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ABSTRACT: INTRODUCTION: Ginsenoside Rg3 is a natural active ingredient that is extracted from Korean red ginseng root. It elevates therapeutic effect of radiotherapy and chemotherapy, but the study found that the application of Rg3 is heavily limited by its low bioavailability and poor absorption via oral administration. METHOD: Rg3-loaded PEG-PLGA-NPs (Rg3-NPs) were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method, and the physicochemical characteristics of Rg3-NPs were investigated in our study. We treated primary glioblastoma with 50 µM Rg3-NPs for 48h. We then used gene expression arrays (Illumina) for genome-wide expression analysis and validated the results for genes of interest by means of Real-Time PCR. Functional annotations were then performed using the DAVID and KEGG online tools. RESULTS: MTT shows that the growth of cells can be significantly inhibited by Rg3-NPs in a dose-dependence manner. FCM test shows Rg3-NPs can be released from the conjugate nanoparticle and react with the genes in the cell nuclei causing changes in the gene molecules. We also found that cancer cells treated with Rg3-NPs undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes as determined by microarray-analysis and verified by Real-Time PCR. Furthermore, Rg3-NPs induced the expression of apoptotic and anti-migratory proteins p53 in cell lines. CONCLUSIONS: The results of the present study, together with the results of earlier studies show that Rg3-NPs targets genes involved in the progression of the M-phase of the cell cycle. It is associated with several important pathways, which include apoptosis (p53). Rg3-NPs may be a potent cell-cycle regulation drug targeting the M-phase in glioblastoma cell lines.

SUBMITTER: Bie L

PROVIDER: S-EPMC3635504 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Project description:Objectives: Myocardial fibrosis in noninfarcted myocardium is emerging as a principal phenotype of vulnerability to adverse events such as mortality and hospitalization for heart failure (HHF), but its optimal noninvasive measurement remains uncertain despite consistently robust histologic validation data for extracellular volume fraction (ECV). We therefore compared ECV, native T1, post contrast T1, the gadolinium contrast partition coefficient (lambda), and the presence of nonischemic scar in their associations with mortality and HHF outcomes. Method: To quantify of myocardial fibrosis, we performed T1 mapping (MOLLI) in basal and mid short axis slices with cardiovascular magnetic resonance (CMR) before contrast and 12-30 minutes post contrast bolus in 1185 consecutive patients without amyloidosis, hypertrophic or stress cardiomyopathy. We assessed associations with outcomes using Kaplan-Meier plots and chi square values from univariable Cox regression models. All standard T1 mapping parameters were obtained: native and post contrast myocardial T1, the partition coefficient lambda, and ECV. ECV = (1-hematocrit) · [?R1myocardium]/[?R1bloodpool], where R1 = 1/T1 Late gadolinium enhancement imaging with phase sensitive reconstruction identified nonischemic scar. Results: Over a median of 1.7 years, 111 individuals experienced events after CMR: 55 HHF events and 74 deaths. ECV yielded better separation of Kaplan-Meier curves in a dose dependent fashion (Figure) and also stronger associations with the combined endpoint of death or HHF. The ECV chi square (77.3, p < 0.001) was at least twice as large as the Native T1 chi square (37.5, p < 0.001), the lambda chi square (34.8, p < 0.001) and nonischemic scar (chi square = 20.5, p<0.001). Post-contrast T1 was not associated with outcomes, even when adjusting further for time after contrast bolus, renal function, and patient weight (chi square <3, p >0.10). Conclusion: Analogous to histologic previously published validation data, quantitative ECV myocardial fibrosis measures associated with outcomes far stronger than other surrogate measures outcome measures such as native T1, post contrast T1 and nonischemic scar on LGE images. These data suggest that ECV is the noninvasive metric of choice to measure myocardial fibrosis. Figure. Kaplan-Meier Plots for T1 mapping parameters.

Project description:Background: The incidence of small renal masses (SRMs) has increased in recent years in line with increased in abdominal imaging. SRMs are defined as enhancing solid lesions measuring ? 4cm. We present our experience with percutaneous renal tumour biopsy (RTB) of SRMs, which to our knowledge, is the largest to date. Methods: We reviewed our database to ascertain the incidence of benign, malignant and non-diagnostic biopsies of SRMs performed at our institution from 2001 to July 2013. A total of 519 RTBs were performed (496 SRMs). The diagnostic rate was compared over time. The accuracy of the biopsies was correlated with the definitive pathology in the cases where the biopsy led to surgery. Results: The mean size of the 519 biopsied lesions was 2.5 (±0.9) cm. The diagnostic rate at the first biopsy was 89.1% (442/496). Of the diagnostic biopsies, 116 (26.2%) were benign and 326 (73.7%) were malignant. Of the 54 non-diagnostic biopsies, 23 (42.6%) had a repeat biopsy. A diagnosis was obtained in 19 cases (82.6%; 8 [42.1%] benign, 11 [57.9%] malignant). Therefore RTB led to a diagnosis in 461 of the 496 SRMs (92.9%). Over time, there was a decrease in the rate of non-diagnostic biopsies from 15.0% to 6.0% (p>0.05). Of the available surgical pathology, there was agreement between histology in 92.5% (125/135). For the conventional cell carcinoma (n=85), there was concordance between histology and grade in 97.6% (83/85) and 96.1% (74/77), respectively. Conclusions: RTB of SRMs provided a diagnosis in 92.9% of the cases. Surgery was avoided in more than 23% of patients following RTB because of benign histology. The rate of non-diagnostic biopsies diminished over time. Finally, there was a high correlation between the biopsy and the final pathology with regards to both histology and grade. In an era where overdiagnosis and overtreatment of favourable cancers is gaining attention, routine RTB for SRM leads to diminished intervention and, going forward ,personalization of care.

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