A5051977856- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Genetic Syndromes and Imprinting
- Radiopharmaceutical Chemistry and Applications
- Parathyroid Disorders and Treatments
- Genetics and Neurodevelopmental Disorders
- Childhood Cancer Survivors' Quality of Life
- Peptidase Inhibition and Analysis
- Vascular Tumors and Angiosarcomas
- Thyroid and Parathyroid Surgery
- Prostate Cancer Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Genomic variations and chromosomal abnormalities
- Glycogen Storage Diseases and Myoclonus
- Cancer, Lipids, and Metabolism
- Colorectal Cancer Treatments and Studies
- Sarcoma Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Cardiac tumors and thrombi
- Medical Imaging and Pathology Studies
- Intestinal Malrotation and Obstruction Disorders
- Congenital heart defects research
- Inflammatory Myopathies and Dermatomyositis
- Extracellular vesicles in disease
Radboud University Nijmegen
1982-2024
Radboud University Medical Center
2018-2024
University Medical Center
2020
Radboud Institute for Molecular Life Sciences
2019
Metastatic castration-resistant prostate cancer (mCRPC) has a highly complex genomic landscape. With the recent development of novel treatments, accurate stratification strategies are needed. Here we present whole-genome sequencing (WGS) analysis fresh-frozen metastatic biopsies from 197 mCRPC patients. Using unsupervised clustering based on features, define eight distinct clusters. We observe potentially clinically relevant genotypes, including microsatellite instability (MSI), homologous...
Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets involved in cancer progression and considered a promising biosource detection, as they alter their RNA content upon local systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the of 18 types. With 99% specificity asymptomatic controls, thromboSeq correctly detected presence two-thirds 1,096 samples stage I–IV half 352 I–III...
Despite their important role in metastatic disease, no general method to detect circulating stromal cells (CStCs) exists. Here, we present the Metabolic Assay-Chip (MA-Chip) as a label-free, droplet-based microfluidic approach allowing single-cell extracellular pH measurement for detection and isolation of highly metabolically active (hm-cells) from tumor microenvironment. Single-cell mRNA-sequencing analysis hm-cells prostate cancer patients revealed that approximately 10% were canonical...
3 siblings with symmetrical calcifications in the strio-pallido-dentate system are described. Parathyroid function was normal and there were no signs of central or peripheral myelinopathy. This is 9th family reported autosomal recessive idiopathic calcinosis first to be investigated by computerized tomography (CT). CT scans appeared superior plain skull radiograms assess localization extent vivo. The least extensive youngest most eldest. It suggested that calcifying process a progressive...
Three siblings with Cockayne's syndrome are reported. Sural nerve biopsies revealed segmental de- and remyelination onion-bulb formation. Disturbed visual brainstem auditory evoked responses indicated demyelination of the central nervous system. The peripheral myelinopathy increased age, suggesting a progressive disorder. Our observations support theory being leukodystrophy.
11513 Background: Angiosarcomas (AS) are rare and aggressive vascular sarcomas that can be subdivided in primary (de novo; pAS) secondary AS (sAS). Secondary arise due to DNA damaging factors like radiotherapy (RT) UV radiation or chronic lymphedema (Stewart Treves AS). Prognosis of locally advanced metastatic is very poor treatment options limited. sAS differ from pAS clinical behavior, genetic molecular background. Instead, show similarities cutaneous squamous-cell carcinoma, for which the...
For individual treatment decisions in patients with metastatic prostate cancer (mPC), molecular diagnostics are increasingly used. Bone metastases frequently the only source for obtaining tumor tissue. However, success rate of CT-guided bone biopsies analyses mPC is approximately 40%. PET using <sup>68</sup>Ga prostate-specific membrane antigen (<sup>68</sup>Ga-PSMA) a promising tool to improve harvest analyses. The aim this study was determine <sup>68</sup>Ga-PSMA–guided patients....
344 Background: Prostate-specific membrane antigen (PSMA) is an ideal target for RLT in mCRPC patients (pts). Alpha-emitting radioisotope Actinium-225 (Ac-225) may be more efficacious than beta-emitting Lutetium-177, due to higher rates of double-strand DNA breaks prostate cancer cells, with less tissue penetration and minimal bystander effects PSMA-negative cells. Limited data available on the clinical efficacy side PSMA-Ac-225 pts. Here we describe our experience so far. Methods: Between...
