- The hallmarks of cancer
Department of Biochemistry, Hormone Research Institute, University of California at San Francisco, 94143, USA
Cell 100:57-70. 2000
- The biology of VEGF and its receptors
Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
Nat Med 9:669-76. 2003
..VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration...
- Angiogenesis in cancer and other diseases
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium
Nature 407:249-57. 2000
..This integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases. But owing to several unanswered questions, caution is needed...
- Hypoxia--a key regulatory factor in tumour growth
Adrian L Harris
Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
Nat Rev Cancer 2:38-47. 2002
..Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting...
- Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy
Rakesh K Jain
E L Steele Lab for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, and Harvard Medical School, COX 7, 100 Blossom Street, Boston, MA 02114, USA
Science 307:58-62. 2005
- Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis
Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, 08907 L Hospitalet de Llobregat, Spain
Cancer Cell 15:220-31. 2009
- Tumor angiogenesis
Robert S Kerbel
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, and the Department of Medical Biophysics, University of Toronto, Toronto
N Engl J Med 358:2039-49. 2008
- Angiogenesis in life, disease and medicine
Center of Transgene Technology and Gene Therapy, University of Leuven, Flanders Interuniversity Institute for Biotechnology VIB, B 3000 Leuven, Belgium
Nature 438:932-6. 2005
..Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments...
- Angiogenesis: an organizing principle for drug discovery?
Childrens Hospital and Harvard Medical School Boston, Massachusetts, USA
Nat Rev Drug Discov 6:273-86. 2007
- Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Cell 121:335-48. 2005
..Our findings indicate that fibroblasts within invasive breast carcinomas contribute to tumor promotion in large part through the secretion of SDF-1...
- Mechanisms of angiogenesis and arteriogenesis
The Center for Transgene Technology and Gene Therapy Flanders Interuniversity Institute for Biotechnology KU Leuven, Leuven, B 3000, Belgium
Nat Med 6:389-95. 2000
- Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis
John M L Ebos
Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
Cancer Cell 15:232-9. 2009
- Tumorigenesis and the angiogenic switch
University of California San Francisco, Department of Neurological Surgery, Brain Tumor Research Center and Comprehensive Cancer Center, HSE 722, 513 Parnassus Avenue, San Francisco, California 94143 0520, USA
Nat Rev Cancer 3:401-10. 2003
- Angiogenesis in health and disease
Center for Transgene Technology and Gene Therapy, Flanders Interuniversitary Institute for Biotechnology, KULeuven, Campus Gasthuisberg, Herestraat 49, B 3000, Leuven, Belgium
Nat Med 9:653-60. 2003
..Molecular insights into these processes are being generated at a rapidly increasing pace, offering new therapeutic opportunities that are currently being evaluated...
- Regulation of angiogenesis by hypoxia: role of the HIF system
Christopher W Pugh
The Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford, OX3 7BN, UK
Nat Med 9:677-84. 2003
..We also discuss the implications of oncogenic activation of extensive, physiologically interconnected hypoxia pathways for the tumor phenotype...
- Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis
Daniel J Hicklin
Department of Experimental Therapeutics, ImClone Systems Incorporated, New York, NY 10014, USA
J Clin Oncol 23:1011-27. 2005
- Modes of resistance to anti-angiogenic therapy
University of California, San Francisco, Department of Neurological Surgery, Brain Tumour Research Center, San Francisco, California 94143, USA
Nat Rev Cancer 8:592-603. 2008
- AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients
Tracy T Batchelor
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Cancer Cell 11:83-95. 2007
..Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor...
- Inflammation and cancer
Lisa M Coussens
Cancer Research Institute, Department of Pathology, University of California, San Francisco, California 94143, USA
Nature 420:860-7. 2002
..These insights are fostering new anti-inflammatory therapeutic approaches to cancer development...
- Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors
Department of Biochemistry and Biophysics, Comprehensive Cancer Center, and Diabetes Center, University of California, San Francisco, San Francisco, California 94143, USA
Cancer Cell 8:299-309. 2005
..These other proangiogenic signals are functionally implicated in the revascularization and regrowth of tumors in the evasion phase, as FGF blockade impairs progression in the face of VEGF inhibition...
