Suppression of lung cancer progression by biocompatible glycerol triacrylate–spermine-mediated delivery of shAkt1

Background: Polyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate-spermine (GT-SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy. Methods: The GT-SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance. Results: The GT-SPE successfully protected the DNA from nucleases. The average particle size of the GT-SPE was 121 nm with a zeta potential of +23.45 mV. The GT-SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT-SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-ras(LA1) lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT-SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively. Conclusion: Our data suggest that GT-SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy

Porphyra tenera Extracts Have Immune Stimulation Activity via Increasing Cytokines in Mouse Primary Splenocytes and RAW264.7 Macrophages

Abstract Porphyra tenera has long been consumed as food in Korea and Asia. The effects of Porphyra tenera extracts on the immune system are largely unknown. Therefore, this study investigated the immune-stimulating effects of ethanol and water extracts of P. tenera. The immunomodulatory potential of P. tenera was evaluated by determining its effect on cell viability and cytokine expression of mouse RAW264.7 cells and splenocytes. We investigated the effect of 10% ethanol extracts of laver (P. tenera) on the RAW264.7 cells. Production of nitric oxide (NO) and cytokines (interleukin [IL]-1β, IL-2, and IL-4, inducible NO synthase, and interferon-γ) in RAW264.7 macrophages was slightly higher after treatment with P. tenera extracts. Ethanol extracts upregulated and enhanced the functions of macrophages, such as NO and cytokines (IL-1β, IL-2, and IL-4, inducible NO synthase, and interferon-γ) production. In addition, cytokine concentrations were significantly increased in cells treated with different doses of P. tenera ethanol extracts compared to the control group. Overall, the results demonstrated that P. tenera extracts enhanced cytokine secretion in mouse splenocytes and macrophages. From these findings, it can be concluded that P. tenera possess a natural compound with immune-stimulatory activity. P. tenera extract is a good immunostimulant from natural compounds

Modified underwater endoscopic mucosal resection for intermediate-sized sessile colorectal polyps

IntroductionUnderwater endoscopic mucosal resection (UEMR) is effective for treating intermediate-sized colorectal polyps. However, it is sometimes difficult to obtain visibility in underwater conditions.MethodsThis prospective, observational, single-center study included consecutive patients with intermediate-sized (10–20 mm) sessile colorectal polyps. Modified UEMR method was used to initially snare the lesion without injection or water infusion. Thereafter, water was infused until the lesion was submerged, then it was resected using electrocautery. We also evaluated the rates of complete resection and procedure-related complications.ResultsForty-two patients with 47 polyps were enrolled in the study. The median procedure time and fluid infusion were 71 s (42–607) and 50 mL (30–130), respectively. The rates of R0 resection and en bloc resection were 80.9 and 97.9%, respectively, with 100% technical success. R0 resection was observed in 42.9% of polyps sized ≥15 mm and 87.5% sized <15 mm (p < 0.01). Muscle entrapment was found in 71.4% of patients with polyps sized ≥15 mm and 10% <15 mm (p < 0.01). Immediate bleeding occurred in 12.8% of cases and was controlled using a snare tip or hemostatic forceps. Snare-tip ablation and hemostatic forceps ablation were performed in 27.7 and 6.4% of patients, respectively. No delayed bleeding, perforation, or any other complications were reported.ConclusionModified UEMR can be used in cases in which securing visibility or performing the existing UEMR is challenging. Careful treatment is required when removing polyps >15 mm in size

CCN1 interlinks integrin and hippo pathway to autoregulate tip cell activity

CCN1 (CYR61) stimulates active angiogenesis in various tumours, although the mechanism is largely unknown. Here, we report that CCN1 is a key regulator of endothelial tip cell activity in angiogenesis. Microvessel networks and directional vascular cell migration patterns were deformed in ccn1-knockdown zebrafish embryos. CCN1 activated VEGFR2 and downstream MAPK/PI3K signalling pathways, YAP/TAZ, as well as Rho effector mDia1 to enhance tip cell activity and CCN1 itself. VEGFR2 interacted with integrin αvβ3 through CCN1. Integrin αvβ3 inhibitor repressed tip cell number and sprouting in postnatal retinas from endothelial cell-specific Ccn1 transgenic mice, and allograft tumours in Ccn1 transgenic mice showed hyperactive vascular sprouting. Cancer patients with high CCN1 expression have poor survival outcomes and positive correlation with ITGAV and ITGB3 and high YAP/WWTR1. Thus, our data underscore the positive feedback regulation of tip cells by CCN1 through integrin αvβ3/VEGFR2 and increased YAP/TAZ activity, suggesting a promising therapeutic intervention for pathological angiogenesis. © 2019, Park et al.1

Current Trends in the Epidemiological and Pathological Characteristics of Gastrointestinal Stromal Tumors in Korea, 2003-2004

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies

Multifunctional properties of Lactobacillus plantarum strains WiKim83 and WiKim87 as a starter culture for fermented food

This study aimed to evaluate the safety (hemolysis and enzyme activity), probiotic properties (gastrointestinal tract tolerance, adhesion, hydrophobicity, and auto‐aggregation), and functional characteristics (antimicrobial, antioxidant, and β‐galactosidase activities) of lactic acid bacteria (LAB), isolated from kimchi, in order to select a multifunctional LAB strain for starter culture in fermented food. The five isolated strains included Lactobacillus plantarum WiKim83, L. plantarum WiKim84, Pediococcus pentosaceus WiKim85, P. pentosaceus WiKim86, and L. plantarum WiKim87, as identified by 16S rRNA gene sequence analysis; they were confirmed to be nonhemolytic and not able to produce β‐glucuronidase, a carcinogenic enzyme. Probiotic properties of the five LAB strains were evaluated relative to those of commercial Lactobacillus rhamnosus GG, and results revealed probiotic potential of three strains (L. plantarum WiKim83, L. plantarum WiKim84, and L. plantarum WiKim87) to be superior. L. plantarum WiKim84 showed high antimicrobial activity against pathogens, and L. plantarum WiKim83 exhibited the highest antioxidant and β‐galactosidase activities. Based on the probiotic and functional properties, the main characteristics of each strain were highlighted and two of them, L. plantarum WiKim83 and L. plantarum WiKim87, were selected as the most potent by principal component analysis. These strains showed antimicrobial, β‐galactosidase, and antioxidant activities, which recommend their suitability as starter culture in various fermented foods