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Tichauer et al. describe a dual-tracer approach to quantify cancer cell receptor concentrations, in this case epidermal growth factor receptor, in lymph nodes, that can also correct for nonspecific uptake.
The next generation of genetically engineered mouse models of pancreatic cancer involving a new inducible dual-recombinase system that combines Flp-FRT and Cre-loxP.
External blood-cleansing device for rapidly removing microorganisms and endotoxins from blood without first needing to identify the source of the infection.
Proteomic-imaging analysis of caveolae shows active transvascular pumping of antibodies across the endothelial cell barrier and into solid tumors against a concentration gradient.
Bioluminescence-based reporter system for monitoring nonsense-mediated mRNA decay (NMD) in live cells, which identifies a group of cardiac glycosides as potent inhibitors of NMD and intracellular calcium as a key regulator of NMD.
Feldman and colleagues describe a plasmonic gold chip for distinguishing type 1 from type 2 diabetes using ultralow volumes of serum and with comparable sensitivity to the current gold standard, radioimmunoassays.
High-throughput screening platform for the testing of small bioactive molecules that promote oligodendrocyte differentiation and remyelination: a new path to the discovery of potential drugs for multiple sclerosis.
Tim Berendsen and colleagues describe an approach for long-term liver preservation based on cryopreservation, supercooling and machine perfusion where rat livers preserved for 4 d remain viable following transplantation.
Repetitive dynamic two-photon imaging of retinoid cycle fluorophores and subcellular details of their location within the retinal pigment epithelium in intact eyes of live mice.
Multidrug and radiation resistance, as well as nonspecific toxic effects of some drugs, currently limit some cancer therapies. Ekaterina Lukianova-Hleb and colleagues address this with the development of an intracellular drug release system using plasmonic nanobubbles for the on-demand release of the encapsulated payload from nanocarriers, achieving high target cell specificity and intracellular concentration and enhanced therapeutic efficacy of both drugs and X-rays. Validation is shown in aggressive and multidrug resistant head and neck squamous cell carcinoma using encapsulated doxorubicin and paclitaxel.
Using an adapted competitive peptide phage display platform, Hong Qin and colleagues identify new candidate peptides specifically binding myeloid-derived suppressor cells (MDSCs), with which they generate peptide-Fc fusion proteins (peptibodies). The peptibodies deplete intra-umoral MDSCs in several mouse tumor models, in addition to those in blood and spleen, with limited off-target activity and superiority over standard depletion methods. Validation of this approach for cell type–specific surface marker discovery identified S100A9 as a target on the surface of MDSCs.
Modeling and documenting malignant progression in vitro without the need for in vivo transplantation represents a clear step forward for cancer investigation. Using an air-liquid interface methodology, Xingnan Li and colleagues show they can robustly model a range of gastrointestinal malignancies from pancreas, stomach and colon in primary epithelial/mesenchymal organoid culture. This setup is able to generate detailed histologic endpoints for oncogenic transformation in vitro and demonstrate in vivo tumorigenicity when the organoids are transplanted.
Whole-exome sequencing (WES) has emerged as a transformative technology for biological discovery, but technical difficulties have so far prevented its widespread clinical use. Here, Eliezer Van Allen and colleagues are able to perform production-scale WES on small amounts of clinically acquired formalin-fixed, paraffin-embedded tumor tissues. Using a newly created WES clinical interpretation algorithm, they apply the complete clinical WES framework prospectively to patients and demonstrate how it can be used to directly affect patient care.
Michael Breckwoldt and colleagues have developed a new approach to follow the mitochondrial redox potential of neurons with high spatio-temporal resolution. This multiparametric in vivo imaging approach is based on the transgenic expression of a biosensor for glutathione redox potential in neuronal mitochondria, with utility demonstrated in mouse models of amyotrophic lateral sclerosis and spinal cord injury. It should prove useful for studying mitochondrial pathology in neurological disease models.
Aaron Newman and his colleagues introduce a next-generation sequencing–based approach for the cost-effective detection and quantitation of tumor-derived circulating DNA in both early- and advanced-stage tumors and with high levels of sensitivity and specificity. CAPP-Seq (cancer personalized profiling by deep sequencing) can simultaneously detect multiple mutations and mutation types, including rearrangements. Here, utility is demonstrated for non–small-cell lung cancer.
A new technique that allows high-resolution in vivo imaging of myelinated fibers without the use of a fluorescent marker is described by Aaron Schain and colleagues. This label-free approach, which does not require histological or immunocytochemical staining, uses spectral confocal reflectance microscopy, can be performed on a conventional confocal microscope and can be used for deep-tissue transcranial imaging up to 400 μm deep, longitudinally tracking fine changes in axonal myelination. It has potential for the in vivo analysis of normal myelin development, as well as demyelinating diseases of the CNS and peripheral nervous system.
Alain Thierry and his colleagues offer a new allele-specific, quantitative PCR–based method designed for the detection of point mutations and determination of mutation load using circulating cell-free DNA isolated from blood. In a blinded study of patients with colorectal cancer, the method exhibited 98% specificity and 92% sensitivity for the seven KRAS point mutations tested and compared favorably with other routinely used detection methods. The approach should help in patients selection for anti-EGFR treatments and for monitoring resistance.
The work of Michael Angelo and colleagues uses multiplexed ion beam imaging (MIBI) to localize and visualize protein expression in a manner analogous to immunohistochemistry (IHC) while circumventing some of the limitations of conventional IHC with clinical samples. MIBI uses secondary ion mass spectrometry to image antibodies tagged with isotopically pure elemental metal reporters, expanding the number of targets that can be analyzed simultaneously to about 100. The approach, used here to image breast tumor tissue sections, offers over a five-log dynamic range and compatibility with standard formalin-fixed, paraffin-embedded tissue sections.