- Distinct role of macrophages in different tumor microenvironments
Claire E Lewis
Academic Unit of Pathology, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom
Cancer Res 66:605-12. 2006
..This review will discuss the evidence for differential regulation of TAMs in these microenvironments and provide an overview of current attempts to target or use TAMs for therapeutic purposes...
- Vascular endothelial growth factor: basic science and clinical progress
Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
Endocr Rev 25:581-611. 2004
..Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration...
- Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization
Department of Medicine, St Elizabeth s Medical Center, Tufts University School of Medicine, Boston, MA, USA
Circ Res 85:221-8. 1999
- The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
P H Maxwell
Wellcome Trust Centre for Human Genetics, Oxford, UK
Nature 399:271-5. 1999
..Thus, constitutive HIF-1 activation may underlie the angiogenic phenotype of VHL-associated tumours. The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing...
- Molecular regulation of vessel maturation
Rakesh K Jain
E L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA
Nat Med 9:685-93. 2003
..Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering...
- Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, California 94143, USA
Nat Cell Biol 2:737-44. 2000
..Absence of MMP-2 does not impair induction of angiogenesis, but retards tumour growth, whereas lack of urokinase has no effect. Our results show that MMP-9 is a component of the angiogenic switch...
- Role of angiogenesis in tumor growth and metastasis
Departments of Surgery and Cell Biology, Harvard Medical School, Boston, MA, USA
Semin Oncol 29:15-8. 2002
..Phase 1 clinical trials of endostatin and angiostatin are ongoing, and preliminary results show minimal toxicities...
- Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors
Michele De Palma
Angiogenesis and Tumor Targeting Research Unit, San Raffaele Institute, Milano, Italy
Cancer Cell 8:211-26. 2005
..Therefore, Tie2 expression characterizes three distinct cell types required for tumor neovascularization: ECs, proangiogenic cells of hematopoietic origin, and pericyte precursors of mesenchymal origin...
- Requirement of vascular integrin alpha v beta 3 for angiogenesis
P C Brooks
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037
Science 264:569-71. 1994
..These findings suggest that alpha v beta 3 may be a useful therapeutic target for diseases characterized by neovascularization...
- Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy
Harold F Dvorak
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
J Clin Oncol 20:4368-80. 2002
..It may also become an important target for cancer therapy...
- VEGF and the quest for tumour angiogenesis factors
Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
Nat Rev Cancer 2:795-803. 2002
..How did this field begin, and how have we arrived at our present understanding of the role of VEGF in tumour progression...
- Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, Belgium
Nat Med 7:575-83. 2001
..By upregulating PlGF and the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders...
Vascular Biology Program, Children s Hospital and Harvard Medical School, Boston, Massachusetts 02115 5737, USA
Annu Rev Med 57:1-18. 2006
..Several types of angiogenesis inhibitors reveal a biphasic, U-shaped curve of efficacy. "Antiangiogenic chemotherapy" is a novel approach to the treatment of drug resistance...
- Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors
Ricky T Tong
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Cancer Res 64:3731-6. 2004
..Thus, vascular normalization may contribute to the improved survival rates in tumor-bearing animals and in colorectal carcinoma patients treated with an anti-VEGF antibody in combination with cytotoxic therapies...
- Macrophages regulate the angiogenic switch in a mouse model of breast cancer
Elaine Y Lin
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Cancer Res 66:11238-46. 2006
..Taken together, this study shows that tumor-associated macrophages play a key role in promoting tumor angiogenesis, an essential step in the tumor progression to malignancy...
- Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis
Regeneron Research Laboratories, 777 Old Saw Mill River Road, Tarrytown, New York 10591, USA
Nature 444:1032-7. 2006
- Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha
Johns Hopkins Oncology Center, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 USA
Genes Dev 14:34-44. 2000
..These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis...
- Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Nat Med 7:1194-201. 2001
..These data demonstrate that recruitment of VEGF-responsive BM-derived precursors is necessary and sufficient for tumor angiogenesis and suggest new clinical strategies to block tumor growth...
- VEGF-D promotes the metastatic spread of tumor cells via the lymphatics
S A Stacker
Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia
Nat Med 7:186-91. 2001
..This study demonstrates that lymphatics can be established in solid tumors and implicates VEGF family members in determining the route of metastatic spread...
