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1. Anti-Cancer Activity of Acriflavine as Metabolic Inhibitor of OXPHOS in Pancreas Cancer Xenografts

Author

Bulle A, Dekervel J, Deschuttere L, Nittner D, Van Cutsem E, Verslype C, and van Pelt J

Subjects
pancreatic ductal adenocarcinoma (pdac), tumor microenvironment, hif1, gene set enrichment analysis (gsea), metabolic reprogramming, drug repurposing., Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Ashenafi Bulle,1 Jeroen Dekervel,1 Lise Deschuttere,1 David Nittner,2,3 Eric Van Cutsem,1 Chris Verslype,1 Jos van Pelt1 1Laboratory of Clinical Digestive Oncology, Department of Oncology, KU Leuven & University Hospitals Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium; 2Histopathology Expertise Center, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium; 3Department of Oncology, KU Leuven, Leuven, BelgiumCorrespondence: Jos van PeltLaboratory of Clinical Digestive Oncology, Department of Oncology, KU Leuven & University Hospitals Leuven and Leuven Cancer Institute (LKI), Leuven, BelgiumTel +32-16-330 694Fax +32-16-330 718Email jos.vanpelt@kuleuven.bePurpose: All currently available therapies for the treatment of pancreatic ductal adenocarcinoma (PDAC) show limited success. PDACs fast progression depends on the tumor characteristics and can be influenced by the microenvironment. The antibacterial drug acriflavine (ACF) has been shown to have anti-cancer activities in cell lines.Materials and Methods: To understand the working mechanism of ACF on cancer progression and tumor-stromal interplay, we evaluated pancreatic cancer in cell culture (Panc-1) (morphology, cell invasion and RNA expression) and the macrophage cell line THP1 (representing innate immune stromal cells). In the translational arm, the activity of ACF on xenograft models of human PDAC tumors representing different clinical subclasses was investigated (tumor growth, morphology and immunofluorescence, RNA expression and pathway analysis).Results: In vitro, ACF reduces epithelial-to-mesenchymal transition (EMT) and invasion of Panc-1 cells and shifts macrophage polarization to a M1-like anti-tumoral phenotype. At non-toxic concentrations, ACF downregulates cell metabolism. In xenografts, effect on tumor growth and metabolism could be confirmed; however, the innate immune stromal cells did not respond. Importantly, only in the moderately differentiated PDAC model, ACF could significantly suppress tumor growth and not in the fast-growing EMT-high model. Pathway analysis shows that ACF highly significantly downregulates metabolic pathways, especially OXPHOS and MYC/cell proliferation pathways in xenografts.Conclusion: ACF, with known pleiotropic effects on cancer cells, is in this study shown to be an attractive therapeutic based on its novel observed metabolic activity. Repurposing this compound for cancer treatment should be in the setting with other targeting agents, which offers reduced chance of resistance development in PDAC. Further evaluation should best be done in biological complex models such as human xenografts or syngeneic cancer models.Keywords: pancreatic ductal adenocarcinoma, PDAC, tumor microenvironment, Hif1α, gene set enrichment analysis, GSEA, metabolic reprogramming, drug repurposing

Published
2020

2. The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022

Author

Ducreux, M., Abou-Alfa, G.K., Bekaii-Saab, T., Berlin, J., Cervantes, A., de Baere, T., Eng, C., Galle, P., Gill, S., Gruenberger, T., Haustermans, K., Lamarca, A., Laurent-Puig, P., Llovet, J.M., Lordick, F., Macarulla, T., Mukherji, D., Muro, K., Obermannova, R., O’Connor, J.-M., O’Reilly, E.M., Osterlund, P., Philip, P., Prager, G., Ruiz-Garcia, E., Sangro, B., Seufferlein, T., Tabernero, J., Verslype, C., Wasan, H., and Van Cutsem, E.

