Maximizing research impacts on cancer prevention: An integrated knowledge translation approach used by the Canadian Population Attributable Risk of Cancer (ComPARe) study.

With a strong focus on end user, or knowledge user, engagement throughout the study, an integrated knowledge translation approach (iKT) is expected to enhance the quality, relevance and reach of research findings. From its initiation, the Canadian Population Attributable Risk of Cancer (ComPARe) study combined the expertise of the knowledge producers (cancer prevention researchers) and select knowledge users in an iKT approach. We describe in detail our iKT approach, including governance, outputs and early reflections. In our model, knowledge users were integrated as members of the research team or members of a KT Advisory Committee. The integrated knowledge users took a lead role on the KT activities for ComPARe, including developing the KT Blueprint, a four phase systematic approach to guide the planning and implementation of KT activities. This approach included planning, knowledge product development, dissemination and evaluation, with advisory committee engagement built in throughout. Our early reflections identified enablers and challenges of an iKT approach for this study. Enablers included co-investigators' commitment and attitude towards iKT, support for iKT from the funding agency, an established partnership early on, understanding of and experience in each other's area of expertise, dedicated funding, clearly delineated roles, advisory committee buy-in and existing tools. Challenges included anticipating all costs, continuity of involvement, competing priorities, relationship management and geographic distance. A future evaluation will determine the effectiveness and impact of the iKT approach and KT Blueprint. In the interim, the approach we describe here can be modeled by others interested in collaborative, action-oriented research.

StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42.

Metastasis remains the main challenge to overcome for treating ovarian cancers. In this study, we investigate the potential role of the Cdc42 GAP StarD13 in the modulation of cell motility, invasion in ovarian cancer cells. StarD13 depletion does not affect the 2D motility of ovarian cancer cells. More importantly, StarD13 inhibits matrix degradation, invadopodia formation and cell invasion through the inhibition of Cdc42. StarD13 does not localize to mature TKS4-labeled invadopodia that possess matrix degradation ability, while a Cdc42 FRET biosensor, detects Cdc42 activation in these invadopodia. In fact, StarD13 localization and Cdc42 activation appear mutually exclusive in invadopodial structures. Finally, for the first time we uncover a potential role of Cdc42 in the direct recruitment of TKS4 to invadopodia. This study emphasizes the specific role of StarD13 as a narrow spatial regulator of Cdc42, inhibiting invasion, suggesting the suitability of StarD13 for targeted therapy.

A long-lived cuprous bis-phenanthroline complex for the photodynamic therapy of cancer.

Copper is an earth-abundant and a biologically essential metal that offers a promising alternative to noble metals in photochemistry and photobiology. In this work, a series of sterically encumbered Cu(i) bis-phenanthroline complexes were investigated for their use in photochemotherapy (PCT). It was found that Cu(dsbtmp)2+ [dsbtmp = 2,9-disec-butyl-3,4,7,8-tetramethyl-1,10-phenanthroline] (compound 3), which possessed the longest excited state lifetime, exhibited significant in vitro photocytotoxicity on A375 (human malignant melanoma) and A549 (human lung carcinoma) cell lines. Fluorescence imaging demonstrated the significant uptake and localization of compound 3 in a perinuclear fashion. A comet assay indicated the induction of DNA damage in the dark. The DNA breaks were significantly amplified upon photoactivation. The light-induced enhancement of cytotoxicity was associated with the formation of reactive oxygen species (ROS), a known intermediate in photodynamic therapy (PDT). This successful demonstration of photocytotoxicity using long-lived cuprous phenanthroline paves the way to exploit this class of photosensitizers for PDT applications.

Metformin Treatment Inhibits Motility and Invasion of Glioblastoma Cancer Cells.

Glioblastoma multiforme (GBM) is one of the most common and deadliest cancers of the central nervous system (CNS). GBMs high ability to infiltrate healthy brain tissues makes it difficult to remove surgically and account for its fatal outcomes. To improve the chances of survival, it is critical to screen for GBM-targeted anticancer agents with anti-invasive and antimigratory potential. Metformin, a commonly used drug for the treatment of diabetes, has recently emerged as a promising anticancer molecule. This prompted us, to investigate the anticancer potential of metformin against GBMs, specifically its effects on cell motility and invasion. The results show a significant decrease in the survival of SF268 cancer cells in response to treatment with metformin. Furthermore, metformin's efficiency in inhibiting 2D cell motility and cell invasion in addition to increasing cellular adhesion was also demonstrated in SF268 and U87 cells. Finally, AKT inactivation by downregulation of the phosphorylation level upon metformin treatment was also evidenced. In conclusion, this study provides insights into the anti-invasive antimetastatic potential of metformin as well as its underlying mechanism of action.