Search

Your search keyword '"Greil, Christine"' showing total 131 results
Start Over Author "Greil, Christine"
131 results on '"Greil, Christine"'

1. Enhancing patient activation: a controlled implementation study of an interprofessional evidence-based counseling program for complementary and integrative healthcare in cancer patients (‘CCC-Integrativ’)

Author

Valentini, Jan, Froehlich, Daniela, Roesel, Inka, Stolz, Regina, Mahler, Cornelia, Martus, Peter, Klafke, Nadja, Horneber, Markus, Witte, Claudia, Kramer, Klaus, Greil, Christine, Gruen, Barbara, Tomaschko-Ubelaender, Katrin, and Joos, Stefanie

Published
2024
Full Text
View/download PDF

6. Radiotherapy to reinvigorate immunotherapy activity after acquired resistance in metastatic non-small-cell lung cancer: A pooled analysis of two institutions prospective phase II single arm trials

Author

Popp, Ilinca, Vaes, Rianne D.W., Wieten, Lotte, Adebahr, Sonja, Hendriks, Lizza, Bavafaye Haghighi, Elham, Degens, Juliette, Schäfer, Henning, Greil, Christine, Peeters, Stéphanie, Waller, Cornelius F., Houben, Ruud, Niedermann, Gabriele, Rawluk, Justyna, Gkika, Eleni, Duyster, Justus, Grosu, Anca-Ligia, and De Ruysscher, Dirk

Published
2024
Full Text
View/download PDF

8. Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma

Author

Keppler-Hafkemeyer, Andrea, Greil, Christine, Wratil, Paul R., Shoumariyeh, Khalid, Stern, Marcel, Hafkemeyer, Annika, Ashok, Driti, Hollaus, Alexandra, Lupoli, Gaia, Priller, Alina, Bischof, Marie L., Ihorst, Gabriele, Engelhardt, Monika, Marks, Reinhard, Finke, Jürgen, Bertrand, Hannah, Dächert, Christopher, Muenchhoff, Maximilian, Badell, Irina, Emmerich, Florian, Halder, Hridi, Spaeth, Patricia M., Knolle, Percy A., Protzer, Ulrike, von Bergwelt-Baildon, Michael, Duyster, Justus, Hartmann, Tanja N., Moosmann, Andreas, and Keppler, Oliver T.

Published
2023
Full Text
View/download PDF

9. Physical activity and exercise motivation of multiple myeloma patients: a prospective cross-sectional study.

Author

Räder, Jan, Ihorst, Gabriele, Möller, Mandy-Deborah, Pahl, Antonia, Greil, Christine, Dreyling, Esther, Arends, Jann, Deibert, Peter, Wäsch, Ralph, and Engelhardt, Monika

Subjects
MULTIPLE myeloma, CROSS-sectional method, SELF-evaluation, HEALTH literacy, PATIENT safety, EXERCISE therapy, QUESTIONNAIRES, INTERVIEWING, DESCRIPTIVE statistics, MOTIVATION (Psychology), LONGITUDINAL method, SPORTS participation, PHYSICAL fitness, AEROBIC exercises, QUALITY of life, CANCER patient psychology, PROGRESSION-free survival, PHYSICAL activity, COMORBIDITY, OVERALL survival
Abstract

Background Multiple myeloma (MM) is the second most common hematological malignancy with its prevalence increasing. Patients with symptomatic MM can show numerous comorbidities, affecting their quality of life (QoL). Physical activity (PA) may improve QoL but is not a standardized intervention of comprehensive cancer centers (CCCs). Since data on the PA of patients with MM are scarce, we aimed to prospectively assess fitness levels and patients' motivation to join PA-interventions at our CCC. Methods We generated an exercise questionnaire to interview consecutive patients MM. We prospectively collected data on (a) past and current PA, defined by the World Health Organization (WHO) recommendations, (b) knowledge on exercise effects, (c) exercise motivation, and (d) willingness to participate in PA-interventions. Demographics, comorbidities, response, progression-free survival (PFS), and overall survival (OS) were assessed in 211 symptomatic patients MM. Results While our patients were elderly and most showed bone involvement, their PA was similar to healthy individuals. Aerobic PA (≥ 60 minutes/week) was performed by 65%, and 25% exercised ≥ 150 minutes/week. WHO PA recommendations were fulfilled by 17% of patients. No sport activities or complete physical inactivity were observed in 35% and 16%, respectively. Notably, 38% were motivated to join MM-specific sport interventions. Self-reported knowledge of PA-induced benefits for patients cancer was high (82%), but only 27% knew which exercises were safe to perform. Conclusion This study provides an overview of the PA of patients MM. Our results suggest that the PA of patients MM might not be much lower than in the age-matched general population. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