Published
2023
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4. Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study

Author

Kelley, RK, Verslype, C, Cohn, AL, Yang, T-S, Su, W-C, Burris, H, Braiteh, F, Vogelzang, N, Spira, A, Foster, P, Lee, Y, and Van Cutsem, E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Liver Disease, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Liver Cancer, Digestive Diseases, Rare Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adult, Aged, Anilides, Carcinoma, Hepatocellular, Disease-Free Survival, Double-Blind Method, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms, Male, Middle Aged, Niacinamide, Phenylurea Compounds, Protein Kinase Inhibitors, Pyridines, Sorafenib, hepatocellular carcinoma, cabozantinib, vascular endothelial growth factor receptor, progression-free survival, overall survival, tumor response, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundCabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts.Patients and methodsEligible patients had Child-Pugh A liver function and ≤1 prior systemic anticancer regimen, completed ≥4 weeks before study entry. The cabozantinib starting dose was 100 mg daily. After an initial 12-week cabozantinib treatment period, patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 were randomized to cabozantinib or placebo. The primary endpoint of the lead-in stage was objective response rate (ORR) at week 12, and the primary endpoint of the randomized stage was progression-free survival (PFS).ResultsAmong the 41 HCC patients enrolled, the week 12 ORR was 5%, with 2 patients achieving a confirmed partial response (PR). The week 12 disease control rate (PR or SD) was 66% (Asian subgroup: 73%). Of patients with ≥1 post-baseline scan, 78% had tumor regression, with no apparent relationship to prior sorafenib therapy. Alpha-fetoprotein (AFP) response (>50% reduction from baseline) occurred in 9 of the 26 (35%) patients with elevated baseline AFP and ≥1 post-baseline measurement. Twenty-two patients with SD at week 12 were randomized. Median PFS after randomization was 2.5 months with cabozantinib and 1.4 months with placebo, although this difference was not statistically significant. Median PFS and overall survival from Day 1 in all patients were 5.2 and 11.5 months, respectively. The most common grade 3/4 adverse events, regardless of attribution, were diarrhea (20%), hand-foot syndrome (15%), and thrombocytopenia (15%). Dose reductions were utilized in 59% of patients.ConclusionsCabozantinib has clinical activity in HCC patients, including objective tumor responses, disease stabilization, and reductions in AFP. Adverse events were managed with dose reductions.Trial registration numberNCT00940225.

Published
2017

7. Belgian guidelines for pathology reporting of neuroendocrine neoplasms of the pancreaticobiliary and gastrointestinal tract. Initialized by the Belgian Group of Digestive Oncology (BGDO) and supported by the BGDO, the BSP (Belgian Society of Pathology) and the BCR (Belgian Cancer Registry)

Author

Hoorens, A, primary, Borbath, I, additional, Vandamme, T, additional, Verslype, C, additional, Demetter, P, additional, Cuyle, P.J., additional, Ribeiro, S, additional, Van Damme, N, additional, and Geboes, K.P., additional

Published
2023
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10. Early tumor shrinkage and response assessment according to mRECIST predict overall survival in hepatocellular carcinoma patients under sorafenib

