Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.4.1 (
phosphodiesterase
)
18,767
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glioblastoma
(
GBM
) is the most common and aggressive primary brain tumor. Currently, treatment is ineffective and the median overall survival is 20.9 months. The poor prognosis of
GBM
is a consequence of several altered signaling pathways that favor the proliferation and survival of neoplastic cells. One of these pathways is the deregulation of phosphodiesterases (PDEs). These enzymes participate in the development of
GBM
and may have value as therapeutic targets to treat
GBM
. Methylxanthines (MXTs) such as caffeine, theophylline, and theobromine are
PDE
inhibitors and constitute a promising therapeutic anti-cancer agent against
GBM
. MTXs also regulate various cell processes such as proliferation, migration, cell death, and differentiation; these processes are related to cancer progression, making MXTs potential therapeutic agents in
GBM
.
...
PMID:Methylxanthines: Potential Therapeutic Agents for Glioblastoma. 3150 Feb 85
Glioblastoma
(
GBM
) is the most aggressive malignant primary brain tumour in adulthood. Despite strong research efforts current treatment options have a limited impact on glioma stem-like cells (GSCs) which contribute to
GBM
formation, progression and chemoresistance. Invasive growth of GSCs is in part associated with epithelial-mesenchymal-like transition (EMT), a mechanism associated with CD73 in several cancers. Here, we show that CD73 regulates the EMT activator SNAIL1 and further investigate the role of enzymatic and non-enzymatic CD73 activity in
GBM
progression. Reduction of CD73 protein resulted in significant suppression of GSC viability, proliferation and clonogenicity, whereas CD73 enzymatic activity exhibited negative effects only on GSC invasion involving impaired downstream adenosine (ADO) signalling. Furthermore, application of
phosphodiesterase
inhibitor pentoxifylline, a potent immunomodulator, effectively inhibited ZEB1 and CD73 expression and significantly decreased viability, clonogenicity, and invasion of GSC in vitro cultures. Given the involvement of adenosine and A
3
adenosine receptor in GSC invasion, we investigated the effect of the pharmacological inhibition of A
3
AR on GSC maintenance. Direct A
3
AR inhibition promoted apoptotic cell death and impaired the clonogenicity of GSC cultures. Taken together, our data indicate that CD73 is an exciting novel target in
GBM
therapy. Moreover, pharmacological interference, resulting in disturbed ADO signalling, provides new opportunities to innovate
GBM
therapy.
...
PMID:Enzymatic Activity of CD73 Modulates Invasion of Gliomas via Epithelial-Mesenchymal Transition-Like Reprogramming. 3318 81
