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3. Genomic Predictors of Outcome in Prostate Cancer

Author

Boström, PJ, Bjartell, AS, Catto, JWF, Eggener, SE, Lilja, H, Loeb, S, Schalken, J, Schlomm, T, and Cooperberg, MR

Subjects
Urology & Nephrology, Clinical Sciences
Abstract

© 2015 European Association of Urology. Context Given the highly variable behavior and clinical course of prostate cancer (PCA) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making. Objective To review the use of genomic biomarkers in the prognostication of PCA outcome and prediction of therapeutic response. Evidence acquisition Systematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014. Evidence synthesis An improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points. Conclusions Major advances have been made in our understanding of PCA biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important. Patient summary We summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests.

Published
2016

4. How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis

Author

N’Dow, J., Smith, E.J., Shepherd, R., Ribal, M., Mottet, N., Moris, L., Lardas, M., Willemse, P-P., Gandaglia, G., Campi, R., Nicoletti, Rossella, Gacci, M., Briganti, A., Ratti, M.M., Alleva, E., Leardini, L., Sisca, E.S., Bangma, R., Roobol, M., Remmers, S., Tilki, D., Visakorpi, T., Talala, K., Tammela, T., van Hemelrijck, M., Bayer, K., Lejeune, S., Byrne, S., Fialho, L., De Meulder, P. Palaiologou B., Auffray, C., Hijazy, A., Power, S., Kermani, N. Zounemat, van Bochove, K., Kalafati, M., Moinat, M., Voss, E., Horgan, D., Fullwood, L., Holtorf, M., Lancet, D., Bernstein, G., Omar, I., MacLennan, S., Maclennan, S., Tripathee, S., Wirth, M., Froehner, M., Brenner, B., Borkowetz, A., Thomas, C., Horn, F., Reiche, K., Kreux, M., Josefsson, A., Tandefekt, D. Gasi, Hugosson, J., Huisman, H., Schalken, J., Hofmacher, T., Lindgren, P., Andersson, E., Fridhammar, A., Zong, J., Butler-Ransohoff, J-E., Herrera, R., Maass, M., Torremante, P., Voss, M.D., Devecseri, Z., Abbott, T., Dau, C., Papineni, K., Snijder, R., Lambrecht, M., Wolfinger, R., Rogiers, S., Servan, A., Antoni, L., Pacoe, K., Robinson, P., Jaton, B., Bakkard, D., Turunen, H., Kilkku, O., Pohjanjousi, P., Voima, O., Nevalaita, L., Reich, C., Araujo, S., Longden-Chapman, E., Burke, D., Agapow, P., Derkits, S., Licour, M., McCrea, C., Payne, S., Yong, A., Thompson, L., Mare, S. Le, Bussmann, M, Kotik, D., Siltari, Aino, Lönnerbro, Ragnar, Pang, Karl, Shiranov, Kirill, Asiimwe, Alex, Evans-Axelsson, Susan, Franks, Billy, Kiran, Amit, Murtola, Teemu J., Schalken, Jack, Steinbeisser, Carl, Bjartell, Anders, and Auvinen, Anssi

Published
2023
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6. How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis

Author

Siltari, Aino, primary, Lönnerbro, Ragnar, additional, Pang, Karl, additional, Shiranov, Kirill, additional, Asiimwe, Alex, additional, Evans-Axelsson, Susan, additional, Franks, Billy, additional, Kiran, Amit, additional, Murtola, Teemu J., additional, Schalken, Jack, additional, Steinbeisser, Carl, additional, Bjartell, Anders, additional, Auvinen, Anssi, additional, N’Dow, J., additional, Smith, E.J., additional, Shepherd, R., additional, Ribal, M., additional, Mottet, N., additional, Moris, L., additional, Lardas, M., additional, Willemse, P-P., additional, Gandaglia, G., additional, Campi, R., additional, Nicoletti, Rossella, additional, Gacci, M., additional, Briganti, A., additional, Ratti, M.M., additional, Alleva, E., additional, Leardini, L., additional, Sisca, E.S., additional, Bangma, R., additional, Roobol, M., additional, Remmers, S., additional, Tilki, D., additional, Visakorpi, T., additional, Talala, K., additional, Tammela, T., additional, van Hemelrijck, M., additional, Bayer, K., additional, Lejeune, S., additional, Byrne, S., additional, Fialho, L., additional, De Meulder, P. Palaiologou B., additional, Auffray, C., additional, Hijazy, A., additional, Power, S., additional, Kermani, N. Zounemat, additional, van Bochove, K., additional, Kalafati, M., additional, Moinat, M., additional, Voss, E., additional, Horgan, D., additional, Fullwood, L., additional, Holtorf, M., additional, Lancet, D., additional, Bernstein, G., additional, Omar, I., additional, MacLennan, S., additional, Maclennan, S., additional, Tripathee, S., additional, Wirth, M., additional, Froehner, M., additional, Brenner, B., additional, Borkowetz, A., additional, Thomas, C., additional, Horn, F., additional, Reiche, K., additional, Kreux, M., additional, Josefsson, A., additional, Tandefekt, D. Gasi, additional, Hugosson, J., additional, Huisman, H., additional, Schalken, J., additional, Hofmacher, T., additional, Lindgren, P., additional, Andersson, E., additional, Fridhammar, A., additional, Zong, J., additional, Butler-Ransohoff, J-E., additional, Herrera, R., additional, Maass, M., additional, Torremante, P., additional, Voss, M.D., additional, Devecseri, Z., additional, Abbott, T., additional, Dau, C., additional, Papineni, K., additional, Snijder, R., additional, Lambrecht, M., additional, Wolfinger, R., additional, Rogiers, S., additional, Servan, A., additional, Antoni, L., additional, Pacoe, K., additional, Robinson, P., additional, Jaton, B., additional, Bakkard, D., additional, Turunen, H., additional, Kilkku, O., additional, Pohjanjousi, P., additional, Voima, O., additional, Nevalaita, L., additional, Reich, C., additional, Araujo, S., additional, Longden-Chapman, E., additional, Burke, D., additional, Agapow, P., additional, Derkits, S., additional, Licour, M., additional, McCrea, C., additional, Payne, S., additional, Yong, A., additional, Thompson, L., additional, Mare, S. Le, additional, Bussmann, M, additional, and Kotik, D., additional

Published
2023
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10. 1388P Interim safety analysis of nivolumab 3mg/kg and ipilimumab 1mg/kg (nivo3/ipi1) in molecular-selected patients (pts) with metastastic castration-resistant prostate cancer (mCRPC)

Author

van Wilpe, S., primary, Westdorp, H., additional, Kloots, I.S.H., additional, Slootbeek, P., additional, den Brok, M., additional, Adema, G., additional, Kerkmeijer, L., additional, Smeenk, R.J., additional, Coskunturk, M., additional, Bloemendal, H., additional, Schalken, J., additional, Erp, N.V., additional, Gerritsen, W.R., additional, and Mehra, N., additional

Published
2022
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11. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

Author

Gillessen, S., Omlin, A., Attard, G., de Bono, J. S., Efstathiou, E., Fizazi, K., Halabi, S., Nelson, P. S., Sartor, O., Smith, M. R., Soule, H. R., Akaza, H., Beer, T. M., Beltran, H., Chinnaiyan, A. M., Daugaard, G., Davis, I. D., De Santis, M., Drake, C. G., Eeles, R. A., Fanti, S., Gleave, M. E., Heidenreich, A., Hussain, M., James, N. D., Lecouvet, F. E., Logothetis, C. J., Mastris, K., Nilsson, S., Oh, W. K., Olmos, D., Padhani, A. R., Parker, C., Rubin, M. A., Schalken, J. A., Scher, H. I., Sella, A., Shore, N. D., Small, E. J., Sternberg, C. N., Suzuki, H., Sweeney, C. J., Tannock, I. F., and Tombal, B.

Published
2015
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12. 642TiP Phase II CA184-585 (INSPIRE) trial of ipilimumab with nivolumab for molecular-selected patients with castration-resistant prostate cancer

Author

Mehra, N., primary, Kloots, I., additional, Slootbeek, P., additional, Brok, M. den, additional, Adema, G., additional, Kerkmeijer, L., additional, Smeenk, R.J., additional, Westdorp, H., additional, Bloemendal, H., additional, Schalken, J., additional, van Erp, N.P., additional, Binder, M., additional, De Vries, J., additional, and Gerritsen, W., additional

Published
2021
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13. Introducing PIONEER: a project to harness big data in prostate cancer research

