Selection of an anti-solvent for efficient and stable cesium-containing triple cation planar perovskite solar cells.

PubMed

Xiao, Meng; Zhao, Li; Geng, Min; Li, Yanyan; Dong, Binghai; Xu, Zuxun; Wan, Li; Li, Wenlu; Wang, Shimin

2018-06-19

The perovskite layer is a crucial component influencing high-performance perovskite solar cells (PSCs). In the one-step solution method, anti-solvents are important for obtaining smooth and uniform perovskite active layers. This work explored the effect of various anti-solvents on the preparation of triple cation perovskite active layers. In general, anti-solvents with low dielectric constants, low polarity, and low boiling point are suitable for the preparation of perovskite films. Microstructural and elemental analyses of the perovskite films were systematically conducted by scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The photoelectric properties, carrier transfer, and recombination process in the PSCs were investigated using photocurrent-voltage characteristic curves and electrochemical impedance spectroscopy. Optimum performance was obtained when the anti-solvent was diethyl ether (DEE) and the ratio of the optimum amount of DEE to the volume of the precursor was 1 : 10. Meanwhile, we found that the partial replacement of formamidinium/methylammonium by cesium could increase the stability of the PSCs and enhance the power conversion efficiency from 15.49% to over 17.38%.

Performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches in VQ codebook generation for image compression

NASA Astrophysics Data System (ADS)

Tsai, Jinn-Tsong; Chou, Ping-Yi; Chou, Jyh-Horng

2015-11-01

The aim of this study is to generate vector quantisation (VQ) codebooks by integrating principle component analysis (PCA) algorithm, Linde-Buzo-Gray (LBG) algorithm, and evolutionary algorithms (EAs). The EAs include genetic algorithm (GA), particle swarm optimisation (PSO), honey bee mating optimisation (HBMO), and firefly algorithm (FF). The study is to provide performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches. The PCA-EA-LBG approaches contain PCA-GA-LBG, PCA-PSO-LBG, PCA-HBMO-LBG, and PCA-FF-LBG, while the PCA-LBG-EA approaches contain PCA-LBG, PCA-LBG-GA, PCA-LBG-PSO, PCA-LBG-HBMO, and PCA-LBG-FF. All training vectors of test images are grouped according to PCA. The PCA-EA-LBG used the vectors grouped by PCA as initial individuals, and the best solution gained by the EAs was given for LBG to discover a codebook. The PCA-LBG approach is to use the PCA to select vectors as initial individuals for LBG to find a codebook. The PCA-LBG-EA used the final result of PCA-LBG as an initial individual for EAs to find a codebook. The search schemes in PCA-EA-LBG first used global search and then applied local search skill, while in PCA-LBG-EA first used local search and then employed global search skill. The results verify that the PCA-EA-LBG indeed gain superior results compared to the PCA-LBG-EA, because the PCA-EA-LBG explores a global area to find a solution, and then exploits a better one from the local area of the solution. Furthermore the proposed PCA-EA-LBG approaches in designing VQ codebooks outperform existing approaches shown in the literature.

Ampicillin Nanoparticles Production via Supercritical CO2 Gas Antisolvent Process.

PubMed

Esfandiari, Nadia; Ghoreishi, Seyyed M

2015-12-01

The micronization of ampicillin via supercritical gas antisolvent (GAS) process was studied. The particle size distribution was significantly controlled with effective GAS variables such as initial solute concentration, temperature, pressure, and antisolvent addition rate. The effect of each variable in three levels was investigated. The precipitated particles were analyzed with scanning electron microscopy (SEM) and Zetasizer Nano ZS. The results indicated that decreasing the temperature and initial solute concentration while increasing the antisolvent rate and pressure led to a decrease in ampicillin particle size. The mean particle size of ampicillin was obtained in the range of 220-430 nm by varying the GAS effective variables. The purity of GAS-synthesized ampicillin nanoparticles was analyzed in contrast to unprocessed ampicillin by FTIR and HPLC. The results indicated that the structure of the ampicillin nanoparticles remained unchanged during the GAS process.

Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore Arrays.

PubMed

Othman, Rahimah; Vladisavljević, Goran T; Simone, Elena; Nagy, Zoltan K; Holdich, Richard G

2017-12-06

Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7-34 μm and was controlled by the PRX concentration in the feed solution (15-25 g L -1 ), antisolvent/solvent volume ratio (5-30), and type of antisolvent (Milli-Q water or 0.1-0.5 wt % aqueous solutions of hydroxypropyl methyl cellulose (HPMC), poly(vinyl alcohol) or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L -1 PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt % HPMC solution stirred at 1500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilization of microcrystals against agglomeration than poly(vinyl alcohol) and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystallizer. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals.

Formation of itraconazole-succinic acid cocrystals by gas antisolvent cocrystallization.

PubMed

Ober, Courtney A; Gupta, Ram B

2012-12-01

Cocrystals of itraconazole, an antifungal drug with poor bioavailability, and succinic acid, a water-soluble dicarboxylic acid, were formed by gas antisolvent (GAS) cocrystallization using pressurized CO(2) to improve itraconazole dissolution. In this study, itraconazole and succinic acid were simultaneously dissolved in a liquid solvent, tetrahydrofuran, at ambient conditions. The solution was then pressurized with CO(2), which decreased the solvating power of tetrahydrofuran and caused crystallization of itraconazole-succinic acid cocrystals. The cocrystals prepared by GAS cocrystallization were compared to those produced using a traditional liquid antisolvent, n-heptane, for crystallinity, chemical structure, thermal behavior, size and surface morphology, potential clinical relevance, and stability. Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy analyses showed that itraconazole-succinic acid cocrystals with physical and chemical properties similar to cocrystals produced using a traditional liquid antisolvent technique can be prepared by CO(2) antisolvent cocrystallization. The dissolution profile of itraconazole was significantly enhanced through GAS cocrystallization with succinic acid, achieving over 90% dissolution in less than 2 h. The cocrystals appeared stable against thermal stress for up to 4 weeks under accelerated stability conditions, showing only moderate decreases in their degree of crystallinity but no change in their crystalline structure. This study shows the utility of an itraconazole-succinic acid cocrystal for improving itraconazole bioavailability while also demonstrating the potential for CO(2) to replace traditional liquid antisolvents in cocrystal preparation, thus making cocrystal production more environmentally benign and scale-up more feasible.

Monitoring of antisolvent crystallization of sodium scutellarein by combined FBRM-PVM-NIR.

PubMed

Liu, Xuesong; Sun, Di; Wang, Feng; Wu, Yongjiang; Chen, Yong; Wang, Longhu

2011-06-01

Antisolvent crystallization can be used as an alternative to cooling or evaporation for the separation and purification of solid product in the pharmaceutical industry. To improve the process understanding of antisolvent crystallization, the use of in-line tools is vital. In this study, the process analytical technology (PAT) tools including focused beam reflectance measurement (FBRM), particle video microscope (PVM), and near-infrared spectroscopy (NIRS) were utilized to monitor antisolvent crystallization of sodium scutellarein. FBRM was used to monitor chord count and chord length distribution of sodium scutellarein particles in the crystallizer, and PVM, as an in-line video camera, provided pictures imaging particle shape and dimension. In addition, a quantitative model of PLS was established by in-line NIRS to detect the concentration of sodium scutellarein in the solvent and good calibration statistics were obtained (r(2) = 0.976) with the residual predictive deviation value of 11.3. The discussion over sensitivities, strengths, and weaknesses of the PAT tools may be helpful in selection of suitable PAT techniques. These in-line techniques eliminate the need for sample preparation and offer a time-saving approach to understand and monitor antisolvent crystallization process. Copyright © 2011 Wiley-Liss, Inc.

Selection and deposition of nanoparticles using CO.sub.2-expanded liquids

DOEpatents

Roberts, Christopher B [Auburn, AL; McLeod, Marshall Chandler [Hillsboro, OR; Anand, Madhu [Auburn, AL

2008-06-10

A method for size selection of nanostructures comprising utilizing a gas-expanded liquids (GEL) and controlled pressure to precipitate desired size populations of nanostructures, e.g., monodisperse. The GEL can comprise CO.sub.2 antisolvent and an organic solvent. The method can be carried out in an apparatus comprising a first open vessel configured to allow movement of a liquid/particle solution to specific desired locations within the vessel, a second pressure vessel, a location controller for controlling location of the particles and solution within the first vessel, a inlet for addition of antisolvent to the first vessel, and a device for measuring the amount of antisolvent added. Also disclosed is a method for forming nanoparticle thin films comprising utilizing a GEL containing a substrate, pressurizing the solution to precipitate and deposit nanoparticles onto the substrate, removing the solvent thereby leaving a thin nanoparticle film, removing the solvent and antisolvent, and drying the film.

Selection of nanoparticles using CO.sub.2-expanded liquids

DOEpatents

Roberts, Christopher B; McLeod, Marshall Chandler; Anand, Madhu

2013-02-19

A method for size selection of nanostructures comprising utilizing a gas-expanded liquids (GEL) and controlled pressure to precipitate desired size populations of nanostructures, e.g., monodisperse. The GEL can comprise CO.sub.2 antisolvent and an organic solvent. The method can be carried out in an apparatus comprising a first open vessel configured to allow movement of a liquid/particle solution to specific desired locations within the vessel, a second pressure vessel, a location controller for controlling location of the particles and solution within the first vessel, a inlet for addition of antisolvent to the first vessel, and a device for measuring the amount of antisolvent added. Also disclosed is a method for forming nanoparticle thin films comprising utilizing a GEL containing a substrate, pressurizing the solution to precipitate and deposit nanoparticles onto the substrate, removing the solvent thereby leaving a thin nanoparticle film, removing the solvent and antisolvent, and drying the film.

Ultrasmooth Perovskite Film via Mixed Anti-Solvent Strategy with Improved Efficiency.

PubMed

Yu, Yu; Yang, Songwang; Lei, Lei; Cao, Qipeng; Shao, Jun; Zhang, Sheng; Liu, Yan

2017-02-01

Most antisolvents employed in previous research were miscible with perovskite precursor solution. They always led to fast formation of perovskite even if the intermediate stage existed, which was not beneficial to obtain high quality perovskite films and made the formation process less controllable. In this work, a novel ethyl ether/n-hexane mixed antisolvent (MAS) was used to achieve high nucleation density and slow down the formation process of perovskite, producing films with improved orientation of grains and ultrasmooth surfaces. These high quality films exhibited efficient charge transport at the interface of perovskite/hole transport material and perovskite solar cells based on these films showed greatly improved performance with the best power conversion efficiency of 17.08%. This work also proposed a selection principle of MAS and showed that solvent engineering by designing the mixed antisolvent system can lead to the fabrication of high-performance perovskite solar cells.

Spectral data compression using weighted principal component analysis with consideration of human visual system and light sources

NASA Astrophysics Data System (ADS)

Cao, Qian; Wan, Xiaoxia; Li, Junfeng; Liu, Qiang; Liang, Jingxing; Li, Chan

2016-10-01

This paper proposed two weight functions based on principal component analysis (PCA) to reserve more colorimetric information in spectral data compression process. One weight function consisted of the CIE XYZ color-matching functions representing the characteristic of the human visual system, while another was made up of the CIE XYZ color-matching functions of human visual system and relative spectral power distribution of the CIE standard illuminant D65. The improvement obtained from the proposed two methods were tested to compress and reconstruct the reflectance spectra of 1600 glossy Munsell color chips and 1950 Natural Color System color chips as well as six multispectral images. The performance was evaluated by the mean values of color difference under the CIE 1931 standard colorimetric observer and the CIE standard illuminant D65 and A. The mean values of root mean square errors between the original and reconstructed spectra were also calculated. The experimental results show that the proposed two methods significantly outperform the standard PCA and another two weighted PCA in the aspects of colorimetric reconstruction accuracy with very slight degradation in spectral reconstruction accuracy. In addition, weight functions with the CIE standard illuminant D65 can improve the colorimetric reconstruction accuracy compared to weight functions without the CIE standard illuminant D65.

Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore Arrays

PubMed Central

2017-01-01

Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7–34 μm and was controlled by the PRX concentration in the feed solution (15–25 g L–1), antisolvent/solvent volume ratio (5–30), and type of antisolvent (Milli-Q water or 0.1–0.5 wt % aqueous solutions of hydroxypropyl methyl cellulose (HPMC), poly(vinyl alcohol) or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L–1 PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt % HPMC solution stirred at 1500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilization of microcrystals against agglomeration than poly(vinyl alcohol) and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystallizer. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals. PMID:29234241

An Efficient Data Compression Model Based on Spatial Clustering and Principal Component Analysis in Wireless Sensor Networks.

PubMed

Yin, Yihang; Liu, Fengzheng; Zhou, Xiang; Li, Quanzhong

2015-08-07

Wireless sensor networks (WSNs) have been widely used to monitor the environment, and sensors in WSNs are usually power constrained. Because inner-node communication consumes most of the power, efficient data compression schemes are needed to reduce the data transmission to prolong the lifetime of WSNs. In this paper, we propose an efficient data compression model to aggregate data, which is based on spatial clustering and principal component analysis (PCA). First, sensors with a strong temporal-spatial correlation are grouped into one cluster for further processing with a novel similarity measure metric. Next, sensor data in one cluster are aggregated in the cluster head sensor node, and an efficient adaptive strategy is proposed for the selection of the cluster head to conserve energy. Finally, the proposed model applies principal component analysis with an error bound guarantee to compress the data and retain the definite variance at the same time. Computer simulations show that the proposed model can greatly reduce communication and obtain a lower mean square error than other PCA-based algorithms.

CH3NH3PbI3 based solar cell: Modified by antisolvent treatment

NASA Astrophysics Data System (ADS)

Nandi, Pronoy; Giri, Chandan; Bansode, Umesh; Topwal, D.

2017-05-01

Solar cells based on new class of organic inorganic hybrid perovskite CH3NH3PbI3 were prepared by Ethyl acetate (EA); antisolvent treatment for the first time. This treatment results in new morphology for CH3NH3PbI3 thin film. FESEM image shows microrod type structures of CH3NH3PbI3 after EA antisolvent treatment. Energy band diagram was constructed using photoluminescence and photoemission studies. A better power conversion efficiency was achieved in EA treated film compare to without EA treated film.

The effect of different anti-solvent and coconut shell content on properties of coconut shell regenerated cellulose biocomposite films

NASA Astrophysics Data System (ADS)

Hahary, Farah Norain; Husseinsyah, Salmah; Mostapha@Zakaria, Marliza

2016-07-01

In this study, coconut shell (CS) regenerated cellulose (RC) biocomposite films was prepared using dimethylacetamide/lithium chloride (DMAc/LiCl) solvent system. The effect of anti-solvents such as water and methanol for regeneration of cellulose and coconut shell content on properties of CS-RC biocomposite films was investigated. The used of water as anti-solvent for cellulose regeneration was found to have higher tensile properties compared to regenerated cellulose using methanol. Besides, the X-Ray diffraction (XRD) analysis also revealed that RC using water as anti-solvent have higher crystallinity index (CrI) than CS-RC biocomposite film using methanol. The tensile strength and modulus elasticity of CS-RC biocomposite films increased up to 3 wt% CS and decreased with further addition of CS. The elongation at break of CS-RC biocomposite films decreased with the increment of CS. The CrI of CS-RC bioocmposite films up to 3 wt% and decreased with at higher content of CS.

Preparation of highly pure zeaxanthin particles from sea water-cultivated microalgae using supercritical anti-solvent recrystallization.

PubMed

Chen, Chao-Rui; Hong, Siang-En; Wang, Yuan-Chuen; Hsu, Shih-Lan; Hsiang, Daina; Chang, Chieh-Ming J

2012-01-01

Xanthophylls, including zeaxanthin, are considered dietary supplements with a potentially positive impact on age-related macular degeneration. Using pilot-scale column fractionation coupled with supercritical anti-solvent (SAS) recrystallization, highly pure zeaxanthin particulates were prepared from ultrasonic extracts of the microalgae, Nannochloropsis oculata, grown in sea water. Column partition chromatography increased the concentration of zeaxanthin from 36.2 mg/g of the ultrasonic extracts to 425.6 mg/g of the collected column fractions. A response surface methodology was systematically designed for the SAS process by changing feed concentration, CO(2) flow rate and anti-solvent pressure. Zeaxanthin-rich particles with a purity of 84.2% and a recovery of 85.3% were produced using supercritical anti-solvent recrystallization from the column eluate at a feed concentration of 1.5 mg/mL, CO(2) flow rate of 48.6 g/min and pressure of 135 bar. Copyright © 2011 Elsevier Ltd. All rights reserved.

Quality Aware Compression of Electrocardiogram Using Principal Component Analysis.

