A5019498255- Intraperitoneal and Appendiceal Malignancies
- Appendicitis Diagnosis and Management
- Hepatocellular Carcinoma Treatment and Prognosis
- Lipoproteins and Cardiovascular Health
- Renal cell carcinoma treatment
- Vitamin K Research Studies
- Ovarian cancer diagnosis and treatment
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cancer Genomics and Diagnostics
- Nanoparticle-Based Drug Delivery
- Luminescence Properties of Advanced Materials
- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Pharmacology and Obesity Treatment
- Cancer Cells and Metastasis
- Cardiovascular Health and Disease Prevention
- Antioxidant Activity and Oxidative Stress
- Adipokines, Inflammation, and Metabolic Diseases
- Genetic factors in colorectal cancer
- Gastrointestinal Tumor Research and Treatment
- Cancer, Lipids, and Metabolism
- Protease and Inhibitor Mechanisms
Cancer Genomics Centre
2019-2024
University Medical Center Utrecht
2019-2024
Utrecht University
2022
University Medical Center Groningen
2011-2012
University of Groningen
2011-2012
Patients with peritoneal metastases from colorectal cancer have a poor prognosis. If the intraperitoneal tumour load is limited, patients may be eligible for cytoreductive surgery followed by hyperthermic chemotherapy (HIPEC). This treatment has improved overall survival, but recurrence rates are high. The aim of this study was to create preclinical platform development more effective strategies.Using organoid technology, five cultures were generated malignant ascites and resected...
Peritoneal metastases (PM) in colorectal cancer (CRC) are associated with therapy resistance and poor survival. Oxaliplatin monotherapy is widely applied the intraperitoneal treatment of PM, but fails to yield clinical benefit. We aimed identify mechanism(s) underlying PM oxaliplatin develop strategies overcoming such resistance.We generated a biobank consisting 35 primary tumour regions 59 paired from 12 patients. All samples were analysed by RNA sequencing. also series PM-derived organoid...
Abstract Tumor‐derived cell‐free DNA (cfDNA) is an emerging biomarker for guiding the personalized treatment of patients with metastatic colorectal cancer (CRC). While CRC liver metastases (CRC‐LM) have relatively high levels plasma cfDNA, little known about peritoneal (CRC‐PM). This study evaluated presence tumor‐derived cfDNA in and fluid (i.e. ascites or washing) 20 isolated CRC‐PM 100 CRC‐LM. Among tumor tissue KRAS/BRAF mutation carriers, was detected by droplet digital polymerase chain...
Background Mesenchymal Consensus Molecular Subtype 4 (CMS4) colon cancer is associated with poor prognosis and therapy resistance. In this proof-of-concept study, we assessed whether a rationally chosen drug could mitigate the distinguishing molecular features of primary CMS4 cancer. Methods ImPACCT trial, informed consent was obtained for subtyping at initial diagnosis using validated RT-qPCR CMS4-test on three biopsies per tumor (Phase-1, n=69 patients), neoadjuvant CMS4-targeting imatinib...
Introduction Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics this setting. This study aims to explore these parameters PM who receive repetitive ePIPAC-OX monotherapy. Methods analysis...
Introduction Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases colorectal origin a low/moderate abdominal disease load. In case cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that less effective against than it haematogenous spread cancer. It suggested may...
Eur J Clin Invest 2011; 41 (8): 820–827 Abstract Background A recent meta-analysis showed that both plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity independently predict cardiovascular events. Notably, Lp-PLA2 but not was found to be a determinant of outcome in type 2 diabetes mellitus. We questioned whether relationships carotid intima media thickness (IMT), measure subclinical atherosclerosis, with differ between diabetic nondiabetic subjects. Materials methods...
Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) cytoreductive surgery in resectable patients shows limited benefit, novel treatments urgently needed. The majority CRC-PMs represent CMS4 molecular subtype CRC, here we queried vulnerabilities this pharmacogenomic databases identify therapies. This reveals copper ionophore elesclomol...
Plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) predicts incident cardiovascular disease and is associated preferentially with negatively charged apolipoprotein B-containing lipoproteins. The plasma cholesteryl ester transfer (CET) process, which contributes to low high-density lipoprotein cholesterol small, dense low-density lipoproteins, affected by the composition concentration of acceptor lipoproteins.We tested relationships CET Lp-PLA(2) in subjects without metabolic...
Introduction Despite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy oxaliplatin (ePIPAC-OX), hereinafter referred to as bidirectional therapy, has never been prospectively investigated in patients colorectal peritoneal metastases (CPM). As a first step address this evidence gap, the present study aims assess safety, feasibility, antitumour activity, patient-reported outcomes, costs and pharmacokinetics...
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2) ) is a novel cardiovascular risk marker, which predominantly complexed to apolipoprotein (apo) B-containing lipoproteins in human plasma. As increasing dietary sodium intake may decrease plasma apoB-containing lipoproteins, we tested whether challenge lowers Lp-PLA(2) mass, as well the levels of lipoprotein particles carrying (apoB-Lp-PLA(2) ), employing newly developed enzyme-linked immunosorbent assay.In 45 women and 31 men (mean age 44...
Abstract Introduction: Circulating tumor DNA (ctDNA) from plasma is a promising biomarker. Patients with metastatic colorectal cancer (CRC) often have high ctDNA levels compared to other types. However, it unclear whether this also the case for patients peritoneal metastases CRC. Aim: To compare propensity of shedding by isolated liver and Methods: Plasma was collected 100 CRC (64% male, mean age 60 [SD=10] years) unresectable metastasis (CRC-LM). ascites were obtained 20 (60% 63 [SD=9.8]...