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1. Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids

Author

Kluiver, Thomas A., Lu, Yuyan, Schubert, Stephanie A., Kraaier, Lianne J., Ringnalda, Femke, Lijnzaad, Philip, DeMartino, Jeff, Megchelenbrink, Wouter L., Amo-Addae, Vicky, Eising, Selma, de Faria, Flavia W., Münter, Daniel, van de Wetering, Marc, Kerl, Kornelius, Duiker, Evelien, van den Heuvel, Marius C., de Meijer, Vincent E., de Kleine, Ruben H., Molenaar, Jan J., Margaritis, Thanasis, Stunnenberg, Hendrik G., de Krijger, Ronald R., Zsiros, József, Clevers, Hans, and Peng, Weng Chuan

Published
2024
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2. Variation in the management of benign liver tumors: A European survey and case vignette study

Author

de Boer, Y.S., de Man, R.A., den Hoed, C.M., Drenth, J.P.H., Garcovich, M.G., Gevers, T.J.G., Klompenhouwer, A.J., Kramer, M., Tushuizen, M.E., van der Meer, A.J., Burgmans, M.C., Cannella, R.C., Caseiro-Alves, F.C., Denecke, T.D., Dwarkasing, R.S., Fehrenbach, U.F., Feshtali, S., Miclea, R.L., Poyanli, A.P., Ronot, M.R., Sartoris, R.S., Thomeer, Maarten, van der Leij, C., van Koeverden, S.K., Vermersch, M.V., Vernuccio, F.V., Willemssen, F.E.J.A., Addeo, P.A., Alexandrino, H., Belli, A., Bemelmans, M.H.A., Boleslawski, E.B., Coelen, R.J.S., de Boer, M.T., de Kleine, R.H., den Dulk, M., Frilling, A.F., Furumaya, A., Irinel, I.P., Regimbeau, J.M., Manuela, M.C., Özden, İ., Sallinen, V.S., Schaapherder, A.F., Schmelzle, M.S., Seehofer, D., Trotovšek, B., Truant, S.T., van den Boezem, P.B., van Rosmalen, B.V., Haring, Martijn P.D., de Haas, Robbert J., van Vilsteren, Frederike G.I., Klaase, Joost M., Duiker, Evelien W., Blokzijl, Hans, de Jong, Koert P., de Meijer, Vincent E., and Cuperus, Frans J.C.

Published
2023
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3. B cells critical for outcome in high grade serous ovarian carcinoma.

Author

Vledder, Annegé, Paijens, Sterre T., Loiero, Dominik, Maagdenberg, Alexis, Duiker, Evelien W., Bart, Joost, Hendriks, Anne M., Jalving, Mathilde, Werner, Naomi, van Rooij, Nienke, Plat, Annechien, Wisman, G. Bea A., Yigit, Refika, Roelofsen, Thijs, Kruse, Arnold J., de Lange, Nastascha M., Koelzer, Viktor H., de Bruyn, Marco, and Nijman, Hans W.

Subjects
TUMOR-infiltrating immune cells, B cells, PROGNOSIS, T cells, ADJUVANT chemotherapy, OVARIAN cancer
Abstract

Recent work has shown evidence for the prognostic significance of tumor infiltrating B cells (B‐TIL) in high grade serous ovarian carcinoma (HGSOC), the predominant histological subtype of ovarian cancer. However, it remains unknown how the favorable prognosis associated with B‐TIL relates to the current standard treatments of primary debulking surgery (PDS) followed by chemotherapy or (neo‐)adjuvant chemotherapy (NACT) combined with interval debulking surgery. To address this, we analyzed the prognostic impact of B‐TIL in relationship to primary treatment and tumor infiltrating T cell status in a highly homogenous cohort of HGSOC patients. This analysis involved a combined approach utilizing histological data and high‐dimensional flow cytometry analysis. Our findings indicate that while HGSOC tumors pre‐treated with NACT are infiltrated with tumor‐reactive CD8+ and CD4+ TIL subsets, only B‐TIL and IgA plasma blasts confer prognostic benefit in terms of overall survival. Importantly, the prognostic value of B‐TIL and IgA plasma blasts was not restricted to patients treated with NACT, but was also evident in patients treated with PDS. Together, our data point to a critical prognostic role for B‐TIL in HGSOC patients independent of T cell status, suggesting that alternative treatment approaches focused on the activation of B cells should be explored for HGSOC. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Multi-dimensional profiling of hepatoblastomas and patient-derived tumor organoids uncovers tumor subpopulations with divergent WNT activation profiles and identifies pan-hepatoblastoma drug sensitivities