- Angiogenesis in brain tumours
Rakesh K Jain
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA
Nat Rev Neurosci 8:610-22. 2007
..This creates a window of opportunity for optimally combining chemotherapeutics and radiation...
- Basement membranes: structure, assembly and role in tumour angiogenesis
Center for Matrix Biology, Department of Medicine, Dana 514, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Nat Rev Cancer 3:422-33. 2003
..Vascular BM components have recently been found to be involved in the regulation of tumour angiogenesis, making them attractive candidate targets for potential cancer therapies...
- An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis
Department of Biochemistry and Biophysics, Diabetes Center, and Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA
J Clin Invest 114:623-33. 2004
- Angiogenesis as a therapeutic target
Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Nature 438:967-74. 2005
..Therapeutic angiogenesis (promoting new vessel growth to treat ischaemic disorders) is an exciting frontier of cardiovascular medicine, but further understanding of the mechanisms of vascular morphogenesis is needed first...
- Tumor response to radiotherapy regulated by endothelial cell apoptosis
Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Science 300:1155-9. 2003
..These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range...
- Clinical translation of angiogenesis inhibitors
Molecular and Cellular Biology Research, Sunnybrook and Women s College Health Sciences Centre, S 218, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada
Nat Rev Cancer 2:727-39. 2002
..What are the most common questions that clinicians ask as they begin to test angiogenesis inhibitors in cancer clinical trials?..
- Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Cancer Cell 6:409-21. 2004
..Our data provide evidence that Gr+CD11b+ cells of immune origin induced by tumors directly contribute to tumor growth and vascularization by producing MMP9 and differentiating into ECs...
- VEGF as a key mediator of angiogenesis in cancer
Center for Transgene Technology and Gene Therapy, Flander s Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium
Oncology 69:4-10. 2005
..These characteristics mean that tumor blood flow is suboptimal, resulting in hypoxia and further VEGF production. This central role of VEGF in the production of tumor vasculature makes it a rational target for anticancer therapy...
- Role of tumor-associated macrophages in tumor progression and invasion
Istituto Clinico Humanitas, 20089 Rozzano, Milan, Italy
Cancer Metastasis Rev 25:315-22. 2006
..Here, we discuss evidence supporting the view that TAM represent a unique and distinct M2-skewed myeloid population and a potential target of anti-cancer therapy...
- Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis
Tumor Biology and Angiogenesis, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
Nature 444:1083-7. 2006
..Therefore, targeting Dll4 might represent a broadly efficacious and well-tolerated approach for the treatment of solid tumours...
- Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis
Immunology Program, H Lee Moffitt Cancer Center and Research Institute, Department of Oncology, University of South Florida College of Medicine, Tampa, Florida, FL 33612, USA
Oncogene 21:2000-8. 2002
..These studies provide evidence that the VEGF gene is regulated directly by Stat3 protein, and indicate that Stat3 represents a common molecular target for blocking angiogenesis induced by multiple signaling pathways in human cancers...
- Retinal angiogenesis in development and disease
Ray F Gariano
Department of Ophthalmology, A 157, 300 Pasteur Drive, Stanford University School of Medicine, Palo Alto, California 94305, USA
Nature 438:960-6. 2005
..The retina and its clinical disorders have a pivotal role in angiogenesis research and provide model systems in which to investigate neurovascular relationships and angiogenic diseases...
- Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us
Dana Farber Cancer Institute and the Department of Radiation Oncology, Harvard Medical School, Boston, MA 02115, USA
J Natl Cancer Inst 94:883-93. 2002
- Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
Nat Med 7:192-8. 2001
..These results establish the occurrence and biological significance of intratumoral lymphangiogenesis in breast cancer and identify VEGF-C as a molecular link between tumor lymphangiogenesis and metastasis...
- The role of myeloid cells in the promotion of tumour angiogenesis
Department of Oral and Maxillofacial Surgery, School of Clinical Dentistry, Beech Hill Road, University of Sheffield, Sheffield, UK
Nat Rev Cancer 8:618-31. 2008
..We also discuss the therapeutic implications of recent findings that specific myeloid cell populations modulate the responses of tumours to agents such as chemotherapy and some anti-angiogenic therapies...
- Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis
L M Coussens
Hormone Research Institute, University of California, San Francisco San Francisco, California 94143 0534, USA
Genes Dev 13:1382-97. 1999
- Rapid vascular regrowth in tumors after reversal of VEGF inhibition
Michael R Mancuso
Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, UCSF, San Francisco, California 94143 0452, USA
J Clin Invest 116:2610-21. 2006
- Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors
Department of Anatomy and Cardiovascular Research Institute and Comprehensive Cancer Center, University of California, San Francisco, California 94143 0130, USA
Am J Pathol 160:985-1000. 2002
..The association of pericytes with endothelial sprouts raises the possibility of an involvement in sprout growth or retraction in tumors...
- Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis
Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
Cytokine Growth Factor Rev 16:159-78. 2005
..Indeed, several experimental evidences point to a role for FGFs in tumor growth and angiogenesis. This review will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization...
- Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells
Genentech, Inc, 1 DNA Way, S San Francisco, California 94080, USA
Nat Biotechnol 25:911-20. 2007
..These findings indicate that, in our models, refractoriness to anti-VEGF treatment is determined by the ability of tumors to prime and recruit CD11b+Gr1+ cells...
- Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium
Nature 394:485-90. 1998
..As hypoxic stress contributes to many (patho)biological disorders, this new role for HIF-1alpha in hypoxic control of cell growth and death may be of general pathophysiological importance...
- The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions
Division of Genetics, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokane dai, Minato ku, Tokyo, 108 8639, Japan
Clin Sci (Lond) 109:227-41. 2005
..Recent progress in the molecular and biological understanding of the VEGF/VEGFR system provides us with novel and promising therapeutic strategies and target proteins for overcoming a variety of diseases...
- Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases
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...
- SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types
T A Fong
SUGEN, Inc, South San Francisco, California 94080, USA
Cancer Res 59:99-106. 1999
..These findings support that pharmacological inhibition of the enzymatic activity of the vascular endothelial growth factor receptor represents a novel strategy for limiting the growth of a wide variety of tumor types...
- Metalloproteinases: role in breast carcinogenesis, invasion and metastasis
M J Duffy
Department of Nuclear Medicine, St Vincent s Hospital, Dublin, Ireland
Breast Cancer Res 2:252-7. 2000
..Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing breast cancer and in blocking metastasis of established tumours..
- Interleukin-8 as a macrophage-derived mediator of angiogenesis
A E Koch
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611
Science 258:1798-801. 1992
..These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair...
- Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3
Dana D Hu-Lowe
Department of Cancer Biology, PGRD La Jolla, Pfizer, Inc, San Diego, California 92121, USA
Clin Cancer Res 14:7272-83. 2008
..We provide a comprehensive description of its in vitro characteristics and activities, in vivo antiangiogenesis, and antitumor efficacy and translational pharmacology data...
- Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium
Nat Med 8:831-40. 2002
..Thus, PlGF and Flt1 constitute potential candidates for therapeutic modulation of angiogenesis and inflammation...
- Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth
Tumor Biology and Angiogenesis, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
Cancer Cell 11:53-67. 2007
..We propose that blocking NRP1 function inhibits vascular remodeling, rendering vessels more susceptible to anti-VEGF therapy...
- Antiangiogenesis in cancer therapy--endostatin and its mechanisms of action
Children s Hospital Harvard Medical School, Cambridge, MA, USA
Exp Cell Res 312:594-607. 2006
- MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer
Diabetes Center, University of California at San Francisco, San Francisco, California 94143, USA
Genes Dev 23:2152-65. 2009
..Many of the miR changes associated with specific stages and hallmark capabilities in the mouse model are similarly altered in human tumors, including cognate pancreatic neuroendocrine tumors, implying a generality...
- Molecular and biological properties of vascular endothelial growth factor
Department of Cardiovascular Research, Genentech Inc, South San Francisco, CA 94080, USA
J Mol Med (Berl) 77:527-43. 1999
..Currently, both therapeutic angiogenesis using recombinant VEGF or VEGF gene transfer and inhibition of VEGF-mediated pathological angiogenesis are being pursued...
