- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Tissue Engineering and Regenerative Medicine
- Esophageal Cancer Research and Treatment
- Angiogenesis and VEGF in Cancer
- Cancer Genomics and Diagnostics
- Gastric Cancer Management and Outcomes
- Radiomics and Machine Learning in Medical Imaging
- MRI in cancer diagnosis
- Spaceflight effects on biology
- High Altitude and Hypoxia
- Heme Oxygenase-1 and Carbon Monoxide
- Pancreatitis Pathology and Treatment
- Cancer, Hypoxia, and Metabolism
- Bone and Dental Protein Studies
- Epigenetics and DNA Methylation
- Heart Rate Variability and Autonomic Control
- Hedgehog Signaling Pathway Studies
- Metastasis and carcinoma case studies
- Cancer Treatment and Pharmacology
- COVID-19 Clinical Research Studies
- Dermatological and COVID-19 studies
- TGF-β signaling in diseases
- Sepsis Diagnosis and Treatment
- Inflammatory mediators and NSAID effects
Australian National University
2022-2024
University of Amsterdam
2018-2020
Amsterdam University Medical Centers
2019-2020
Oncode Institute
2019-2020
Amsterdam UMC Location University of Amsterdam
2015-2018
Cancer Center Amsterdam
2017
Wilhelmina Children's Hospital
2015
University Medical Center Utrecht
2013-2015
Esophageal adenocarcinoma (EAC) has a dismal prognosis, and survival benefits of recent multimodality treatments remain small. Cancer-associated fibroblasts (CAFs) are known to contribute poor outcome by conferring therapy resistance various cancer types, but this not been explored in EAC. Importantly, targeted strategy circumvent CAF-induced yet be identified. By using EAC patient-derived CAFs, organoid cultures, xenograft models we identified IL-6 as the stromal driver activated...
Abstract Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all common cancers. However, divergent outcomes exist between patients, suggesting distinct underlying tumor biology. Here, we delineated this heterogeneity, compared interconnectivity classification systems, and experimentally addressed biology that drives poor outcome. RNA-sequencing 90 resected specimens unsupervised revealed four subgroups associated with outcomes. The worst-prognosis subtype was characterized by...
The upper gastrointestinal tract is home to some of most notorious cancers like esophagogastric and pancreatic cancer. Several factors contribute the lethality these tumors, but one that stands out for both tumor types strong inter- as well intratumor heterogeneity. Unfortunately, genetic models do not match this heterogeneity, esophageal cancer no adequate exist. To allow an improved understanding diseases, tissue banks with sufficient amount samples cover extent diversity human are...
To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in treatment hospitalised patients with COVID-19.Retrospective, uncontrolled multicentre single-arm case series laboratory-confirmed COVID-19, treated UFH (5000 IU q8h, 10 000 q4h, or 25 q6h) for 6 ± 3 (mean standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before (baseline) highest-level during (peak), adverse events including bleeding. Exploratory efficacy...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundance of stroma. Multiple molecular classification efforts have identified a mesenchymal tumor subtype that consistently high-grade growth and poor clinical outcome. The relation between PDAC stroma subtypes still unclear. Here, we aimed to identify how cells instruct the main cellular component stroma, pancreatic stellate (PSCs). We found in primary tissue had reduced collagen deposition compared low-grade PDAC. Xenografts...
Patient stratification based on biological variation in pancreatic ductal adenocarcinoma (PDAC) subtypes could help to improve clinical outcome. However, noninvasive assessment of the entire tumor microenvironment remains challenging. In this study, we investigate basis dynamic contrast-enhanced (DCE), intravoxel incoherent motion (IVIM), and R2*-derived magnetic resonance imaging (MRI) parameters for characterization PDAC evaluate their prognostic potential patients. Patients diagnosed with...
Pancreatic ductal adenocarcinoma (PDAC) is marked by an abundant stromal deposition. This stroma suspected to harbor both tumor-promoting and tumor-suppressing properties. underscored the disappointing results of targeting in clinical studies. Given complexity tumor-stroma interaction PDAC, there a need identify proteins that are predominantly tumor-promoting. One possible candidate SPOCK1 we previously identified screening effort PDAC. We extensively mined PDAC gene expression datasets,...
Reconstruction of the bladder by means both natural and synthetic materials remains a challenge due to severe adverse effects such as mechanical failure. Here we investigate application spider major ampullate gland-derived dragline silk from Nephila edulis spider, biomaterial with outstanding properties slow degradation rate, potential scaffold for reconstruction studying cellular response primary cells this biomaterial. We demonstrate that without any additional biological coating supports...
Multimodality treatment has advanced the outcome of esophageal adenocarcinoma (EAC), but overall survival remains poor. Therapeutic pressure activates effective resistance mechanisms and we characterized these in response to currently used neoadjuvant against EAC: carboplatin, paclitaxel radiotherapy. We developed an vitro approximation this regimen applied it primary patient‐derived cultures. observed a heterogeneous epithelial‐to‐mesenchymal (EMT) high therapeutic exerted by...
Astronauts in a microgravity environment will experience significant changes their cardiopulmonary system. Up until now, there has always been the reassurance that they have real-time contact with experts on Earth. Mars crew however gaps communication of 20 min or more. In silico experiments are therefore needed to assess fitness fly for those future space flights Mars. this study, we present an open-source controlled lumped mathematical model system is able simulate short-term adaptations...
Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety PVP-I remains controversial. Its extended in current SARS-CoV-2 virus pandemic urges need to clarify features on cellular level. Our investigation epithelial, mesothelial, endothelial, and innate immune cells revealed that toxicity is caused by diatomic iodine (I 2 ), which rapidly released from fuel organic halogenation with fast first-order kinetics. Eukaryotic manifests at...
Anti‐angiogenic agents combined with chemotherapy is an important strategy for the treatment of solid tumors. However, survival benefit limited, urging improvement combination therapies. We aimed to clarify effects vascular endothelial growth factor receptor 2 (VEGFR2) targeting on hemodynamic function and penetration drugs in esophagogastric adenocarcinoma (EAC). Patient‐derived xenograft (PDX) models EAC were subjected long‐term short‐term anti‐VEGFR2 therapy followed by injection or...
Angiogenesis is essential for colorectal cancer (CRC) progression, as demonstrated by the beneficial clinical effects of therapeutics inhibiting VEGF signaling. However, alternative mechanisms neovascularization can develop, resulting in treatment failure. Previously we NF-κB-inducing kinase (NIK) contributes to pathological angiogenesis. Here, investigate NIK a therapeutic target endothelial cells (EC) CRC. To determine expression levels CRC tissues, immunostained both primary tumors and...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma and a hypoxic microenvironment. stellate cells (PSC) are activated hypoxia promote excessive desmoplasia, further contributing to the development of hypoxia. We aimed explore how interact contribute invasive growth in PDAC. [18F]HX4 PET/CT was found be feasible non-invasive method assess tumor 42 patients correlated with HIF1α immunohistochemistry matched surgical specimens. uptake were strong prognostic markers for...
Angiogenesis is critical to the growth of tumors. Vascularization-targeting agents, with or without cytotoxic drugs, are widely used for treatment several solid tumors including esophagogastric adenocarcinoma. However, little known about systemic effects anti-angiogenic therapies and how this affects pharmacokinetics intratumoral delivery agents. In study, patient-derived xenograft mouse models esophageal adenocarcinoma were identify DC101, a murine vascular endothelial factor receptor 2...
The space tourism industry is growing due to advances in rocket technology. Privatised travel exposes non-professional astronauts with health profiles comprising underlying conditions microgravity. Prior research has typically focused on the effects of microgravity human physiology healthy astronauts, and little known how may play out pathophysiology medical conditions, such as heart failure. This study used an established, controlled lumped mathematical model cardiopulmonary system simulate...
Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) ranks 4th on the list of cancer-related deaths which is mostly due to therapy resistance. The tumor microenvironment one main hallmarks contribute resistance in tumors are characterized by large amounts stroma deposition, and hypovascularization. In this study we assess use non-invasive functional magnetic resonance imaging (MRI) for characterization these characteristics its prognostic predictive role. Diffusion weighted (DWI)...
You have accessJournal of UrologyTrauma/Reconstruction: Trauma & Reconstructive Surgery III1 Apr 2014MP9-20 PRIMARY HUMAN UROTHELIAL CELL CULTURE ON A MATRIX OF SPIDER SILK; NOVEL TECHNIQUE IN BLADDER RECONSTRUCTION Anne Steins, Pieter Dik, Aart van Apeldoorn, Kerstin Reimers, Klijn, Tom de Jong, Paul Coffer, and Koen Schepers SteinsAnne Steins More articles by this author , DikPieter Dik ApeldoornAart Apeldoorn ReimersKerstin Reimers KlijnAart Klijn JongTom Jong CofferPaul Coffer...
: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all common cancers, but strongly divergent outcomes are apparent between patients. To reveal and address intertumor heterogeneity that contributes to this, we have performed RNA-Seq gene expression analysis on a large number resected PDAC samples (n=90). Unsupervised class discovery in this single-center PDAC-only dataset identified four subgroups with distinct clinical manifestations. Biological interpretation network...