Author

Omar M. I., Roobol M. J., Ribal M. J., Abbott T., Agapow P. -M., Araujo S., Asiimwe A., Auffray C., Balaur I., Beyer K., Bernini C., Bjartell A., Briganti A., Butler-Ransohoff J. -E., Campi R., Cavelaars M., De Meulder B., Devecseri Z., Voss M. D., Dimitropoulos K., Evans-Axelsson S., Franks B., Fullwood L., Horgan D., Smith E. J., Kiran A., Kivinummi K., Lambrecht M., Lancet D., Lindgren P., MacLennan S., Nogueira M. M., Moen F., Moinat M., Papineni K., Reich C., Reiche K., Rogiers S., Sartini C., van Bochove K., van Diggelen F., Van Hemelrijck M., Van Poppel H., Zong J., N'Dow J., Andersson E., Arala H., Auvinen A., Bangma C., Burke D., Cardone A., Casariego J., Cuperus G., Dabestani S., Esperto F., Fossati N., Fridhammar A., Gandaglia G., Tandefelt D. G., Horn F., Huber J., Hugosson J., Huisman H., Josefsson A., Kilkku O., Kreuz M., Lardas M., Lawson J., Lefresne F., Lejeune S., Longden-Chapman E., McVie G., Moris L., Mottet N., Murtola T., Nicholls C., Pang K. H., Pascoe K., Picozzi M., Plass K., Pohjanjousi P., Reaney M., Remmers S., Robinson P., Schalken J., Schravendeel M., Seisen T., Servan A., Shiranov K., Snijder R., Steinbeisser C., Taibi N., Talala K., Tilki D., Van den Broeck T., Vassilev Z., Voima O., Vradi E., Waldeck R., Weistra W., Willemse P. -P., Wirth M., Wolfinger R., Kermani N. Z., Omar, M. I., Roobol, M. J., Ribal, M. J., Abbott, T., Agapow, P. -M., Araujo, S., Asiimwe, A., Auffray, C., Balaur, I., Beyer, K., Bernini, C., Bjartell, A., Briganti, A., Butler-Ransohoff, J. -E., Campi, R., Cavelaars, M., De Meulder, B., Devecseri, Z., Voss, M. D., Dimitropoulos, K., Evans-Axelsson, S., Franks, B., Fullwood, L., Horgan, D., Smith, E. J., Kiran, A., Kivinummi, K., Lambrecht, M., Lancet, D., Lindgren, P., Maclennan, S., Nogueira, M. M., Moen, F., Moinat, M., Papineni, K., Reich, C., Reiche, K., Rogiers, S., Sartini, C., van Bochove, K., van Diggelen, F., Van Hemelrijck, M., Van Poppel, H., Zong, J., N'Dow, J., Andersson, E., Arala, H., Auvinen, A., Bangma, C., Burke, D., Cardone, A., Casariego, J., Cuperus, G., Dabestani, S., Esperto, F., Fossati, N., Fridhammar, A., Gandaglia, G., Tandefelt, D. G., Horn, F., Huber, J., Hugosson, J., Huisman, H., Josefsson, A., Kilkku, O., Kreuz, M., Lardas, M., Lawson, J., Lefresne, F., Lejeune, S., Longden-Chapman, E., Mcvie, G., Moris, L., Mottet, N., Murtola, T., Nicholls, C., Pang, K. H., Pascoe, K., Picozzi, M., Plass, K., Pohjanjousi, P., Reaney, M., Remmers, S., Robinson, P., Schalken, J., Schravendeel, M., Seisen, T., Servan, A., Shiranov, K., Snijder, R., Steinbeisser, C., Taibi, N., Talala, K., Tilki, D., Van den Broeck, T., Vassilev, Z., Voima, O., Vradi, E., Waldeck, R., Weistra, W., Willemse, P. -P., Wirth, M., Wolfinger, R., Kermani, N. Z., Publica, and Urology

Subjects
0301 basic medicine, Prioritization, Knowledge management, Urology, media_common.quotation_subject, education, Big data, Disease, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Multidisciplinary approach, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Medicine, Quality (business), media_common, business.industry, Patient-centered outcomes, medicine.disease, 3. Good health, Patient management, 030104 developmental biology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, business
Abstract

Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate cancer management by unlocking the potential of big data. The project has identified critical evidence gaps in prostate cancer care, via a detailed prioritization exercise including all key stakeholders. By standardizing and integrating existing high-quality and multidisciplinary data sources from patients with prostate cancer across different stages of the disease, the resulting big data will be assembled into a single innovative data platform for research. Based on a unique set of methodologies, PIONEER aims to advance the field of prostate cancer care with a particular focus on improving prostate-cancer-related outcomes, health system efficiency by streamlining patient management, and the quality of health and social care delivered to all men with prostate cancer and their families worldwide.Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. In this Perspectives article, the authors introduce the PIONEER project and describe its aims and plans for ultimately improving prostate cancer care through the use of big data.