Author

Kluiver, Thomas A, primary, Lu, Yuyan, additional, Schubert, Stephanie A, additional, Kraaier, Lianne J, additional, Ringnalda, Femke, additional, Lijnzaad, Philip, additional, DeMartino, Jeff, additional, Megchelenbrink, Wout L, additional, Amo-Addae, Vicky, additional, Eising, Selma, additional, de Faria, Flavia W, additional, Munter, Daniel J, additional, van de Wetering, Marc, additional, Kerl, Kornelius, additional, Duiker, Evelien, additional, van den Heuvel, Marius, additional, de Meijer, Vincent E, additional, de Kleine, Ruben H, additional, de Krijger, Ronald R, additional, Molenaar, Jan J, additional, Margaritis, Thanasis, additional, Stunnenberg, Henk, additional, Zsiros, Jozsef, additional, Clevers, Hans, additional, and Peng, Weng Chuan, additional

Published
2023
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7. Supplementary Methods from Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Author

Wouters, Maartje C.A., primary, Komdeur, Fenne L., primary, Workel, Hagma H., primary, Klip, Harry G., primary, Plat, Annechien, primary, Kooi, Neeltje M., primary, Wisman, G. Bea A., primary, Mourits, Marian J.E., primary, Arts, Henriette J.G., primary, Oonk, Maaike H.M., primary, Yigit, Refika, primary, de Jong, Steven, primary, Melief, Cornelis J.M., primary, Hollema, Harry, primary, Duiker, Evelien W., primary, Daemen, Toos, primary, de Bruyn, Marco, primary, and Nijman, Hans W., primary

Published
2023
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8. Figure S1 from Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma

Author

Caumanns, Joseph J., primary, Berns, Katrien, primary, Wisman, G. Bea A., primary, Fehrmann, Rudolf S.N., primary, Tomar, Tushar, primary, Klip, Harry, primary, Meersma, Gert J., primary, Hijmans, E. Marielle, primary, Gennissen, Annemiek M.C., primary, Duiker, Evelien W., primary, Weening, Desiree, primary, Itamochi, Hiroaki, primary, Kluin, Roelof J.C., primary, Reyners, Anna K.L., primary, Birrer, Michael J., primary, Salvesen, Helga B., primary, Vergote, Ignace, primary, van Nieuwenhuysen, Els, primary, Brenton, James, primary, Braicu, E. Ioana, primary, Kupryjanczyk, Jolanta, primary, Spiewankiewicz, Beata, primary, Mittempergher, Lorenza, primary, Bernards, René, primary, van der Zee, Ate G.J., primary, and de Jong, Steven, primary

Published
2023
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9. Table S2 from Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma

Author

Caumanns, Joseph J., primary, Berns, Katrien, primary, Wisman, G. Bea A., primary, Fehrmann, Rudolf S.N., primary, Tomar, Tushar, primary, Klip, Harry, primary, Meersma, Gert J., primary, Hijmans, E. Marielle, primary, Gennissen, Annemiek M.C., primary, Duiker, Evelien W., primary, Weening, Desiree, primary, Itamochi, Hiroaki, primary, Kluin, Roelof J.C., primary, Reyners, Anna K.L., primary, Birrer, Michael J., primary, Salvesen, Helga B., primary, Vergote, Ignace, primary, van Nieuwenhuysen, Els, primary, Brenton, James, primary, Braicu, E. Ioana, primary, Kupryjanczyk, Jolanta, primary, Spiewankiewicz, Beata, primary, Mittempergher, Lorenza, primary, Bernards, René, primary, van der Zee, Ate G.J., primary, and de Jong, Steven, primary

