A5013238098- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- T-cell and B-cell Immunology
- Neurogenesis and neuroplasticity mechanisms
- Immune Cell Function and Interaction
- Lanthanide and Transition Metal Complexes
- Advanced Breast Cancer Therapies
- Brain Metastases and Treatment
- MRI in cancer diagnosis
- HER2/EGFR in Cancer Research
- Ultrasound and Hyperthermia Applications
- Melanoma and MAPK Pathways
- Hereditary Neurological Disorders
- Nanoparticle-Based Drug Delivery
- COVID-19 and healthcare impacts
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Mathematical Biology Tumor Growth
- Cellular Mechanics and Interactions
- Immunotherapy and Immune Responses
Massachusetts General Hospital
2015-2022
Marion General Hospital
2022
University of Lausanne
2018-2022
Harvard University
2015-2021
University Hospital of Lausanne
2018
University of Freiburg
2008
Significance Improving survival of patients with glioblastoma (GBM) using antiangiogenic therapy remains a challenge. In this study we show that dual blockade angiopoietin-2 and vascular endothelial growth factor delays tumor enhances benefits through reprogramming tumor-associated macrophages toward an antitumor phenotype as well by pruning immature vessels. The immunomodulatory potential supports clinical testing approach for GBM other immunotherapeutic approaches such checkpoint blockers.
Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2) compromises the benefits receptor (VEGFR) treatment in murine GBM models and circulating Ang-2 levels patients rebound after an initial decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor) administration. Here we tested whether dual inhibition VEGFR/Ang-2 could improve survival two orthotopic GBM, Gl261 U87. Dual therapy using...
Significance Improved penetration along with accurate prediction and mechanistic understanding of anticancer agent delivery across the blood–brain/blood–tumor barrier (BBB/BTB) are essential for rational development effective therapeutic strategies in intracranial malignancies. In this study, we provide insights drug pharmacokinetics brain metastases after focused ultrasound-induced BBB/BTB disruption by integrating quantitative microscopy mathematical modeling. We demonstrate that...
Abstract Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma (GBM) trials. Here, we show that regulatory T (Treg) cells play a key role GBM resistance to ICBs experimental gliomas. Targeting glucocorticoid-induced TNFR-related receptor (GITR) Treg using an agonistic antibody (αGITR) promotes CD4 cell differentiation into effector cells, alleviates cell-mediated suppression of anti-tumor immune response, and induces potent GBM. The reprogrammed GBM-infiltrating express...
The brain microenvironment triggers HER3-dependent de novo resistance to therapies targeting PI3K or HER2 in HER2-positive and/or PIK3CA -mutant breast cancer cells.
The cerebral cortex is essential for integration and processing of information that required most behaviors. exquisitely precise laminar organization the arises during embryonic development when neurons migrate successively from ventricular zones to coalesce into specific cortical layers. While radial glia act as guide rails projection neuron migration, pre-formed vascular networks provide support guidance cues GABAergic interneuron migration. This study provides novel conceptual mechanistic...
Central nervous system (CNS) metastases represent a major problem in the treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer because disappointing efficacy HER2-targeted therapies against brain lesions. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown trastuzumab-resistant systemic cancer. Here, we tested hypothesis that T-DM1 could overcome trastuzumab resistance murine models metastases. We treated female nude mice bearing BT474 or...
Abstract OBJECTIVE: We aimed to enhance the efficacy of anti-VEGF therapy in glioblastoma (GBM) through additional inhibition Angiopoietin-2 (Ang-2), a potential mediator resistance antiangiogenic using VEGF inhibition. INTRODUCTION: Glioblastoma is uniformly lethal primary brain tumor affecting more than 12.000 patients every year US alone. The standard regimen for this highly angiogenic entity comprises maximal safe resection and chemoradiation with temozolomide. addition (anti-VEGF) care...
Abstract OBJECTIVE: Here we aimed to overcome resistance anti-VEGF therapy in glioblastoma (GBM), the most common and aggressive adult primary brain tumor. INTRODUCTION: Current standard of care, including chemo-radiation, confers modest overall survival benefits less than 1.5 years patients. GBMs are highly dependent on angiogenesis, is a promising approach prolong survival. While prolongs progression-free GBM, patients rapidly become refractory not increased. We previously demonstrated...
Abstract Glioblastoma (GBM) shows high level of resistance to currently available treatments including the standard care and immunotherapy, representing most fatal cancer type. Our study revealed that immune suppression by regulatory T cells (Treg) secondary therapy with checkpoint blocker (anti-PD1) confers this resistance. In GBM tumor microenvironment, Treg increased suppressive phenotype were found which frequency anergic increase after ICB therapy, potentially contributing Targeting has...
Glioblastoma almost always recurs following standard therapy with surgery and chemoradiation. The addition of anti-VEGF to the treatment regimen did not increase dissatisfactory overall survival GBM patients. Our previous clinical data suggest that may reduce anti-tumor immune response. Furthermore we have previously shown angiopoietin-2 (Ang-2) overexpression confers resistance in preclinical GBM. Here show combined Ang-2/VEGF inhibition a bispecific monoclonal antibody could overcome by...
Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2) compromises the benefits anti- VEGF receptor (VEGFR) treatment in murine GBM models and circulating Ang-2 levels patients rebound after an initial decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor) administration. Here we tested whether dual inhibition VEGFR/Ang-2 could improve survival two orthotopic GBM, Gl261 U87. Dual...
Abstract Brain metastases represent a devastating progression of luminal breast cancer. While targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed evade PI3K inhibition despite efficient drug delivery. comparison extracranial disease, there is increased HER3 expression and phosphorylation lesions. blockade overcomes...
Removed.
Blood-brain/blood-tumor barriers (BBB and BTB) interstitial transport may constitute major obstacles to the of therapeutics in brain tumors. In this study, we examined impact focused ultrasound (FUS) combination with microbubbles on two relevant chemotherapy-based anticancer agents HER2-positive breast cancer metastases at cellular resolution: doxorubicin, a non-targeted low molecular weight chemotherapeutic, ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate. Using orthotopic...
Abstract The compression of brain tissue by a tumor mass is believed to be major cause the clinical symptoms seen in patients. However, biological consequences these physical stresses on are unknown. Using imaging and preclinical studies, we discovered that subgroup primary metastatic tumors, classified as nodular based growth pattern, exert compressive solid stress surrounding tissue, leading decrease local vascular perfusion, well neuronal death impaired function. We demonstrated causal...