172 results on '"von Amsberg G"'
Search Results
2. Aktuelle Therapie des metastasierten Prostatakarzinoms
- Author
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Sehn, F., Merseburger, A. S., and von Amsberg, G.
- Published
- 2021
- Full Text
- View/download PDF
3. Utilizing patient-derived organoids of prostate cancer to predict functional homologous recombination repair deficiency and targeted therapy response
- Author
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Elsesy, M.E., primary, Oh-Hohenhorst, S.J., additional, Oing, C., additional, Eckhardt, A., additional, Burdak-Rothkamm, S., additional, Alawi, M., additional, Müller, C., additional, Schüller, U., additional, Maurer, T., additional, Von Amsberg, G., additional, Petersen, C., additional, Rothkamm, K., additional, and Mansour, W.Y., additional
- Published
- 2024
- Full Text
- View/download PDF
4. Therapie des metastasierten kastrationsresistenten Prostatakarzinoms
- Author
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von Amsberg, G. and Merseburger, A. S.
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- 2020
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- View/download PDF
5. Therapiesituation beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) und die Auswirkungen im klinischen Alltag
- Author
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Wülfing, C., Bögemann, M., Goebell, P. J., Hammerer, P., Machtens, S., Pfister, D., Schwentner, C., Steuber, T., von Amsberg, G., and Schostak, M.
- Published
- 2019
- Full Text
- View/download PDF
6. Advanced Prostate Cancer Consensus Conference 2017: Diskussion der Empfehlungen zur Diagnostik und Therapie des metastasierten Prostatakarzinoms durch ein deutsches Expertengremium
- Author
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Schostak, M., König, F., Bögemann, M., Goebell, P., Hammerer, P., Machtens, S., Schwentner, C., Thomas, C., von Amsberg, G., von Rundstedt, F.-C., and Heidenreich, A.
- Published
- 2018
- Full Text
- View/download PDF
7. Aktuelle Systemtherapie des metastasierten Harnblasenkarzinoms
- Author
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Horn, T., von Amsberg, G., Tauber, R., and Retz, M.
- Published
- 2018
- Full Text
- View/download PDF
8. Onkologische Notfälle in der Chemotherapie: Febrile Neutropenie, Tumorlysesyndrom und Paravasate
- Author
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von Amsberg, G.
- Published
- 2018
- Full Text
- View/download PDF
9. Aktuelle Systemtherapie des metastasierten Harnblasenkarzinoms
- Author
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Horn, T., von Amsberg, G., Tauber, R., and Retz, M.
- Published
- 2017
- Full Text
- View/download PDF
10. Metabolites of the Marine Fungus Aspergillus candidus KMM 4676 Associated with a Kuril Colonial Ascidian
- Author
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Yurchenko, A. N., Ivanets, E. V., Smetanina, O. F., Pivkin, M. V., Dyshlovoi, S. A., von Amsberg, G., and Afiyatullov, Sh. Sh.
- Published
- 2017
- Full Text
- View/download PDF
11. 1363MO Cabazitaxel every 2 weeks versus every 3 weeks in older patients with metastatic castration-resistant prostate cancer (mCRPC): The CABASTY randomized phase III trial
- Author
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Oudard, S., primary, Beuzeboc, P., additional, Voog, E., additional, Barthelemy, P., additional, Thiery-Vuillemin, A., additional, Bennamoun, M., additional, Hasbini, A., additional, Aldabbagh, K., additional, Saldana, C., additional, Sevin, E., additional, Amela, Y.E., additional, Von Amsberg, G., additional, Houede, N., additional, Besson, D., additional, Feyerabend, S., additional, Boegemann, M., additional, Pfister, D., additional, Schostak, M., additional, Huillard, O., additional, and Helissey, C., additional
- Published
- 2022
- Full Text
- View/download PDF
12. Bosutinib in the management of chronic myelogenous leukemia
- Author
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Keller-von Amsberg G and Schafhausen P
- Subjects
Medicine (General) ,R5-920 - Abstract
Gunhild Keller-von Amsberg, Philippe SchafhausenDepartment of Hematology and Oncology and, Stem Cell Transplantation and Pulmonology Division, Oncological Center, University Hospital Hamburg-Eppendorf, Hamburg, GermanyAbstract: Bosutinib (SKI-606) is an orally available, once-daily dual Src and Abl kinase inhibitor, approved by the US Food and Drug Administration for the treatment of adults with chronic, accelerated, or blast-phase Philadelphia chromosome-positive chronic myelogenous leukemia who are intolerant of or resistant to first- or second-generation tyrosine kinase inhibitors. Bosutinib effectively overcomes the majority of imatinib-resistance-conferring BCR-ABL mutations except V299L and T315I. In the Bosutinib Efficacy and Safety in chronic myeloid LeukemiA (BELA) trial, bosutinib attained a faster and deeper molecular response than imatinib in newly diagnosed chronic-phase chronic myelogenous leukemia patients. Treatment-emergent adverse events are usually very manageable. Low grade, mostly self-limiting diarrhea represents the most frequently observed toxicity of bosutinib. Anti-diarrheal drugs, antiemetic agents, and/or fluid replacement should be used to treat these patients. The improved hematological toxicity of bosutinib compared with other tyrosine kinase inhibitors has been ascribed to its minimal activity against platelet-derived growth factor receptor and KIT. In this review, we give an overview on the profile of bosutinib, the clinical potential and treatment-emergent adverse events.Keywords: CML, BCR-ABL, SRC/ABL kinase inhibitor, resistance-conferring mutation
- Published
- 2013
13. Therapiewahl beim metastasierten kastrationsresistenten Prostatakarzinom
- Author
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von Amsberg, G., Steuber, T., and Lorch, A.
- Published
- 2015
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14. Erratum zu: Therapiesituation beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) und die Auswirkungen im klinischen Alltag
- Author
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Wülfing, C., Bögemann, M., Goebell, P. J., Hammerer, P., Machtens, S., Pfister, D., Schwentner, C., Steuber, T., von Amsberg, G., and Schostak, M.
- Published
- 2019
- Full Text
- View/download PDF
15. A1087 - Utilizing patient-derived organoids of prostate cancer to predict functional homologous recombination repair deficiency and targeted therapy response
- Author
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Elsesy, M.E., Oh-Hohenhorst, S.J., Oing, C., Eckhardt, A., Burdak-Rothkamm, S., Alawi, M., Müller, C., Schüller, U., Maurer, T., Von Amsberg, G., Petersen, C., Rothkamm, K., and Mansour, W.Y.
- Published
- 2024
- Full Text
- View/download PDF
16. P304 - ARASAFE - a randomized, phase 3 trial comparing 3-weekly Docetaxel 75 mg/m2 (in a 3-week cycle) versus 2-weekly Docetaxel 50 mg/m2 (in a 4-week cycle) in combination with Darolutamide + ADT in patients with mHSPC
- Author
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Von Amsberg, G., Roessler, A., Heers, H., Roghmann, F., Degener, S., Casuscelli, J., Zengerling, F., and Grimm, M-O.
