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One or more keywords matched the following properties of Padera, Timothy
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overview As part of the Edwin L. Steele Laboratories for Tumor Biology, the Padera Laboratory examines the function of lymphatic vessels in health and disease, with an emphasis on the pathophysiology of tumor associated lymphatic vessels and lymphatic metastasis. Lymphatic vessels are responsible for draining interstitial fluid from tissues and for transporting immune cells to lymph nodes to maintain the body's immune surveillance. Lymphatic vessels also facilitate the dissemination of cancer cells from a primary tumor to regional lymph nodes. The mechanisms used by cancer cells to form lymph node metastasis are starting to be understood, with the hope of identifying treatment strategies to lower mortality due to disseminated cancer. In contrast to hematogenous metastasis, in which the primary tumor has functional blood vessels for cancer cells to invade, the story for lymphatic metastasis is likely more complicated as solid tumors seem to lack functional intratumor lymphatic vessels. Functional lymphatic vessels in the margin of tumors, however, seem sufficient for lymphatic metastasis to occur. Using intravital microscopy, we have investigated the individual steps of lymphatic metastasis. We can monitor lymphatic vessels in the tumor margin, observe tumor cells moving in lymphatic vessels, measure lymph flow and quantify the number of tumor cells that arrive in the draining lymph node. Our studies have shown that VEGF-C, which is associated with lymphatic metastasis in patients, increases the size of the tumor margin lymphatic vessels, making them more vulnerable to invasion. Our data suggests that VEGF-C needs to be blocked very early in the metastatic process to be able to reduce VEGF-C enhanced lymphatic metastasis. In addition to our work on metastasis, we have studied the molecular mechanisms that regulate the autonomous lymphatic contractions that drive lymph flow. Using novel animal models and intravital microscopy, we have shown that normal lymphatic contractions are reliant upon nitric oxide that is produced in specific locations at specific times. When the spatial and temporal control is lost during inflammation, the contractions stop and lymph function is impaired. Our future studies will continue to dissect the physical and molecular determinants of lymphatic vessel function and lymphangiogenesis in both normal and disease states. In addition we will continue to understand the mechanisms of cancer dissemination through lymphatic vessels and subsequent growth in lymph nodes. Through the use of our novel imaging technologies and animal models, we will answer timely questions that can lead to the development of treatments for lymphatic metastasis and lymphedema.
One or more keywords matched the following items that are connected to Padera, Timothy
Item TypeName
Academic Article Tumor oxygenation in hormone-dependent tumors during vascular endothelial growth factor receptor-2 blockade, hormone ablation, and chemotherapy.
Academic Article Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function.
Academic Article Prevention and treatment of lymphatic metastasis by antilymphangiogenic therapy.
Academic Article Development. Lymphatics make the break.
Academic Article Pathology: cancer cells compress intratumour vessels.
Academic Article Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular function and leukocyte recruitment: role of VEGF-receptor 2 and host VEGF-A.
Academic Article In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts.
Academic Article Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib.
Academic Article Anti-VEGFR-3 therapy and lymph node metastasis [corrected].
Academic Article LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.
Academic Article VEGFR3: a new target for antiangiogenesis therapy?
Academic Article Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging.
Academic Article Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis.
Academic Article Lymphatic metastasis in the absence of functional intratumor lymphatics.
Academic Article Multiscale measurements distinguish cellular and interstitial hindrances to diffusion in vivo.
Academic Article Impaired lymphatic contraction associated with immunosuppression.
Academic Article Local imbalance of proangiogenic and antiangiogenic factors: a potential mechanism of focal necrosis and dormancy in tumors.
Academic Article Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: therapeutic implications.
Academic Article Molecular mechanisms of metastasis.
Academic Article Correspondence re: S. Maula et al., intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinoma of the head and neck. Cancer Res., 63: 1920-1926, 2003.
Academic Article Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis.
Concept Colonic Neoplasms
Concept Breast Neoplasms
Concept Neoplasms, Hormone-Dependent
Concept Head and Neck Neoplasms
Concept Neoplasms, Experimental
Concept Meningeal Neoplasms
Concept Colorectal Neoplasms
Concept Pancreatic Neoplasms
Concept Mammary Neoplasms, Experimental
Concept Brain Neoplasms
Concept Lung Neoplasms
Concept Heart Neoplasms
Concept Skin Neoplasms
Concept Neoplasms
Concept Lymphatic Metastasis
Concept Soft Tissue Neoplasms
Concept Liver Neoplasms
Concept Neoplasm Metastasis
Academic Article Effects of vascular-endothelial protein tyrosine phosphatase inhibition on breast cancer vasculature and metastatic progression.
Academic Article Lymphatic function and immune regulation in health and disease.
Academic Article Novel molecular pathways in Gorham disease: implications for treatment.
Academic Article Compression of pancreatic tumor blood vessels by hyaluronan is caused by solid stress and not interstitial fluid pressure.
Academic Article Imaging the lymphatic system.
Academic Article Significance of lymph node metastasis in cancer dissemination of head and neck cancer.
Academic Article Local failure in parameningeal rhabdomyosarcoma correlates with poor response to induction chemotherapy.
Academic Article The lymph node microenvironment and its role in the progression of metastatic cancer.
Academic Article Cardiac and inflammatory biomarkers do not correlate with volume of heart or lung receiving radiation.
Academic Article Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases.
Academic Article Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation.
Academic Article The Lymphatic System in Disease Processes and Cancer Progression.
Grant Lymphatic Radiobiology
Grant Lymphatic Radiobiology
Grant Characterizing lymphatic micrometastases: prognostic and therapeutic implications
Academic Article Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy.
Grant Targeting lymph node metastases to prevent cancer progression
Academic Article Targeting CXCR4-dependent immunosuppressive Ly6Clow monocytes improves antiangiogenic therapy in colorectal cancer.
Academic Article Growth and Immune Evasion of Lymph Node Metastasis.
Academic Article Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice.
Academic Article Breast cancer metastasis through the lympho-vascular system.
Academic Article Inducible Nitric Oxide Synthase and CD11b+Gr1+ Cells Impair Lymphatic Contraction of Tumor-Draining Lymphatic Vessels.
Academic Article The Impact of Taxane-based Chemotherapy on the Lymphatic System.
Academic Article Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium.
Academic Article A Novel Approach to Quantifying Lymphatic Contractility during Indocyanine Green Lymphangiography.
Academic Article A retrospective analysis of commonly prescribed medications and the risk of developing breast cancer related lymphedema.
Academic Article Fate Mapping of Cancer Cells in Metastatic Lymph Nodes Using Photoconvertible Proteins.
Academic Article Progression of Metastasis through Lymphatic System.
Academic Article Mechanisms of breast cancer metastasis.
Academic Article Solid stress impairs lymphocyte infiltration into lymph-node metastases.
Search Criteria
  • Cancer
  • metastasis
Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.