title: DCE-MRI assessment of the effect of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme on tumor vasculature in patients with nasopharyngeal carcinomas.
abstract: BACKGROUND
  EBV-encoded latent membrane protein 1 (EBV-LMP1) is an important oncogenic protein for nasopharyngeal carcinoma (NPC) and has been shown to engage a plethora of signaling pathways. Correspondingly, an LMP1-targeted DNAzyme was found to inhibit the growth of NPC cells both in vivo and in vitro by suppressing cell proliferation and inducing apoptosis. However, it remains unknown whether an LMP1-targeted DNAzyme would affect the vasculature of NPC. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been applied in the clinical trials of anti-angiogenic drugs for more than ten years, and Ktrans has been recommended as a primary endpoint. Therefore, the objective of the current study was to use DCE-MRI to longitudinally study the effect of an EBV-LMP1-targeted DNAzyme on the vasculature of patients with NPC.
  
  
  METHODS
  Twenty-four patients were randomly divided into two groups: a combined treatment group (radiotherapy + LMP1-targeted DNAzyme) and a radiotherapy alone group (radiotherapy + normal saline). DCE-MRI scans were conducted 1 ~ 2 days before radiotherapy (Pre-RT), during radiotherapy (RT 50 Gy), upon completion of radiotherapy (RT 70 Gy), and three months after radiotherapy (3 months post-RT). Parameters of vascular permeability and intra- and extravascular volumes were subsequently obtained (e.g., Ktrans, kep, ve) using nordicICE software.
  
  
  RESULTS
  Both Ktrans and kep values for NPC tumor tissues decreased for both groups after treatment. Moreover, a statistically significant difference in Ktrans values at the pre-therapy and post-therapy timepoints emerged earlier for the combined treatment group (RT 50 Gy, P =0.045) compared to the radiotherapy alone group (3 months post-RT, P = 0.032). For the kep values, the downward trend observed for both the combined treatment group and the radiotherapy alone group were similar. In contrast, ve values for all of the tumor tissues increased following therapy.
  
  
  CONCLUSIONS
  The EBV-LMP1-targeted DNAzyme that was tested was found to accelerate the decline of Ktrans values for patients with NPC. Correspondingly, the LMP1-targeted DNAzyme treatments were found to affect the angiogenesis and microvascular permeability of NPC.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01449942. Registered 6 October 2011.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Liao
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Yang
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liu
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Zhou
authors.forename: Wu-Zhong
authors.initials: WZ
authors.lastname: Jiang
authors.forename: Bob-Lei
authors.initials: BL
authors.lastname: Hou
authors.forename: Lun-Quan
authors.initials: LQ
authors.lastname: Sun
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China. ycao98@vip.sina.com.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Wang
mesh_terms: D000328:Adult; D002277:Carcinoma; D015331:Cohort Studies; D003131:Combined Modality Therapy; D021881:DNA, Catalytic / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000235:genetics*
chemical_list: D021881:DNA, Catalytic; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins