Search

© 2019, The Author(s). In the original version of this Article, Luisa Marcelino was incorrectly affiliated with ‘Department of Chemistry, University of Cambridge, Lensfield Road, UK’ and ‘Scripps Institution of Oceanography, University of California, San Diego, USA’. The correct affiliations are listed below. Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL, USA Integrative Research Center, Field Museum of Natural History, Chicago, IL, USA This error has now been corrected in the PDF and HTML versions of the Article.

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U.S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

The success of reef-building corals for >200 million years has been dependent on the mutualistic interaction between the coral host and its photosynthetic endosymbiont dinoflagellates (family Symbiodiniaceae) that supply the coral host with nutrients and energy for growth and calcification. While multiple light scattering in coral tissue and skeleton significantly enhance the light microenvironment for Symbiodiniaceae, the mechanisms of light propagation in tissue and skeleton remain largely unknown due to a lack of technologies to measure the intrinsic optical properties of both compartments in live corals. Here we introduce ISOCT (inverse spectroscopic optical coherence tomography), a non-invasive approach to measure optical properties and three-dimensional morphology of living corals at micron- and nano-length scales, respectively, which are involved in the control of light propagation. ISOCT enables measurements of optical properties in the visible range and thus allows for characterization of the density of light harvesting pigments in coral. We used ISOCT to characterize the optical scattering coefficient (μs) of the coral skeleton and chlorophyll a concentration of live coral tissue. ISOCT further characterized the overall micro- and nano-morphology of live tissue by measuring differences in the sub-micron spatial mass density distribution (D) that vary throughout the tissue and skeleton and give rise to light scattering, and this enabled estimates of the spatial directionality of light scattering, i.e., the anisotropy coefficient, g. Thus, ISOCT enables imaging of coral nanoscale structures and allows for quantifying light scattering and pigment absorption in live corals. ISOCT could thus be developed into an important tool for rapid, non-invasive monitoring of coral health, growth and photophysiology with unprecedented spatial resolution.

The success of reef-building corals for >200 million years has been dependent on the mutualistic interaction between the coral host and its photosynthetic endosymbiont dinoflagellates (family Symbiodiniaceae) that supply the coral host with nutrients and energy for growth and calcification. While multiple light scattering in coral tissue and skeleton significantly enhance the light microenvironment for Symbiodiniaceae, the mechanisms of light propagation in tissue and skeleton remain largely unknown due to a lack of technologies to measure the intrinsic optical properties of both compartments in live corals. Here we introduce ISOCT (inverse spectroscopic optical coherence tomography), a non-invasive approach to measure optical properties and three-dimensional morphology of living corals at micron- and nano-length scales, respectively, which are involved in the control of light propagation. ISOCT enables measurements of optical properties in the visible range and thus allows for characterization of the density of light harvesting pigments in coral. We used ISOCT to characterize the optical scattering coefficient (μs) of the coral skeleton and chlorophyll a concentration of live coral tissue. ISOCT further characterized the overall micro- and nano-morphology of live tissue by measuring differences in the sub-micron spatial mass density distribution (D) that vary throughout the tissue and skeleton and give rise to light scattering, and this enabled estimates of the spatial directionality of light scattering, i.e., the anisotropy coefficient, g. Thus, ISOCT enables imaging of coral nanoscale structures and allows for quantifying light scattering and pigment absorption in live corals. ISOCT could thus be developed into an important tool for rapid, non-invasive monitoring of coral health, growth and photophysiology with unprecedented spatial resolution.

