1 2004, Pages 981-986 Real-time reverse transcriptase PCR assay for detection of human metapneumoviruses from all known genetic lineages. Maertzdorf J, Wang CK, Brown JB, Quinto JD, Chu M, de Graaf M, van den Hoogen BG, Spaete R, Osterhaus AD, Fouchier RA
The discovery of human metapneumovirus and its implications for respiratory tract disease have emphasized the need for a sensitive, specific, and rapid assay to detect this virus in a clinical setting. It recently became clear that human metapneumovirus can be grouped into at least four genetic lineages. Previously described assays for the detection of human metapneumovirus were developed by using limited sequence information and failed to detect viruses from all four genetic lineages with compa... Abstract
Cited 9 times since 2003 (0.4 per year) source: EuropePMC
Biochemical pharmacology, Volume 65, Issue 11, 1 1 2003, Pages 1875-1881 Cytosolic beta-glycosidases for activation of glycoside prodrugs of daunorubicin. de Graaf M, Pinedo HM, Quadir R, Haisma HJ, Boven E
Human cytosolic beta-glycosidase is a small monomeric enzyme that is active under physiological conditions, which might be ideal for enzyme-prodrug therapy. We have previously reported the synthesis of a galactoside (DNR-GlA3) and a glucoside (DNR-GsA3) prodrug of daunorubicin. In the present study, we established that cellular uptake of DNR-GlA3 and DNR-GsA3 was low in contrast to that of daunorubicin. Recombinant human beta-glycosidase converted both prodrugs to daunorubicin as shown by liquid... Abstract
Cited 24 times since 2002 (1.1 per year) source: EuropePMC
British journal of cancer, Volume 87, Issue 6, 1 1 2002, Pages 659-664 Secreted and tumour targeted human carboxylesterase for activation of irinotecan. Oosterhoff D, Pinedo HM, van der Meulen IH, de Graaf M, Sone T, Kruyt FA, van Beusechem VW, Haisma HJ, Gerritsen WR
Irinotecan (CPT-11) is an anticancer agent for the treatment of colon cancer. CPT-11 can be considered as a prodrug, since it needs to be activated into the toxic drug SN-38 by the enzyme carboxylesterase. An approach to achieve tumour specific activation of CPT-11 is to transduce the cDNA encoding carboxylesterase into tumour cells. A secreted form of carboxylesterase may diffuse through a tumour mass and may activate CPT-11 extracellularly. This could enhance the antitumour efficacy by exertin... Abstract
Cited 20 times since 2002 (0.9 per year) source: EuropePMC
British journal of cancer, Volume 86, Issue 5, 1 1 2002, Pages 811-818 A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug. de Graaf M, Boven E, Oosterhoff D, van der Meulen-Muileman IH, Huls GA, Gerritsen WR, Haisma HJ, Pinedo HM
Monoclonal antibodies against tumour-associated antigens could be useful to deliver enzymes selectively to the site of a tumour for activation of a non-toxic prodrug. A completely human fusion protein may be advantageous for repeated administration, as host immune responses may be avoided. We have constructed a fusion protein consisting of a human single chain Fv antibody, C28, against the epithelial cell adhesion molecule and the human enzyme beta-glucuronidase. The sequences encoding C28 and h... Abstract
Cited 5 times since 2002 (0.2 per year) source: EuropePMC
Methods in molecular biology (Clifton, N.J.), Volume 178, 1 1 2002, Pages 379-387 Expression of scFvs and scFv fusion proteins in eukaryotic cells. de Graaf M, van der Meulen-Muileman IH, Pinedo HM, Haisma HJ
Cited 56 times since 2002 (2.5 per year) source: EuropePMC
Current pharmaceutical design, Volume 8, Issue 15, 1 1 2002, Pages 1391-1403 Beta-glucuronidase-mediated drug release. de Graaf M, Boven E, Scheeren HW, Haisma HJ, Pinedo HM
The selective activation of a relatively non-toxic prodrug by an enzyme present only in the tumour should enhance the drug concentration at the tumour site and result in a better anti-tumour effect and a reduction in systemic toxicity as compared to conventional chemotherapy. beta-Glucuronidase is such an enzyme. It is normally expressed in the lysosomes of cells. In larger tumours, however, high levels of the enzyme are present in necrotic areas. Several glucuronide prodrugs have been synthesis... Abstract
Cited 21 times since 2001 (0.9 per year) source: EuropePMC
The Biochemical journal, Volume 356, Issue Pt 3, 1 1 2001, Pages 907-910 Cloning and characterization of human liver cytosolic beta-glycosidase. de Graaf M, van Veen IC, van der Meulen-Muileman IH, Gerritsen WR, Pinedo HM, Haisma HJ
Cytosolic beta-glucosidase (EC 3.2.1.21) from mammalian liver is a member of the family 1 glycoside hydrolases and is known for its ability to hydrolyse a range of beta-D-glycosides, including beta-D-glucoside and beta-D-galactoside. We therefore refer to this enzyme as cytosolic beta-glycosidase. We cloned the cDNA encoding the human cytosolic beta-glycosidase by performing PCR on cDNA prepared from total human liver RNA. Specific primers were based on human expressed sequence tags found in the... Abstract
Cited 15 times since 1998 (0.6 per year) source: EuropePMC
