A5065827707- Lymphatic System and Diseases
- Angiogenesis and VEGF in Cancer
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Sympathectomy and Hyperhidrosis Treatments
- Photoacoustic and Ultrasonic Imaging
- Planarian Biology and Electrostimulation
- Optical Coherence Tomography Applications
- Lymphatic Disorders and Treatments
- Cardiovascular Health and Disease Prevention
- Advanced Fluorescence Microscopy Techniques
- Cellular Mechanics and Interactions
- Immune Cell Function and Interaction
- Cerebrospinal fluid and hydrocephalus
- Vascular Tumors and Angiosarcomas
- Cancer, Hypoxia, and Metabolism
- Nanoplatforms for cancer theranostics
- Cardiac tumors and thrombi
- Cancer Genomics and Diagnostics
- Lattice Boltzmann Simulation Studies
- Immune cells in cancer
- Vascular Malformations and Hemangiomas
- Diagnosis and Treatment of Venous Diseases
- Cancer Research and Treatments
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Lear (United States)
2023
Bucknell University
2023
Beth Israel Deaconess Medical Center
2019
Samsung Medical Center
2015
Sungkyunkwan University
2015
Duke Medical Center
2015
Brigham Young University
2015
University of Calgary
2015
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...
Profound hearing loss is a serious complication of neurofibromatosis type 2, genetic condition associated with bilateral vestibular schwannomas, benign tumors that arise from the eighth cranial nerve. There no medical treatment for such tumors.We determined expression pattern vascular endothelial growth factor (VEGF) and three its receptors, VEGFR-2, neuropilin-1, neuropilin-2, in paraffin-embedded samples 21 schwannomas 2 22 sporadic schwannomas. Ten consecutive patients progressive who...
An alternate route for metastatic cells Metastatic tumor are thought to reach distant organs by traveling through the blood circulation or lymphatic system. Two studies of mouse models now suggest a hybrid cell dissemination. Pereira et al. and Brown used distinct methodologies monitor fate in lymph nodes. They found that could invade local vessels within node, exit node entering circulation, then go on colonize lung. Whether this dissemination occurs cancer patients is unknown; answer...
Abstract Preclinical and clinical studies positively correlate the expression of vascular endothelial growth factor (VEGF)-C in tumors incidence lymph node metastases. However, how VEGF-C regulates individual steps transport tumor cells from primary to draining nodes is poorly understood. Here, we image quantify these growing tip mouse ear using intravital microscopy lymphatic vessels node, which receives spontaneously shed cells. We show that overexpression cancer induces hyperplasia...
To trigger an effective immune response, antigen and antigen-presenting cells travel to the lymph nodes via collecting lymphatic vessels. However, our understanding of regulation vessel function transport is limited. dissect molecular control function, we developed a unique mouse model that allows intravital imaging autonomous contraction. Using this method, demonstrated endothelial nitric oxide synthase (eNOS) in required for robust contractions under physiological conditions. By contrast,...
Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival benefit, as tumors rapidly develop resistance to these agents. Here, we have uncovered an immunosuppressive role nonclassical Ly6Clo monocytes that mediates anti-VEGFR2 treatment. We found the chemokine CX3CL1 was upregulated in both human and murine following VEGF signaling blockade, resulting recruitment of CX3CR1+Ly6Clo into tumor. also treatment with VEGFA reduced expression endothelial cells vitro....
Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vascular endothelial growth factor (VEGF)-C and VEGF-D were identified. However, the mechanistic understanding lymphatic still in infancy. Nitric oxide (NO) plays crucial role regulating blood vessel function well function. NO synthase (NOS) expression correlates with metastasis. causal relationship between NOS has not been documented. To this end, we first show that both...
Antiangiogenic therapy with antibodies against VEGF (bevacizumab) or VEGFR2 (ramucirumab) has been proven efficacious in colorectal cancer (CRC) patients. However, the improvement overall survival is modest and only combination chemotherapy. Thus, there an urgent need to identify potential underlying mechanisms of resistance specific antiangiogenic develop strategies overcome them. Here we found that anti-VEGFR2 up-regulates both C-X-C chemokine ligand 12 (CXCL12) receptor 4 (CXCR4)...
The solid tumor microvasculature is characterized by structural and functional abnormality mediates several deleterious aspects of behavior. Here we determine the role vascular endothelial protein tyrosine phosphatase (VE-PTP), which deactivates cell (EC) Tie-2 receptor kinase, thereby impairing maturation vessels.AKB-9778 a first-in-class VE-PTP inhibitor. We examined its effects on ECs in vitro embryonic angiogenesis vivo using zebrafish assays. studied impact AKB-9778 therapy vasculature,...
Background:To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth not been reported.
An adjuvant composed of saponin and a TLR4 agonist acts by enhancing lymph flow antigen entry into nodes.
Tumor-draining lymph nodes (TDLNs) are important for tumor antigen–specific T cell generation and effective anticancer immune responses. However, TDLNs often the primary site of metastasis, causing suppression worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer heterogeneity, plasticity, evasion during breast progression node metastasis (LNM). A subset cells in exhibited elevated MHC class II (MHC-II) gene expression both mice humans....