PubMed

Gupta, Rajarshi

2016-05-01

Electrocardiogram (ECG) compression finds wide application in various patient monitoring purposes. Quality control in ECG compression ensures reconstruction quality and its clinical acceptance for diagnostic decision making. In this paper, a quality aware compression method of single lead ECG is described using principal component analysis (PCA). After pre-processing, beat extraction and PCA decomposition, two independent quality criteria, namely, bit rate control (BRC) or error control (EC) criteria were set to select optimal principal components, eigenvectors and their quantization level to achieve desired bit rate or error measure. The selected principal components and eigenvectors were finally compressed using a modified delta and Huffman encoder. The algorithms were validated with 32 sets of MIT Arrhythmia data and 60 normal and 30 sets of diagnostic ECG data from PTB Diagnostic ECG data ptbdb, all at 1 kHz sampling. For BRC with a CR threshold of 40, an average Compression Ratio (CR), percentage root mean squared difference normalized (PRDN) and maximum absolute error (MAE) of 50.74, 16.22 and 0.243 mV respectively were obtained. For EC with an upper limit of 5 % PRDN and 0.1 mV MAE, the average CR, PRDN and MAE of 9.48, 4.13 and 0.049 mV respectively were obtained. For mitdb data 117, the reconstruction quality could be preserved up to CR of 68.96 by extending the BRC threshold. The proposed method yields better results than recently published works on quality controlled ECG compression.

Settlement behavior of municipal solid waste due to internal and external environmental factors in a lysimeter.

PubMed

Melo, Márcio C; Caribé, Rômulo M; Ribeiro, Libânia S; Sousa, Raul B A; Monteiro, Veruschka E D; de Paiva, William

2016-12-05

Long-term settlement magnitude is influenced by changes in external and internal factors that control the microbiological activity in the landfill waste body. To improve the understanding of settlement phenomena, it is instructive to study lysimeters filled with MSW. This paper aims to understand the settlement behavior of MSW by correlating internal and external factors that influence waste biodegradation in a lysimeter. Thus, a lysimeter was built, instrumented and filled with MSW from the city of Campina Grande, the state of Paraíba, Brazil. Physicochemical analysis of the waste (from three levels of depth of the lysimeter) was carried out along with MSW settlement measurements. Statistical tools such as descriptive analysis and principal component analysis (PCA) were also performed. The settlement/compression, coefficient of variation and PCA results indicated the most intense rate of biodegradation in the top layer. The PCA results of intermediate and bottom levels presented fewer physicochemical and meteorological variables correlated with compression data in contrast with the top layer. It is possible to conclude that environmental conditions may influence internal indicators of MSW biodegradation, such as the settlement.

Application of supercritical antisolvent method in drug encapsulation: a review

PubMed Central

Kalani, Mahshid; Yunus, Robiah

2011-01-01

The review focuses on the application of supercritical fluids as antisolvents in the pharmaceutical field and demonstrates the supercritical antisolvent method in the use of drug encapsulation. The main factors for choosing the solvent and biodegradable polymer to produce fine particles to ensure effective drug delivery are emphasized and the effect of polymer structure on drug encapsulation is illustrated. The review also demonstrates the drug release mechanism and polymeric controlled release system, and discusses the effects of the various conditions in the process, such as pressure, temperature, concentration, chemical compositions (organic solvents, drug, and biodegradable polymer), nozzle geometry, CO2 flow rate, and the liquid phase flow rate on particle size and its distribution. PMID:21796245

Micronization of Taxifolin by Supercritical Antisolvent Process and Evaluation of Radical Scavenging Activity

PubMed Central

Zu, Shuchong; Yang, Lei; Huang, Jinming; Ma, Chunhui; Wang, Wenjie; Zhao, Chunjian; Zu, Yuangang

2012-01-01

The aim of this study was to prepare micronized taxifolin powder using the supercritical antisolvent precipitation process to improve the dissolution rate of taxifolin. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters, such as temperature (35–65 °C), pressure (10–25 MPa), solution flow rate (3–6 mL/min) and concentration of the liquid solution (5–20 mg/mL) on the precipitate crystals were investigated. With a lower temperature, a stronger pressure and a lower concentration of the liquid solution, the size of crystals decreased. The precipitation temperature, pressure and concentration of taxifolin solution had a significant effect. However, the solution flow rate had a negligible effect. It was concluded that the physicochemical properties and dissolution rate of crystalline taxifolin could be improved by physical modification such as particle size reduction using the supercritical antisolvent (SAS) process. Further, the SAS process was a powerful methodology for improving the physicochemical properties and radical scavenging activity of taxifolin. PMID:22942740

Method and apparatus for physical separation of different sized nanostructures

DOEpatents

Roberts, Christopher B.; Saunders, Steven R.

2012-07-10

The present application provides apparatuses and methods for the size-selective fractionation of ligand-capped nanoparticles that utilizes the tunable thermophysical properties of gas-expanded liquids. The nanoparticle size separation processes are based on the controlled reduction of the solvent strength of an organic phase nanoparticle dispersion through increases in concentration of the antisolvent gas, such as CO.sub.2, via pressurization. The method of nanomaterial separation contains preparing a vessel having a solvent and dispersed nanoparticles, pressurizing the chamber with a gaseous antisolvent, and causing a first amount of the nanoparticles to precipitate, transporting the solution to a second vessel, pressurizing the second vessel with the gaseous antisolvent and causing further nanoparticles to separate from the solution.

Enhanced Efficiency and Stability of Perovskite Solar Cells via Anti-Solvent Treatment in Two-Step Deposition Method.

PubMed

Li, Minghua; Yan, Xiaoqin; Kang, Zhuo; Liao, Xinqin; Li, Yong; Zheng, Xin; Lin, Pei; Meng, Jingjing; Zhang, Yue

2017-03-01

The low-cost inorganic-organic lead halide perovskite materials become particularly promising for solar cells with high photovoltaic conversion efficiency. The uniform and pinhole-free perovskite films play an important role for high-performance solar cells. We demonstrate an antisolvent treatment by controlling the PbI 2 morphology to enhance the perovskite conversion and photophysical properties, including high absorption, crystallinity, and rapid carrier transfer. The fabricated perovskite solar cells show tremendous PCE improvement to about 16.1% from 12% with less hysteresis, and retain over 90% initial PCE after 30 days in ambient and dark atmosphere. In prospect, this antisolvent treatment will be a feasible route to prepare high-quality perovskite films including favorite photophysical properties.

Standardized processing of MALDI imaging raw data for enhancement of weak analyte signals in mouse models of gastric cancer and Alzheimer's disease.

PubMed

Schwartz, Matthias; Meyer, Björn; Wirnitzer, Bernhard; Hopf, Carsten

2015-03-01

Conventional mass spectrometry image preprocessing methods used for denoising, such as the Savitzky-Golay smoothing or discrete wavelet transformation, typically do not only remove noise but also weak signals. Recently, memory-efficient principal component analysis (PCA) in conjunction with random projections (RP) has been proposed for reversible compression and analysis of large mass spectrometry imaging datasets. It considers single-pixel spectra in their local context and consequently offers the prospect of using information from the spectra of adjacent pixels for denoising or signal enhancement. However, little systematic analysis of key RP-PCA parameters has been reported so far, and the utility and validity of this method for context-dependent enhancement of known medically or pharmacologically relevant weak analyte signals in linear-mode matrix-assisted laser desorption/ionization (MALDI) mass spectra has not been explored yet. Here, we investigate MALDI imaging datasets from mouse models of Alzheimer's disease and gastric cancer to systematically assess the importance of selecting the right number of random projections k and of principal components (PCs) L for reconstructing reproducibly denoised images after compression. We provide detailed quantitative data for comparison of RP-PCA-denoising with the Savitzky-Golay and wavelet-based denoising in these mouse models as a resource for the mass spectrometry imaging community. Most importantly, we demonstrate that RP-PCA preprocessing can enhance signals of low-intensity amyloid-β peptide isoforms such as Aβ1-26 even in sparsely distributed Alzheimer's β-amyloid plaques and that it enables enhanced imaging of multiply acetylated histone H4 isoforms in response to pharmacological histone deacetylase inhibition in vivo. We conclude that RP-PCA denoising may be a useful preprocessing step in biomarker discovery workflows.

[Discrimination among different brands of coffee by using vis-near infrared spectra].

PubMed

Wang, Yan-Yan; He, Yong; Shao, Yong-Ni; Zhang, Zhi-Fei

2007-04-01

Near infrared spectroscopy technology was used to distinguish three different brands of coffee bought from the supermarket. Two models, PCA-BP and WT-BP, were employed for the analysis and prediction of the samples. The discrimination among the different brands of coffee was based on the combination of the function of data compression in the PCA and WT technology and the ability of learning and prediction of the artificial neural network. In the experiment, 60 samples were used for model calibration and 30 for brand prediction. The result showed that both the PCA-BP and WT-BP models achieved 100% discrimination rate, and the wavelet transforms technology is superior to the principal component analysis both in time-consuming and the capability of data compression. It is indicated that the model set up by the combination of WT technology and BP neural network in the present study is rapid in analysis and precise in pattern discrimination. It can be concluded that a new approach to distinguishing pure coffee was of fered and the result of this experiment established the foundation for the determination of the raw material (coffee bean) of different brands of coffee in the market.

An ECG signals compression method and its validation using NNs.

PubMed

Fira, Catalina Monica; Goras, Liviu

2008-04-01

This paper presents a new algorithm for electrocardiogram (ECG) signal compression based on local extreme extraction, adaptive hysteretic filtering and Lempel-Ziv-Welch (LZW) coding. The algorithm has been verified using eight of the most frequent normal and pathological types of cardiac beats and an multi-layer perceptron (MLP) neural network trained with original cardiac patterns and tested with reconstructed ones. Aspects regarding the possibility of using the principal component analysis (PCA) to cardiac pattern classification have been investigated as well. A new compression measure called "quality score," which takes into account both the reconstruction errors and the compression ratio, is proposed.

Anti-solvent derived non-stacked reduced graphene oxide for high performance supercapacitors.

PubMed

Yoon, Yeoheung; Lee, Keunsik; Baik, Chul; Yoo, Heejoun; Min, Misook; Park, Younghun; Lee, Sae Mi; Lee, Hyoyoung

2013-08-27

An anti-solvent for graphene oxide (GO), hexane, is introduced to increase the surface area and the pore volume of the non-stacked GO/reduced GO 3D structure and allows the formation of a highly crumpled non-stacked GO powder, which clearly shows ideal supercapacitor behavior. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of process control agent on the porous structure and mechanical properties of a biomedical Ti-Sn-Nb alloy produced by powder metallurgy.

PubMed

Nouri, A; Hodgson, P D; Wen, C E

2010-04-01

The influence of different amounts and types of process control agent (PCA), i.e., stearic acid and ethylene bis-stearamide, on the porous structure and mechanical properties of a biomedical Ti-16Sn-4Nb (wt.%) alloy was investigated. Alloy synthesis was performed on elemental metal powders using high-energy ball milling for 5h. Results indicated that varying the PCA content during ball milling led to a drastic change in morphology and particle-size distribution of the ball-milled powders. Porous titanium alloy samples sintered from the powders ball milled with the addition of various amounts of PCA also revealed different pore morphology and porosity. The Vickers hardness of the sintered titanium alloy samples exhibited a considerable increase with increasing PCA content. Moreover, the addition of larger amounts of PCA in the powder mixture resulted in a significant increase in the elastic modulus and peak stress for the sintered porous titanium alloy samples under compression. It should also be mentioned that the addition of PCA introduced contamination (mainly carbon and oxygen) into the sintered porous product. Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.

Preparation of theophylline-hydroxypropylmethylcellulose matrices using supercritical antisolvent precipitation: a preliminary study.

PubMed

Moneghini, M; Perissutti, B; Kikic, I; Grassi, M; Cortesi, A; Princivalle, F

2006-01-01

Several controlled release systems of drugs have been elaborated using a supercritical fluid process. Indeed, recent techniques using a supercritical fluid as a solvent or as an antisolvent are considered to be useful alternatives to produce fine powders. In this preliminary study, the effect of Supercritical Anti Solvent process (SAS) on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC) was investigated. Two grades of HPMC (HPMC E5 and K100) as carriers were considered in order to prepare a sustained delivery system for theophylline which was used as a model drug. The characterization of the drug before and after SAS treatment, and the coprecipitates with carriers, was performed by X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The dissolution rate of theophylline, theophylline-coprecipitates, and matricial tablets prepared with coprecipitates were determined. The physical characterizations revealed a substantial correspondence of the drug solid state before and after supercritical fluid treatment while drug-polymer interactions in the SAS-coprecipitates were attested. The dissolution studies of the matrices prepared compressing the coprecipitated systems showed that the matrices based on HPMC K100 were able to promote a sustained release of the drug. Further, this advantageous dissolution performance was found to be substantially independent of the pH of the medium. The comparison with the matrices prepared with untreated substances demonstrated that matrices obtained with SAS technique can provide a slower theophylline release rate. A new mathematical model describing the in vitro dissolution kinetics was proposed and successfully tested on these systems.

Countercurrent flow of supercritical anti-solvent in the production of pure xanthophylls from Nannochloropsis oculata.

PubMed

Cho, Yueh-Cheng; Wang, Yuan-Chuen; Shieh, Chwen-Jen; Lin, Justin Chun-Te; Chang, Chieh-Ming J; Han, Esther

2012-08-10

This study examined pilot scaled elution chromatography coupled with supercritical anti-solvent precipitation (using countercurrent flow) in generating zeaxanthin-rich particulates from a micro-algal species. Ultrasonic agitated acetone extract subjected to column fractionation successfully yielded a fraction containing 349.4 mg/g of zeaxanthin with a recovery of 85%. Subsequently, supercritical anti-solvent (SAS) precipitation of the column fraction at 150 bar and 343 K produced submicron-sized particulates with a concentration of 845.5mg/g of zeaxanthin with a recovery of 90%. Experimental results from a two-factor response surface method SAS precipitation indicated that purity, mean size and morphology of the precipitates were significantly affected by the flow type configuration, feed flow rate and injection time. Copyright © 2012 Elsevier B.V. All rights reserved.

Antisolvent crystallization of a cardiotonic drug in ionic liquids: Effect of mixing on the crystal properties

NASA Astrophysics Data System (ADS)

de Azevedo Jacqueline, Resende; Fabienne, Espitalier; Jean-Jacques, Letourneau; Inês, Ré Maria

2017-08-01

LASSBio-294 (3,4-methylenedioxybenzoyl-2-thienylhydrazon) is a poorly soluble drug which has been proposed to have major advantages over other cardiotonic drugs. Poorly water soluble drugs present limited bioavailability due to their low solubility and dissolution rate. An antisolvent crystallization processing can improve the dissolution rate by decreasing the crystals particle size. However, LASSBio-294 is also poorly soluble in organic solvents and this operation is limited. In order to open new perspectives to improve dissolution rate, this work has investigated LASSBio-294 in terms of its antisolvent crystallization in 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH3O(H)PO2] as solvent and water as antisolvent. Two modes of mixing are tested in stirred vessel with different pre-mixers (Roughton or T-mixers) in order to investigate the mixing effect on the crystal properties (crystalline structure, particle size distribution, residual solvent and in vitro dissolution rate). Smaller drug particles with unchanged crystalline structure were obtained. Despite the decrease of the elementary particles size, the recrystallized particles did not achieve a better dissolution profile. However, this study was able to highlight a certain number of findings such as the impact of the hydrodynamic conditions on the crystals formation and the presence of a gel phase limiting the dissolution rate.

Selective Adsorption and Separation of Organic Dyes with Spherical Polyelectrolyte Brushes and Compressed Carbon Dioxide.

PubMed

Zhang, Rui; Yu, Zhenchuan; Wang, Lei; Shen, Qizhe; Hou, Xiaoyan; Guo, Xuhong; Wang, Junwei; Zhu, Xuedong; Yao, Yuan

2017-10-04

Dye-containing wastewater has caused serious environmental pollution. Herein, rationally designed spherical polyelectrolyte brushes (SPBs) with cationic charges, polystyrene-poly(2-aminoethylmethacrylate hydrochloride) (PS-PAEMH) as the absorbent, and compressed carbon dioxide as the antisolvent are proposed for the separation of the anionic dye eosin Y (EY) from a solution of mixed dyes. The adsorption behavior of EY onto PS-PAEMH was highly dependent on CO 2 pressure, contact time, and initial concentration. The maximum adsorption capacity of PS-PAEMH was 335.20 mg g -1 . FTIR and UV/Vis measurements proved that the electrostatic interactions between EY and PS-PAEMH played an important role in the absorbance process. The adsorption process fitted the pseudo-second-order kinetic model and Freundlich isotherm model very well. The combined dye and polymer brush could be easily separated through ion exchange by adding an aqueous solution of NaCl. Recovered PS-PAEMH retained a high adsorption capacity even after ten cycles of regeneration. This method provides a simple and effective way to separate ionic materials for environmental engineering. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Realizing Full Coverage of Stable Perovskite Film by Modified Anti-Solvent Process

NASA Astrophysics Data System (ADS)

Ji, Long; Zhang, Ting; Wang, Yafei; Zhang, Peng; Liu, Detao; Chen, Zhi; Li, Shibin

2017-05-01

Lead-free solution-processed solid-state photovoltaic devices based on formamidinium tin triiodide (FASnI3) and cesium tin triiodide (CsSnI3) perovskite semiconductor as the light harvester are reported. In this letter, we used solvent engineering and anti-solvent dripping method to fabricate perovskite films. SnCl2 was used as an inhibitor of Sn4+ in FASnI3 precursor solution. We obtained the best films under the function of toluene or chlorobenzene in anti-solvent dripping method and monitored the oxidation of FASnI3 films in air. We chose SnF2 as an additive of CsSnI3 precursor solution to prevent the oxidation of the Sn2+, improving the stability of CsSnI3. The experimental results we obtained can pave the way for lead-free tin-based perovskite solar cells (PSCs).

Controllable synthesis of Ce{sub 1-x}Zr{sub x}O{sub 2} hollow nanospheres via supercritical anti-solvent precipitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang Haoxi; Post-Doctor Station for Science and Technology of Chemical Engineering and Technology, Tianjin University, Tianjin 300072; Post-Doctor Workstation for Science and Technology, Shandong Haihua Group Co. Ltd, Weifang, Shandong 262737

2012-01-15

Nanocrystalline Ce{sub 1-x}Zr{sub x}O{sub 2} hollow nanospheres were successfully synthesized via supercritical anti-solvent precipitation using supercritical CO{sub 2} as the anti-solvent. It was found that the as-produced samples exhibited hollow spherical structures with uniform diameters ranging from 30 to 50 nm and the sphere walls were composed of various oriented nanocrystallites, with sizes of 3-7 nm. The results of high-resolution transmission electron microscopy showed that the formation of the hollow structures could be controlled by adjusting the solution concentration. The results of temperature-programmed reduction and oxygen storage capacity measurements showed that the hollow nanospheres had enhanced redox properties. A possiblemore » mechanism for the formation of Ce{sub 1-x}Zr{sub x}O{sub 2} hollow nanospheres has also been proposed and experimental investigated.« less

Posterior cricoarytenoid muscle electrophysiologic changes are predictive of vocal cord paralysis with recurrent laryngeal nerve compressive injury in a canine model.

PubMed

Puram, Sidharth V; Chow, Harold; Wu, Che-Wei; Heaton, James T; Kamani, Dipti; Gorti, Gautham; Chiang, Feng Yu; Dionigi, Gianlorenzo; Barczynski, Marcin; Schneider, Rick; Dralle, Henning; Lorenz, Kerstin; Randolph, Gregory W

2016-12-01

Injury to the recurrent laryngeal nerve (RLN) is a dreaded complication of endocrine surgery. Intraoperative neural monitoring (IONM) has been increasingly utilized to assess the functional status of the RLN. Although the posterior cricoarytenoid muscle (PCA) is innervated by the RLN as the abductor of the larynx, PCA electromyography (EMG) is infrequently recorded during IONM and PCA activity after RLN compressive injury remains poorly characterized. Single-subject prospective animal study. We employed a canine model to identify postcricoid EMG correlates of postoperative vocal cord paralysis (VCP). Postcricoid electrode recordings were obtained before and after compressive RLN injury associated with VCP. Normative postcricoid recordings revealed mean amplitude of 1288 microvolt (μV) and latency of 8.2 millisecond (ms) with maximum (1 milliamp [mA]) vagal stimulation, and mean amplitude of 1807 μV and latency of 3.5 ms with maximum (1 mA) RLN stimulation. Following injury that was associated with VCP, there was 62.1% decrement in postcricoid EMG amplitude with maximum vagal stimulation and 80% decrement with maximum RLN stimulation. Threshold stimulation of the vagus increased by 23%, and there was a corresponding 42% decrease in amplitude. For RLN stimulation, latency increased by 17.3% following injury, whereas threshold stimulation increased by 61% with 35.5% decrement in EMG amplitude. Thus, if RLN amplitude decreases by ≥ 80%, with absolute amplitude of ≤ 300 μV or less and latency increase of ≥ 10%, RLN injury is likely associated with VCP. Our results predict postoperative VCP based on postcricoid electromyographic IONM and may guide surgical decision making. NA Laryngoscope, 126:2744-2751, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Simple motion correction strategy reduces respiratory-induced motion artifacts for k-t accelerated and compressed-sensing cardiovascular magnetic resonance perfusion imaging.

PubMed

Zhou, Ruixi; Huang, Wei; Yang, Yang; Chen, Xiao; Weller, Daniel S; Kramer, Christopher M; Kozerke, Sebastian; Salerno, Michael

2018-02-01

Cardiovascular magnetic resonance (CMR) stress perfusion imaging provides important diagnostic and prognostic information in coronary artery disease (CAD). Current clinical sequences have limited temporal and/or spatial resolution, and incomplete heart coverage. Techniques such as k-t principal component analysis (PCA) or k-t sparcity and low rank structure (SLR), which rely on the high degree of spatiotemporal correlation in first-pass perfusion data, can significantly accelerate image acquisition mitigating these problems. However, in the presence of respiratory motion, these techniques can suffer from significant degradation of image quality. A number of techniques based on non-rigid registration have been developed. However, to first approximation, breathing motion predominantly results in rigid motion of the heart. To this end, a simple robust motion correction strategy is proposed for k-t accelerated and compressed sensing (CS) perfusion imaging. A simple respiratory motion compensation (MC) strategy for k-t accelerated and compressed-sensing CMR perfusion imaging to selectively correct respiratory motion of the heart was implemented based on linear k-space phase shifts derived from rigid motion registration of a region-of-interest (ROI) encompassing the heart. A variable density Poisson disk acquisition strategy was used to minimize coherent aliasing in the presence of respiratory motion, and images were reconstructed using k-t PCA and k-t SLR with or without motion correction. The strategy was evaluated in a CMR-extended cardiac torso digital (XCAT) phantom and in prospectively acquired first-pass perfusion studies in 12 subjects undergoing clinically ordered CMR studies. Phantom studies were assessed using the Structural Similarity Index (SSIM) and Root Mean Square Error (RMSE). In patient studies, image quality was scored in a blinded fashion by two experienced cardiologists. In the phantom experiments, images reconstructed with the MC strategy had higher SSIM (p < 0.01) and lower RMSE (p < 0.01) in the presence of respiratory motion. For patient studies, the MC strategy improved k-t PCA and k-t SLR reconstruction image quality (p < 0.01). The performance of k-t SLR without motion correction demonstrated improved image quality as compared to k-t PCA in the setting of respiratory motion (p < 0.01), while with motion correction there is a trend of better performance in k-t SLR as compared with motion corrected k-t PCA. Our simple and robust rigid motion compensation strategy greatly reduces motion artifacts and improves image quality for standard k-t PCA and k-t SLR techniques in setting of respiratory motion due to imperfect breath-holding.

Production of pure indinavir free base nanoparticles by a supercritical anti-solvent (SAS) method.

PubMed

Imperiale, Julieta C; Bevilacqua, Gabriela; Rosa, Paulo de Tarso Vieira E; Sosnik, Alejandro

2014-12-01

This work investigated the production of pure indinavir free base nanoparticles by a supercritical anti-solvent method to improve the drug dissolution in intestine-like medium. To increase the dissolution of the drug by means of a supercritical fluid processing method. Acetone was used as solvent and supercritical CO2 as antisolvent. Products were characterized by dynamic light scattering (size, size distribution), scanning electron microscopy (morphology), differential scanning calorimetry (thermal behaviour) and X-rays diffraction (crystallinity). Processed indinavir resulted in particles of significantly smaller size than the original drug. Particles showed at least one dimension at the nanometer scale with needle or rod-like morphology. Results of X-rays powder diffraction suggested the formation of a mixture of polymorphs. Differential scanning calorimetry analysis showed a main melting endotherm at 152 °C. Less prominent transitions due to the presence of small amounts of bound water (in the raw drug) or an unstable polymorph (in processed IDV) were also visible. Finally, drug particle size reduction significantly increased the dissolution rate with respect to the raw drug. Conversely, the slight increase of the intrinsic solubility of the nanoparticles was not significant. A supercritical anti-solvent method enabled the nanonization of indinavir free base in one single step with high yield. The processing led to faster dissolution that would improve the oral bioavailability of the drug.

Synthesis, stabilization, and characterization of metal nanoparticles

NASA Astrophysics Data System (ADS)

White, Gregory Von, II

Wet chemical synthesis techniques offer the ability to control various nanoparticle characteristics including size, shape, dispersibility in both aqueous and organic solvents, and tailored surface chemistries appropriate for different applications. Large quantities of stabilizing ligands or surfactants are often required during synthesis to achieve these nanoparticle characteristics. Unfortunately, excess reaction byproducts, surfactants, and ligands remaining in solution after nanoparticle synthesis can impede application, and therefore post-synthesis purification must be employed. A liquid-liquid solvent/antisolvent pair (typically ethanol/toluene or ethanol/hexane for gold nanoparticles, GNPs) can be used to both purify and size-selectively fractionate hydrophobically modified nanoparticles. Alternatively, carbon dioxide may be used in place of a liquid antisolvent, a "green" approach, enabling both nanoparticle purification and size-selective fractionation while simultaneously eliminating mixed solvent waste and allowing solvent recycle. We have used small-angle neutron scattering (SANS) to investigate the ligand structure and composition response of alkanethiol modified gold and silver nanoparticles at varying anti-solvent conditions (CO2 or ethanol). The ligand lengths and ligand solvation for alkanethiol gold and silver NPs were found to decrease with increased antisolvent concentrations directly impacting their dispersibility in solution. Calculated Flory-Huggins interaction parameters support our SANS study for dodecanethiol dispersibility in the mixed organic solvents. This research has led to a greater understanding of the liquid-liquid precipitation process for metal nanoparticles, and provides critical results for future interaction energy modeling.

Preparation and characterization of Tripterygium wilfordii multi-glycoside nanoparticle using supercritical anti-solvent process.

PubMed

Chen, Fengli; Li, Tong; Li, Shuangyang; Hou, Kexin; Liu, Zaizhi; Li, Lili; Cui, Guoqiang; Zu, Yuangang; Yang, Lei

2014-02-17

The aim of this study was to prepare nanosized Tripterygium wilfordii multi-glycoside (GTW) powders by the supercritical antisolvent precipitation process (SAS), and to evaluate the anti-inflammatory effects. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters such as precipitation pressure (15-35 MPa), precipitation temperature (45-65 °C), drug solution flow rates (3-7 mL/min) and drug concentrations (10-30 mg/mL) were investigated. The nanospheres obtained with mean diameters ranged from 77.5 to 131.8 nm. The processed and unprocessed GTW were characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy and thermal gravimetric analysis. The present study was designed to investigate the beneficial effect of the GTW nanoparticles on adjuvant-induced arthritis in albino rats. The processed and unprocessed GTW were tested against Freund's complete adjuvant-induced arthritis in rats. Blood samples were collected for the estimation of interleukins (IL-1α, IL-1β) and tumor necrosis factor-α (TNF-α). It was concluded that physicochemical properties and anti-inflammatory activity of GTW nanoparticles could be improved by physical modification, such as particle size reduction using supercritical antisolvent (SAS) process. Further, SAS process was a powerful methodology for improving the physicochemical properties and anti-inflammatory activity of GTW.

Preparation and Characterization of Tripterygium wilfordii Multi-Glycoside Nanoparticle Using Supercritical Anti-Solvent Process

PubMed Central

Chen, Fengli; Li, Tong; Li, Shuangyang; Hou, Kexin; Liu, Zaizhi; Li, Lili; Cui, Guoqiang; Zu, Yuangang; Yang, Lei

2014-01-01

The aim of this study was to prepare nanosized Tripterygium wilfordii multi-glycoside (GTW) powders by the supercritical antisolvent precipitation process (SAS), and to evaluate the anti-inflammatory effects. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters such as precipitation pressure (15–35 MPa), precipitation temperature (45–65 °C), drug solution flow rates (3–7 mL/min) and drug concentrations (10–30 mg/mL) were investigated. The nanospheres obtained with mean diameters ranged from 77.5 to 131.8 nm. The processed and unprocessed GTW were characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy and thermal gravimetric analysis. The present study was designed to investigate the beneficial effect of the GTW nanoparticles on adjuvant-induced arthritis in albino rats. The processed and unprocessed GTW were tested against Freund’s complete adjuvant-induced arthritis in rats. Blood samples were collected for the estimation of interleukins (IL-1α, IL-1β) and tumor necrosis factor-α (TNF-α). It was concluded that physicochemical properties and anti-inflammatory activity of GTW nanoparticles could be improved by physical modification, such as particle size reduction using supercritical antisolvent (SAS) process. Further, SAS process was a powerful methodology for improving the physicochemical properties and anti-inflammatory activity of GTW. PMID:24549173

Gas anti-solvent precipitation assisted salt leaching for generation of micro- and nano-porous wall in bio-polymeric 3D scaffolds.

PubMed

Flaibani, Marina; Elvassore, Nicola

2012-08-01

The mass transport through biocompatible and biodegradable polymeric 3D porous scaffolds may be depleted by non-porous impermeable internal walls. As consequence the concentration of metabolites and growth factors within the scaffold may be heterogeneous leading to different cell fate depending on spatial cell location, and in some cases it may compromise cell survival. In this work, we fabricated polymeric scaffolds with micro- and nano-scale porosity by developing a new technique that couples two conventional scaffold production methods: solvent casting-salt leaching and gas antisolvent precipitation. 10-15 w/w solutions of a hyaluronic benzyl esters (HYAFF11) and poly-(lactic acid) (PLA) were used to fill packed beds of 0.177-0.425 mm NaCl crystals. The polymer precipitation in micro and nano-porous structures between the salt crystals was induced by high-pressure gas, then its flushing extracted the residual solvent. The salt was removed by water-wash. Morphological analysis by scanning electron microscopy showed a uniform porosity (~70%) and a high interconnectivity between porous. The polymeric walls were porous themselves counting for 30% of the total porosity. This wall porosity did not lead to a remarkable change in compressive modulus, deformation, and rupture pressure. Scaffold biocompatibility was tested with murine muscle cell line C2C12 for 4 and 7 days. Viability analysis and histology showed that micro- and nano-porous scaffolds are biocompatible and suitable for 3D cell culture promoting cell adhesion on the polymeric wall and allowing their proliferation in layers. Micro- and nano-scale porosities enhance cell migration and growth in the inner part of the scaffold. Copyright © 2012 Elsevier B.V. All rights reserved.

Antisolvent precipitation technique: A very promising approach to crystallize curcumin in presence of polyvinyl pyrrolidon for solubility and dissolution enhancement.

PubMed

Sadeghi, Fatemeh; Ashofteh, Mohammad; Homayouni, Alireza; Abbaspour, Mohammadreza; Nokhodchi, Ali; Garekani, Hadi Afrasiabi

2016-11-01

Curcumin with a vast number of pharmacological activities is a poorly water soluble drug which its oral bioavailability is profoundly limited by its dissolution or solubility in GI tract. Curcumin could be a good anticancer drug if its solubility could be increased. Therefore, the aim of the present study was to increase the dissolution rate of curcumin by employing antisolvent crystallization technique and to investigate the effect of polyvinyl pyrrolidone K30 (PVP) as colloidal particles in crystallization medium on resultant particles. Curcumin was crystalized in the presence of different amounts of PVP by antisolvent crystallization method and their physical mixtures were prepared for comparison purposes. The samples were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR). The solubility and dissolution of the treated and untreated curcumin were also determined. Antisolvent crystallization of curcumin led to the formation of particles with no definite geometric shape. It was interesting to note that the DSC and XRPD studies indicated the formation of a new polymorph and less crystallinity for particles crystallized in the absence of PVP. However, the crystallized curcumin in the presence of PVP was completely amorphous. All crystalized curcumin samples showed much higher dissolution rate compared to untreated curcumin. The amount of curcumin dissolved within 10 for treated curcumin in the presence of PVP (1:1 curcumin:PVP) was 7 times higher than untreated curcumin and this enhancement in the dissolution for curcumin samples crystallized in the absence of PVP was around 5 times. Overall' the results of this study showed that antisolvent crystallization method in the absence or presence of small amounts of PVP is very efficient in increasing the dissolution rate of curcumin to achieve better efficiency for curcumin. Copyright © 2016 Elsevier B.V. All rights reserved.

System and process for polarity swing assisted regeneration of gas selective capture liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heldebrant, David J.; Tegrotenhuis, Ward E.; Freeman, Charles J.

A polarity swing-assisted regeneration (PSAR) process is disclosed for improving the efficiency of releasing gases chemically bound to switchable ionic liquids. Regeneration of the SWIL involves addition of a quantity of non-polar organic compound as an anti-solvent to destabilize the SWIL, which aids in release of the chemically bound gas. The PSAR decreases gas loading of a SWIL at a given temperature and increases the rate of gas release compared to heating in the absence of anti-solvent.

Simultaneous production and co-mixing of microparticles of nevirapine with excipients by supercritical antisolvent method for dissolution enhancement.

