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281 results on '"van der Ent, C. K."'

2. FDA-approved drug screening in patient-derived organoids demonstrates potential of drug repurposing for rare cystic fibrosis genotypes

Author

de Poel, E., Spelier, S., Hagemeijer, M. C., van Mourik, P., Suen, S. W.F., Vonk, A. M., Brunsveld, J. E., Ithakisiou, G. N., Kruisselbrink, E., Oppelaar, H., Berkers, G., de Winter de Groot, K. M., Heida-Michel, S., Jans, S. R., van Panhuis, H., Bakker, M., van der Meer, R., Roukema, J., Dompeling, E., Weersink, E. J.M., Koppelman, G. H., Blaazer, A. R., Muijlwijk-Koezen, J. E., van der Ent, C. K., Beekman, J. M., de Poel, E., Spelier, S., Hagemeijer, M. C., van Mourik, P., Suen, S. W.F., Vonk, A. M., Brunsveld, J. E., Ithakisiou, G. N., Kruisselbrink, E., Oppelaar, H., Berkers, G., de Winter de Groot, K. M., Heida-Michel, S., Jans, S. R., van Panhuis, H., Bakker, M., van der Meer, R., Roukema, J., Dompeling, E., Weersink, E. J.M., Koppelman, G. H., Blaazer, A. R., Muijlwijk-Koezen, J. E., van der Ent, C. K., and Beekman, J. M.

Abstract

Background: Preclinical cell-based assays that recapitulate human disease play an important role in drug repurposing. We previously developed a functional forskolin induced swelling (FIS) assay using patient-derived intestinal organoids (PDIOs), allowing functional characterization of CFTR, the gene mutated in people with cystic fibrosis (pwCF). CFTR function-increasing pharmacotherapies have revolutionized treatment for approximately 85% of people with CF who carry the most prevalent F508del-CFTR mutation, but a large unmet need remains to identify new treatments for all pwCF. Methods: We used 76 PDIOs not homozygous for F508del-CFTR to test the efficacy of 1400 FDA-approved drugs on improving CFTR function, as measured in FIS assays. The most promising hits were verified in a secondary FIS screen. Based on the results of this secondary screen, we further investigated CFTR elevating function of PDE4 inhibitors and currently existing CFTR modulators. Results: In the primary screen, 30 hits were characterized that elevated CFTR function. In the secondary validation screen, 19 hits were confirmed and categorized in three main drug families: CFTR modulators, PDE4 inhibitors and tyrosine kinase inhibitors. We show that PDE4 inhibitors are potent CFTR function inducers in PDIOs where residual CFTR function is either present, or created by additional compound exposure. Additionally, upon CFTR modulator treatment we show rescue of CF genotypes that are currently not eligible for this therapy. Conclusion: This study exemplifies the feasibility of high-throughput compound screening using PDIOs. We show the potential of repurposing drugs for pwCF carrying non-F508del genotypes that are currently not eligible for therapies. One-sentence summary: We screened 1400 FDA-approved drugs in CF patient-derived intestinal organoids using the previously established functional FIS assay, and show the potential of repurposing PDE4 inhibitors and CFTR modulators for rare CF genotypes.

Published
2023
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3. Targeted locus amplification reveals heterogeneity between and within CFTR genotypes and association with CFTR function in patient-derived intestinal organoids

Author

Cancer, Longziekten onderzoek 2, CMM, CMM Groep De Ridder, Longziekten onderzoek 1, MS MDL 1, Arts Assistenten Longziekten, Longziekten patientenzorg, Speerpunt Child Health, Child Health, Infection & Immunity, Hubrecht Institute with UMC, Onderzoek, Regenerative Medicine and Stem Cells, Lefferts, J. W., Boersma, V., Nieuwenhuijze, N. D.A., Suen, S. W.F., Hajo, K., Collantes, N. Sanchez, Vermeulen, C., Groeneweg, T., Hagemeijer, M. C., de Jonge, H. R., van der Ent, C. K., Splinter, E., Beekman, J. M., Cancer, Longziekten onderzoek 2, CMM, CMM Groep De Ridder, Longziekten onderzoek 1, MS MDL 1, Arts Assistenten Longziekten, Longziekten patientenzorg, Speerpunt Child Health, Child Health, Infection & Immunity, Hubrecht Institute with UMC, Onderzoek, Regenerative Medicine and Stem Cells, Lefferts, J. W., Boersma, V., Nieuwenhuijze, N. D.A., Suen, S. W.F., Hajo, K., Collantes, N. Sanchez, Vermeulen, C., Groeneweg, T., Hagemeijer, M. C., de Jonge, H. R., van der Ent, C. K., Splinter, E., and Beekman, J. M.

