Ensemble-Empirical-Mode-Decomposition based micro-Doppler signal separation and classification

The target echo signals obtained by Synthetic Aperture Radar (SAR) and Ground Moving Target Indicator (GMTI platforms are mainly composed of two parts, the micro-Doppler signal and the target body part signal. The wheeled vehicle and the track vehicle are classified according to the different character of their micro-Doppler signal. In order to overcome the mode mixing problem in Empirical Mode Decomposition (EMD), Ensemble Empirical Mode Decomposition (EEMD) is employed to decompose the original signal into a number of Intrinsic Mode Functions (IMF). The correlation analysis is then carried out to select IMFs which have a relatively high correlation with the micro-Doppler signal. Thereafter, four discriminative features are extracted and Support Vector Machine (SVM) classifier is applied for classification. The experimental results show that the features extracted after EEMD decomposition are effective, with up 90% success rate for classification using one feature. In addition, these four features are complementary in different target velocity and azimuth angles

Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT)

Bone marrow-derived mesenchymal stem cells (MSCs) are known to specifically migrate to and engraft at tumour sites. Understanding interactions between cancer cells and MSCs has become fundamental to determining whether MSC-tumour interactions should be harnessed for delivery of therapeutic agents or considered a target for intervention. Breast Cancer Cell lines (MDA-MB-231, T47D & SK-Br3) were cultured alone or on a monolayer of MSCs, and retrieved using epithelial specific magnetic beads. Alterations in expression of 90 genes associated with breast tumourigenicity were analysed using low-density array. Expression of markers of epithelial–mesenchymal transition (EMT) and array results were validated using RQ-PCR. Co-cultured cells were analysed for changes in protein expression, growth pattern and morphology. Gene expression and proliferation assays were also performed on indirect co-cultures. Following direct co-culture with MSCs, breast cancer cells expressed elevated levels of oncogenes (NCOA4, FOS), proto-oncogenes (FYN, JUN), genes associated with invasion (MMP11), angiogenesis (VEGF) and anti-apoptosis (IGF1R, BCL2). However, universal downregulation of genes associated with proliferation was observed (Ki67, MYBL2), and reflected in reduced ATP production in response to MSC-secreted factors. Significant upregulation of EMT specific markers (N-cadherin, Vimentin, Twist and Snail) was also observed following co-culture with MSCs, with a reciprocal downregulation in E-cadherin protein expression. These changes were predominantly cell contact mediated and appeared to be MSC specific. Breast cancer cell morphology and growth pattern also altered in response to MSCs. MSCs may promote breast cancer metastasis through facilitation of EMT.National Breast Cancer Research Institute (NBCRI), a Royal College of Surgeons in Ireland (RCSI) Surgical Research Grant a Health Research Board Project Grant and a ScienceFoundation Ireland CSET award.Deposited by bulk impor

Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer

Extracellular vesicles (EVs) shuttle microRNA (miRNA) throughout the circulation and are believed to represent a fingerprint of the releasing cell. We isolated and characterized serum EVs of breast tumour-bearing animals, breast cancer (BC) patients, and healthy controls. EVs were characterized using transmission electron microscopy (TEM), protein quantification, western blotting, and nanoparticle tracking analysis (NTA). Absolute quantitative (AQ)-PCR was employed to analyse EV-miR-451a expression. Isolated EVs had the appropriate morphology and size. Patient sera contained significantly more EVs than did healthy controls. In tumour-bearing animals, a correlation between serum EV number and tumour burden was observed. There was no significant relationship between EV protein yield and EV quantity determined by NTA, highlighting the requirement for direct quantification. Using AQ-PCR to relate miRNA copy number to EV yield, a significant increase in miRNA-451a copies/EV was detected in BC patient sera, suggesting potential as a novel biomarker of breast cancer

Solvent-selective routing for centrifugally automated solid-phase purification of RNA

The final publication is available at Springer via https://doi.org/10.1007/s10404-014-1477-9.We present a disc-based module for rotationally controlled solid-phase purification of RNA from cell lysate. To this end, multi-stage routing of a sequence of aqueous and organic liquids into designated waste and elution reservoirs is implemented by a network of strategically placed, solvent-selective composite valves. Using a bead-based stationary phase at the entrance of the router, we show that total RNA is purified with high integrity from cultured MCF7 and T47D cell lines, human leucocytes and Haemophilus influenzae cell lysates. Furthermore, we demonstrate the broad applicability of the device through the in vitro amplification of RNA purified on-disc using RT-PCR and NASBA. Our novel router will be at the pivot of a forthcoming, fully integrated and automated sample preparation system for RNA-based analysis.Peer reviewe

Mesenchymal Stem Cells (MSCs) and cancer: tumour specific delivery vehicles or therapeutic targets?

Mesenchymal stem cells (MSCs) are a subset of nonhematopoietic multipotent cells found primarily within the bone marrow stroma. The ability of MSCs to specifically home to sites of tumors and their metastases, while escaping host immune surveillance, holds tremendous promise for tumor-targeted delivery of therapeutic agents. Concerns that MSCs may have an inherent capacity for transformation have led to a number of studies investigating their stability in vitro, as significant ex vivo expansion will be necessary to yield the number of cells required for therapeutic applications. MSCs have also been seen to influence the morphology and proliferation of cells within their vicinity through a combination of cell-to-cell interactions and the secretion of chemoattractant cytokines. Understanding interactions between MSCs and tumor cells is required to support realization of their clinical potential. This review discusses MSCs and cancer in terms of (1) potential for transformation and de novo tumor formation, (2) interactions with epithelial cancer cells in tumor establishment, and (3) potential role after engraftment at the site of an established tumor. Elucidation of any potential negative effect of MSCs in the tumor setting will support development of protocols to minimize these effects while taking full advantage of the remarkable tumor-homing capacity of these cells. This review by Drs. Dwyer and Kerin discusses mesenchymal stem cells and cancer in terms of (1) potential for transformation and de novo tumor formation, (2) interactions with epithelial cancer cells in tumor establishment, and (3) potential role after engraftment at the site of an established tumor.Funding for this work was provided by the Health Research Board of Ireland and National Breast Cancer Research Institute.peer-reviewe