- Published
- 2024
- Full Text
- View/download PDF
17. Docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer: a real-life analysis
- Author
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Tsaur, I., primary, Heidegger, I., additional, Bektic, J., additional, Kafka, M., additional, Van Den Bergh, R.C.N., additional, Hunting, J.C.B., additional, Thomas, A., additional, Brandt, M.P., additional, Höfner, T., additional, Debedde, E., additional, Thibault, C., additional, Ermacora, P., additional, Zattoni, F., additional, Foti, S., additional, Kretschmer, A., additional, Rodler, S., additional, Ploussard, G., additional, Von Amsberg, G., additional, Tilki, D., additional, Surcel, C., additional, Rosenzweig, B., additional, Gadot, M., additional, Gandaglia, G., additional, and Dotzauer, R., additional
- Published
- 2021
- Full Text
- View/download PDF
18. Therapiesituation beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) und die Auswirkungen im klinischen Alltag
- Author
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Martin Bögemann, David G. Pfister, von Amsberg G, Stefan Machtens, Martin Schostak, Peter Hammerer, Christian Schwentner, Thomas Steuber, Christian Wülfing, and P. J. Goebell
- Subjects
Oncology ,Chemotherapy ,medicine.medical_specialty ,Combination therapy ,business.industry ,Urology ,medicine.medical_treatment ,medicine.disease ,Systemic therapy ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Castration ,Docetaxel ,chemistry ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030212 general & internal medicine ,Stage (cooking) ,business ,medicine.drug - Abstract
There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naive stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.
- Published
- 2019
- Full Text
- View/download PDF
19. Abiraterone versus Docetaxel in der Erstlinientherapie des metastasierten hormonsensitiven Prostatakarzinoms – ein multizentrischer Vergleich
- Author
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Dotzauer, R, Heidegger, I, Bektic, J, Kafka, M, Van den Bergh, R, Hunting, J, Thomas, A, Brandt, M, Höfner, T, Debedde, E, Thibault, C, Ermacora, P, Zattoni, F, Foti, S, Kretschmer, A, Ploussard, G, Rodler, S, von Amsberg, G, Tilki, D, Gandaglia, G, and Tsaur, I
- Subjects
ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Fragestellung: Docetaxel (D) oder eine sekundäre Hormonmanipulation (SHT) kombiniert mit einer Androgendeprivationstherapie (ADT) sind mögliche Behandlungsoptionen bei Patienten mit metastasiertem hormonsensitiven Prostatakarzinom (mHSPC). In Anbetracht der mangelnden Real-World-Evidenz war[zum vollständigen Text gelangen Sie über die oben angegebene URL], 61. Jahrestagung der Südwestdeutschen Gesellschaft für Urologie e.V.
- Published
- 2021
- Full Text
- View/download PDF
20. 1808P Pain response and health-related quality of life (HRQL) analysis in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel every 2 weeks (16 mg/m2) versus every 3 weeks (25 mg/m2) in the CABASTY phase III trial
- Author
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Oudard, S., Ratta, R., Voog, E., Barthelemy, P., Thiery-Vuillemin, A., Bennamoun, M., Hasbini, A., Aldabbagh, K., Saldana, C., Von Amsberg, G., Houede, N., Besson, D., Feyerabend, S., Boegemann, M., Falcoz, A., Vernerey, D., Belhouari, H., Kotti, S., Tran, Y., and Helissey, C.
- Published
- 2023
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21. Effect of holothurians triterpene glycosides, cucumariosideA2-2 and frondoside A, on human prostate cancer: TUE-081
- Author
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Menchinskaia, E., Dyshlovoy, S., Jacobsen, C., Venz, S., Scharf, C., Aminin, D., Honecker, F., and von Amsberg, G.
- Published
- 2014
22. NutRiCaP – Nutrition Risk Assessment bei Patienten mit Prostatakarzinom
- Author
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Forster, T, additional, von Amsberg, G, additional, Thederan, I, additional, and Zyriax, B-C, additional
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- 2020
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23. AR-V7 – ein neuer prädiktiver und prognostischer Biomarker: Therapieindividualisierung beim kastrationsresistenten Prostatakarzinom
- Author
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Oing, C., von Amsberg, G., and Bokemeyer, C.
- Published
- 2015
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24. Treatment situation in metastastic Castration Naive Prostate Cancer (mCRPC) and the implications on clinical routine
- Author
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Wuelfing, C., Boegemann, M., Goebell, P. J., Hammerer, P., Machtens, S., Pfister, D., Schwentner, C., Steuber, T., von Amsberg, G., Schostak, M., Wuelfing, C., Boegemann, M., Goebell, P. J., Hammerer, P., Machtens, S., Pfister, D., Schwentner, C., Steuber, T., von Amsberg, G., and Schostak, M.
- Abstract
There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naive stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.
- Published
- 2019
25. P063 - Docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer: a real-life analysis
- Author
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Tsaur, I., Heidegger, I., Bektic, J., Kafka, M., Van Den Bergh, R.C.N., Hunting, J.C.B., Thomas, A., Brandt, M.P., Höfner, T., Debedde, E., Thibault, C., Ermacora, P., Zattoni, F., Foti, S., Kretschmer, A., Rodler, S., Ploussard, G., Von Amsberg, G., Tilki, D., Surcel, C., Rosenzweig, B., Gadot, M., Gandaglia, G., and Dotzauer, R.
- Published
- 2021
- Full Text
- View/download PDF
26. Advanced Prostate Cancer Consensus Conference 2017. Discussion of the recommendations for diagnosis and treatment of metastatic prostate cancer by a German panel of experts
- Author
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Schostak, M., Koenig, F., Boegemann, M., Goebell, P., Hammerer, P., Machtens, S., Schwentner, C., Thomas, C., von Amsberg, G., von Rundstedt, F. -C., Heidenreich, A., Schostak, M., Koenig, F., Boegemann, M., Goebell, P., Hammerer, P., Machtens, S., Schwentner, C., Thomas, C., von Amsberg, G., von Rundstedt, F. -C., and Heidenreich, A.
- Abstract
In March 2017 the aEuroeAdvanced Prostate Cancer Consensus Conference' (APCCC) took place in St. Gallen (Switzerland). The APCCC-panelists are internationally well known experts. With the actual data in mind they discussed treatment options for patients with advanced prostate cancer in order to update the international APCCC-recommendations from the previous meeting in 2015. Recently these consensus recommendations have been published in European Urology. A group of German experts discussed this year APCCC-votes during the meeting and the recommendations that were concluded from the votes from the German perspective. Reasons for an additional German discussion are country-specific variations that may have influenced the APCCC-votes und recommendations. Due to the concept of the APCCC-meeting the wording of the questions could not always be as necessary. One focus of this year consensus discussion was the treatment of metastatic castration-naive prostate cancer (mCNPC). There are new data which may also influence the therapeutic situation of patients with metastatic castration-resistant prostate cancer (mCRPC). Further points of discussion were the impact of new imaging procedures in the clinical setting as well as the treatment of oligometastatic prostate cancer.
