title: Therapeutic evaluation of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme for treating of nasopharyngeal carcinomas.
abstract: 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 K(trans) 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.
authors: Cancer Research Institute and Key laboratory of Ministry of Education, Central South University, Changsha, China. Electronic address: ycao98@vip.sina.com.
authors: Ya
authors: Y
authors: Cao
authors: Cancer Research Institute and Key laboratory of Ministry of Education, Central South University, Changsha, China.
authors: Lifang
authors: L
authors: Yang
authors: Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors: Wuzhong
authors: W
authors: Jiang
authors: Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
authors: Xiaoyi
authors: X
authors: Wang
authors: Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
authors: Weihua
authors: W
authors: Liao
authors: Department of ENT, Xiangya Third Hospital, Central South University, Changsha, China.
authors: Guolin
authors: G
authors: Tan
authors: Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors: Yuping
authors: Y
authors: Liao
authors: Department of ENT, Xiangya Hospital, Central South University, Changsha, China.
authors: Yuanzheng
authors: Y
authors: Qiu
authors: Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
authors: Deyun
authors: D
authors: Feng
authors: Department of Clinical Chemistry, Xiangya Hospital, Central South University, Changsha, China.
authors: Faqing
authors: F
authors: Tang
authors: Department of Radiology, West Virginia University, Morgantown, West Virginia, USA.
authors: Bob L
authors: BL
authors: Hou
authors: Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors: Ling
authors: L
authors: Zhang
authors: Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors: Jia
authors: J
authors: Fu
authors: Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors: Fengjiao
authors: F
authors: He
authors: Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
authors: Xiaoyu
authors: X
authors: Liu
authors: Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors: Wenjuan
authors: W
authors: Jiang
authors: School of Public Health, Central South University, Changsha, China.
authors: Tubao
authors: T
authors: Yang
authors: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China. Electronic address: lunquansun@csu.edu.cn.
authors: Lun-Quan
authors: LQ
authors: Sun
mesh_terms: D000328:Adult; D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D021881:DNA, Catalytic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics* / Q000378:metabolism; D004279:DNA, Viral; D004195:Disease Models, Animal; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D017930:Genes, Reporter; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000821:virology; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D021881:DNA, Catalytic; D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins