PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-3 (3)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
more »
Year of Publication
Document Types
1.  Therapeutic Evaluation of Epstein-Barr Virus-encoded Latent Membrane Protein-1 Targeted DNAzyme for Treating of Nasopharyngeal Carcinomas 
Molecular Therapy  2013;22(2):371-377.
The ability of the 10–23 DNAzyme to specifically cleave RNA with high efficiency has fuelled expectation that this agent may have useful applications for targeted therapy. Here, we, for the first time, investigated the antitumor and radiosensitizing effects of a DNAzyme (DZ1) targeted to the Epstein-Barr virus (EBV)-LMP1 mRNA of nasopharyngeal carcinoma (NPC) in patients. Preclinical studies indicated that the DNAzyme was safe and well tolerated. A randomized and double-blind clinical study was conducted in 40 NPC patients who received DZ1 or saline intratumorally, in conjunction with radiation therapy. Tumor regression, patient survival, EBV DNA copy number and tumor microvascular permeability were assessed in a 3-month follow-up. The mean tumor regression rate at week 12 was significantly higher in DZ1 treated group than in the saline control group. Molecular imaging analysis showed that DZ1 impacted on tumor microvascular permeability as evidenced by a faster decline of the Ktrans in DZ1-treated patients. The percentage of the samples with undetectable level of EBV DNA copy in the DZ1 group was significantly higher than that in the control group. No adverse events that could be attributed to the DZ1 injection were observed in patients.
doi:10.1038/mt.2013.257
PMCID: PMC3916047  PMID: 24322331
2.  Antiangiogenic and Antitumoral Effects Mediated by a Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1)-Targeted DNAzyme 
Molecular Medicine  2013;19(1):377-386.
Antiangiogenesis is a promising antitumor strategy that inhibits tumor vascular formation to suppress tumor growth. DNAzymes are synthetic single-strand deoxyribonucleic acid (DNA) molecules that can cleave ribonucleic acids (RNAs). Here, we conducted a comprehensive in vitro selection of active DNAzymes for their activity to cleave the vascular endothelial growth factor receptor (VEGFR-1) mRNA and screened for their biological activity in a matrigel tube-formation assay. Among the selected DNAzymes, DT18 was defined as a lead molecule that was further investigated in several model systems. In a rat corneal vascularization model, DT18 demonstrated significant and specific antiangiogenic activity, as evidenced by the reduced area and vessel number in VEGF-induced corneal angiogenesis. In a mouse melanoma model, DT18 was shown to inhibit B16 tumor growth, whereas it did not affect B16 cell proliferation. We further assessed the DT18 effect in mice with established human nasopharyngeal carcinoma (NPC). A significant inhibition of tumor growth was observed, which accompanied downregulation of VEGFR-1 expression in NPC tumor tissues. To evaluate DT18 effect on vasculature, we performed dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) on the human NPC xenograft mice treated with DT18 and showed a reduction of the parameter of Ktrans (volume constant for transfer of contrast agent), which reflects the condition of tumor microvascular permeability. When examining the safety and tolerability of DT18, intravenous administration of Dz18 to healthy mice caused no substantial toxicities, as shown by parameters such as body weight, liver/kidney function, and histological and biochemical analyses. Taken together, our data suggest that the anti-VEGFR-1 DNAzyme may be used as a therapeutic agent for the treatment of cancer, such as NPC.
doi:10.2119/molmed.2013.00090
PMCID: PMC3883960  PMID: 24306423
3.  Cerebral sparganosis in children: epidemiological, clinical and MR imaging characteristics 
BMC Pediatrics  2012;12:155.
Background
Cerebral sparganosis in children is an extremely rare disease of central nervous system, and caused by a tapeworm larva from the genus of Spirometra. In this study, we discussed and summarized epidemiological, clinical and MR imaging characteristics of eighteen children with cerebral sparganosis for a better diagnosis and treatment of the disease.
Methods
Eighteen children with cerebral sparganosis verified by pathology, serological tests and MR presentations were retrospectively investigated, and the epidemiologic and clinical characteristics of the disease were studied.
Results
Twenty-seven lesions were found in the eighteen children. Twelve lesions in twelve patients were solitary while the lesions in the rest six patients were multiple and asymmetrical. The positions of the lesions were: seven in frontal, eleven in parietal, four in temporal and two in occipital lobes, one in basal ganglia, one in cerebella hemisphere and one in pons. The lesions were presented as slight hypointensity on T1-weighted images but moderate hyperintensity on T2-weighted images with perilesional brain parenchyma edema. Enhanced MR scans by using Gadopentetic Acid Dimeglumine Salt were performed in the patients, and the images demonstrated abnormal enhancements with the patterns of a peripheral ring, or a tortuous beaded, or a serpiginous tubular shape. Follow-up MR scans were preformed for eight patients, and three out of the eight cases exposed migrations and changes in shapes of the lesion areas.
Conclusions
The MR presentations in our study in general were similar to those in previous studies. However serpiginous tubular and comma-shaped enhancements of lesions have not been previously reported. The enhanced MR imaging and follow-up MR scans with the positive results from serological tests are the most important methods for the clinical diagnosis of cerebral sparganosis in children.
doi:10.1186/1471-2431-12-155
PMCID: PMC3484034  PMID: 23006504

Results 1-3 (3)