Niels Weinhold

Heidelberg University

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Co-Authors

Hartmut Goldschmidt

Heidelberg University

209

Marc S. Raab

German Cancer Research Center

172

Gareth J. Morgan

Children's Hospital Colorado

124

Faith E. Davies

NYU Langone Health

Leo Rasche

Universitätsklinikum Würzburg

Roman Hájek

University Hospital Ostrava

Joaquín Martínez‐López

Hospital Universitario 12 De Octubre

K. Elias

University Hospital Heidelberg

Kari Hemminki

Heidelberg University

Alexandra M. Poos

Heidelberg University

Cooperative Institutions

Heidelberg University

414

University Hospital Heidelberg

297

German Cancer Research Center

284

University of Arkansas for Medical Sciences

110

University College London

National Center for Tumor Diseases

DKFZ-ZMBH Alliance

Harvard University

Memorial Sloan Kettering Cancer Center

Institute of Cancer Research

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Malignant liver tumors treated with MR imaging-guided laser-induced thermotherapy: technique and prospective results.

Radiology (1995)

Thomas J. Vogl P. Müller R Hammerstingl Niels Weinhold M. G. Mack

PURPOSE: To evaluate magnetic resonance (MR) imaging-guided laser-induced thermotherapy (LITT) of liver metastases. MATERIALS AND METHODS: In a phase II study, 20 patients with 33 metastases from colorectal carcinoma (75%) or other primary tumors (25%) underwent LITT. MR thermometry performed with fast low-angle shot sequences was used to monitor therapy on-line, and dynamic and static contrast material-enhanced MR images enabled estimation of the degree of resultant necrosis. Follow-up studies were performed 3 months after thermotherapy. RESULTS: The thermosequences enabled accurate on-line monitoring in 85% of lesions. In 69% of lesions 20 mm in diameter or smaller, contrast-enhanced MR images depicted substantial necrosis, with a local tumor control rate of 69% after 6 months and 44% after 12 months. Among lesions larger than 20 mm, necrosis was frequently incomplete, with a local control rate of only 41% after 6 months and 27% after 12 months. CONCLUSION: MR imaging-guided LITT of liver metastases is a safe and promising therapy for liver metastases.

Dynamic contrast

10.1148/radiology.196.1.7540310

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Citations (342)

Spatial Dissection of the Bone Marrow Microenvironment in Multiple Myeloma By High Dimensional Multiplex Tissue Imaging

Blood (2023)

Marc‐Andrea Baertsch Alexander Brobeil John W. Hickey Maximilian Haist Alexandra M. Poos

Multiplex

10.1182/blood-2023-189255

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Citations (2)

Enrichment of B cell receptor signaling and epidermal growth factor receptor pathways in monoclonal gammopathy of undetermined significance: a genome-wide genetic interaction study

Molecular Medicine (2018)

Subhayan Chattopadhyay Hauke Thomsen Miguel Inácio da Silva Filho Niels Weinhold Per Hoffmann

Recent identification of 10 germline variants predisposing to monoclonal gammopathy of undetermined significance (MGUS) explicates genetic dependency of this asymptomatic precursor condition with multiple myeloma (MM). Yet much of genetic burden as well as functional links remain unexplained. We propose a workflow to expand the search for susceptibility loci with genome-wide interaction and for subsequent identification of genetic clusters and pathways. Polygenic interaction analysis on 243 cases/1285 controls identified 14 paired risk loci belonging to unique chromosomal bands which were then replicated in two independent sets (case only study, 82 individuals; case/control study 236 cases/ 2484 controls). Further investigation on gene-set enrichment, regulatory pathway and genetic network was carried out with stand-alone in silico tools separately for both interaction and genome-wide association study-detected risk loci. Intronic-PREX1 (20q13.13), a reported locus predisposing to MM was confirmed to have contribution to excess MGUS risk in interaction with SETBP1, a well-established candidate predisposing to myeloid malignancies. Pathway enrichment showed B cell receptor signaling pathway (P < 5.3 × 10− 3) downstream to allograft rejection pathway (P < 5.6 × 10− 4) and autoimmune thyroid disease pathway (P < 9.3 × 10− 4) as well as epidermal growth factor receptor regulation pathway (P < 2.4 × 10− 2) to be differentially regulated. Oncogene ALK and CDH2 were also identified to be moderately interacting with rs10251201 and rs16966921, two previously reported risk loci for MGUS. We described novel pathways and variants potentially causal for MGUS. The methodology thus proposed to facilitate our search streamlines risk locus-based interaction, genetic network and pathway enrichment analyses.

