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29 results on '"Majoor, Christof J."'

1. Targeted exhaled breath analysis for detection of Pseudomonas aeruginosa in cystic fibrosis patients

Author

Kos, Renate, Brinkman, Paul, Neerincx, Anne H., Paff, Tamara, Gerritsen, Marije G., Lammers, Ariana, Kraneveld, Aletta D., Heijerman, Harry G.M., Janssens, Hettie M., Davies, Jane C., Majoor, Christof J., Weersink, Els J., Sterk, Peter J., Haarman, Eric G., Bos, Lieuwe D., Maitland-van der Zee, Anke H., Kos, Renate, Brinkman, Paul, Neerincx, Anne H., Paff, Tamara, Gerritsen, Marije G., Lammers, Ariana, Kraneveld, Aletta D., Heijerman, Harry G.M., Janssens, Hettie M., Davies, Jane C., Majoor, Christof J., Weersink, Els J., Sterk, Peter J., Haarman, Eric G., Bos, Lieuwe D., and Maitland-van der Zee, Anke H.

Abstract

Background: Pseudomonas aeruginosa (PA) is an important respiratory pathogen for cystic fibrosis (CF) patients. Routine microbiology surveillance is time-consuming, and is best performed on expectorated sputum. As alternative, volatile organic compounds (VOCs) may be indicative of PA colonisation. In this study, we aimed to identify VOCs associated with PA in literature and perform targeted exhaled breath analysis to recognize PA positive CF patients non-invasively. Methods: This study consisted of 1) a literature review to select VOCs of interest, and 2) a cross-sectional CF study. Definitions used: A) PA positive, PA culture at visit/chronically; B) PA free, no PA culture in ≥12 months. Exhaled VOCs were identified via quadrupole MS. The primary endpoint was the area under the receiver operating characteristics curve (AUROCC) of individual VOCs as well as combined VOCs against PA culture. Results: 241 VOCs were identified in literature, of which 56 were further evaluated, and 13 could be detected in exhaled breath in our cohort. Exhaled breath of 25 pediatric and 28 adult CF patients, PA positive (n=16) and free (n=28) was available. 3/13 VOCs were significantly (p<0.05) different between PA groups in children; none were in adults. Notably, a composite model based on 5 or 1 VOC(s) showed an AUROCC of 0.86 (CI 0.71–1.0) and 0.87 (CI 0.72–1.0) for adults and children, respectively. Conclusions: Targeted VOC analysis appears to discriminate children and adults with and without PA positive cultures with clinically acceptable sensitivity values.

Published
2022

2. Individual and group response of treatment with ivacaftor on airway and gut microbiota in people with cf and a s1251n mutation

Author

Kristensen, Maartje I., de Winter-De Groot, Karin M., Berkers, Gitte, Chu, Mei Ling J.N., Arp, Kayleigh, Ghijsen, Sophie, Heijerman, Harry G.M., Arets, Hubertus G.M., Majoor, Christof J., Janssens, Hettie M., van der Meer, Renske, Bogaert, Debby, van der Ent, Cornelis K., Kristensen, Maartje I., de Winter-De Groot, Karin M., Berkers, Gitte, Chu, Mei Ling J.N., Arp, Kayleigh, Ghijsen, Sophie, Heijerman, Harry G.M., Arets, Hubertus G.M., Majoor, Christof J., Janssens, Hettie M., van der Meer, Renske, Bogaert, Debby, and van der Ent, Cornelis K.

Abstract

Ivacaftor has been shown to restore the functionality of the S1251N (also known as c.3752G>A) mutated CFTR, which may cause alterations in both airway and gut physiology and micro-environment, resulting in a change of microbiota in these organs. The aim of the present study was to analyze the effects of ivacaftor on the microbial community composition of both airway and gut in subjects with CF carrying one S1251N mutation, using a 16S rRNA gene-based sequencing approach. In 16 subjects with CF, repetitive samples from airways and gut were collected just before, and 2 months after, and, for 8 patients, also 9 and 12 months after, start of ivacaftor. 16S rRNA based sequencing identified 344 operational taxonomical units (OTUs) in a total of 139 samples (35 nasopharyngeal, 39 oropharyngeal, 29 sputum, and 36 fecal samples). Ivacaftor significantly enhanced bacterial diversity and overall microbiota composition in the gut (p < 0.01). There were no significant changes in the overall microbial composition and alpha diversity in upper and lower airways of these patients after ivacaftor treatment. Treatment with ivacaftor induces changes in gut microbiota whereas airway microbiota do not change significantly over time.