PubMed

Sanganwar, Ganesh P; Sathigari, Sateeshkumar; Babu, R Jayachandra; Gupta, Ram B

2010-01-31

Microparticles of a poorly water-soluble model drug, nevirapine (NEV) were prepared by supercritical antisolvent (SAS) method and simultaneously deposited on the surface of excipients such as lactose and microcrystalline cellulose in a single step to reduce drug-drug particle aggregation. In the proposed method, termed supercritical antisolvent-drug excipient mixing (SAS-DEM), drug particles were precipitated in supercritical CO(2) vessel containing excipient particles in suspended state. Drug/excipient mixtures were characterized for surface morphology, crystallinity, drug-excipient physico-chemical interactions, and molecular state of drug. In addition, the drug content uniformity and dissolution rate were determined. A highly ordered NEV-excipient mixture was produced. The SAS-DEM treatment was effective in overcoming drug-drug particle aggregation and did not affect the crystallinity or physico-chemical properties of NEV. The produced drug/excipient mixture has a significantly faster dissolution rate as compared to SAS drug microparticles alone or when physically mixed with the excipients. Copyright 2009 Elsevier B.V. All rights reserved.

Enhanced Crystallization by Methanol Additive in Anti-solvent for Achieving High-quality MAPbI3 Perovskite Films in Humid Atmosphere.

PubMed

Yang, Fu; Kamarudin, Muhammad Akmal; Zhang, PuTao; Kapil, Gaurav; Ma, Tingli; Hayase, Shuzi

2018-05-04

Perovskite solar cells have attracted considerable attention owing to easy and low-cost solution manufacturing process with high power conversion efficiency. However, the fabrication process is usually performed inside glovebox to avoid the moisture, as organometallic halide perovskite is easily dissolved in water. In this study, we propose one-step fabrication of high-quality MAPbI3 perovskite films in 50 % RH humid ambient air by using diethyl ether as an anti-solvent and methanol as an additive into this anti-solvent. Because of the existence of methanol, the water molecules can be efficiently removed from the gaps of perovskite precursors and the perovskite film formation can be slightly controlled leading to pinhole-free and low roughness film. Concurrently, methanol can modify a proper DMSO ratio in the intermediate perovskite phase to regulate perovskite formation. Planar solar cells fabricated by using this method exhibited the best efficiency of 16.4 % with a reduced current density-voltage hysteresis. This efficiency value is approximately 160 % higher than the devices fabrication by using only diethyl ether treatment. From the impedance measurement, it is also found that the recombination reaction has been suppressed when the device prepared with additive anti-solvent way. This method presents a new path for controlling the growth and morphology of perovskite films in the humid climates and uncontrolled laboratories. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Production of all trans-beta-carotene by using impinging flow of supercritical carbon dioxide anti-solvent pulverization.

PubMed

Shen, Yi-Chen; Chng, Lee-Muei; Wang, Yuan-Chuen; Shieh, Chwen-Jen; Lin, Kuo-Li; Hsu, Shih-Lan; Chou, Hong-Nong; Chang, Chieh-Ming J

2012-12-28

This work investigated column elution chromatography coupled with supercritical anti-solvent precipitation to produce carotenoid rich microsized particulates from microalgal Dunaliella salina species. The extract contained carotenoids ranging from 61.3 mg/g(salina) to 72.5 mg/g(salina) using ultrasonic stirred ethyl ether or tetrahydrofuran (THF) extraction. When 10 L of ethyl alcohol was employed to elute the THF extract, purity of trans-β-carotene is 823.6 mg/g with a recovery of 86.2%. It was found that the supercritical anti-solvent of THF solution at 160 bar and 318 K produced powdered particulates with a purity of carotenoids above 90%. Subsequently, a central composite response surface design method was used to design supercritical anti-solvent precipitation of carotenoid-rich THF solution. This was accomplished by increasing the pressure from 140 bar to 180 bar and the time from 40 min to 60 min at a feed flow rate of 0.2 mL/min. A CO(2) flow rate of 15 L/min and a temperature of 318 K were also used to determine the effects on purity and recovery of trans-β-carotene. The combined process produced micronized precipitates with a mean particle size ranging from 3.5 μm to 19 μm and the purity of trans-β-carotene attained was 926.8 mg/g with a recovery of 54%. Copyright © 2012 Elsevier B.V. All rights reserved.

A Streaming PCA VLSI Chip for Neural Data Compression.

PubMed

Wu, Tong; Zhao, Wenfeng; Guo, Hongsun; Lim, Hubert H; Yang, Zhi

2017-12-01

Neural recording system miniaturization and integration with low-power wireless technologies require compressing neural data before transmission. Feature extraction is a procedure to represent data in a low-dimensional space; its integration into a recording chip can be an efficient approach to compress neural data. In this paper, we propose a streaming principal component analysis algorithm and its microchip implementation to compress multichannel local field potential (LFP) and spike data. The circuits have been designed in a 65-nm CMOS technology and occupy a silicon area of 0.06 mm. Throughout the experiments, the chip compresses LFPs by 10 at the expense of as low as 1% reconstruction errors and 144-nW/channel power consumption; for spikes, the achieved compression ratio is 25 with 8% reconstruction errors and 3.05-W/channel power consumption. In addition, the algorithm and its hardware architecture can swiftly adapt to nonstationary spiking activities, which enables efficient hardware sharing among multiple channels to support a high-channel count recorder.

System and process for capture of H.sub.2S from gaseous process streams and process for regeneration of the capture agent

DOEpatents

Heldenbrant, David J; Koech, Phillip K; Rainbolt, James E; Bearden, Mark D; Zheng, Feng

2014-02-18

A system and process are disclosed for selective removal and recovery of H.sub.2S from a gaseous volume, e.g., from natural gas. Anhydrous organic, sorbents chemically capture H.sub.2S gas to form hydrosulfide salts. Regeneration of the capture solvent involves addition of an anti-solvent that releases the captured H.sub.2S gas from the capture sorbent. The capture sorbent and anti-solvent are reactivated for reuse, e.g., by simple distillation.

Dry-spraying of ascorbic acid or acetaminophen solutions with supercritical carbon dioxide

NASA Astrophysics Data System (ADS)

Wubbolts, F. E.; Bruinsma, O. S. L.; van Rosmalen, G. M.

1999-03-01

Carbon dioxide is a very poor solvent for many organic compounds, which makes it a good anti-solvent. When a solution is sprayed into carbon dioxide vapour the anti-solvent reduces the solubility within several tens of milliseconds and the solute precipitates. Two distinct regions can be identified, below and above the mixture critical pressure. Below this critical pressure the yield remains relatively low and the process is not well controlled. Above the critical pressure small crystals are obtained of about 2 μm with a yield of 90%.

Real time on-chip sequential adaptive principal component analysis for data feature extraction and image compression

NASA Technical Reports Server (NTRS)

Duong, T. A.

2004-01-01

In this paper, we present a new, simple, and optimized hardware architecture sequential learning technique for adaptive Principle Component Analysis (PCA) which will help optimize the hardware implementation in VLSI and to overcome the difficulties of the traditional gradient descent in learning convergence and hardware implementation.

Preparation of nanoparticles of poorly water-soluble antioxidant curcumin by antisolvent precipitation methods

NASA Astrophysics Data System (ADS)

Kakran, Mitali; Sahoo, Nanda Gopal; Tan, I.-Lin; Li, Lin

2012-03-01

The objective of this study was to enhance the solubility and dissolution rate of a poorly water-soluble antioxidant, curcumin, by fabricating its nanoparticles with two methods: antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN). For APSP, process parameters like flow rate, stirring speed, solvent to antisolvent (SAS) ratio, and drug concentration were investigated to obtain the smallest particle size. For EPN, factors like drug concentration and the SAS ratio were examined. The effects of these process parameters on the supersaturation, nucleation, and growth rate were studied and optimized to obtain the smallest particle size of curcumin by both the methods. The average particle size of the original drug was about 10-12 μm and it was decreased to a mean diameter of 330 nm for the APSP method and to 150 nm for the EPN method. Overall, decreasing the drug concentration or increasing the flow rate, stirring rate, and antisolvent amount resulted in smaller particle sizes. Differential scanning calorimetry studies suggested lower crystallinity of curcumin particles fabricated. The solubility and dissolution rates of the prepared curcumin particles were significantly higher than those the original curcumin. The antioxidant activity, studied by the DPPH free radical-scavenging assay, was greater for the curcumin nanoparticles than the original curcumin. This study demonstrated that both the methods can successfully prepare curcumin into submicro to nanoparticles. However, drug particles prepared by EPN were smaller than those by APSP and hence, showed the slightly better solubility, dissolution rate, and antioxidant activity than the latter.

Production of salbutamol sulfate for inhalation by high-gravity controlled antisolvent precipitation.

PubMed

Chiou, Herbert; Li, Li; Hu, Tingting; Chan, Hak-Kim; Chen, Jian-Feng; Yun, Jimmy

2007-02-22

The purpose of this study was to produce salbutamol sulfate (SS) as a model anti-asthmatic drug using high-gravity controlled precipitation (HGCP) through antisolvent crystallisation. An aqueous solution of SS was passed through a HGCP reactor with isopropanol as antisolvent to induce precipitation. Spray drying was employed to obtain dry powders. Scanning electron microscopy, X-ray powder diffraction (XRD), density measurement, thermal gravimetric analysis, and dynamic vapour sorption were carried out to characterise the powder physical properties. The aerosol performance of the powders was measured using an Aeroliser connected to a multiple stage liquid impinger operating at 60 L/min. The HGCP SS particles were elongated with 0.1 microm in width but varying length of several mum, which formed spherical agglomerates when spray dried. The particles showed the same XRD pattern and true density (1.3g/cm3) as the raw material, indicating that they belonged to the same crystalline form. However, the spray dried agglomerates had a much lower tapped density (0.1g/cm3) than the raw material (0.6g/cm3). Compared with the powder obtained by spray drying directly from an aqueous solution, the SS powders obtained from HGCP were much less hygroscopic (0.6% versus 10% water uptake at 90% RH). The in vitro aerosol performance showed a fine particle fraction FPFloaded and FPFemitted up to 54.5+/-4.9% and 71.3+/-10.0%, respectively. In conclusion, SS powder with suitable physical and aerosol properties can be obtained through antisolvent HGCP followed by spray drying.

Method of Real-Time Principal-Component Analysis

NASA Technical Reports Server (NTRS)

Duong, Tuan; Duong, Vu

2005-01-01

Dominant-element-based gradient descent and dynamic initial learning rate (DOGEDYN) is a method of sequential principal-component analysis (PCA) that is well suited for such applications as data compression and extraction of features from sets of data. In comparison with a prior method of gradient-descent-based sequential PCA, this method offers a greater rate of learning convergence. Like the prior method, DOGEDYN can be implemented in software. However, the main advantage of DOGEDYN over the prior method lies in the facts that it requires less computation and can be implemented in simpler hardware. It should be possible to implement DOGEDYN in compact, low-power, very-large-scale integrated (VLSI) circuitry that could process data in real time.

Controlled morphology and size of curcumin using ultrasound in supercritical CO2 antisolvent.

PubMed

Jia, Jingfu; Wang, Wucong; Gao, Yahui; Zhao, Yaping

2015-11-01

Controllable morphology and size of crystal materials prepared by using a supercritical antisolvent (SAS) technique is still challenge. In this study, ultrasound was introduced into the SAS process to produce the particles of curcumin, a model compound. The effects of ultrasound power on the particle morphology and size were investigated in the range of 0 and 240 W at three different pressures. The observation of jet flow indicated ultrasound could accelerate the mixing speed between the liquid solution and the CO2, and thus reduced the gaseous region and the local saturation gradient. Mixed polymorphic and uniform particles of the curcumin were produced at a low and high mixing speed, respectively, confirmed by scanning electron microscopy. The needle- or rod-like particle, irregular lumpy particle and nano spherical particle were generated with the increase of the ultrasound power, attributed to the changes of the degree of supersaturation. Therefore, the ultrasound can be potentially applied to adjust the morphology and size of the crystal materials in supercritical CO2 antisolvent. Copyright © 2015 Elsevier B.V. All rights reserved.

Improved performance of mesostructured perovskite solar cells via an anti-solvent method

NASA Astrophysics Data System (ADS)

Hao, Jiabin; Hao, Huiying; Cheng, Feiyu; Li, Jianfeng; Zhang, Haiyu; Dong, Jingjing; Xing, Jie; Liu, Hao; Wu, Jian

2018-06-01

One-step solution process is a facile and widely used procedure to prepare organic-inorganic perovskite materials. However, the poor surface morphology of the films attributed to the uncontrollable nucleation and crystal growth in the process is unfavorable to solar cells. In this study, an anti-solvent treatment during the one-step solution process, in which ethyl acetate (EA) was dropped on the sample during spinning the precursor solution containing CH3NH3Cl, was adopted to fabricate perovskite materials and solar cells. It was found that the morphology of the perovskite film was significantly improved due to the rapid nucleation and slow crystal growth process. The modified process enabled us to fabricate the mesoporous solar cell with power conversion efficiency of 14%, showing an improvement of 40% over the efficiency of 9.7% of the device prepared by conventional one-step method. The controlling effect of annealing time on the morphology, crystal structure and transport properties of perovskite layer as well as the performance of device fabricated by the anti-solvent method were investigated and the possible mechanism was discussed.

Application of precipitation methods for the production of water-insoluble drug nanocrystals: production techniques and stability of nanocrystals.

PubMed

Xia, Dengning; Gan, Yong; Cui, Fude

2014-01-01

This review focuses on using precipitation (bottom-up) method to produce water-insoluble drug nanocrystals, and the stability issues of nanocrystals. The precipitation techniques for production of ultra-fine particles have been widely researched for last few decades. In these techniques, precipitation of solute is achieved by addition of a non-solvent for solute called anti-solvent to decrease the solvent power for the solute dissolved in a solution. The anti-solvent can be water, organic solvents or supercritical fluids. In this paper, efforts have been made to review the precipitation techniques involving the anti-solvent precipitation by simple mixing, impinging jet mixing, multi-inlet vortex mixing, the using of high-gravity, ultrasonic waves and supercritical fluids. The key to the success of yielding stable nanocrystals in these techniques is to control the nucleation kinetics and particle growth through mixing during precipitation based on crystallization theories. The stability issues of the nanocrystals, such as sedimentation, Ostwald ripening, agglomeration and cementing of crystals, change of crystalline state, and the approaches to stabilizing nanocrystals are also discussed in detail.

High-resolution imaging of the supercritical antisolvent process

NASA Astrophysics Data System (ADS)

Bell, Philip W.; Stephens, Amendi P.; Roberts, Christopher B.; Duke, Steve R.

2005-06-01

A high-magnification and high-resolution imaging technique was developed for the supercritical fluid antisolvent (SAS) precipitation process. Visualizations of the jet injection, flow patterns, droplets, and particles were obtained in a high-pressure vessel for polylactic acid and budesonide precipitation in supercritical CO2. The results show two regimes for particle production: one where turbulent mixing occurs in gas-like plumes, and another where distinct droplets were observed in the injection. Images are presented to demonstrate the capabilities of the method for examining particle formation theories and for understanding the underlying fluid mechanics, thermodynamics, and mass transport in the SAS process.

Preparation and Reinforcement of Dual-Porous Biocompatible Cellulose Scaffolds for Tissue Engineering.

PubMed

Pircher, Nicole; Fischhuber, David; Carbajal, Leticia; Strauß, Christine; Nedelec, Jean-Marie; Kasper, Cornelia; Rosenau, Thomas; Liebner, Falk

2015-09-01

1Biocompatible cellulose-based aerogels composed of nanoporous struts, which embed interconnected voids of controlled micron-size, have been prepared employing temporary templates of fused porogens, reinforcement by interpenetrating PMMA networks and supercritical carbon dioxide drying. Different combinations of cellulose solvent (Ca(SCN) 2 /H 2 O/LiCl or [EMIm][OAc]/DMSO) and anti-solvent (EtOH), porogen type (paraffin wax or PMMA spheres) and porogen size (various fractions in the range of 100-500 μm) as well as intensity of PMMA reinforcement have been investigated to tailor the materials for cell scaffolding applications. All aerogels exhibited an open and dual porosity (micronporosity >100 μm and nanoporosity extending to the low micrometer range). Mechanical properties of the dual-porous aerogels under compressive stress were considerably improved by introduction of interpenetrating PMMA networks. The effect of the reinforcing polymer on attachment, spreading, and proliferation of NIH 3T3 fibroblast cells, cultivated on selected dual-porous aerogels to pre-evaluate their biocompatibility was similarly positive.

Dissolution enhancement of Deflazacort using hollow crystals prepared by antisolvent crystallization process.

