PMID- 16041398
OWN - NLM
STAT- MEDLINE
DCOM- 20060425
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 146
IP  - 3
DP  - 2005 Oct
TI  - A comparison of the effects of unfractionated heparin, dalteparin and danaparoid 
      on vascular endothelial growth factor-induced tumour angiogenesis and heparanase 
      activity.
PG  - 333-43
AB  - Disseminated intravascular coagulation (DIC) is the most common complication of 
      solid tumours. In this study, the effectiveness of three polysaccharide 
      anticoagulants (PSAs), at therapeutic doses, at inhibiting solid tumour growth 
      was investigated. Mice with tumour xenografts were subcutaneously injected with 
      either unfractionated heparin (UFH; 200 units kg(-1) day(-1)), dalteparin (75 
      units kg(-1) day(-1)) or danaparoid (50 units kg(-1) day(-1)). At these 
      concentrations, these PSAs are equieffective at inhibiting blood coagulation 
      activated factor X. In mice with Lewis lung carcinoma (LLC) tumours dalteparin 
      and, to a lesser extent, UFH inhibited both tumour growth and angiogenesis, 
      whereas danaparoid did not. In contrast, in mice with KLN205 tumours, all the 
      PSAs inhibited tumour growth and angiogenesis. All the PSAs significantly 
      inhibited proliferation, migration of endothelial cells and vessel formation in 
      matrigel plugs containing vascular endothelial growth factor (VEGF) and there 
      were no significant differences between these effects of the PSAs. The PSAs had 
      no effect on endothelial cell tubular formation in vitro. Although all the PSAs 
      inhibited VEGF production in KLN205 tumours in vivo and cells in vitro, in LLC 
      tumours and cells only UFH and dalteparin inhibited VEGF production, whereas 
      danaparoid did not. In both LLC and KLN205 tumours in vivo, heparanase activity 
      was inhibited by UFH and dalteparin, but not by danaparoid. Hence, UFH and 
      dalteparin may be more effective than danaparoid at inhibiting cancer progression 
      in DIC patients with solid tumours, due at least in part to their ability to 
      suppress VEGF and heparanase in tumours.
FAU - Takahashi, Hidenori
AU  - Takahashi H
AD  - Department of Geriatric and Respiratory Medicine, Tohoku University School of 
      Medicine, Aoba-ku, Sendai, Japan.
FAU - Ebihara, Satoru
AU  - Ebihara S
FAU - Okazaki, Tatsuma
AU  - Okazaki T
FAU - Asada, Masanori
AU  - Asada M
FAU - Sasaki, Hidetada
AU  - Sasaki H
FAU - Yamaya, Mutsuo
AU  - Yamaya M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anticoagulants)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 24967-94-0 (Dermatan Sulfate)
RN  - 9001-29-0 (Factor X)
RN  - 9005-49-6 (Heparin)
RN  - 9007-28-7 (Chondroitin Sulfates)
RN  - 9050-30-0 (Heparitin Sulfate)
RN  - BI6GY4U9CW (danaparoid)
RN  - EC 3.2.1.- (heparanase)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/pharmacology
MH  - Bleeding Time
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Chondroitin Sulfates/*pharmacology
MH  - Dalteparin/*pharmacology
MH  - Dermatan Sulfate/*pharmacology
MH  - Endothelial Cells/cytology/drug effects
MH  - Factor X/analysis/antagonists & inhibitors
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Glucuronidase/genetics/*metabolism
MH  - Heparin/*pharmacology
MH  - Heparitin Sulfate/*pharmacology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Neovascularization, Pathologic
MH  - RNA, Messenger/analysis/metabolism
MH  - Tumor Burden/drug effects
MH  - Vascular Endothelial Growth Factor A
PMC - PMC1576289
EDAT- 2005/07/26 09:00
MHDA- 2006/04/28 09:00
PMCR- 2006/10/01
CRDT- 2005/07/26 09:00
PHST- 2005/07/26 09:00 [pubmed]
PHST- 2006/04/28 09:00 [medline]
PHST- 2005/07/26 09:00 [entrez]
PHST- 2006/10/01 00:00 [pmc-release]
AID - 0706344 [pii]
AID - 10.1038/sj.bjp.0706344 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2005 Oct;146(3):333-43. doi: 10.1038/sj.bjp.0706344.