Research Update in
Neuroscience for Neurosurgeons

Patricia A. D'Amore
Harvard Medical School
Schepens Eye Institute

"Angiogenesis and Neoplasia"

The process of angiogenesis encompasses the growth and regression of capillary blood vessels. Angiogenesis is finely regulated at the molecular and genetic levels, not unlike other physiologic processes such as coagulation, glucose metabolism, and blood pressure. During the development of the field of angiogenesis research over the past three decades, fundamental concepts have been introduced along the way in an attempt where possible, to unify new data from a variety of different laboratories. I have assembled here the major concepts, which underlie the angiogenic process as we currently understand it. Many of these are now taken for granted, but this was not always the case, and I have tried to show how they were developed. My goal is to provide a conceptual framework for those basic scientists or clinicians who may enter this rapidly expanding field. Each concept discussed here is accompanied by a few key references as a guide to the pertinent literature.

Reviews

1. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 2008 Aug;8(8):592-603.
   
   
2. Cao Y, Molecular mechanisms and therapeutic development of angiogenesis inhibitors. Adv Canc Res 100; 113-131.


3. D'Amore PA. Vascular endothelial cell growth factor-a: not just for endothelial cells fanymore. Am J Pathol. 2007 Jul;171:14-8.


4. Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov. 2007 Apr;6(4):273-86.
   
   
5. Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT. Angiogenesis in brain tumours. Nat Rev Neurosci. 2007 Aug;8:610-22. Laquente B, Vinals F, Germa JR. Metronomic chemotherapy: an antiangiogenic scheduling. Clin Transl Oncol. 2007 Feb;9::93-8.
   
   
6. Laquente B, Vinals F, Germa JR. Metronomic chemotherapy: an antiangiogenic scheduling. Clin Transl Oncol. 2007 Feb;9::93-8.
   
   
7. Loges S, Mazzone M, Hohensinner P, Carmeliet P. Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell. 2009 Mar 3;15(3):167-70.
   
   
8. Wong ET, Brem S. Antiangiogenesis treatment for glioblastoma multiforme: challenges and opportunities. J Natl Compr Canc Netw. 2008 May;6(5):515-22. Review.
   
   

Primary papers

1. Kamba T, et al., (2005) VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H560-76.
   
   
2. Kuhnert F, Tam BY, Sennino B, Gray JT, Yuan J, Jocson A, Nayak NR, Mulligan RC, McDonald DM, Kuo CJ. Soluble receptor-mediated selective inhibition of VEGFR and PDGFRbeta signaling during physiologic and tumor angiogenesis.Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10185-90. Epub 2008 Jul 16.
   
   
3. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis.Cancer Cell. 2009 15:232-9.
   
   
4. Maharaj AS, Walshe TE, Saint-Geniez M, Venkatesha S, Maldonado AE, Himes NC, Matharu KS, Karumanchi SA, D'Amore PA. VEGF and TGF-beta are required for the maintenance of the choroid plexus and ependyma. J Exp Med. 2008 Feb 18;205(2):491-501. Epub 2008 Feb 11.
   
   
5. Maharaj AS, Saint-Geniez M, Maldonado AE, D'Amore PA. (2006) Vascular endothelial growth factor localization in the adult. Am J Pathol. 2006 Feb;168(2):639-48.
   
   

Copyright © 2008 The Society of Neurological Surgeons