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1. Understanding homologous recombination repair deficiency in biliary tract cancers: clinical implications and correlation with platinum sensitivity

Author

Mavroeidi, I.-A., Burghofer, J., Kalbourtzis, S., Taghizadeh, H., Webersinke, G., Piringer, G., Kasper, S., Schreil, G., Liffers, S.T., Reichinger, A., Kirchweger, P., Heibl, S., Hamacher, R., Schmitt, C.A., Schuler, M., Prager, G.W., Kersting, D., Treckmann, J., Schildhaus, H.-U., Rumpold, H., Siveke, J.T., and Doleschal, B.

Published
2024
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2. Changes over time in the course of advanced pancreatic cancer treatment with systemic chemotherapy: a pooled analysis of five clinical trials from two decades of the German AIO study group

Author

Weiss, L., Fischer, L.E., Heinemann, V., Gieseler, F., Hoehler, T., Mayerle, J., Quietzsch, D., Reinacher-Schick, A., Schenk, M., Seipelt, G., Siveke, J.T., Stahl, M., Kaiser, U., Waldschmidt, D.T., Dorman, K., Zhang, D., Westphalen, C.B., Boeck, S., and Haas, M.

Published
2024
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3. Prognostic value of deep learning-derived body composition in advanced pancreatic cancer—a retrospective multicenter study

Author

Keyl, J., Bucher, A., Jungmann, F., Hosch, R., Ziller, A., Armbruster, R., Malkomes, P., Reissig, T.M., Koitka, S., Tzianopoulos, I., Keyl, P., Kostbade, K., Albers, D., Markus, P., Treckmann, J., Nassenstein, K., Haubold, J., Makowski, M., Forsting, M., Baba, H.A., Kasper, S., Siveke, J.T., Nensa, F., Schuler, M., Kaissis, G., Kleesiek, J., and Braren, R.

Published
2024
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6. Prognostic and predictive value of CA 19-9 in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: results from a prospective, multicenter phase II trial (NEOLAP-AIO-PAK-0113)

Author

Hartlapp, I., Valta-Seufzer, D., Siveke, J.T., Algül, H., Goekkurt, E., Siegler, G., Martens, U.M., Waldschmidt, D., Pelzer, U., Fuchs, M., Kullmann, F., Boeck, S., Ettrich, T.J., Held, S., Keller, R., Anger, F., Germer, C.T., Stang, A., Kimmel, B., Heinemann, V., and Kunzmann, V.

Published
2022
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7. Prognosis and tumor biology of pancreatic cancer patients with isolated lung metastases: translational results from the German multicenter AIO-YMO-PAK-0515 study

Author

Kruger, S.F., Lohneis, A., Abendroth, A., Berger, A.W., Ettrich, T.J., Waidmann, O., Kapp, M., Steiner, B., Kumbrink, J., Reischer, A., Haas, M., Westphalen, C.B., Zhang, D., Miller-Phillips, L., Burger, P.J., Kobold, S., Werner, J., Subklewe, M., von Bergwelt-Baildon, M., Kunzmann, V., Seufferlein, T., Siveke, J.T., Sinn, M., Heinemann, V., Ormanns, S., and Boeck, S.

Published
2022
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9. Corrigendum to “Prognostic and predictive value of CA 19-9 in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: results from a prospective, multicenter phase II trial (NEOLAP-AIO-PAK-0113)”: [ESMO Open 7 (2024) 100552]

Author

Hartlapp, I., Valta-Seufzer, D., Siveke, J.T., Algül, H., Goekkurt, E., Siegler, G., Martens, U.M., Waldschmidt, D., Pelzer, U., Fuchs, M., Kullmann, F., Boeck, S., Ettrich, T.J., Held, S., Keller, R., Anger, F., Germer, C.T., Stang, A., Kimmel, B., Heinemann, V., and Kunzmann, V.

Published
2024
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10. Efficacy of gemcitabine plus erlotinib in rash-positive patients with metastatic pancreatic cancer selected according to eligibility for FOLFIRINOX: A prospective phase II study of the ‘Arbeitsgemeinschaft Internistische Onkologie’

Author

Haas, M., Siveke, J.T., Schenk, M., Lerch, M.M., Caca, K., Freiberg-Richter, J., Fischer von Weikersthal, L., Kullmann, F., Reinacher-Schick, A., Fuchs, M., Kanzler, S., Kunzmann, V., Ettrich, T.J., Kruger, S., Westphalen, C.B., Held, S., Heinemann, V., and Boeck, S.

