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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.
PMCID: PMC3916047  PMID: 24322331
2.  Correlation of Volume Transfer Coefficient Ktrans with Histopathologic Grades of Gliomas 
To evaluate the roles of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and optimum tracer kinetic parameters in the noninvasive grading of the glial brain tumors with histopathological grades (I–IV).
Materials and Methods
Twenty eight patients with histopathologically graded gliomas were imaged. Images with five flip angles were acquired before injection of gadolinium-DTPA and were processed to calculate the T1 value of each regions of interest (ROI). All the DCE-MRI data acquired during the injection were processed based on the MRI signal and pharmacokinetic models to establish concentration-time curves in the ROIs drawn within the tumors, counterlateral normal areas, and area of the individual artery input functions (iAIF) of each patient. A nonlinear least square fitting method was used to obtain tracer kinetic parameters. Kruskal-Wallis H-test and Mann-Whitney U-test were applied to these parameters in different histopathological grade groups for statistical differences (P<0.05).
Volume transfer coefficient (Ktrans) and extravascular extracellular space volume fraction (Ve) calculated by using iAIFs can be used not only to distinguish the low (i.e., I and II) from the high (i.e., III and IV) grade gliomas (P(Ktrans) <0.001 and PVe<0.001), but also grade II from III (P(Ktrans) =0.016 and PVe=0.033).
Ktrans is the most sensitive and specific parameter in the noninvasive grading, distinguishing the high (III and IV) from the low (I and II) grade and high grade III from low grade II gliomas.
PMCID: PMC3399966  PMID: 22581762
MR perfusion imaging; gliomas; microvascular permeability; pharmacokinetics; grades of glioma
3.  Safety and Efficacy of Bevacizumab with Hypofractionated Stereotactic Irradiation for Recurrent Malignant Gliomas 
Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of the concurrent use of bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas.
Methods and Materials
After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg IV) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in 5 fractions after the first cycle of bevacizumab.
Twenty-five patients (20 GBM and 5 AG) median age of 56 years (range, 30 to 80) and median KPS 90 (range, 70 to 100) received a median of 7 cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment due to: grade 3 CNS intratumoral hemorrhage, wound dehiscence and bowel perforation. Other non-hematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously-irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression free survival was 65%; median overall survival was 12.5 months and 1-year survival was 54%.
Bevacizumab in combination with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control and survival suggest that this regimen is active in recurrent malignant glioma.
PMCID: PMC3659401  PMID: 19167838
malignant gliomas; glioblastoma; bevacizumab; anti-angiogenesis; intensity-modulated radiation therapy
4.  Cerebral sparganosis in children: epidemiological, clinical and MR imaging characteristics 
BMC Pediatrics  2012;12:155.
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.
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.
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.
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.
PMCID: PMC3484034  PMID: 23006504
5.  Functional magnetic resonance imaging (fMRI) changes and saliva production associated with acupuncture at LI-2 acupuncture point: a randomized controlled study 
Clinical studies suggest that acupuncture can stimulate saliva production and reduce xerostomia (dry mouth). We were interested in exploring the neuronal substrates involved in such responses.
In a randomized, sham acupuncture controlled, subject blinded trial, twenty healthy volunteers received true and sham acupuncture in random order. Cortical regions that were activated or deactivated during the interventions were evaluated by functional magnetic resonance imaging (fMRI). Saliva production was also measured.
Unilateral manual acupuncture stimulation at LI-2, a point commonly used in clinical practice to treat xerostomia, was associated with bilateral activation of the insula and adjacent operculum. Sham acupuncture at an adjacent site induced neither activation nor deactivation. True acupuncture induced more saliva production than sham acupuncture.
Acupuncture at LI-2 was associated with neuronal activations absent during sham acupuncture stimulation. Neuroimaging signal changes appear correlated to saliva production.
PMCID: PMC2474572  PMID: 18606019

Results 1-5 (5)