Therapeutic Effect of Glypican-3 Gene Silencing Using siRNA for Ovarian Cancer in a Murine Peritoneal Dissemination Model

Ovarian cancer is known to be the most lethal gynecologic cancer. It has been reported that Glypican-3 (Gpc3) expression induces immune responses, promotes the progression in ovarian cancer. Then, we focused on this Gpc3 gene silencing, tried to prepare siRNA delivery system. In this chapter, we introduce one of the therapeutic proposals in terms of novel drug delivery system using siRNA as a targeting medicine. This chapter introduces our works about preparation of siRNA-PLGA hybrid micelles to deliver the siRNA into the ovarian cancer cells and to evaluate gene silencing effects in mice model. As a result, siRNA-PLGA hybrid micelles were shown to effectively inhibit Gpc3 expression in vitro. In addition, siRNA-PLGA hybrid micelles also decreased the number of tumor nodes in the mesentery in vivo. These results suggested that Gpc3 could be a target molecule for ovarian cancer treatment and siRNA-PLGA hybrid micelles could be an effective siRNA delivery tool even in vivo

Evolutionary acquisition of promoter-associated non-coding RNA (pancRNA) repertoires diversifies species-dependent gene activation mechanisms in mammals

Diversity of conserved pancRNA expression profile of the five tissues in the five species. Hierarchical clustering and symmetrical heat map of Spearman correlation coefficients of conserved pancRNA (A) and their corresponding mRNA (B) expression profiles. Samples are colored according to the tissues and the species. (PDF 301 kb

Streptococcus thermophilus ST28 Ameliorates Colitis in Mice Partially by Suppression of Inflammatory Th17 Cells

The effects of Streptococcus thermophilus ST28 on cytokine production by murine splenocytes stimulated with transforming growth factor-β plus interleukin- (IL-) 6 were evaluated. The addition of ST28 significantly repressed IL-17 production compared to ATCC 19258 (type strain). ST28 also decreased the number of Th17 cells in the stimulated splenocytes. The anti-inflammatory effects of ST28 administration were evaluated in mice with colitis induced by dextran sodium sulphate (DSS). Oral treatment of mice with ST28 ameliorated the intestinal lesions by DSS. Upon DSS treatment, IL-17 production in lamina propria lymphocytes (LPLs) was induced, but ST28 significantly decreased its production. ST28 also decreased the percentage of Th17 cells in LPL from DSS-induced colitis. The present results imply that ST28 suppresses the Th17 response in inflamed intestines and would be useful in the treatment of Th17-mediated diseases, such as inflammatory bowel disease

Expression of the CCCH-tandem zinc finger protein gene OsTZF5 under a stress-inducible promoter mitigates the effect of drought stress on rice grain yield under field conditions

Increasing drought resistance without sacrificing grain yield remains an ongoing challenge in crop improvement. In this study, we report that Oryza sativa CCCH‐tandem zinc finger protein 5 (OsTZF5) can confer drought resistance and increase grain yield in transgenic rice plants. Expression of OsTZF5 was induced by abscisic acid, dehydration and cold stress. Upon stress, OsTZF5‐GFP localized to the cytoplasm and cytoplasmic foci. Transgenic rice plants overexpressing OsTZF5 under the constitutive maize ubiquitin promoter exhibited improved survival under drought but also growth retardation. By introducing OsTZF5 behind the stress‐responsive OsNAC6 promoter in two commercial upland cultivars, Curinga and NERICA4, we obtained transgenic plants that showed no growth retardation. Moreover, these plants exhibited significantly increased grain yield compared to non‐transgenic cultivars in different confined field drought environments. Physiological analysis indicated that OsTZF5 promoted both drought tolerance and drought avoidance. Collectively, our results provide strong evidence that OsTZF5 is a useful biotechnological tool to minimize yield losses in rice grown under drought conditions