Chlorin e6 – polyvinylpyrrolidone mediated photosensitization is effective against human non-small cell lung carcinoma compared to small cell lung carcinoma xenografts

10.1186/1471-2210-7-15BMC Pharmacology7-BPMH

Molecular profiling of angiogenesis in hypericin mediated photodynamic therapy

<p>Abstract</p> <p>Background</p> <p>Photodynamic therapy (PDT) involves the administration of a tumor-localizing photosensitizing drug, which is activated by light of specific wavelength in the presence of molecular oxygen thus generating reactive oxygen species that is toxic to the tumor cells. PDT selectively destroys photosensitized tissue leading to various cellular and molecular responses. The present study was designed to examine the angiogenic responses at short (0.5 h) and long (6 h) drug light interval (DLI) hypericin-PDT (HY-PDT) treatment at 24 h and 30 days post treatment in a human bladder carcinoma xenograft model. As short DLI targets tumor vasculature and longer DLI induces greater cellular damage, we hypothesized a differential effect of these treatments on the expression of angiogenic factors.</p> <p>Results</p> <p>Immunohistochemistry (IHC) results showed minimal CD31 stained endothelium at 24 h post short DLI PDT indicating extensive vascular damage. Angiogenic proteins such as vascular endothelial growth factor (VEGF), tumor necrosis growth factor-α (TNF-α), interferon-α (IFN-α) and basic fibroblast growth factor (bFGF) were expressed to a greater extent in cellular targeting long DLI PDT compared to vascular mediated short DLI PDT. Gene expression profiling for angiogenesis pathway demonstrated downregulation of adhesion molecules – cadherin 5, collagen alpha 1 and 3 at 24 h post treatment. Hepatocyte growth factor (HGF) and Ephrin-A3 (EFNA3) were upregulated in all treatment groups suggesting a possible activation of c-Met and Ephrin-Eph signaling pathways.</p> <p>Conclusion</p> <p>In conclusion, long DLI HY-PDT induces upregulation of angiogenic proteins. Differential expression of genes involved in the angiogenesis pathway was observed in the various groups treated with HY-PDT.</p

In-vivo optical detection of cancer using chlorin e6 – polyvinylpyrrolidone induced fluorescence imaging and spectroscopy

<p>Abstract</p> <p>Background</p> <p>Photosensitizer based fluorescence imaging and spectroscopy is fast becoming a promising approach for cancer detection. The purpose of this study was to examine the use of the photosensitizer chlorin e6 (Ce6) formulated in polyvinylpyrrolidone (PVP) as a potential exogenous fluorophore for fluorescence imaging and spectroscopic detection of human cancer tissue xenografted in preclinical models as well as in a patient.</p> <p>Methods</p> <p>Fluorescence imaging was performed on MGH human bladder tumor xenografted on both the chick chorioallantoic membrane (CAM) and the murine model using a fluorescence endoscopy imaging system. In addition, fiber optic based fluorescence spectroscopy was performed on tumors and various normal organs in the same mice to validate the macroscopic images. In one patient, fluorescence imaging was performed on angiosarcoma lesions and normal skin in conjunction with fluorescence spectroscopy to validate Ce6-PVP induced fluorescence visual assessment of the lesions.</p> <p>Results</p> <p>Margins of tumor xenografts in the CAM model were clearly outlined under fluorescence imaging. Ce6-PVP-induced fluorescence imaging yielded a specificity of 83% on the CAM model. In mice, fluorescence intensity of Ce6-PVP was higher in bladder tumor compared to adjacent muscle and normal bladder. Clinical results confirmed that fluorescence imaging clearly captured the fluorescence of Ce6-PVP in angiosarcoma lesions and good correlation was found between fluorescence imaging and spectral measurement in the patient.</p> <p>Conclusion</p> <p>Combination of Ce6-PVP induced fluorescence imaging and spectroscopy could allow for optical detection and discrimination between cancer and the surrounding normal tissues. Ce6-PVP seems to be a promising fluorophore for fluorescence diagnosis of cancer.</p