Author

Öcal, Osman, Schinner, Regina, Schütte, Kerstin, de Toni, Enrico N., Loewe, Christian, van Delden, Otto, Vandecaveye, Vincent, Gebauer, Bernhard, Zech, Christoph J., Sengel, Christian, Bargellini, Irene, Gasbarrini, Antonio, Sangro, Bruno, Pech, Maciej, Malfertheiner, Peter, Ricke, Jens, Seidensticker, Max, Kettner, E., Amthauer, H., Cwikla, J., Walecki, J., Klümpen, H., Schott, E., Kolligs, F., Rosmorduc, O., Menu, Y., Leroy, V., Mayerle, J., Trumm, C., Bartenstein, P., Reiser, M., Berg, T., Moche, M., Bilbao, I., Gossner, L., Reimer, P., Popovic, P., Stabuc, B., Piasecki, P., Podgajny, Z., Sacco, R., Peck-Radosavljevic, M., Lammer, J., Maleux, G., Verslype, C., Rosenberg, C., Nitsche, D., Waldenberger, P., Vergniol, J., Cassinotto, C., Yalcin, S., Peynircioglu, B., Zavaglia, C., Rampoldi, A., Tran, A., Chevallier, P., Anty, R., Trautwein, C., Kuhl, C., Grazioli, L., Vogl, T., Trojan, J., Bartolozzi, C., Iezzi, R., Bronowicki, J. P., Palmer, D., Evans, J., Sharma, R., Weir, G., Hubner, R., Basu, B., Ross, P., Internal medicine, Apollo - University of Cambridge Repository, Kettner, E., Amthauer, H., Cwikla, J., Walecki, J., Klümpen, H., Schott, E., Kolligs, F., Rosmorduc, O., Menu, Y., Leroy, V., Mayerle, J., Trumm, C., Bartenstein, P., Reiser, M., Berg, T., Moche, M., Bilbao, I., Gossner, L., Reimer, P., Popovic, P., Stabuc, B., Piasecki, P., Podgajny, Z., Sacco, R., Peck-Radosavljevic, M., Lammer, J., Maleux, G., Verslype, C., Rosenberg, C., Nitsche, D., Waldenberger, P., Vergniol, J., Cassinotto, C., Yalcin, S., Peynircioglu, B., Zavaglia, C., Rampoldi, A., Tran, A., Chevallier, P., Anty, R., Trautwein, Christian, Kuhl, Christiane, Grazioli, L., Vogl, T., Trojan, J., Bartolozzi, C., Iezzi, R., Bronowicki, J. P., Palmer, D., Evans, J., Sharma, R., Weir, G., Hubner, R., Basu, B., Ross, P., Radiology and Nuclear Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Oncology, and CCA - Cancer Treatment and Quality of Life

Subjects
Male, Carcinoma, Hepatocellular, Radiological and Ultrasound Technology, Hepatocellular carcinoma, Settore MED/09 - MEDICINA INTERNA, Liver Neoplasms, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Antineoplastic Agents, General Medicine, Sorafenib, mRECIST, Medical physics. Medical radiology. Nuclear medicine, Early tumor shrinkage, Treatment Outcome, Oncology, Objective response, Humans, Radiology, Nuclear Medicine and imaging, RC254-282, Research Article, Retrospective Studies
Abstract

Cancer imaging 22, 1 (2022). doi:10.1186/s40644-021-00439-x, Published by BioMed Central, London

Published
2022
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11. SO-13 Pembrolizumab in patients with advanced hepatocellular carcinoma (aHCC) previously treated with sorafenib: Updated data from the open-label, phase 2 KEYNOTE-224 study

Author

Vogel, A., primary, Edeline, J., additional, Ogasawara, S., additional, Kudo, M., additional, Finn, R., additional, Palmer, D., additional, Verslype, C., additional, Zagonel, V., additional, Fartoux, L., additional, Sarker, D., additional, Verset, G., additional, Chan, S., additional, Knox, J., additional, Cheng, A., additional, Daniele, B., additional, Yau, T., additional, Wang, A., additional, Hatogai, K., additional, Siegel, A., additional, and Cattan, S., additional

Published
2022
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12. Corrigendum to “Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”

Author

Vogel, A., primary, Cervantes, A., additional, Chau, I., additional, Daniele, B., additional, Llovet, J.M., additional, Meyer, T., additional, Nault, J.-C., additional, Neumann, U., additional, Ricke, J., additional, Sangro, B., additional, Schirmacher, P., additional, Verslype, C., additional, Zech, C.J., additional, Arnold, D., additional, and Martinelli, E., additional

Published
2022
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13. ENETS standardized (synoptic) reporting for endoscopy in neuroendocrine tumors

Author

Borbath, I., Pape, U. -F., Deprez, P. H., Bartsch, D. K., Caplin, M., Falconi, M., Garcia-Carbonero, R., Grozinsky-Glasberg, S., Jensen, R. T., Arnold, R., Ruszniewski, P., Toumpanakis, C., Valle, J. W., O'Toole, D., Belli, S. H., Castano, J. P., Chen, J., Costa, F. P., Couvelard, A., de Herder, W. W., Deroose, C. M., Dromain, C., Faggiano, A., Falkerby, J., Fazio, N., Frilling, A., Grande, E., Hand, P., Hicks, R. J., Horsch, D., Howe, J. R., Kloppel, G., Kolarova, T., Kos-Kudla, B., Koumarianou, A., Krejs, G. J., Krenning, E. P., Krishna, B. A., Leyden, S., Masui, T., Niederle, B., Nieveen van Dijkum, E. J., Oberg, K., Pavel, M., Perren, A., Prasad, V., Ramage, J. K., Reed, N. S., Rindi, G., Gemelli, A., Rinke, A., Rothmund, M., Singh, S., Sundin, A., Velthuysen, M. F. V., Verslype, C., Vullierme, M. P., Welin, S., Wiedenmann, B., Zhao, H., Graduate School, Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de gastro-entérologie, and UCL - (SLuc) Unité d'oncologie médicale