Published
2018
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11. Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma.

Author

Dorst, D.N., Smeets, Esther M.M., Klein, C., Frielink, C., Geijs, D.J., Trajkovic-Arsic, M., Cheung, P.F.Y., Stommel, M.W.J., Gotthardt, M., Siveke, J.T., Aarntzen, E.H.J.G., Lith, S.A. van, Dorst, D.N., Smeets, Esther M.M., Klein, C., Frielink, C., Geijs, D.J., Trajkovic-Arsic, M., Cheung, P.F.Y., Stommel, M.W.J., Gotthardt, M., Siveke, J.T., Aarntzen, E.H.J.G., and Lith, S.A. van

Abstract

Contains fulltext : 296006.pdf (Publisher’s version ) (Open Access), Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5 year survival of 9%. One important limiting factor for treatment efficacy is the dense tumor-supporting stroma. The cancer-associated fibroblasts in this stroma deposit excessive amounts of extracellular matrix components and anti-inflammatory mediators, which hampers the efficacy of chemo- and immunotherapies. Systemic depletion of all activated fibroblasts is, however, not feasible nor desirable and therefore a local approach should be pursued. Here, we provide a proof-of-principle of using fibroblast activation protein (FAP)-targeted photodynamic therapy (tPDT) to treat PDAC. FAP-targeting antibody 28H1 and irrelevant control antibody DP47GS were conjugated to the photosensitizer IRDye700DX (700DX) and the chelator diethylenetriaminepentaacetic acid. In vitro binding and cytotoxicity were evaluated using the fibroblast cell-line NIH-3T3 stably transfected with FAP. Biodistribution of (111)In-labeled antibody-700DX constructs was determined in mice carrying syngeneic tumors of the murine PDAC cell line PDAC299, and in a genetically engineered PDAC mouse model (CKP). Then, tPDT was performed by exposing the subcutaneous or the spontaneous PDAC tumors to 690 nm light. Induction of apoptosis after treatment was assessed using automated analyses of immunohistochemistry for cleaved caspase-3. 28H1-700DX effectively bound to 3T3-FAP cells and induced cytotoxicity upon exposure to 690 nm light, whereas no binding or cytotoxic effects were observed for DP47GS-700DX. Although both 28H1-700DX and DP47GS-700DX accumulated in subcutaneous PDAC299 tumors, autoradiography demonstrated that only 28H1-700DX reached the tumor core. On the contrary, control antibody DP47GS-700DX was only present at the tumor rim. In CKP mice, both antibodies accumulated in the tumor, but tumor-to-blood ratios of 28H1-700DX were higher than that of the control. Notably, in vivo FAP-tPDT caused upregulation of cleaved caspase-3 sta

Published
2023

12. Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers

Author

Jahn, A., primary, Rump, A., additional, Widmann, T.J., additional, Heining, C., additional, Horak, P., additional, Hutter, B., additional, Paramasivam, N., additional, Uhrig, S., additional, Gieldon, L., additional, Drukewitz, S., additional, Kübler, A., additional, Bermudez, M., additional, Hackmann, K., additional, Porrmann, J., additional, Wagner, J., additional, Arlt, M., additional, Franke, M., additional, Fischer, J., additional, Kowalzyk, Z., additional, William, D., additional, Weth, V., additional, Oster, S., additional, Fröhlich, M., additional, Hüllein, J., additional, Valle González, C., additional, Kreutzfeldt, S., additional, Mock, A., additional, Heilig, C.E., additional, Lipka, D.B., additional, Möhrmann, L., additional, Hanf, D., additional, Oleś, M., additional, Teleanu, V., additional, Allgäuer, M., additional, Ruhnke, L., additional, Kutz, O., additional, Knurr, A., additional, Laßmann, A., additional, Endris, V., additional, Neumann, O., additional, Penzel, R., additional, Beck, K., additional, Richter, D., additional, Winter, U., additional, Wolf, S., additional, Pfütze, K., additional, Geörg, C., additional, Meißburger, B., additional, Buchhalter, I., additional, Augustin, M., additional, Aulitzky, W.E., additional, Hohenberger, P., additional, Kroiss, M., additional, Schirmacher, P., additional, Schlenk, R.F., additional, Keilholz, U., additional, Klauschen, F., additional, Folprecht, G., additional, Bauer, S., additional, Siveke, J.T., additional, Brandts, C.H., additional, Kindler, T., additional, Boerries, M., additional, Illert, A.L., additional, von Bubnoff, N., additional, Jost, P.J., additional, Metzeler, K.H., additional, Bitzer, M., additional, Schulze-Osthoff, K., additional, von Kalle, C., additional, Brors, B., additional, Stenzinger, A., additional, Weichert, W., additional, Hübschmann, D., additional, Fröhling, S., additional, Glimm, H., additional, Schröck, E., additional, and Klink, B., additional

