PMID- 17294805
OWN - NLM
STAT- MEDLINE
DCOM- 20070326
LR  - 20191110
IS  - 0965-0407 (Print)
IS  - 0965-0407 (Linking)
VI  - 16
IP  - 5
DP  - 2006
TI  - In vitro study of low molecular weight heparin effect on cell growth and cell 
      invasion in primary cell cultures of high-grade gliomas.
PG  - 245-50
AB  - Heparins represent the first choice for prevention and treatment of venous 
      thromboembolism. In particular, low molecular weight heparins (LMWHs) provide 
      pharmacokinetic advantages compared to unfractionated heparin (UFH): longer 
      half-life, better bioavailability, and lower binding to plasma proteins. In the 
      last years results of preclinical and clinical studies have suggested that LMWH 
      may be able to inhibit cell growth, cell invasion, and angiogenesis, which are 
      key mechanisms involved in tumor progression, possibly influencing favorable 
      clinical outcome in at least a proportion of cancer patients. In this work we 
      investigated the effect of LMWH (enoxaparin) on cell growth and cell invasion in 
      primary cell cultures obtained from high-grade glioma specimens: 5 anaplastic 
      astrocytoma (AA) and 13 glioblastoma multiforme (GBM). Apoptosis and expression 
      of the thrombin receptor PAR1 were also assessed. A significant decrease in tumor 
      cell growth was observed after treatment with 10 U/ml (-21%; p = 0.001) and 100 
      U/ml (-26%; p < 0.001); tumor cells from AA (grade III; WHO) were more affected 
      by LMWH treatment compared to cell lines from GBM (grade IV; WHO). The 
      antiproliferative effect was more pronounced in cell cultures displaying higher 
      expression of PAR1. Glioma cell cultures were able to invade a model of basement 
      membrane (Matrigel matrix) in standard culture conditions, but migration was not 
      modulated significantly by LMWH treatment at any of the concentrations tested (1, 
      10, 100 U/ml). In conclusion, our results confirm the antineoplastic effect of 
      LMWH, suggesting a potential direct role on tumor cell growth in high grade 
      gliomas.
FAU - Balzarotti, Marco
AU  - Balzarotti M
AD  - Laboratory of Clinical Investigation, Department of Neurology, Department of 
      Neurosurgery, National Neurological Institute "C. Besta," Via Celoria 11, 20133 
      Milan, Italy.
FAU - Fontana, Federica
AU  - Fontana F
FAU - Marras, Carlo
AU  - Marras C
FAU - Boiardi, Amerigo
AU  - Boiardi A
FAU - Croci, Danilo
AU  - Croci D
FAU - Ciusani, Emilio
AU  - Ciusani E
FAU - Salmaggi, Andrea
AU  - Salmaggi A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncol Res
JT  - Oncology research
JID - 9208097
RN  - 0 (Enoxaparin)
RN  - 0 (Receptor, PAR-1)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Apoptosis/drug effects
MH  - Brain Neoplasms/*drug therapy/metabolism
MH  - Cell Proliferation/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Enoxaparin/*pharmacology
MH  - Female
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Neoplastic/drug effects/genetics
MH  - Glioma/*drug therapy/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Weight
MH  - Neoplasm Invasiveness
MH  - Receptor, PAR-1/biosynthesis/drug effects/genetics
MH  - Sensitivity and Specificity
MH  - Structure-Activity Relationship
MH  - Tumor Cells, Cultured
EDAT- 2007/02/14 09:00
MHDA- 2007/03/27 09:00
CRDT- 2007/02/14 09:00
PHST- 2007/02/14 09:00 [pubmed]
PHST- 2007/03/27 09:00 [medline]
PHST- 2007/02/14 09:00 [entrez]
AID - 10.3727/000000006783981053 [doi]
PST - ppublish
SO  - Oncol Res. 2006;16(5):245-50. doi: 10.3727/000000006783981053.