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author:("Sun, lizhong")
1.  Preclinical Study of Locoregional Therapy of Hepatocellular Carcinoma by Bioelectric Ablation with Microsecond Pulsed Electric Fields (μsPEFs) 
Scientific Reports  2015;5:9851.
Unresectable hepatocellular carcinoma (HCC) needs locoregional ablation as a curative or downstage therapy. Microsecond Pulsed Electric Fields (μsPEFs) is an option. A xenograft tumor model was set up on 48 nude mice by injecting human hepatocellular carcinoma Hep3B cells subcutaneously. The tumor-bearing mice were randomly divided into 3 groups: μsPEFs treated, sham and control group. μsPEFs group was treated by μsPEFs twice in 5 days. Tumor volume, survival, pathology, mitochondria function and cytokines were followed up. μsPEFs was also conducted on 3 swine to determine impact on organ functions. The tumors treated by μsPEFs were completely eradicated while tumors in control and sham groups grew up to 2 cm3 in 3 weeks. The μsPEFs-treated group indicated mitochondrial damage and tumor necrosis as shown in JC-1 test, flow cytometry, H&E staining and TEM. μsPEFs activates CD56+ and CD68+ cells and inhibits tumor proliferating cell nuclear antigen. μsPEFs inhibits HCC growth in the nude mice by causing mitochondria damage, tumor necrosis and non-specific inflammation. μsPEFs treats porcine livers without damaging vital organs. μsPEFs is a feasible minimally invasive locoregional ablation option.
PMCID: PMC4415577  PMID: 25928327
2.  Recent Advances in Molecular Magnetic Resonance Imaging of Liver Fibrosis 
BioMed Research International  2015;2015:595467.
Liver fibrosis is a life-threatening disease with high morbidity and mortality owing to its diverse causes. Liver biopsy, as the current gold standard for diagnosing and staging liver fibrosis, has a number of limitations, including sample variability, relatively high cost, an invasive nature, and the potential of complications. Most importantly, in clinical practice, patients often reject additional liver biopsies after initiating treatment despite their being necessary for long-term follow-up. To resolve these problems, a number of different noninvasive imaging-based methods have been developed for accurate diagnosis of liver fibrosis. However, these techniques only reflect morphological or perfusion-related alterations in the liver, and thus they are generally only useful for the diagnosis of late-stage liver fibrosis (liver cirrhosis), which is already characterized by “irreversible” anatomic and hemodynamic changes. Thus, it is essential that new approaches are developed for accurately diagnosing early-stage liver fibrosis as at this stage the disease may be “reversed” by active treatment. The development of molecular MR imaging technology has potential in this regard, as it facilitates noninvasive, target-specific imaging of liver fibrosis. We provide an overview of recent advances in molecular MR imaging for the diagnosis and staging of liver fibrosis and we compare novel technologies with conventional MR imaging techniques.
PMCID: PMC4385649  PMID: 25874221
3.  Research into europium complexes as magnetic resonance imaging contrast agents (Review) 
Europium (Eu) is a paramagnetic lanthanide element that possesses an outstanding luminescent property. Eu complexes are ideal fluorescence imaging (FI) agents. Eu2+ has satisfactory relaxivity and optical properties, and can realize magnetic resonance (MRI)-FI dual imaging applications when used with appropriate cryptands that render it oxidatively stable. By contrast, based on the chemical exchange saturation transfer (CEST) mechanism, Eu3+ complexes can provide enhanced MRI sensitivity when used with optimal cryptands, incorporated into polymeric CEST agents or blended with Gd3+. Eu complexes are promising in MRI-FI dual imaging applications and have a bright future.
PMCID: PMC4471668  PMID: 26136858
europium; magnetic resonance imaging; cryptand; longitudinal relaxivity; transverse relaxivity
4.  Radiofrequency Heat-Enhanced Chemotherapy for Breast Cancer: Towards Interventional Molecular Image-Guided Chemotherapy 
Theranostics  2014;4(11):1145-1152.
Breast cancer is the most common malignancy in women worldwide. Recent developments in minimally invasive interventional radiology techniques have significantly improved breast cancer treatment. This study aimed to develop a novel technique for the local management of breast cancers using radiofrequency heat (RFH). We performed both in vitro experiments using human breast cancer cells and in vivo validation in xenograft animal models with magnetic resonance imaging (MRI) and pathological correlation to investigate the feasibility of our approach. Four treatment groups, including (1) no treatment (control), (2) RFH-only, (3) chemo (doxorubicin)-only, and (4) combination therapy with both doxorubicin and RFH, were conducted in each experiment. In vitro combination therapy significantly decreased breast cancer cell proliferation while increased their apoptosis index compared to the other three groups. MRI demonstrated a significant tumor size reduction in animals treated with combination therapy compared to those receiving other treatments in vivo. Such result was further confirmed by pathological examination. In conclusion, our findings suggests that RFH can enhance the therapeutic efficiency of doxorubicin on breast cancers, thus establishing the basis for future development of interventional molecular image-guided local chemotherapy for breast malignancies.
