Integrated genomic and transcriptomic analyses of radiation-induced malignancies

Cancer is a genetic disease caused by an unregulated expansion of a clone of cells (Sompayrac, 2004). The genetic abnormalities in cancer are the consequences of defective DNA replication, repair, maintenance, and modification, genetic background, and exposure to mutagens (Alexandrov et al., 2013). Ionizing radiation (IR), a mutagen exposed to cancer patients during clinical radiotherapy (RT), can cause DNA damage, genomic instability, and mutagenesis (Sherborne et al., 2015). While RT has been effective in treating cancer, it increases the risk of second malignant neoplasm (SMN), a severe delayed complication associated with mainly pediatric cancer survivors many decades after the treatment of their first cancer (Robison & Hudson, 2014). As the mortality of patients with childhood cancer has been decreasing, cases of radiation-induced cancers has been increasing (Robison & Hudson, 2014). The considerable contribution by RT to SMN risk illustrate the need to characterize the genetic mechanism directly responsible for radiation-induced malignancies. To better our understanding of the mutational landscape of SMNs, our specific aims are to identify potential driver mutations implicated in radiation-induced malignancies through genome and transcriptome analysis and to assess whether genetic background, specifically germline polymorphisms and mutations in tumor suppressor gene TP53, has an impact on the formation of secondary malignancies

Optical nanoparticle sensors for quantitative intracellular imaging

Real-time measurements of biological/chemical/physical processes, with no interferences, are an ultimate goal for in vivo intracellular studies. To construct intracellular biosensors that meet such a goal, nanoparticle (NP) platforms seem to be most promising, because of their small size and excellent engineerability. This review describes the development of NP-based opical sensors and their intracellular applications. The sensor designs are classified into two types, based on the sensor structures regarding analyte receptor and signal transducer. Type 1 sensors, with a single component for both receptor and transducer, work by mechanisms similar to those of ‘molecular probes’. Type 2 sensors, with a separate component for receptor and transducer, work by different mechanisms that require the presence of specific NPs. A synergistic increase in optical signal or selectivity has been reported for these second type of NP sensors. With ongoing rapid advances in nanotechnology and instrumentation, these NP systems will soon be capable of sensing at the single-molecule level, at the point of interest within the living cell, and capable of simultaneously detecting multiple analytes and physical parameters. Copyright © 2008 John Wiley & Sons, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61310/1/2_ftp.pd

Bright color optical switching device by polymer network liquid crystal with a specular reflector

The color optical switching device by polymer network liquid crystal (PNLC) with color filter on a specular reflector shows excellent performance; white reflectance of 22%, color gamut of 32%, and contrast ratio up to 50:1 in reflective mode measurement. The view-angle dependence of the reflectance can be adjusted by changing the PNLC thickness. The color chromaticity shown by the device is close to the limit value of color filters, and its value nearly remains with respect to the operating voltage. These optical properties of the device can be explained from the prediction based on multiple interactions between the light and the droplets of liquid crystal. The high reflectance, vivid color image, and moderate responds time allow the PNLC device to drive good color moving image. It can widely extend the applications of the reflective device. © 2011 Optical Society of America.1

Two‐Photon Fluorescence Imaging Super‐Enhanced by Multishell Nanophotonic Particles, with Application to Subcellular pH

A novel nanophotonic method for enhancing the two‐photon fluorescence signal of a fluorophore is presented. It utilizes the second harmonic (SH) of the exciting light generated by noble metal nanospheres in whose near‐field the dye molecules are placed, to further enhance the dye's fluorescence signal in addition to the usual metal‐enhanced fluorescence phenomenon. This method enables demonstration, for the first time, of two‐photon fluorescence enhancement inside a biological system, namely live cells. A multishell hydrogel nanoparticle containing a silver core, a protective citrate capping, which serves also as an excitation quenching inhibitor spacer, a pH indicator dye shell, and a polyacrylamide cladding are employed. Utilizing this technique, an enhancement of up to 20 times in the two‐photon fluorescence of the indicator dye is observed. Although a significant portion of the enhanced fluorescence signal is due to one‐photon processes accompanying the SH generation of the exciting light, this method preserves all the advantages of infrared‐excited, two‐photon microscopy: enhanced penetration depth, localized excitation, low photobleaching, low autofluorescence, and low cellular damage. The two‐photon fluorescence signal of a fluorophore is enhanced by utilizing the second harmonic of the exciting light generated by noble metal nanospheres in whose near‐field dye molecules are placed. A multishell hydrogel nanoparticle containing a silver core, protective citrate capping, pH indicator dye, and polyacrylamide cladding is utilized for pH sensing and fluorescence imaging in live cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92437/1/2213_ftp.pd

Cocoa polyphenols suppress TNF-α-induced vascular endothelial growth factor expression by inhibiting phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase kinase-1 (MEK1) activities in mouse epidermal cells

Cocoa polyphenols have antioxidant and anti-inflammatory effects. TNF-α is a pro-inflammatory cytokine that has a vital role in the pathogenesis of inflammatory diseases such as cancer and psoriasis. Vascular endothelial growth factor (VEGF) expression is associated with tumorigenesis, CVD, rheumatoid arthritis and psoriasis. We tested whether cocoa polyphenol extract (CPE) inhibited TNF-α-induced VEGF expression in promotion-sensitive JB6 mouse epidermal cells. CPE significantly inhibited TNF-α-induced up-regulation of VEGF via reducing TNF-α-induced activation of the nuclear transcription factors activator protein-1 (AP-1) and NF-κB, which are key regulators of VEGF expression. CPE also inhibited TNF-α-induced phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase. CPE blocked activation of their downstream kinases, p70 kDa ribosomal protein S6 kinase and p90 kDa ribosomal protein S6 kinase. CPE suppressed phosphoinositide 3-kinase (PI3K) activity via binding PI3K directly. CPE did not affect TNF-α-induced phosphorylation of mitogen-activated protein kinase kinase-1 (MEK1) but suppressed TNF-α-induced MEK1 activity. Collectively, these results indicate that CPE reduced TNF-α-induced up-regulation of VEGF by directly inhibiting PI3K and MEK1 activities, which may contribute to its chemopreventive potentia