PubMed

Paulino, A S; Rauber, G; Campos, C E M; Maurício, M H P; de Avillez, R R; Capobianco, G; Cardoso, S G; Cuffini, S L

2013-05-13

Deflazacort (DFZ), a derivate of prednisolone, is a poorly soluble drug which has been proposed to have major advantages over other corticosteroids. Poorly soluble drugs present limited bioavailability due to their low solubility and dissolution rate and several strategies have been developed in order to find ways to improve them. In general, pharmaceutical laboratories use a micronized process to reduce the particle size in order to increase the dissolution of the drugs. However, this process causes changes such as polymorphic transitions, particle agglomeration and a reduction in fluidity and wettability. These solid-state properties affect the dissolution behavior and stability performance of drugs. Crystallization techniques are widely used in the pharmaceutical industry and antisolvent crystallization has been used to obtain ultrafine particles. In this study, DFZ was investigated in terms of its antisolvent crystallization in different solvents and under various preparation conditions (methanol/water ratio, stirring and evaporation rate, etc.), in order to compare the physicochemical properties between crystallized samples and raw materials available on the Brazilian market with and without micronization. Crystalline structure, morphology, and particle size, and their correlation with the Intrinsic Dissolution Rate (IDR) and dissolution profile as relevant biopharmaceutical properties were studied. Crystallization conditions were achieved which provided crystalline samples of hollow-shaped crystals with internal channels, which increased the dissolution rate of DFZ. The antisolvent crystallization process allowed the formation of hollow crystals, which demonstrated a better dissolution profile than the raw material (crystalline and micronized), making this a promising technique as a crystallization strategy for improving the dissolution and thus the bioavailability of poorly soluble drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Didanosine polymorphism in a supercritical antisolvent process.

PubMed

Bettini, R; Menabeni, R; Tozzi, R; Pranzo, M B; Pasquali, I; Chierotti, M R; Gobetto, R; Pellegrino, L

2010-04-01

Solid-state properties of active ingredients are crucial in pharmaceutical development owing to their significant clinical and economical implications. In the present work we investigated the solid-state properties and the solubility in water of didanosine, DDI, re-crystallized from a dimethylsulfoxide solution using supercritical CO(2) as an antisolvent (SAS process) for comparison with the commercially available drug product. We also applied modern solid-state NMR (SS NMR) techniques, namely 2D (1)H DQ CRAMPS (Combined Rotation And Multiple Pulse Spectroscopy) and (1)H-(13)C on- and off-resonance CP (cross polarization) FSLG-HETCOR experiments, known for providing reliable information about (1)H-(1)H and (1)H-(13)C intra- and intermolecular proximities, in order to address polymorphism issues arising from the crystallization of a new form in the supercritical process. A new polymorph of didanosine was obtained from the supercritical antisolvent process and characterized by means of 1D and 2D multinuclear ((1)H, (13)C, (15)N) SS NMR. The particle size of the new crystal phase was reduced by varying the antisolvent density through a pressure increase. The structural differences between the commercial product and the SAS re-crystallized DDI are highlighted by X-ray diffractometry and well described by solid-state NMR. The carbon C6 (13)C chemical shift suggests that both commercial and re-crystallized didanosine samples are in the enol form. The analysis of homo- and heteronuclear proximities obtained by means of 2D NMR experiments shows that commercial and SAS re-crystallized DDI possess very similar molecular conformation and hydrogen bond network, but different packing. The new polymorph proved to be a metastable form at ambient conditions, showing higher solubility in water and lower stability to mechanical stress. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Pectus Carinatum Evaluation Questionnaire (PCEQ): a novel tool to improve the follow-up in patients treated with brace compression.

PubMed

Pessanha, Inês; Severo, Milton; Correia-Pinto, Jorge; Estevão-Costa, José; Henriques-Coelho, Tiago

2016-03-01

A questionnaire (Pectus Carinatum Evaluation Questionnaire, PCEQ) was developed to be applied in follow-up of patients with Pectus Carinatum (PC). After validation of the PCEQ, we aimed to quantify the compliance to brace compression and to assess factors that could influence this treatment in patients with PC. From July 2008 to July 2014, 56 patients with PC were treated with the Calgary Protocol of compressive bracing at Paediatric Surgery Department of Hospital São João. Forty patients (71%) completed the questionnaire. The PCEQ was divided into four sections: (i) compliance; (ii) symptoms; (iii) social influence; (iv) activities. For the validation process of the PCEQ, principal components analysis (PCA), orthogonal varimax or oblimin rotation and Cronbach's α coefficient were used. To evaluate the association between compliance and other sections of the questionnaire, we estimated the Pearson's correlation between compliance factor scores ('Compliance Days' and 'Compliance Hours') and the final score of each new questionnaire component identified by PCA ('Chest Pain', 'Dyspnoea', 'Back Pain', 'Parents' Influence', 'Friends' Influence', 'Activities', 'Time To Compliance'). For the sections 'Symptoms', 'Social Influence' and 'Activities', we estimated final scores as the sum of the questions that constitute each component. For the section 'Compliance', the factor scores were estimated by the regression method. After PCA analysis, the PCEQ found nine different components with high reliability. When analysing the compliance of our study group, the final score for 'Activities' revealed a significant correlation with the factor score for 'Compliance Hours' (r = 0.382, P = 0.015). The final score for 'Time To Compliance' showed a significant correlation with both factor scores for 'Compliance Hours' (r = -0.765, P < 0.001) and 'Compliance Days' (r = -0.345, P < 0.029). The PCEQ seems to be an important tool to follow up patients with PC treated by brace compression. Practical steps, such as developing a tight schedule in the early follow-up period or applying the PCEQ in first visits after initiating brace therapy, can be taken in order to increase compliance with brace therapy and improve the quality of life. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Tampered Region Localization of Digital Color Images Based on JPEG Compression Noise

NASA Astrophysics Data System (ADS)

Wang, Wei; Dong, Jing; Tan, Tieniu

With the availability of various digital image edit tools, seeing is no longer believing. In this paper, we focus on tampered region localization for image forensics. We propose an algorithm which can locate tampered region(s) in a lossless compressed tampered image when its unchanged region is output of JPEG decompressor. We find the tampered region and the unchanged region have different responses for JPEG compression. The tampered region has stronger high frequency quantization noise than the unchanged region. We employ PCA to separate different spatial frequencies quantization noises, i.e. low, medium and high frequency quantization noise, and extract high frequency quantization noise for tampered region localization. Post-processing is involved to get final localization result. The experimental results prove the effectiveness of our proposed method.

SU-E-I-58: Objective Models of Breast Shape Undergoing Mammography and Tomosynthesis Using Principal Component Analysis.

PubMed

Feng, Ssj; Sechopoulos, I

2012-06-01

To develop an objective model of the shape of the compressed breast undergoing mammographic or tomosynthesis acquisition. Automated thresholding and edge detection was performed on 984 anonymized digital mammograms (492 craniocaudal (CC) view mammograms and 492 medial lateral oblique (MLO) view mammograms), to extract the edge of each breast. Principal Component Analysis (PCA) was performed on these edge vectors to identify a limited set of parameters and eigenvectors that. These parameters and eigenvectors comprise a model that can be used to describe the breast shapes present in acquired mammograms and to generate realistic models of breasts undergoing acquisition. Sample breast shapes were then generated from this model and evaluated. The mammograms in the database were previously acquired for a separate study and authorized for use in further research. The PCA successfully identified two principal components and their corresponding eigenvectors, forming the basis for the breast shape model. The simulated breast shapes generated from the model are reasonable approximations of clinically acquired mammograms. Using PCA, we have obtained models of the compressed breast undergoing mammographic or tomosynthesis acquisition based on objective analysis of a large image database. Up to now, the breast in the CC view has been approximated as a semi-circular tube, while there has been no objectively-obtained model for the MLO view breast shape. Such models can be used for various breast imaging research applications, such as x-ray scatter estimation and correction, dosimetry estimates, and computer-aided detection and diagnosis. © 2012 American Association of Physicists in Medicine.

Artificial neural networks modelling the prednisolone nanoprecipitation in microfluidic reactors.

PubMed

Ali, Hany S M; Blagden, Nicholas; York, Peter; Amani, Amir; Brook, Toni

2009-06-28

This study employs artificial neural networks (ANNs) to create a model to identify relationships between variables affecting drug nanoprecipitation using microfluidic reactors. The input variables examined were saturation levels of prednisolone, solvent and antisolvent flow rates, microreactor inlet angles and internal diameters, while particle size was the single output. ANNs software was used to analyse a set of data obtained by random selection of the variables. The developed model was then assessed using a separate set of validation data and provided good agreement with the observed results. The antisolvent flow rate was found to have the dominant role on determining final particle size.

Processing of polyphenolic composites with supercritical fluid anti-solvent technology

NASA Astrophysics Data System (ADS)

Kurniawansyah, Firman; Mammucari, Raffaella; Foster, Neil R.

2017-05-01

Polyphenols have been developed, primarily exploiting their robust antioxidant properties, for medical and food applications. In spite of their advantages, polyphenolic compounds have drawbacks from their natural characteristics of being poorly soluble in aqueous solutions, thermo-labile and low oral bioavailaibility. In this article, strategy of processing with supercritical fluid (SCF) anti-solvent to improve the shortcomings is overviewed. Information obtained from the existing studies commonly confirms SCF technology applicability to produce composites of polyphenols with various morphology, size distributions and crystallinity. The application of SCF technology also enables to develop polyphenolic composites for alternative drug delivery such as in the pulmonary administrations.

Modification of solid-state property of sulfasalazine by using the supercritical antisolvent process

NASA Astrophysics Data System (ADS)

Wu, Wei-Yi; Su, Chie-Shaan

2017-02-01

In this study, the supercritical antisolvent (SAS) process was used to recrystallize an active pharmaceutical ingredient, sulfasalazine, to modify the solid-state properties including particle size, crystal habit and polymorphic form. Supercritical CO2 and tetrahydrofuran were used as the antisolvent and solvent, respectively. SAS results obtained from different operating temperatures (35, 45, 55 and 65 °C) were compared and discussed. The results indicate that at 55 °C, spherical sulfasalazine crystals were produced and that their mean particle size was micronized to approximately 1 μm. In addition, according to the analytical results of powder X-ray diffractometry (PXRD), a novel polymorphic form of sulfasalazine was obtained after SAS. Furthermore, the spectroscopic and thermal behavior of produced sulfasalazine crystals were also studied by Fourier transform infrared spectrometry (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Finally, SAS results obtained from different operating temperature was discussed on the basis of the mixture critical point (MCP) of CO2 and tetrahydrofuran. Operation at slightly higher than the MCP is favorable for recrystallization of sulfasalazine through SAS. These results demonstrate that the SAS process is an efficient tool for controlling and modifying the solid-state property of sulfasalazine.

[Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Cai, Jin-Yuan; Huang, De-Chun; Wang, Zhi-Xiang; Dang, Bei-Lei; Wang, Qiu-Ling; Su, Xin-Guang

2012-06-01

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

One-Step Method to Prepare PLLA Porous Microspheres in a High-Voltage Electrostatic Anti-Solvent Process

PubMed Central

Wang, Ying; Zhu, Li-Hui; Chen, Ai-Zheng; Xu, Qiao; Hong, Yu-Juan; Wang, Shi-Bin

2016-01-01

A one-step method using a high-voltage electrostatic anti-solvent process was employed to fabricate poly-l-lactide (PLLA) porous microspheres (PMs). To address the simplification and control of the preparation process, a 24 full factorial experiment was performed to optimize the operating process and analyze the effect of the factors on the morphology and aerodynamic properties of the PLLA PMs, and various characterization tests were also performed. The resulting PLLA PMs exhibited an even and porous morphology with a density less than 0.4 g/cm3, a geometric mean diameter (Dg) of 10–30 μm, an aerodynamic diameter (Da) of 1–5 μm, a fine particle fraction (FPF) of 56.3%, and a porosity of 76.2%, meeting the requirements for pulmonary drug delivery. The physicochemical characterizations reveal that no significant chemical change occurred in the PLLA during the process. An investigation of its in vitro cytotoxicity and pulmonary toxicity shows no obvious toxic response, indicating good biosafety. This study indicates that the one-step method using a high-voltage electrostatic anti-solvent process has great potential in developing an inhalable drug carrier for pulmonary drug delivery. PMID:28773489

Time-oriented hierarchical method for computation of principal components using subspace learning algorithm.

PubMed

Jankovic, Marko; Ogawa, Hidemitsu

2004-10-01

Principal Component Analysis (PCA) and Principal Subspace Analysis (PSA) are classic techniques in statistical data analysis, feature extraction and data compression. Given a set of multivariate measurements, PCA and PSA provide a smaller set of "basis vectors" with less redundancy, and a subspace spanned by them, respectively. Artificial neurons and neural networks have been shown to perform PSA and PCA when gradient ascent (descent) learning rules are used, which is related to the constrained maximization (minimization) of statistical objective functions. Due to their low complexity, such algorithms and their implementation in neural networks are potentially useful in cases of tracking slow changes of correlations in the input data or in updating eigenvectors with new samples. In this paper we propose PCA learning algorithm that is fully homogeneous with respect to neurons. The algorithm is obtained by modification of one of the most famous PSA learning algorithms--Subspace Learning Algorithm (SLA). Modification of the algorithm is based on Time-Oriented Hierarchical Method (TOHM). The method uses two distinct time scales. On a faster time scale PSA algorithm is responsible for the "behavior" of all output neurons. On a slower scale, output neurons will compete for fulfillment of their "own interests". On this scale, basis vectors in the principal subspace are rotated toward the principal eigenvectors. At the end of the paper it will be briefly analyzed how (or why) time-oriented hierarchical method can be used for transformation of any of the existing neural network PSA method, into PCA method.

Enlightening discriminative network functional modules behind Principal Component Analysis separation in differential-omic science studies

PubMed Central

Ciucci, Sara; Ge, Yan; Durán, Claudio; Palladini, Alessandra; Jiménez-Jiménez, Víctor; Martínez-Sánchez, Luisa María; Wang, Yuting; Sales, Susanne; Shevchenko, Andrej; Poser, Steven W.; Herbig, Maik; Otto, Oliver; Androutsellis-Theotokis, Andreas; Guck, Jochen; Gerl, Mathias J.; Cannistraci, Carlo Vittorio

2017-01-01

Omic science is rapidly growing and one of the most employed techniques to explore differential patterns in omic datasets is principal component analysis (PCA). However, a method to enlighten the network of omic features that mostly contribute to the sample separation obtained by PCA is missing. An alternative is to build correlation networks between univariately-selected significant omic features, but this neglects the multivariate unsupervised feature compression responsible for the PCA sample segregation. Biologists and medical researchers often prefer effective methods that offer an immediate interpretation to complicated algorithms that in principle promise an improvement but in practice are difficult to be applied and interpreted. Here we present PC-corr: a simple algorithm that associates to any PCA segregation a discriminative network of features. Such network can be inspected in search of functional modules useful in the definition of combinatorial and multiscale biomarkers from multifaceted omic data in systems and precision biomedicine. We offer proofs of PC-corr efficacy on lipidomic, metagenomic, developmental genomic, population genetic, cancer promoteromic and cancer stem-cell mechanomic data. Finally, PC-corr is a general functional network inference approach that can be easily adopted for big data exploration in computer science and analysis of complex systems in physics. PMID:28287094

Using compressive measurement to obtain images at ultra low-light-level

NASA Astrophysics Data System (ADS)

Ke, Jun; Wei, Ping

2013-08-01

In this paper, a compressive imaging architecture is used for ultra low-light-level imaging. In such a system, features, instead of object pixels, are imaged onto a photocathode, and then magnified by an image intensifier. By doing so, system measurement SNR is increased significantly. Therefore, the new system can image objects at ultra low-ligh-level, while a conventional system has difficulty. PCA projection is used to collect feature measurements in this work. Linear Wiener operator and nonlinear method based on FoE model are used to reconstruct objects. Root mean square error (RMSE) is used to quantify system reconstruction quality.

pyPcazip: A PCA-based toolkit for compression and analysis of molecular simulation data

NASA Astrophysics Data System (ADS)

Shkurti, Ardita; Goni, Ramon; Andrio, Pau; Breitmoser, Elena; Bethune, Iain; Orozco, Modesto; Laughton, Charles A.

The biomolecular simulation community is currently in need of novel and optimised software tools that can analyse and process, in reasonable timescales, the large generated amounts of molecular simulation data. In light of this, we have developed and present here pyPcazip: a suite of software tools for compression and analysis of molecular dynamics (MD) simulation data. The software is compatible with trajectory file formats generated by most contemporary MD engines such as AMBER, CHARMM, GROMACS and NAMD, and is MPI parallelised to permit the efficient processing of very large datasets. pyPcazip is a Unix based open-source software (BSD licenced) written in Python.

Compressive strength of human openwedges: a selection method

NASA Astrophysics Data System (ADS)

Follet, H.; Gotteland, M.; Bardonnet, R.; Sfarghiu, A. M.; Peyrot, J.; Rumelhart, C.

2004-02-01

A series of 44 samples of bone wedges of human origin, intended for allograft openwedge osteotomy and obtained without particular precautions during hip arthroplasty were re-examined. After viral inactivity chemical treatment, lyophilisation and radio-sterilisation (intended to produce optimal health safety), the compressive strength, independent of age, sex and the height of the sample (or angle of cut), proved to be too widely dispersed [ 10{-}158 MPa] in the first study. We propose a method for selecting samples which takes into account their geometry (width, length, thicknesses, cortical surface area). Statistical methods (Principal Components Analysis PCA, Hierarchical Cluster Analysis, Multilinear regression) allowed final selection of 29 samples having a mean compressive strength σ_{max} =103 MPa ± 26 and with variation [ 61{-}158 MPa] . These results are equivalent or greater than average materials currently used in openwedge osteotomy.

Enhancing the solubility and bioavailability of poorly water-soluble drugs using supercritical antisolvent (SAS) process.