Published
2022
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13. 1497P Safety and efficacy of [90Y]Y-FAPI-46 radioligand therapy in patients with advanced sarcomas and other cancer entities

Author

Hamacher, R.W., primary, Pabst, K.M., additional, Kessler, L., additional, Costa, P.F., additional, Ferdinandus, J., additional, Weber, M., additional, Lippert, M., additional, Lueckerath, K., additional, Hirmas, N., additional, Kostbade, K., additional, Mavroeidi, I.A., additional, Schuler, M.H.H., additional, Ahrens, M., additional, Rischpler, C., additional, Bauer, S., additional, Herrmann, K., additional, Siveke, J.T., additional, and Fendler, W.P., additional

Published
2022
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14. 487P Randomized phase II study of trabectedin/olaparib compared to physician’s choice in subjects with previously treated advanced or recurrent solid tumors harboring DNA repair deficiencies

Author

Heilig, C.E., primary, Teleanu, M-V., additional, Bhatti, I.A., additional, Richter, S., additional, Siveke, J.T., additional, Wagner, S., additional, Kopp, H-G., additional, Kindler, T., additional, Illert, L., additional, Golf, A., additional, Dormann, K., additional, Benner, A., additional, Süsse, H., additional, Freitag, A., additional, Von Kalle, C., additional, Glimm, H., additional, Hübschmann, D., additional, Fröhling, S., additional, and Schlenk, R.F., additional

Published
2022
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16. LBA25 Randomized phase III trial of ramucirumab in combination with TAS102 (Trifluridin/Tipiracil) vs. TAS102 monotherapy in heavily pretreated metastatic colorectal cancer: The RAMTAS/IKF643 trial of the German AIO (AIO-KRK-0316)

Author

Kasper-Virchow, S., Hofheinz, R.D., Stintzing, S., Dechow, T.N., Ettrich, T.J., Sinn, M., Roderburg, C., Fischer von Weikersthal, L., Graeven, U., Mueller, C., Meiler, J., Stein, A., Modest, D.P., Pauligk, C., Virchow, I., Siveke, J.T., Al-Batran, S-E., Schuler, M.H.H., and Goetze, T.O.

Published
2024
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17. 196P Randomized phase II study of trabectedin/olaparib compared to physician’s choice in subjects with previously treated advanced or recurrent solid tumors harboring DNA repair deficiencies

Author

Schlenk, R.F., Rübsam, M., Teleanu, M-V., Richter, S., Siveke, J.T., Wagner, S., Kopp, H-G., Kindler, T., Illert, L., Golf, A.H-E., Dorman, K., Schreck, N., Benner, A., Süsse, H., Freitag, A., von Kalle, C., Glimm, H., Hübschmann, D., Fröhling, S., and Heilig, C.E.

