PMID- 20679253
OWN - NLM
STAT- MEDLINE
DCOM- 20110131
LR  - 20240109
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 12
IP  - 11
DP  - 2010 Nov
TI  - Survivin knockdown and concurrent 4-HPR treatment controlled human glioblastoma 
      in vitro and in vivo.
PG  - 1088-101
LID - 10.1093/neuonc/noq079 [doi]
AB  - Survivin is highly expressed in most cancers, including glioblastoma, and it 
      plays a significant role in inhibiting apoptosis and promoting tumor growth. 
      Treatment of cancer cells with N-(4-hydroxyphenyl) retinamide (4-HPR) induces 
      apoptosis through destabilization of mitochondrial membrane and activation of 
      caspase-mediated apoptotic pathways. We studied the efficacy of a combination of 
      survivin knockdown and 4-HPR treatment to induce apoptosis and inhibit invasion, 
      angiogenesis, and growth of human glioblastomas in vitro and in vivo. Using a 
      plasmid encoding survivin shRNA, we downregulated survivin in glioblastoma U251MG 
      and U118MG cells and simultaneously treated with 1 microM 4-HPR for 48 hours. Cells 
      following treatments were subjected to the terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) and invasion assays. In vivo 
      angiogenesis and tumor regression studies were performed in nude mice. TUNEL 
      assay demonstrated apoptosis in more than 80% of cells after survivin knockdown 
      and 4-HPR treatment. Matrigel invasion assays demonstrated marked decreases in 
      tumor cell invasion. In vivo angiogenesis studies depicted a remarkable 
      inhibition of neovascularization due to the knockdown of survivin and 4-HPR 
      treatment. Imaging of intracerebral tumorigenesis and longitudinal studies on 
      subcutaneous solid tumor formation showed dramatic decreases in tumorigenesis and 
      solid tumor progression, respectively, after treatment with the combination. 
      Studies to elucidate the molecular mechanisms of the inhibition of angiogenesis 
      and tumor regression demonstrated marked decreases in proliferating cell nuclear 
      antigen, metalloproteinase-9, vascular endothelial growth factor, basic 
      fibroblast growth factor, and CD31 in solid tumors. Our data demonstrated that 
      survivin knockdown and concurrent 4-HPR treatment could be a novel therapeutic 
      strategy for controlling growth of human glioblastomas.
FAU - George, Joseph
AU  - George J
AD  - Department of Pathology, Microbiology, and Immunology, University of South 
      Carolina School of Medicine, Columbia, SC 29209, USA.
FAU - Banik, Naren L
AU  - Banik NL
FAU - Ray, Swapan K
AU  - Ray SK
LA  - eng
GR  - R01 CA-91460/CA/NCI NIH HHS/United States
GR  - R01 NS-57811/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100802
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Antineoplastic Agents)
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Survivin)
RN  - 187EJ7QEXL (Fenretinide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects/genetics
MH  - Blotting, Western
MH  - Brain Neoplasms/*therapy
MH  - Combined Modality Therapy/methods
MH  - Fenretinide/*pharmacology
MH  - Gene Knockdown Techniques
MH  - Genetic Therapy/*methods
MH  - Glioblastoma/genetics/*therapy
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Inhibitor of Apoptosis Proteins
MH  - Mice
MH  - Mice, Nude
MH  - Microtubule-Associated Proteins/*antagonists & inhibitors/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survivin
MH  - Transfection
MH  - Xenograft Model Antitumor Assays
PMC - PMC3098031
EDAT- 2010/08/04 06:00
MHDA- 2011/02/01 06:00
PMCR- 2011/11/01
CRDT- 2010/08/04 06:00
PHST- 2010/08/04 06:00 [entrez]
PHST- 2010/08/04 06:00 [pubmed]
PHST- 2011/02/01 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - noq079 [pii]
AID - 10.1093/neuonc/noq079 [doi]
PST - ppublish
SO  - Neuro Oncol. 2010 Nov;12(11):1088-101. doi: 10.1093/neuonc/noq079. Epub 2010 Aug 
      2.