Published
2023
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10. Data from Enhanced Antitumor Efficacy of a DR5-Specific TRAIL Variant over Recombinant Human TRAIL in a Bioluminescent Ovarian Cancer Xenograft Model

Author

Duiker, Evelien W., primary, de Vries, Elisabeth G.E., primary, Mahalingam, Devalingam, primary, Meersma, Gert Jan, primary, Boersma-van Ek, Wytske, primary, Hollema, Harry, primary, Lub-de Hooge, Marjolijn N., primary, van Dam, Go M., primary, Cool, Robbert H., primary, Quax, Wim J., primary, Samali, Afshin, primary, van der Zee, Ate G.J., primary, and de Jong, Steven, primary

Published
2023
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11. Supplementary Figure S1 from Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Author

Wouters, Maartje C.A., primary, Komdeur, Fenne L., primary, Workel, Hagma H., primary, Klip, Harry G., primary, Plat, Annechien, primary, Kooi, Neeltje M., primary, Wisman, G. Bea A., primary, Mourits, Marian J.E., primary, Arts, Henriette J.G., primary, Oonk, Maaike H.M., primary, Yigit, Refika, primary, de Jong, Steven, primary, Melief, Cornelis J.M., primary, Hollema, Harry, primary, Duiker, Evelien W., primary, Daemen, Toos, primary, de Bruyn, Marco, primary, and Nijman, Hans W., primary

Published
2023
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12. Supplementary figures and tables legends from Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma

Author

Caumanns, Joseph J., primary, Berns, Katrien, primary, Wisman, G. Bea A., primary, Fehrmann, Rudolf S.N., primary, Tomar, Tushar, primary, Klip, Harry, primary, Meersma, Gert J., primary, Hijmans, E. Marielle, primary, Gennissen, Annemiek M.C., primary, Duiker, Evelien W., primary, Weening, Desiree, primary, Itamochi, Hiroaki, primary, Kluin, Roelof J.C., primary, Reyners, Anna K.L., primary, Birrer, Michael J., primary, Salvesen, Helga B., primary, Vergote, Ignace, primary, van Nieuwenhuysen, Els, primary, Brenton, James, primary, Braicu, E. Ioana, primary, Kupryjanczyk, Jolanta, primary, Spiewankiewicz, Beata, primary, Mittempergher, Lorenza, primary, Bernards, René, primary, van der Zee, Ate G.J., primary, and de Jong, Steven, primary

Published
2023
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13. Supplementary Methods from Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma

Author

Caumanns, Joseph J., primary, Berns, Katrien, primary, Wisman, G. Bea A., primary, Fehrmann, Rudolf S.N., primary, Tomar, Tushar, primary, Klip, Harry, primary, Meersma, Gert J., primary, Hijmans, E. Marielle, primary, Gennissen, Annemiek M.C., primary, Duiker, Evelien W., primary, Weening, Desiree, primary, Itamochi, Hiroaki, primary, Kluin, Roelof J.C., primary, Reyners, Anna K.L., primary, Birrer, Michael J., primary, Salvesen, Helga B., primary, Vergote, Ignace, primary, van Nieuwenhuysen, Els, primary, Brenton, James, primary, Braicu, E. Ioana, primary, Kupryjanczyk, Jolanta, primary, Spiewankiewicz, Beata, primary, Mittempergher, Lorenza, primary, Bernards, René, primary, van der Zee, Ate G.J., primary, and de Jong, Steven, primary

Published
2023
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14. Data from Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Author

Wouters, Maartje C.A., primary, Komdeur, Fenne L., primary, Workel, Hagma H., primary, Klip, Harry G., primary, Plat, Annechien, primary, Kooi, Neeltje M., primary, Wisman, G. Bea A., primary, Mourits, Marian J.E., primary, Arts, Henriette J.G., primary, Oonk, Maaike H.M., primary, Yigit, Refika, primary, de Jong, Steven, primary, Melief, Cornelis J.M., primary, Hollema, Harry, primary, Duiker, Evelien W., primary, Daemen, Toos, primary, de Bruyn, Marco, primary, and Nijman, Hans W., primary

