A5063906475- Cancer, Hypoxia, and Metabolism
- Advanced MRI Techniques and Applications
- Electron Spin Resonance Studies
- Medical Imaging Techniques and Applications
- Lanthanide and Transition Metal Complexes
- Cutaneous Melanoma Detection and Management
- Cancer, Lipids, and Metabolism
- melanin and skin pigmentation
- Melanoma and MAPK Pathways
- MRI in cancer diagnosis
- Advanced NMR Techniques and Applications
- ATP Synthase and ATPases Research
- bioluminescence and chemiluminescence research
- Cancer Immunotherapy and Biomarkers
- Mitochondrial Function and Pathology
- Radiopharmaceutical Chemistry and Applications
- Cancer Research and Treatments
- Advanced Neuroimaging Techniques and Applications
- Protein Tyrosine Phosphatases
- Metabolism, Diabetes, and Cancer
- Lung Cancer Treatments and Mutations
- Radiation Effects and Dosimetry
- HER2/EGFR in Cancer Research
- Sulfur Compounds in Biology
- Redox biology and oxidative stress
UCLouvain
2013-2024
Solvay (Belgium)
2023-2024
Moffitt Cancer Center
2013
Cliniques Universitaires Saint-Luc
2012
Solid tumors are generally characterized by an acidic tumor microenvironment (TME) that favors cancer progression, therapy resistance and immune evasion. By single-cell RNA-sequencing analysis in individuals with pancreatic ductal adenocarcinoma (PDAC), we reveal solute carrier family 4 member (SLC4A4) as the most abundant bicarbonate transporter, predominantly expressed epithelial cells. Functionally, SLC4A4 inhibition PDAC cells mitigates acidosis of TME due to accumulation extracellular...
Background Despite their revolutionary success in cancer treatment over the last decades, immunotherapies encounter limitations certain tumor types and patients. The efficacy of depends on antigen-specific CD8 T-cell viability functionality within immunosuppressive microenvironment, where oxygen levels are often low. Hypoxia can reduce fitness several ways T cells mostly excluded from hypoxic regions. Given challenges to achieve durable reduction hypoxia clinic, ameliorating survival...
Abstract Lactate exchange between glycolytic and oxidative cancer cells is proposed to optimize tumor growth. Blocking lactate uptake through monocarboxylate transporter 1 (MCT1) represents an attractive therapeutic strategy but may stimulate glucose consumption by cells. We report here that inhibition of mitochondrial pyruvate carrier (MPC) activity fulfils the tasks blocking use while preventing metabolism. Using in vitro 13 C-glucose vivo hyperpolarized C-pyruvate, we identify 7ACC2 as a...
Anti-epidermal growth factor receptor (EGFR) therapy (cetuximab) shows a limited clinical benefit for patients with locally advanced or recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), due to the frequent occurrence of secondary resistance mechanisms. Here we report that cetuximab-resistant HNSCC cells display peroxisome proliferator-activated alpha (PPARα)-mediated lipid metabolism reprogramming, increased fatty acid uptake oxidation capacities, while glycolysis is not...
Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance treatments. Targeting transporters involved in the regulation tumor pH constitutes a promising anti-tumor approach, would disrupt cellular homeostasis negatively impact growth. In this study, we evaluated syrosingopine, inhibitor MCT1 MCT4, modulator metabolism extracellular human breast cancer (MDA-MB-231) pharyngeal squamous cell...
Abstract Purpose Low frequency EPR can noninvasively detect endogenous free radical melanin in melanocytic skin lesions and could potentially discriminate between benign atypical nevi malignant melanoma lesions. We recently succeeded demonstrating the ability of clinical to patients. However, signal-to-noise ratio (SNR) was extremely low warranting further research boost sensitivity detection. In present study, we assessed performance a system with capability perform multi-harmonic (MH)...
Targeted chemotherapeutic agents often do not result in tumor shrinkage, so new biomarkers that correlate with clinical efficacy are needed. In this study, we investigated noninvasive imaging protocols to monitor responses sorafenib, a multikinase inhibitor approved for treatment of renal cell and hepatocellular carcinoma. Healthy cells impermeable fumarate, conversion metabolite malate as detected by (13)C-magnetic resonance spectroscopy (MRS) has been suggested one marker death response...
Abstract Hexafluorobenzene (HFB) and perfluoro‐15‐crown‐5‐ether (15C5) were compared as fluorine reporter probes of tissue oxygenation using 19 F MRI for dynamic assessment muscle oxygenation, with special focus on toxicity the probes, consecutive alteration animal behavior. The latter also in terms sensitivity to changes well signal‐to‐noise ratio accurate p O 2 measurements. For that purpose, mouse muscles imaged at 11.7 T, 2‐ 36‐h after intramuscular injection HFB or 15C5. Histological...
