A5054729546- Cancer, Lipids, and Metabolism
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Fatty Acid Research and Health
- Cholesterol and Lipid Metabolism
- Immune cells in cancer
- Inflammatory mediators and NSAID effects
- Mesenchymal stem cell research
- Cancer Research and Treatments
- Chemokine receptors and signaling
- Drug Transport and Resistance Mechanisms
- Cancer Treatment and Pharmacology
- Sphingolipid Metabolism and Signaling
- 14-3-3 protein interactions
- Monoclonal and Polyclonal Antibodies Research
- Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- TGF-β signaling in diseases
- Diet, Metabolism, and Disease
- Cancer therapeutics and mechanisms
- Lipid metabolism and biosynthesis
- RNA modifications and cancer
- Tissue Engineering and Regenerative Medicine
- Management of metastatic bone disease
- MicroRNA in disease regulation
The Netherlands Cancer Institute
2014-2024
Oncode Institute
2016-2023
Cancer Genomics Centre
2017
University Medical Center Utrecht
2011-2014
Utrecht University
2011-2014
Abstract Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function heterogeneity, little is known regarding origin CAFs. Understanding CAF heterogeneity needed to develop successful CAF-based targeted therapies. Through various transplantation studies mice, we show that CAFs both invasive lobular breast cancer triple-negative originate from mammary...
Metastatic breast cancer cannot be treated successfully. Currently, the targeted therapies for metastatic disease are limited to human epidermal growth factor receptor 2 and hormone antagonists. Understanding mechanisms of metastasis is therefore crucial development new intervention strategies. Here, we show that FER kinase (FER) controls migration invasive cell lines by regulating α6- β1-integrin-dependent adhesion. Conversely, overexpression in non-metastatic cells induces pro-invasive...
Our research group previously identified specific endogenous platinum-induced fatty acids (PIFAs) that, in picomolar quantities, activate splenic macrophages leading to resistance chemotherapy mouse models. Fish oil was shown contain the PIFA 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) and when administered mice neutralized activity.Because patients with cancer frequently use fish supplements, we set out determine exposure after intake of or oil.(1) In November 2011, 400 undergoing...
Bone is one of the most frequent sites for breast cancer metastasis. Breast bone metastasis (BCBM) leads to skeletal morbidities including pain, fractures, and spinal compression, all which severely impact quality life. Immunotherapy a promising therapy patients with advanced cancer, but whether it may provide benefit metastatic currently unknown. Thus, better understanding immune landscape bone-disseminated cancers reveal new therapeutic strategies. In this study, we use histopathological...
Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) induces systemic resistance a broad range of DNA-damaging chemotherapeutics. We show that exerts its effect by activating splenic F4/80+/CD11blow macrophages, which results in production chemoprotective lysophosphatidylcholines (LPCs). Pharmacologic studies, together with analysis expression patterns,...
Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development alcoholism caused by alcohol-induced maladaptive changes in neural circuits involved emotions, motivation, and decision-making. Because its involvement these processes, the amygdala thought to be key structure alcohol addiction. However, molecular mechanisms govern are incompletely understood. We have previously shown limited access choice paradigm, C57BL/6J mice progressively escalate their...
GREMLIN1 (GREM1) is member of a family structurally and functionally related secreted cysteine knot proteins, which act to sequester inhibit the action multifunctional bone morphogenetic proteins (BMPs). GREM1 binds directly BMP dimers, thereby preventing BMP-mediated activation type I II receptors. Multiple reports identify overexpression as contributing factor in broad range cancers. Additionally, gene amplified rare autosomal dominant inherited form colorectal cancer. The inhibitory...
Mesenchymal stem cells (MSCs) can play a vital role in tumor progression and anticancer therapy response, as demonstrated by various vitro vivo model systems. Their ability to home developing tumors modulate the microenvironment, suppressing T-cell responses contributing stroma, is suggested have significant impact on disease progression, metastasis formation, response. Most evidence, however, derived from artificial models using exogenously administered MSCs. The contribution of endogenous...
Abstract Immunotherapy has been far less effective in breast cancer compared to other types, with only a small fraction of patients having clinical benefit. Historically, invasive lobular carcinomas (ILC), the second most common histological subtype cancer, have categorized as immunological cold tumors, but recent studies suggest that ILCs may recruit myeloid-rich immunosuppressive immune landscape. Cancer cell intrinsic features such genetic makeup tumor cells can dictate spatial...
Abstract Although chemotherapy is designed to eradicate tumor cells it also has a significant impact on normal tissues. These host-responses can have large effects the efficacy of treatment and overall survival. Fatty acids are increasingly recognized play important signaling roles. 12-S-HHT 16:4(n-3) two platinum-induced fatty (PIFAs) that induce systemic resistance broad range DNA-damaging chemotherapeutics. PIFAs exert their chemoprotective effect via an indirect mechanism involving...
Abstract The development of resistance to chemotherapy is one the most important obstacles continued effective treatment cancer in patients. We recently identified an network that responsible for reversible systemic chemotherapy. Mesenchymal stem cells (MSCs), activated by chemotherapy, secrete two specific polyunsaturated fatty acids confer a broad spectrum anti-cancer agents. These distinct platinum-induced (PIFAs), 12-S-keto-5,8,10-heptadecatrienoic acid (KHT) and...
Abstract Background: Chemotherapy remains the primary treatment for most disseminated cancers. However, response to chemotherapy is often transient and development of resistance one significant obstacles effective cancer therapy. Although various tumor-cell intrinsic mechanisms drug have been identified, it becoming increasingly clear that tumor micro-environment plays a key role in We recently identified two unique polyunsaturated fatty acids (PIFAs), 12-oxo-5,8,10-heptadecatrienoic acid...
Abstract Background: We recently identified two fatty acids (PIFAs) that induced chemoresistance in mouse models. At picomolar concentrations, PIFAs 16:4(n-3) and KHT interfered with the antitumor activity of a broad spectrum chemotherapeutics. Our aim was to unravel mechanism through which prevent chemotherapy-induced tumor cell death. Results: In several animal models, were found interfere early effects Four hours after administration cisplatin significant decreases proliferation (BrdU)...