PubMed

Abuzar, Sharif Md; Hyun, Sang-Min; Kim, Jun-Hee; Park, Hee Jun; Kim, Min-Soo; Park, Jeong-Sook; Hwang, Sung-Joo

2018-03-01

Poor water solubility and poor bioavailability are problems with many pharmaceuticals. Increasing surface area by micronization is an effective strategy to overcome these problems, but conventional techniques often utilize solvents and harsh processing, which restricts their use. Newer, green technologies, such as supercritical fluid (SCF)-assisted particle formation, can produce solvent-free products under relatively mild conditions, offering many advantages over conventional methods. The antisolvent properties of the SCFs used for microparticle and nanoparticle formation have generated great interest in recent years, because the kinetics of the precipitation process and morphologies of the particles can be accurately controlled. The characteristics of the supercritical antisolvent (SAS) technique make it an ideal tool for enhancing the solubility and bioavailability of poorly water-soluble drugs. This review article focuses on SCFs and their properties, as well as the fundamentals of overcoming poorly water-soluble drug properties by micronization, crystal morphology control, and formation of composite solid dispersion nanoparticles with polymers and/or surfactants. This article also presents an overview of the main aspects of the SAS-assisted particle precipitation process, its mechanism, and parameters, as well as our own experiences, recent advances, and trends in development. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved performance of mesoscopic perovskite solar cell using an accelerated crystalline formation method

NASA Astrophysics Data System (ADS)

Sidhik, Siraj; Esparza, Diego; Martínez-Benítez, Alejandro; López-Luke, Tzarara; Carriles, Ramón; De la Rosa, Elder

2017-10-01

Highly smooth organo-lead halide perovskite (OHP) films with less intra-granular defects are necessary to minimize the non-radiative carrier recombination in photovoltaic devices. Herein, a simple air-extraction anti-solvent deposition (AAD) technique is proposed to improve the quality of perovskite films. An air extraction process accompanied by anti-solvent washing helps to improve the morphology of perovskite, leading to smooth, homogeneous, compact, pin-hole free and densely packed films. Perovskite films with an average roughness of 5.01 nm, which is the smoothest morphology in mesoscopic-perovskite solar cell to the extent of our knowledge, high crystallinity, and a crystallite size in the range of ∼500 nm to 1 μm have been achieved. Average power conversion efficiency (PCE) of 16.99% for 15 cells and a best PCE of 17.70% with a high open circuit voltage of 1.075 and fill factor of 74.22% were achieved using the AAD approach without a glove box. The cells exhibit virtually no hysteresis. These efficiency values are approximately 37.68% higher than the cells fabricated using anti-solvent process without air-extraction, where an average efficiency of 12.34% was measured. This method demonstrates high reproducibility and can be employed for the large scale production of PSC at reduced cost.

Effect of solvent type on the nanoparticle formation of atorvastatin calcium by the supercritical antisolvent process.

PubMed

Kim, Min-Soo; Song, Ha-Seung; Park, Hee Jun; Hwang, Sung-Joo

2012-01-01

The aims of this study were to identify how the solvent selection affects particle formation and to examine the effect of the initial drug solution concentration on mean particle size and particle size distribution in the supercritical antisolvent (SAS) process. Amorphous atorvastatin calcium was precipitated from seven different solvents using the SAS process. Particles with mean particle size ranging between 62.6 and 1493.7 nm were obtained by varying organic solvent type and solution concentration. By changing the solvent, we observed large variations in particle size and particle size distribution, accompanied by different particle morphologies. Particles obtained from acetone and tetrahydrofuran (THF) were compact and spherical fine particles, whereas those from N-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) were agglomerated, with rough surfaces and relatively larger particle sizes. Interestingly, the mean particle size of atorvastatin calcium increased with an increase in the boiling point of the organic solvent used. Thus, for atorvastatin particle formation via the SAS process, particle size was determined mainly by evaporation of the organic solvent into the antisolvent phase. In addition, the mean particle size was increased with increasing drug solution concentration. In this study, from the aspects of particle size and solvent toxicity, acetone was the better organic solvent for controlling nanoparticle formation of atorvastatin calcium.

[Preparation of curcumin-EC sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Bai, Wei-li; Yan, Ting-yuan; Wang, Zhi-xiang; Huang, De-chun; Yan, Ting-xuan; Li, Ping

2015-01-01

Curcumin-ethyl-cellulose (EC) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading and yield of inclusion complex as evaluation indexes, on the basis of single factor tests, orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experiments such as drug loading, yield, particle size distribution, electron microscope analysis (SEM) , infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 45 degrees C, crystallization pressure 10 MPa, curcumin concentration 8 g x L(-1), solvent flow rate 0.9 mL x min(-1), and CO2 velocity 4 L x min(-1). Under the optimal conditions, the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97%, and the average particle size of the particles was 20.632 μm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro dissolution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Development and in-vivo assessment of the bioavailability of oridonin solid dispersions by the gas anti-solvent technique.

PubMed

Li, Songming; Liu, Ying; Liu, Tao; Zhao, Ling; Zhao, Jihui; Feng, Nianping

2011-06-15

We developed solid dispersions, using the gas anti-solvent technique (GAS), to improve the oral bioavailability of the poorly water-soluble active component oridonin. The solubility of oridonin in supercritical carbon dioxide was measured under various pressures and temperatures. To prepare oridonin solid dispersions using the GAS technique, ethanol was used as the solvent, CO(2) was used as the anti-solvent and the hydrophilic polymer polyvinylpyrrolidone K17 (PVP K17) was used as the drug carrier matrix. Characterization of the obtained preparations was undertaken using scanning electron microscopy (SEM), X-ray diffraction (XRD) analyses and a drug release study. Oridonin solid dispersions were formed and oridonin was present in an amorphous form in these dispersions. Oridonin solid dispersions significantly increased the drug dissolution rate compared with that of oridonin powder, primarily through drug amorphization. Compared with the physical mixture of oridonin and PVP K17, oridonin solid dispersions gave higher values of AUC and C(max), and the absorption of oridonin from solid dispersions resulted in 26.4-fold improvement in bioavailability. The present study illustrated the feasibility of applying the GAS technique to prepare oridonin solid dispersions, and of using them for the delivery of oridonin via the oral route. Copyright © 2011 Elsevier B.V. All rights reserved.

Fast and accurate face recognition based on image compression

NASA Astrophysics Data System (ADS)

Zheng, Yufeng; Blasch, Erik

2017-05-01

Image compression is desired for many image-related applications especially for network-based applications with bandwidth and storage constraints. The face recognition community typical reports concentrate on the maximal compression rate that would not decrease the recognition accuracy. In general, the wavelet-based face recognition methods such as EBGM (elastic bunch graph matching) and FPB (face pattern byte) are of high performance but run slowly due to their high computation demands. The PCA (Principal Component Analysis) and LDA (Linear Discriminant Analysis) algorithms run fast but perform poorly in face recognition. In this paper, we propose a novel face recognition method based on standard image compression algorithm, which is termed as compression-based (CPB) face recognition. First, all gallery images are compressed by the selected compression algorithm. Second, a mixed image is formed with the probe and gallery images and then compressed. Third, a composite compression ratio (CCR) is computed with three compression ratios calculated from: probe, gallery and mixed images. Finally, the CCR values are compared and the largest CCR corresponds to the matched face. The time cost of each face matching is about the time of compressing the mixed face image. We tested the proposed CPB method on the "ASUMSS face database" (visible and thermal images) from 105 subjects. The face recognition accuracy with visible images is 94.76% when using JPEG compression. On the same face dataset, the accuracy of FPB algorithm was reported as 91.43%. The JPEG-compressionbased (JPEG-CPB) face recognition is standard and fast, which may be integrated into a real-time imaging device.

Principal elementary mode analysis (PEMA).

PubMed

Folch-Fortuny, Abel; Marques, Rodolfo; Isidro, Inês A; Oliveira, Rui; Ferrer, Alberto

2016-03-01

Principal component analysis (PCA) has been widely applied in fluxomics to compress data into a few latent structures in order to simplify the identification of metabolic patterns. These latent structures lack a direct biological interpretation due to the intrinsic constraints associated with a PCA model. Here we introduce a new method that significantly improves the interpretability of the principal components with a direct link to metabolic pathways. This method, called principal elementary mode analysis (PEMA), establishes a bridge between a PCA-like model, aimed at explaining the maximum variance in flux data, and the set of elementary modes (EMs) of a metabolic network. It provides an easy way to identify metabolic patterns in large fluxomics datasets in terms of the simplest pathways of the organism metabolism. The results using a real metabolic model of Escherichia coli show the ability of PEMA to identify the EMs that generated the different simulated flux distributions. Actual flux data of E. coli and Pichia pastoris cultures confirm the results observed in the simulated study, providing a biologically meaningful model to explain flux data of both organisms in terms of the EM activation. The PEMA toolbox is freely available for non-commercial purposes on http://mseg.webs.upv.es.

Dependence of Acetate-Based Antisolvents for High Humidity Fabrication of CH3NH3PbI3 Perovskite Devices in Ambient Atmosphere.

PubMed

Yang, Fu; Kapil, Gaurav; Zhang, Putao; Hu, Zhaosheng; Kamarudin, Muhammad Akmal; Ma, Tingli; Hayase, Shuzi

2018-05-16

High-efficiency perovskite solar cells (PSCs) need to be fabricated in the nitrogen-filled glovebox by the atmosphere-controlled crystallization process. However, the use of the glovebox process is of great concern for mass level production of PSCs. In this work, notable efficient CH 3 NH 3 PbI 3 solar cells can be obtained in high humidity ambient atmosphere (60-70% relative humidity) by using acetate as the antisolvent, in which dependence of methyl, ethyl, propyl, and butyl acetate on the crystal growth mechanism is discussed. It is explored that acetate screens the sensitive perovskite intermediate phases from water molecules during perovskite film formation and annealing. It is revealed that relatively high vapor pressure and high water solubility of methyl acetate (MA) leads to the formation of highly dense and pinhole free perovskite films guiding to the best power conversion efficiency (PCE) of 16.3% with a reduced hysteresis. The devices prepared using MA showed remarkable shelf life stability of more than 80% for 360 h in ambient air condition, when compared to the devices fabricated using other antisolvents with low vapor pressure and low water solubility. Moreover, the PCE was still kept at 15.6% even though 2 vol % deionized water was added in the MA for preparing the perovskite layer.

Estimation of the nucleation kinetics for the anti-solvent crystallisation of paracetamol in methanol/water solutions

NASA Astrophysics Data System (ADS)

Ó'Ciardhá, Clifford T.; Frawley, Patrick J.; Mitchell, Niall A.

2011-08-01

In this work the primary nucleation kinetics have been estimated for the anti-solvent crystallisation of paracetamol in methanol-water solutions from metastable zone widths (MSZW) and induction times at 25 °C. Laser back-scattering via a focused beam reflectance Measurement (FBRM ®) is utilised to detect the onset of nucleation. The theoretical approach of Kubota was employed to estimate the nucleation kinetics, which accounts for the sensitivity of the nucleation detection technique. This approach is expanded in this work to analyse the induction time for an anti-solvent crystallisation process. Solvent composition is known to have a significant impact on the measured induction times and MSZW. The induction time in this paper was measured from 40% to 70% mass water and the MSZW is measured from 40% to 60% mass water. The primary focus of the paper was to gauge the extent of how solvent composition affects nucleation kinetics so that this effect may be incorporated into a population balance model. Furthermore, the effects of solvent composition on the estimated nucleation rates are investigated. The primary nucleation rates were found to decrease with dynamic solvent composition, with the extent of their reduction linked to the gradient of the solubility curve. Finally, both MSZW and induction time methods have been found to produce similar estimates for the nucleation parameters.

Spectral images browsing using principal component analysis and set partitioning in hierarchical tree

NASA Astrophysics Data System (ADS)

Ma, Long; Zhao, Deping

2011-12-01

Spectral imaging technology have been used mostly in remote sensing, but have recently been extended to new area requiring high fidelity color reproductions like telemedicine, e-commerce, etc. These spectral imaging systems are important because they offer improved color reproduction quality not only for a standard observer under a particular illuminantion, but for any other individual exhibiting normal color vision capability under another illuminantion. A possibility for browsing of the archives is needed. In this paper, the authors present a new spectral image browsing architecture. The architecture for browsing is expressed as follow: (1) The spectral domain of the spectral image is reduced with the PCA transform. As a result of the PCA transform the eigenvectors and the eigenimages are obtained. (2) We quantize the eigenimages with the original bit depth of spectral image (e.g. if spectral image is originally 8bit, then quantize eigenimage to 8bit), and use 32bit floating numbers for the eigenvectors. (3) The first eigenimage is lossless compressed by JPEG-LS, the other eigenimages were lossy compressed by wavelet based SPIHT algorithm. For experimental evalution, the following measures were used. We used PSNR as the measurement for spectral accuracy. And for the evaluation of color reproducibility, ΔE was used.here standard D65 was used as a light source. To test the proposed method, we used FOREST and CORAL spectral image databases contrain 12 and 10 spectral images, respectively. The images were acquired in the range of 403-696nm. The size of the images were 128*128, the number of bands was 40 and the resolution was 8 bits per sample. Our experiments show the proposed compression method is suitable for browsing, i.e., for visual purpose.

Improving the dissolution properties of curcumin using dense gas antisolvent technology.

PubMed

Kurniawansyah, Firman; Quachie, Lisa; Mammucari, Raffaella; Foster, Neil R

2017-04-15

The dissolution properties of curcumin are notoriously poor and hinder its bioavailability. To improve its dissolution properties, curcumin has been formulated with methyl-β-cyclodextrin and polyvinylpyrrolidone by the atomized rapid injection solvent extraction (ARISE) system. The compounds were co-precipitated from organic solutions using carbon dioxide at 30°C and 95bar as the antisolvent. Curcumin formulations were also produced by physical mixing and freeze drying for comparative purposes. The morphology, crystallinity, solid state molecular interactions, apparent solubility and dissolution profiles of samples were observed. The results indicate that the ARISE process is effective in the preparation of curcumin micro-composites with enhanced dissolution profiles compared to unprocessed material and products from physical mixing and freeze drying. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled Self-Assembly of Low-Dimensional Alq3 Nanostructures from 1D Nanowires to 2D Plates via Intermolecular Interactions

NASA Astrophysics Data System (ADS)

Gu, Jianmin; Yin, Baipeng; Fu, Shaoyan; Jin, Cuihong; Liu, Xin; Bian, Zhenpan; Li, Jianjun; Wang, Lu; Li, Xiaoyu

2018-03-01

Due to the intense influence of the shape and size of the photon building blocks on the limitation and guidance of optical waves, an important strategy is the fabrication of different structures. Herein, organic semiconductor tris-(8-hydroxyquinoline)aluminium (Alq3) nanostructures with controllable morphology, ranging from one-dimensional nanowires to two-dimensional plates, have been prepared through altering intermolecular interactions with employing the anti-solvent diffusion cooperate with solvent-volatilization induced self-assembly method. The morphologies of the formed nanostructures, which are closely related to the stacking modes of the molecules, can be exactly controlled by altering the polarity of anti-solvents that can influence various intermolecular interactions. The synthesis strategy reported here can potentially be extended to other functional organic nanomaterials.

Eigenvectors of optimal color spectra.

PubMed

Flinkman, Mika; Laamanen, Hannu; Tuomela, Jukka; Vahimaa, Pasi; Hauta-Kasari, Markku

2013-09-01

Principal component analysis (PCA) and weighted PCA were applied to spectra of optimal colors belonging to the outer surface of the object-color solid or to so-called MacAdam limits. The correlation matrix formed from this data is a circulant matrix whose biggest eigenvalue is simple and the corresponding eigenvector is constant. All other eigenvalues are double, and the eigenvectors can be expressed with trigonometric functions. Found trigonometric functions can be used as a general basis to reconstruct all possible smooth reflectance spectra. When the spectral data are weighted with an appropriate weight function, the essential part of the color information is compressed to the first three components and the shapes of the first three eigenvectors correspond to one achromatic response function and to two chromatic response functions, the latter corresponding approximately to Munsell opponent-hue directions 9YR-9B and 2BG-2R.

Model Classes, Approximation, and Metrics for Dynamic Processing of Urban Terrain Data

DTIC Science & Technology

2013-01-01

Sensing,” DARPA IPTO Retreat, Annapolis, 2008. R. Baraniuk, “Compressive Sensing, Wavelets, and Sparsity,” SPIE Defense + Security (acceptance speech ... Speech and Signal Processing (ICASSP). 2011/05/22 00:00:00, Prague, Czech Republic. : , 08/31/2011 33.00 Sang-Mook Lee, Jeong Joon Im, Bo-Hee Lee... KNN ) points to define a local intrinsic coordinate system using PCA and to construct the manifold and function locally using least squares. Local

Acoustically enhanced microfluidic mixer to synthesize highly uniform nanodrugs without the addition of stabilizers.