Published
2023
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15. Supplementary Data from Enhanced Antitumor Efficacy of a DR5-Specific TRAIL Variant over Recombinant Human TRAIL in a Bioluminescent Ovarian Cancer Xenograft Model

Author

Duiker, Evelien W., primary, de Vries, Elisabeth G.E., primary, Mahalingam, Devalingam, primary, Meersma, Gert Jan, primary, Boersma-van Ek, Wytske, primary, Hollema, Harry, primary, Lub-de Hooge, Marjolijn N., primary, van Dam, Go M., primary, Cool, Robbert H., primary, Quax, Wim J., primary, Samali, Afshin, primary, van der Zee, Ate G.J., primary, and de Jong, Steven, primary

Published
2023
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16. Variation in the management of benign liver tumors: A European survey and case vignette study

Author

Haring, Martijn P.D., primary, de Haas, Robbert J., additional, van Vilsteren, Frederike G.I., additional, Klaase, Joost M., additional, Duiker, Evelien W., additional, Blokzijl, Hans, additional, de Jong, Koert P., additional, de Meijer, Vincent E., additional, Cuperus, Frans J.C., additional, de Boer, Y.S., additional, de Man, R.A., additional, den Hoed, C.M., additional, Drenth, J.P.H., additional, Garcovich, M.G., additional, Gevers, T.J.G., additional, Klompenhouwer, A.J., additional, Kramer, M., additional, Tushuizen, M.E., additional, van der Meer, A.J., additional, Burgmans, M.C., additional, Cannella, R.C., additional, Caseiro-Alves, F.C., additional, Denecke, T.D., additional, Dwarkasing, R.S., additional, Fehrenbach, U.F., additional, Feshtali, S., additional, Miclea, R.L., additional, Poyanli, A.P., additional, Ronot, M.R., additional, Sartoris, R.S., additional, Thomeer, Maarten, additional, van der Leij, C., additional, van Koeverden, S.K., additional, Vermersch, M.V., additional, Vernuccio, F.V., additional, Willemssen, F.E.J.A., additional, Addeo, P.A., additional, Alexandrino, H., additional, Belli, A., additional, Bemelmans, M.H.A., additional, Boleslawski, E.B., additional, Coelen, R.J.S., additional, de Boer, M.T., additional, de Kleine, R.H., additional, den Dulk, M., additional, Frilling, A.F., additional, Furumaya, A., additional, Irinel, I.P., additional, Regimbeau, J.M., additional, Manuela, M.C., additional, Özden, İ., additional, Sallinen, V.S., additional, Schaapherder, A.F., additional, Schmelzle, M.S., additional, Seehofer, D., additional, Trotovšek, B., additional, Truant, S.T., additional, van den Boezem, P.B., additional, and van Rosmalen, B.V., additional

Published
2023
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17. Study protocol for a multicentre nationwide prospective cohort study to investigate the natural course and clinical outcome in benign liver tumours and cysts in the Netherlands: the BELIVER study

Author

Furumaya, Alicia, primary, Haring, Martijn P D, additional, van Rosmalen, Belle V, additional, Klompenhouwer, Anne J, additional, Besselink, Marc G, additional, de Man, Robert A, additional, IJzermans, Jan N M, additional, Thomeer, Maarten G J, additional, Kramer, Matthijs, additional, Coolsen, Mariëlle M E, additional, Tushuizen, Maarten E, additional, Schaapherder, Alexander F, additional, de Haas, Robbert J, additional, Duiker, Evelien W, additional, Kazemier, Geert, additional, van Delden, Otto M, additional, Verheij, Joanne, additional, Takkenberg, R Bart, additional, Cuperus, Frans J C, additional, De Meijer, Vincent E, additional, and Erdmann, Joris I, additional

Published
2022
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18. Study protocol for a multicentre nationwide prospective cohort study to investigate the natural course and clinical outcome in benign liver tumours and cysts in the Netherlands:the BELIVER study