Published
2020

14. Author Correction: Introducing PIONEER: a project to harness big data in prostate cancer research (Nature Reviews Urology, (2020), 17, 6, (351-362), 10.1038/s41585-020-0324-x)

Author

Omar M. I., Roobol M. J., Ribal M. J., Abbott T., Agapow P. -M., Araujo S., Asiimwe A., Auffray C., Balaur I., Beyer K., Bernini C., Bjartell A., Briganti A., Butler-Ransohoff J. -E., Campi R., Cavelaars M., De Meulder B., Devecseri Z., Voss M. D., Dimitropoulos K., Evans-Axelsson S., Franks B., Fullwood L., Horgan D., Smith E. J., Kiran A., Kivinummi K., Lambrecht M., Lancet D., Lindgren P., MacLennan S., Nogueira M. M., Moen F., Moinat M., Papineni K., Reich C., Reiche K., Rogiers S., Sartini C., van Bochove K., van Diggelen F., Van Hemelrijck M., Van Poppel H., Zong J., N'Dow J., Andersson E., Arala H., Auvinen A., Bangma C., Burke D., Cardone A., Casariego J., Cuperus G., Dabestani S., Esperto F., Fossati N., Fridhammar A., Gandaglia G., Tandefelt D. G., Horn F., Huber J., Hugosson J., Huisman H., Josefsson A., Kilkku O., Kreuz M., Lardas M., Lawson J., Lefresne F., Lejeune S., Longden-Chapman E., McVie G., Moris L., Mottet N., Murtola T., Nicholls C., Pang K. H., Pascoe K., Picozzi M., Plass K., Pohjanjousi P., Reaney M., Remmers S., Robinson P., Schalken J., Schravendeel M., Seisen T., Servan A., Shiranov K., Snijder R., Steinbeisser C., Taibi N., Talala K., Tilki D., Van den Broeck T., Vassilev Z., Voima O., Vradi E., Waldeck R., Weistra W., Willemse P. -P., Wirth M., Wolfinger R., Kermani N. Z., Omar, M. I., Roobol, M. J., Ribal, M. J., Abbott, T., Agapow, P. -M., Araujo, S., Asiimwe, A., Auffray, C., Balaur, I., Beyer, K., Bernini, C., Bjartell, A., Briganti, A., Butler-Ransohoff, J. -E., Campi, R., Cavelaars, M., De Meulder, B., Devecseri, Z., Voss, M. D., Dimitropoulos, K., Evans-Axelsson, S., Franks, B., Fullwood, L., Horgan, D., Smith, E. J., Kiran, A., Kivinummi, K., Lambrecht, M., Lancet, D., Lindgren, P., Maclennan, S., Nogueira, M. M., Moen, F., Moinat, M., Papineni, K., Reich, C., Reiche, K., Rogiers, S., Sartini, C., van Bochove, K., van Diggelen, F., Van Hemelrijck, M., Van Poppel, H., Zong, J., N'Dow, J., Andersson, E., Arala, H., Auvinen, A., Bangma, C., Burke, D., Cardone, A., Casariego, J., Cuperus, G., Dabestani, S., Esperto, F., Fossati, N., Fridhammar, A., Gandaglia, G., Tandefelt, D. G., Horn, F., Huber, J., Hugosson, J., Huisman, H., Josefsson, A., Kilkku, O., Kreuz, M., Lardas, M., Lawson, J., Lefresne, F., Lejeune, S., Longden-Chapman, E., Mcvie, G., Moris, L., Mottet, N., Murtola, T., Nicholls, C., Pang, K. H., Pascoe, K., Picozzi, M., Plass, K., Pohjanjousi, P., Reaney, M., Remmers, S., Robinson, P., Schalken, J., Schravendeel, M., Seisen, T., Servan, A., Shiranov, K., Snijder, R., Steinbeisser, C., Taibi, N., Talala, K., Tilki, D., Van den Broeck, T., Vassilev, Z., Voima, O., Vradi, E., Waldeck, R., Weistra, W., Willemse, P. -P., Wirth, M., Wolfinger, R., and Kermani, N. Z.

