| 1. |
- Weinstein, John N., et al.
(author)
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The cancer genome atlas pan-cancer analysis project
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 2. |
- Bergström, Christel A. S., et al.
(author)
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Early pharmaceutical profiling to predict oral drug absorption : Current status and unmet needs
- 2014
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57, s. 173-199
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Journal article (peer-reviewed)abstract
- Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silica and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. (C) 2013 Elsevier B.V. All rights reserved.
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| 3. |
- Cook, David C., et al.
(author)
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Plant biosecurity policy-making modelled on the human immune system: What would it look like?
- 2014
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In: Environmental Science and Policy. - : Elsevier BV. - 1462-9011. ; 41, s. 1-10
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Journal article (peer-reviewed)abstract
- This paper takes inspiration from the field of bio-mimicry to suggest what a plant biosecurity system might look like if it was modelled on the human immune system. We suggest structural and institutional changes to current biosecurity systems that would facilitate adaptive preparation and response policies, focusing particularly on the Australian plant biosecurity system. By improving information exchanges, interpretation and managing overlapping complementary response capabilities of this system, novel policies emerge that increase resilience to harmful weeds, pests and diseases. This is achieved by adding an element of flexibility in invasion response to cope with different circumstances and contexts, rather than a 'one size fits all' approach. While we find bio-mimicry to be a potentially useful system design tool, there are key differences between the immune and biosecurity systems that the analogy makes clear. Perhaps the most important of these stems from the inability of immune systems to imagine future threats. (C) 2014 Elsevier Ltd. All rights reserved.
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| 4. |
- Elkabets, Moshe, et al.
(author)
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Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice
- 2011
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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 121:2, s. 784-799
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Journal article (peer-reviewed)abstract
- Systemic instigation is a process by which endocrine signals sent from certain tumors (instigators) stimulate BM cells (BMCs), which are mobilized into the circulation and subsequently foster the growth of otherwise indolent carcinoma cells (responders) residing at distant anatomical sites. The identity of the BMCs and their specific contribution or contributions to responder tumor growth have been elusive. Here, we have demonstrated that Scal(+)cKit(-) hematopoietic BMCs of mouse hosts bearing instigating tumors promote the growth of responding tumors that form with a myofibroblast-rich, desmoplastic stroma. Such stroma is almost always observed in malignant human adenocarcinomas and is an indicator of poor prognosis. We then identified granulin (GRN) as the most upregulated gene in instigating Scal(+)cKit(-) BMCs relative to counterpart control cells. The GRN(+) BMCs that were recruited to the responding tumors induced resident tissue fibroblasts to express genes that promoted malignant tumor progression; indeed, treatment with recombinant GRN alone was sufficient to promote desmoplastic responding tumor growth. Further, analysis of tumor tissues from a cohort of breast cancer patients revealed that high GRN expression correlated with the most aggressive triple-negative, basal-like tumor subtype and reduced patient survival. Our data suggest that GRN and the unique hematopoietic BMCs that produce it might serve as novel therapeutic targets.
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