12. Body weight and composition endpoints in cancer cachexia clinical trials: Systematic Review 4 of the cachexia endpoints series.

Author

Brown, Leo R., Sousa, Mariana S., Yule, Michael S., Baracos, Vickie E., McMillan, Donald C., Arends, Jann, Balstad, Trude R., Bye, Asta, Dajani, Olav, Dolan, Ross D., Fallon, Marie T., Greil, Christine, Hjermstad, Marianne J., Jakobsen, Gunnhild, Maddocks, Matthew, McDonald, James, Ottestad, Inger O., Phillips, Iain, Sayers, Judith, and Simpson, Melanie R.

Published
2024
Full Text
View/download PDF

13. Quality of life endpoints in cancer cachexia clinical trials: Systematic review 3 of the cachexia endpoints series.

Author

Hjermstad, Marianne J., Jakobsen, Gunnhild, Arends, Jann, Balstad, Trude R., Brown, Leo R., Bye, Asta, Coats, Andrew J.S., Dajani, Olav F., Dolan, Ross D., Fallon, Marie T., Greil, Christine, Grzyb, Alexandra, Kaasa, Stein, Koteng, Lisa H., May, Anne M., McDonald, James, Ottestad, Inger, Philips, Iain, Roeland, Eric J., and Sayers, Judith

Published
2024
Full Text
View/download PDF

14. Appetite and dietary intake endpoints in cancer cachexia clinical trials: Systematic Review 2 of the cachexia endpoints series.

Author

Vagnildhaug, Ola Magne, Balstad, Trude R., Ottestad, Inger, Bye, Asta, Greil, Christine, Arends, Jann, Baracos, Vickie, Brown, Leo R., Dajani, Olav F., Dolan, Ross D., Fallon, Marie, Fraser, Eilidh, Grzyb, Aleksandra, Hjermstad, Marianne J., Jakobsen, Gunnhild, Kaasa, Stein, McDonald, James, Philips, Iain, Sayers, Judith, and Simpson, Melanie R.

Published
2024
Full Text
View/download PDF

15. Radiotherapy to reinvigorate immunotherapy activity after acquired resistance in metastatic non-small-cell lung cancer: A pooled analysis of two institutions prospective phase II single arm trials

Author

Popp, Ilinca, primary, Vaes, Rianne D.W., additional, Wieten, Lotte, additional, Adebahr, Sonja, additional, Hendriks, Lizza, additional, Bavafaye Haghighi, Elham, additional, Degens, Juliette, additional, Schäfer, Henning, additional, Greil, Christine, additional, Peeters, Stéphanie, additional, Waller, Cornelius F., additional, Houben, Ruud, additional, Niedermann, Gabriele, additional, Rawluk, Justyna, additional, Gkika, Eleni, additional, Duyster, Justus, additional, Grosu, Anca-Ligia, additional, and De Ruysscher, Dirk, additional

Published
2023
Full Text
View/download PDF

20. Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma

Author

Keppler-Hafkemeyer, Andrea, primary, Greil, Christine, additional, Wratil, Paul R., additional, Shoumariyeh, Khalid, additional, Stern, Marcel, additional, Hafkemeyer, Annika, additional, Ashok, Driti, additional, Hollaus, Alexandra, additional, Lupoli, Gaia, additional, Priller, Alina, additional, Bischof, Marie L., additional, Ihorst, Gabriele, additional, Engelhardt, Monika, additional, Marks, Reinhard, additional, Finke, Jürgen, additional, Bertrand, Hannah, additional, Dächert, Christopher, additional, Muenchhoff, Maximilian, additional, Badell, Irina, additional, Emmerich, Florian, additional, Halder, Hridi, additional, Spaeth, Patricia M., additional, Knolle, Percy A., additional, Protzer, Ulrike, additional, von Bergwelt-Baildon, Michael, additional, Duyster, Justus, additional, Hartmann, Tanja N., additional, Moosmann, Andreas, additional, and Keppler, Oliver T., additional