Markers of left ventricular decompensation in aortic stenosis

Calcified aortic stenosis is a condition that affects the valve and the myocardium. As the valve narrows, left ventricular hypertrophy occurs initially as an adaptive mechanism to maintain cardiac output. Ultimately, the ventricle decompensates and patients transition towards heart failure and adverse events. Current guidelines recommend aortic valve replacement in patients with severe aortic stenosis and evidence of decompensation based on either symptoms or an impaired ejection fraction <50%. However, symptoms can be subjective and correlate only modestly with the severity of aortic stenosis whilst impaired ejection fraction is an advanced manifestation and often irreversible. In this review, the authors will discuss the pathophysiology of left ventricular hypertrophy and the transition to heart failure. Subsequently, the authors will examine novel biomarkers that may better identify the transition from hypertrophy to heart failure and therefore guide the optimal timing for aortic valve replacement

SeqEntropy: Genome-Wide Assessment of Repeats for Short Read Sequencing

<div><p>Background</p><p>Recent studies on genome assembly from short-read sequencing data reported the limitation of this technology to reconstruct the entire genome even at very high depth coverage. We investigated the limitation from the perspective of information theory to evaluate the effect of repeats on short-read genome assembly using idealized (error-free) reads at different lengths.</p> <p>Methodology/Principal Findings</p><p>We define a metric H^(k) to be the entropy of sequencing reads at a read length k and use the relative loss of entropy ΔH^(k) to measure the impact of repeats for the reconstruction of whole-genome from sequences of length k. In our experiments, we found that entropy loss correlates well with de-novo assembly coverage of a genome, and a score of ΔH^(k)>1% indicates a severe loss in genome reconstruction fidelity. The minimal read lengths to achieve ΔH^(k)<1% are different for various organisms and are independent of the genome size. For example, in order to meet the threshold of ΔH^(k)<1%, a read length of 60 bp is needed for the sequencing of human genome (3.2 10⁹ bp) and 320 bp for the sequencing of fruit fly (1.8×10⁸ bp). We also calculated the ΔH^(k) scores for 2725 prokaryotic chromosomes and plasmids at several read lengths. Our results indicate that the levels of repeats in different genomes are diverse and the entropy of sequencing reads provides a measurement for the repeat structures.</p> <p>Conclusions/Significance</p><p>The proposed entropy-based measurement, which can be calculated in seconds to minutes in most cases, provides a rapid quantitative evaluation on the limitation of idealized short-read genome sequencing. Moreover, the calculation can be parallelized to scale up to large euakryotic genomes. This approach may be useful to tune the sequencing parameters to achieve better genome assemblies when a closely related genome is already available.</p> </div

Entropy losses at different read lengths for different

<p><b>organisms.</b> In the five organisms, the genomes of zebra fish (<i>D. rerio</i>) and fruit fly (<i>D. melanogaster</i>) will lose more entropy regardless of any read length used for sequencing. In particular, the fruit fly loses >2% of entropy loss even with read length of 120 bp. It will be <1% of entropy loss at read length of 230 bp. On the other hand, the genomes of Yeast (<i>S. cerevisiae</i>) and Nematode (<i>C. elegans</i>) have minor entropy loss even with very short reads. The detail results of entropy measurements are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059484#pone-0059484-t005" target="_blank"><b>Table 5</b></a>.</p

Entropy loss of selected prokaryotic whole genomes with reads of lengths 36, 500 and 1000 bps.

<p>Entropy loss of selected prokaryotic whole genomes with reads of lengths 36, 500 and 1000 bps.</p

Model of typical short read sequencing.

<p>(a) The target sequence is randomly broken into fragments and filtered by their lengths to form a sequencing library. (b) The end or ends of the DNA fragments are sequenced in parallel to generate a massive set of short reads. We assumed the sequencing is random so that each position is more or less covered by equal numbers of fixed-length reads.</p