Author

Furumaya, Alicia, Haring, Martijn P.D., Van Rosmalen, Belle V., Klompenhouwer, Anne J., Besselink, Marc G., De Man, Robert A., Ijzermans, Jan N.M., Thomeer, Maarten G.J., Kramer, Matthijs, Coolsen, Mariëlle M.E., Tushuizen, Maarten E., Schaapherder, Alexander F., De Haas, Robbert J., Duiker, Evelien W., Kazemier, Geert, Van Delden, Otto M., Verheij, Joanne, Takkenberg, R. Bart, Cuperus, Frans J.C., De Meijer, Vincent E., Erdmann, Joris I., Furumaya, Alicia, Haring, Martijn P.D., Van Rosmalen, Belle V., Klompenhouwer, Anne J., Besselink, Marc G., De Man, Robert A., Ijzermans, Jan N.M., Thomeer, Maarten G.J., Kramer, Matthijs, Coolsen, Mariëlle M.E., Tushuizen, Maarten E., Schaapherder, Alexander F., De Haas, Robbert J., Duiker, Evelien W., Kazemier, Geert, Van Delden, Otto M., Verheij, Joanne, Takkenberg, R. Bart, Cuperus, Frans J.C., De Meijer, Vincent E., and Erdmann, Joris I.

Abstract

Introduction Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease. Methods and analysis A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course. Ethics and dissemination The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal. Study registration NL8231 - 10 December 2019; Netherlands Trial Register.

Published
2022

19. Indeterminate pediatric acute liver failure:Clinical characteristics of a temporal cluster of five children in the Netherlands in the spring of 2022

Author

Lexmond, Willem S., de Meijer, Vincent E., Scheenstra, René, Bontemps, Sander T.H., Duiker, Evelien W., Schölvinck, Elisabeth H., Zhou, Xuewei, von Eije, Karin J., Reyntjens, Koen M.E.M., Verkade, Henkjan J., Porte, Robert J., de Kleine, Ruben H., Lexmond, Willem S., de Meijer, Vincent E., Scheenstra, René, Bontemps, Sander T.H., Duiker, Evelien W., Schölvinck, Elisabeth H., Zhou, Xuewei, von Eije, Karin J., Reyntjens, Koen M.E.M., Verkade, Henkjan J., Porte, Robert J., and de Kleine, Ruben H.

Abstract

There is increasing global concern of severe acute hepatitis of unknown etiology in young children. In early 2022, our center for liver transplantation in the Netherlands treated five children who presented in short succession with indeterminate acute liver failure. Four children underwent liver transplantation, one spontaneously recovered. Here we delineate the clinical course and comprehensive diagnostic workup of these patients. Three of five patients showed a gradual decline of liver synthetic function and had mild neurological symptoms. Their clinical and histological findings were consistent with hepatitis. These three patients all had a past SARS-CoV-2 infection and two of them were positive for adenovirus DNA. The other two patients presented with advanced liver failure and encephalopathy and underwent dialysis as a bridge to transplantation. One of these children spontaneously recovered. We discuss this cluster of patients in the context of the currently elevated incidence of severe acute hepatitis in children.

Published
2022

20. Indeterminate pediatric acute liver failure: Clinical characteristics of a temporal cluster of five children in the Netherlands in the spring of 2022

Author

Lexmond, Willem S., primary, de Meijer, Vincent E., additional, Scheenstra, René, additional, Bontemps, Sander T. H., additional, Duiker, Evelien W., additional, Schölvinck, Elisabeth H., additional, Zhou, Xuewei, additional, von Eije, Karin J., additional, Reyntjens, Koen M. E. M., additional, Verkade, Henkjan J., additional, Porte, Robert J., additional, and de Kleine, Ruben H., additional

Published
2022
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21. Intraoperative Molecular Fluorescence Imaging of Pancreatic Cancer by Targeting Vascular Endothelial Growth Factor: A Multicenter Feasibility Dose-Escalation Study

Author

Mulder, Babs G. Sibinga, primary, Koller, Marjory, additional, Duiker, Evelien W., additional, Sarasqueta, Arantza Farina, additional, Burggraaf, Jakobus, additional, Meijer, Vincent E. de, additional, Vahrmeijer, Alexander L., additional, Hoogwater, Frederik J.H., additional, Bonsing, Bert A., additional, van Dam, Gooitzen M., additional, Mieog, J. Sven D., additional, and Pranger, Bobby K., additional

