title: Macromolecule extravasation-xenograft size matters: a systematic study using probe-based confocal laser endomicroscopy (pCLE).
abstract: OBJECTIVE
  Profound changes of the vasculature in tumors critically impact drug delivery and therapy response. We aimed at developing a procedure to monitor morphological and functional parameters of the vasculature in subcutaneous xenograft models commonly applied for therapy testing by using probe-based confocal laser endomicroscopy.
  
  
  METHODS
  By monitoring various normal and diseased tissues, we established an experimental and analytical set-up to systematically analyze tracer extravasation from the microvasculature. Application of the approach in two xenograft models (HCT-116 and SW620) was realized consecutively throughout tumor growth.
  
  
  RESULTS
  The incidence of dilated vessels increased with xenograft size in both models while macromolecule extravasation and tracer accumulation in the tumor tissue, respectively, was significantly reduced throughout growth. The development of dilated/ultradilated vessels correlated with tracer extravasation only in the HCT-116 but not the SW620 model. The underlying mechanisms are still ambiguous and discussed.
  
  
  CONCLUSIONS
  Our findings clearly indicate that both xenograft type and size matter for drug delivery and therapy testing.
authors: Tumor Pathophysiology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Fetscherstraße 74, P.O. Box 41 , 01307, TU Dresden, Germany.
authors: Antje
authors: A
authors: Dietrich
authors: James
authors: J
authors: Stewart
authors: Melanie
authors: M
authors: Huether
authors: Mario
authors: M
authors: Helm
authors: Christina
authors: C
authors: Schuetze
authors: Hans-Joachim
authors: HJ
authors: Schnittler
authors: David A
authors: DA
authors: Jaffray
authors: Leoni A
authors: LA
authors: Kunz-Schughart
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000473:pathology*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods*; D009132:Muscles / Q000098:blood supply / Q000473:pathology; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic / Q000473:pathology*; D014059:Tongue / Q000098:blood supply / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
references: Eur J Cancer. 2004 Apr;40(6):827-36
references: 15120038
references: Nat Rev Cancer. 2004 Oct;4(10):806-13
references: 15510161
references: Gastroenterology. 2009 Nov;137(5):1584-92.e1
references: 19632230
references: Cancer Res. 1992 Apr 1;52(7):1993-5
references: 1551128
references: Lab Invest. 2000 Jan;80(1):99-115
references: 10653008
references: EMBO J. 2005 Oct 5;24(19):3400-10
references: 16148944
references: Int J Radiat Biol. 2009 Nov;85(11):1013-25
references: 19895278
references: J Clin Oncol. 2002 Nov 1;20(21):4368-80
references: 12409337
references: J Cell Biochem. 2007 Jul 1;101(4):937-49
references: 17171643
references: Nat Med. 2003 Jun;9(6):713-25
references: 12778170
references: Nature. 2000 Sep 14;407(6801):249-57
references: 11001068
references: APMIS. 2008 Jul-Aug;116(7-8):695-715
references: 18834413
references: Int J Exp Pathol. 2009 Jun;90(3):195-221
references: 19563606
references: Am J Pathol. 1988 Oct;133(1):95-109
references: 2459969
references: Angiogenesis. 2010 Jun;13(2):113-30
references: 20623252
references: Adv Drug Deliv Rev. 2011 Mar 18;63(3):136-51
references: 20441782
references: Br J Cancer. 2009 Mar 24;100(6):865-9
references: 19240721
references: Transl Oncol. 2008 Jul;1(2):84-94
references: 18633456
references: J Physiol Pharmacol. 2012 Jun;63(3):303-7
references: 22791645
references: Cancer Res. 1995 Sep 1;55(17):3752-6
references: 7641188
references: J Natl Cancer Inst. 2006 Mar 1;98(5):335-44
references: 16507830
references: N Engl J Med. 1986 Dec 25;315(26):1650-9
references: 3537791
references: Jpn J Cancer Res. 1998 Mar;89(3):307-14
references: 9600125
references: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):149-68
references: 11259838
references: Technol Cancer Res Treat. 2011 Feb;10(1):49-57
references: 21214288
references: J Vasc Res. 2004 Sep-Oct;41(5):400-11
references: 15467299
references: PLoS One. 2012;7(6):e40006
references: 22768196
references: J Histochem Cytochem. 2001 Apr;49(4):419-32
references: 11259444
references: Acta Pharmacol Toxicol (Copenh). 1969;27(5):331-48
references: 5395758
references: Neoplasia. 2000 Jan-Apr;2(1-2):53-61
references: 10933068
references: Angiogenesis. 2008;11(2):109-19
references: 18293091
references: Endoscopy. 2007 May;39(5):407-11
references: 17516346
references: BMC Cancer. 2008 Jan 07;8:2
references: 18179711
references: Biochim Biophys Acta. 2013 Jul;1832(7):1070-8
references: 23123598
references: Cancer Treat Res. 2006;130:1-38
references: 16610701
references: Cancer Chemother Pharmacol. 2003 Apr;51(4):321-7
references: 12721760