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

16. The prostate cancer urinary exosome protein biomarker landscape

Author

Bijnsdorp, I., primary, Erozenci, L.A., additional, Koetsier, J., additional, Feenstra, F., additional, Piersma, S.R., additional, Van Moorselaar, R.J., additional, Vis, A., additional, Jenster, G., additional, Schalken, J., additional, Verhaegh, G., additional, and Jimenez, C.R., additional

Published
2020
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22. In-depth assessment of metastatic prostate cancer with high tumour mutational burden

Author

Mehra, N., primary, van Riet, J., additional, Smits, M., additional, Westdorp, H., additional, Gorris, M., additional, van Ee, T., additional, van der Doelen, M., additional, van Oort, I., additional, Sedelaar, M., additional, Textor, J., additional, Cuppen, E., additional, Grunberg, K., additional, Ligtenberg, M.J.L., additional, Zwart, W., additional, Bergman, A., additional, van de Werken, H.J.G., additional, Schalken, J., additional, de Vries, I.J.M., additional, Lolkema, M.P., additional, and Gerritsen, W.R., additional

Published
2018
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24. Urine cell based DNA methylation classifier for monitoring bladder cancer

Author

Van Der Heijden, A., primary, Mengual, L., additional, Ingelmo-Torres, M., additional, Lozano, J.J., additional, Van Rijt-Van De Westerlo, C., additional, Sousa, C., additional, Geavlete, B., additional, Moldoveanu, C., additional, Ene, C., additional, Dinney, C., additional, Czerniak, B., additional, Schalken, J., additional, Kiemeney, L., additional, Ribal, M., additional, Witjes, A., additional, and Alcaraz, A., additional

Published
2018
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26. Synergy Between Plasma-Assisted ALD and Roll-to-Roll Atmospheric Pressure PE-CVD Processing of Moisture Barrier Films on Polymers

Author

Starostin, S.A., Keuning, W., Schalken, J., Creatore, M., Kessels, W.M. M., Bouwstra, J.B., van de Sanden, M.C. M., de Vries, H.W., Plasma & Materials Processing, Applied Physics and Science Education, Interfaces in future energy technologies, Atomic scale processing, and Processing of low-dimensional nanomaterials

Abstract

The synergy between fast (1600 nm · min−1), roll-to-roll plasma-enhanced chemical vapor deposited (PE-CVD) SiO2 layers and plasma-assisted atomic layer deposited (PA-ALD) ultra-thin Al2O3 films has been investigated in terms of moisture permeation barrier properties. The effective and intrinsic water vapor transmission rates (WVTR) were studied as a function of the number of ALD cycles. It was demonstrated that a synergistic combination of a silica buffer layer deposited on polymer with an ultra-thin (≤ 2 nm) alumina barrier film can provide excellent intrinsic (10−5–10−6 g · m−2 · day−1) and good effective (∼10−3 g · m−2 · day−1) WVTR values, whereas both single layers individually exhibit poor barrier performances with effective WVTR values of ≥ 1.0 g · m−2 · day−1.

Published
2016
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28. Adjuvant androgen deprivation therapy for high-risk androgen receptor-positive salivary duct carcinoma

Author

Boxtel, W., primary, Locati, L.D., additional, Tooten, S., additional, Bos, E., additional, Bergamini, C., additional, van Engen-van Grunsven, A.C.H., additional, Boon, E., additional, Fiets, E., additional, Cavalieri, S., additional, Verhaegh, G., additional, Schalken, J., additional, Licitra, L., additional, and Herpen, C.M.L., additional

Published
2017
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29. Urine based DNA methylation biomarkers for monitoring bladder cancer

Author

Van Der Heijden, A., primary, Mengual, L., additional, Ingelmo-Torres, M., additional, Lozano, J., additional, Van Rijt-Van De Westerlo, C., additional, Santos, P., additional, Geavlete, B., additional, Moldoveanu, C., additional, Ene, C., additional, Dinney, C., additional, Czerniak, B., additional, Schalken, J., additional, Kiemeney, L., additional, Ribal, M., additional, Witjes, J., additional, and Alcaraz, A., additional

Published
2017
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31. Improving the barrier function of damaged cultured urothelium using chondroitin sulfate.

Author

Rozenberg, Boy. B., Janssen, D. A. W., Jansen, C. F. J., Schalken, J. A., and Heesakkers, J. P. F. A.

Subjects
CHONDROITIN sulfates, INTERSTITIAL cystitis, UROTHELIUM, CELL differentiation, TIGHT junctions, TREATMENT effectiveness
Abstract