- Published
- 2018
27. Aktuelle Therapiekonzepte bei kastrationsresistenten Prostatakarzinom
- Author
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Bokemeyer C, Steuber T, von Amsberg G, and P. Stroelin
- Subjects
Oncology ,medicine.medical_specialty ,Taxane ,medicine.drug_class ,business.industry ,medicine.medical_treatment ,General Medicine ,Immunotherapy ,Castration resistant ,medicine.disease ,Androgen ,Antiandrogen ,Prostate cancer ,chemistry.chemical_compound ,Endocrinology ,Docetaxel ,chemistry ,Internal medicine ,medicine ,Enzalutamide ,business ,medicine.drug - Abstract
Metastasized castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen depletion therapy (ADT). While until recently a life-prolonging effect could only be demonstrated for the taxane docetaxel, various alternative therapeutic options based on different mechanisms of action are available today: CYP17-inhibitor abiraterone and antiandrogen enzalutamide target the androgen receptor-signaling pathway, which maintains a crucial role in mCRPC. Cabazitxel - a semisynthetic taxane derivate - is the only second line chemotherapy, which results in a prolongation of overall survival to date. Alpha emitter Radium-223 has the ability to mimic calcium and target bone metastases. Thus, it is a reasonable therapeutic alternative for patients suffering from symptomatic bone metastases. In 2013, Sipuleucel-T was the first immunotherapy approved for CRPC in Europe. In this review we introduce the different therapeutic options to the reader, reflect the possible therapeutic sequences and give a perspective on novel pipeline medications.
- Published
- 2014
- Full Text
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28. Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia
- Author
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Keller-von Amsberg G and Koschmieder S
- Subjects
hemic and lymphatic diseases ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 - Abstract
Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation), University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606) is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML). Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML.Keywords: bosutinib, chronic myeloid leukemia, BCR-ABL, Src/Abl kinase inhibitor, point mutation, imatinib resistance
- Published
- 2013
29. Marine alkaloid Monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization
- Author
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Dyshlovoy, S A, Hauschild, J, Amann, K, Tabakmakher, K M, Venz, S, Walther, R, Guzii, A G, Makarieva, T N, Shubina, L K, Fedorov, S N, Stonik, V A, Bokemeyer, C, Balabanov, S, Honecker, F, von Amsberg, G, University of Zurich, and Dyshlovoy, S A
- Subjects
10032 Clinic for Oncology and Hematology ,610 Medicine & health ,2730 Oncology - Published
- 2015
30. Aktuelle Therapiekonzepte bei kastrationsresistenten Prostatakarzinom
- Author
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von Amsberg, G., additional, Stroelin, P., additional, Bokemeyer, C., additional, and Steuber, T., additional
- Published
- 2014
- Full Text
- View/download PDF
31. The Inhibitory Activity of Luzonicosides from the Starfish Echinaster luzonicus against Human Melanoma Cells
- Author
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Olesya S. Malyarenko, Sergey A. Dyshlovoy, Alla A. Kicha, Natalia V. Ivanchina, Timofey V. Malyarenko, Bokemeyer Carsten, von Amsberg Gunhild, Valentin A. Stonik, and Svetlana P. Ermakova
- Subjects
starfish ,Echinaster luzonicus ,steroids ,cyclic glycosides ,melanoma ,cytotoxicity ,cell cycle ,apoptosis ,migration ,Biology (General) ,QH301-705.5 - Abstract
Malignant melanoma is the most dangerous form of skin cancer, with a rapidly increasing incidence rate. Despite recent advances in melanoma research following the approval of several novel targeted and immuno-therapies, the majority of oncological patients will ultimately perish from the disease. Thus, new effective drugs are still required. Starfish steroid glycosides possess different biological activities, including antitumor activity. The current study focused on the determination of the in vitro inhibitory activity and the mechanism of action of cyclic steroid glycosides isolated from the starfish Echinaster luzonicus—luzonicoside A (LuzA) and luzonicoside D (LuzD)—in human melanoma RPMI-7951 and SK-Mel-28 cell lines. LuzA inhibited proliferation, the formation of colonies, and the migration of SK-Mel-28 cells significantly more than LuzD. Anti-cancer activity has been ascribed to cell cycle regulation and apoptosis induction. The molecular mechanism of action appears to be related to the regulation of the activity of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), along with Survivin, Bcl-2, p21 and cyclin D1 level. Overall, our findings support a potential anti-cancer efficacy of luzonicosides A and D on human melanoma cells.
- Published
- 2017
- Full Text
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32. A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer
- Author
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Tsaur, Igor, Heidegger, Isabel, Bektic, Jasmin, Kafka, Mona, Van Den Bergh, Roderick C. N., Hunting, Jarmo C. B., Thomas, Anita, Brandt, Maximilian P., Höfner, Thomas, Debedde, Eliott, Thibault, Constance, Ermacora, Paola, Zattoni, Fabio, Foti, Silvia, Kretschmer, Alexander, Ploussard, Guillaume, Rodler, Severin, Amsberg, Gunhild Von, Tilki, Derya, Surcel, Christian, Rosenzweig, Barak, Gadot, Moran, Gandaglia, Giorgio, Dotzauer, Robert, Tsaur, I., Heidegger, I., Bektic, J., Kafka, M., van den Bergh, R. C. N., Hunting, J. C. B., Thomas, A., Brandt, M. P., Hofner, T., Debedde, E., Thibault, C., Ermacora, P., Zattoni, F., Foti, S., Kretschmer, A., Ploussard, G., Rodler, S., von Amsberg, G., Tilki, D., Surcel, C., Rosenzweig, B., Gadot, M., Gandaglia, G., and Dotzauer, R.
- Subjects
Male ,hormonal therapy ,610 Medizin ,Abiraterone Acetate ,Clinical Cancer Research ,Androgen Antagonists ,Docetaxel ,Middle Aged ,chemotherapy ,prostate cancer ,hormone‐sensitive ,Progression-Free Survival ,Prostatic Neoplasms, Castration-Resistant ,610 Medical sciences ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,hormone-sensitive ,metastasis ,Research Articles ,Aged ,Retrospective Studies ,Research Article - Abstract
Background Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone‐sensitive prostate cancer (mHSPC). Real‐world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC. Methods In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression‐free survival 1 (PFS1), and progression‐free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan–Meier method and log‐rank test. The Cox‐proportional hazards model was used for univariate and multivariate regression analyses. Results Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log‐rank testing (23 vs. 13 mos., p, Abiratreone acetate outperforms docetaxel in terms of PFS and PFS2, while the impact on OS as well as the rate of side effects is similar between both groups in real‐life utilization. Prospective randomized trials of available agents in mHSPC are required to generate high‐level evidence to facilitate sensible drug selection
- Published
- 2021
33. Applications of Nanopore sequencing in precision cancer medicine.
- Author
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Dyshlovoy SA, Paigin S, Afflerbach AK, Lobermeyer A, Werner S, Schüller U, Bokemeyer C, Schuh AH, Bergmann L, von Amsberg G, and Joosse SA
- Subjects
- Humans, High-Throughput Nucleotide Sequencing methods, Biomarkers, Tumor genetics, Sequence Analysis, DNA methods, Epigenesis, Genetic, Precision Medicine methods, Neoplasms genetics, Nanopore Sequencing methods
- Abstract
Oxford Nanopore Technologies sequencing, also referred to as Nanopore sequencing, stands at the forefront of a revolution in clinical genetics, offering the potential for rapid, long read, and real-time DNA and RNA sequencing. This technology is currently making sequencing more accessible and affordable. In this comprehensive review, we explore its potential regarding precision cancer diagnostics and treatment. We encompass a critical analysis of clinical cases where Nanopore sequencing was successfully applied to identify point mutations, splice variants, gene fusions, epigenetic modifications, non-coding RNAs, and other pivotal biomarkers that defined subsequent treatment strategies. Additionally, we address the challenges of clinical applications of Nanopore sequencing and discuss the current efforts to overcome them., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2024
- Full Text
- View/download PDF
34. Lectins CGL and MTL, representatives of mytilectin family, exhibit different antiproliferative activity in Burkitt's lymphoma cells.
