Dynamic Nuclear Polarization of Selectively 29Si-Enriched Core@shell Silica Nanoparticles.

29Si silica nanoparticles (SiO2 NPs) are promising magnetic resonance imaging (MRI) probes that possess advantageous properties for in vivo applications, including suitable biocompatibility, tailorable properties, and high water dispersibility. Dynamic nuclear polarization (DNP) is used to enhance 29Si MR signals via enhanced nuclear spin alignment; to date, there has been limited success employing DNP for SiO2 NPs due to the lack of endogenous electronic defects that are required for the process. To create opportunities for SiO2-based 29Si MRI probes, we synthesized variously featured SiO2 NPs with selective 29Si isotope enrichment on homogeneous and core@shell structures (shell thickness: 10 nm, core size: 40 nm), and identified the critical factors for optimal DNP signal enhancement as well as the effective hyperpolarization depth when using an exogenous radical. Based on the synthetic design, this critical factor is the proportion of 29Si in the shell layer regardless of core enrichment. Furthermore, the effective depth of hyperpolarization is less than 10 nm between the surface and core, which demonstrates an approximately 40% elongated diffusion length for the shell-enriched NPs compared to the natural abundance NPs. This improved regulation of surface properties facilitates the development of isotopically enriched SiO2 NPs as hyperpolarized contrast agents for in vivo MRI.

Background free in vivo29Si MR imaging with hyperpolarized PEGylated silicon nanoparticles.

This study demonstrated the potential of 50 nm PEGylated Si NPs for high-resolution in vivo29Si MR imaging, emphasizing their biocompatibility and water dispersibility. The acquisition of in vivo Si MR images using the lowest reported dose after subcutaneous and intraperitoneal administration opens new avenues for future 29Si MR studies.

L-glutamine as a T2 exchange contrast agent.

PURPOSE: The potential of L-glutamine as a T2 exchange contrast agent in MRI was investigated. METHODS: The T2 relaxation rate of L-glutamine solutions prepared in various concentrations was measured at 9.4 T. A series of T2 -weighted images in a mouse cancer model was acquired with an L-glutamine solution infusion. RESULTS: The T2 relaxivity caused by the exchange (R2ex ) at 37°C was 0.069 s-1 mM-1 and 0.102 s-1 mM-1 for glutamine and glutamate solutions at pH = 7.2, respectively. The R2ex of glutamine at pH = 6.1-6.7 was in the 0.097-0.1 s-1 mM-1 range. No significant dependence of T1 on the concentration of glutamine was observed. The dynamic measurement of T2 -weighted images in vivo showed that the glutamine uptake was primarily observed at the localized part of the tumor CONCLUSION: L-glutamine can be used as a T2 exchange contrast agent and images of glutamine uptake in vivo can be acquired.

Clinical and oncologic outcomes of totally robotic total mesorectal excision for rectal cancer: initial results in a center for minimally invasive surgery.

PURPOSE: A robotic system was mainly designed to allow precise dissection in deep and narrow spaces. We report the clinical and oncologic outcomes of totally robotic total mesorectal excision for rectal cancer. METHODS: Between July 2009 and January 2012, 60 consecutive patients undergoing robotic surgery for rectal cancer at the Eulji University Hospital were included. RESULTS: The mean total operation time, docking time, and surgeon console time were 466.8 ± 115.6, 7.5 ± 6.7, and 261 ± 87.5 min, respectively. Oral intake of diet was started at 3.3 ± 0.9 days and the mean hospital stay was 8.6 ± 2.4 days. All 60 procedures were technically successful without the need for conversion to open or laparoscopic surgery. Complications included anastomotic leakage, anastomotic stricture, postoperative bleeding, ileus, and perineal wound infection in 3 (5 %), 1 (1.7 %), 2 (3.3 %), 2 (3.3 %), and 1 (1.7 %) patient, respectively. The mean distal resection margin and total number of lymph nodes harvested was 3.1 ± 1.7 cm and 20.1 ± 11.5, respectively. During the mean follow-up period of 48.5 months (range, 7-75), the 4-year overall and disease-free survival rates were 87.7 and 72.8 %, respectively. CONCLUSIONS: A totally robotic approach for rectal cancer operations was a time-consuming procedure, although we already had a lot experience in laparoscopic colorectal surgery. However, the dexterity of the robotic surgery could enable the surgeon to expand the choice of surgical methods according to the condition of the rectal cancer without the need for conversion.