PubMed

Le, Nguyen Hoai An; Van Phan, Hoang; Yu, Jiaqi; Chan, Hak-Kim; Neild, Adrian; Alan, Tuncay

2018-01-01

This article presents an acoustically enhanced microfluidic mixer to generate highly uniform and ultra-fine nanoparticles, offering significant advantages over conventional liquid antisolvent techniques. The method employed a 3D microfluidic geometry whereby two different phases - solvent and antisolvent - were introduced at either side of a 1 μm thick resonating membrane, which contained a through-hole. The vibration of the membrane rapidly and efficiently mixed the two phases, at the location of the hole, leading to the formation of nanoparticles. The versatility of the device was demonstrated by synthesizing budesonide (a common asthma drug) with a mean diameter of 135.7 nm and a polydispersity index of 0.044. The method offers a 40-fold reduction in the size of synthesized particles combined with a substantial improvement in uniformity, achieved without the need of stabilizers.

Simultaneous micronization and purification of bioactive fraction by supercritical antisolvent technology

PubMed Central

Hiendrawan, Stevanus; Veriansyah, Bambang; Widjojokusumo, Edward; Tjandrawinata, Raymond R.

2017-01-01

Simultaneous micronization and purification of DLBS3233 bioactive fraction, a combination of two Indonesian herbals Lagerstroemia speciosa and Cinnamomum burmannii has been successfully performed via supercritical anti-solvent (SAS) technology. The objective of the present study was to investigate the effectiveness of SAS technology to micronize and reduce coumarin content of DLBS3233. The effects of four SAS process parameters, i.e. pressure, temperature, concentration and solution flow rate on particle formation were investigated. In SAS process, DLBS3233 was dissolved in dimethylformamide (DMF) as the liquid solvent. The solution was then pumped through a nozzle into a chamber simultaneously with supercritical carbon dioxide (SC-CO2) which acts as the anti-solvent, resulting in DLBS3233 precipitation. Physicochemical properties of unprocessed DLBS3233 and SAS-processed DLBS3233 particles were analyzed using scanning electron microscopy (SEM) and high pressure liquid chromatography (HPLC). Total polyphenol content (TPC) was also analyzed. Particles with mean particle size ranging from 0.107±0.028 μm to 0.298±0.138 μm were obtained by varying the process parameters. SAS-processed DLBS3233 particles showed no coumarin content in all experiments studied in this work. Results of TPC analysis revealed no significant change in SAS-processed DLBS3233 particles compared to unprocessed DLBS3233. Nano-sized DLBS3233 particles with no coumarin content have been successfully produced using SAS process. This study demonstrates the ability of SAS for processing herbal medicine in single step process. PMID:28516056

Preparation, characterization and in vivo assessment of the bioavailability of glycyrrhizic acid microparticles by supercritical anti-solvent process.

PubMed

Sui, Xiaoyu; Wei, Wei; Yang, Lei; Zu, Yuangang; Zhao, Chunjian; Zhang, Lin; Yang, Fengjian; Zhang, Zhonghua

2012-02-28

In this study, glycyrrhizic acid (GA) microparticles were successfully prepared using a supercritical anti-solvent (SAS) process. Carbon dioxide and ethanol were used as the anti-solvent and solvent, respectively. The influences of several process parameters on the mean particle size (MPS), particle size distribution (PSD) and total yield were investigated. Processed particle sizes gradually decreased as temperature and solution flow rate increased. In addition, processed particle sizes increased from 119 to 205 nm as GA concentration increased. However, CO(2) flow rate did not significantly affect particle size. The optimized process conditions were applied, those included temperature (65 °C), pressure (250 bar), CO(2) and drug solution flow rate (15 and 8 mL min(-1)), drug concentration in ethanol (20 mg mL(-1)). Microparticles with a span of PSD ranging from 95 and 174 nm, MPS of 128 nm were obtained, and total yield was 63.5%. The X-ray diffraction patterns of glycyrrhizic acid microparticles show apparent amorphous nature. Fourier transform infrared (FT-IR) spectroscopy results show that no chemical structural changes occurred. The in vitro dissolution tests showed that the GA microparticles exhibited great enhancement of dissolution performance when compared to GA original drug. Furthermore, the in vivo studies revealed that the microparticles provided improved pharmacokinetic parameter after oral administration to rats as compared with original drug. Copyright © 2011 Elsevier B.V. All rights reserved.

Simultaneous micronization and purification of bioactive fraction by supercritical antisolvent technology.

PubMed

Hiendrawan, Stevanus; Veriansyah, Bambang; Widjojokusumo, Edward; Tjandrawinata, Raymond R

2017-01-01

Simultaneous micronization and purification of DLBS3233 bioactive fraction, a combination of two Indonesian herbals Lagerstroemia speciosa and Cinnamomum burmannii has been successfully performed via supercritical anti-solvent (SAS) technology. The objective of the present study was to investigate the effectiveness of SAS technology to micronize and reduce coumarin content of DLBS3233. The effects of four SAS process parameters, i.e. pressure, temperature, concentration and solution flow rate on particle formation were investigated. In SAS process, DLBS3233 was dissolved in dimethylformamide (DMF) as the liquid solvent. The solution was then pumped through a nozzle into a chamber simultaneously with supercritical carbon dioxide (SC-CO2) which acts as the anti-solvent, resulting in DLBS3233 precipitation. Physicochemical properties of unprocessed DLBS3233 and SAS-processed DLBS3233 particles were analyzed using scanning electron microscopy (SEM) and high pressure liquid chromatography (HPLC). Total polyphenol content (TPC) was also analyzed. Particles with mean particle size ranging from 0.107±0.028 μ m to 0.298±0.138 μ m were obtained by varying the process parameters. SAS-processed DLBS3233 particles showed no coumarin content in all experiments studied in this work. Results of TPC analysis revealed no significant change in SAS-processed DLBS3233 particles compared to unprocessed DLBS3233. Nano-sized DLBS3233 particles with no coumarin content have been successfully produced using SAS process. This study demonstrates the ability of SAS for processing herbal medicine in single step process.

Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance.

PubMed

Latif, Sumera; Abbas, Nasir; Hussain, Amjad; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Afzal, Hafsa; Riffat, Sualeha; Ahmad, Zeeshan

2018-07-01

Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90-97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and C max . A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and C max of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.

Representation of Probability Density Functions from Orbit Determination using the Particle Filter

NASA Technical Reports Server (NTRS)

Mashiku, Alinda K.; Garrison, James; Carpenter, J. Russell

2012-01-01

Statistical orbit determination enables us to obtain estimates of the state and the statistical information of its region of uncertainty. In order to obtain an accurate representation of the probability density function (PDF) that incorporates higher order statistical information, we propose the use of nonlinear estimation methods such as the Particle Filter. The Particle Filter (PF) is capable of providing a PDF representation of the state estimates whose accuracy is dependent on the number of particles or samples used. For this method to be applicable to real case scenarios, we need a way of accurately representing the PDF in a compressed manner with little information loss. Hence we propose using the Independent Component Analysis (ICA) as a non-Gaussian dimensional reduction method that is capable of maintaining higher order statistical information obtained using the PF. Methods such as the Principal Component Analysis (PCA) are based on utilizing up to second order statistics, hence will not suffice in maintaining maximum information content. Both the PCA and the ICA are applied to two scenarios that involve a highly eccentric orbit with a lower apriori uncertainty covariance and a less eccentric orbit with a higher a priori uncertainty covariance, to illustrate the capability of the ICA in relation to the PCA.

Pressure-induced electronic topological transitions in the charge-density-wave material In 4 Se 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yuhang; Song, Liyan; Shao, Xuecheng

2017-08-01

High-pressure in situ angle dispersive X-ray diffraction (ADXRD) measurements were performed on the charge-density-wave (CDW) material In4Se3 up to 48.8 GPa. Pressure-induced structural changes were observed at 7.0 and 34.2 GPa, respectively. Using the CALYPSO methodology, the first high-pressure phase was solved as an exotic Pca21 structure. The compressional behaviors of the initial Pnnm and the Pca21 phases were all determined. Combined with first-principle calculations, we find that, unexpectedly, the Pnnm phase probably experiences twice electronic topological transitions (ETTs), from the initial possible CDW state to a semimetallic state at about 2.3 GPa and then back to a possible CDWmore » state at around 3.5 GPa, which was uncovered for the first time in CDW systems. In the both possible CDW states, pressure provokes a decrease of band-gap. The observation of a bulk metallic state was ascribed to structural transition to the Pca21 phase. Besides, based on electronic band structure calculations, the thermoelectric property of the Pnnm phase under compression was discussed. Our results show that pressure play a dramatic role in tuning In4Se3's structure and transport properties.« less

Towards Improved Radiative Transfer Simulations of Hyperspectral Measurements for Cloudy Atmospheres

NASA Astrophysics Data System (ADS)

Natraj, V.; Li, C.; Aumann, H. H.; Yung, Y. L.

2016-12-01

Usage of hyperspectral measurements in the infrared for weather forecasting requires radiative transfer (RT) models that can accurately compute radiances given the atmospheric state. On the other hand, it is necessary for the RT models to be fast enough to meet operational processing processing requirements. Until recently, this has proven to be a very hard challenge. In the last decade, however, significant progress has been made in this regard, due to computer speed increases, and improved and optimized RT models. This presentation will introduce a new technique, based on principal component analysis (PCA) of the inherent optical properties (such as profiles of trace gas absorption and single scattering albedo), to perform fast and accurate hyperspectral RT calculations in clear or cloudy atmospheres. PCA is a technique to compress data while capturing most of the variability in the data. By performing PCA on the optical properties, we limit the number of computationally expensive multiple scattering RT calculations to the PCA-reduced data set, and develop a series of PC-based correction factors to obtain the hyperspectral radiances. This technique has been showed to deliver accuracies of 0.1% of better with respect to brute force, line-by-line (LBL) models such as LBLRTM and DISORT, but is orders of magnitude faster than the LBL models. We will compare the performance of this method against other models on a large atmospheric state data set (7377 profiles) that includes a wide range of thermodynamic and cloud profiles, along with viewing geometry and surface emissivity information. 2016. All rights reserved.

Operating Mechanisms of Mesoscopic Perovskite Solar Cells through Impedance Spectroscopy and J-V Modeling.

PubMed

Zarazúa, Isaac; Sidhik, Siraj; Lopéz-Luke, Tzarara; Esparza, Diego; De la Rosa, Elder; Reyes-Gomez, Juan; Mora-Seró, Iván; Garcia-Belmonte, Germà

2017-12-21

The performance of perovskite solar cell (PSC) is highly sensitive to deposition conditions, the substrate, humidity, and the efficiency of solvent extraction. However, the physical mechanism involved in the observed changes of efficiency with different deposition conditions has not been elucidated yet. In this work, PSCs were fabricated by the antisolvent deposition (AD) and recently proposed air-extraction antisolvent (AAD) process. Impedance analysis and J-V curve fitting were used to analyze the photogeneration, charge transportation, recombination, and leakage properties of PSCs. It can be elucidated that the improvement in morphology of perovskite film promoted by AAD method leads to increase in light absorption, reduction in recombination sites, and interstitial defects, thus enhancing the short-circuit current density, open-circuit voltage, and fill factor. This study will open up doors for further improvement of device and help in understanding its physical mechanism and its relation to the deposition methods.

Insights Into the Solution Crystallization of Oriented Alq3 and Znq2 Microprisms and Nanorods.

PubMed

Boulet, Joel; Mohammadpour, Arash; Shankar, Karthik

2015-09-01

Optimized solution-based methods to grow high quality micro- and nanocrystals of organic semi-conductors with defined size, shape and orientation are important to a variety of optoelectronic applications. In this context, we report the growth of single crystal micro- and nanostructures of the organic semiconductors Tris(8-hydroxyquinoline)aluminum (Alq3) and bis(8-hydroxyquinoline)zinc (Znq2) terminating in flat crystal planes using a combination of evaporative and antisolvent crystallization. By controlling substrate-specific nucleation and optimizing the conditions of growth, we generate vertically-oriented hexagonal prism arrays of Alq3, and vertical half-disks and sharp-edged rectangular prisms of Znq2. The effect of process variables such as ambient vapour pressure, choice of anti-solvent and temperature on the morphology and crystal habit of the nanostructures were studied and the results of varying them catalogued to gain a better understanding of the mechanism of growth.

Spray printing of organic semiconducting single crystals

NASA Astrophysics Data System (ADS)

Rigas, Grigorios-Panagiotis; Payne, Marcia M.; Anthony, John E.; Horton, Peter N.; Castro, Fernando A.; Shkunov, Maxim

2016-11-01

Single-crystal semiconductors have been at the forefront of scientific interest for more than 70 years, serving as the backbone of electronic devices. Inorganic single crystals are typically grown from a melt using time-consuming and energy-intensive processes. Organic semiconductor single crystals, however, can be grown using solution-based methods at room temperature in air, opening up the possibility of large-scale production of inexpensive electronics targeting applications ranging from field-effect transistors and light-emitting diodes to medical X-ray detectors. Here we demonstrate a low-cost, scalable spray-printing process to fabricate high-quality organic single crystals, based on various semiconducting small molecules on virtually any substrate by combining the advantages of antisolvent crystallization and solution shearing. The crystals' size, shape and orientation are controlled by the sheer force generated by the spray droplets' impact onto the antisolvent's surface. This method demonstrates the feasibility of a spray-on single-crystal organic electronics.

Controlled delivery of a hydrophilic drug from a biodegradable microsphere system by supercritical anti-solvent precipitation technique.

PubMed

Lee, S; Kim, M S; Kim, J S; Park, H J; Woo, J S; Lee, B C; Hwang, S J

2006-11-01

The purpose of this study was to prepare microspheres loaded with hydrophilic drug, bupivacaine HCl using poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). Microspheres were prepared with varying the PLGA/PLLA ratio with two different levels of bupivacaine HCl (5 and 10%) using a supercritical anti-solvent (SAS) technique. Microspheres ranging from 4-10 microm in geometric mean diameter could be prepared, with high loading efficiency. Powder X-ray diffraction (PXRD) revealed that bupivacaine HCl retained its crystalline state within the polymer and was present as a dispersion within the polymer phase after SAS processing. The release of bupivacaine HCl from biodegradable polymer microspheres was rapid up to 4 h, thereafter bupivacaine HCl was continuously and slowly released for at least 7 days according to the PLGA/PLLA ratio and the molecular weight of PLLA.

Different approaches in Partial Least Squares and Artificial Neural Network models applied for the analysis of a ternary mixture of Amlodipine, Valsartan and Hydrochlorothiazide

NASA Astrophysics Data System (ADS)

Darwish, Hany W.; Hassan, Said A.; Salem, Maissa Y.; El-Zeany, Badr A.

2014-03-01

Different chemometric models were applied for the quantitative analysis of Amlodipine (AML), Valsartan (VAL) and Hydrochlorothiazide (HCT) in ternary mixture, namely, Partial Least Squares (PLS) as traditional chemometric model and Artificial Neural Networks (ANN) as advanced model. PLS and ANN were applied with and without variable selection procedure (Genetic Algorithm GA) and data compression procedure (Principal Component Analysis PCA). The chemometric methods applied are PLS-1, GA-PLS, ANN, GA-ANN and PCA-ANN. The methods were used for the quantitative analysis of the drugs in raw materials and pharmaceutical dosage form via handling the UV spectral data. A 3-factor 5-level experimental design was established resulting in 25 mixtures containing different ratios of the drugs. Fifteen mixtures were used as a calibration set and the other ten mixtures were used as validation set to validate the prediction ability of the suggested methods. The validity of the proposed methods was assessed using the standard addition technique.

Hyperspectral image compressing using wavelet-based method

NASA Astrophysics Data System (ADS)

Yu, Hui; Zhang, Zhi-jie; Lei, Bo; Wang, Chen-sheng

2017-10-01

Hyperspectral imaging sensors can acquire images in hundreds of continuous narrow spectral bands. Therefore each object presented in the image can be identified from their spectral response. However, such kind of imaging brings a huge amount of data, which requires transmission, processing, and storage resources for both airborne and space borne imaging. Due to the high volume of hyperspectral image data, the exploration of compression strategies has received a lot of attention in recent years. Compression of hyperspectral data cubes is an effective solution for these problems. Lossless compression of the hyperspectral data usually results in low compression ratio, which may not meet the available resources; on the other hand, lossy compression may give the desired ratio, but with a significant degradation effect on object identification performance of the hyperspectral data. Moreover, most hyperspectral data compression techniques exploits the similarities in spectral dimensions; which requires bands reordering or regrouping, to make use of the spectral redundancy. In this paper, we explored the spectral cross correlation between different bands, and proposed an adaptive band selection method to obtain the spectral bands which contain most of the information of the acquired hyperspectral data cube. The proposed method mainly consist three steps: First, the algorithm decomposes the original hyperspectral imagery into a series of subspaces based on the hyper correlation matrix of the hyperspectral images between different bands. And then the Wavelet-based algorithm is applied to the each subspaces. At last the PCA method is applied to the wavelet coefficients to produce the chosen number of components. The performance of the proposed method was tested by using ISODATA classification method.