- Author
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Kuzmich AS, Filshtein AP, Likhatskaya GN, Gorpenchenko TY, Chikalovets IV, Mizgina TO, Hua KF, von Amsberg G, Dyshlovoy SA, and Chernikov OV
- Subjects
- Humans, Animals, Cell Line, Tumor, Mytilus metabolism, Reactive Oxygen Species metabolism, Cell Cycle drug effects, MAP Kinase Signaling System drug effects, Burkitt Lymphoma pathology, Burkitt Lymphoma metabolism, Burkitt Lymphoma drug therapy, Lectins pharmacology, Lectins metabolism, Lectins chemistry, Cell Proliferation drug effects
- Abstract
Lectins are carbohydrate-binding proteins, whose biological effects are exerted via binding to glycoconjugates expressed on the surface of cells. Exposure to lectins can lead not only to a change in the structure and properties of cells but also to their death. Here, we studied the biological activity of lectins from the mussels Crenomytilus graynus (CGL) and Mytilus trossulus (MTL) and showed that these proteins can affect the proliferation of human lymphoma cells. Both lectins suppressed the formation of colonies as well as cell cycle progression. The mechanism of action of these lectins was not mediated by reactive oxygen species but included damaging of mitochondria, inhibition of key cell cycle points, and activation of MAPK signaling pathway in tumor cells. Computer modeling suggested that various effects of CGL and MTL on lymphoma cells may be due to the difference in the energy of binding of these lectins to carbohydrate ligands on the cell surface. Thus, molecular recognition of residues of terminal carbohydrates on the surface of tumor cells is a key factor in the manifestation of the biological action of lectins., (© 2024 International Union of Biochemistry and Molecular Biology.)
- Published
- 2024
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- View/download PDF
35. [Paradigm shift in systemic therapy for metastatic urothelial carcinoma-antibody-drug conjugates (ADCs) and fibroblast growth factor receptor (FGFR) inhibitors].
- Author
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Casuscelli J, von Amsberg G, and Retz M
- Subjects
- Humans, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal therapeutic use, Cisplatin pharmacology, Cisplatin therapeutic use, Deoxycytidine analogs & derivatives, Deoxycytidine pharmacology, Deoxycytidine therapeutic use, Gemcitabine, Neoplasm Metastasis, Nivolumab pharmacology, Nivolumab therapeutic use, Pyrazoles, Receptors, Fibroblast Growth Factor antagonists & inhibitors, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Transitional Cell drug therapy, Carcinoma, Transitional Cell secondary, Carcinoma, Transitional Cell pathology, Immunoconjugates therapeutic use, Immunoconjugates pharmacology, Immunoconjugates administration & dosage, Urologic Neoplasms drug therapy, Urologic Neoplasms pathology
- Abstract
Background: Patients with locally advanced or metastatic urothelial carcinoma face a poor prognosis. Standard first-line treatment involves platinum-based combinations followed by avelumab maintenance therapy. Follow-up therapies include enfortumab vedotin, vinflunine, and taxanes., Objective: To analyze new drug combinations in first-line and follow-up treatment for metastatic urothelial carcinoma concerning their clinical relevance, toxicities, and novel treatment sequences., Materials and Methods: Analysis of new study data from EV-302/KN-A39 (enfortumab vedotin and pembrolizumab) and CheckMate-901 (nivolumab and gemcitabine-cisplatin) for untreated metastatic patients as well as TROPHY-U-01 (sacituzumab govitecan) and THOR (erdafitinib) for later lines., Results: The new standard in first-line treatment for metastatic urothelial carcinoma is the combination of enfortumab vedotin and pembrolizumab. For cisplatin-eligible patients with contraindications to enfortumab vedotin, the combination of nivolumab and gemcitabine-cisplatin offers an alternative. Erdafitinib presents a new biomarker-based option in the follow-up treatment of metastatic urothelial carcinoma., Conclusion: These novel combinations are revolutionizing the treatment standard for metastatic urothelial carcinoma and necessitate a new approach to managing side effects., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
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- 2024
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36. Stonikacidin A, an Antimicrobial 4-Bromopyrrole Alkaloid Containing L-Idonic Acid Core from the Northwestern Pacific Marine Sponge Lissodendoryx papillosa .
- Author
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Tabakmakher KM, Makarieva TN, Sabutski YE, Kokoulin MS, Menshov AS, Popov RS, Guzii AG, Shubina LK, Chingizova EA, Chingizov AR, Yurchenko EA, Fedorov SN, Grebnev BB, von Amsberg G, Dyshlovoy SA, Ivanchina NV, and Dmitrenok PS
- Subjects
- Animals, Molecular Docking Simulation, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents isolation & purification, Pyrroles pharmacology, Pyrroles chemistry, Pyrroles isolation & purification, Biofilms drug effects, Microbial Sensitivity Tests, Bacterial Proteins, Pacific Ocean, Cysteine Endopeptidases, Aminoacyltransferases, Porifera chemistry, Staphylococcus aureus drug effects, Alkaloids pharmacology, Alkaloids chemistry, Alkaloids isolation & purification, Escherichia coli drug effects
- Abstract
Stonikacidin A ( 1 ), the first representative of a new class of 4-bromopyrrole alkaloids containing an aldonic acid core, was isolated from the marine sponge Lissodendoryx papillosa . The compound is named in honor of Prof. Valentin A. Stonik, who is one of the outstanding investigators in the field of marine natural chemistry. The structure of 1 was determined using NMR, MS analysis, and chemical correlations. The L-idonic acid core was established by the comparison of GC, NMR, MS, and optical rotation data of methyl-pentaacetyl-aldonates obtained from the hydrolysis products of 1 and standard hexoses. The L-form of the idonic acid residue in 1 was confirmed by GC analysis of pentaacetate of ( S )-2-butyl ester of the hydrolysis product from 1 and compared with corresponding derivatives of L- and D-idonic acids. The biosynthetic pathway for stonikacidin A ( 1 ) was proposed. The alkaloid 1 inhibited the growth of Staphylococcus aureus and Escherichia coli test strains, as well as affected the formation of S. aureus and E. coli biofilms. Compound 1 inhibited the activity of sortase A. Molecular docking data showed that stonikacidin A ( 1 ) can bind with sortase A due to the interactions between its bromine atoms and some amino acid residues of the enzyme.
- Published
- 2024
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37. Pain and Health-related Quality of Life with Biweekly Versus Triweekly Cabazitaxel Schedule in Older Men with Metastatic Castration-resistant Prostate Cancer in the Multicenter, Randomized CABASTY Trial.
