Intraperitoneal Nanotherapy for Metastatic Ovarian Cancer Based on siRNA-Mediated Suppression of DJ-1 Protein Combined with a Low Dose of Cisplatin

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks

Intraperitoneal Nanotherapy for Metastatic Ovarian Cancer Based on siRNA-Mediated Suppression of DJ-1 Protein Combined with a Low Dose of Cisplatin

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks

Acoustic absorption of hemp-lime construction

Hemp-lime concrete is a sustainable alternative to standard wall construction materials. It boasts excellent hygrothermal properties in part deriving from its porous structure. This paper investigates the acoustic properties of hemp-lime concrete, using binders developed from hydrated lime and pozzolans as well as hydraulic and cementicious binders. To assess the acoustic absorption of hemp-lime walls, as they are commonly finished in practical construction, wall sections are rendered and the resulting impact on absorption is evaluated. Hemp-concretes with lime-pozzolan binders display superior acoustic properties relative to more hydraulic binders. These are diminished when rendered, as the open surface porosity is affected, however hemp-lime construction offers the potential to meet standard and guideline targets for spaces requiring acoustic treatment

A study of the sources and sinks of methane and methyl chloroform using a global three-dimensional Lagrangian tropospheric tracer transport model

By comparison with methyl chloroform observations a global average tropospheric hydroxyl radical concentration of 6.4 × 105 cm-3 was found to be consistent with published methyl chloroform emission data for the year 1980. Published methyl chloroform emissions data for 1981-1984 were found to be inconsistent with the observed methyl chloroform concentration increases. Using the hydroxyl radical field calibrated to the methyl chloroform observations, two source function models of the spatial and temporal distribution of the flux of methane to the atmosphere were developed. The first model was based on the assumption that methane is emitted as a proportion of net primary productivity (NPP). With the average hydroxyl radical concentration fixed, the methane source term was computed as ~623 Tg CH4, giving an atmospheric lifetime for methane ~8.3 years. The second model identified source regions for methane from rice paddies, wetlands, enteric fermentation, termites, and biomass burning based on high-resolution land use data. This methane source distribution resulted in an estimate of the global total methane source of ~611 Tg CH4, giving an atmospheric lifetime for methane ~8.5 years. -from Author