Subjects
Cellular and Molecular Neuroscience, Neuroendocrine Tumors, Endocrinology, neuroendocrine neoplasms, Endocrine and Autonomic Systems, Endocrinology, Diabetes and Metabolism, Humans, Endoscopy, endoscopy, standardised reporting
Abstract

Despite efforts from various endoscopy societies, reporting in the field of endoscopy remains extremely heterogeneous. Harmonisation of clinical practice in endoscopy has been highlighted by application of many clinical practice guidelines and standards pertaining to the endoscopic procedures and reporting are underlined. The aim of the proposed "standardised reporting" is to (1) facilitate recognition of gastrointestinal neuroendocrine neoplasms (NEN) on initial endoscopy, (2) to enable interdisciplinary decision making for treatment by a multidisciplinary team, (3) to provide a basis for a standardised endoscopic follow-up which allows detection of recurrence or progression reliably, (4) to make endoscopic reports on NEN comparable between different units, and (5) to allow research collaboration between NEN centres in terms of consistency of their endoscopic data. The ultimate goal is to improve disease management, patient outcome and reduce the diagnostic burden on the side of the patient by ensuring the highest possible diagnostic accuracy and validity of endoscopic exams and possibly interventions.

Published
2022

14. Long-term outcome of liver transplantation for unresectable liver metastases from Neuroendocrine neoplasms: a Belgian retrospective multi-centre study

Author

Bonaccorsi Riani, Eliano, Pulido Cloquell, Ignacio, Detry, O, Meurisse, N, Ysebaert, D, Pirenne, J, Verslype, C, Berrevoet, F, Vanlander, A, Lucidi, V, Coubeau, Laurent, Dahlqvist, Géraldine, Ciccarelli, Olga, Borbath, Ivan, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Service de gastro-entérologie, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, and UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie

Published
2022

19. Evaluating the accuracy of three international guidelines in identifying the risk of malignancy in pancreatic cysts : a retrospective analysis of a surgical treated population

Author

Vanden Bulcke, A, primary, Jaekers, J, additional, Topal, H, additional, Vanbeckevoort, D, additional, Vandecaveye, V, additional, Roskams, T, additional, Weynand, B.A., additional, Dekervel, J, additional, Van Cutsem, E, additional, van Malenstein, H, additional, Verslype, C, additional, Laleman, W, additional, and van der Merwe, S, additional

Published
2021
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21. 933P Updated results for pembrolizumab (pembro) monotherapy as first-line therapy for advanced hepatocellular carcinoma (HCC) in the phase II KEYNOTE-224 study

Author

Laethem, J-L. van, primary, Borbath, I., additional, Karwal, M., additional, Verslype, C., additional, Van Vlierberghe, H., additional, Kardosh, A., additional, Zagonel, V., additional, Stal, P., additional, Sarker, D., additional, Palmer, D., additional, Vogel, A., additional, Edeline, J., additional, Cattan, S., additional, Kudo, M., additional, Cheng, A-L., additional, Ogasawara, S., additional, Siegel, A.B., additional, Chisamore, M., additional, Wang, A., additional, and Zhu, A., additional

Published
2021
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22. The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 10th World Congress on Gastrointestinal Cancer, Barcelona, 2008

Author

Verslype, C., Van Cutsem, E., Dicato, M., Arber, N., Berlin, J.D., Cunningham, D., De Gramont, A., Diaz-Rubio, E., Ducreux, M., Gruenberger, T., Haller, D., Haustermans, K., Hoff, P., Kerr, D., Labianca, R., Moore, M., Nordlinger, B., Ohtsu, A., Rougier, P., Scheithauer, W., Schmoll, H.-J., Sobrero, A., Tabernero, J., and van de Velde, C.