Published
2022
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29. Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma

Author

Caumanns, Joseph J., primary, Berns, Katrien, additional, Wisman, G. Bea A., additional, Fehrmann, Rudolf S.N., additional, Tomar, Tushar, additional, Klip, Harry, additional, Meersma, Gert J., additional, Hijmans, E. Marielle, additional, Gennissen, Annemiek M.C., additional, Duiker, Evelien W., additional, Weening, Desiree, additional, Itamochi, Hiroaki, additional, Kluin, Roelof J.C., additional, Reyners, Anna K.L., additional, Birrer, Michael J., additional, Salvesen, Helga B., additional, Vergote, Ignace, additional, van Nieuwenhuysen, Els, additional, Brenton, James, additional, Braicu, E. Ioana, additional, Kupryjanczyk, Jolanta, additional, Spiewankiewicz, Beata, additional, Mittempergher, Lorenza, additional, Bernards, René, additional, van der Zee, Ate G.J., additional, and de Jong, Steven, additional

Published
2018
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32. Targeting the extrinsic apoptosis pathway in ovarian cancer

Author

Duiker, Evelien Wilma, Duiker, Evelien Wilma, Duiker, Evelien Wilma, and Duiker, Evelien Wilma

Abstract

Ovarian cancer is among the most lethal of all malignancies in women. In The Netherlands its incidence is about 10 times lower than for breast cancer, whereas its mortality rate is three times higher (1). The main cause of this high lethality is the advanced stage of disease present in the majority of patients at the time of initial diagnosis. As the disease is generally asymptomatic early in its progression and the molecular pathogenesis is poorly understood, strategies for early detection and prevention have not yet been successful. Treatment of advanced stage ovarian cancer, consisting of combined modality treatment with surgery and chemotherapy, yields initial response rates of over 80%, with 40-60% complete responses (2). However, the vast majority of patients dies within five years after disease manifestation with drug-resistant cancers. The possibility to escape apoptosis is defined as one of the hallmarks of carcinogenesis (3) and is a major factor involved in chemotherapy resistance (4). Apoptosis results from caspase activation brought upon through two separate pathways. Since the intrinsic pathway is commonly disrupted in cancer cells, targeting the extrinsic pathway by ligand-activation of cell-surface death receptors is regarded as a promising strategy to overcome apoptosis resistance. The recombinant human form of the TNF-family member TRAIL and other drugs directed at its agonistic receptors DR4 or DR5 induce apoptosis in a wide variety of human cancer cell lines and their xenografts, including ovarian carcinoma cells, without being toxic to normal tissues. Furthermore, combination of these agents with conventional chemotherapeutics and radiotherapy results in enhanced cytotoxicity. RhTRAIL and monoclonal antibodies targeting DR4 or DR5 are currently evaluated in early phase clinical studies. The aim of this thesis was to explore the potential of rhTRAIL and DR4 or DR5targeting drugs as anticancer agents, with the focus on ovarian cancer.

Published
2008

33. Abstract A108: CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

Author

Nijman, Hans, primary, Komdeur, Fenne, additional, Wouters, Maartje, additional, Workel, Hagma, additional, Brunekreeft, Kim, additional, Plat, Annechien, additional, Eggink, Florine, additional, Wisman, Bea, additional, Daemen, Toos, additional, Duiker, Evelien, additional, Hollema, Harry, additional, and Bruyn, Marco de, additional

Published
2016
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35. CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

Author

Komdeur, Fenne L., primary, Wouters, Maartje C.A., additional, Workel, Hagma H., additional, Tijans, Aline M., additional, Terwindt, Anouk L.J., additional, Brunekreeft, Kim L., additional, Plat, Annechien, additional, Klip, Harry G., additional, Eggink, Florine A., additional, Leffers, Ninke, additional, Helfrich, Wijnand, additional, Samplonius, Douwe F., additional, Bremer, Edwin, additional, Wisman, G. Bea A., additional, Daemen, Toos, additional, Duiker, Evelien W., additional, Hollema, Harry, additional, Nijman, Hans W., additional, and de Bruyn, Marco, additional