Aims: To determine whether glycosaminoglycan (GAG) replenishment is able to improve recovery of a deficient urothelial barrier, chondroitin sulfate (CS) instillations were tested using an in vitro model. Porcine urothelial cells (Ucells) were terminally differentiated in culture conditions to construct a urothelial layer with a functional barrier. This layer was damaged to compromise barrier function to simulate a key characteristic of bladder pain syndrome/interstitial cystitis. The functional effect of subsequent treatment with CS was evaluated. Methods: Primary porcine Ucells were isolated and cultured on inserts. Differentiation of cells was evaluated with immunohistochemical analysis for the presence of umbrella cells, tight junctions and CS. Transepithelial electrical resistance (TEER) measurements were performed to evaluate barrier function. Protamine was used to simulate mild urothelial damage. CS 0.2% (vol/vol), a GAG, was subsequently instilled in the treatment group. The recovery of barrier function was further evaluated with TEER measurements. The Student t test was used for the analysis of results. Results: After induction of differentiation, the Ucells expressed barrier markers and a functional barrier was established (measured by high TEER). TEER decreased significantly after instillation with protamine. CS instillation improved recovery of TEER significantly measured after 7 hours (84% vs 22% in controls). After 24 hours; however, the TEER was comparable in both experimental groups. Conclusion: CS instillation improves the recovery of the urothelial barrier after damage in vitro. This functional experiment shows that CS improves recovery of damaged urothelial function, which supports the hypothesis behind the mechanism of action of GAG‐replenishment therapy. [ABSTRACT FROM AUTHOR]

Published
2020
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33. Ellipsoid segmentation model for analyzing light-attenuated 3D confocal image stacks of fluorescent multi-cellular spheroids

Author

Barbier, M. (Michaël), Jaensch, S. (Steffen), Cornelissen, F. (Frans), Vidic, S. (Suzana), Gjerde, K. (Kjersti), Hoogt, R. (Ronald) de, Graeser, R. (Ralph), Gustin, E. (Emmanuel), Chong, Y.T. (Yolanda T.), Hickman, J.A. (John A.), Burbridge, M. (Mike), Verschuren, E.W. (Emmy W.), Kallioniemi, O. (Olli), Klefström, J. (Juha), Brisken, C. (Cathrin), Rotter, V. (Varda), Oren, M. (Moshe), Brito, C. (Catarina), Schalken, J. (Jack), Jenster, G. (Guido), Van Weerden, W. (Wystke), Vilo, J. (Jaak), Schueler, J. (Julia), Monni, O. (Outi), Barry, S.T. (Simon T.), Grünewald, S. (Sylvia), Kallio, P. (Pekka), Mueller, H.-J. (Hans-Joachim), Nopora, A. (Adam), Sommergruber, W. (Wolfgang), Anderson, E. (Elizabeth), Van Der Kuip, H. (Heiko), Smalley, M. (Matthew), Boghaert, E. (Erwin), Barbier, M. (Michaël), Jaensch, S. (Steffen), Cornelissen, F. (Frans), Vidic, S. (Suzana), Gjerde, K. (Kjersti), Hoogt, R. (Ronald) de, Graeser, R. (Ralph), Gustin, E. (Emmanuel), Chong, Y.T. (Yolanda T.), Hickman, J.A. (John A.), Burbridge, M. (Mike), Verschuren, E.W. (Emmy W.), Kallioniemi, O. (Olli), Klefström, J. (Juha), Brisken, C. (Cathrin), Rotter, V. (Varda), Oren, M. (Moshe), Brito, C. (Catarina), Schalken, J. (Jack), Jenster, G. (Guido), Van Weerden, W. (Wystke), Vilo, J. (Jaak), Schueler, J. (Julia), Monni, O. (Outi), Barry, S.T. (Simon T.), Grünewald, S. (Sylvia), Kallio, P. (Pekka), Mueller, H.-J. (Hans-Joachim), Nopora, A. (Adam), Sommergruber, W. (Wolfgang), Anderson, E. (Elizabeth), Van Der Kuip, H. (Heiko), Smalley, M. (Matthew), and Boghaert, E. (Erwin)

Abstract

In oncology, two-dimensional in-vitro culture models are the standard test beds for the discovery and development of cancer treatments, but in the last decades, evidence emerged that such models have low predictive value for clinical efficacy. Therefore they are increasingly complemented by more physiologically relevant 3D models, such as spheroid microtumor cultures. If suitable fluorescent labels are applied, confocal 3D image stacks can characterize the structure of such volumetric cultures and, for example, cell proliferation. However, several issues hamper accurate analysis. In particular, signal attenuation within the tissue of the spheroids prevents the acquisition of a complete image for spheroids over 100 micrometers in diameter. And quantitative analysis of large 3D image data sets is challenging, creating a need for methods which can be applied to large-scale experiments and account for impeding factors. We present a robust, computationally inexpensive 2.5D method for the segmentation of spheroid cultures and for counting proliferating cells within them. The spheroids are assumed to be approximately ellipsoid in shape. They are identified from information present in the Maximum Intensity Projection (MIP) and the corresponding height view, also known as Z-buffer. It alerts the user when potential bias-introducing factors cannot be compensated for and includes a compensation for signal attenuation.