Published
2024
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19. Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression

Author

Cheung, P.F., Yang, J., Fang, R., Borgers, A., Krengel, K., Stoffel, A., Althoff, K., Yip, C.W., Siu, E.H.L., Ng, L.W.C., Lang, K.S., Cham, L.B., Engel, D.R., Soun, C., Cima, I., Scheffler, B., Striefler, J.K., Sinn, M., Bahra, M., Pelzer, U., Oettle, H., Markus, P., Smeets, E.M.M., Aarntzen, E.H.J.G., Savvatakis, K., Liffers, S.T., Lueong, S.S., Neander, C., Bazarna, A., Zhang, X., Paschen, A., Crawford, H.C., Chan, A.W., Cheung, S.T., Siveke, J.T., Cheung, P.F., Yang, J., Fang, R., Borgers, A., Krengel, K., Stoffel, A., Althoff, K., Yip, C.W., Siu, E.H.L., Ng, L.W.C., Lang, K.S., Cham, L.B., Engel, D.R., Soun, C., Cima, I., Scheffler, B., Striefler, J.K., Sinn, M., Bahra, M., Pelzer, U., Oettle, H., Markus, P., Smeets, E.M.M., Aarntzen, E.H.J.G., Savvatakis, K., Liffers, S.T., Lueong, S.S., Neander, C., Bazarna, A., Zhang, X., Paschen, A., Crawford, H.C., Chan, A.W., Cheung, S.T., and Siveke, J.T.

Abstract

Item does not contain fulltext, Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall survival in PDAC. Multiplex immunohistochemistry shows low MHC class I (MHCI) expression and lack of CD8(+) T cell infiltration in PGRN-high tumors. Inhibition of PGRN abrogates autophagy-dependent MHCI degradation and restores MHCI expression on PDAC cells. Antibody-based blockade of PGRN in a PDAC mouse model remarkably decelerates tumor initiation and progression. Notably, tumors expressing LCMV-gp33 as a model antigen are sensitized to gp33-TCR transgenic T cell-mediated cytotoxicity upon PGRN blockade. Overall, our study shows a crucial function of tumor-derived PGRN in regulating immunogenicity of primary PDAC.

Published
2022

20. Functional noninvasive detection of glycolytic pancreatic ductal adenocarcinoma

Author

Heid, Irina, Muench, Corinna, Karakaya, Sinan, Lueong, S.S., Winkelkotte, Alina M., Liffers, S.T., Smeets, Esther M.M., Aarntzen, E.H.J.G., Trajkovic-Arsic, Marija, Siveke, J.T., Heid, Irina, Muench, Corinna, Karakaya, Sinan, Lueong, S.S., Winkelkotte, Alina M., Liffers, S.T., Smeets, Esther M.M., Aarntzen, E.H.J.G., Trajkovic-Arsic, Marija, and Siveke, J.T.

Abstract

Item does not contain fulltext

Published
2022

21. Improved tumor detection for Ga-68-FAPI versus F-18-FDG PET/CT in patients with cholangiocellular carcinoma (CCC)

Author

Pabst, K.M., additional, Bartel, T., additional, Seifert, R., additional, Kessler, L., additional, Schaarschmidt, B.M., additional, Siveke, J.T., additional, Kasper, S., additional, Herrmann, K., additional, Hirmas, N., additional, Nader, M., additional, Schmidt, H.H., additional, Hamacher, R., additional, and Fendler, W.P., additional

Published
2022
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22. Imaging with Ga-68-FAPI PET/CT: Results from a FAPI Registry Study

Author

Hirmas, N., additional, Sraieb, M., additional, Kessler, L., additional, Pabst, K.M., additional, Bartel, T., additional, Hamacher, R., additional, Siveke, J.T., additional, Kasper, S., additional, Oster, C., additional, Hadaschik, B., additional, Nader, M., additional, Herrmann, K., additional, and Fendler, W.P., additional

Published
2022
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24. ECG scoring for the evaluation of therapy-naïve cancer patients to predict cardiotoxicity

Author

Pohl, J., Mincu, R.I., Mrotzek, S.M., Wakili, R., Mahabadi, A.A., Potthoff, S.K., Siveke, J.T., Keller, U., Landmesser, U., Rassaf, T., Anker, M.S., and Totzeck, M.

