Journal Article

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

Liu, Xiao-Yu, Liao, Wei-Hua, Jiang, Wu-Zhong, Cao, Ya, Yang, Li-Fang, Zhou, Gao-Feng, Wang, Xiao-Yi, Hou, Bob-Lei, Sun, Lun-Quan

2014

Overview

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 K trans 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., K trans , k ep , v e ) using nordicICE software. Results Both K trans and k ep values for NPC tumor tissues decreased for both groups after treatment. Moreover, a statistically significant difference in K trans 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 k ep values, the downward trend observed for both the combined treatment group and the radiotherapy alone group were similar. In contrast, v e 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 K trans values for patients with NPC. Correspondingly, the LMP1-targeted DNAzyme treatments were found to affect the angiogenesis and microvascular permeability of NPC. Trial registration ClinicalTrials.gov: NCT01449942 . Registered 6 October 2011.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Adult / Angiogenesis / Apoptosis / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer therapies / Carcinoma / Clinical oncology / Cohort Studies / Combined Modality Therapy / DNA, Catalytic - administration & dosage / DNA, Catalytic - adverse effects / DNA, Catalytic - genetics / Down-Regulation / Drug dosages / Epstein-Barr virus / Female / Gene expression / Gene Expression Regulation / Health Promotion and Disease Prevention / Hospitals / Humans / Image Processing, Computer-Assisted / Kinases / Magnetic Resonance Imaging - methods / Male / Medical research / Medicine/Public Health / Middle Aged / Nasopharyngeal Carcinoma / Nasopharyngeal Neoplasms - diagnosis / Nasopharyngeal Neoplasms - genetics / Nasopharyngeal Neoplasms - pathology / Nasopharyngeal Neoplasms - therapy / Neoplasm Staging / Neovascularization, Pathologic - diagnosis / Neovascularization, Pathologic - genetics / NMR / Nuclear magnetic resonance / Oncology / Permeability / Plasma / Proteins / Radiation therapy / Radiotherapy - adverse effects / Research Article / Studies / Surgical Oncology / Treatment Outcome / Viral Matrix Proteins - genetics