35 research outputs found
Tourism policy and destination marketing in developing countries: the chain of influence
Tourism marketers including destination marketing organisations (DMOs) and international tour operators play a pivotal role in destination marketing, especially in creating destination images. These images, apparent in tourist brochures, are designed to influence tourist decision-making and behaviour. This paper proposes the concept of a “chain of influence” in destination marketing and image-making, suggesting that the content of marketing materials is influenced by the priorities of those who design these materials, e.g. tour operators and DMOs. A content analysis of 2,000 pictures from DMO and tour operator brochures revealed synergies and divergence between these marketers. The brochure content was then compared to the South African tourism policy, concluding that the dominant factor in the chain of influence in the South African context is in fact its organic image
Depicting the tree of life in museums: guiding principles from psychological research
The Tree of Life is revolutionizing our understanding of life on Earth, and, accordingly, evolutionary trees are increasingly important parts of exhibits on biodiversity and evolution. The authors argue that in using these trees to effectively communicate evolutionary principles, museums need to take into account research results from cognitive, developmental, and educational psychology while maintaining a focus on visitor engagement and enjoyment. Six guiding principles for depicting evolutionary trees in museum exhibits distilled from this research literature were used to evaluate five current or recent museum trees. One of the trees was then redesigned in light of the research while preserving the exhibit’s original learning goals. By attending both to traditional factors that influence museum exhibit design and to psychological research on how people understand diagrams in general and Tree of Life graphics in particular, museums can play a key role in fostering 21st century scientific literacy
Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer
BACKGROUND: Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer.
METHODS: We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models.
RESULTS: Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model.
CONCLUSIONS: In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies
Nutrient partitioning in the tumor microenvironment and FDG-PET imaging
Abstract
The tumor microenvironment is composed of multiple cell types, including malignant cancer cells and tumor-infiltrating leukocytes (TIL). A possible mechanism of immunosuppression in the tumor microenvironment (TME) is cancer cells outcompeting anti-cancer TIL for nutrients such as glucose. 18F-deoxyglucose (FDG) positron emission tomography (PET) imaging is a staple of diagnosing and monitoring many types of cancer and is based on the Warburg model in which cancer cells within the tumor utilize glucose for growth and proliferation. Here, we use magnetic bead sorting to fractionate FDG-avid murine tumors and measure tumor cell-specific glucose uptake. We find that CD45+ immune cells are more FDG-avid than CD45− cancer cells. We further fractionate immune cell subsets into CD4/8+ T cells and CD11b+ myeloid cells to demonstrate that TIL T cells take up more glucose than CD45− cancer cells and resting splenic T cells. Strikingly, CD11b+ myeloid cells are the most FDG-avid cells in the TME. In MC38 colorectal cancer tumors, we show that CD11b+ F4/80 hi macrophages have high glucose uptake, and by extracellular flux analysis demonstrate higher metabolic activity than tumor T cells and CD45− cancer cells. Intriguingly, while glucose uptake is low in CD45− cancer cells, 18F-glutamine uptake is higher in cancer cells than immune cells. Our results illustrate a novel approach to measuring nutrient uptake in the TME and suggest that TIL are not starved of nutrients in the TME. Future work will determine the effects of immunotherapy and metabolism-targeted therapeutics on cell-specific glucose and glutamine uptake in the TME, as well as determine the immune contribution to cancer PET scans in the context of immunotherapy response.</jats:p
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Nutrient partitioning in the tumor microenvironment
Abstract
The tumor microenvironment (TME) includes cancer and infiltrating immune cells. Tumors canonically consume glucose through Warburg metabolism, a process forming the basis of cancer imaging by positron emission tomography (PET). Activated immune cells also rely on glucose, and impaired immune cell metabolism in the TME contributes to tumor progression. It remains uncertain, however, if immune cell metabolism is dysregulated in the TME by cell intrinsic programs or by competition with cancer cells for limiting nutrients. Here we used PET tracers to measure access and uptake of glucose and glutamine by specific cell subsets in the TME. Surprisingly, myeloid cells had the greatest capacity to uptake glucose in vivo, followed by T cells and cancer cells across a range of cancer models. Cancer cells, in contrast, demonstrated high glutamine uptake. This distinct nutrient partitioning was cell intrinsically programmed through mTORC1 signaling and glucose and glutamine-related gene expression. Inhibiting glutamine uptake enhanced glucose uptake across tumor resident cell types, suggesting that glutamine metabolism suppresses glucose uptake without glucose being limiting in the TME. Thus, cell intrinsic programs dictate the preferential immune and cancer cell acquisition of glucose and glutamine. Cell selective partitioning of these nutrients may be exploited to develop therapies and imaging strategies to enhance or monitor the metabolism and activities of specific cell populations in the TME.</jats:p
