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Article ; Online: Energy overpowers sweet tooth in FL.

Veelken, Hendrik

2023 Volume 142, Issue 26, Page(s) 2226–2229

MeSH term(s)	Humans ; Glycosylation ; Lymphoma, Follicular ; Receptors, Antigen, B-Cell
Chemical Substances	Receptors, Antigen, B-Cell
Language	English
Publishing date	2023-12-26
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023022268
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Article: Idelalisib.

Zirlik, Katja / Veelken, Hendrik

Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer

2018 Volume 212, Page(s) 243–264

Abstract: Idelalisib (GS-1101, CAL-101, ... ...

Abstract	Idelalisib (GS-1101, CAL-101, Zydelig
MeSH term(s)	Antineoplastic Agents/pharmacology ; Enzyme Inhibitors/pharmacology ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Purines/pharmacology ; Quinazolinones/pharmacology
Chemical Substances	Antineoplastic Agents ; Enzyme Inhibitors ; Purines ; Quinazolinones ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; idelalisib (YG57I8T5M0)
Language	English
Publishing date	2018-08-01
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0080-0015
ISSN	0080-0015
DOI	10.1007/978-3-319-91439-8_12
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Article ; Online: COVID-19 and systemic anticancer therapy: exploiting uncertainty.

Gelderblom, Hans / Veelken, Hendrik / Stiggelbout, Anne M

The Lancet. Oncology

2020 Volume 22, Issue 1, Page(s) 3–5

MeSH term(s)	COVID-19 ; Clinical Decision-Making ; England ; Humans ; Pandemics ; Retrospective Studies ; SARS-CoV-2 ; Uncertainty
Language	English
Publishing date	2020-11-27
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(20)30700-2
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Article ; Online: Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL.

Eken, Janneke A / Koning, Marvyn T / Kupcova, Kristyna / Sepúlveda Yáñez, Julieta H / de Groen, Ruben A L / Quinten, Edwin / Janssen, Jurriaan / van Bergen, Cornelis A M / Vermaat, Joost S P / Cleven, Arjen / Navarrete, Marcelo A / Ylstra, Bauke / de Jong, Daphne / Havranek, Ondrej / Jumaa, Hassan / Veelken, Hendrik

The Journal of experimental medicine

2024 Volume 221, Issue 5

Abstract: Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-κB activation, which can be explained by activating mutations of the BCR ... ...

Abstract	Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-κB activation, which can be explained by activating mutations of the BCR signaling cascade in a minority of cases. We demonstrate that autonomous BCR signaling, akin to its essential pathogenetic role in chronic lymphocytic leukemia (CLL), can explain chronic active BCR signaling in ABC-DLBCL. 13 of 18 tested DLBCL-derived BCR, including 12 cases selected for expression of IgM, induced spontaneous calcium flux and increased phosphorylation of the BCR signaling cascade in murine triple knockout pre-B cells without antigenic stimulation or external BCR crosslinking. Autonomous BCR signaling was associated with IgM isotype, dependent on somatic BCR mutations and individual HCDR3 sequences, and largely restricted to non-GCB DLBCL. Autonomous BCR signaling represents a novel immunological oncogenic driver mechanism in DLBCL originating from individual BCR sequences and adds a new dimension to currently proposed genetics- and transcriptomics-based DLBCL classifications.
MeSH term(s)	Animals ; Mice ; B-Lymphocytes ; Lymphoma, Large B-Cell, Diffuse/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; Receptors, Antigen, B-Cell ; Immunoglobulin M
Chemical Substances	Receptors, Antigen, B-Cell ; Immunoglobulin M
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20230941
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Article ; Online: Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation.

Koster, Eva A S / von dem Borne, Peter A / van Balen, Peter / Marijt, Erik W A / Tjon, Jennifer M L / Snijders, Tjeerd J F / van Lammeren, Daniëlle / Veelken, Hendrik / Falkenburg, J H Frederik / Halkes, Constantijn J M / de Wreede, Liesbeth C

Frontiers in immunology

2024 Volume 15, Page(s) 1335341

Abstract: Introduction: Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the ... ...

Abstract	Introduction: Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI. Methods: We investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection ( Results: For both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x10 Conclusion: These data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI.
MeSH term(s)	Humans ; T-Lymphocytes ; Lymphocyte Transfusion/adverse effects ; Hematopoietic Stem Cell Transplantation/adverse effects ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Leukemia, Myeloid, Acute/complications ; Unrelated Donors ; Virus Diseases/complications
Language	English
Publishing date	2024-03-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1335341
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Article ; Online: Mapping AML heterogeneity - multi-cohort transcriptomic analysis identifies novel clusters and divergent ex-vivo drug responses.

