No abstract

No abstract

BackgroundOvarian cancer is a leading cause of cancer mortality in women, and only a small percentage of cases are caught at an early stage. Novel treatments with improved e cacy are needed to ght ovarian cancer and to overcome resistance to traditional therapies. Double-stranded (ds) RNA, including the synthetic polyinosinic cytidylic acid (poly (I:C), has shown promise as a cancer therapeutic. Two ovarian cancer cell lines were tested for their ability to produce an immune response to poly (I:C) delivered using a nanoparticle carrier, a biodegradable phytoglycogen derived from sweet corn, called nanodendrix (NDX). SKOV-3 and OVCAR-3 have been previously identi ed as dsRNA-resistant and dsRNA-sensitive, respectively. ResultsFirstly, NDX was found to effectively bind poly (I:C), at a w/w ratio of 2:1 NDX:poly (I:C), the resulting particles, poly (I:C)-NDX, were tested for biological activity through uptake and two therapeutic modes of action, cytotoxicity and stimulation of the innate immune response. Both cell lines bound poly (I:C)-NDX, as observed using immunocytochemistry. In OVCAR-3 poly (I:C)-NDX caused signi cant cell death, even at concentrations as low as 62.5ng/mL, measured using the cell viability indicator dye alamarBlue; no cell death was observed with poly (I:C) alone across all concentrations, up to 5µg/mL in SKOV-3 and 0.5µg/mL in OVCAR-3. In both OVCAR-3 and SKOV-3, poly (I:C)-NDX stimulated the production of an innate immune chemokine, CXCL10, at the transcript and protein levels, at signi cantly higher levels than poly (I:C) alone. Interestingly, in response to poly (I:C)-NDX SKOV-3 produced a more robust immune response compared and higher levels of capase-3/-7 activation compared to OVCAR-3, despite showing no signi cant cell death. ConclusionsPoly (I:C)-NDX represents a robust and multifunctional therapy with demonstrated e cacy against a range of ovarian tumour cells, potentiating poly (I:C) and sensitizing resistant cells. Additionally, the SKOV-3 and OVCAR-3 combination represents a powerful comparative model to help unravel dsRNA-mediated immune responses in ovarian cancer cells.

In order to avoid suspicion, opposition, and even inquisition, visionaries of the late Middle Ages did well to deny their capacities as either readers or writers. In A Revelation of Love , Julian of Norwich nullifies her role in uncovering the meaning of the divine 'text' she receives by demonstrating that the interpretation, and the processes by which it was achieved, are the responsibility of an interpretive community. The legitimacy of the interpretation is established by the authority of this community which, as a union between God, Church, and Christian souls, is a picture of Christendom itself.

Lollard writing is characterised by a p reoccup ation with the end times, but the kind of eschatological mindset the texts reflect has become a matter of    Issue Section: Articles