Dai Fukumura

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability
    D Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 98:2604-9. 2001
  2. ncbi Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models
    Dai 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
  3. ncbi The role of nitric oxide in tumour progression
    Dai Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Nat Rev Cancer 6:521-34. 2006
  4. ncbi Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize
    Dai Fukumura
    Department of Radiation Oncology, Edwin L Steele Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    J Cell Biochem 101:937-49. 2007
  5. ncbi Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization
    Dai Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street Cox 7, Boston, MA 02114, USA
    Microvasc Res 74:72-84. 2007
  6. ncbi Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo
    D Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 61:6020-4. 2001
  7. ncbi Imaging angiogenesis and the microenvironment
    Dai Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    APMIS 116:695-715. 2008
  8. ncbi Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis
    Johanna Lahdenranta
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 69:2801-8. 2009
  9. ncbi Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases
    Frank 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
  10. ncbi NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels
    Satoshi 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

Research Grants

  1. NO in Tumor Angiogenesis,Microcirculation & Rad.Therapy
    Dai Fukumura; Fiscal Year: 2006
  2. Nitric Oxide in Tumor Angiogenesis, Microcirculation and Radiation Therapy
    Dai Fukumura; Fiscal Year: 2010

Collaborators

Detail Information

Publications77

  1. ncbi Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability
    D Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 98:2604-9. 2001
    ..Thus, selective modulation of eNOS activity is a promising strategy for altering angiogenesis and vascular permeability in vivo...
  2. ncbi Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models
    Dai 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...
  3. ncbi The role of nitric oxide in tumour progression
    Dai Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Nat Rev Cancer 6:521-34. 2006
    ..We also discuss potential strategies for cancer treatment that modulate NO production and/or its downstream signalling pathways...
  4. ncbi Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize
    Dai Fukumura
    Department of Radiation Oncology, Edwin L Steele Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    J Cell Biochem 101:937-49. 2007
    ..Combined anti-angiogenic and conventional therapies have shown promise in the clinic...
  5. ncbi Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization
    Dai Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street Cox 7, Boston, MA 02114, USA
    Microvasc Res 74:72-84. 2007
    ..Combination of cytotoxic therapy and anti-angiogenic treatment during the vascular normalization exhibits synergistic effect...
  6. ncbi Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo
    D Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 61:6020-4. 2001
    ..These results suggest that VEGF transcription in brain tumors is regulated by both tissue pO(2) and pH via distinct pathways...
  7. ncbi Imaging angiogenesis and the microenvironment
    Dai Fukumura
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    APMIS 116:695-715. 2008
    ..Administration of cytotoxic therapy during the vascular normalization would enhance its efficacy...
  8. ncbi Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis
    Johanna Lahdenranta
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 69:2801-8. 2009
    ..Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system...
  9. ncbi Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases
    Frank 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...
  10. ncbi NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels
    Satoshi 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...
  11. ncbi Paradoxical effects of PDGF-BB overexpression in endothelial cells on engineered blood vessels in vivo
    Patrick 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...
  12. ncbi Impaired lymphatic contraction associated with immunosuppression
    Shan Liao
    EL Steele Laboratory, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 108:18784-9. 2011
    ..Our unique method allows the study of lymphatic function and its molecular regulation during inflammation, lymphedema, and lymphatic metastasis...
  13. ncbi 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
    Tohru Hoshida
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Cancer Res 66:8065-75. 2006
    ....
  14. ncbi Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases
    David P Kodack
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 109:E3119-27. 2012
    ..These findings support the clinical development of this three-drug regimen for the treatment of HER2-amplified breast cancer brain metastases...
  15. ncbi VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases but is not required for spontaneous metastasis formation
    Michelle R Dawson