Genome-wide Association Study

10.1186/s10020-018-0031-8

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Citations (10)

Selective elimination of immunosuppressive T cells in patients with multiple myeloma

Leukemia (2021)

Mohamed H.S. Awwad Abdelrahman Mahmoud Heiko Bruns Hakim Echchannaoui Katharina Kriegsmann

Abstract Elimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8 + CD28 - CD57 + Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7 + CD8 + T cells exhibited decreased immunoreactivity towards the MART-1 aa26–35*A27L antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7 + CD8 + T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8 + Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.

10.1038/s41375-021-01172-x

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Citations (45)

Additional file 2 of Profound impact of sample processing delay on gene expression of multiple myeloma plasma cells

Figshare (2015)

Tobias MeiĂNer Anja Seckinger Kari Hemminki Uta Bertsch Asta Foersti

Table S1 - Differentially Expressed Genes. Table listing the 6802 genes differentially expressed between shipped and in-house samples. (XLSX 554 KB)

Sample (material)

10.6084/m9.figshare.c.3628991_d8

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Citations (0)

Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression

Nature Communications (2016)

Ni Li David C. Johnson Niels Weinhold James B. Studd Giulia Orlando

Abstract Genome-wide association studies have identified several risk loci for multiple myeloma (MM); however, the mechanisms by which they influence MM are unknown. Here by using genetic association data and functional characterization, we demonstrate that rs4487645 G>T, the most highly associated variant ( P = 5.30 × 10 −25 ), resides in an enhancer element 47 kb upstream of the transcription start site of c-Myc-interacting CDCA7L . The G-risk allele, associated with increased CDCA7L expression ( P =1.95 × 10 −36 ), increases IRF4 binding and the enhancer interacts with the CDCA7L promoter. We show that suppression of CDCA7L limits MM proliferation through apoptosis, and increased CDCA7L expression is associated with adverse patient survival. These findings implicate IRF4-mediated CDCA7L expression in MM biology and indicate how germline variation might confer susceptibility to MM.

IRF4

Genome-wide Association Study

10.1038/ncomms13656

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Citations (35)

Daratumumab in high‐risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome

British Journal of Haematology (2019)

Meera Mohan Niels Weinhold Carolina Schinke Sharmilan Thanedrarajan Leo Rasche

Gain of chromosome 1q21 and the gene expression-based GEP70 risk score are established prognostic markers for newly diagnosed Multiple Myeloma (MM) patients. Here we addressed the prognostic impact of these two markers in 81 relapsed/refractory (RR) MM patients treated with the CD38-antibody daratumumab. Fluorescence in situ hybridization for 1q21 was performed at initial presentation, while the GEP70 score was determined at initial presentation and prior to daratumumab treatment. While the GEP70 at initial presentation showed a trend for inferior survival, the GEP70 collected prior to daratumumab treatment was significantly associated with poor outcome (P < 0·05). The worst outcome was seen for patients who were positive for gain(1q) and classified as GEP70 high risk prior to daratumumab [progression-free (PFS) and overall survival (OS) of 0·3 years (95% CI: 0·15-1·4 years) and 0·8 years (95% CI: 0·5-1·9 years) respectively], while the median PFS and OS were not reached by patients without gain(1q) and GEP70 low-risk status. In conclusion, gain(1q) and the GEP70 are powerful prognostic markers for RR MM patients treated with daratumumab, and patients classified as high risk according to these markers experience shorter treatment response.

Daratumumab

Refractory (planetary science)

10.1111/bjh.16292

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Citations (49)

Supplementary Table 3 from Single-Nucleotide Variants and Epimutations Induce Proteasome Inhibitor Resistance in Multiple Myeloma

Larissa Haertle Santiago Barrio Umair Munawar Seungbin Han Xiang Zhou

<p>Primers used for luciferase reporter assay.</p>

Table (database)

10.1158/1078-0432.22489562

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Citations (0)