Determining PTEN Functional Status by Network Component Deduced Transcription Factor Activities

PTEN-controlled PI3K-AKT-mTOR pathway represents one of the most deregulated signaling pathways in human cancers. With many small molecule inhibitors that target PI3K-AKT-mTOR pathway being exploited clinically, sensitive and reliable ways of stratifying patients according to their PTEN functional status and determining treatment outcomes are urgently needed. Heterogeneous loss of PTEN is commonly associated with human cancers and yet PTEN can also be regulated on epigenetic, transcriptional or post-translational levels, which makes the use of simple protein or gene expression-based analyses in determining PTEN status less accurate. In this study, we used network component analysis to identify 20 transcription factors (TFs) whose activities deduced from their target gene expressions were immediately altered upon the re-expression of PTEN in a PTEN-inducible system. Interestingly, PTEN controls the activities (TFA) rather than the expression levels of majority of these TFs and these PTEN-controlled TFAs are substantially altered in prostate cancer mouse models. Importantly, the activities of these TFs can be used to predict PTEN status in human prostate, breast and brain tumor samples with enhanced reliability when compared to straightforward IHC-based or expression-based analysis. Furthermore, our analysis indicates that unique sets of PTEN-controlled TFAs significantly contribute to specific tumor types. Together, our findings reveal that TFAs may be used as “signatures” for predicting PTEN functional status and elucidate the transcriptional architectures underlying human cancers caused by PTEN loss

Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer.

PMC3648524Triple negative breast cancers (TNBC) are difficult to treat due to a lack of targets and heterogeneity. Inhibition of angiogenesis is a promising therapeutic strategy, but has had limited effectiveness so far in breast cancer. To quantify heterogeneity in angiogenesis-related gene expression in breast cancer, we focused on two families--VEGFs and semaphorins--that compete for neuropilin co-receptors on endothelial cells. We compiled microarray data for over 2,600 patient tumor samples and analyzed the expression of VEGF- and semaphorin-related ligands and receptors. We used principal component analysis to identify patterns of gene expression, and clustering to group samples according to these patterns. We used available survival data to determine whether these clusters had prognostic as well as therapeutic relevance. TNBC was highly associated with dysregulation of VEGF- and semaphorin-related genes; in particular, it appeared that expression of both VEGF and semaphorin genes were altered in a pro-angiogenesis direction. A pattern of high VEGFA expression with low expression of secreted semaphorins was associated with 60% of triple-negative breast tumors. While all TNBC groups demonstrated poor prognosis, this signature also correlated with lower 5-year survival rates in non-TNBC samples. A second TNBC pattern, including high VEGFC expression, was also identified. These pro-angiogenesis signatures may identify cancers that are more susceptible to VEGF inhibition.JH Libraries Open Access Fun

eCommerce Platforms Evaluation Framework for Government

The international trade flow of e-commerce goods have reached unprecedented volumes. Ensuring undisrupted flow of cross-border eCommerce goods has become one of the top priorities for customs administrations around the world. Customs has a role in safeguarding public values such as safety and security, revenue collection, and stimulation of the economy. Customs administrations are now looking into innovative ways to be able to fulfil their duties for controlling the trade flows while at the same time not hindering trade. But in a broader sense, other government agencies also have responsibilities for safeguarding public values such as product and consumer safety or sustainability and are currently confronted with these eCommerce flows. While eCommerce is a phenomenon that is widely studied in business literature, it is largely unexplored both in research and practice how governments can understand and engage with these eCommerce developments. In this study we focus on the issue revenue collection related to cross-border eCommerce goods. Empirically, our paper builds on insights from the PROFILE EU project, which focuses on the use of data analytics for customs. Theoretically we build on research on control mechanisms in eCommerce platforms and digital trade infrastructures. We present an eCommerce platforms evaluation framework for customs. The evaluation framework consists of two distinct perspectives (i.e. a data analytics and a partnership perspective) that customs can explore when defining their engagement strategies with eCommerce platforms. We limited our study to the interactions of customs with eCommerce platforms and the issue of revenue collection. Further research can study the safeguarding of a wider range of public values by a range of government organisations to account for effects of the vast growth in international flows of goods via eCommerce platforms, such as monitoring product safety and sustainability effects.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Information and Communication Technolog

Interventional Cardio-Oncology: Adding a New Dimension to the Cardio-Oncology Field

The management of cardiovascular disease in patients with active cancer presents a unique challenge in interventional cardiology. Cancer patients often suffer from significant comorbidities such as thrombocytopenia and coagulopathic and/or hypercoagulable states, which complicates invasive evaluation and can specifically be associated with an increased risk for vascular access complications. Furthermore, anticancer therapies cause injury to the vascular endothelium as well as the myocardium. Meanwhile, improvements in diagnosis and treatment of various cancers have contributed to an increase in overall survival rates in cancer patients. Proper management of this patient population is unclear, as cancer patients are largely excluded from randomized clinical trials on percutaneous coronary intervention (PCI) and national PCI registries. In this review, we will discuss the role of different safety measures that can be applied prior to and during these invasive cardiovascular procedures as well as the role of intravascular imaging techniques in managing these high risk patients

eCommerce Platforms Evaluation Framework for Government

The international trade flow of e-commerce goods have reached unprecedented volumes. Ensuring undisrupted flow of cross-border eCommerce goods has become one of the top priorities for customs administrations around the world. Customs has a role in safeguarding public values such as safety and security, revenue collection, and stimulation of the economy. Customs administrations are now looking into innovative ways to be able to fulfil their duties for controlling the trade flows while at the same time not hindering trade. But in a broader sense, other government agencies also have responsibilities for safeguarding public values such as product and consumer safety or sustainability and are currently confronted with these eCommerce flows. While eCommerce is a phenomenon that is widely studied in business literature, it is largely unexplored both in research and practice how governments can understand and engage with these eCommerce developments. In this study we focus on the issue revenue collection related to cross-border eCommerce goods. Empirically, our paper builds on insights from the PROFILE EU project, which focuses on the use of data analytics for customs. Theoretically we build on research on control mechanisms in eCommerce platforms and digital trade infrastructures. We present an eCommerce platforms evaluation framework for customs. The evaluation framework consists of two distinct perspectives (i.e. a data analytics and a partnership perspective) that customs can explore when defining their engagement strategies with eCommerce platforms. We limited our study to the interactions of customs with eCommerce platforms and the issue of revenue collection. Further research can study the safeguarding of a wider range of public values by a range of government organisations to account for effects of the vast growth in international flows of goods via eCommerce platforms, such as monitoring product safety and sustainability effects