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1دورية أكاديمية
المؤلفون: Jeroen H. A. Creemers, Maarten J. van der Doelen, Sandra van Wilpe, Rick Hermsen, Tjitske Duiveman-de Boer, Diederik M. Somford, Marcel J. R. Janssen, J. P. Michiel Sedelaar, Niven Mehra, Johannes Textor, Harm Westdorp
المصدر: Frontiers in Oncology, Vol 11 (2021)
مصطلحات موضوعية: metastatic castration-resistant prostate cancer (mCRPC), immune checkpoints, radionuclide therapy, radium-223, immunophenotyping, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: BackgroundRadium-223 improves overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (mCRPC). While the exact mechanism behind this survival benefit remains unclear, radium-induced immunological mechanisms might contribute to the OS advantage. We performed a comprehensive evaluation of the immunological changes in mCRPC patients by phenotyping the peripheral blood mononuclear cells (PBMCs) during radium-223 therapy.Materials and MethodsIn this prospective, single-arm, exploratory study, PBMCs of 30 mCRPC patients were collected before, during, and after treatment with radium-223. Lymphocyte and monocyte counts were analyzed to get insight into general immune cell trends. Next, we analyzed changes in T cell subsets, myeloid-derived suppressor cells (MDSCs), and immune checkpoint expression using linear regression models. Per subset, the 6-month change (% of baseline) was determined. Bootstrapped 95% confidence intervals were used to measure the degree of uncertainty of our findings.ResultsWe observed a substantial decrease in absolute lymphocyte counts (-0.12 * 10^9 cells/L per injection, 95% CI: -0.143 - -0.102). Simultaneously, an increase was observed in the proportion of T cells that expressed costimulatory (ICOS) or inhibitory (TIM-3, PD-L1, and PD-1) checkpoint molecules. Moreover, the fraction of two immunosuppressive subsets – the regulatory T cells and the monocytic MDSCs – increased throughout treatment. These findings were not more pronounced in patients with an alkaline phosphatase response during therapy.ConclusionImmune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2021.667658/fullTest; https://doaj.org/toc/2234-943XTest
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المؤلفون: Jeroen H. A. Creemers (9561569), Maarten J. van der Doelen (10813803), Sandra van Wilpe (10813806), Rick Hermsen (10813809), Tjitske Duiveman-de Boer (6197000), Diederik M. Somford (8568981), Marcel J. R. Janssen (10813812), J. P. Michiel Sedelaar (8568987), Niven Mehra (7867451), Johannes Textor (610955), Harm Westdorp (3478268)
مصطلحات موضوعية: Cancer, Cancer Cell Biology, Cancer Diagnosis, Cancer Genetics, Cancer Therapy (excl. Chemotherapy and Radiation Therapy), Chemotherapy, Haematological Tumours, Molecular Targets, Radiation Therapy, Solid Tumours, Oncology and Carcinogenesis not elsewhere classified, metastatic castration-resistant prostate cancer (mCRPC), immune checkpoints, radionuclide therapy, radium-223, immunophenotyping
الوصف: Background Radium-223 improves overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (mCRPC). While the exact mechanism behind this survival benefit remains unclear, radium-induced immunological mechanisms might contribute to the OS advantage. We performed a comprehensive evaluation of the immunological changes in mCRPC patients by phenotyping the peripheral blood mononuclear cells (PBMCs) during radium-223 therapy. Materials and Methods In this prospective, single-arm, exploratory study, PBMCs of 30 mCRPC patients were collected before, during, and after treatment with radium-223. Lymphocyte and monocyte counts were analyzed to get insight into general immune cell trends. Next, we analyzed changes in T cell subsets, myeloid-derived suppressor cells (MDSCs), and immune checkpoint expression using linear regression models. Per subset, the 6-month change (% of baseline) was determined. Bootstrapped 95% confidence intervals were used to measure the degree of uncertainty of our findings. Results We observed a substantial decrease in absolute lymphocyte counts (-0.12 * 10^9 cells/L per injection, 95% CI: -0.143 - -0.102). Simultaneously, an increase was observed in the proportion of T cells that expressed costimulatory (ICOS) or inhibitory (TIM-3, PD-L1, and PD-1) checkpoint molecules. Moreover, the fraction of two immunosuppressive subsets – the regulatory T cells and the monocytic MDSCs – increased throughout treatment. These findings were not more pronounced in patients with an alkaline phosphatase response during therapy. Conclusion Immune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes.