Molecular Imaging of CD44-Overexpressing Gastric Cancer in Mice Using T2 MR Imaging.

Novel diagnostic techniques have been developed in many research area using targetable contrast agents with magnetic resonance imaging (MRI) for cancer diagnosis. For cancer diagnosis, the use of MRI with biocompatible targeting moieties and manganese ferrite nanoparticles (MFNPs) is preferred. Thus, we synthesized MFNPs using a thermal decomposition method which enables sensitive T2 or T2 Turbo Spin Echo (TSE) MRI and coated them with hyaluronic acid (HA). The high targeting ability of HA-MFNPs was observed at MKN-45 cells (gastric cancer cell line) which high-expressing CD44 in contrast with MKN-28 cells which low-expressing CD44. We also prepared the gastric cancer mice model using MKN-45 cells which has the stem-like property was implanted into BALB/c nude mice. And then HA-MFNPs of the T2 contrast enhancement effects and targeting ability were investigated by in vivo MR imaging. As a result of these studies, we conclude that HA coated MFNPs can be effectively used as a novel probes for visualizing gastric cancer stem cells.

Irradiation-induced localization of IL-12-expressing mesenchymal stem cells to enhance the curative effect in murine metastatic hepatoma.

Irradiation in conjunction with gene therapy is considered for efficient cancer treatment. Mesenchymal stem cells (MSCs), due to their irradiation-promotable tumor tropism, are ideal delivery vehicles for gene therapy. In this study, we investigated whether treatment with radiation and interleukin (IL)-12-expressing MSCs (MSCs/IL-12) exerts improved antitumor effects on murine metastatic hepatoma. HCa-I and Hepa 1-6 cells were utilized to generate heterotopic murine hepatoma models. Tumor-bearing mice were treated with irradiation or MSCs/IL-12 alone, or a combination. Monocyte chemoattractant protein-1 (MCP-1/CCL2) expression was assessed in irradiated hepatoma tissues to confirm a chemotactic effect. Combination treatment strategies were established and their therapeutic efficacies were evaluated by monitoring tumor growth, metastasis and survival rate. IL-12 expression was assessed and the apoptotic activity and immunological alterations in the tumor microenvironment were examined. MCP-1/CCL2 expression and localization of MSCs/IL-12 increased in the irradiated murine hepatoma cells. The antitumor effects, including suppression of pulmonary metastasis and survival rate improvements, were increased by the combination treatment with irradiation and MSCs/IL-12. IL-12 expression was increased in tumor cells, causing proliferation of cluster of differentiation 8(+) T-lymphocytes and natural killer cells. The apoptotic activity increased, indicating that the cytotoxicity of immune cells was involved in the antitumor effect of the combined treatment. Treatment with irradiation and MSCs/IL-12 showed effectiveness in treating murine metastatic hepatoma. IL-12-induced proliferation of immune cells played an important role in apoptosis of tumor cells. Our results suggest that treatment with irradiation and MSCs/IL-12 may be a useful strategy for enhancing antitumor activity in metastatic hepatoma.

Prognostic values of vascular endothelial growth factor and matrix metalloproteinase-2 in hepatocellular carcinoma after radiotherapy.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a highly vascularized tumor. In this study, we investigated the prognostic and predictive values of proangiogenic factors in HCC patients receiving radiotherapy. METHODS: Between September 2008 and December 2009, a total of 50 patients treated with radiotherapy were prospectively enrolled in this study. Serum and urine samples were collected <1 week before and after radiotherapy. RESULTS: After completion of radiotherapy, serum vascular endothelial growth factor (VEGF)/platelet (Plt) levels were significantly increased (p < 0.01). Patients who experienced hepatic tumor recurrence outside the radiation field showed higher VEGF-A/Plt levels before and after radiotherapy than patients who did not (p = 0.04), whereas patients who had hepatic tumor recurrence inside the radiation field showed significantly higher matrix metalloproteinase (MMP)-2 levels after radiotherapy (p = 0.04). On multivariate analyses, a high level of either VEGF/Plt or MMP-2 (≥median) before radiotherapy was a significant independent prognostic factor for a worse progression-free survival (p = 0.04). CONCLUSIONS: In HCC patients receiving radiotherapy, levels of VEGF/Plt and MMP-2 before radiotherapy can be useful to predict treatment outcome. This study also suggests the necessity of anti-angiogenic therapy, such as sorafenib, since radiotherapy increases VEGF/Plt levels, and higher levels of VEGF/Plt are associated with a poor outcome.