Abstract Treatment of castration-resistant prostate cancer remains a challenging clinical problem. Despite the promising effects immunotherapy in other solid cancers, has remained largely unresponsive. Oncolytic viruses represent therapeutic avenue, as oncolytic virus treatment combines tumour cell lysis with activation immune system and mounting effective anti-tumour responses. Mammalian Orthoreoviruses are non-pathogenic human preference lytic replication cells. In this study, we evaluated...
Molecular tumour boards (MTB) optimally match oncological therapies to patients with genetic aberrations. Prostate cancer (PCa) is underrepresented in these MTB discussions. This study describes the impact of routine profiling and referral on outcome PCa a tertiary centre.All that received next-generation sequencing results and/or were discussed at an between Jan 1, 2017 2020 included. Genetically matched (GMT) clinical trials or compassionate use linked actionable alterations. Response...
248 Background: Response to anti-PD1/PDL1 checkpoint therapy has been witnessed in only a minority of patients with castration-resistant prostate cancer (CRPC). Microsatellite instability (MSI) is the biomarker predictive response; additional immune and genomic correlates are needed improve proportion that may benefit from immunotherapy. Methods: CRPC were treated anti-PD1 immunotherapy two basket-studies, depending on PDL1-positivity ( > 1%) or presence MSI, consented prospective...
Precision medicine expands the treatment options for metastatic castration-resistant prostate cancer (mCRPC) by targeting druggable genetic aberrations. Aberrations can be identified following molecular analysis of tissue. Bone metastases, commonly present in mCRPC, hinder precision due to a high proportion biopsies with insufficient tumor cells next-generation DNA sequencing. We aimed investigate feasibility incorporating advanced target planning and needle guidance bone whether this...
PURPOSE Although most patients with microsatellite instable (MSI) metastatic castration-resistant prostate cancer (mCRPC) respond to immune checkpoint blockade (ICB), only a small subset of stable (MSS) tumors have similar benefit. Biomarkers defining ICB-susceptible subsets MSS mCRPC are urgently needed. METHODS Using next-generation T-cell repertoire sequencing, we explored signatures in 54 and MSI who were treated or without ICB. We defined subset-specific metrics as well clusters...
Developing and optimizing targeted therapies in metastatic castration-resistant prostate cancer (mCRPC) necessitates molecular characterization. Obtaining sufficient tumor material for characterization has been challenging. We aimed to identify clinical imaging variables of imaging-guided bone biopsies patients that associate with yield success obtaining results, design a predictive model: Clinical data were collected retrospectively from who underwent biopsy histological characteristics,...
Abstract During the last decade several new therapies have been investigated and approved for metastatic prostate cancer that greatly impacts patients’ quality of life outcome. Nevertheless, optimal sequencing algorithms are still lacking, as combinatory strategies deliver long-term disease stabilization. Precision medicine, utilizing molecular profiles from tissue biopsies, will help us patient care by identifying patients may benefit targeted- immunotherapy, guide treatment decisions use...
Abstract Here we present whole-genome sequencing (WGS) analysis of fresh-frozen metastatic biopsies from 197 castration-resistant prostate cancer patients. Using hierarchical unsupervised clustering based on genomic aberrations only, defined eight different clusters. We detected four distinct and potentially clinically relevant genotypes harboring unique features, including: 1) Microsatellite Instability; 2) Homologous Recombination Deficiency (HRD) with enriched deletions BRCA2 aberrations;...
Angiosarcomas (AS) are rare and aggressive vascular sarcomas that can be subdivided in primary (de novo) secondary AS. Secondary AS frequently located the skin, arising due to DNA damaging noxes like radiotherapy UV radiation or chronic lymphedema (Stewart Treves AS). Prognosis of metastatic is extremely poor treatment options limited chemotherapy, tyrosine kinase inhibitor pazopanib. differ from clinical behavior, genetic molecular background, with a more T-cell infiltrated tumor...
5036 Background: Predictive biomarkers are needed to improve the proportion of pts with mCRPC that may benefit from anti-PD-1/PD-L1 ICB. A comprehensive characterization both genomic alterations as immunological landscape during ICB prove fundamental. Methods: We investigated correlates response and progression in treated anti-PD-1 Pts were selected by PD-L1 > 1% and/or MMRd. Optional pre-treatment post-progression biopsies collected for whole-genome sequencing multiplex IHC. 8-color flow...