59 research outputs found
Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting
Cell-based therapy exploits modified human cells to treat diseases but its targeted application
in specific tissues, particularly those lying deep in the body where direct injection is not
possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to
direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour
sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic
iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the
tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into
tumours, resulting in increased tumour macrophage infiltration and reduction in tumour
burden and metastasis. Our study indicates that clinical MRI scanners can not only track the
location of magnetically labelled cells but also have the potential to steer them into one or
more target tissues
Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models
Cytotoxic chemotherapy is an effective treatment for invasive breast cancer. However, experimental studies in mice also suggest that chemotherapy has pro-metastatic effects. Primary tumours release extracellular vesicles (EVs), including exosomes, that can facilitate the seeding and growth of metastatic cancer cells in distant organs, but the effects of chemotherapy on tumour-derived EVs remain unclear. Here we show that two classes of cytotoxic drugs broadly employed in pre-operative (neoadjuvant) breast cancer therapy, taxanes and anthracyclines, elicit tumour-derived EVs with enhanced pro-metastatic capacity. Chemotherapy-elicited EVs are enriched in annexin A6 (ANXA6), a Ca2+-dependent protein that promotes NF-κB-dependent endothelial cell activation, Ccl2 induction and Ly6C+CCR2+ monocyte expansion in the pulmonary pre-metastatic niche to facilitate the establishment of lung metastasis. Genetic inactivation of Anxa6 in cancer cells or Ccr2 in host cells blunts the prometastatic effects of chemotherapy-elicited EVs. ANXA6 is detected, and potentially enriched, in the circulating EVs of breast cancer patients undergoing neoadjuvant chemotherapy
Comparison of methods for the identification of microorganisms isolated from blood cultures
Perivascular macrophages in health and disease
Macrophages are a heterogeneous group of cells that are capable of carrying out distinct functions in different tissues, as well as in different locations within a given tissue. Some of these tissue macrophages lie on, or close to, the outer (abluminal) surface of blood vessels and perform several crucial activities at this interface between the tissue and the blood. In steady-state tissues, these perivascular macrophages maintain tight junctions between endothelial cells and limit vessel permeability, phagocytose potential pathogens before they enter tissues from the blood and restrict inappropriate inflammation. They also have a multifaceted role in diseases such as cancer, Alzheimer disease, multiple sclerosis and type 1 diabetes. Here, we examine the important functions of perivascular macrophages in various adult tissues and describe how these functions are perturbed in a broad array of pathological conditions
Comparative transcriptome analysis reveals different strategies for degradation of steam-exploded sugarcane bagasse by Aspergillus niger and Trichoderma reesei
Nanoparticles for the delivery of zoledronic acid to prostate cancer cells: A comparative analysis through time lapse video-microscopy technique
Cancer in the spotlight: Using intravital imaging in cancer research
Intravital imaging can provide unique insights into cancer biology and has been particularly useful for research into therapy responses, metastasis, and immune responses. Here, we discuss the protocols that we routinely use for intravital imaging of mammary tumors to follow drug responses and for imaging of lungs to study metastatic seeding. These methods include: (1) the skin-flap technique used to image mammary tumors in a single, long experiment; (2) the use of an implantable imaging window for long-term serial imaging of mammary glands; and (3) the use of a thoracic window for intravital imaging of lungs to study the processes involved in the metastatic spread to lungs. We discuss common technical issues encountered when using each of these methods and provide our solutions for overcoming them. Finally, we discuss some of the exciting, new techniques on the horizon for intravital imaging in cancer biology
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