Published
2009
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28. Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management. Belgian multidisciplinary expert discussion based on a modified Delphi method

Author

Cuyle, P. -J, Geboes, K., Carton, S., Casneuf, V., Decaestecker, J., Man, M., Demolin, G., Deroose, C. M., Vleeschouwer, C., Flamen, P., Hendlisz, A., Hoorens, A., Janssens, J., Karfis, I., Lybaert, W., Machiels, G., Monsaert, E., Sinapi, I., Cutsem, E., Vandamme, T., Ivan Borbath, Verslype, C., UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de gastro-entérologie, and UCL - (SLuc) Unité d'oncologie médicale

Subjects
Neuroendocrine Tumors, Belgium, Intestinal Neoplasms, neuroendocrine carcinoma, Humans, Human medicine, Somatostatin, multidisciplinary team (MDT), Carcinoma, Neuroendocrine, neuro-endocrine tumor
Abstract

Background and study aims: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel Patients and methods: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. Results: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). Conclusions: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance.

Published
2020

29. The management of metastatic pancreatic cancer: expert discussion and recommendations from the 14th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2012

Author

Verslype, C., Van Cutsem, E., Dicato, M., Arber, N., Berlin, J. D., Büchler, M. W., Cervantes, A., Ciardiello, F., Ducreux, M., Douillard, J. Y., Grothey, A., Haller, D., Haustermans, K., Heinemann, V., Hidalgo, M., Labianca, R., Li, J., Marshall, J. L., Nordlinger, B., OʼReilly, E. M., Roth, A., Rougier, P., Ryan, D., Schmiegel, W., Seufferlein, T., Schmoll, H. J., Sobrero, A., Tabernero, J., Tempero, M., Van Laethem, J. L., Ychou, M., and Zalcberg, J.

Published
2013
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34. New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel†

Author

Van Laethem, J.-L., Verslype, C., Iovanna, J. L., Michl, P., Conroy, T., Louvet, C., Hammel, P., Mitry, E., Ducreux, M., Maraculla, T., Uhl, W., Van Tienhoven, G., Bachet, J. B., Maréchal, R., Hendlisz, A., Bali, M., Demetter, P., Ulrich, F., Aust, D., Luttges, J., Peeters, M., Mauer, M., Roth, A., Neoptolemos, J. P., and Lutz, M.

Published
2012
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43. The management of pancreatic cancer. Current expert opinion and recommendations derived from the 8th World Congress on Gastrointestinal Cancer, Barcelona, 2006

Author

Verslype, C., Van Cutsem, E., Dicato, M., Cascinu, S., Cunningham, D., Diaz-Rubio, E., Glimelius, B., Haller, D., Haustermans, K., Heinemann, V., Hoff, P., Johnston, P. G., Kerr, D., Labianca, R., Louvet, C., Minsky, B., Moore, M., Nordlinger, B., Pedrazzoli, S., Roth, A., Rothenberg, M., Rougier, P., Schmoll, H.-J., Tabernero, J., Tempero, M., van de Velde, C., Van Laethem, J.-L., and Zalcberg, J.

Published
2007

48. Final results of a phase II quality of life (QOL) randomized, cross-over (CO) study with gemcitabine (Gem) and nab-paclitaxel (n-P) in locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC): QOLINPAC

Author

Chiritescu, G., primary, Dumon, K., additional, Verslype, C., additional, Houbiers, G., additional, Peeters, M., additional, Janssens, J., additional, van Daele, D., additional, Laurent, S., additional, Arts, J., additional, Hendrickx, K., additional, Borbath, I., additional, Ferrante, M., additional, Bastin, F.M., additional, Goeminne, J.-C., additional, van Laethem, J.-L., additional, Vanderstraeten, E., additional, Decaestecker, J., additional, van Vaerenbergh, W., additional, Delhougne, B., additional, and Van Cutsem, E., additional

Published
2018
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