Published
2022
Full Text
View/download PDF

21. Multidisciplinary tumor board analysis: validation study of a central tool in tumor centers

Author

Frank, Benedikt, primary, Ihorst, Gabriele, additional, Herget, Georg, additional, Schäfer, Henning, additional, Neubauer, Jakob, additional, Calba, Marc-Antoine, additional, Textor, Daniel, additional, Möller, Mandy-Deborah, additional, Wenger, Sina, additional, Jung, Johannes, additional, Waldschmidt, Johannes, additional, Miething, Cornelius, additional, Rassner, Michael, additional, Greil, Christine, additional, Wäsch, Ralph, additional, and Engelhardt, Monika, additional

Published
2022
Full Text
View/download PDF

22. The Role of the APC/C and Its Coactivators Cdh1 and Cdc20 in Cancer Development and Therapy

Author

Greil, Christine, Engelhardt, Monika, and Wäsch, Ralph

Subjects
Genetics, Molecular Medicine, Genetics (clinical)
Abstract

To sustain genomic stability by correct DNA replication and mitosis, cell cycle progression is tightly controlled by the cyclic activity of cyclin-dependent kinases, their binding to cyclins in the respective phase and the regulation of cyclin levels by ubiquitin-dependent proteolysis. The spindle assembly checkpoint plays an important role at the metaphase-anaphase transition to ensure a correct separation of sister chromatids before cytokinesis and to initiate mitotic exit, as an incorrect chromosome distribution may lead to genetically unstable cells and tumorigenesis. The ubiquitin ligase anaphase-promoting complex or cyclosome (APC/C) is essential for these processes by mediating the proteasomal destruction of cyclins and other important cell cycle regulators. To this end, it interacts with the two regulatory subunits Cdh1 and Cdc20. Both play a role in tumorigenesis with Cdh1 being a tumor suppressor and Cdc20 an oncogene. In this review, we summarize the current knowledge about the APC/C-regulators Cdh1 and Cdc20 in tumorigenesis and potential targeted therapeutic approaches.

Published
2022
Full Text
View/download PDF

26. Early assessment of circulating tumor DNA after curative‐intent resection predicts tumor recurrence in early‐stage and locally advanced non‐small‐cell lung cancer

Author

Waldeck, Silvia, primary, Mitschke, Jan, additional, Wiesemann, Sebastian, additional, Rassner, Michael, additional, Andrieux, Geoffroy, additional, Deuter, Max, additional, Mutter, Jurik, additional, Lüchtenborg, Anne‐Marie, additional, Kottmann, Daniel, additional, Titze, Laurin, additional, Zeisel, Christoph, additional, Jolic, Martina, additional, Philipp, Ulrike, additional, Lassmann, Silke, additional, Bronsert, Peter, additional, Greil, Christine, additional, Rawluk, Justyna, additional, Becker, Heiko, additional, Isbell, Lisa, additional, Müller, Alexandra, additional, Doostkam, Soroush, additional, Passlick, Bernward, additional, Börries, Melanie, additional, Duyster, Justus, additional, Wehrle, Julius, additional, Scherer, Florian, additional, and von Bubnoff, Nikolas, additional

Published
2021
Full Text
View/download PDF

29. Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients

Author

Riebl, Veronika, primary, Dold, Sandra Maria, additional, Wider, Dagmar, additional, Follo, Marie, additional, Ihorst, Gabriele, additional, Waldschmidt, Johannes M., additional, Jung, Johannes, additional, Rassner, Michael, additional, Greil, Christine, additional, Wäsch, Ralph, additional, and Engelhardt, Monika, additional

