Research Topics
Species | Lance MunnSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
Aberrant vascular architecture in tumors and its importance in drug-based therapiesLance L Munn
Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA
Drug Discov Today 8:396-403. 2003..However, as more is learned about the formation of tumor vasculature and how it differs from that in normal tissue, more effective and directed therapies to fight cancer might be developed...
Particulate nature of blood determines macroscopic rheology: a 2-D lattice Boltzmann analysisChenghai Sun
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Biophys J 88:1635-45. 2005..This powerful and flexible model can be used to predict blood flow properties in any vessel geometry and with any blood composition...- PDGF and microvessel wall remodeling in adult rat lung: imaging PDGF-AA and PDGF-Ralpha molecules in progenitor smooth muscle cells developing in experimental pulmonary hypertensionRosemary Jones
Department of Anesthesia and Critical Care, Harvard Medical School, Massachusetts General Hospital, MGH East, Charlestown, MA 02129, USA
Cell Tissue Res 326:759-69. 2006.... - Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: insights from a mathematical modelRakesh K Jain
E L Steele Lab for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
Cancer Res 67:2729-35. 2007..Finally, decreased fluid convection into the peritumor tissue would decrease peritumor edema associated with brain tumors and ascites accumulation in the peritoneal or pleural cavity, a major complication with a number of malignancies... - Red blood cells initiate leukocyte rolling in postcapillary expansions: a lattice Boltzmann analysisChenghai Sun
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Biophys J 85:208-22. 2003..The model predicts that an optimal configuration of the trailing red blood cells is required to drive the white blood cell to the wall... - Non-uniform plasma leakage affects local hematocrit and blood flow: implications for inflammation and tumor perfusionChenghai Sun
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Ann Biomed Eng 35:2121-9. 2007..Normalization of tumor vessels by anti-angiogenic therapy may improve tumor perfusion via the first two mechanisms... - Blood cell interactions and segregation in flowLance L Munn
E L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 100 Blossom St, COX 7, Boston, MA 02114, USA
Ann Biomed Eng 36:534-44. 2008..Here we summarize efforts in our lab to continue this tradition and to further our understanding of how blood cells interact with each other and with the blood vessel wall... - Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical modelsDai Fukumura
Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Microcirculation 17:206-25. 2010..Administration of cytotoxic therapy during periods of vascular normalization has the potential to enhance treatment efficacy... - Dissecting tumour pathophysiology using intravital microscopyRakesh K Jain
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA
Nat Rev Cancer 2:266-76. 2002..Intravital microscopy has provided unprecedented molecular, cellular, anatomical and functional insights into these barriers and has revealed new approaches to improved detection and treatment... - Lymphatic metastasis in the absence of functional intratumor lymphaticsTimothy P Padera
E. L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA
Science 296:1883-6. 2002..These findings suggest that the functional lymphatics in the tumor margin alone are sufficient for lymphatic metastasis and should be targeted therapeutically... - PDGF-C induces maturation of blood vessels in a model of glioblastoma and attenuates the response to anti-VEGF treatmentEmmanuelle di Tomaso
E L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 4:e5123. 2009..Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy... - Mosaic tumor vessels: cellular basis and ultrastructure of focal regions lacking endothelial cell markersEmmanuelle di Tomaso
Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Cancer Res 65:5740-9. 2005..More than 80% of the defects lacked immunoreactivity for multiple basement membrane proteins... - Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinasesFrank Winkler
E.L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA
Cancer Cell 6:553-63. 2004..During the normalization window, but not before or after it, VEGFR2 blockade increases pericyte coverage of brain tumor vessels via upregulation of Ang1 and degrades their pathologically thick basement membrane via MMP activation... - Micro-environmental mechanical stress controls tumor spheroid size and morphology by suppressing proliferation and inducing apoptosis in cancer cellsGang Cheng
Edwin L Steele Laboratory of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 4:e4632. 2009.... - Simultaneous measurement of RBC velocity, flux, hematocrit and shear rate in vascular networksWalid S Kamoun
Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Nat Methods 7:655-60. 2010..Furthermore, we show that subpopulations of vessels, classified by functional parameters, exist in and around a tumor and in normal brain tissue... - Angiopoietin-2 interferes with anti-VEGFR2-induced vessel normalization and survival benefit in mice bearing gliomasSung Suk Chae
Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Clin Cancer Res 16:3618-27. 2010..Here, we used an orthotopic glioma model to test the hypothesis that Ang-2 is an additional target for improving the efficacy of current anti-VEGF therapies in glioma patients... - A mathematical model of the contribution of endothelial progenitor cells to angiogenesis in tumors: implications for antiangiogenic therapyBrian R Stoll
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Blood 102:2555-61. 2003..The model offers new insight into tumor angiogenesis with implications for the rational design of antiangiogenic therapy... - Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imagingBenjamin J Vakoc
Wellman Center for Photomedicine, Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA
Nat Med 15:1219-23. 2009.... - Red blood cells augment leukocyte rolling in a virtual blood vesselCristiano Migliorini
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA
Biophys J 83:1834-41. 2002..This novel approach can be applied to a large number of biological and industrial problems involving the complex flow of particulate suspensions... - Solid stress generated by spheroid growth estimated using a linear poroelasticity model small star, filledTiina Roose