- Author
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Oudard S, Tran Y, Helissey C, Vauchier C, Ratta R, Bennamoun M, Voog E, Hasbini A, Thiery-Vuillemin A, Aldabbagh K, Saldana C, Sevin E, Amela E, Von Amsberg G, Houede N, Besson D, Feyerabend S, Boegemann M, Pfister D, Schostak M, Huillard O, Di Fiore F, Quivy A, Vernerey D, Falcoz A, Youcef-Ali K, Kotti S, Lepicard EM, and Barthelemy P
- Abstract
Background and Objective: The CABASTY study showed that more frequent administration of a lower dose of cabazitaxel (CBZ) reduced toxicity in older men with metastatic castration-resistant prostate cancer (mCRPC), without compromising efficacy. Here, we investigated the impact of a biweekly CBZ schedule on patient-reported pain and health-related quality of life (HRQoL)., Methods: We randomized 196 patients from 25 centers (1:1, stratified by age and G8 score) to the biweekly CBZ16 (CBZ 16 mg/m
2 ) experimental arm or the triweekly CBZ25 (CBZ 25 mg/m2 ) control arm (CABASTY study, NCT02961257). We assessed pain using the Numeric Pain Rating Scale and HRQoL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire., Key Findings and Limitations: A total of 141 patients were available for a pain and 160 for an HRQoL analysis. Median time to pain progression (stratified hazard ratio [HR]: 1.7, confidence interval [CI]: 0.67-4.22, p = 0.3) and median time to first opiate use (stratified HR: 1.05, CI: 0.44-2.55, p = 0.9) did not differ between arms. We did not see a significant difference in median time to deterioration of FACT-P total score between treatments (stratified HR: 0.88, CI: 0.47-1.7, p = 0.7). Interestingly, the time to onset of several adverse events was significantly longer in the biweekly CBZ16 group., Conclusions and Clinical Implications: HRQoL did not significantly differ between the biweekly CBZ16 and the standard schedule. Additionally, onset of some adverse events was delayed. These results may increase health care providers' confidence in using CBZ in older patients with mCRPC who are denied chemotherapy., Patient Summary: Androgen receptor pathway inhibitors are often preferred to taxane chemotherapy as a treatment of second or subsequent line in older metastatic castration-resistant prostate cancer patients due to more frequent treatment-related toxicities. Here, we showed that quality of life and pain did not differ significantly with an adapted schedule of cabazitaxel (CBZ), compared with the standard regimen. This CBZ schedule could increase eligibility of older patients for chemotherapy., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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38. Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2.
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Goradia N, Werner S, Mullapudi E, Greimeier S, Bergmann L, Lang A, Mertens H, Węglarz A, Sander S, Chojnowski G, Wikman H, Ohlenschläger O, von Amsberg G, Pantel K, and Wilmanns M
- Subjects
- Humans, Male, Cryoelectron Microscopy, Cell Line, Tumor, DNA-Binding Proteins metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins chemistry, Protein Binding, HEK293 Cells, Adaptor Proteins, Signal Transducing metabolism, Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing chemistry, Amino Acid Motifs, Co-Repressor Proteins metabolism, Co-Repressor Proteins genetics, Prostatic Neoplasms metabolism, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Alcohol Oxidoreductases metabolism, Alcohol Oxidoreductases genetics, Alcohol Oxidoreductases chemistry, Polymerization
- Abstract
While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions., (© 2024. The Author(s).)
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- 2024
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39. Synthesis and new DNA targeting activity of 6- and 7-tert-butylfascaplysins.
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Dyshlovoy SA, Mansour WY, Ramm NA, Hauschild J, Zhidkov ME, Kriegs M, Zielinski A, Hoffer K, Busenbender T, Glumakova KA, Spirin PV, Prassolov VS, Tilki D, Graefen M, Bokemeyer C, and von Amsberg G
- Subjects
- Humans, Cell Line, Tumor, Indoles pharmacology, Indoles chemistry, Apoptosis drug effects, Structure-Activity Relationship, Male, Ataxia Telangiectasia Mutated Proteins metabolism, Ataxia Telangiectasia Mutated Proteins antagonists & inhibitors, DNA metabolism, Animals, DNA Breaks, Double-Stranded drug effects, Quaternary Ammonium Compounds, Carbolines, Indolizines, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Checkpoint Kinase 1 metabolism, Checkpoint Kinase 1 antagonists & inhibitors
- Abstract
Fascaplysin is a red cytotoxic pigment with anticancer properties isolated from the marine sponge Fascaplysinopsis sp. Recently, structure-activity relationship analysis reported by our group suggested that selective cytotoxicity of fascaplysin derivatives towards tumor cells negatively correlates with their ability to intercalate into DNA. To validate this hypothesis, we synthesized 6- and 7-tert-butylfascaplysins which reveal mitigated DNA-intercalating properties. These derivatives were found to be strongly cytotoxic to drug-resistant human prostate cancer cells, albeit did not demonstrate improved selectivity towards cancer cells when compared to fascaplysin. At the same time, kinome analysis suggested an activation of CHK1/ATR axis in cancer cells shortly after the drug exposure. Further experiments revealed induction of replication stress that is eventually converted to the toxic DNA double-strand breaks, resulting in caspase-independent apoptosis-like cell death. Our observations highlight new DNA-targeting effect of some fascaplysin derivatives and indicate more complex structure-activity relationships within the fascaplysin family, suggesting that cytotoxicity and selectivity of these alkaloids are influenced by multiple factors. Furthermore, combination with clinically-approved inhibitors of ATR/CHK1 as well as testing in tumors particularly sensitive to the DNA damage should be considered in further studies., (© 2024. The Author(s).)
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- 2024
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40. A Combined Cyto- and Histopathological Diagnostic Approach Reduces Time to Diagnosis and Time to Therapy in First Manifestation of Metastatic Spinal Disease: A Cohort Study.
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Leonhardt LG, Heuer A, Stangenberg M, Schroeder M, Schmidt G, Welker L, von Amsberg G, Strahl A, Krüger L, Dreimann M, Bokemeyer C, Viezens L, and Asemissen AM
- Abstract
Malignant spinal lesions (MSLs) are frequently the first manifestation of malignant disease. Spinal care, diagnostic evaluation, and the initiation of systemic therapy are crucial for outcomes in patients (pts) with advanced cancer. However, histopathology (HP) may be time consuming. The additional evaluation of spinal lesions using cytopathology (CP) has the potential to reduce the time to diagnosis (TTD) and time to therapy (TTT). CP and HP specimens from spinal lesions were evaluated in parallel in 61 pts (CP/HP group). Furthermore, 139 pts in whom only HP was performed were analyzed (HP group). We analyzed the TTD of CP and HP within the CP/HP group. Furthermore, we compared the TTD and TTT between the groups. The mean TTD in CP was 1.7 ± 1.7 days (d) and 8.4 ± 3.6 d in HP ( p < 0.001). In 13 pts in the CP/HP group (24.1%), specific therapy was initiated based on the CP findings in combination with imaging and biomarker results before completion of HP. The mean TTT in the CP/HP group was 21.0 ± 15.8 d and was significantly shorter compared to the HP group (28.6 ± 23.3 d) ( p = 0.034). Concurrent CP for MSLs significantly reduces the TTD and TTT. As a result, incorporating concurrent CP for analyzing spinal lesions suspected of malignancy might have the potential to enhance pts' quality of life and prognosis in advanced cancer. Therefore, we recommend implementing CP as a standard procedure for the evaluation of MSLs., Competing Interests: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The authors declare that they have no relevant, conflicting financial or nonfinancial interests to disclose regarding this work.
- Published
- 2024
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41. Limited prognostic role of routine serum markers (AP, CEA, LDH and NSE) in oligorecurrent prostate cancer patients undergoing PSMA-radioguided surgery.