Subjects
Cancer Research
Abstract

OBJECTIVE: To evaluate a new electrocardiographic (ECG) score reflecting domains of electrical and structural alterations in therapy-naïve cancer patients to assess their risk of cardiotoxicity. METHODS: We performed a retrospective analysis of 134 therapy-naïve consecutive cancer patients in our two university hospitals concerning four ECG score parameters: Contiguous Q-waves, markers of left ventricular (LV) hypertrophy, QRS duration and JTc prolongation. Cardiotoxicity was assessed after a short-term follow-up (up to 12 months). RESULTS: Of all the patients (n = 25), 19% reached 0 points, 50% (n = 67) reached 1 point, 25% (n = 33) reached 2 points, 5% (n = 7) reached 3 points and 0.7% reached 4 or 5 points (n = 1 respectively). The incidence of cardiotoxicity (n = 28 [21%]) increased with the ECG score, with 0 points at 0%, 1 point 7.5%, 2 points 55%, 3 points 71% and ≥3 points 50%. In the ROC (Receiver operating curves) analysis, the best cut-off for predicting cardiotoxicity was an ECG score of ≥2 points (sensitivity 82%, specificity 82%, AUC 0.84, 95% CI 0.77-0.92, p < 0.0001) which was then defined as a high-risk score. High-risk patients did not differ concerning their age, LV ejection fraction, classical cardiovascular risk factors or cardiac biomarkers compared to those with a low-risk ECG score. CONCLUSION: ECG scoring prior to the start of anti-cancer therapies may help to identify therapy-naïve cancer patients at a higher risk for the development of cardiotoxicity. SIMPLE SUMMARY: Due to improved survival upon effective anti-cancer therapies, the management of treatment-related side-effects is of increasing interest and importance. Cardiovascular side-effects of chemo-, targeted- and/or immunotherapies are common and can be harmful. To date, the identification of patients who could experience those cardiovascular side-effects prior to the anti-cancer therapy start is difficult. We show that the use of a simple electrocardiographic (ECG) score can help to predict the occurrence of cardiovascular toxicity of anti-cancer therapies.

Published
2021

25. Map kinase activity drives a subtype specific subset of CAFS in PDAC

Author

Delfino, P., primary, Veghini, L., additional, Filippini, D., additional, D'Agosto, S.L., additional, Vicentini, C., additional, Fiorini, E., additional, Lupo, F., additional, Pasini, D., additional, Stirbu, I., additional, De Sanctis, F., additional, Ugel, S., additional, Bronte, V., additional, Scarpa, A., additional, Cheung, P.F., additional, Siveke, J.T., additional, and Corbo, V., additional

Published
2021
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27. The predictive and prognostic significance of cell‐free DNA concentration in melanoma

Author

Váraljai, R., primary, Elouali, S., additional, Lueong, S.S., additional, Wistuba‐Hamprecht, K., additional, Seremet, T., additional, Siveke, J.T., additional, Becker, J.C., additional, Sucker, A., additional, Paschen, A., additional, Horn, P.A., additional, Neyns, B., additional, Weide, B., additional, Schadendorf, D., additional, and Roesch, A., additional

Published
2020
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28. The predictive and prognostic significance of cell‐free DNA concentration in melanoma.

Author

Váraljai, R., Elouali, S., Lueong, S.S., Wistuba‐Hamprecht, K., Seremet, T., Siveke, J.T., Becker, J.C., Sucker, A., Paschen, A., Horn, P.A., Neyns, B., Weide, B., Schadendorf, D., and Roesch, A.

Subjects
CIRCULATING tumor DNA, PROGNOSIS, DNA, SKIN cancer
Abstract

Background: Melanoma is the leading cause of skin cancer‐related deaths worldwide. While there have been significant improvements in the treatment of advanced melanoma in the past decade, biomarker development lagged behind. Objectives: The majority of liquid biopsy biomarkers rely on the analyses of oncogenic mutations; however, about 20% of melanoma patients are wild type. Therefore, validation of universal predictive and prognostic biomarkers is urgently needed. Methods: We analysed plasma samples in a discovery cohort (n = 20) and expansion cohort (n = 166) of metastatic melanoma patients and healthy donors (n = 116). Total plasma circulating cell‐free DNA (cfDNA) concentrations were measured on the Qubit® platform using assays for single‐(ss) and double (ds)‐stranded DNA, DNA spectrophotometry and RNase P qPCR. We explored the diagnostic, predictive and prognostic potential of cfDNA concentration by bio‐statistical methods and established a cfDNA threshold for risk stratification. Results: Our selected best method was Qubit® dsDNA assay which quantified higher plasma cfDNA concentrations in melanoma patients than in healthy controls (AUC 72%). Measurement of baseline cfDNA concentration revealed that high cfDNA was associated with presence of metastases and higher AJCC stage (P < 0.05). Furthermore, high baseline cfDNA was an indicator of shorter overall survival in patients with oncogenic mutations (HR 2.12, P = 0.0008), and in wild‐type patients (HR 5.55, P < 0.0001). Conclusions: We provide evidence that total cfDNA can be used as a biomarker for melanoma irrespective of the tumour genotype and can provide information on tumour load, risk of progression and risk of death. [ABSTRACT FROM AUTHOR]