Diagnostic and therapeutic mesenchymal stem cells for breast cancer treatment

[No abstract available]Peer reviewe

Emerging Evidence of the Functional Impact of the miR379/miR656 Cluster (C14MC) in Breast Cancer

Many microRNAs exist in clusters that share comparable sequence homology and may target genes in a common pathway. The miR-379/miR-656 (C14MC) cluster is imprinted in the DLK1-Dio3 region of 14q32.3 and contains 42 miRNAs. It plays a functional role in numerous biological pathways including vascular remodeling and early development. With many C14MC miRNAs highlighted as potential tumor suppressors in a variety of cancers, the role of this cluster in breast cancer (BC) has garnered increased attention in recent years. This review focuses on C14MC in BC, providing an overview of the constituent miRNAs and addressing each in terms of functional impact, potential target genes/pathways, and, where relevant, biomarker capacity. Studies have revealed the regulation of key factors in disease progression and metastasis including tyrosine kinase pathways and factors critical to epithelial–mesenchymal transition (EMT). This has potentially important clinical implications, with EMT playing a critical role in BC metastasis and tyrosine kinase inhibitors (TKIs) in widespread use for the treatment of BC. While the majority of studies have reported tumor-suppressing roles for these miRNAs, some have highlighted their potential as oncomiRs. Understanding the collective contribution of miRNAs within C14MC to BC may support improved understanding of disease etiology and present novel approaches to targeted therapy

Mesenchymal Stem Cells (MSCs) and cancer: tumour specific delivery vehicles or therapeutic targets?

Mesenchymal stem cells (MSCs) are a subset of nonhematopoietic multipotent cells found primarily within the bone marrow stroma. The ability of MSCs to specifically home to sites of tumors and their metastases, while escaping host immune surveillance, holds tremendous promise for tumor-targeted delivery of therapeutic agents. Concerns that MSCs may have an inherent capacity for transformation have led to a number of studies investigating their stability in vitro, as significant ex vivo expansion will be necessary to yield the number of cells required for therapeutic applications. MSCs have also been seen to influence the morphology and proliferation of cells within their vicinity through a combination of cell-to-cell interactions and the secretion of chemoattractant cytokines. Understanding interactions between MSCs and tumor cells is required to support realization of their clinical potential. This review discusses MSCs and cancer in terms of (1) potential for transformation and de novo tumor formation, (2) interactions with epithelial cancer cells in tumor establishment, and (3) potential role after engraftment at the site of an established tumor. Elucidation of any potential negative effect of MSCs in the tumor setting will support development of protocols to minimize these effects while taking full advantage of the remarkable tumor-homing capacity of these cells. This review by Drs. Dwyer and Kerin discusses mesenchymal stem cells and cancer in terms of (1) potential for transformation and de novo tumor formation, (2) interactions with epithelial cancer cells in tumor establishment, and (3) potential role after engraftment at the site of an established tumor.Funding for this work was provided by the Health Research Board of Ireland and National Breast Cancer Research Institute

Role of Extracellular Vesicles (EVs) in Cell Stress Response and Resistance to Cancer Therapy

Extracellular vesicles (EVs) are nanosized particles released by all cells that have been heralded as novel regulators of cell-to-cell communication. It is becoming increasingly clear that in response to a variety of stress conditions, cells employ EV-mediated intercellular communication to transmit a pro-survival message in the tumor microenvironment and beyond, supporting evasion of cell death and transmitting resistance to therapy. Understanding changes in EV cargo and secretion pattern during cell stress may uncover novel, targetable mechanisms underlying disease progression, metastasis and resistance to therapy. Further, the profile of EVs released into the circulation may provide a circulating biomarker predictive of response to therapy and indicative of microenvironmental conditions linked to disease progression, such as hypoxia. Continued progress in this exciting and rapidly expanding field of research will be dependent upon widespread adoption of transparent reporting standards and implementation of guidelines to establish a consensus on methods of EV isolation, characterisation and nomenclature employed

Exosome-encapsulated micrornas as circulating biomarkers for breast cancer

Breast cancer is a highly prevalent disease, accounting for 29% of invasive cancers in women. Survival from this disease depends on the stage at diagnosis, with patients who are detected earlier having more favourable outcomes. It is because of this that research groups are focusing on the development of a blood-based biomarker for breast cancer. Such biomarkers may facilitate the detection of breast cancer in its infancy before it has spread beyond the primary site. MicroRNAs (miRNAs) have shown immense potential in this setting. These short, non-coding RNA sequences have been shown to be dysregulated in breast cancer. Despite showing immense promise, miRNAs have not been successfully implemented in the clinical setting due to a lack of a standardised approach which has resulted in conflicting results. These challenges may be addressed at least in part through the study of exosomes. The biomarker potential for exosomes holds huge promise and may revolutionise the way in which we diagnose and manage breast cancer. These nanovesicles may be isolated from a variety of bodily fluids, including serum, and their miRNA content has been shown to reflect that of the parent breast cancer cell. This review will highlight the nomenclature and defining characteristics of exosomes, and current methods of isolation of serum-derived exosomes. Initial promising reports on the potential utility of exosomal miRNAs to be used as breast cancer biomarkers will also be addressed