Because of its paramagnetic properties, oxygen may act as an endogenous magnetic resonance imaging contrast agent by changing proton relaxation rates. Changes in tissue concentrations have been shown to produce changes rate R1 water. The aim the study was improve sensitivity enhanced exploiting higher solubility lipids (as compared with water) sensitively monitor levels selectively measuring lipids.The method, acronym "MOBILE" (mapping enhancement), applied different mouse models hypoxic...
We explored the capability of low-frequency Electron Paramagnetic Resonance (EPR) to noninvasively detect melanin (a stable semiquinone free radical) in human skin. As previous vitro studies on biopsies suggested that EPR signal from was different when measured skin melanomas or benign nevi, we conducted a prospective first-in-man clinical study patients with lesions suspicious melanoma. spectra were obtained using spectrometer operating at 1 GHz, surface coil placed over area interest. Two...
Abstract Epidemiological studies have shown that obese subjects an increased risk of developing triple‐negative breast cancer (TNBC) and overall reduced survival. However, the relation between obesity TNBC remains difficult to understand. We hypothesize apelin, adipokine whose levels are in obesity, could be a major factor contributing both tumour growth metastatization patients. observed development under high‐fat diet tumour‐bearing mice significantly growth. By showing no effect...
(1) Background: The acidosis of the tumor micro-environment may have profound impact on cancer progression and efficacy treatments. In present study, we evaluated a treatment with UK-5099, mitochondrial pyruvate carrier (MPC) inhibitor extracellular pH (pHe); (2) Methods: glucose consumption, lactate secretion acidification rate (ECAR) were measured in vitro after exposure cervix SiHa cells breast 4T1 to UK-5099 (10 µM). Mice bearing model treated daily during four days (3 mg/kg). pHe was...
Obesity is characterized by an excessive fat mass accumulation associated with multiple disorders, including impaired glucose homeostasis, altered adipokine levels, and hyperlipidemia. Despite clear associations between tumor progression obesity, the effects of these disorders on metabolism remain largely unknown. Thus, we studied metabolic differences tumors obese lean mice in murine models triple-negative breast cancer (E0771 PY8819). For this purpose, a real-time hyperpolarized...
There is currently no consensus to determine which advanced melanoma patients will benefit from targeted therapy, immunotherapy, or a combination of both, highlighting the critical need identify early-response biomarkers therapy. The goal this review provide scientific rationale highlight potential role metabolic imaging assess response and/or immune therapy in cancer. For that purpose, brief overview current treatments provided. Then, knowledge with respect metabolism described an emphasis...
Melanoma is the most dangerous form of skin cancer and its incidence rising each year. Because current methods diagnosis based on visual aspect tumor show limitations, several new techniques are emerging to help in this diagnosis, amongst which magnetic resonance imaging (MRI) electron paramagnetic (EPR). The origin typical contrast pattern observable melanoma T 1 ‐ 2 ‐weighted images remains be elucidated a source controversy. In addition, melanin could create sufficient inhomogeneities...
The cholinic phenotype, characterized by elevated phosphocholine and a high production of total-choline (tCho)-containing metabolites, is metabolic hallmark cancer. It can be exploited for targeted therapy. Non-invasive imaging biomarkers are required to evaluate an individual's response anticancer agents that usually do not rapidly cause tumor shrinkage. Because changes manifest at earlier stages therapy than in size, the aim current study was (1)H-MRS diffusion-weighted MRI (DW-MRI) as...
Abstract Nearly all melanoma patients with a BRAF‐activating mutation will develop resistance after an initial clinical benefit from BRAF inhibition (BRAFi). The aim of this work is to evaluate whether metabolic imaging using hyperpolarized (HP) 13 C pyruvate can serve as marker early response BRAFi in melanoma, by exploiting the effects BRAFi. Mice bearing human xenografts were treated vemurafenib or vehicle. In vivo HP magnetic resonance spectroscopy was performed at baseline and 24 hours...
Optimal head and neck squamous cell carcinoma (HNSCC) patient selection for anti-EGFR-based therapy remains an unmet need since only a minority of patients derive long-term benefit from cetuximab treatment. We assessed the ability state-of-the-art noninvasive in vivo metabolic imaging to probe shift cetuximab-sensitive -resistant HNSCC patient-derived tumor xenografts (PDTXs).Three models selected based on their known sensitivity (cetuximab-sensitive or acquired-resistant HNC007 PDTXs,...
Abstract Hypoxic tumors are radioresistant stemming from the fact that oxygen promotes reactive species (ROS) propagation after water radiolysis and stabilizes irradiation-induced DNA damage. Therefore, an attractive strategy to radiosensitize solid is increase tumor oxygenation at time of irradiation, ideally above a partial pressure 10 mm-Hg which full radiosensitization can be reached. Historically, many attempts vascular O 2 delivery have had limited efficacy, but mathematical models...