Published
2021
Full Text
View/download PDF

30. Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management

Author

Wehrle, Julius; https://orcid.org/0000-0001-6514-4230, Philipp, Ulrike, Jolic, Martina; https://orcid.org/0000-0002-3152-2413, Follo, Marie; https://orcid.org/0000-0002-3090-7442, Hussung, Saskia, Waldeck, Silvia, Deuter, Max; https://orcid.org/0000-0002-1055-4803, Rassner, Michael; https://orcid.org/0000-0003-0964-9511, Braune, Jan, Rawluk, Justyna, Greil, Christine, Waller, Cornelius F; https://orcid.org/0000-0002-5777-0212, Becker, Heiko, Duque-Afonso, Jesús; https://orcid.org/0000-0002-8287-5673, Illert, Anna-L, Fritsch, Ralph M, Meiss, Frank; https://orcid.org/0000-0002-4044-9094, Duyster, Justus, von Bubnoff, Nikolas, Scherer, Florian, Wehrle, Julius; https://orcid.org/0000-0001-6514-4230, Philipp, Ulrike, Jolic, Martina; https://orcid.org/0000-0002-3152-2413, Follo, Marie; https://orcid.org/0000-0002-3090-7442, Hussung, Saskia, Waldeck, Silvia, Deuter, Max; https://orcid.org/0000-0002-1055-4803, Rassner, Michael; https://orcid.org/0000-0003-0964-9511, Braune, Jan, Rawluk, Justyna, Greil, Christine, Waller, Cornelius F; https://orcid.org/0000-0002-5777-0212, Becker, Heiko, Duque-Afonso, Jesús; https://orcid.org/0000-0002-8287-5673, Illert, Anna-L, Fritsch, Ralph M, Meiss, Frank; https://orcid.org/0000-0002-4044-9094, Duyster, Justus, von Bubnoff, Nikolas, and Scherer, Florian

Abstract

BACKGROUND Circulating tumor DNA (ctDNA) in the blood plasma of cancer patients is an emerging biomarker used across oncology, facilitating noninvasive disease monitoring and genetic profiling at various disease milestones. Digital droplet PCR (ddPCR) technologies have demonstrated high sensitivity and specificity for robust ctDNA detection at relatively low costs. Yet, their value for ctDNA-based management of a broad population of cancer patients beyond clinical trials remains elusive. METHODS We developed mutation-specific ddPCR assays that were optimized for their use in real-world cancer management, covering 12 genetic aberrations in common cancer genes, such as EGFR, BRAF, KIT, KRAS, and NRAS. We assessed the limit of detection (LOD) and the limit of blank (LOB) for each assay and validated their performance for ctDNA detection using matched tumor sequencing. RESULTS We applied our custom ddPCR assays to 352 plasma samples from 96 patients with solid tumors. Mutation detection in plasma was highly concordant with tumor sequencing, demonstrating high sensitivity and specificity across all assays. In 20 cases, radiographic cancer progression was mirrored by an increase of ctDNA concentrations or the occurrence of novel mutations in plasma. Moreover, ctDNA profiling at diagnosis and during disease progression reflected personalized treatment selection through the identification of actionable gene targets in 20 cases. CONCLUSION Collectively, our work highlights the potential of ctDNA assessment by sensitive ddPCR for accurate disease monitoring, robust identification of resistance mutations, and upfront treatment selection in patients with solid tumors. We envision an increasing future role for ctDNA profiling within personalized cancer management in daily clinical routine.

Published
2020

31. Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management

Author

Wehrle, Julius, primary, Philipp, Ulrike, additional, Jolic, Martina, additional, Follo, Marie, additional, Hussung, Saskia, additional, Waldeck, Silvia, additional, Deuter, Max, additional, Rassner, Michael, additional, Braune, Jan, additional, Rawluk, Justyna, additional, Greil, Christine, additional, Waller, Cornelius F., additional, Becker, Heiko, additional, Duque-Afonso, Jesús, additional, Illert, Anna L., additional, Fritsch, Ralph M., additional, Meiss, Frank, additional, Duyster, Justus, additional, von Bubnoff, Nikolas, additional, and Scherer, Florian, additional

Published
2020
Full Text
View/download PDF

33. Early assessment of circulating tumor DNA after curative‐intent resection predicts tumor recurrence in early‐stage and locally advanced non‐small‐cell lung cancer.

