PMID- 12059028
OWN - NLM
STAT- MEDLINE
DCOM- 20021206
LR  - 20190815
IS  - 0142-9612 (Print)
IS  - 0142-9612 (Linking)
VI  - 23
IP  - 13
DP  - 2002 Jul
TI  - Effects of NFkappaB decoy oligonucleotides released from biodegradable polymer 
      microparticles on a glioblastoma cell line.
PG  - 2773-81
AB  - The objectives of this study were to investigate a nuclear factor-kappa B 
      (NFkappaB) decoy oligonucleotide (ODN) strategy on the inhibition of glioblastoma 
      (GBM) cell line growth and to evaluate a poly(DL-lactic-co-glycolic acid) (PLGA) 
      microparticle delivery system for the NFKB decoy ODNs in vitro. We have 
      demonstrated that NFkappaB activation is important in regulating GBM cell line 
      growth. Aberrant nuclear expression of NFkappaB was found in a panel of GBM cell 
      lines, while untransformed glial cells did not display NFkappaB activity. Nuclear 
      translocation of NFkappaB was inhibited by using a 'decoy" ODN strategy. NFkappaB 
      decoy ODNs designed to inhibit NFkappaB resulted in a significant reduction in 
      cell number (up to 45%) compared to control cultures after 2 days. The reduction 
      in cell number correlated with a decrease in cyclin D1 protein expression and a 
      commensurate decrease in Cdk-4 activity. These results provide evidence 
      suggesting that NFkappaB mediates cell cycle progression and demonstrates a 
      mechanism linking increased NFkappaB activity with GBM cell growth and cell cycle 
      disregulation. Decoy ODNs were encapsulated at a yield of 66% in PLGA 
      microparticles and released in a controlled manner in phosphate buffered saline 
      for up to 28 days. Approximately 83% of entrapped ODNs were released by day 28. 
      During 3 days of GBM cell line culture, the released decoy ODNs retained their 
      biologic activity and led to significantly reduced cell number as compared to 
      control cultures. These findings offer a potential therapeutic strategy in the 
      control of human GBM cell line growth in vitro and suggest that PLGA 
      microparticles may be appropriate as delivery vehicles for the "decoy" ODN 
      strategy.
FAU - Gill, Jagjit S
AU  - Gill JS
AD  - Molecular Neuroscience Program, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Zhu, Xun
AU  - Zhu X
FAU - Moore, Michael J
AU  - Moore MJ
FAU - Lu, Lichun
AU  - Lu L
FAU - Yaszemski, Michael J
AU  - Yaszemski MJ
FAU - Windebank, Anthony J
AU  - Windebank AJ
LA  - eng
GR  - NS39764/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Biocompatible Materials)
RN  - 0 (NF-kappa B)
RN  - 0 (Oligonucleotides)
RN  - 0 (Polymers)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 136601-57-5 (Cyclin D1)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Biocompatible Materials/*pharmacology
MH  - *Biodegradation, Environmental
MH  - Blotting, Western
MH  - Cell Division
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cyclin D1/metabolism
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinases/metabolism
MH  - Glioblastoma/drug therapy
MH  - Humans
MH  - Immunoblotting
MH  - Kinetics
MH  - Lactic Acid/pharmacology
MH  - NF-kappa B/metabolism/*pharmacology
MH  - Neuroglia/cytology
MH  - Oligonucleotides/*pharmacology
MH  - Polyglycolic Acid/pharmacology
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Polymers/*pharmacology
MH  - *Proto-Oncogene Proteins
MH  - Time Factors
MH  - Tumor Cells, Cultured
EDAT- 2002/06/13 10:00
MHDA- 2002/12/07 04:00
CRDT- 2002/06/13 10:00
PHST- 2002/06/13 10:00 [pubmed]
PHST- 2002/12/07 04:00 [medline]
PHST- 2002/06/13 10:00 [entrez]
AID - S0142-9612(02)00013-3 [pii]
AID - 10.1016/s0142-9612(02)00013-3 [doi]
PST - ppublish
SO  - Biomaterials. 2002 Jul;23(13):2773-81. doi: 10.1016/s0142-9612(02)00013-3.