Published
2021

3. Individual and Group Response of Treatment with Ivacaftor on Airway and Gut Microbiota in People with CF and a S1251N Mutation

Author

Child Health, Longziekten onderzoek 1, Klinische zorg, Longziekten patientenzorg, Longziekten, Infection & Immunity, Cluster B, Speerpunt Child Health, Kristensen, Maartje I, de Winter-de Groot, Karin M, Berkers, Gitte, Chu, Mei Ling J N, Arp, Kayleigh, Ghijsen, Sophie, Heijerman, Harry G M, Arets, Hubertus G M, Majoor, Christof J, Janssens, Hettie M, van der Meer, Renske, Bogaert, Debby, van der Ent, Cornelis K, Child Health, Longziekten onderzoek 1, Klinische zorg, Longziekten patientenzorg, Longziekten, Infection & Immunity, Cluster B, Speerpunt Child Health, Kristensen, Maartje I, de Winter-de Groot, Karin M, Berkers, Gitte, Chu, Mei Ling J N, Arp, Kayleigh, Ghijsen, Sophie, Heijerman, Harry G M, Arets, Hubertus G M, Majoor, Christof J, Janssens, Hettie M, van der Meer, Renske, Bogaert, Debby, and van der Ent, Cornelis K

Published
2021

4. Clinical effects of the three CFTR potentiator treatments curcumin, genistein and ivacaftor in patients with the CFTR-S1251N gating mutation

Author

Longziekten onderzoek 1, Child Health, Beleid & Communicatie, CTI, Longziekten, Infection & Immunity, Longziekten onderzoek 2, Onderzoek, Regenerative Medicine and Stem Cells, Longziekten patientenzorg, Speerpunt Child Health, Berkers, Gitte, van der Meer, Renske, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Suen, Sylvia Wf, Heijerman, Harry Gm, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Janssens, Hettie M, de Rijke, Yolanda B, Kemper, E Marleen, Beekman, Jeffrey M, van der Ent, Cornelis K, de Jonge, Hugo R, Longziekten onderzoek 1, Child Health, Beleid & Communicatie, CTI, Longziekten, Infection & Immunity, Longziekten onderzoek 2, Onderzoek, Regenerative Medicine and Stem Cells, Longziekten patientenzorg, Speerpunt Child Health, Berkers, Gitte, van der Meer, Renske, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Suen, Sylvia Wf, Heijerman, Harry Gm, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Janssens, Hettie M, de Rijke, Yolanda B, Kemper, E Marleen, Beekman, Jeffrey M, van der Ent, Cornelis K, and de Jonge, Hugo R

Published
2020

5. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, van der Ent, Cornelis K, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, and van der Ent, Cornelis K

Published
2019

6. Home videos of cystic fibrosis patients using tobramycin inhalation powder : Relation of flow and cough

Author

Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, Tiddens, Harm A W M, Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, and Tiddens, Harm A W M

Published
2019

7. Eosinophils capture viruses, a capacity that is defective in asthma

Author

Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, Lutter, René, Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, and Lutter, René

Published
2019

8. Home videos of cystic fibrosis patients using tobramycin inhalation powder : Relation of flow and cough

Author

Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, Tiddens, Harm A W M, Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, and Tiddens, Harm A W M

Published
2019

9. Eosinophils capture viruses, a capacity that is defective in asthma

Author

Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, Lutter, René, Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, and Lutter, René

Published
2019

10. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, van der Ent, Cornelis K, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, and van der Ent, Cornelis K

Published
2019

11. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, van der Ent, Cornelis K, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, and van der Ent, Cornelis K

Abstract

In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolin-induced swelling and studied the correlation with in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and change in sweat chloride concentration. Receiver operating characteristic curves indicated good-to-excellent accuracy of the organoid-based test for defining clinical responses. This study indicates that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients and suggests that biobanked stem cell resources can be used to tailor individual treatments in a cost-effective and patient-friendly manner.

