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May 01, 2011 (Vol. 31, No. 9)

New Cancer Research Tools Change Paradigm

Increased Speed, Automation, and Visualization Should Bring Field to Another Level

  • A range of new technologies and products made their debut at the AACR annual meeting in April, each designed to make cancer research faster, easier, and more biologically and clinically relevant. With an emphasis on automation, genetic and epigenetic analysis, and in vivo cell, tissue, and live-animal imaging, the new technologies on display target key bottlenecks in the drug discovery pipeline.
    Compact and easy to use, the new Moxi Z mini automated cell counter from Orflo combines the Coulter Principle (change in impedance) with a thin-film sensor technology to perform particle sizing (range 2–34 microns) and counting and viability reporting of a 75 µL sample in 8 seconds, for a cost of about $1.50/test.
    Later this month, Sigma-Aldrich plans to introduce a genetically modified breast cancer model cell line as part of its family of oncology cell lines developed with the CompoZr® Zinc Finger Nuclease (ZFN) technology. The first oncology products introduced were colorectal and lung cancer models. The technology allows for the introduction of targeted, heritable changes to create either knock-out disease models or knock-in models in which a specific mutation is created in a gene that remains under the control of its endogenous promoter.
    In the third quarter, Randox expects to launch the QuantiPlasma Array system for biomarker discovery. Designed for analyzing proteome dynamics in plasma samples from normal and disease populations, QuantiPlasma Array kits each contain 300 monoclonal antibodies spotted across 18 biochips. The Biochip Array Technology allows for simultaneous testing of all 300 antibodies in less than 3 hours using as little as 5 µL of sample, the firm reported.
    A poster presented at AACR by NanoInk described the development of a nano-scale sandwich ELISA assay platform using the company’s dip-pen nanolithography (DPN™) technology. These protein nanoarray assays can reportedly achieve sensitivity in the hundreds of femtograms per milliliter range and detect biomarkers in as little as 2–4 µL of sample.
    Olink Bioscience launched the Proseek® homogeneous, real-time PCR-based assay, capable of protein quantification in a 1 µL plasma or serum sample.
    Cerulean Pharma outlined plans for a Phase II clinical trial in 140 patients with non-small-cell lung cancer (NSCLC) of its tumor-targeted nanopharmaceutical CRLX101, composed of camptothecin-containing nanoparticles.
    At AACR, Cerulean and its collaborators presented data from an ongoing 36-patient Phase IIa expansion study of CRLX101 to evaluate the biological activity and tolerability of the drug in patients with solid tumors who had failed standard therapy. Multiple patients with advanced NSCLC who have been treated with the drug during the Phase IIa trial have had stable disease for longer than six months. The size and surface properties of the nanoparticle carrier target the drug to the tumor, where the complex takes advantage of the leaky neovasculature to penetrate the tumor, where the drug is released from the nanoparticles, which break down and are excreted from the body.

  • Real-Time Imaging

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    Sentinel lymph node detection using photoacoustic imaging: 3-D image of mouse axillia showing the lymph node and associated lymph vessels, imaged using contrast dye—methylene blue at 680 nm. [VisualSonics]

    VisualSonics (a subsidiary of Sonosite), launched the Vevo LAXR photoacoustic imaging system designed for preclinical in vivo imaging. It combines high frequency ultrasound and laser-based optical imaging. The ability to perform multispectral imaging allows for visualization of the tumor microenvironment and vasculature and supports detection of lymph nodes and metastatic disease, monitoring of therapeutic response, nanoparticle research, oxygen saturation quantification, and assessment of angiogenesis.

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    Multispectral brightfield and fluorescence imaging (upper-left images) can be used to more effectively separate stains and probes in the same tissue section and improve tissue and cell segmentation (lower-right images). Since there is no need to utilize serial sections, one can gain a better understanding of the specimen. [Caliper Life Sciences]

    With the acquisition of Cambridge Research & Instrumentation (CRi), Caliper Life Sciences added new multiplexed in vivo and tissue imaging technology to its existing family of Quantum FX µCT and IVIS® preclinical imaging systems. The newly acquired instruments include CRi’s Nuance™ and TRIO™ for multispectral imaging on brightfield and fluorescence microscopes, Vectra™ for high-throughput slide imaging, and Maestro™ for in vivo optical imaging.

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    PerkinElmer’s Multispecies Imaging Module (MSIM) enables researchers to generate 3-D datasets of animal models relevant to disease research, including imaging capability for larger animals.

    PerkinElmer introduced a Multispecies Imaging Module (MSIM) for its Fluorescence Molecular Tomography (FMT) in vivo imaging systems, which can be used to generate quantitative 3-D datasets from small and large animal models. The company has upgraded its TrueQuant™ analysis software for the new module. The FMT 2500 LX in vivo imaging system can perform multiplexed analysis using up to four different fluorophores, according to company literature.

    The iBox Explorer fluorescence imaging microscope, new from UVP , allows for imaging of whole organs down to the cellular level using a CCD camera and optics that span the visible to near-infrared spectrums and a range of BioLite™ filters. The imager captures signals from green fluorescent protein and red fluorescent protein.

    At AACR, CompuCyte featured its iCys cytometric software for performing live-cell analysis on its iGeneration laser-scanning cytometers. The company is developing a live-cell analysis chamber that will enable repetitive scanning studies.

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    Demonstration of an optimized bioluminescent biosensor (from Promega) for the detection of cell death in living animals: Representative images taken at indicated time points of intratibial implanted 1833 reporter cells. TRAIL treatment (8 mg/kg) resulted in a 100–200 fold induction of bioluminescence activity that correlated with cell death as demonstrated by increased cleavage of caspase-3. The high signal to noise and dynamic range of reporter activity provides a sensitive and quantitative surrogate for the evaluation of experimental therapeutics.

    A poster presented by researchers from University of Michigan described the use of Promega’s GloSensor™ luciferase biosensor technology to develop a bioluminescent imaging assay designed to detect caspase-dependent cell death in living mice as a surrogate marker to assess the efficacy of cancer therapeutics.

    With GloSensor constructs, increasing amounts of caspase-3/7 in a cell that stably expresses genetically modified luciferase results in a conformational change in the molecule that allows a signal to be generated. The poster describes the use of a bioluminescent reporter to image apoptosis in cancer cell lines and mouse models in a high-throughput screening format.

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