Published
2021
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29. CDK4/6 inhibition in locally advanced/metastatic chordoma (NCT PMO-1601)

Author

Fröhling, S., primary, Barth, T.F., additional, Gröschel, S., additional, Folprecht, G., additional, Richter, S., additional, Mayer-Steinacker, R., additional, Schultheiss, M., additional, Möller, P., additional, Bauer, S., additional, Siveke, J.T., additional, Dettmer, S., additional, Richter, D., additional, Heining, C., additional, Horak, P., additional, Glimm, H., additional, Jäger, D., additional, Von Kalle, C., additional, and Schlenk, R., additional

Published
2017
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30. Prognostic value of baseline neutrophil-to-lymphocyte ratio for predicting clinical outcome in metastatic pancreatic ductal adenocarcinoma (mPDAC) patients treated with liposomal irinotecan (nal-IRI) + 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV alone

Author

Hubner, R.A., primary, Chen, L-T., additional, Li, C-P., additional, Bodoky, G., additional, Dean, A., additional, Lee, K-H., additional, Cunningham, D., additional, Siveke, J.T., additional, Braiteh, F.S., additional, de Jong, F.A., additional, Belanger, B., additional, Walls, R., additional, Mody, P.D., additional, von Hoff, D.D., additional, and Wang-Gillam, A., additional

Published
2017
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31. A randomized, double-blind, multi-center phase III study evaluating paclitaxel with and without RAD001 in patients with gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC)

Author

Pauligk, C., primary, Lorenzen, S., additional, Goetze, T., additional, Riera Knorrenschild, J., additional, Hegewisch Becker, S., additional, Seraphin, J., additional, Thuss-Patience, P., additional, Kopp, H-G., additional, Dechow, T., additional, Vogel, A., additional, Luley, K., additional, Pink, D., additional, Stahl, M., additional, Kullmann, F., additional, Hebart, H., additional, Siveke, J.T., additional, Egger, M., additional, Homann, N., additional, Probst, S., additional, and Al-Batran, S-E., additional

Published
2017
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32. 242P Effects of nal-IRI (MM-398) ± 5-fluorouracil on quality of life (QoL) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine based therapy: Results from NAPOLI-1

Author

Hubner, R., primary, Cubillo, A., additional, Blanc, J-F., additional, Melisi, D., additional, von Hoff, D.D., additional, Wang-Gillam, A., additional, Chen, L-T., additional, Becker, C., additional, Mamlouk, K., additional, Belanger, B., additional, Yang, Y., additional, de Jong, F., additional, and Siveke, J.T., additional

Published
2016
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33. 242P Effects of nal-IRI (MM-398) 6 5-fluorouracil on quality of life (QoL) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine based therapy: Results from NAPOLI-1

Author

Hubner, R., primary, Cubillo, A., additional, Blanc, J.-F., additional, Melisi, D., additional, von Hoff, D.D., additional, Wang-Gillam, A., additional, Chen, L.-T., additional, Becker, C., additional, Mamlouk, K., additional, Belanger, B., additional, Yang, Y., additional, de Jong, F., additional, and Siveke, J.T., additional

Published
2016
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34. TIMP-1 creates a pre-metastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice

Author

Seubert, B., Grünwald, B., Kobuch, J., Cui, H., Schelter, F., Schaten, S., Siveke, J.T., Lim, N.H., Nagase, H., Simonavicius, N., Heikenwälder, M., Reinheckel, T., Sleeman, J.P., Janssen, K.P., Knolle, P.A., and Krüger, A.