Published
2019

12. Eosinophils capture viruses, a capacity that is defective in asthma

Author

Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, Lutter, René, Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, and Lutter, René

Published
2019

13. Home videos of cystic fibrosis patients using tobramycin inhalation powder : Relation of flow and cough

Author

Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, Tiddens, Harm A W M, Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, and Tiddens, Harm A W M

Published
2019

14. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, van der Ent, Cornelis K, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, and van der Ent, Cornelis K

Published
2019

15. Home videos of cystic fibrosis patients using tobramycin inhalation powder: Relation of flow and cough

Author

Longziekten patientenzorg, Child Health, Longziekten, Infection & Immunity, Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, Tiddens, Harm A W M, Longziekten patientenzorg, Child Health, Longziekten, Infection & Immunity, Meerburg, Jennifer J, Albasri, Mehdi, van der Wiel, Els C, Andrinopoulou, Eleni-Rosalina, van der Eerden, Menno M, Majoor, Christof J, Arets, Hubertus G M, Heijerman, Harry G M, and Tiddens, Harm A W M

Published
2019

16. Eosinophils capture viruses, a capacity that is defective in asthma

Author

Experimentele Afdeling Longziekten, Cancer, Infection & Immunity, Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, Lutter, René, Experimentele Afdeling Longziekten, Cancer, Infection & Immunity, Sabogal Piñeros, Yanaika S, Bal, Suzanne M, Dijkhuis, Annemiek, Majoor, Christof J, Dierdorp, Barbara S, Dekker, Tamara, Hoefsmit, Esmée P, Bonta, Peter I, Picavet, Daisy, van der Wel, Nicole N, Koenderman, Leo, Sterk, Peter J, Ravanetti, Lara, and Lutter, René

Published
2019

17. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Longziekten onderzoek 1, Child Health, CTI, Longziekten patientenzorg, MDL, Longziekten, Infection & Immunity, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Hubrecht Institute with UMC, CMM Sectie Molecular Cancer Research, Regenerative Medicine and Stem Cells, Longziekten onderzoek 2, Onderzoek, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, van der Ent, Cornelis K, Longziekten onderzoek 1, Child Health, CTI, Longziekten patientenzorg, MDL, Longziekten, Infection & Immunity, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Hubrecht Institute with UMC, CMM Sectie Molecular Cancer Research, Regenerative Medicine and Stem Cells, Longziekten onderzoek 2, Onderzoek, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, and van der Ent, Cornelis K

Published
2019

18. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Author

Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, van der Ent, Cornelis K, Berkers, Gitte, van Mourik, Peter, Vonk, Annelotte M, Kruisselbrink, Evelien, Dekkers, Johanna F, de Winter-de Groot, Karin M, Arets, Hubertus G M, Marck-van der Wilt, Rozemarijn E P, Dijkema, Jasper S, Vanderschuren, Maaike M, Houwen, Roderick H J, Heijerman, Harry G M, van de Graaf, Eduard A, Elias, Sjoerd G, Majoor, Christof J, Koppelman, Gerard H, Roukema, Jolt, Bakker, Marleen, Janssens, Hettie M, van der Meer, Renske, Vries, Robert G J, Clevers, Hans C, de Jonge, Hugo R, Beekman, Jeffrey M, and van der Ent, Cornelis K

Abstract

In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolin-induced swelling and studied the correlation with in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and change in sweat chloride concentration. Receiver operating characteristic curves indicated good-to-excellent accuracy of the organoid-based test for defining clinical responses. This study indicates that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients and suggests that biobanked stem cell resources can be used to tailor individual treatments in a cost-effective and patient-friendly manner.