Author

Waldeck, Silvia, Mitschke, Jan, Wiesemann, Sebastian, Rassner, Michael, Andrieux, Geoffroy, Deuter, Max, Mutter, Jurik, Lüchtenborg, Anne‐Marie, Kottmann, Daniel, Titze, Laurin, Zeisel, Christoph, Jolic, Martina, Philipp, Ulrike, Lassmann, Silke, Bronsert, Peter, Greil, Christine, Rawluk, Justyna, Becker, Heiko, Isbell, Lisa, and Müller, Alexandra

Abstract

Circulating tumor DNA (ctDNA) has demonstrated great potential as a noninvasive biomarker to assess minimal residual disease (MRD) and profile tumor genotypes in patients with non‐small‐cell lung cancer (NSCLC). However, little is known about its dynamics during and after tumor resection, or its potential for predicting clinical outcomes. Here, we applied a targeted‐capture high‐throughput sequencing approach to profile ctDNA at various disease milestones and assessed its predictive value in patients with early‐stage and locally advanced NSCLC. We prospectively enrolled 33 consecutive patients with stage IA to IIIB NSCLC undergoing curative‐intent tumor resection (median follow‐up: 26.2 months). From 21 patients, we serially collected 96 plasma samples before surgery, during surgery, 1–2 weeks postsurgery, and during follow‐up. Deep next‐generation sequencing using unique molecular identifiers was performed to identify and quantify tumor‐specific mutations in ctDNA. Twelve patients (57%) had detectable mutations in ctDNA before tumor resection. Both ctDNA detection rates and ctDNA concentrations were significantly higher in plasma obtained during surgery compared with presurgical specimens (57% versus 19% ctDNA detection rate, and 12.47 versus 6.64 ng·mL−1, respectively). Four patients (19%) remained ctDNA‐positive at 1–2 weeks after surgery, with all of them (100%) experiencing disease progression at later time points. In contrast, only 4 out of 12 ctDNA‐negative patients (33%) after surgery experienced relapse during follow‐up. Positive ctDNA in early postoperative plasma samples was associated with shorter progression‐free survival (P = 0.013) and overall survival (P = 0.004). Our findings suggest that, in early‐stage and locally advanced NSCLC, intraoperative plasma sampling results in high ctDNA detection rates and that ctDNA positivity early after resection identifies patients at risk for relapse. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

35. Phase I/II study on cytarabine and idarubicin combined with escalating doses of clofarabine in newly diagnosed patients with acute myeloid leukaemia and high risk for induction failure (AMLSG 17-10 CIARA trial)

Author

Krauter, Jürgen, primary, Fiedler, Walter, additional, Schlenk, Richard F., additional, Paschka, Peter, additional, Thol, Felicitas, additional, Lübbert, Michael, additional, Wattad, Mohammed, additional, Verbeek, Mareike, additional, Könecke, Christian, additional, Neuhaus, Barbara, additional, Papkalla, Armin, additional, Kebenko, Maxim, additional, Janning, Melanie, additional, Döhner, Konstanze, additional, Gaidzik, Verena I., additional, Becker, Heiko, additional, Greil, Christine, additional, Reimer, Peter, additional, Götze, Katharina S., additional, Döhner, Hartmut, additional, Ganser, Arnold, additional, and Heuser, Michael, additional

Published
2018
Full Text
View/download PDF

36. Allogeneic transplantation of multiple myeloma patients may allow long-term survival in carefully selected patients with acceptable toxicity and preserved quality of life

Author

Greil, Christine, primary, Engelhardt, Monika, additional, Ihorst, Gabriele, additional, Schoeller, Katja, additional, Bertz, Hartmut, additional, Marks, Reinhard, additional, Zeiser, Robert, additional, Duyster, Justus, additional, Einsele, Hermann, additional, Finke, Jürgen, additional, and Wäsch, Ralph, additional

Published
2018
Full Text
View/download PDF

38. Stem cell mobilization in poor mobilizers with multiple myeloma or lymphoma before and after introduction of plerixafor: a single-center comparative analysis using a cost-efficient single fixed-dose schedule