Objectives: Emerging evidence implicates the SNAIL family of transcriptional repressors in cancer development; however, the role of SNAIL in colorectal cancer has not been established. To investigate the importance of SNAIL in colorectal carcinogenesis, we examined the phenotypic and cellular consequences of SNAIL down-regulation in the MIN mouse. Methods: Twenty-eight male MIN mice were randomized to treatment with an antisense phosphorodiamidate morpholino oligomer (AS-PMO) to SNAIL, saline, or a scrambled sequence control for 6 weeks. Tumors were scored and the molecular/cellular effects of anti-SNAIL treatment were evaluated through immunohistochemical analysis of the uninvolved intestinal mucosa for SNAIL and E-cadherin levels along with rates of apoptosis and proliferation. Furthermore, microarchitectural alterations were determined through measurement of fractal dimension. Results: In the uninvolved mucosa, SNAIL AS-PMO treatment moderately decreased SNAIL protein when compared with saline-treated animals (immunohistochemistry scores 3.0 ± 0.8 versus 2.1 ± 0.6, respectively; P = 0.01) with a concomitant increase in E-cadherin expression (1.8 ± 0.6 versus 2.4 ± 0.5; P < 0.05). Anti-SNAIL PMO, but not scramble control, resulted in a significant decrease in both total tumor number and incidence of tumors >2 mm (22% and 54%, respectively; P < 0.05). Furthermore, this was accompanied by an increased apoptosis rate (2-fold), decreased proliferation (3-fold), and normalization of the fractal dimension in the uninvolved intestinal mucosa. Conclusions: We show, for the first time, that SNAIL overexpression is important in intestinal tumorigenesis. While this PMO regimen afforded modest SNAIL suppression and hence tumor reduction, this provides compelling evidence for the role of SNAIL overexpression in colonic neoplasia.

Cancerous and precancerous growths often exhibit changes in scattering, and therefore depolarization, as well as collagen breakdown, causing changes in birefringent effects. Simple difference of linear polarization imaging is unable to represent anisotropic effects like birefringence, and Mueller polarimetry is time-consuming and difficult to implement clinically. This work presents a dual-polarization endoscope to collect co- and cross-polarized images for each of two polarization states, and further incorporates narrow band detection to increase vascular contrast, particularly vascular remodeling present in diseased tissue, and provide depth sensitivity. The endoscope was shown to be sensitive to both isotropic and anisotropic materials in phantom and in vivo experiments.

Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerization- volume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.

There are several challenges when fibre image guides (FIG) are used for endoscopic speckle acquisition: cross talk between fibre cores, FIG fixed pattern noise, the small probe diameter and low sensitivity and resolution due to the decreased number of speckles and their low transmission through the FIG. In this paper, an endoscopic laser speckle contrast analysis system (ELASCA) based on a leached fibre image guide (LFIG) is presented. Different methods of acquiring LASCA images through LFIGs were investigated including the effect of changing the number of speckles per fibre, defocusing the FIG image onto the CCD and processing speckle images with masks and Butterworth filters to deal with the LFIG fixed pattern and noise from the cladding. The experimental results based on a phantom consisting of intralipid suspension pumped at varying speed showed that this system could detect speed changes and that in the case of multiple speckles per fibre the Nyquist frequency criterion need not be applied since the speckle may be transferred through the fibres to some extent. In contrast to the previously reported ELASCA results, this system can both give a map of the observed area and the temporal change in flow. An additional benefit is the small size of the LFIG, which is compatible with current endoscopic instrument channels and may allow additional surgical applications.

We report on the modeling of a photopolymerizable hydrogel and its application as a replacement of the interior of the intervertebral disc (so called Nucleus Pulposus). The hydrogel is initially injected in its liquid form and then photopolymerized via a small catheter. Therefore also the light necessary for the photopolymerization is constrained to a small light guide to keep the surgical procedure as minimally invasive as possible. Hence the hydrogel is photopolymerized inside. For applications with restricted physical access and illumination time such as an Nucleus Pulposus replacement photopolymerization of volumes with a large volume/illumination area ratio becomes highly challenging. During polymerization the material’s absorption and scattering coefficients change and directly influence local polymerization rates. By understanding and controlling such polymerization patterns local material properties can be engineered (e.g. elastic modulus swelling ratio) to match the set of mechanical requirements for the implant. Thus it is essential to better understand and model photopolymerization reactions. Experiments were conducted by polymerizing a hydrogel in a column like volume using an optical fiber for light delivery. Quantitative scattering and absorption values as well as monomer conversion rates of the hydrogel sample were validated using a newly established Monte Carlo model for photopolymerization. The results were used to study and predict 3D polymerization patterns for different illumination configurations. In particular we show an example of a lumbar intervertebral disc replacement where the jelly core of the intervertebral disc (Nucleus Pulposus) is replaced by an in situ photopolymerized hydrogel. The results provide insights for the development of novel endoscopic light scattering polymerization probes paving the way for a new generation of implantable hydrogels. © (2013) COPYRIGHT Society of Photo Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.