    Steele Laboratory for Tumor Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 4:e6525. 2009
    ..Prevention of metastasis will require further identification and exploration of cellular and molecular pathways that mediate the priming of the metastatic soil...
  16. ncbi Perivascular nitric oxide gradients normalize tumor vasculature
    Satoshi Kashiwagi
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA
    Nat Med 14:255-7. 2008
    ..Creation of perivascular NO gradients may be an effective strategy for normalizing abnormal vasculature...
  17. ncbi Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors
    Dan G Duda
    Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, COX 734, 100 Blossom St, Boston, MA 02114, USA
    Blood 107:2774-6. 2006
    ..We demonstrate that BMD-ECs incorporate in perfused tumor vessels, and that this contribution varies with organ site and mouse strain...
  18. ncbi Angiopoietin-2 interferes with anti-VEGFR2-induced vessel normalization and survival benefit in mice bearing gliomas
    Sung 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...
  19. ncbi Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models
    Lei Xu
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 66:3971-7. 2006
    ..Our study shows that PlGF overexpression decreases VEGF homodimer formation and inhibits tumor progression...
  20. ncbi Role of host microenvironment in angiogenesis and microvascular functions in human breast cancer xenografts: mammary fat pad versus cranial tumors
    Wayne L Monsky
    Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Clin Cancer Res 8:1008-13. 2002
    ..Collectively, host microenvironment is an important determinant of tumor gene expression and microvascular functions, and, thus, orthotopic breast tumor models should be useful for obtaining clinically relevant information...
  21. ncbi Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging
    Benjamin 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
    ....
  22. ncbi Normalization of the vasculature for treatment of cancer and other diseases
    Shom Goel
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Physiol Rev 91:1071-121. 2011
    ..Here, we review the pathophysiology of tumor angiogenesis, the molecular underpinnings and functional consequences of vascular normalization, and the implications for treatment of cancer and nonmalignant diseases...
  23. ncbi Green fluorescent protein (GFP)-expressing tumor model derived from a spontaneous osteosarcoma in a vascular endothelial growth factor (VEGF)-GFP transgenic mouse
    Peigen Huang
    Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Comp Med 55:236-43. 2005
    ..This in vitro and in vivo transplantable and metastatic osteosarcoma (Os-P0107) is an attractive model for further study of tumor pathophysiology and treatment efficiency affecting VEGF expression...
  24. ncbi Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts
    Maximilian Bockhorn
    Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital, 100 Blossom Street, Boston, MA 02114, USA
    Clin Cancer Res 9:4221-6. 2003
    ..Anti-VEGF strategy appears promising for pancreatic cancer treatment...
  25. ncbi Lack of lymphatic vessel phenotype in LYVE-1/CD44 double knockout mice
    Mai X Luong
    Department of Radiation Oncology, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    J Cell Physiol 219:430-7. 2009
    ..These data suggest that LYVE-1 and CD44 are not required for the formation or function of lymphatics, but do not rule out a role for LYVE-1 in inflammation...
  26. ncbi Targeting tumor vasculature and cancer cells in orthotopic breast tumor by fractionated photosensitizer dosing photodynamic therapy
    Dennis E J G J Dolmans
    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 62:4289-94. 2002
    ..The long-term effect of the fractionated drug PDT on blood flow was also more extensive than single-dose PDT. Fractionated photosensitizer dosing PDT offers a new strategy to optimize PDT therapy...
  27. ncbi PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer
    Jieqiong Liu
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Clin Cancer Res 17:3638-48. 2011
    ..Unlike platelet-derived growth factor-B (PDGF-B), the role of PDGF-D in tumor progression or treatment is largely unknown. To this end, we determined the role of PDGF-D in breast cancer progression, metastasis, and response to chemotherapy...
  28. ncbi Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation
    Sachie Hiratsuka
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 108:3725-30. 2011
    ..Thus, localized activation of endothelial FAK and E-selectin in the lung vasculature mediates the initial homing of metastatic cancer cells to specific foci in the lungs...
  29. ncbi Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice
    Walid 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...
  30. ncbi Differential transplantability of tumor-associated stromal cells
    Dan 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...
  31. ncbi Malignant cells facilitate lung metastasis by bringing their own soil
    Dan G Duda
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 107:21677-82. 2010
    ..Demonstration of the direct involvement of primary tumor stroma in metastasis has important conceptual and clinical implications for the colonization step in tumor progression...
