A5027437473- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Angiogenesis and VEGF in Cancer
- Cancer Research and Treatments
- Herpesvirus Infections and Treatments
- Protease and Inhibitor Mechanisms
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Cancer, Stress, Anesthesia, and Immune Response
- Ultrasound and Hyperthermia Applications
- Neuroendocrine Tumor Research Advances
- Viral Infectious Diseases and Gene Expression in Insects
- 3D Printing in Biomedical Research
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Nanoplatforms for cancer theranostics
- MRI in cancer diagnosis
- Mechanisms of cancer metastasis
- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Cancer Treatment and Pharmacology
- Hepatocellular Carcinoma Treatment and Prognosis
Université Paris Cité
2015-2025
Sorbonne Paris Cité
2024-2025
Pitié-Salpêtrière Hospital
2025
Sorbonne Université
2025
Assistance Publique – Hôpitaux de Paris
2022-2025
Inserm
2025
Massachusetts General Hospital
2014-2024
Harvard University
2014-2024
University of Zagreb
2022
Poznan University of Medical Sciences
2022
Abstract Elevated interstitial fluid pressure, a hallmark of solid tumors, can compromise the delivery therapeutics to tumors. Here we show that blocking vascular endothelial growth factor (VEGF) signaling by DC101 (a VEGF-receptor-2 antibody) decreases not restoring lymphatic function, but producing morphologically and functionally “normalized” network. We demonstrate normalization process prunes immature vessels improves integrity function remaining vasculature enhancing perivascular cell...
Lymphatic metastasis contributes to mortality from solid tumors. Whether metastasizing cancer cells reach lymph nodes via intratumor lymphatic vessels is unknown. Here, we examine functional lymphatics associated with mouse tumors expressing normal or elevated levels of vascular endothelial growth factor-C (VEGF-C), a molecule that stimulates lymphangiogenesis. Although VEGF-C overexpression increased surface area in the tumor margin and metastasis, these contained no lymphatics, as assessed...
Cancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels, thus reducing vascular perfusion. Tumour interstitial matrix also contributes solid stress, with hyaluronan implicated as the primary molecule responsible for vessel compression because of its swelling behaviour. Here we show, unexpectedly, that compresses vessels only in collagen-rich tumours, suggesting collagen together are critical targets decompressing vessels. We demonstrate...
The presence of growth-induced solid stresses in tumors has been suspected for some time, but these were largely estimated using mathematical models. Solid can deform the surrounding tissues and compress intratumoral lymphatic blood vessels. Compression vessels elevates interstitial fluid pressure, whereas compression reduces flow. Reduced flow, turn, leads to hypoxia, which promotes tumor progression, immunosuppression, inflammation, invasion, metastasis lowers efficacy chemo-, radio-,...
The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan--a clinically approved angiotensin II receptor antagonist with noted antifibrotic activity--can enhance nanomedicine. found that losartan inhibited I production by carcinoma-associated fibroblasts isolated from breast cancer biopsies. Additionally, it led to a dose-dependent reduction stromal desmoplastic models human breast, pancreatic, skin mice....
The large size of many novel therapeutics impairs their transport through the tumor extracellular matrix and thus limits therapeutic effectiveness. We propose that composition, structure, distribution determine properties in tumors. Furthermore, because characteristics largely depend on tumor–host interactions, we postulate diffusion macromolecules will vary with type as well anatomical location. Diffusion coefficients liposomes tumors growing cranial windows (CWs) dorsal chambers (DCs) were...
Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such affects tumor cell behavior. Here we show that stimulates migration of mammary carcinoma cells. The enhanced accomplished by subset “leader cells” extend filopodia at the leading edge sheet. Formation these leader cells dependent on microorganization and stress. Accompanied fibronectin deposition stronger cell–matrix adhesion, transition to leader-cell phenotype...
To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer explore biomarkers for response.
Significance Preclinical studies have suggested that Hedgehog (Hh) pathway inhibition reduces growth and metastasis of pancreatic ductal adenocarcinoma (PDA), but ensuing clinical trials Hh antagonists combined with cytotoxic chemotherapy not succeeded. Here, we find in three distinct genetically engineered mouse models genetic pharmacologic activity actually accelerates PDA progression. Furthermore, the acute modulation regulates balance between epithelial stromal elements, causing...
Patients with locally advanced pancreatic cancer have historically poor outcomes. Evaluation of a total neoadjuvant approach is warranted.To evaluate the margin-negative (R0) resection rate FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) losartan followed by chemoradiotherapy for cancer.A single-arm phase 2 clinical trial was conducted at large academic hospital from August 22, 2013, to May 2018, among 49 patients previously untreated unresectable as determined...
Abstract Oncolytic viral therapy provides a promising approach to treat certain human malignancies. These vectors improve on replication-deficient by increasing the load within tumors through preferential replication tumor cells. However, inability efficiently propagate throughout entire and infect cells distant from injection site has limited capacity of oncolytic viruses achieve consistent therapeutic responses. Here we show that spread herpes simplex virus (HSV) vector MGH2 melanoma Mu89...
It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, promotes inflammation and fibrosis. We found mouse models of PDAC that also desmoplasia associated accelerated tumor growth impaired delivery/efficacy chemotherapeutics through reduced perfusion. Genetic pharmacologic inhibition angiotensin-II type-1 receptor reverses obesity-augmented improves response to chemotherapy. Augmented activation stellate cells...