- Tumor angiogenesis: past, present and the near future
R S Kerbel
Sunnybrook and Women s College Health Sciences Centre, Division of Cancer Biology Research, S 218 Research Building, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada
Carcinogenesis 21:505-15. 2000
..Also of concern is that the expected need to use anti-angiogenic drugs chronically will lead to delayed toxic side effects in humans, which do not appear in rodents, especially in short-term studies...
- The anti-angiogenic basis of metronomic chemotherapy
Robert S Kerbel
Molecular and Cellular Biology Research, Sunnybrook and Women s College Health Sciences Centre, S 217, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada
Nat Rev Cancer 4:423-36. 2004
- JunD reduces tumor angiogenesis by protecting cells from oxidative stress
Unit of Gene Expression and Diseases, CNRS URA 1644, Pasteur Institute, 25 rue du Docteur Roux, 75724 Paris, Cedex 15, France
Cell 118:781-94. 2004
..Furthermore, we provide new insights into the regulation of PHD activity, allowing immediate reactive adaptation to changes in O2 or iron levels in the cell...
- Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption
J L Rubenstein
Division of Hematology Oncology, University of California, San Francisco, USA
Neoplasia 2:306-14. 2000
- Origin of endothelial progenitors in human postnatal bone marrow
Stem Cell Institute, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
J Clin Invest 109:337-46. 2002
..Because MAPCs can be expanded in culture without obvious senescence for more than 80 population doublings, they may be an important source of endothelial cells for cellular pro- or anti-angiogenic therapies...
- Vascular endothelial growth factor is a secreted angiogenic mitogen
D W Leung
Department of Molecular Biology, Genetech, South San Francisco, CA 94080
Science 246:1306-9. 1989
..Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF...
- Hypoxia signalling in cancer and approaches to enforce tumour regression
Institute of Signalling, Developmental Biology and Cancer Research, CNRS UMR 6543, University of Nice, Centre Antoine Lacassagne, 33 Avenue Valombrose, 06189 Nice, France
Nature 441:437-43. 2006
..There are new approaches to enforce necrotic cell death and tumour regression by targeting tumour metabolism and pH(i)-control systems...
- Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin
Center for Matrix Biology, Department of Medicine and Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
Cancer Cell 3:589-601. 2003
..These results indicate that MMP-generated fragments of basement membrane collagen can have endogenous function as integrin-mediated suppressors of pathologic angiogenesis and tumor growth...
- A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer
James C Yang
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
N Engl J Med 349:427-34. 2003
..We conducted a clinical trial to evaluate bevacizumab, a neutralizing antibody against vascular endothelial growth factor, in patients with metastatic renal-cell carcinoma...
- Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis
M S Pepper
Department of Morphology, University Medical Center, Geneva, Switzerland
Arterioscler Thromb Vasc Biol 21:1104-17. 2001
..Antiproteolysis, particularly in the context of angiogenesis, has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization...
- Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors
Dawid G Nowak
Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
J Cell Sci 121:3487-95. 2008
- Vascular endothelial growth factor signaling pathways: therapeutic perspective
Genentech, Inc, South San Francisco, California 94080, USA
Clin Cancer Res 12:5018-22. 2006
..Aberrant VEGF signaling is also a feature of several other pathologic conditions, such as age-related macular degeneration and rheumatoid arthritis...
- Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization
Daniel J Nolan
Cancer Genome Research Center, Cold Spring Harbor Laboratory, Woodbury, New York 11797, USA
Genes Dev 21:1546-58. 2007
..Our results demonstrate that BM-derived EPCs are critical components of the earliest phases of tumor neoangiogenesis...
- Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response
Mark W Dewhirst
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA
Nat Rev Cancer 8:425-37. 2008
..HIF1 can then promote endothelial and tumour cell survival. As discussed here, a constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit...
- 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF
Nicola J Mabjeesh
Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
Cancer Cell 3:363-75. 2003
..These data establish 2ME2 as a small molecule inhibitor of HIF-1 and provide a mechanistic link between the disruption of the MT cytoskeleton and inhibition of angiogenesis...