Published
2016
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46. Urothelium update: how the bladder mucosa measures bladder filling.

Author

Janssen, D. A. W., Schalken, J. A., and Heesakkers, J. P. F. A.

Subjects
*SIGNALING (Psychology), *BLADDER, *UROTHELIUM, *ADENOSINE triphosphate, *MUCOUS membranes
Abstract

Aim This review critically evaluates the evidence on mechanoreceptors and pathways in the bladder urothelium that are involved in normal bladder filling signalling. Methods Evidence from in vitro and in vivo studies on (i) signalling pathways like the adenosine triphosphate pathway, cholinergic pathway and nitric oxide and adrenergic pathway, and (ii) different urothelial receptors that are involved in bladder filling signalling like purinergic receptors, sodium channels and TRP channels will be evaluated. Other potential pathways and receptors will also be discussed. Results Bladder filling results in continuous changes in bladder wall stretch and exposure to urine. Both barrier and afferent signalling functions in the urothelium are constantly adapting to cope with these dynamics. Current evidence shows that the bladder mucosa hosts essential pathways and receptors that mediate bladder filling signalling. Intracellular calcium ion increase is a dominant factor in this signalling process. However, there is still no complete understanding how interacting receptors and pathways create a bladder filling signal. Currently, there are still novel receptors investigated that could also be participating in bladder filling signalling. Conclusions Normal bladder filling sensation is dependent on multiple interacting mechanoreceptors and signalling pathways. Research efforts need to focus on how these pathways and receptors interact to fully understand normal bladder filling signalling. [ABSTRACT FROM AUTHOR]

Published
2017
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48. TRPV4 channels in the human urogenital tract play a role in cell junction formation and epithelial barrier.

Author

Janssen, D. A. W., Jansen, C. J. F., Hafmans, T. G., Verhaegh, G. W., Hoenderop, J. G., Heesakkers, J. P. F. A., and Schalken, J. A.

Subjects
TRPV cation channels, CELL junctions, EPITHELIAL cells, TRANSGENIC mice, IMMUNOPRECIPITATION
Abstract

Aim The molecular interactions between transient receptor potential vanilloid subtype 4 channels ( TRPV4) and cell junction formation were investigated in the human and mouse urogenital tract. Materials and Methods A qualitative study was performed to investigate TRPV4 channels, adherence junctions ( AJs) and tight junctions ( TJs) in kidney, ureter and bladder tissues from humans and wild-type and transgenic TRPV4 knockout (−/−) mice with immunohistochemistry, Western blotting, immunoprecipitation and reverse trasnscription- PCR. Cell junction formation in the wild-type and TRPV4 knockout (−/−) mouse was evaluated with immunohistochemistry and transmission electron microscope ( TEM) techniques. Results TRPV4 channels are predominantly located in membranes of epithelial cells of the bladder, ureter and the collecting ducts of the kidney. There is a molecular interaction between the TRPV4 channel and the AJ. TEM evaluation showed that AJ formation is disrupted in the TRPV4 −/− mouse resulting in deficient intercellular connections and integrity of the epithelium. Conclusions TRPV4 is believed to be a mechanoreceptor in the bladder. This study demonstrates that TRPV4 is also involved in intercellular connectivity and structural integrity of the epithelium. [ABSTRACT FROM AUTHOR]

Published
2016
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49. Liquid biopsy in bladder cancer: State of the art and future perspectives

Author

Felice Crocetto, Biagio Barone, Matteo Ferro, Gian Maria Busetto, Evelina La Civita, Carlo Buonerba, Giuseppe Di Lorenzo, Daniela Terracciano, Jack A. Schalken, Crocetto, F., Barone, B., Ferro, M., Busetto, G. M., La Civita, E., Buonerba, C., Di Lorenzo, G., Terracciano, D., and Schalken, J. A.

Subjects
Oncology, Urinary Bladder Neoplasms, Liquid biopsy, Urinary biomarker, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Bladder cancer, Biomarkers, Tumor, Humans, Hematology, Cystoscopy, Cytology
Abstract

Contains fulltext : 248285.pdf (Publisher’s version ) (Closed access) Bladder cancer is the most common malignancy of the urinary tract. Cystoscopy represents the gold standard in the diagnosis of suspicious bladder lesions. However, the procedure is invasive and burdened by pain, discomfort and infective complications. Cytology, which represents an alternative diagnostic possibility is limited by poor sensitivity. Considering the limitations of both procedures, and the necessity to perform multiple evaluations in patients who are in follow-up for bladder cancer, an improved non-invasive methodology is required in the clinical management of this disease. Liquid biopsy, e.g. the detection of clinical biomarkers in urine, represent a promising novel and non-invasive approach that could overcome those limitations and be integrated into the current clinical practice. The aim of this review is to summarize the state of the art of this approach and the latest novelties regarding detection, prognosis and surveillance of bladder cancer.