Severens, Jeppe F / Karakaslar, E Onur / van der Reijden, Bert A / Sánchez-López, Elena / van den Berg, Redmar R / Halkes, Constantijn J M / van Balen, Peter / Veelken, Hendrik / Reinders, Marcel J T / Griffioen, Marieke / van den Akker, Erik B

Leukemia

2024 Volume 38, Issue 4, Page(s) 751–761

Abstract: Subtyping of acute myeloid leukaemia (AML) is predominantly based on recurrent genetic abnormalities, but recent literature indicates that transcriptomic phenotyping holds immense potential to further refine AML classification. Here we integrated five ... ...

Abstract	Subtyping of acute myeloid leukaemia (AML) is predominantly based on recurrent genetic abnormalities, but recent literature indicates that transcriptomic phenotyping holds immense potential to further refine AML classification. Here we integrated five AML transcriptomic datasets with corresponding genetic information to provide an overview (n = 1224) of the transcriptomic AML landscape. Consensus clustering identified 17 robust patient clusters which improved identification of CEBPA-mutated patients with favourable outcomes, and uncovered transcriptomic subtypes for KMT2A rearrangements (2), NPM1 mutations (5), and AML with myelodysplasia-related changes (AML-MRC) (5). Transcriptomic subtypes of KMT2A, NPM1 and AML-MRC showed distinct mutational profiles, cell type differentiation arrests and immune properties, suggesting differences in underlying disease biology. Moreover, our transcriptomic clusters show differences in ex-vivo drug responses, even when corrected for differentiation arrest and superiorly capture differences in drug response compared to genetic classification. In conclusion, our findings underscore the importance of transcriptomics in AML subtyping and offer a basis for future research and personalised treatment strategies. Our transcriptomic compendium is publicly available and we supply an R package to project clusters to new transcriptomic studies.
MeSH term(s)	Humans ; Nuclear Proteins/genetics ; Transcriptome/genetics ; Nucleophosmin ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Mutation ; Gene Expression Profiling ; Prognosis
Chemical Substances	Nuclear Proteins ; Nucleophosmin (117896-08-9)
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-024-02137-6
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Article: A transcriptomic based deconvolution framework for assessing differentiation stages and drug responses of AML.

Karakaslar, E Onur / Severens, Jeppe F / Sánchez-López, Elena / van Veelen, Peter A / Zlei, Mihaela / van Dongen, Jacques J M / Otte, Annemarie M / Halkes, Constantijn J M / van Balen, Peter / Veelken, Hendrik / Reinders, Marcel J T / Griffioen, Marieke / van den Akker, Erik B

NPJ precision oncology

2024 Volume 8, Issue 1, Page(s) 105

Abstract: The diagnostic spectrum for AML patients is increasingly based on genetic abnormalities due to their prognostic and predictive value. However, information on the AML blast phenotype regarding their maturational arrest has started to regain importance due ...

Abstract	The diagnostic spectrum for AML patients is increasingly based on genetic abnormalities due to their prognostic and predictive value. However, information on the AML blast phenotype regarding their maturational arrest has started to regain importance due to its predictive power for drug responses. Here, we deconvolute 1350 bulk RNA-seq samples from five independent AML cohorts on a single-cell healthy BM reference and demonstrate that the morphological differentiation stages (FAB) could be faithfully reconstituted using estimated cell compositions (ECCs). Moreover, we show that the ECCs reliably predict ex-vivo drug resistances as demonstrated for Venetoclax, a BCL-2 inhibitor, resistance specifically in AML with CD14+ monocyte phenotype. We validate these predictions using LUMC proteomics data by showing that BCL-2 protein abundance is split into two distinct clusters for NPM1-mutated AML at the extremes of CD14+ monocyte percentages, which could be crucial for the Venetoclax dosing patients. Our results suggest that Venetoclax resistance predictions can also be extended to AML without recurrent genetic abnormalities and possibly to MDS-related and secondary AML. Lastly, we show that CD14+ monocytic dominated Ven/Aza treated patients have significantly lower overall survival. Collectively, we propose a framework for allowing a joint mutation and maturation stage modeling that could be used as a blueprint for testing sensitivity for new agents across the various subtypes of AML.
Language	English
Publishing date	2024-05-18
Publishing country	England
Document type	Journal Article
ISSN	2397-768X
ISSN	2397-768X
DOI	10.1038/s41698-024-00596-9
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Article ; Online: Acquisition of a glycosylated B-cell receptor drives follicular lymphoma toward a dark zone phenotype.

van Bergen, Cornelis A M / Kloet, Susan L / Quinten, Edwin / Sepúlveda Yáñez, Julieta H / Menafra, Roberta / Griffioen, Marieke / Jansen, Patty M / Koning, Marvyn T / Knijnenburg, Jeroen / Navarrete, Marcelo A / Kiełbasa, Szymon M / Veelken, Hendrik

Blood advances

2023 Volume 7, Issue 19, Page(s) 5812–5816

Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023010725
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Article ; Online: A Comparison of Immunoglobulin Variable Region N-Linked Glycosylation in Healthy Donors, Autoimmune Disease and Lymphoma.