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Mehring G, Steinbach C, Pose R, Knipper S, Koehler D, Werner S, Riethdorf S, von Amsberg G, Ambrosini F, and Maurer T
- Subjects
- Aged, Humans, Male, Middle Aged, Antigens, Surface blood, Glutamate Carboxypeptidase II blood, Prognosis, Prostatectomy methods, Retrospective Studies, Alkaline Phosphatase blood, Biomarkers, Tumor blood, Carcinoembryonic Antigen blood, L-Lactate Dehydrogenase blood, Neoplasm Recurrence, Local blood, Neoplasm Recurrence, Local diagnostic imaging, Phosphopyruvate Hydratase blood, Prostatic Neoplasms blood, Prostatic Neoplasms surgery, Prostatic Neoplasms therapy
- Abstract
Introduction: We evaluated the prognostic role of pre-salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) serum levels of alkaline phosphatase (AP), carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and neuron-specific enolase (NSE)., Materials and Methods: Patients who consecutively underwent PSMA-RGS for prostate cancer (PCa) oligorecurrence between January 2019 and January 2022 were selected. Biomarkers were assessed one day before surgery. Cox regression and logistic regression models tested the relationship between biochemical recurrence-free survival (BFS), 6- and 12-month biochemical recurrence (BCR), and several independent variables, including biomarkers., Results: 153 consecutive patients were analyzed. In the univariable Cox regression analysis, none of the biomarkers achieved predictor status (AP: hazard ratio [HR] = 1.03, 95% CI 0.99, 1.01; p = 0.19; CEA: HR = 1.73, 95% CI 0.94, 1.21; p = 0.34; LDH: HR = 1.01, 95% CI 1.00, 1.01; p = 0.05; NSE: HR = 1.02, 95% CI 0.98, 1.06; p = 0.39). The only independent predictor of BFS was the number of positive lesions on PSMA PET (HR = 1.17, 95% CI 1.02, 1.30; p = 0.03). The number of positive lesions was confirmed as independent predictor for BCR within 6 and 12 months (BCR < 6 months: odds ratio [OR] = 1.1, 95% CI 1.0, 1.3; p = 0.04; BCR < 12 months: OR = 1.1, 95% CI 1.0, 1.3; p = 0.04)., Conclusion: The assessment of AP, CEA, LDH, and NSE before salvage PSMA-RGS showed no prognostic impact. Further studies are needed to identify possible predictors that will optimize patient selection for salvage PSMA-RGS., (© 2024. The Author(s).)
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- 2024
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42. [Molecular testing of prostate cancer: timing, methods and consequences].
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von Amsberg G and Paulsen FO
- Subjects
- Male, Humans, BRCA1 Protein genetics, BRCA2 Protein genetics, Molecular Diagnostic Techniques, Prostatic Neoplasms diagnosis, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics, Prostatic Neoplasms, Castration-Resistant diagnosis, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant genetics
- Abstract
Metastatic prostate cancer is a heterogeneous disease. To date, however, treatment decisions are often based on the extent and symptom burden of the tumour, concomitant diseases, and the patient's wishes. Molecular pathology aspects are rarely taken into account. Declining costs and the increasing use of next-generation sequencing (NGS) have led to an increase in molecular testing and a better understanding of the significance of molecular alterations for the development and spread of prostate cancer. More consistent germline testing reveals hereditary predispositions. Following the approval of olaparib for the treatment of BRCA1/2 mutated, castration-resistant prostate cancer, further targeted therapeutic approaches are currently under development. In our review article, we provide an overview of current molecular testing in prostate cancer and discuss possible consequences., Competing Interests: GvA: Anstellungsverhältnis oder Führungsposition: nein; Beratungs- bzw. Gutachtertätigkeit im Rahmen von Advisory Boards: Roche, BMS, Astellas, Sanofi, Janssen, MSD, Ipsen, Pfizer, Astra Zeneca, Merck, Amgen, Novartis, Lilly. Besitz von Geschäftsanteilen, Aktien oder Fonds: nein; Patent, Urheberrecht, Verkaufslizenz: nein. Honorare/Vorträge/Reisekosten/Kongressunterstützung: Roche, BMS, Astellas, Sanofi, Ipsen, EISAI, Pierre Fabre, MSD, Astra Zeneca, Janssen, Merck, Amgen. Finanzierung wissenschaftlicher Untersuchungen im Rahmen Industrie-gesponserter Studien Roche, BMS, MSD, Astra Zeneca, Sanofi, Pfizer, AvenCell, Lilly. Andere finanzielle Beziehungen und immaterielle Interessenkonflikte: nein., (Thieme. All rights reserved.)
- Published
- 2024
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43. [Androgen deprivation therapy and cardiovascular morbidity in prostate cancer: a narrative review].
- Author
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Klemm J, von Deimling M, Fisch M, Kramer G, Tilki D, Steuber T, von Amsberg G, Hengstenberg C, and Shariat SF
- Subjects
- Male, Humans, Aged, Androgen Antagonists adverse effects, Androgens, Gonadotropin-Releasing Hormone therapeutic use, Prostatic Neoplasms drug therapy, Cardiovascular Diseases epidemiology, Metabolic Syndrome epidemiology
- Abstract
Prostate cancer is the most common malignancy in men, mostly affecting older men who harbor an increased prevalence of cardiovascular disease and metabolic syndrome. Androgen deprivation therapy (ADT), the standard therapy for various stages of prostate cancer, further increases the risk for cardiovascular disease and for metabolic syndrome. Therefore, screening for cardiovascular risk factors should be performed prior to the initiation of ADT, and, if necessary, cardiological evaluation and interdisciplinary management should be provided during and after completion of ADT. Moreover, the use of a gonadotropin-releasing hormone (GnRH) antagonist may help reduce cardiovascular risk in patients with cardiovascular disease., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2024
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44. [Advanced renal cell carcinoma - an overview of current systemic therapy].
- Author
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Kaune M, Bokemeyer C, and von Amsberg G
- Subjects
- Aged, Humans, Combined Modality Therapy, Protein Kinase Inhibitors therapeutic use, Treatment Outcome, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy
- Abstract
Renal cell carcinoma (RCC) is one of the more common tumor diseases in older adults. The only curative treatment method is surgical resection in the localized stage. Based on current study data, drug (combination) therapy in the metastatic stage is the most effective treatment option for non-resectable/metastatic RCC (mRCC). Immuno-oncological combinations of 2 Checkpoint-Inhibitors (CPI) or CPIs and Tyrosine kinase inhibitors (TKI) are now standard in the first-line treatment of metastatic RCC. Since the results of foundational combination therapy studies are not fully comparable due to different study design and patient populations, additional clinical and patient-related criteria are required when making individual treatment decisions. The systemic therapy of advanced RCC is therefore based on tumor extent, treatment pressure, concomitant diseases, and personal circumstances. A decision on first-line therapy should be made individually as part of a "shared decision" with the patient. The selection of a second-line systemic therapy is based on individual criteria; the data available for a well-founded classification of a possible therapy sequence after progression to first-line therapy is sparse. Further investigations to optimize systemic therapy (expansion of combination therapy to triple combination of CPI+CPI+TKI) or evaluation of therapy in other histological subtypes of renal cell carcinoma are the subject of ongoing clinical studies., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
- Published
- 2024
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45. Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A 2 -2 in Human Prostate Cancer Cells.