Subjects
Liver Metastasis, Microenvironment, Natural Protease Inhibitor, Neutrophil Granulocytes, Organ Susceptibility
Abstract

Due to its ability to inhibit pro-metastatic matrix metalloproteinases, tissue inhibitor of metalloproteinases (TIMP)-1 has been thought to suppress tumor metastasis. However, elevated systemic levels of TIMP-1 correlate with poor prognosis in cancer patients suggesting a metastasis-stimulating role of TIMP-1. In colorectal cancer patients, tumor as well as plasma TIMP-1 levels were correlated with synchronous liver metastasis or distant metastasis-associated disease relapse. In mice, high systemic TIMP-1 levels increased the liver susceptibility towards metastasis by triggering the formation of a pre-metastatic niche. This promoted hepatic metastasis independent of origin or intrinsic metastatic potential of tumor cells. High systemic TIMP-1 led to increased hepatic SDF-1 levels, which in turn promoted recruitment of neutrophils to the liver. Both inhibition of SDF-1-mediated neutrophil recruitment and systemic depletion of neutrophils reduced TIMP-1-induced increased liver susceptibility towards metastasis. This indicates a crucial functional role of neutrophils in the TIMP-1-induced pre-metastatic niche. Conclusion: Our results identify TIMP-1 as an essential promoter of hepatic pre-metastatic niche formation.

Published
2015

35. Selective in vivo imaging of tumors with a tumor cell-specific Hsp70 peptide-based probe

Author

Stangl, S., Varga, J., Freysoldt, B., Trajkovic-Arsic, M., Siveke, J.T., Greten, F.R., Ntziachristos, V., and Multhoff, G.

Abstract

Although in vivo targeting of tumors using fluorescently-labeled probes has greatly gained in importance over the last few years, most of the clinically applied reagents lack tumor cell specificity. Our novel tumor cell-penetrating peptide-based probe (TPP) recognizes an epitope of Hsp70 that is exclusively present on the cell surface of a broad variety of human and mouse tumors and metastases, but not on normal tissues. Due to the rapid turn-over rate of membrane-Hsp70, fluorescently-labeled TPP is continuously internalized into syngeneic, spontaneous, chemically/genetically induced and xenograft tumors following intravenous administration, thereby enabling site-specific labeling of primary tumors and metastases. In contrast to the commercially available non-peptide small molecule alpha v beta3-integrin antagonist IntegriSense (trademark), TPP exhibits a significantly higher tumor-to-background contrast and stronger tumor-specific signal intensity in all tested tumor models. Moreover, in contrast to IntegriSense (trademark), TPP reliably differentiates between tumor cells and cells of the tumor microenvironment, such as tumor-associated macrophages and fibroblasts which were found to be membrane-Hsp70 negative. Therefore, TPP provides a useful tool for multimodal imaging of tumors and metastases that might help to improve our understanding of tumorigenesis and allow the establishment of improved diagnostic procedures and more accurate therapeutic monitoring. TPP might also be a promising platform for tumor-specific drug delivery and other Hsp70- based targeted therapies.

Published
2014

36. Time course of selected treatment emergent adverse events (TEAEs) in NAPOLI-1: A phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy

Author

Hubner, R.A., primary, Chen, L.-T., additional, Siveke, J.T., additional, Li, C.-P., additional, Bodoky, G., additional, Dean, A., additional, Shan, Y.-S., additional, Jameson, G.S., additional, Macarulla, T., additional, Lee, K.-H., additional, Cunningham, D., additional, Blanc, J.-F., additional, Chiu, C.-F., additional, Schwartsmann, G., additional, Braiteh, F., additional, Mamlouk, K., additional, Belanger, B., additional, de Jong, F., additional, von Hoff, D.D., additional, and Wang-Gillam, A., additional

Published
2016
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37. Final results of NAPOLI-1: A phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy

Author

Chen, L.-T., primary, Wang-Gillam, A., additional, Li, C.-P., additional, Bodoky, G., additional, Dean, A., additional, Shan, Y.-S., additional, Jameson, G.S., additional, Macarulla, T., additional, Lee, K.-H., additional, Cunningham, D., additional, Blanc, J.-F., additional, Hubner, R., additional, Chiu, C.-F., additional, Schwartsmann, G., additional, Braiteh, F., additional, Belanger, B., additional, Bayever, E., additional, de Jong, F., additional, von Hoff, D.D., additional, and Siveke, J.T., additional