- Matrix metalloproteinases and angiogenesis
Joyce E Rundhaug
Department of Carcinogenesis, Science Park Research Division, The University of Texas M D Anderson Cancer Center, Smithville, TX, 78957, USA
J Cell Mol Med 9:267-85. 2005
..However, because of the multiple effects of MMPs on angiogenesis, careful testing of these MMP inhibitors is necessary to show that these compounds do not actually enhance angiogenesis...
- Fibroblasts in cancer
Center for Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Nat Rev Cancer 6:392-401. 2006
..Fibroblasts are therefore a key determinant in the malignant progression of cancer and represent an important target for cancer therapies...
- Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells
Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 279:1304-9. 2004
..These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells...
- Role of angiogenesis in human tumor dormancy: animal models of the angiogenic switch
George N Naumov
Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA
Cell Cycle 5:1779-87. 2006
- Bone marrow-derived cells do not incorporate into the adult growing vasculature
Max Planck Institute for Clinical and Physiological Research, Bad Nauheim, Germany
Circ Res 94:230-8. 2004
..Our findings suggest that in the adult organism, bone marrow-Derived cells do not promote vascular growth by incorporating into vessel walls but may function as supporting cells...
- Reduced angiogenesis and tumor progression in gelatinase A-deficient mice
Shionogi Institute for Medical Science, Shionogi and Co, Ltd, Osaka, Japan
Cancer Res 58:1048-51. 1998
..014 and P < 0.0015, respectively). These results indicated that host-derived gelatinase A plays an important role in angiogenesis and tumor progression, suggesting the usefulness of gelatinase A inhibitors for anticancer chemotherapy...
- Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles 90095, USA
J Cell Biol 169:681-91. 2005
..Our findings support the view that matrix-bound VEGF and nontethered VEGF provide different signaling outcomes. These findings reveal a novel aspect in the regulation of extracellular VEGF that holds significance for vascular patterning...
- ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration
Stephen R Wedge
Department of Cancer and Infection Research, AstraZeneca, Cheshire SK10 4TG, United Kingdom
Cancer Res 62:4645-55. 2002
..4 cm(3) volume. ZD6474 is currently in Phase I clinical development as a once-daily oral therapy in patients with advanced cancer...
- Alternative vascularization mechanisms in cancer: Pathology and therapeutic implications
Department of Tumor Biology and Thoracic Oncology, National Koranyi Institute of Pulmonology, Budapest, Hungary
Am J Pathol 170:1-15. 2007
..This review intends to integrate our recent knowledge in this field into a rational strategy that could be the basis for developing effective clinical modalities using antivascular therapy for cancer...
- The hypoxic response of tumors is dependent on their microenvironment
Molecular Biology Section, Division of Biological Sciences, University of California at San Diego, Pacific Hall Room 1212, MC 0366, 9500 Gilman Drive, La Jolla, CA 92093, USA
Cancer Cell 4:133-46. 2003
..These results demonstrate that HIF-1alpha has differential roles in tumor progression, which are greatly dependent on the extant microenvironment of the tumor...
- Loss of HIF-1alpha in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis
Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, San Diego, California 92093, USA
Cancer Cell 6:485-95. 2004
..We thus show that a HIF-1alpha-driven, VEGF-mediated autocrine loop in EC is an essential component of solid tumor angiogenesis...
- Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1
K M Dameron
Department of Microbiology Immunology, Northwestern University Medical School, Chicago, IL 60611
Science 265:1582-4. 1994
..These data indicate that, in fibroblasts, wild-type p53 inhibits angiogenesis through regulation of TSP-1 synthesis...
- Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo
Kathleen M Leahy
Pharmacia, Mail Zone AA4C, 700 Chesterfield Parkway, Chesterfield, Missouri 63017, USA
Cancer Res 62:625-31. 2002
..2-3.0-fold) in response to celecoxib. Thus, the antitumor activity of celecoxib may be attributable, at least in part, to a direct effect on host stromal elements, such as the angiogenic vasculature...
- Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize
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...
- Antiangiogenic therapy: a universal chemosensitization strategy for cancer?
Robert S Kerbel
Sunnybrook Health Sciences Centre, Departments of Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M4N 3M5, Canada
Science 312:1171-5. 2006
..I then discuss how these potential mechanisms might be exploited to maximize therapeutic efficacy...