Published
2019

19. β2-Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis

Author

Vijftigschild, Lodewijk A W, Berkers, Gitte, Dekkers, Johanna F, Zomer-van Ommen, Domenique D, Matthes, Elizabeth, Kruisselbrink, Evelien, Vonk, Annelotte, Hensen, Chantal E, Heida-Michel, Sabine, Geerdink, Margot, Janssens, Hettie M, van de Graaf, Eduard A, Bronsveld, Inez, de Winter-de Groot, Karin M, Majoor, Christof J, Heijerman, Harry G M, de Jonge, Hugo R, Hanrahan, John W, van der Ent, Cornelis K, Beekman, Jeffrey M, Vijftigschild, Lodewijk A W, Berkers, Gitte, Dekkers, Johanna F, Zomer-van Ommen, Domenique D, Matthes, Elizabeth, Kruisselbrink, Evelien, Vonk, Annelotte, Hensen, Chantal E, Heida-Michel, Sabine, Geerdink, Margot, Janssens, Hettie M, van de Graaf, Eduard A, Bronsveld, Inez, de Winter-de Groot, Karin M, Majoor, Christof J, Heijerman, Harry G M, de Jonge, Hugo R, Hanrahan, John W, van der Ent, Cornelis K, and Beekman, Jeffrey M

Published
2016

20. Intestinal Organoid Swelling And Relation With Disease Severity And Response To Therapy

Author

Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, van der Ent, Cornelis K., Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, and van der Ent, Cornelis K.

Published
2016

21. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., Beekman, Jeffrey M, Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., and Beekman, Jeffrey M

Published
2016

22. Intestinal Organoid Swelling And Relation With Disease Severity And Response To Therapy

Author

Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, van der Ent, Cornelis K., Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, and van der Ent, Cornelis K.

Published
2016

23. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., Beekman, Jeffrey M, Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., and Beekman, Jeffrey M

Published
2016

24. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Dekkers, Johanna F, Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, de Jonge, Hugo R, Janssens, Hettie M, Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P, Escher, Johanna C, de Rijke, Yolanda B, Majoor, Christof J, Heijerman, Harry G M, de Winter-de Groot, Karin M, Clevers, Hans, van der Ent, Cornelis K, Beekman, Jeffrey M, Dekkers, Johanna F, Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, de Jonge, Hugo R, Janssens, Hettie M, Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P, Escher, Johanna C, de Rijke, Yolanda B, Majoor, Christof J, Heijerman, Harry G M, de Winter-de Groot, Karin M, Clevers, Hans, van der Ent, Cornelis K, and Beekman, Jeffrey M

Abstract

Identifying subjects with cystic fibrosis (CF) who may benefit from cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs is time-consuming, costly, and especially challenging for individuals with rare uncharacterized CFTR mutations. We studied CFTR function and responses to two drugs-the prototypical CFTR potentiator VX-770 (ivacaftor/KALYDECO) and the CFTR corrector VX-809 (lumacaftor)-in organoid cultures derived from the rectal epithelia of subjects with CF, who expressed a broad range of CFTR mutations. We observed that CFTR residual function and responses to drug therapy depended on both the CFTR mutation and the genetic background of the subjects. In vitro drug responses in rectal organoids positively correlated with published outcome data from clinical trials with VX-809 and VX-770, allowing us to predict from preclinical data the potential for CF patients carrying rare CFTR mutations to respond to drug therapy. We demonstrated proof of principle by selecting two subjects expressing an uncharacterized rare CFTR genotype (G1249R/F508del) who showed clinical responses to treatment with ivacaftor and one subject (F508del/R347P) who showed a limited response to drug therapy both in vitro and in vivo. These data suggest that in vitro measurements of CFTR function in patient-derived rectal organoids may be useful for identifying subjects who would benefit from CFTR-correcting treatment, independent of their CFTR mutation.

Published
2016

25. Intestinal Organoid Swelling And Relation With Disease Severity And Response To Therapy

Author

Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, van der Ent, Cornelis K., Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, and van der Ent, Cornelis K.