Published
2016
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38. Effects of nanoliposomal irinotecan (nal-IRI; MM-398) ± 5-fluorouracil and leucavorin (5-FU/LV) on quality of life (QoL) in patients (pts) with metastatic pancreatic adenocarcinoma (mPAC) previously treated with gemcitabine-based therapy: results from the phase 3 NAPOLI-1 study

Author

Melisi, D., primary, Melisi, D., additional, Siveke, J.T., additional, Blanc, J., additional, Von Hoff, D.D., additional, Wang-Gillam, A., additional, Chen, L., additional, Becker, C., additional, Mamlouk, K., additional, De Jong, F., additional, and Hubner, R., additional

Published
2016
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40. 741P - Prognostic value of baseline neutrophil-to-lymphocyte ratio for predicting clinical outcome in metastatic pancreatic ductal adenocarcinoma (mPDAC) patients treated with liposomal irinotecan (nal-IRI) + 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV alone

Author

Hubner, R.A., Chen, L-T., Li, C-P., Bodoky, G., Dean, A., Lee, K-H., Cunningham, D., Siveke, J.T., Braiteh, F.S., de Jong, F.A., Belanger, B., Walls, R., Mody, P.D., von Hoff, D.D., and Wang-Gillam, A.

Published
2017
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41. 670P - A randomized, double-blind, multi-center phase III study evaluating paclitaxel with and without RAD001 in patients with gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC)

Author

Pauligk, C., Lorenzen, S., Goetze, T., Riera Knorrenschild, J., Hegewisch Becker, S., Seraphin, J., Thuss-Patience, P., Kopp, H-G., Dechow, T., Vogel, A., Luley, K., Pink, D., Stahl, M., Kullmann, F., Hebart, H., Siveke, J.T., Egger, M., Homann, N., Probst, S., and Al-Batran, S-E.

Published
2017
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42. 693P - Time course of selected treatment emergent adverse events (TEAEs) in NAPOLI-1: A phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy

Author

Hubner, R.A., Chen, L.-T., Siveke, J.T., Li, C.-P., Bodoky, G., Dean, A., Shan, Y.-S., Jameson, G.S., Macarulla, T., Lee, K.-H., Cunningham, D., Blanc, J.-F., Chiu, C.-F., Schwartsmann, G., Braiteh, F., Mamlouk, K., Belanger, B., de Jong, F., von Hoff, D.D., and Wang-Gillam, A.

Published
2016
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43. 622PD - Final results of NAPOLI-1: A phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy

Author

Chen, L.-T., Wang-Gillam, A., Li, C.-P., Bodoky, G., Dean, A., Shan, Y.-S., Jameson, G.S., Macarulla, T., Lee, K.-H., Cunningham, D., Blanc, J.-F., Hubner, R., Chiu, C.-F., Schwartsmann, G., Braiteh, F., Belanger, B., Bayever, E., de Jong, F., von Hoff, D.D., and Siveke, J.T.

Published
2016
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50. Correspondence.

Author

Myoken, Yoshinari, Kyo, Tai-ichi, Kohara, Tadahiro, Fujihara, Megumu, Sugata, Tatsumi, Mikami, Yuzuru, Chuman, Yoshiko, Takata, Tohru, Sameshima, Hisako, Takeuchi, Shogo, Takatsuka, Yoshifusa, Makino, Torahiko, Blaser, Martin J., Utsunomiya, Atae, Siveke, J.T., Bogner, J.R., Bellmann, Romuald, Egger, Petra, and Wiedermann, Christian J.

Subjects
COMMUNICABLE diseases, CANDIDA albicans, GALLSTONES, BACTEREMIA
Abstract

Cites clinical reports related to infectious diseases. Fungemia caused by azole-resistant Candida albicans in neutropenic patients with acute leukemia; Campylobacter fetus bacteremia in a patient with adult T cell leukemia; Cholelithiasis possibly induced by protease inhibitors in three patients.

Published
2003

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