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: UMLS:C0017636 (
glioblastoma
)
18,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH
2
), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH
2
carrying mature miR-34a targets
C-MET
, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH
2
, miRNA is stable in plasma and able to cross the blood-brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH
2
-miR-34a in a human
glioblastoma
mouse model. We hereby present a promising technology using dPG-NH
2
-miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity.
...
PMID:Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex. 2726 33
Positron emission tomography (PET) imaging can assist in the early-phase diagnostic and therapeutic evaluation of tumors. Here, we report the radiosynthesis, small animal PET imaging, and biological evaluation of a L-type amino acid transporter 1 (LAT1)-specific PET probe,
18
F-FIMP. This probe demonstrates increased tumor specificity, compared to existing tumor-specific PET probes (
18
F-FET,
11
C-MET
, and
18
F-FDG). Evaluation of probes by in vivo PET imaging,
18
F-FIMP showed intense accumulation in LAT1-positive tumor tissues, but not in inflamed lesions, whereas intense accumulation of
18
F-FDG was observed in both tumor tissues and in inflamed lesions. Metabolite analysis showed that
18
F-FIMP was stable in liver microsomes, and mice tissues (plasma, urine, liver, pancreas, and tumor). Investigation of the protein incorporation of
18
F-FIMP showed that it was not incorporated into protein. Furthermore, the expected mean absorbed dose of
18
F-FIMP in humans was comparable or slightly higher than that of
18
F-FDG and indicated that
18
F-FIMP may be a safe PET probe for use in humans.
18
F-FIMP may provide improved specificity for tumor diagnosis, compared to
18
F-FDG,
18
F-FET, and
11
C-MET
. This probe may be suitable for PET imaging for
glioblastoma
and the early-phase monitoring of cancer therapy outcomes.
...
PMID:
18
F-FIMP: a LAT1-specific PET probe for discrimination between tumor tissue and inflammation. 3167 30