Steele Laboratory for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, 100 Blossom Street, COX 7, Boston, MA 02114-2617, USA
Microvasc Res 66:204-12. 2003..This leads to the interesting possibility that cell size could be a direct indicator of solid stress level inside the tumors in clinical setting... - Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancerChristopher G Willett
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Nat Med 10:145-7. 2004..These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors... - Differential transplantability of tumor-associated stromal cellsDan G Duda
E. L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
Cancer Res 64:5920-4. 2004..These studies of tumor tissue transplantation provide a platform for exploring the role of epithelial-stromal interactions in studies of tumor heterogeneity and drug resistance... - Paradoxical effects of PDGF-BB overexpression in endothelial cells on engineered blood vessels in vivoPatrick Au
Department of RadiationOncology, Edwin L Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
Am J Pathol 175:294-302. 2009..These results suggest a potential negative interaction between angiogenic growth factors and vascular cells; their use in combination should be carefully tested in vivo for such opposing effects... - Antibody-directed effector cell therapy of tumors: analysis and optimization using a physiologically based pharmacokinetic modelStuart W Friedrich
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Neoplasia 4:449-63. 2002..Our results suggest that the design of the BFA is critical and the binding constants of the antigen and lymphocyte binding epitopes need to be optimized for successful therapy... - Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in miceWalid S Kamoun
Edwin L Steele Laboratory, Department of Radiation Oncology, Stephen E and Catherine Pappas Center for Neuro Oncology, and AA Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
J Clin Oncol 27:2542-52. 2009..Our goal was to determine whether alleviation of edema by anti-VEGF agents alone could increase survival in mice... - In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblastsJean Y Perentes
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA
Nat Methods 6:143-5. 2009..We show that the matrix-modifying hormone relaxin increased tumor-associated fibroblast (TAF) interaction with collagen fibers by stimulating beta1-integrin activity, which is necessary for fiber remodeling by matrix metalloproteinases... - Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumorsRobert B Campbell
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Cancer Res 62:6831-6. 2002..Our results suggest that optimizing physicochemical properties of liposomes that exploit physiological features of tumors and control the intratumor distribution of these drug carriers should improve vascular-specific delivery... - Differential gene expression in metastasizing cells shed from kidney tumorsMaximilian Bockhorn
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Cancer Res 64:2469-73. 2004..Furthermore, resistance to apoptosis may enhance metastasis in the higher metastatic tumor... - Lack of telopeptides in fibrillar collagen I promotes the invasion of a metastatic breast tumor cell lineZoe N Demou
Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Cancer Res 65:5674-82. 2005..Thus, the higher RhoA activity of MDA-MB-435S cells in telopeptide-free collagen enhances the changes in cellular morphodynamics associated with motility and invasion... - NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vesselsSatoshi Kashiwagi
Edwin L. Steele Laboratory, Department of Radiation Oncology, and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
J Clin Invest 115:1816-27. 2005..These data indicate that endothelial cell-derived NO induces mural cell recruitment as well as subsequent morphogenesis and stabilization of angiogenic vessels... - Biomimetic autoseparation of leukocytes from whole blood in a microfluidic deviceSergey S Shevkoplyas
Visual and Circulatory Biophysics Laboratory, Department of Biomedical Engineering, Boston University, 36 Cummington Street, Boston, MA 02215, USA
Anal Chem 77:933-7. 2005..Its integration into microanalytical devices that require leukocyte enrichment will enable accelerated transition of these devices into the field for point-of-care clinical testing... - Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactionsTriantafyllos Stylianopoulos
Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Biophys J 99:1342-9. 2010..Taken together, we conclude that optimal particles for delivery to tumors should be initially cationic to target the tumor vessels and then change to neutral charge after exiting the blood vessels... - Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed?Maximilian Bockhorn
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Germany
Lancet Oncol 8:444-8. 2007..We discuss the evidence for and against this passive-shedding hypothesis and the implications for future treatments... - Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patientsChristopher G Willett
J Clin Oncol 23:8136-9. 2005
Research Grants
- Microfluidic Device for Isolating Rare Blood CellsLance Munn; Fiscal Year: 2007..When fully-developed, this technology will be a necessary and integral component of any microfluidic device analyzing nucleated blood cell populations by eliminating the need for preliminary blood processing steps. ..
- Blood rheology, cell adhesion and endothelial activationLance Munn; Fiscal Year: 2007..A combination of in vivo experiments and mathematical modeling will be used to assess the combination of fluid forces and vessel geometries that lead to atherosclerotic lesions. ..
- Blood Rheology and Leukocyte MechanicsLance Munn; Fiscal Year: 2005..The unique combination of experimental and theoretical approaches will form the basis of my independent scientific career. ..
- CELL-SURFACE ADHESION--INFLUENCE OF BLOOD RHEOLOGYLance Munn; Fiscal Year: 2003....
- Flow-based remodeling and function of tumor vasculatureLance L Munn; Fiscal Year: 2010..We will apply a mathematical model to determine how changes in vessel leakiness and network structure individually influence oxygen and drug delivery throughout tumor. ..