Published
2016

26. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., Beekman, Jeffrey M, Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., and Beekman, Jeffrey M

Published
2016

27. Intestinal Organoid Swelling And Relation With Disease Severity And Response To Therapy

Author

Longziekten onderzoek 1, Other research (not in main researchprogram), Child Health, Longziekten patientenzorg, CTI, Longziekten onderzoek 2, MDL patientenzorg, Cluster C, Longziekten, Infection & Immunity, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Cancer, Regenerative Medicine and Stem Cells, Beekman, Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, van der Ent, Cornelis K., Longziekten onderzoek 1, Other research (not in main researchprogram), Child Health, Longziekten patientenzorg, CTI, Longziekten onderzoek 2, MDL patientenzorg, Cluster C, Longziekten, Infection & Immunity, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Cancer, Regenerative Medicine and Stem Cells, Beekman, Berkers, Gitte, de Winter-de Groot, Karin M., Dekkers, Johanna F., Vonk, Annelotte M., Kruisselbrink, Evelien, Hagemeijer, Marne C., Heida-Michel, Sabine, Geerdink, Margot, Arets, Hubertus G., van der Wilt, Roos E., Houwen, Roderick H., van de Graaf, Ed, Majoor, Christof J., Koppelman, Gerard H., Roukema, Jolt, Heijerman, H., van der Meer, Renske, Vries, Robert, Clevers, Hans C., de Jonge, Hugo, Escher, J. C., Tiddens, Harm, Janssens, Hettie, Beekman, Jeffrey, and van der Ent, Cornelis K.

Published
2016

28. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Longziekten onderzoek 1, Other research (not in main researchprogram), CTI, Longziekten, Infection & Immunity, Zorg en O&O, Child Health, Regenerative Medicine and Stem Cells, MDL patientenzorg, Cluster C, MS MDL Oncologie, Cancer, MS MDL 1, Longziekten patientenzorg, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Beekman, Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., Beekman, Jeffrey M, Longziekten onderzoek 1, Other research (not in main researchprogram), CTI, Longziekten, Infection & Immunity, Zorg en O&O, Child Health, Regenerative Medicine and Stem Cells, MDL patientenzorg, Cluster C, MS MDL Oncologie, Cancer, MS MDL 1, Longziekten patientenzorg, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Beekman, Dekkers, Johanna F., Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, De Jonge, Hugo R., Janssens, Hettie M., Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P., Escher, Johanna C., De Rijke, Yolanda B., Majoor, Christof J., Heijerman, Harry G M, De Winter-De Groot, Karin M., Clevers, Hans, Van Der Ent, Cornelis K., and Beekman, Jeffrey M

Published
2016

29. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Author

Dekkers, Johanna F, Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, de Jonge, Hugo R, Janssens, Hettie M, Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P, Escher, Johanna C, de Rijke, Yolanda B, Majoor, Christof J, Heijerman, Harry G M, de Winter-de Groot, Karin M, Clevers, Hans, van der Ent, Cornelis K, Beekman, Jeffrey M, Dekkers, Johanna F, Berkers, Gitte, Kruisselbrink, Evelien, Vonk, Annelotte, de Jonge, Hugo R, Janssens, Hettie M, Bronsveld, Inez, van de Graaf, Eduard A, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Vleggaar, Frank P, Escher, Johanna C, de Rijke, Yolanda B, Majoor, Christof J, Heijerman, Harry G M, de Winter-de Groot, Karin M, Clevers, Hans, van der Ent, Cornelis K, and Beekman, Jeffrey M

Abstract

Identifying subjects with cystic fibrosis (CF) who may benefit from cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs is time-consuming, costly, and especially challenging for individuals with rare uncharacterized CFTR mutations. We studied CFTR function and responses to two drugs-the prototypical CFTR potentiator VX-770 (ivacaftor/KALYDECO) and the CFTR corrector VX-809 (lumacaftor)-in organoid cultures derived from the rectal epithelia of subjects with CF, who expressed a broad range of CFTR mutations. We observed that CFTR residual function and responses to drug therapy depended on both the CFTR mutation and the genetic background of the subjects. In vitro drug responses in rectal organoids positively correlated with published outcome data from clinical trials with VX-809 and VX-770, allowing us to predict from preclinical data the potential for CF patients carrying rare CFTR mutations to respond to drug therapy. We demonstrated proof of principle by selecting two subjects expressing an uncharacterized rare CFTR genotype (G1249R/F508del) who showed clinical responses to treatment with ivacaftor and one subject (F508del/R347P) who showed a limited response to drug therapy both in vitro and in vivo. These data suggest that in vitro measurements of CFTR function in patient-derived rectal organoids may be useful for identifying subjects who would benefit from CFTR-correcting treatment, independent of their CFTR mutation.

Published
2016

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