Published
2023

4. FDA-approved drug screening in patient-derived organoids demonstrates potential of drug repurposing for rare cystic fibrosis genotypes

Author

Longziekten onderzoek 2, Child Health, Arts Assistenten Longziekten, Beleid & Communicatie, CTI, Translational Neuroscience, Revalidatiegeneeskunde Onderwijs, Longziekten patientenzorg, Afdeling Hartcatheterisatie, Epi Kanker Team A, Longziekten, Speerpunt Child Health, Infection & Immunity, Onderzoek, Regenerative Medicine and Stem Cells, de Poel, E., Spelier, S., Hagemeijer, M. C., van Mourik, P., Suen, S. W.F., Vonk, A. M., Brunsveld, J. E., Ithakisiou, G. N., Kruisselbrink, E., Oppelaar, H., Berkers, G., de Winter de Groot, K. M., Heida-Michel, S., Jans, S. R., van Panhuis, H., Bakker, M., van der Meer, R., Roukema, J., Dompeling, E., Weersink, E. J.M., Koppelman, G. H., Blaazer, A. R., Muijlwijk-Koezen, J. E., van der Ent, C. K., Beekman, J. M., Longziekten onderzoek 2, Child Health, Arts Assistenten Longziekten, Beleid & Communicatie, CTI, Translational Neuroscience, Revalidatiegeneeskunde Onderwijs, Longziekten patientenzorg, Afdeling Hartcatheterisatie, Epi Kanker Team A, Longziekten, Speerpunt Child Health, Infection & Immunity, Onderzoek, Regenerative Medicine and Stem Cells, de Poel, E., Spelier, S., Hagemeijer, M. C., van Mourik, P., Suen, S. W.F., Vonk, A. M., Brunsveld, J. E., Ithakisiou, G. N., Kruisselbrink, E., Oppelaar, H., Berkers, G., de Winter de Groot, K. M., Heida-Michel, S., Jans, S. R., van Panhuis, H., Bakker, M., van der Meer, R., Roukema, J., Dompeling, E., Weersink, E. J.M., Koppelman, G. H., Blaazer, A. R., Muijlwijk-Koezen, J. E., van der Ent, C. K., and Beekman, J. M.

Published
2023

5. Effectiveness of alpine climate treatment for children with difficult to treat atopic dermatitis: Results of a pragmatic randomized controlled trial (DAVOS trial)

Author

Fieten, K. B., Schappin, R., Zijlstra, W. T., Figee, L., Beutler, J., Raymakers, F., van Os‐Medendorp, H., Stellato, R., Vandewall, M., Winkelhof, J., Uniken Venema, M., Bruijnzeel‐Koomen, C. A. F. M., Rijssenbeek‐Nouwens, L., van der Ent, C. K., van Hoffen, E., Meijer, Y., and Pasmans, S. G. M. A.

Published
2018
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7. Functional Restoration of CFTR Nonsense Mutations in Intestinal Organoids

Author

de Poel, E., Spelier, S., Suen, S. W.F., Kruisselbrink, E., Graeber, S. Y., Mall, M. A., Weersink, E. J.M., van der Eerden, M. M., Koppelman, G. H., van der Ent, C. K., Beekman, J. M., de Poel, E., Spelier, S., Suen, S. W.F., Kruisselbrink, E., Graeber, S. Y., Mall, M. A., Weersink, E. J.M., van der Eerden, M. M., Koppelman, G. H., van der Ent, C. K., and Beekman, J. M.

Abstract

Background: Pharmacotherapies for people with cystic fibrosis (pwCF) who have premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are under development. Thus far, clinical studies focused on compounds that induce translational readthrough (RT) at the mRNA PTC location. Recent studies using primary airway cells showed that PTC functional restoration can be achieved through combining compounds with multiple mode-of-actions. Here, we assessed induction of CFTR function in PTC-containing intestinal organoids using compounds targeting RT, nonsense mRNA mediated decay (NMD) and CFTR protein modulation. Methods: Rescue of PTC CFTR protein was assessed by forskolin-induced swelling of 12 intestinal organoid cultures carrying distinct PTC mutations. Effects of compounds on mRNA CFTR level was assessed by RT-qPCRs. Results: Whilst response varied between donors, significant rescue of CFTR function was achieved for most donors with the quintuple combination of a commercially available pharmacological equivalent of the RT compound (ELX-02-disulfate or ELX-02ds), NMD inhibitor SMG1i, correctors VX-445 and VX-661 and potentiator VX-770. The quintuple combination of pharmacotherapies reached swelling quantities higher than the mean swelling of three VX-809/VX-770-rescued F508del/F508del organoid cultures, indicating level of rescue is of clinical relevance as VX-770/VX-809-mediated F508del/F508del rescue in organoids correlate with substantial improvement of clinical outcome. Conclusions: Whilst variation in efficacy was observed between genotypes as well as within genotypes, the data suggests that strong pharmacological rescue of PTC requires a combination of drugs that target RT, NMD and protein function.