Author

Greil, Christine, primary, Ihorst, Gabriele, additional, Kiote-Schmidt, Chrissoula, additional, Hildenbeutel, Steffi, additional, Kühbach, Katja, additional, Bosse, Roland, additional, Duyster, Justus, additional, Engelhardt, Monika, additional, and Wäsch, Ralph, additional

Published
2017
Full Text
View/download PDF

41. Tracing the development of acute myeloid leukemia in CBL syndrome

Author

Becker, Heiko, Yoshida, Kenichi, Blagitko-Dorfs, Nadja, Claus, Rainer, Pantic, Milena, Abdelkarim, Mahmoud, Niemöller, Christoph, Greil, Christine, Hackanson, Björn, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Miyano, Satoru, Döhner, Konstanze, Schnittger, Susanne, Henneke, Philipp, Niemeyer, Charlotte M., Flotho, Christian, Pfeifer, Dietmar, Ogawa, Seishi, and Lübbert, Michael

Published
2014
Full Text
View/download PDF

42. Phase I/II Study on Cytarabine and Idarubicin Combined with Escalating Doses of Clofarabine in Untreated Patients with Acute Myeloid Leukemia and High Risk for Induction Failure (AMLSG 17-10 CIARA)

Author

Krauter, Juergen, primary, Fiedler, Walter, additional, Schlenk, Richard F., additional, Paschka, Peter, additional, Thol, Felicitas, additional, Lübbert, Michael, additional, Wattad, Mohammad Amen, additional, Verbeek, Mareike, additional, Koenecke, Christian, additional, Neuhaus, Barbara, additional, Kebenko, Maxim, additional, Janning, Melanie, additional, Dohner, Konstanze, additional, Gaidzik, Verena I., additional, Becker, Heiko, additional, Greil, Christine, additional, Reimer, Peter, additional, Götze, Katharina, additional, Döhner, Hartmut, additional, Ganser, Arnold, additional, and Heuser, Michael, additional

Published
2016
Full Text
View/download PDF

44. Stem cell mobilization in poor mobilizers with multiple myeloma or lymphoma before and after introduction of plerixafor: a single-center comparative analysis using a cost-efficient single fixed-dose schedule.

Author

Greil, Christine, Ihorst, Gabriele, Kiote-Schmidt, Chrissoula, Hildenbeutel, Steffi, Kühbach, Katja, Bosse, Roland, Duyster, Justus, Engelhardt, Monika, and Wäsch, Ralph

Subjects
*HUMAN stem cells, *MULTIPLE myeloma treatment, *LYMPHOMA treatment
Published
2018
Full Text
View/download PDF

45. Single Cell Genotyping of Inv(16) AML in CBL Mutated Clonal Hematopoiesis Characterizes Clonal Architecture and Evolution of Exome Sequencing-Identified Mutations in the Protein Tyrosine Phosphatase Ptprt and Other Genes

Author

Niemöller, Christoph, primary, Bleul, Sabine, additional, Blagitko-Dorfs, Nadja, additional, Greil, Christine, additional, Yoshida, Kenichi, additional, Claus, Rainer, additional, Pfeifer, Dietmar, additional, Ogawa, Seishi, additional, Lübbert, Michael, additional, and Becker, Heiko, additional

Published
2015
Full Text
View/download PDF

46. Allogeneic Stem Cell Transplantation in Multiple Myeloma.

Author

Greil, Christine, Engelhardt, Monika, Finke, Jürgen, and Wäsch, Ralph

Subjects
*DISEASE progression, *GRAFT versus host disease, *HEMATOPOIETIC stem cell transplantation, *MULTIPLE myeloma, *IMMUNOTHERAPY
Abstract