Published
2016
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36. Abstract A37: Dual wavelength near-infrared fluorescence imaging of VEGF-A and IGF-1R in ovarian cancer patient-derived xenografts

Author

Tomar, Tushar, primary, Alkema, Nicolette G., additional, Visser, Jolanda A.L., additional, Scheltinga, Anton G. Terwisscha van, additional, Meersma, Gert Jan, additional, Klip, Harry G., additional, Duiker, Evelien W., additional, Vries, Elisabeth G.E. De, additional, Zee, Ate G.J. Van der, additional, and Jong, Steven De, additional

Published
2016
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37. Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Author

Wouters, Maartje C.A., primary, Komdeur, Fenne L., additional, Workel, Hagma H., additional, Klip, Harry G., additional, Plat, Annechien, additional, Kooi, Neeltje M., additional, Wisman, G. Bea A., additional, Mourits, Marian J.E., additional, Arts, Henriette J.G., additional, Oonk, Maaike H.M., additional, Yigit, Refika, additional, de Jong, Steven, additional, Melief, Cornelis J.M., additional, Hollema, Harry, additional, Duiker, Evelien W., additional, Daemen, Toos, additional, de Bruyn, Marco, additional, and Nijman, Hans W., additional

Published
2016
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38. HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in‐situ hybridisation.

Author

Koopman, Timco, Vegt, Bert, Dijkstra, Marcel, Bart, Joost, Duiker, Evelien, Wisman, G. Bea A., Bock, Geertruida H., and Hollema, Harry

Subjects
IMMUNOGLOBULINS, IMMUNOHISTOCHEMISTRY, EPIDERMAL growth factor
Abstract

Aims: Treatment with anti‐HER2 therapy could be beneficial for patients with HER2‐positive endometrial and ovarian clear cell carcinoma (CCC). We studied HER2 overexpression by immunohistochemistry (IHC) using three different antibodies, including concordance with amplification by in‐situ hybridisation (ISH). Methods and results: IHC and ISH were performed on tissue microarrays of 101 tumours: 58 endometrial pure CCC, 19 endometrial mixed carcinomas with a CCC component and 24 ovarian pure CCC. IHC was performed using SP3, 4B5 and HercepTest antibodies, and was scored by two independent observers. ISH was performed using dual‐colour silver ISH. Using IHC, agreement was poor between SP3/4B5 (61.4%), poor between SP3/HercepTest (68.3%) and reasonable between 4B5/HercepTest (75.2%). Interobserver agreement was substantial to almost perfect for all antibodies (SP3: linear weighted κ = 0.89, 4B5: κ = 0.90, HercepTest: κ = 0.76). HER2‐positivity by ISH was 17.8% (endometrial pure CCC: 24.1%, endometrial mixed: 0%, ovarian pure CCC: 16.7%). IHC/ISH concordance was poor, with a high false‐negative rate of all three IHC antibodies: sensitivity (38.9–50.0%) and positive predictive value (PPV) (37.5–58.3%) were poor; specificity (81.9–94.0%) and negative predictive value (NPV) (87.1–88.3%) were reasonable. When excluding 2+ cases, sensitivity declined (26.7–43.8%) but PPV (80.0–87.5%) and specificity (98.6–98.7%) improved. Conclusions: In ovarian and endometrial CCC, there is considerable difference in HER2 overexpression by different IHC antibodies and marked discordance with ISH. As such, no single antibody can be considered conclusive for determining HER2 status in CCC. Based on these results, the lack of predictive value of different HER2 testing methods, as used in other studies, could be explained. [ABSTRACT FROM AUTHOR]

Published
2018
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40. Enhanced Antitumor Efficacy of a DR5-Specific TRAIL Variant over Recombinant Human TRAIL in a Bioluminescent Ovarian Cancer Xenograft Model

