Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.17.21 (prostate-specific membrane antigen)
 1,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To screen different combinations of prostate-specific membrane antigen (PSMA) promoter/enhancer with the strongest transcriptional activity in prostate-specific cells, we used PSMA regulatory elements to control specific expression of the target gene in gene therapy of prostate adenocarcinoma. PSMA promoter and enhancer DNA sequences were amplified from the LNCaP human prostate cancer cell line by polymerase chain reaction, then recombinant plasmids of the enhanced green fluorescent protein (EGFP: pEGFP-PSMA(Pro), pEGFP-PSMA(E-P), pEGFP-PSMA(E(r)-P), pEGFP-PSMA(E(d)-P), and pEGFP-PSMA(E(t)-P)) were constructed with molecular clonal techniques. At the same time, all experimental cell lines were analyzed for the expression of PSMA with the use of PSMA monoclonal antibody and the ABC immunohistochemical assay kit. After plasmids were transfected via liposome, we observed the expression of the reporter gene (EGFP) under a fluorescent microscope and compared the different levels of EGFP expression with reverse transcriptase polymerase chain reaction and flow cytometry so that we could choose the one with the highest transcriptional activity. Only the LNCaP cell line expressed PSMA positively with immunohistochemical stain. The PSMA promoter/enhancer had transcriptional activity in PSMA(+) cell lines and no activity in PSMA(-) cell lines. PSMA(E-P) achieved the strongest activity in different PSMA promoter/enhancer combinations. We confirmed the specific expression of PSMA in prostate cells again. Similarly, transcriptional activity of the PSMA promoter/enhancer was prostate specific. PSMA(E-P) achieved the strongest transcriptional activity among PSMA promoter/enhancer combinations, which could be used in advanced research for tissue-specific treatment.
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PMID:Construction of prostate-specific expressed recombinant plasmids with high transcriptional activity of prostate-specific membrane antigen (PSMA) promoter/enhancer. 1571 27

Multifunctional nanoparticle probes based on semiconductor quantum dots (QDs) are developed for simultaneous targeting and imaging of cancer cells in living animals. The structural design involves encapsulating luminescent QDs with an ABC triblock copolymer, and linking this polymer to tumor-targeting ligands, such as antibodies and drug-delivery functionalities. In vivo targeting studies of human prostate cancer growing in nude mouse show that the QD probes can be delivered to tumor sites by both enhanced permeation and retention (passive targeting) and by antibody binding to cancer-specific cell surface biomarkers such as prostate-specific membrane antigen (active targeting). Using both subcutaneous injection of QD-tagged cancer cells and the systemic injection of multifunctional QD probes, multicolor fluorescence imaging of as few as 10-100 cancer cells can be achieved under in vivo conditions. The use of spectrally resolved imaging can efficiently remove autofluorescence background and precisely delineate weak spectral signatures in vivo. These results suggest that QD probes and spectral imaging can be combined for multiplexed imaging and detection of genes, proteins, and small-molecule drugs in single living cells, and that this imaging modality can be adopted for real-time visualization of cancer cell metastasis in live animals.
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PMID:Quantum dots for in vivo molecular and cellular imaging. 1723 36

A novel amphiphilic ABC triblock copolymer, poly(N-isopropylacrylamide)-b-poly(styrene-alternate-maleic anhydride)-b-polystyrene (PNIPAAm-b-PSMA-b-PSt), was designed and synthesized by reversible addition fragmentation chain transfer polymerization. The copolymer can disperse in aqueous media at room temperature to self-assemble into pH- and thermo-responsive core-shell-corona micelles, with the hydrophobic PSt block as core, the pH-sensitive PSMA block as shell, and the thermo-sensitive PNIPAAm block as corona. The aqueous copolymer solutions exhibited lower critical solution temperature (LCST) values around 33.5-35 degrees C under pH 2.1-9.2 conditions via optical transmittance measurements. The critical micelle concentration values of the self-assembled micelles were about 18.6 mg/L at pH 2.1 and 21.1 mg/L at pH 6.9, respectively, relying on fluorescent probe techniques. An interesting pH- and thermo-dependent size of the micelles was observed by dynamic light scattering techniques, which showed that the micelle diameters were about 100-120 nm at 40 degrees C and 120-160 nm at 25 degrees C, corresponding to pH 2.1-9.2, respectively. Transmission electron microscopy observations showed that the resulting micelles as uniform nanoparticles existed in regularly spherical shapes. The folic acid-loaded micelles showed a remarkable pH- and thermo-responsive drug release behavior. These results indicate that the copolymer micelles may serve as a promising "intelligent" drug delivery system.
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PMID:Preparation of an amphiphilic triblock copolymer with pH- and thermo-responsiveness and self-assembled micelles applied to drug release. 1946 19