Published
2022

8. Functional Restoration of CFTR Nonsense Mutations in Intestinal Organoids

Author

Longziekten onderzoek 2, CTI, Longziekten patientenzorg, Speerpunt Child Health, Child Health, Infection & Immunity, Onderzoek, Regenerative Medicine and Stem Cells, de Poel, E., Spelier, S., Suen, S. W.F., Kruisselbrink, E., Graeber, S. Y., Mall, M. A., Weersink, E. J.M., van der Eerden, M. M., Koppelman, G. H., van der Ent, C. K., Beekman, J. M., Longziekten onderzoek 2, CTI, Longziekten patientenzorg, Speerpunt Child Health, Child Health, Infection & Immunity, Onderzoek, Regenerative Medicine and Stem Cells, de Poel, E., Spelier, S., Suen, S. W.F., Kruisselbrink, E., Graeber, S. Y., Mall, M. A., Weersink, E. J.M., van der Eerden, M. M., Koppelman, G. H., van der Ent, C. K., and Beekman, J. M.

Published
2022

9. Forskolin induced swelling (FIS) assay in intestinal organoids to guide eligibility for compassionate use treatment in a CF patient with a rare genotype

Author

Onderzoek Longziekten, Infection & Immunity, Longziekten patientenzorg, Speerpunt Child Health, Child Health, Longziekten onderzoek 2, Onderzoek, Regenerative Medicine and Stem Cells, Longziekten, Aalbers, B L, Brunsveld, J E, van der Ent, C K, van den Eijnden, J C, Beekman, J M, Heijerman, H G M, Onderzoek Longziekten, Infection & Immunity, Longziekten patientenzorg, Speerpunt Child Health, Child Health, Longziekten onderzoek 2, Onderzoek, Regenerative Medicine and Stem Cells, Longziekten, Aalbers, B L, Brunsveld, J E, van der Ent, C K, van den Eijnden, J C, Beekman, J M, and Heijerman, H G M

Published
2022

12. Females with cystic fibrosis have a larger decrease in sweat chloride in response to lumacaftor/ivacaftor compared to males

Author

Onderzoek Longziekten, Infection & Immunity, Longziekten, Longziekten patientenzorg, Child Health, Verpleegkundig Specialisten Longziekten, Speerpunt Child Health, Aalbers, B. L., Hofland, R. W., Bronsveld, I., de Winter-de Groot, K. M., Arets, H. G.M., de Kiviet, A. C., van Oirschot-van de Ven, M. M.M., Kruijswijk, M. A., Schotman, S., Michel, S., van der Ent, C. K., Heijerman, H. G.M., Onderzoek Longziekten, Infection & Immunity, Longziekten, Longziekten patientenzorg, Child Health, Verpleegkundig Specialisten Longziekten, Speerpunt Child Health, Aalbers, B. L., Hofland, R. W., Bronsveld, I., de Winter-de Groot, K. M., Arets, H. G.M., de Kiviet, A. C., van Oirschot-van de Ven, M. M.M., Kruijswijk, M. A., Schotman, S., Michel, S., van der Ent, C. K., and Heijerman, H. G.M.

Published
2021

18. Risk factors for atopic diseases and recurrent respiratory tract infections in children

Author

Kansen, H. M., Lebbink, M. A., de Mul, J., van Erp, F. C., van Engelen, M., de Vries, E., Prevaes, S. M. P. J., Le , T. M., van der Ent, C. K., Verhagen, L. M., Kansen, H. M., Lebbink, M. A., de Mul, J., van Erp, F. C., van Engelen, M., de Vries, E., Prevaes, S. M. P. J., Le , T. M., van der Ent, C. K., and Verhagen, L. M.