Author

Duiker, Evelien W., primary, de Vries, Elisabeth G.E., additional, Mahalingam, Devalingam, additional, Meersma, Gert Jan, additional, Boersma-van Ek, Wytske, additional, Hollema, Harry, additional, Lub-de Hooge, Marjolijn N., additional, van Dam, Go M., additional, Cool, Robbert H., additional, Quax, Wim J., additional, Samali, Afshin, additional, van der Zee, Ate G.J., additional, and de Jong, Steven, additional

Published
2009
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42. TRAIL VARIANTS FOR TREATING CANCER

Author

SAMALI AFSHIN, SZEGEZDI EVA, MAHALINGHAM DEVALINHAM, DE VRIES EMMA GEERTRUIDA ELISABETH, DUIKER EVELIEN WILMA, DE JONG STEVEN, RODRIGUES DOS REIS CARLOS RICARDO, DE RUIJTER MARIEKE, COOL ROBBERT HANS, QUAX WILHELMUS JOHANNES, Almer van der Sloot, and SERRANO LUIS

43. RAD51 recruitment but not replication fork stability associates with PARP inhibitor response in ovarian cancer patient-derived xenograft models.

Author

Talens F, Teixeira VON, Kok YP, Chen M, Rosenberg EH, Debipersad R, Duiker EW, van den Tempel N, Janatova M, Zemankova P, Nederlof PM, Wisman GBA, Kleibl Z, de Jong S, and van Vugt MATM

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are currently used to treat BRCA1/2 mutant cancers. Although PARPi sensitivity has been attributed to homologous recombination (HR) defects, other roles of HR factors have also been linked to response to PARPi, including replication fork protection. In this study, we investigated PARPi sensitivity in ovarian cancer patient-derived xenograft (PDX) models in relation to HR proficiency and replication fork protection. Analysis of BRCA1/2 status showed that in our cohort of 31 ovarian cancer PDX models 22.6% harbored a BRCA1/2 alteration (7/31), and 48.3% (15/31) were genomically unstable as measured by copy number alteration analysis. In vivo , PARPi olaparib response was measured in 15 selected PDX models. Functional assessment of HR using ex vivo irradiation-induced RAD51 foci formation identified all olaparib-sensitive PDX models, including four models without BRCA1/2 alterations. In contrast, replication fork protection or replication speed in ex vivo tumor tissue did not correlate with olaparib response. Targeted panel sequencing in olaparib-sensitive models lacking BRCA1/2 alterations revealed a MUS81 variant as a possible mechanism underlying PARPi sensitivity. Combined, we show that ex vivo RAD51 analysis effectively predicts in vivo olaparib response and revealed a subset of PARPi-sensitive, HR-deficient ovarian cancer PDX models, lacking a BRCA1/2 alteration., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Cancer.)

Published
2024
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44. [A female patient with liver failure and pseudocirrhosis].

Author

Hoogland P, Duiker EW, Pennings JP, de Meijer VE, and Blokzijl H

Subjects
Aged, Female, Humans, Liver Cirrhosis complications, Liver Cirrhosis diagnosis, Tomography, X-Ray Computed, Acute-On-Chronic Liver Failure complications, Breast Neoplasms complications, Breast Neoplasms pathology, Liver Neoplasms diagnosis, Liver Neoplasms secondary
Abstract

Background: Acute-on-chronic liver failure encompasses an acute deterioration of liver function in patients with pre-existent cirrhosis. Sometimes the clinical picture of acute-on-chronic liver failure is misleading and may not be secondary to primary liver disease, as described in our case., Case Description: A 65-year-old woman with cirrhosis was transferred to our transplantation centre because of suspected acute-on-chronic liver failure. Given her medical history of breastcancer and suspicious laboratory results, we performed a liver biopsy. This showed diffuse metastases of mammary carcinoma. Earlier CT-scans showed features of cirrhosis without signs of malignancy: a misleading phenomenon called pseudocirrhosis., Conclusion: Diffuse malignant hepatic infiltration can resemble cirrhosis and acute-on-chronic liver failure, both in clinical presentation as in imaging. Liver transplantation is contraindicated in malignant liver failure. To assure a solid indication for transplantation, a liver biopsy has to be considered, even in emergency situations.

Published
2022

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