- Author
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Menchinskaya ES, Dyshlovoy SA, Venz S, Jacobsen C, Hauschild J, Rohlfing T, Silchenko AS, Avilov SA, Balabanov S, Bokemeyer C, Aminin DL, von Amsberg G, and Honecker F
- Subjects
- Male, Humans, Glycosides pharmacology, Prostate, Prostatic Neoplasms, Castration-Resistant, Triterpenes pharmacology
- Abstract
Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), treatment is inevitably hampered by the development of drug resistance. Thus, new drugs are urgently needed. We investigated the efficacy, toxicity, and mechanism of action of the marine triterpene glycoside cucumarioside A
2 -2 (CA2 -2) using an in vitro CRPC model. CA2 -2 induced a G2 /M-phase cell cycle arrest in human prostate cancer PC-3 cells and caspase-dependent apoptosis executed via an intrinsic pathway. Additionally, the drug inhibited the formation and growth of CRPC cell colonies at low micromolar concentrations. A global proteome analysis performed using the 2D-PAGE technique, followed by MALDI-MS and bioinformatical evaluation, revealed alterations in the proteins involved in cellular processes such as metastatic potential, invasion, and apoptosis. Among others, the regulation of keratin 81, CrkII, IL-1β, and cathepsin B could be identified by our proteomics approach. The effects were validated on the protein level by a 2D Western blotting analysis. Our results demonstrate the promising anticancer activity of CA2 -2 in a prostate cancer model and provide insights on the underlying mode of action.- Published
- 2023
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46. Biweekly vs Triweekly Cabazitaxel in Older Patients With Metastatic Castration-Resistant Prostate Cancer: The CABASTY Phase 3 Randomized Clinical Trial.
- Author
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Oudard S, Ratta R, Voog E, Barthelemy P, Thiery-Vuillemin A, Bennamoun M, Hasbini A, Aldabbagh K, Saldana C, Sevin E, Amela E, Von Amsberg G, Houede N, Besson D, Feyerabend S, Boegemann M, Pfister D, Schostak M, Huillard O, Di Fiore F, Quivy A, Lange C, Phan L, Belhouari H, Tran Y, Kotti S, and Helissey C
- Subjects
- Male, Humans, Aged, Prospective Studies, Treatment Outcome, Taxoids administration & dosage, Prednisolone administration & dosage, Prednisolone adverse effects, Granulocyte Colony-Stimulating Factor adverse effects, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant pathology, Neutropenia chemically induced
- Abstract
Importance: Many patients 65 years or older with metastatic castration-resistant prostate cancer (mCRPC) are denied taxane chemotherapy because this treatment is considered unsuitable., Objective: To determine whether biweekly cabazitaxel (CBZ), 16 mg/m2 (biweekly CBZ16), plus prophylactic granulocyte colony-stimulating factor (G-CSF) at each cycle reduces the risk of grade 3 or higher neutropenia and/or neutropenic complications (eg, febrile neutropenia, neutropenic infection, or sepsis) compared with triweekly CBZ, 25 mg/m2 (triweekly CBZ25), plus G-CSF (standard regimen)., Design, Setting, and Participants: A total of 196 patients 65 years or older with progressive mCRPC were enrolled in this prospective phase 3 randomized clinical trial conducted in France (18 centers) and Germany (7 centers) between May 5, 2017, and January 7, 2021. All patients had received docetaxel and at least 1 novel androgen receptor-targeted agent., Interventions: Patients were randomly assigned 1:1 to receive biweekly CBZ16 plus G-CSF and daily prednisolone (experimental group) or triweekly CBZ25 plus G-CSF and daily prednisolone (control group)., Main Outcome and Measures: The primary end point was the occurrence of grade 3 or higher neutropenia measured at nadir and/or neutropenic complications., Results: Among 196 patients (97 in the triweekly CBZ25 group and 99 in the biweekly CBZ16 group), the median (IQR) age was 74.6 (70.4-79.3) years, and 181 (92.3%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median (IQR) follow-up duration was 31.3 (22.5-37.5) months. Relative dose intensities were comparable between groups (median [IQR], 92.7% [83.7%-98.9%] in the triweekly CBZ25 group vs 92.8% [87.0%-98.9%] in the biweekly CBZ16 group). The rate of grade 3 or higher neutropenia and/or neutropenic complications was significantly higher with triweekly CBZ25 vs biweekly CBZ16 (60 of 96 [62.5%] vs 5 of 98 [5.1%]; odds ratio, 0.03; 95% CI, 0.01-0.08; P < .001). Grade 3 or higher adverse events were more common with triweekly CBZ25 (70 of 96 [72.9%]) vs biweekly CBZ16 (55 of 98 [56.1%]). One patient (triweekly CBZ25 group) died of a neutropenic complication., Conclusions and Relevance: In this randomized clinical trial, compared with the standard regimen, biweekly CBZ16 plus G-CSF significantly reduced by 12-fold the occurrence of grade 3 or higher neutropenia and/or neutropenic complications, with comparable clinical outcomes. The findings suggest that biweekly CBZ16 regimen should be offered to patients 65 years or older with mCRPC for whom the standard regimen is unsuitable., Trial Registration: ClinicalTrials.gov Identifier: NCT02961257.
- Published
- 2023
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47. [Metastatic castration-resistant prostate cancer-emerging trends in therapy].
- Author
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von Amsberg G and Todenhöfer T
- Subjects
- Male, Humans, Signal Transduction, Mutation, Tumor Microenvironment, Prostatic Neoplasms, Castration-Resistant genetics
- Abstract
Background: An increasing understanding of the cellular processes involved in growth, metastasis and development of resistance enable the development of new treatment strategies for advanced prostate cancer., Objectives: Using selected examples, the aim of this report is to present current developments to the reader and to give an outlook on possible upcoming changes in the treatment of advanced prostate cancer., Materials and Methods: Narrative report based on expert consensus, supported by a literature search in PubMed (MEDLINE) and the abstract databases of the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO). Examples were selected to illustrate current developments without claiming completeness., Results: The androgen receptor (AR) signal transduction pathway remains a focus of scientific interest. Androgen synthesis inhibitors and AR degraders are promising new approaches to overcome resistance mediated by AR mutations or splice variants. Inhibition of key switch sites of alternative signaling pathways such as AKT or CDK4/6 provide additional treatment options, including combinational strategies through a tight linkage with the AR signaling pathway. A better understanding of tumor microenvironment and immune response is required for novel immunotherapeutic strategies using bispecific T‑cell engagers (BiTEs) and chimeric antigen receptor (CAR) T cells., Conclusion: New treatment strategies give hope that we will be able to intervene even more effectively in the course of disease of advanced prostate cancer in the future. However, a major challenge, especially for the implementation of targeted treatment approaches, is likely to be the heterogeneity of tumor progression not only inter- but also intrapersonally., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2023
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48. Rhizochalinin Exhibits Anticancer Activity and Synergizes with EGFR Inhibitors in Glioblastoma In Vitro Models.