Abstract

Introduction: The simultaneously increased prevalence of atopic diseases and decreased prevalence of infectious diseases might point to a link between the two entities. Past work mainly focused on either atopic diseases or recurrent infections. We aim to investigate whether risk factors for atopic diseases (ie, asthma, allergic rhinitis, atopic dermatitis, and/or food allergy) differ from risk factors for recurrent respiratory tract infections (RRTIs) in children. Methods: Cross-sectional data were used from 5517 children aged 1 to 18 years who participated in an Electronic Portal for children between 2011 and 2019. Univariable/multivariable logistic regression analyses were performed to determine risk factors for any atopic disease and RRTIs. Results: Children aged ≥5 years were more likely to have any atopic disease (adjusted odds ratio [OR]: 1.50-2.77) and less likely to have RRTIs (OR: 0.68-0.84) compared to children aged less than 5 years. Female sex (OR: 0.72; 95% confidence interval [CI]: 0.63-0.81), low birth weight (OR: 0.74; 95% CI: 0.57-0.97) and dog ownership (OR: 0.79; 95% CI: 0.66-0.95) reduced the odds of any atopic disease, but not of RRTIs. Daycare attendance (OR: 1.22; 95% CI: 1.02-1.47) was associated with RRTIs, but not with atopic diseases. A family history of asthma, allergic rhinitis, atopic dermatitis, and RRTIs was significantly associated with the same entity in children, with OR varying from 1.58 (95% CI: 1.35-1.85) in allergic rhinitis to 2.20 (95% CI: 1.85-2.61) in asthma. Conclusion: Risk factors for atopic diseases are distinct from risk factors for RRTIs, suggesting that the changing prevalence of both entities is not related to shared risk factors.

Published
2020

19. Long-term effects of ivacaftor on nonpulmonary outcomes in individuals with cystic fibrosis, heterozygous for a S1251N mutation

Author

Activity&Health sectie exercise, Longziekten onderzoek 1, Child Health, Afdeling Dietetiek, Longziekten patientenzorg, Speerpunt Child Health, Infection & Immunity, Longziekten, Burghard, M., Berkers, G., Ghijsen, S., Hollander-Kraaijeveld, F. M., de Winter-de Groot, K. M., van der Ent, C. K., Heijerman, H. G.M., Takken, T., Hulzebos, H. J., Activity&Health sectie exercise, Longziekten onderzoek 1, Child Health, Afdeling Dietetiek, Longziekten patientenzorg, Speerpunt Child Health, Infection & Immunity, Longziekten, Burghard, M., Berkers, G., Ghijsen, S., Hollander-Kraaijeveld, F. M., de Winter-de Groot, K. M., van der Ent, C. K., Heijerman, H. G.M., Takken, T., and Hulzebos, H. J.

Published
2020

20. Prevalence and predictors of uncontrolled asthma in children referred for asthma and other atopic diseases

Author

Longziekten onderzoek 1, MS Dermatologie/Allergologie, Cardiovasculaire Epi Team 4, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Longziekten patientenzorg, Infection & Immunity, Child Health, Speerpunt Child Health, Unit Opleiding Dermatologie, Kansen, H. M., Le, T. M., Uiterwaal, C. S.P.M., van Ewijk, B. E., Balemans, W. A.F., Gorissen, D. M.W., de Vries, E., van Velzen, M. F., Slabbers, G. H.P.R., Meijer, Y., Knulst, A. C., van der Ent, C. K., van Erp, F. C., Longziekten onderzoek 1, MS Dermatologie/Allergologie, Cardiovasculaire Epi Team 4, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Longziekten patientenzorg, Infection & Immunity, Child Health, Speerpunt Child Health, Unit Opleiding Dermatologie, Kansen, H. M., Le, T. M., Uiterwaal, C. S.P.M., van Ewijk, B. E., Balemans, W. A.F., Gorissen, D. M.W., de Vries, E., van Velzen, M. F., Slabbers, G. H.P.R., Meijer, Y., Knulst, A. C., van der Ent, C. K., and van Erp, F. C.

Published
2020

21. Clinical effect of lumacaftor/ivacaftor in F508del homozygous CF patients with FEV1 ≥ 90% predicted at baseline

Author

Onderzoek Longziekten, Infection & Immunity, Longziekten patientenzorg, Child Health, Longziekten, Verpleegkundig Specialisten Longziekten, Speerpunt Child Health, Aalbers, B L, de Winter-de Groot, K M, Arets, H G M, Hofland, R W, de Kiviet, A C, van Oirschot-van de Ven, M M M, Kruijswijk, M A, Schotman, S, Michel, S, van der Ent, C K, Heijerman, H G M, Onderzoek Longziekten, Infection & Immunity, Longziekten patientenzorg, Child Health, Longziekten, Verpleegkundig Specialisten Longziekten, Speerpunt Child Health, Aalbers, B L, de Winter-de Groot, K M, Arets, H G M, Hofland, R W, de Kiviet, A C, van Oirschot-van de Ven, M M M, Kruijswijk, M A, Schotman, S, Michel, S, van der Ent, C K, and Heijerman, H G M

Published
2020

33. Specifieke allergenen bij de diagnostiek van pinda-allergie

Author

van Erp, Francine C., Le, T. M., Kansen, H. M., Meijer, Y., van der Ent, C. K., Knol, E. F., and Knulst, A. C.