Simple Summary: Due to its graft-versus-myeloma effect, allogeneic hematopoietic stem cell transplantation (allo-SCT) can enable long-term survival or even cure in carefully selected patients with multiple myeloma (MM), but remains controversial due to its relevant treatment-related toxicity. Current data suggest that allo-SCT should be considered in young MM-patients without relevant comorbidities in case of a high-risk constellation according to cytogenetics or stage, primarily as part of a tandem approach with autologous-SCT followed by allo-SCT and early in the course of the disease. Prospective studies are warranted, due to a suspected synergism especially those including new immunotherapeutic approaches for induction, conditioning and maintenance therapy. The development of new inhibitory and immunological agents and combination therapies significantly improved response rates and survival of patients diagnosed with multiple myeloma (MM) in the last decade, but the disease is still considered to be incurable by current standards and the prognosis is dismal especially in high-risk groups and in relapsed and/or refractory patients. Allogeneic hematopoietic stem cell transplantation (allo-SCT) may enable long-term survival and even cure for individual patients via an immune-mediated graft-versus-myeloma (GvM) effect, but remains controversial due to relevant transplant-related risks, particularly immunosuppression and graft-versus-host disease, and a substantial non-relapse mortality. The decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Here, allo-SCT should be considered within clinical trials in first-line as part of a tandem approach to separate myeloablation achieved by high-dose chemotherapy with autologous SCT, and following allo-SCT with a reduced-intensity conditioning to minimize treatment-related organ toxicities but allow GvM effect. Our review aims to better define the role of allo-SCT in myeloma treatment particularly in the context of new immunomodulatory approaches. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

47. Single Cell Genotyping of Inv(16) AML in CBLMutated Clonal Hematopoiesis Characterizes Clonal Architecture and Evolution of Exome Sequencing-Identified Mutations in the Protein Tyrosine Phosphatase Ptprtand Other Genes

Author

Niemöller, Christoph, Bleul, Sabine, Blagitko-Dorfs, Nadja, Greil, Christine, Yoshida, Kenichi, Claus, Rainer, Pfeifer, Dietmar, Ogawa, Seishi, Lübbert, Michael, and Becker, Heiko

Abstract

We recently described the first case of the evolution of inv(16) AML on the background of a clonal hematopoiesis due to a germline CBLmutation (defining the CBLsyndrome), and we identified possibly cooperating mutations by exome sequencing (Becker et al. Blood 2014;123:1883-6). Among the mutated genes was PTPRT, encoding a protein tyrosine phosphatase that inhibits STAT3 activity and is commonly mutated in cancer (reviewed by Zhao et al. Oncogene 2015;34:3885-94). Here, we investigated the co-occurrence of mutated PTPRTwith other mutated genes by single cell genotyping in order gain insights into the clonal architecture and sequence of mutation acquisition.

Published
2015
Full Text
View/download PDF

49. Targeting mitotic exit in solid tumors.

Author

Greil C, Felthaus J, Follo M, Ihorst G, Ewerth D, Schüler J, Schnerch D, Duyster J, Engelhardt M, and Wäsch R

Abstract

Targeting mitosis by taxanes is one of the most common chemotherapeutic approaches in various malignant solid tumors, but cancer cells may survive antimitotic treatment with attainable in vivo concentrations due to mitotic slippage with a residual activity of the ubiquitin ligase anaphase-promoting complex (APC/C) and a continuous slow ubiquitin-proteasome-dependent cyclin B-degradation leading to mitotic exit. Therefore, blocking cyclin B-proteolysis via additional proteasome (PI) or APC/C-inhibition may have the potential to enhance tumor cell eradication by inducing a more robust mitotic block and mitotic cell death. Here, we analyzed this approach in different cell lines and more physiological patient-derived xenografts (PDX) from lung and breast cancer. The sequential combination of paclitaxel with the PI bortezomib enhanced cell death, but in contrast to the hypothesis during interphase and not in mitosis in both lung and breast cancer. APC/C-inhibition alone or in sequential combination with paclitaxel led to strong mitotic cell death in lung cancer. But in breast cancer, with high expression of the anti-apoptotic regulator Mcl-1, cell death in interphase was induced. Here, combined APC/C- and Mcl-1-inhibition with or without paclitaxel was highly lethal but still resulted in interphase cell death. Taken together, the combination of antimitotic agents with a clinically approved PI or inhibitors of the APC/C and Mcl-1 is a promising approach to improve treatment response in different solid tumors, even though they act entity-dependent at different cell cycle phases., Competing Interests: None., (AJCR Copyright © 2021.)

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results