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المؤلفون: Jeroen H. A. Creemers, Maarten J. van der Doelen, Sandra van Wilpe, Rick Hermsen, Tjitske Duiveman-de Boer, Diederik M. Somford, Marcel J. R. Janssen, J. P. Michiel Sedelaar, Niven Mehra, Johannes Textor, Harm Westdorp
مصطلحات موضوعية: Cancer, Cancer Cell Biology, Cancer Diagnosis, Cancer Genetics, Cancer Therapy (excl. Chemotherapy and Radiation Therapy), Chemotherapy, Haematological Tumours, Molecular Targets, Radiation Therapy, Solid Tumours, Oncology and Carcinogenesis not elsewhere classified, metastatic castration-resistant prostate cancer (mCRPC), immune checkpoints, radionuclide therapy, radium-223, immunophenotyping
الوصف: Background Radium-223 improves overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (mCRPC). While the exact mechanism behind this survival benefit remains unclear, radium-induced immunological mechanisms might contribute to the OS advantage. We performed a comprehensive evaluation of the immunological changes in mCRPC patients by phenotyping the peripheral blood mononuclear cells (PBMCs) during radium-223 therapy. Materials and Methods In this prospective, single-arm, exploratory study, PBMCs of 30 mCRPC patients were collected before, during, and after treatment with radium-223. Lymphocyte and monocyte counts were analyzed to get insight into general immune cell trends. Next, we analyzed changes in T cell subsets, myeloid-derived suppressor cells (MDSCs), and immune checkpoint expression using linear regression models. Per subset, the 6-month change (% of baseline) was determined. Bootstrapped 95% confidence intervals were used to measure the degree of uncertainty of our findings. Results We observed a substantial decrease in absolute lymphocyte counts (-0.12 * 10^9 cells/L per injection, 95% CI: -0.143 - -0.102). Simultaneously, an increase was observed in the proportion of T cells that expressed costimulatory (ICOS) or inhibitory (TIM-3, PD-L1, and PD-1) checkpoint molecules. Moreover, the fraction of two immunosuppressive subsets – the regulatory T cells and the monocytic MDSCs – increased throughout treatment. These findings were not more pronounced in patients with an alkaline phosphatase response during therapy. Conclusion Immune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes.
الإتاحة: https://doi.org/10.3389/fonc.2021.667658.s009Test
https://figshare.com/articles/dataset/DataSheet_9_Immunophenotyping_Reveals_Longitudinal_Changes_in_Circulating_Immune_Cells_During_Radium-223_Therapy_in_Patients_With_Metastatic_Castration-Resistant_Prostate_Cancer_docx/14609586Test -
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المؤلفون: Nielka P. van Erp, Guillemette E. Benoist, Niven Mehra, Maarten J. van der Doelen, Rob ter Heine
المصدر: British Journal of Clinical Pharmacology, 84, 5, pp. 1064-1067
British Journal of Clinical Pharmacology, 84, 1064-1067مصطلحات موضوعية: Oncology, medicine.medical_specialty, Case Reports, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], 030226 pharmacology & pharmacy, 03 medical and health sciences, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], medicine, Pharmacology (medical), Adverse effect, Pharmacology, medicine.diagnostic_test, business.industry, Abiraterone acetate, Carbamazepine, medicine.disease, Discontinuation, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, Concomitant, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Prednisolone, business, medicine.drug
الوصف: Adverse event Decreased abiraterone exposure after introducing carbamazepine. Drugs implicated Abiraterone acetate and carbamazepine. The patient A 65-year-old man with metastatic castration resistant prostate cancer, was treated with abiraterone acetate and prednisolone, and received concomitant carbamazepine for treatment of facial neuropathy. Evidence that links the drug to the event The interaction was confirmed by a decrease in abiraterone exposure >2-fold (area-under-the-curve and trough levels). After discontinuation of carbamazepine therapy, the abiraterone exposure normalized. No alternative causes were found that explain the decrease in abiraterone exposure. Mechanism Induction of CYP3A and potentially phase I metabolism (SULT2A1) by carbamazepine. Implications for therapy Clinicians and pharmacists should be aware of this clinically relevant interaction. The national drug-drug interaction checker does not warn for this interaction, whereas both the Lexicomp® and Micromedex® advice to avoid if possible or to increase the abiraterone dose frequency to twice daily. Carbamazepine should not be combined with abiraterone to avoid underexposure and suboptimal therapy. Therapeutic drug monitoring of abiraterone is useful to guide therapy when drug-drug interactions cannot be avoided.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::02e165996a1e89bbf3360ebdd98fed82Test
https://europepmc.org/articles/PMC5903233Test/
النص الكامل