PMCID: PMC4165778  PMID: 25250095
breast cancer; radiofrequency; doxorubicin; MRI; hyperthermia.
5.  Development of Nanoparticle-Based Magnetic Resonance Colonography 
Magnetic Resonance in Medicine  2010;65(3):673-679.
This study was to develop a novel method of nanoparticle-based MR colonography. Two types of solid lipid nanoparticles (SLNs) were synthesized with loading of (a) gadolinium-diethylenetriaminepenta-acetic-acid (Gd-DTPA) to construct Gd-SLNs as an MR T1 contrast agent; and (b) otcadecylamine-fluorescein-isothiocyanate (ODA-FITC) to construct Gd-FITC-SLNs for histologic confirmation of MR findings. Through an in vitro experiment, we first evaluated the size distribution and Gd-DTPA entrapment efficiency of these SLNs. The SLNs displayed a size distribution of 50–300 nm and a Gd-DTPA entrapment efficiency of 56%. For in vivo validation, thirty mice were divided into five groups, each of which was administered a transrectal enema using: (i) Gd-SLNs (n=6); (ii) Gd-FITC-SLNs (n=6); (iii) blank SLNs (n=6); (iv) Gd-DTPA (n=6); and (v) water (n=6). T1-weighted FLAIR MRI was then performed on mice after transrectal infusion of Gd-SLNs or Gd-FITC-SLNs, which demonstrated bright enhancement of the colonic walls, with decrease in T1 relaxation time. When Gd-FITC-SLNs were delivered, green fluorescent spots were visualized in both the extracellular space and the cytoplasm through colonic walls under confocal microscopy and fluorescence microscopy. This study establishes the “proof-of-principle” of a new imaging technique, called “nanoparticle-based MR colonography,” which may provide a useful imaging tool for the diagnosis of colorectal diseases.
PMCID: PMC2997759  PMID: 21337401
Magnetic resonance (MR); Colonography; Solid lipid nanoparticles (SLNs); Gadolinium diethylenetriaminepenta acetic acid (Gd-DTPA)
6.  Magnetic Resonance Imaging of Bone Marrow Cell-Mediated Interleukin-10 Gene Therapy of Atherosclerosis 
PLoS ONE  2011;6(9):e24529.
A characteristic feature of atherosclerosis is its diffuse involvement of arteries across the entire human body. Bone marrow cells (BMC) can be simultaneously transferred with therapeutic genes and magnetic resonance (MR) contrast agents prior to their transplantation. Via systemic transplantation, these dual-transferred BMCs can circulate through the entire body and thus function as vehicles to carry genes/contrast agents to multiple atherosclerosis. This study was to evaluate the feasibility of using in vivo MR imaging (MRI) to monitor BMC-mediated interleukin-10 (IL-10) gene therapy of atherosclerosis.
For in vitro confirmation, donor mouse BMCs were transduced by IL-10/lentivirus, and then labeled with a T2-MR contrast agent (Feridex). For in vivo validation, atherosclerotic apoE−/− mice were intravenously transplanted with IL-10/Feridex-BMCs (Group I, n = 5) and Feridex-BMCs (Group II, n = 5), compared to controls without BMC transplantation (Group III, n = 5). The cell migration to aortic atherosclerotic lesions was monitored in vivo using 3.0T MRI with subsequent histology correlation. To evaluate the therapeutic effect of BMC-mediated IL-10 gene therapy, we statistically compared the normalized wall indexes (NWI) of ascending aortas amongst different mouse groups with various treatments.
Principal Findings
Of in vitro experiments, simultaneous IL-10 transduction and Feridex labeling of BMCs were successfully achieved, with high cell viability and cell labeling efficiency, as well as IL-10 expression efficiency (≥90%). Of in vivo experiments, MRI of animal groups I and II showed signal voids within the aortic walls due to Feridex-created artifacts from the migrated BMCs in the atherosclerotic plaques, which were confirmed by histology. Histological quantification showed that the mean NWI of group I was significantly lower than those of group II and group III (P<0.05).
This study has confirmed the possibility of using MRI to track, in vivo, IL-10/Feridex-BMCs recruited to atherosclerotic lesions, where IL-10 genes function to prevent the progression of atherosclerosis.
PMCID: PMC3168522  PMID: 21915349
7.  Neonatal Systemic Juvenile Xanthogranuloma with an Ominous Presentation and Successful Treatment 
This case report originated from a case of neonatal multisystemic juvenile xanthogranuloma (JXG). The patient presented with blue muffin rush, cervical mass, bone destruction, lung nodule, hepatosplenomegaly, and coagulopathy and was successfully treated with Langerhans cell histiocytosis (LCH) based chemotherapy treatment. Similar cases in literature were reviewed and it seems that JXG, a relatively benign entity, when presented in its systemic form with liver involvement, could have an aggressive course and portend quite poor prognosis. Challenges and special consideration of the diagnosis, treatment, and future case observation are discussed.
PMCID: PMC3117631  PMID: 21695102
Juvenile xanthogranuloma; liver; neonatal; histiocytic disorder

Results 1-7 (7)