  32. ncbi Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner
    Vikash P Chauhan
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Nat Nanotechnol 7:383-8. 2012
    ..Our results further suggest that smaller (∼12 nm) nanomedicines are ideal for cancer therapy due to their superior tumour penetration...
  33. ncbi Blockade of VEGFR2 and not VEGFR1 can limit diet-induced fat tissue expansion: role of local versus bone marrow-derived endothelial cells
    Joshua Tam
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    PLoS ONE 4:e4974. 2009
    ..e., angiogenesis) or bone marrow-derived cells (BMDCs, i.e. vasculogenesis) and if antiangiogenic treatment by blockade of vascular endothelial growth factor (VEGF) receptors can prevent diet-induced obesity (DIO)...
  34. ncbi Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib
    Timothy P Padera
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA
    Mol Cancer Ther 7:2272-9. 2008
    ..Collectively, these data indicate that the response of lymphatic vessels to a TKI can determine the incidence of lymphatic metastasis, independent of the effect of the TKI on blood vessels...
  35. ncbi Hypoxia-induced activation of p38 mitogen-activated protein kinase and phosphatidylinositol 3'-kinase signaling pathways contributes to expression of interleukin 8 in human ovarian carcinoma cells
    Lei Xu
    Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Clin Cancer Res 10:701-7. 2004
    ....
  36. ncbi Secreted Gaussia luciferase as a biomarker for monitoring tumor progression and treatment response of systemic metastases
    Euiheon Chung
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 4:e8316. 2009
    ..To this end, we engineered tumor cells to express a naturally secreted Gaussia luciferase (Gluc), and investigated its use as a circulating biomarker for monitoring viable metastatic or primary tumor growth and their treatment responses...
  37. ncbi Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function
    Naohide Isaka
    E L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA
    Cancer Res 64:4400-4. 2004
    ..Surprisingly, these new, functional lymphatic vessels displayed a retrograde draining pattern, which indicates possible dysfunction of the intraluminal valves of these vessels...
  38. ncbi Studying primary tumor-associated fibroblast involvement in cancer metastasis in mice
    Annique M M J Duyverman
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital MGH and Harvard Medical School, Boston, Massachusetts, USA
    Nat Protoc 7:756-62. 2012
    ..g., transgenic expression of the DT receptor in specific cells) may eventually allow analogous models using syngeneic cells. Studying the role of stromal cells in metastasis using the model outlined above may take 8 weeks...
  39. ncbi Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature
    Patrick Au
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Blood 111:4551-8. 2008
    ..In conclusion, hMSCs are perivascular cell precursors and may serve as an attractive source of cells for use in vascular tissue engineering and for the study of perivascular cell differentiation...
  40. ncbi Dissecting tumour pathophysiology using intravital microscopy
    Rakesh 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...
  41. ncbi VEGFR1-activity-independent metastasis formation
    Michelle R Dawson
    Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 461:E4; discussion E5. 2009
    ..Therefore, alternative pathways probably mediate the priming of tissues for metastasis...
  42. ncbi Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo
    Mark Stroh
    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
    Nat Med 11:678-82. 2005
    ..These examples show the versatility of quantum dots for studying tumor pathophysiology and creating avenues for treatment...
  43. ncbi Simultaneous measurement of RBC velocity, flux, hematocrit and shear rate in vascular networks
    Walid 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...
  44. ncbi In vivo wide-area cellular imaging by side-view endomicroscopy
    Pilhan Kim
    Wellman Center for Photomedicine, Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA
    Nat Methods 7:303-5. 2010
    ..We monitored cell infiltration, vascular changes and tumor progression during inflammation and tumorigenesis in colon over several months...
  45. ncbi Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactions
    Triantafyllos 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...
  46. ncbi Engineered blood vessel networks connect to host vasculature via wrapping-and-tapping anastomosis
    Gang Cheng
    Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA
    Blood 118:4740-9. 2011
    ..These findings open the door to new strategies for improving perfusion of tissue grafts and may have implications for other physiologic and pathologic processes involving postnatal vasculogenesis...
  47. ncbi Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis
    Dai Fukumura
    Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Mass 02114, USA
    Circ Res 93:e88-97. 2003
    ..The full text of this article is available online at http://www.circresaha.org...
  48. ncbi Endothelial nitric oxide synthase regulates microlymphatic flow via collecting lymphatics