Subjects
Component-resolved diagnostics, Peanut, Infectious Diseases, SIgE, food and beverages, Critical Care and Intensive Care Medicine
Abstract

Self-reported peanut allergy is common and has a major impact on quality of life. It is therefore important to accurately diagnose or exclude peanut allergy. Recent publications have shown that using specific IgE to a peanut component (Ara h 2) can optimize the diagnostic work-up in patients with suspected peanut allergy. In this article, we describe the use of these component-resolved diagnostics in daily practice based on three children with suspected peanut allergy. The presented flowchart based on Ara h 2 can improve the diagnostic flow of children with suspected peanut allergy and prevent unnecessary double blind placebo controlled food challenges.

Published
2019

43. Specifieke allergenen bij de diagnostiek van pinda-allergie

Author

Afdeling Dermatologie/Allergologie, KTO Office, Unit Opleiding Dermatologie, MS Dermatologie/Allergologie, Infection & Immunity, Longziekten onderzoek 1, Longziekten patientenzorg, Child Health, Speerpunt Child Health, CTI, van Erp, Francine C., Le, T. M., Kansen, H. M., Meijer, Y., van der Ent, C. K., Knol, E. F., Knulst, A. C., Afdeling Dermatologie/Allergologie, KTO Office, Unit Opleiding Dermatologie, MS Dermatologie/Allergologie, Infection & Immunity, Longziekten onderzoek 1, Longziekten patientenzorg, Child Health, Speerpunt Child Health, CTI, van Erp, Francine C., Le, T. M., Kansen, H. M., Meijer, Y., van der Ent, C. K., Knol, E. F., and Knulst, A. C.

Published
2019

44. The relationship between energy intake and body-growth in children with cystic fibrosis

Author

Afdeling Dietetiek, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Public Health Practice, Child Health, MDL patientenzorg, Woestenenk, J. W., Dalmeijer, G. W., van der Ent, C. K., Houwen, R. H., Afdeling Dietetiek, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Public Health Practice, Child Health, MDL patientenzorg, Woestenenk, J. W., Dalmeijer, G. W., van der Ent, C. K., and Houwen, R. H.

Published
2019

45. Excess early postnatal weight gain and blood pressure in healthy young children

Author

Public Health Epidemiologie, Cardiovasculaire Epi Team 4, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Speerpunt Child Health, Longziekten patientenzorg, Child Health, Infection & Immunity, Cardiovasculaire Epi Team 9, Jansen, M. A. C., Uiterwaal, C. S. P. M., van der Ent, C. K., Grobbee, D. E., Dalmeijer, G. W., Public Health Epidemiologie, Cardiovasculaire Epi Team 4, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Speerpunt Child Health, Longziekten patientenzorg, Child Health, Infection & Immunity, Cardiovasculaire Epi Team 9, Jansen, M. A. C., Uiterwaal, C. S. P. M., van der Ent, C. K., Grobbee, D. E., and Dalmeijer, G. W.

Published
2019

46. Authors’ response: Letter to the Editor ‘Anaemia and iron deficiency in relation to fatigue in cystic fibrosis’

Author

UMC Utrecht, Sociale pediatrie onderzoek 1, Activity&Health sectie exercise, Child Health, Longziekten, Infection & Immunity, Integrale & Alg. Kindergen Patientenzorg, Nap-van der Vlist, M. M., Burghard, M., Hulzebos, H. J., Doeleman, W. R., Heijerman, H. G.M., van der Ent, C. K., Nijhof, S. L., UMC Utrecht, Sociale pediatrie onderzoek 1, Activity&Health sectie exercise, Child Health, Longziekten, Infection & Immunity, Integrale & Alg. Kindergen Patientenzorg, Nap-van der Vlist, M. M., Burghard, M., Hulzebos, H. J., Doeleman, W. R., Heijerman, H. G.M., van der Ent, C. K., and Nijhof, S. L.

Published
2019

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