Vletter, Esther M / Koning, Marvyn T / Scherer, Hans Ulrich / Veelken, Hendrik / Toes, Rene E M

Frontiers in immunology

2020 Volume 11, Page(s) 241

Abstract: N-linked glycans play an important role in immunity. Although the role of N-linked glycans in the Fragment crystallizable (Fc) region of immunoglobulins has been thoroughly described, the function of N-linked glycans present in Ig-variable domains is ... ...

Abstract	N-linked glycans play an important role in immunity. Although the role of N-linked glycans in the Fragment crystallizable (Fc) region of immunoglobulins has been thoroughly described, the function of N-linked glycans present in Ig-variable domains is only just being appreciated. Most of the N-linked glycans harbored by immunoglobulin variable domain are of the complex biantennary type and are found as a result of the presence of N-linked glycosylation that most often have been introduced by somatic hypermutation. Furthermore, these glycans are ubiquitously present on autoantibodies observed in some autoimmune diseases as well as certain B-cell lymphomas. For example, variable domain glycans are abundantly found by anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) as well as by the B-cell receptors of follicular lymphoma (FL). In FL, variable domain glycans are postulated to convey a selective advantage through interaction with lectins and/or microbiota, whereas the contribution of variable domain glycans on autoantibodies is not known. To aid the understanding how these seemingly comparable phenomena contribute to a variety of deranged B-responses in such different diseases this study summarizes the characteristics of ACPA and other auto-antibodies with FL and healthy donor immunoglobulins, to identify the commonalities and differences between variable domain glycans in autoimmune and malignant settings. Our finding indicate intriguing differences in variable domain glycan distribution, frequency and glycan composition in different conditions. These findings underline that variable domain glycosylation is a heterogeneous process that may lead to a number of pathogenic outcomes. Based on the current body of knowledge, we postulate three disease groups with distinct variable domain glycosylation patterns, which might correspond with distinct underlying pathogenic processes.
MeSH term(s)	Anti-Citrullinated Protein Antibodies/immunology ; Arthritis, Rheumatoid/immunology ; Autoimmune Diseases/immunology ; Glycosylation ; Humans ; Immunoglobulin Variable Region/chemistry ; Immunoglobulin Variable Region/metabolism ; Lectins/chemistry ; Lupus Erythematosus, Systemic/immunology ; Lymphoma/immunology ; Myasthenia Gravis/immunology ; Polysaccharides/analysis ; Polysaccharides/chemistry ; Protein Domains
Chemical Substances	Anti-Citrullinated Protein Antibodies ; Immunoglobulin Variable Region ; Lectins ; Polysaccharides
Language	English
Publishing date	2020-02-18
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00241
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Article: Active immunotherapy in follicular lymphoma.

Veelken, Hendrik

Seminars in cancer biology

2003 Volume 13, Issue 3, Page(s) 241–247

Abstract: The antigen receptors expressed by follicular lymphomas represent tumor-specific antigens ("idiotypes"). In murine models, vaccination with tumor-derived idiotype in a variety of formulations can induce protective lymphoma-specific immunity. Phase II ... ...

Abstract	The antigen receptors expressed by follicular lymphomas represent tumor-specific antigens ("idiotypes"). In murine models, vaccination with tumor-derived idiotype in a variety of formulations can induce protective lymphoma-specific immunity. Phase II clinical trials in follicular lymphoma have also demonstrated idiotype-specific immune responses. Clinical data from these trials indicate sustained progression-free survival, disappearance of minimal residual disease, and even frank lymphoma regression in some cases. Phase III trials to prove the beneficial effects of active immunotherapy are currently being conducted. Additional research efforts focus on the most efficacious vaccination route and on the development of convenient methods to manufacture individual idiotype vaccines.
MeSH term(s)	Animals ; Cancer Vaccines/therapeutic use ; Clinical Trials as Topic ; Disease Models, Animal ; Humans ; Immunotherapy, Active/methods ; Lymphoma, Follicular/drug therapy ; Lymphoma, Follicular/immunology
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2003-08-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/s1044-579x(03)00020-8
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