- Author
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Dyshlovoy SA, Hauschild J, Venz S, Krisp C, Kolbe K, Zapf S, Heinemann S, Fita KD, Shubina LK, Makarieva TN, Guzii AG, Rohlfing T, Kaune M, Busenbender T, Mair T, Moritz M, Poverennaya EV, Schlüter H, Serdyuk V, Stonik VA, Dierlamm J, Bokemeyer C, Mohme M, Westphal M, Lamszus K, von Amsberg G, and Maire CL
- Subjects
- Humans, Proto-Oncogene Proteins c-akt metabolism, Proteomics, Apoptosis, Cell Proliferation, ErbB Receptors, Cell Line, Tumor, Glioblastoma drug therapy, Brain Neoplasms drug therapy
- Abstract
Rhizochalinin (Rhiz) is a recently discovered cytotoxic sphingolipid synthesized from the marine natural compound rhizochalin. Previously, Rhiz demonstrated high in vitro and in vivo efficacy in various cancer models. Here, we report Rhiz to be highly active in human glioblastoma cell lines as well as in patient-derived glioma-stem like neurosphere models. Rhiz counteracted glioblastoma cell proliferation by inducing apoptosis, G2/M-phase cell cycle arrest, and inhibition of autophagy. Proteomic profiling followed by bioinformatic analysis suggested suppression of the Akt pathway as one of the major biological effects of Rhiz. Suppression of Akt as well as IGF-1R and MEK1/2 kinase was confirmed in Rhiz-treated GBM cells. In addition, Rhiz pretreatment resulted in a more pronounced inhibitory effect of γ-irradiation on the growth of patient-derived glioma-spheres, an effect to which the Akt inhibition may also contribute decisively. In contrast, EGFR upregulation, observed in all GBM neurospheres under Rhiz treatment, was postulated to be a possible sign of incipient resistance. In line with this, combinational therapy with EGFR-targeted tyrosine kinase inhibitors synergistically increased the efficacy of Rhiz resulting in dramatic inhibition of GBM cell viability as well as a significant reduction of neurosphere size in the case of combination with lapatinib. Preliminary in vitro data generated using a parallel artificial membrane permeability (PAMPA) assay suggested that Rhiz cannot cross the blood brain barrier and therefore alternative drug delivery methods should be used in the further in vivo studies. In conclusion, Rhiz is a promising new candidate for the treatment of human glioblastoma, which should be further developed in combination with EGFR inhibitors.
- Published
- 2023
- Full Text
- View/download PDF
49. [Sequential therapy of advanced bladder cancer after prior perioperative systemic treatment : Recommendations from the Interdisciplinary Bladder Carcinoma Working Group (IABC) of the DKG e. V.]
- Author
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Retz M, Kirchhoff FP, von Amsberg G, De Santis M, Krege S, Gschwend JE, and Niegisch G
- Subjects
- Humans, Neoplasm Recurrence, Local drug therapy, Cisplatin therapeutic use, Immunotherapy, Urinary Bladder pathology, Urinary Bladder Neoplasms drug therapy
- Abstract
Guidelines can only give treatment recommendations for defined patient groups if high quality and meaningful evidence is available. However, patients included in clinical trials for the treatment of metastatic and/or locally advanced bladder cancer (mUC) are generally not representative for the spectrum of patients encountered in daily clinical practice. In particular, patients with different systemic pretreatments, variable prestudy responses or variable time to tumor progression are not sufficiently considered in trials and guideline recommendations. Accordingly, recommendations for the treatment of mUC patients with previous perioperative systemic therapy are lacking. To provide some guidance for daily uro-oncological practice despite the limited evidence, we sought to develop expert opinion-based treatment recommendations. These recommendations focus on palliative first-line therapy of mUC. Both perioperative pretreatment with classical cisplatin-based systemic therapy and/or immunotherapy, as well as the time to tumor recurrence have been considered., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
50. Preclinical Comparison of the 64 Cu- and 68 Ga-Labeled GRPR-Targeted Compounds RM2 and AMTG, as Well as First-in-Humans [ 68 Ga]Ga-AMTG PET/CT.
- Author
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Koller L, Joksch M, Schwarzenböck S, Kurth J, Heuschkel M, Holzleitner N, Beck R, von Amsberg G, Wester HJ, Krause BJ, and Günther T
- Subjects
- Male, Humans, Animals, Mice, Gallium Radioisotopes, Positron Emission Tomography Computed Tomography, Tissue Distribution, Receptors, Bombesin, Neoplasms
- Abstract
Despite the recent success of prostate-specific membrane antigen (PSMA)-targeted compounds for theranostic use in prostate cancer (PCa), alternative options for the detection and treatment of PSMA-negative lesions are needed. We have recently developed a novel gastrin-releasing peptide receptor (GRPR) ligand with improved metabolic stability, which might improve diagnostic and therapeutic efficacy and could be valuable for PSMA-negative PCa patients. Our aim was to examine its suitability for theranostic use. We performed a comparative preclinical study on [
64 Cu]Cu-/[68 Ga]Ga-AMTG ([64 Cu]Cu-/[68 Ga]Ga-α-Me-l-Trp8 -RM2) using [64 Cu]Cu-/[68 Ga]Ga-RM2 ([64 Cu]Cu-/[68 Ga]Ga-DOTA-Pip5 -Phe6 -Gln7 -Trp8 -Ala9 -Val10 -Gly11 -His12 -Sta13 -Leu14 -NH2 ) as a reference compound and investigated [68 Ga]Ga-AMTG in a proof-of-concept study in a PCa patient. Methods: Peptides were labeled with64 Cu (80 °C, 1.0 M NaOAc, pH 5.50) and68 Ga (90 °C, 0.25 M NaOAc, pH 4.50). GRPR affinity (half-maximal inhibitory concentration, room temperature, 2 h) and GRPR-mediated internalization (37 °C, 60 min) were examined on PC-3 cells. Biodistribution studies were performed at 1 h after injection in PC-3 tumor-bearing mice. For a first-in-humans application, 173 MBq of [68 Ga]Ga-AMTG were administered intravenously and whole-body PET/CT scans were acquired at 75 min after injection. Results:64 Ga-labeling proceeded almost quantitatively (>98%). All compounds revealed similarly high GRPR affinity (half-maximal inhibitory concentration, 1.5-4.0 nM) and high receptor-bound fractions (79%-84% of cell-associated activity). In vivo, high activity levels (percentage injected dose per gram) were found in the PC-3 tumor (14.1-15.1 %ID/g) and the pancreas (12.6-30.7 %ID/g), whereas further off-target accumulation was low at 1 h after injection, except for elevated liver uptake observed for both68 Ga-labeling proceeded almost quantitatively (>98%). All compounds revealed similarly high GRPR affinity (half-maximal inhibitory concentration, 1.5-4.0 nM) and high receptor-bound fractions (79%-84% of cell-associated activity). In vivo, high activity levels (percentage injected dose per gram) were found in the PC-3 tumor (14.1-15.1 %ID/g) and the pancreas (12.6-30.7 %ID/g), whereas further off-target accumulation was low at 1 h after injection, except for elevated liver uptake observed for both64 Cu-labeled compounds. Overall biodistribution profiles and tumor-to-background ratios were comparable but slightly enhanced for the68 Ga-labeled analogs in most organs. [68 Ga]Ga-AMTG confirmed the favorable pharmacokinetics-as evident from preclinical studies-in a patient with metastasized castration-resistant PCa showing intense uptake in several lesions. Conclusion: AMTG is eligible for theranostic use, as labeling with64 Cu and68 Ga, as well as177 Lu (known from previous study), does not have a negative influence on its favorable biodistribution pattern. For this reason, further clinical evaluation is warranted., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
- Full Text
- View/download PDF
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