Published
2022

50. Consensus on molecular imaging and theranostics in prostate cancer

Author

Frédéric Lecouvet, Hebert Alberto Vargas, Silke Gillessen, Ken Herrmann, Piet Ost, Sam Gledhill, Anwar R. Padhani, Silvia Minozzi, Hans-Jürgen Wester, Alberto Briganti, Ian Banks, Wim J.G. Oyen, Heindrik Van Poppel, Karim Fizazi, Jack A. Schalken, Noel W. Clarke, R. Jeroen A. van Moorselaar, Arturo Chiti, Rodney J. Hicks, Howard I. Scher, Bertrand Tombal, Uwe Haberkorn, Rodolfo Montironi, Gerald Antoch, Matthias Eiber, Ignasi Carrió, Wolfgang A. Weber, Johann S. de Bono, Stefano Fanti, Jochen Walz, Joe M. O'Sullivan, Fanti, S., Minozzi, S., Antoch, G., Banks, I., Briganti, A., Carrio, I., Chiti, A., Clarke, N., Eiber, M., De Bono, J., Fizazi, K., Gillessen, S., Gledhill, S., Haberkorn, U., Herrmann, K., Hicks, R. J., Lecouvet, F., Montironi, R., Ost, P., O'Sullivan, J. M., Padhani, A. R., Schalken, J. A., Scher, H. I., Tombal, B., van Moorselaar, R. J. A., Van Poppel, H., Vargas, H. A., Walz, J., Weber, W. A., Wester, H. -J., Oyen, W. J. G., and Fanti S, Minozzi S, Antoch G, Banks I, Briganti A, Carrio I, Chiti A, Clarke N, Eiber M, De Bono J, Fizazi K, Gillessen S, Gledhill S, Haberkorn U, Herrmann K, Hicks RJ, Lecouvet F, Montironi R, Ost P, O'Sullivan JM, Padhani AR, Schalken JA, Scher HI, Tombal B, van Moorselaar RJA, Van Poppel H, Vargas HA, Walz J, Weber WA, Wester HJ, Oyen WJG.

Subjects
Male, Biochemical recurrence, medicine.medical_specialty, Consensus, Delphi Technique, medicine.medical_treatment, Medizin, Delphi method, MEDLINE, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Theranostic Nanomedicine, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Predictive Value of Tests, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Biomarkers, Tumor, medicine, Humans, Medical physics, prostate cancer, theranostics, medicine.diagnostic_test, business.industry, Clinical study design, Prostatic Neoplasms, medicine.disease, Molecular Imaging, Radiation therapy, Treatment Outcome, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Cancer biomarkers, business
Abstract

Contains fulltext : 200014.pdf (Publisher’s version ) (Closed access) Rapid developments in imaging and treatment with radiopharmaceuticals targeting prostate cancer pose issues for the development of guidelines for their appropriate use. To tackle this problem, international experts representing medical oncologists, urologists, radiation oncologists, radiologists, and nuclear medicine specialists convened at the European Association of Nuclear Medicine Focus 1 meeting to deliver a balanced perspective on available data and clinical experience of imaging in prostate cancer, which had been supported by a systematic review of the literature and a modified Delphi process. Relevant conclusions included the following: diphosphonate bone scanning and contrast-enhanced CT are mentioned but rarely recommended for most patients in clinical guidelines; MRI (whole-body or multiparametric) and prostate cancer-targeted PET are frequently suggested, but the specific contexts in which these methods affect practice are not established; sodium fluoride-18 for PET-CT bone scanning is not widely advocated, whereas gallium-68 or fluorine-18 prostate-specific membrane antigen gain acceptance; and, palliative treatment with bone targeting radiopharmaceuticals (rhenium-186, samarium-153, or strontium-89) have largely been replaced by radium-223 on the basis of the survival benefit that was reported in prospective trials, and by other systemic therapies with proven survival benefits. Although the advances in MRI and PET-CT have improved the accuracy of imaging, the effects of these new methods on clinical outcomes remains to be established. Improved communication between imagers and clinicians and more multidisciplinary input in clinical trial design are essential to encourage imaging insights into clinical decision making.

Published
2018
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