    Jeroen Hagendoorn
    Department of Radiation Oncology, E L Steele Laboratory for Tumor Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass 02114, USA
    Circ Res 95:204-9. 2004
    ..Our results provide the first in vivo evidence that eNOS affects function of the whole microlymphatic system and that it is regulated via the collecting lymphatics...
  49. ncbi Tumour biology: herceptin acts as an anti-angiogenic cocktail
    Yotaro Izumi
    Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Nature 416:279-80. 2002
    ..As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments...
  50. ncbi Responses to antiangiogenesis treatment of spontaneous autochthonous tumors and their isografts
    Yotaro Izumi
    Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 63:747-51. 2003
    ..Although passaged tumors behave differently, it is encouraging that the tumor growth rates under DC101 treatment are comparable among different passage generations...
  51. ncbi Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels
    Patrick Au
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Blood 111:1302-5. 2008
    ..Thus, umbilical cord blood EPCs hold great therapeutic potential, and their use should be pursued for vascular engineering...
  52. ncbi Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma
    Matija Snuderl
    Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell 152:1065-76. 2013
    ..This critical tumor-stroma interaction-mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes-supports the development of therapies targeting PlGF/Nrp1 pathway...
  53. ncbi A transient parabiosis skin transplantation model in mice
    Annique M M J Duyverman
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital MGH and Harvard Medical School, Boston, Massachusetts, USA
    Nat Protoc 7:763-70. 2012
    ..Studying the role of stromal cells in metastasis using this model typically takes up to 11 weeks...
  54. ncbi An isolated tumor perfusion model in mice
    Annique M M J Duyverman
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital MGH and Harvard Medical School, Boston, Massachusetts, USA
    Nat Protoc 7:749-55. 2012
    ..Studying the role of stromal cells in circulating tumor fragments using this model may take 2-10 weeks, depending on the growth rate of the primary tumor...
  55. ncbi Small blood vessel engineering
    Patrick Au
    Department of Radiation Oncology, Edwin L Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, USA
    Methods Mol Med 140:183-95. 2007
    ..The engineered vessels are stable and functional, and they persist for more than 1 year in vivo. This approach may potentially lead to the creation of a well-vascularized-engineered tissue...
  56. ncbi Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors
    Robert 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...
  57. ncbi Influence of tumor cell and stroma sensitivity on tumor response to radiation
    Kazuhiko Ogawa
    Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Cancer Res 67:4016-21. 2007
    ..The relative contribution of host and tumor cell sensitivity on tumor response was unchanged for single doses of 1 x 15 and 6 x 3 Gy-fractionated dose irradiation...
  58. ncbi Acidic extracellular pH induces vascular endothelial growth factor (VEGF) in human glioblastoma cells via ERK1/2 MAPK signaling pathway: mechanism of low pH-induced VEGF
    Lei Xu
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 277:11368-74. 2002
    ..These results show that acidic pH activates Ras and the ERK1/2 MAPK pathway to enhance VEGF transcription via AP-1, leading to increased VEGF production...
  59. ncbi Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis
    Jeroen Hagendoorn
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom Street, Boston, MA 02114, USA
    Cancer Res 66:3360-4. 2006
    ..In addition, the lymphatic vessels in hyperplastic/dysplastic lesions were partly compressed and nonfunctional. These novel insights may aid early detection and treatment strategies for cancer...
  60. ncbi Sparse initial entrapment of systemically injected Salmonella typhimurium leads to heterogeneous accumulation within tumors
    Neil S Forbes
    E. L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Cancer Res 63:5188-93. 2003
    ..Although S. typhimurium is a promising delivery vehicle because of its tumor specificity, increasing its intra-tumoral motility should improve its therapeutic effectiveness...
  61. ncbi CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies?
    Dan G Duda
    Steele Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Clin Cancer Res 17:2074-80. 2011
    ..g., AMD3100, NOX-A12, or CCX2066) as sensitizers to currently available therapies by targeting the CXCL12/CXCR4 and CXCL12/CXCR7 pathways...
  62. ncbi C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated protein kinase in myeloid differentiation antigen (Gr-1)-positive cells
    Sachie Hiratsuka
    Steele Laboratory for Tumor Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 108:302-7. 2011
    ..Thus, combining CXCR4 blockade with inhibition of VEGFR1 may induce greater tumor growth delay and prevent or inhibit metastasis...
  63. ncbi A mathematical model of murine metabolic regulation by leptin: energy balance and defense of a stable body weight
    Joshua Tam
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Cell Metab 9:52-63. 2009
    ..Finally, our model has identified potential avenues for future investigations...
  64. ncbi Histopathologic findings and establishment of novel tumor lines from spontaneous tumors in FVB/N mice
    Peigen Huang
    Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Comp Med 58:253-63. 2008
    ..Establishment of these novel tumor lines will benefit both in vivo and in vitro studies on the pathophysiology of cancer in this relatively new but widely used mouse strain...
  65. ncbi Role of eNOS in neovascularization: NO for endothelial progenitor cells
    Dan G Duda
    E L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom Street, COX 7, Boston, MA 02114, USA
    Trends Mol Med 10:143-5. 2004
    ..In addition, successes in gene therapy, together with the recent development of an eNOS-specific inhibitor, suggest that the modulation of eNOS might be a potent new strategy for the control of pathological neovascularization...
  66. ncbi Targeting PDGF signaling in carcinoma-associated fibroblasts controls cervical cancer in mouse model
    Rakesh K Jain
    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 5:e24. 2008
  67. ncbi Molecular regulation of microlymphatic formation and function: role of nitric oxide
    Jeroen Hagendoorn
    E.L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Trends Cardiovasc Med 15:169-73. 2005
    ..Here, we review the role of nitric oxide within the regulation of lymphatic formation and function and point out key unanswered questions for its translation into clinical therapy...
  68. ncbi The biology of brain metastases-translation to new therapies
    April F Eichler
    Stephen E and Catherine Pappas Center for Neuro Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Nat Rev Clin Oncol 8:344-56. 2011
    ..This Review discusses what is known about the biology of brain metastases, what preclinical models are available to study the disease, and which novel therapeutic strategies are being studied in patients...
  69. ncbi Photodynamic therapy for cancer
    Dennis E J G J Dolmans
    Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nat Rev Cancer 3:380-7. 2003
    ..How does PDT work, and how can it be used to treat cancer and other diseases?..
  70. ncbi Tissue engineering: creation of long-lasting blood vessels
    Naoto Koike
    Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 428:138-9. 2004
    ..These networks are stable and functional for one year in vivo...
  71. ncbi Spontaneous nonthymic tumors in SCID mice
    Peigen Huang
    Department of Radiation Oncology, Edwin L Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Comp Med 61:227-34. 2011
    ..To our knowledge, this report is the first comprehensive description of spontaneous nonthymic tumors, including 8 myoepitheliomas and 3 rhabdomyosarcomas, from the same SCID mouse colony...
  72. ncbi Feasibility of in vivo imaging of fluorescent proteins using lifetime contrast
    Anand T N Kumar
    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Opt Lett 34:2066-8. 2009
    ..These results suggest the potential for exploiting fluorescence lifetime for imaging FPs for a variety of whole-body small-animal imaging applications...
  73. ncbi Vascular accumulation of a novel photosensitizer, MV6401, causes selective thrombosis in tumor vessels after photodynamic therapy
    Dennis E J G J Dolmans
    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 62:2151-6. 2002
    ..In concert with the stasis, a dose-dependent tumor growth delay was observed. This study provides mechanistic insights into antitumor vascular effects of PDT and suggests novel strategies for tumor treatment with PDT...
  74. ncbi Influence of the site of human gallbladder xenograft (Mz-ChA-1) on angiogenesis at the distant site
    Takeshi Gohongi
    Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba shi 305 8575, Japan
    Oncol Rep 11:803-7. 2004
    ..The results of the present study together with our previous study imply that the primary tumor microenvironment is conducive to the angiogenesis at a distant site by the production of the endogenous angiogenesis inhibitor TGFbeta1...
  75. ncbi Genetic evidence for a tumor suppressor role of HIF-2alpha
    Till Acker
    Edinger Institute, Neuropathology, Johann Wolfgang Goethe University, 60528 Frankfurt, Germany
    Cancer Cell 8:131-41. 2005
    ..These findings urge careful consideration of using HIF inhibitors as cancer therapeutic strategies...
  76. ncbi Anti-VEGFR-3 therapy and lymph node metastasis [corrected]
    Timothy P Padera
    Cancer Res 67:5055; author reply 5056. 2007
  77. ncbi Engineering vascularized tissue
    Rakesh K Jain
    Nat Biotechnol 23:821-3. 2005

Research Grants8

  1. NO in Tumor Angiogenesis,Microcirculation & Rad.Therapy
    Dai Fukumura; Fiscal Year: 2006
    ..e. normalization of tumor vessels) to overcome some of the physiological barriers to the delivery of therapeutic agents to solid tumors and introduce a new paradigm to study cell-cell interaction in vivo. ..
  2. Nitric Oxide in Tumor Angiogenesis, Microcirculation and Radiation Therapy
    Dai Fukumura; Fiscal Year: 2010
    ..This project will advance the basic understanding of NO-mediated vessel maturation and help develop novel strategies to improve the delivery of drugs and oxygen to tumors. ..