Development, growth & differentiation, Volume 40, Issue 6, 1 1 1998, Pages 577-582 Hormone-inducible expression of secreted factors in zebrafish embryos. de Graaf M, Zivkovic D, Joore J
The study of gene function at later stages of embryonic development by overexpression experiments is often complicated by genes exerting different functions at multiple stages of development, which renders analysis of stage-specific effects difficult. To address this problem an inducible expression system that supports timed expression of essentially any protein, including secreted proteins was designed. The system is based on a two step mechanism. A glucocorticoid inducible, Gal4-site binding c... Abstract
Cited 8 times since 1998 (0.3 per year) source: EuropePMC
Developmental medicine and child neurology, Volume 40, Issue 8, 1 1 1998, Pages 563-567 Development of visual function in hemihydranencephaly. Porro G, Wittebol-Post D, de Graaf M, van Nieuwenhuizen O, Schenk-Rootlieb AJ, Treffers WF
This study reports on the findings of longitudinal follow-up of visual function in a 12-year-old girl affected by congenital right hemihydranencephaly. This extremely rare unilateral brain malformation allowed the authors to gather new information on neuronal plasticity and functional compensations of the visual system across a period of 10 years. An extension of the preserved right visual hemifields above the middle line and strategical eye or head positions developed to increase visual functio... Abstract
Cited 14 times since 1997 (0.5 per year) source: EuropePMC
Biochemical and biophysical research communications, Volume 236, Issue 3, 1 1 1997, Pages 544-548 Autosomal recessive liver phosphorylase kinase deficiency caused by a novel splice-site mutation in the gene encoding the liver gamma subunit (PHKG2). van Beurden EA, de Graaf M, Wendel U, Gitzelmann R, Berger R, van den Berg IE
To facilitate mutation analysis of patients with an autosomal recessive form of liver phosphorylase kinase deficiency, the genomic structure of the gene encoding the testis/liver gamma subunit (PHKG2) was established. The gene consist of 10 exons. The translation start site is located in exon 2. Analysis of DNA from two female siblings, affected with liver phosphorylase kinase deficiency, by exon specific amplification followed by direct sequencing, revealed a single donor splice site mutation i... Abstract
Cited 1 times since 1994 (0 per year) source: EuropePMC
The Netherlands journal of medicine, Volume 44, Issue 2, 1 1 1994, Pages 60-64 Q-fever in a patient with a ventriculo-peritoneal drain. Case report and short review of the literature. Lohuis PJ, Ligtenberg PC, Diepersloot RJ, de Graaf M
Although Q-fever is still a relatively rare disease in the Netherlands, its incidence seems to be increasing. In this article we describe the case-history of a 65-year-old woman with a Pudenz-drain, who acquired Q-fever pneumonia while manuring her garden. The course of the disease was deviant, which most likely was caused by colonization of the ventriculo-peritoneal drain with Coxiella burnetii. Q-fever usually presents as a self-limiting illness. In the case of chronic Q-fever, complications s... Abstract
Cited 54 times since 1990 (1.6 per year) source: EuropePMC
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, Volume 9, Issue 12, 1 1 1990, Pages 864-868 Detection of Chlamydia trachomatis in clinical specimens by the polymerase chain reaction. Claas HC, Melchers WJ, de Bruijn IH, de Graaf M, van Dijk WC, Lindeman J, Quint WG
Sequences derived from the endogenous plasmid of Chlamydia trachomatis and from the genes coding for ribosomal 16S RNA of Chlamydia psittaci were used as primers and oligonucleotide probes for detection of chlamydiae by the polymerase chain reaction. The endogenous plasmid primers generated specific amplified products of 517 bp with all known Chlamydia trachomatis serovars. No specific products of Chlamydia psittaci and Chlamydia pneumoniae could be detected using these primers. With the rRNA pr... Abstract
Cited 29 times since 1989 (0.8 per year) source: EuropePMC
Molecular microbiology, Volume 3, Issue 5, 1 1 1989, Pages 645-652 Detection and identification of FaeC as a minor component of K88 fibrillae of Escherichia coli. Oudega B, de Graaf M, de Boer L, Bakker D, Vader CE, Mooi FR, de Graaf FK
A tribrid gene containing ompF, faeC, and lacZ sequences was constructed by subcloning a large central segment of the K88ab gene encoding the fibrillar subunit-like protein FaeC into the open reading frame expression vector pORF2. The resulting tribrid protein was isolated and used to raise antibodies against the FaeC protein. These antibodies were then used for the detection and subcellular localization of the FaeC protein in Escherichia coli harbouring the K88ab-encoding plasmid pFM205 or muta... Abstract
Cited 4 times since 1976 (0.1 per year) source: EuropePMC
Virology, Volume 74, Issue 1, 1 1 1976, Pages 232-235 The primary structure of the coat protein of alfalfa mosaic virus (strain 425). Kraal B, van Beynum GM, De Graaf M, Castel A, Bosch L