Insecticides chlorantraniliprole and flubendiamide in Aster scaber: Dissipation kinetics, processing effects, and risk assessment.

The residue characteristics, processing effects of washing and drying, and dietary risks of chlorantraniliprole (CAP) and flubendiamide (FBD) to Koreans were investigated using Aster scaber in a greenhouse. Following foliar application, the initial FBD residues were 3-10 times higher than those of CAP. However, the biological half-lives were similar at 6.0-8.3 and 6.8-9.9 days for CAP and FBD, respectively. The pre-harvest residue limits (PHRLs) 7 days before harvest, derived from the dissipation rates and maximum residue limits, were 12.2 and 33.2 mg/kg for CAP and FBD, respectively. For the removal of CAP and FBD from A. scaber, washing with a neutral detergent was more effective than running under or dipping in tap water (86.5 % and 66.2 %, respectively). Processing factors in fields I and II were 2.6 and 5.1 for CAP and 2.0 and 5.7 for FBD, respectively. Drying removal efficiencies in fields I and II averaged 46.4 % and 52.3 % for CAP and 48.4 % and 49.2 % for FBD, respectively. Chronic health risk assessments indicated that dietary exposure to CAP and FBD is acceptable for Korean health.

Organophosphate Detection in Animal-Derived Foods Using a Modified Quick, Easy, Cheap, Effective, Rugged, and Safe Method with Liquid Chromatography-Mass Spectrometry.

Organophosphates are widely used in the livestock industry. In this study, we developed a method for detecting 27 organophosphate insecticides in animal-derived foods, including beef, pork, chicken, milk, and eggs, using liquid chromatography-tandem mass spectrometry. A modified QuEChERS method was optimized for sample pretreatment. A mixture of acetonitrile and acetone was used as the extraction solvent, and MgSO4 and NaCl were used as salts. Among the five different dispersive solid-phase extraction systems, MgSO4, primary secondary amines, and C18 were selected for purification because they had the highest recovery rates and least matrix effects. The matrix-dependent limit of quantitation was 0.0005-0.005 mg/kg, and the correlation coefficient of the matrix-matched calibration curve was >0.99, which was acceptable for quantifying residues below 0.01 mg/kg-the default maximum residue limit in a positive list system. The recovery efficiencies ranged from 71.9 to 110.5%, with standard deviations ranging from 0.2% to 12.5%, satisfying the SANTE guidelines. The established analytical method was used to monitor organophosphates in animal-derived foods obtained from a local market, and no pesticides were detected. With respect to industry standards, our proposed method is recommended for practical organophosphate detection in animal-derived foods.

Galactosylated manganese ferrite nanoparticles for targeted MR imaging of asialoglycoprotein receptor.

Cancer cells can express specific biomarkers, such as cell membrane proteins and signaling factors. Thus, finding biomarkers and delivering diagnostic agents are important in the diagnosis of cancer. In this study, we investigated a biomarker imaging agent for the diagnosis of hepatic cancers. The asialoglycoprotein receptor (ASGPr) was selected as a biomarker for hepatoma cells and the ASGPr-targetable imaging agent bearing a galactosyl group was prepared using manganese ferrite nanoparticles (MFNP) and galactosylgluconic acid. The utility of the ASGPr-targetable imaging agent, galactosylated MFNP (G-MFNP) was assessed by several methods in ASGPr-expressing HepG2 cells as target cells and ASGPr-deficient MCF7 cells. Physical and chemical properties of G-MFNP were examined using Fourier-transform infrared spectroscopy, dynamic light scattering, zeta potential analysis, and transmission electron microscopy. No significant cytotoxicity was observed in either cell line. Targeting ability was assessed using flow cytometry, magnetic resonance imaging, inductively coupled plasma atomic emission spectroscopy, absorbance analysis, dark-field microscopy, Prussian blue staining, and transmission electron microscopy. We demonstrated that G-MFNP target successfully and bind to ASGPr-expressing HepG2 cells specifically. We suggest that these results will be useful in strategies for cancer diagnoses based on magnetic resonance imaging.