Principal component analysis acceleration of rovibrational coarse-grain models for internal energy excitation and dissociation

NASA Astrophysics Data System (ADS)

Bellemans, Aurélie; Parente, Alessandro; Magin, Thierry

2018-04-01

The present work introduces a novel approach for obtaining reduced chemistry representations of large kinetic mechanisms in strong non-equilibrium conditions. The need for accurate reduced-order models arises from compression of large ab initio quantum chemistry databases for their use in fluid codes. The method presented in this paper builds on existing physics-based strategies and proposes a new approach based on the combination of a simple coarse grain model with Principal Component Analysis (PCA). The internal energy levels of the chemical species are regrouped in distinct energy groups with a uniform lumping technique. Following the philosophy of machine learning, PCA is applied on the training data provided by the coarse grain model to find an optimally reduced representation of the full kinetic mechanism. Compared to recently published complex lumping strategies, no expert judgment is required before the application of PCA. In this work, we will demonstrate the benefits of the combined approach, stressing its simplicity, reliability, and accuracy. The technique is demonstrated by reducing the complex quantum N2(g+1Σ) -N(S4u ) database for studying molecular dissociation and excitation in strong non-equilibrium. Starting from detailed kinetics, an accurate reduced model is developed and used to study non-equilibrium properties of the N2(g+1Σ) -N(S4u ) system in shock relaxation simulations.

Fast clustering algorithm for large ECG data sets based on CS theory in combination with PCA and K-NN methods.

PubMed

Balouchestani, Mohammadreza; Krishnan, Sridhar

2014-01-01

Long-term recording of Electrocardiogram (ECG) signals plays an important role in health care systems for diagnostic and treatment purposes of heart diseases. Clustering and classification of collecting data are essential parts for detecting concealed information of P-QRS-T waves in the long-term ECG recording. Currently used algorithms do have their share of drawbacks: 1) clustering and classification cannot be done in real time; 2) they suffer from huge energy consumption and load of sampling. These drawbacks motivated us in developing novel optimized clustering algorithm which could easily scan large ECG datasets for establishing low power long-term ECG recording. In this paper, we present an advanced K-means clustering algorithm based on Compressed Sensing (CS) theory as a random sampling procedure. Then, two dimensionality reduction methods: Principal Component Analysis (PCA) and Linear Correlation Coefficient (LCC) followed by sorting the data using the K-Nearest Neighbours (K-NN) and Probabilistic Neural Network (PNN) classifiers are applied to the proposed algorithm. We show our algorithm based on PCA features in combination with K-NN classifier shows better performance than other methods. The proposed algorithm outperforms existing algorithms by increasing 11% classification accuracy. In addition, the proposed algorithm illustrates classification accuracy for K-NN and PNN classifiers, and a Receiver Operating Characteristics (ROC) area of 99.98%, 99.83%, and 99.75% respectively.

SandiaMRCR

DOE Office of Scientific and Technical Information (OSTI.GOV)

2012-01-05

SandiaMCR was developed to identify pure components and their concentrations from spectral data. This software efficiently implements the multivariate calibration regression alternating least squares (MCR-ALS), principal component analysis (PCA), and singular value decomposition (SVD). Version 3.37 also includes the PARAFAC-ALS Tucker-1 (for trilinear analysis) algorithms. The alternating least squares methods can be used to determine the composition without or with incomplete prior information on the constituents and their concentrations. It allows the specification of numerous preprocessing, initialization and data selection and compression options for the efficient processing of large data sets. The software includes numerous options including the definition ofmore » equality and non-negativety constraints to realistically restrict the solution set, various normalization or weighting options based on the statistics of the data, several initialization choices and data compression. The software has been designed to provide a practicing spectroscopist the tools required to routinely analysis data in a reasonable time and without requiring expert intervention.« less

Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process.

PubMed

Ha, Eun-Sol; Kim, Jeong-Soo; Baek, In-Hwan; Yoo, Jin-Wook; Jung, Yunjin; Moon, Hyung Ryong; Kim, Min-Soo

2015-01-01

In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0-24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate.

Formation of indomethacin-saccharin cocrystals using supercritical fluid technology.

PubMed

Padrela, Luis; Rodrigues, Miguel A; Velaga, Sitaram P; Matos, Henrique A; de Azevedo, Edmundo Gomes

2009-08-12

The main objective of the present work is to check the feasibility of supercritical fluid (SCF) technologies in the screening and design of cocrystals (novel crystalline solids). The cocrystal formation tendencies in three different SCF techniques, focusing on distinct supercritical fluid properties - solvent, anti-solvent and atomization enhancer - were investigated. The effect of processing parameters on the cocrystal formation behaviour and particle properties in these techniques was also studied. A recently reported indomethacin-saccharin (IND-SAC) cocrystalline system was our model system. A 1:1 molar ratio of indomethacin (gamma-form) and saccharin was used as a starting material. The SCF techniques employed in the study include the CSS technique (cocrystallization with supercritical solvent), the SAS technique (supercritical anti-solvent), and the AAS technique (atomization and anti-solvent). The resulting cocrystalline phase was identified using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform-Raman (FT-Raman). The particle morphologies and size distributions were determined using scanning electron microscopy (SEM) and aerosizer, respectively. The pure IND-SAC cocrystals were obtained from SAS and AAS processes, whilst partial to no cocrystal formation occurred in the CSS process. However, no remarkable differences were observed in terms of cocrystal formation at different processing conditions in SAS and AAS processes. Particles from CSS processes were agglomerated and large, whilst needle-to-block-shaped and spherical particles were obtained from SAS and AAS processes, respectively. The particle size distribution of these particles was 0.2-5microm. Particulate IND-SAC cocrystals with different morphologies and sizes (nano-to-micron) were produced using supercritical fluid techniques. This work demonstrates the potential of SCF technologies as screening methods for cocrystals with possibilities for particle engineering.

Continuous nanoparticle production by microfluidic-based emulsion, mixing and crystallization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Y.-F.; Kim, H.; Kovenklioglu, S.

2007-09-15

BaSO{sub 4} and 2,2'-dipyridylamine (DPA) nanoparticles were synthesized as reactive crystallization and anti-solvent recrystallization examples, respectively, of using the microfluidic-based emulsion and mixing approach as a new avenue of continuously producing inorganic and organic nanoparticles. BaSO{sub 4} nanoparticles in the size range of 15-100 nm were reactively precipitated within the confinement of an aqueous droplet which was coalesced from two separate aqueous droplets containing BaCl{sub 2} and (NH{sub 4}){sub 2}SO{sub 4} using a three T-junction micromixer configuration constructed with commercially available simple tubing and fitting supplies. Also, DPA nanoparticles of about 200 nm were crystallized by combining DPA+ethanol and watermore » droplets using the same micromixer configuration. - Graphical abstract: BaSO{sub 4} and 2,2'-dipyridylamine (DPA) nanoparticles were synthesized as reactive crystallization and anti-solvent recrystallization examples, respectively, of using the microfluidic-based emulsion and mixing approach as a new avenue of continuously producing inorganic and organic nanoparticles.« less

Effect of supercritical fluid density on nanoencapsulated drug particle size using the supercritical antisolvent method.

PubMed

Kalani, Mahshid; Yunus, Robiah

2012-01-01

The reported work demonstrates and discusses the effect of supercritical fluid density (pressure and temperature of supercritical fluid carbon dioxide) on particle size and distribution using the supercritical antisolvent (SAS) method in the purpose of drug encapsulation. In this study, paracetamol was encapsulated inside L-polylactic acid, a semicrystalline polymer, with different process parameters, including pressure and temperature, using the SAS process. The morphology and particle size of the prepared nanoparticles were determined by scanning electron microscopy and transmission electron microscopy. The results revealed that increasing temperature enhanced mean particle size due to the plasticizing effect. Furthermore, increasing pressure enhanced molecular interaction and solubility; thus, particle size was reduced. Transmission electron microscopy images defined the internal structure of nanoparticles. Thermal characteristics of nanoparticles were also investigated via differential scanning calorimetry. Furthermore, X-ray diffraction pattern revealed the changes in crystallinity structure during the SAS process. In vitro drug release analysis determined the sustained release of paracetamol in over 4 weeks.

Supercritical fluid technology: a promising approach in pharmaceutical research.

PubMed

Girotra, Priti; Singh, Shailendra Kumar; Nagpal, Kalpana

2013-02-01

Supercritical fluids possess the unique properties of behaving like liquids and gases, above their critical point. Supercritical fluid technology has recently emerged as a green and novel technique for various processes such as solubility enhancement of poorly soluble drugs, plasticization of polymers, surface modification, nanosizing and nanocrystal modification, and chromatographic extraction. Research interest in this area has been fuelled because of the numerous advantages that the technology offers over the conventional methods. This work aims to review the merits, demerits, and various processes such as rapid expansion of supercritical solutions (RESS), particles from gas saturated solutions (PGSS), gas antisolvent process (GAS), supercritical antisolvent process (SAS) and polymerization induced phase separation (PIPS), that have enabled this technology to considerably raise the interest of researchers over the past two decades. An insight has been given into the numerous applications of this technology in pharmaceutical industry and the future challenges which must be appropriately dealt with to make it effective on a commercial scale.

Antisolvent Recrystallization Strategy to Screen Appropriate Carriers to Stabilize Filgotinib Amorphous Solid Dispersions.

PubMed

Ren, Fuzheng; Sun, Hanjing; Cui, Lin; Si, Yike; Chen, Ning; Ren, Guobin; Jing, Qiufang

2018-06-01

Drugs in amorphous solid dispersions (ASDs) are highly dispersed in hydrophilic polymeric carriers, which also help to restrain recrystallization and stabilize the ASDs. In this study, microscopic observation after antisolvent recrystallization was developed as a rapid screening method to select appropriate polymers for the initial design filgotinib (FTN) ASDs. Using solvent evaporation, FTN ASDs with the polymers were prepared, and accelerated experimentation validated this screening method. Fourier-transform infrared spectroscopy, Raman scattering, and nuclear magnetic resonance revealed hydrogen-bonding formation in the drug-polymer binary system, which was critical for ASDs stabilization. A Flory-Huggins interaction parameter and water sorption isotherms were applied to evaluate the strength of the interaction between FTN and the polymers. The dissolution rate was also significantly improved by ASDs formulation, and the presence of the polymers exerted solubilization effects. These results suggested the efficacy of this screening method as a preliminary tool for polymer selection in ASDs design. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effect of supercritical fluid density on nanoencapsulated drug particle size using the supercritical antisolvent method

PubMed Central

Kalani, Mahshid; Yunus, Robiah

2012-01-01

The reported work demonstrates and discusses the effect of supercritical fluid density (pressure and temperature of supercritical fluid carbon dioxide) on particle size and distribution using the supercritical antisolvent (SAS) method in the purpose of drug encapsulation. In this study, paracetamol was encapsulated inside L-polylactic acid, a semicrystalline polymer, with different process parameters, including pressure and temperature, using the SAS process. The morphology and particle size of the prepared nanoparticles were determined by scanning electron microscopy and transmission electron microscopy. The results revealed that increasing temperature enhanced mean particle size due to the plasticizing effect. Furthermore, increasing pressure enhanced molecular interaction and solubility; thus, particle size was reduced. Transmission electron microscopy images defined the internal structure of nanoparticles. Thermal characteristics of nanoparticles were also investigated via differential scanning calorimetry. Furthermore, X-ray diffraction pattern revealed the changes in crystallinity structure during the SAS process. In vitro drug release analysis determined the sustained release of paracetamol in over 4 weeks. PMID:22619552

Recrystallization of fluconazole using the supercritical antisolvent (SAS) process.

PubMed

Park, Hee Jun; Kim, Min-Soo; Lee, Sibeum; Kim, Jeong-Soo; Woo, Jong-Soo; Park, Jeong-Sook; Hwang, Sung-Joo

2007-01-10

The supercritical antisolvent (SAS) process was used to modify solid state characteristics of fluconazole. Fluconazole was recrystallized at various temperatures (60-80 degrees C) and pressures (8-16MPa) using dichloromethane (DCM) as a solvent. Acetone and ethanol were also employed as solvents. The fluconazole polymorphs prepared by the SAS process were characterized by differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Furthermore, the equilibrium solubility of the samples in aqueous solution was determined. Fluconazole anhydrate form I was obtained at low temperature (40 degrees C) and anhydrate form II was obtained at high temperature (80 degrees C). The variation of pressure during the SAS process may influence the preferred orientation. Anhydrate forms I and II were also obtained using various solvents. Therefore, it was shown that solid state characteristics of fluconazole, including the polymorphic form and preferred orientation, can be controlled by changing operating conditions of the SAS process such as temperature, pressure, and solvent.

Preparation and Physicochemical Properties of 10-Hydroxycamptothecin (HCPT) Nanoparticles by Supercritical Antisolvent (SAS) Process

PubMed Central

Zhao, Xiuhua; Zu, Yuangang; Jiang, Ru; Wang, Ying; Li, Yong; Li, Qingyong; Zhao, Dongmei; Zu, Baishi; Zhang, Baoyou; Sun, Zhiqiang; Zhang, Xiaonan

2011-01-01

The goal of the present work was to study the feasibility of 10-hydroxycamptothecin (HCPT) nanoparticle preparation using supercritical antisolvent (SAS) precipitation. The influences of various experimental factors on the mean particle size (MPS) of HCPT nanoparticles were investigated. The optimum micronization conditions are determined as follows: HCPT solution concentration 0.5 mg/mL, the flow rate ratio of CO2 and HCPT solution 19.55, precipitation temperature 35 °C and precipitation pressure 20 MPa. Under the optimum conditions, HCPT nanoparticles with a MPS of 180 ± 20.3 nm were obtained. Moreover, the HCPT nanoparticles obtained were characterized by Scanning electron microscopy, Dynamic light scattering, Fourier-transform infrared spectroscopy, High performance liquid chromatography-mass spectrometry, X-ray diffraction and Differential scanning calorimetry analyses. The physicochemical characterization results showed that the SAS process had not induced degradation of HCPT. Finally, the dissolution rates of HCPT nanoparticles were investigated and the results proved that there is a significant increase in dissolution rate compared to unprocessed HCPT. PMID:21731466

Physicochemical properties and oral bioavailability of ursolic acid nanoparticles using supercritical anti-solvent (SAS) process.

PubMed

Yang, Lei; Sun, Zhen; Zu, Yuangang; Zhao, Chunjian; Sun, Xiaowei; Zhang, Zhonghua; Zhang, Lin

2012-05-01

The objective of the study was to prepare ursolic acid (UA) nanoparticles using the supercritical anti-solvent (SAS) process and evaluate its physicochemical properties and oral bioavailability. The effects of four process variables, pressure, temperature, drug concentration and drug solution flow rate, on drug particle formation during SAS process, were investigated. Particles with mean particle size ranging from 139.2±19.7 to 1039.8±65.2nm were obtained by varying the process parameters. The UA was characterised by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, thermal gravimetric analysis, specific surface area, dissolution test and bioavailability test. It was concluded that physicochemical properties and bioavailability of crystalline UA could be improved by physical modification, such as particle size reduction and generation of amorphous state using SAS process. Further, SAS process was a powerful methodology for improving the physicochemical properties and bioavailability of UA. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ultrafast High Accuracy PCRTM_SOLAR Model for Cloudy Atmosphere

NASA Technical Reports Server (NTRS)

Yang, Qiguang; Liu, Xu; Wu, Wan; Yang, Ping; Wang, Chenxi

2015-01-01

An ultrafast high accuracy PCRTM_SOLAR model is developed based on PCA compression and principal component-based radiative transfer model (PCRTM). A fast algorithm for simulation of multi-scattering properties of cloud and/or aerosols is integrated into the fast infrared PCRTM. We completed radiance simulation and training for instruments, such as IASI, AIRS, CrIS, NASTI and SHIS, under diverse conditions. The new model is 5 orders faster than 52-stream DISORT with very high accuracy for cloudy sky radiative transfer simulation. It is suitable for hyperspectral remote data assimilation and cloudy sky retrievals.

EM in high-dimensional spaces.

PubMed

Draper, Bruce A; Elliott, Daniel L; Hayes, Jeremy; Baek, Kyungim

2005-06-01

This paper considers fitting a mixture of Gaussians model to high-dimensional data in scenarios where there are fewer data samples than feature dimensions. Issues that arise when using principal component analysis (PCA) to represent Gaussian distributions inside Expectation-Maximization (EM) are addressed, and a practical algorithm results. Unlike other algorithms that have been proposed, this algorithm does not try to compress the data to fit low-dimensional models. Instead, it models Gaussian distributions in the (N - 1)-dimensional space spanned by the N data samples. We are able to show that this algorithm converges on data sets where low-dimensional techniques do not.

Nonlinear Peculiar-Velocity Analysis and PCA

NASA Astrophysics Data System (ADS)

Dekel, Avishai; Eldar, Amiram; Silberman, Lior; Zehavi, Idit

We allow for nonlinear effects in the likelihood analysis of peculiar velocities, and obtain ˜35%-lower values for the cosmological density parameter and for the amplitude of mass-density fluctuations. The power spectrum in the linear regime is assumed to be of the flat ΛCDM model (h = 0.65, n = 1) with only Ω_m free. Since the likelihood is driven by the nonlinear regime, we "break" the power spectrum at k_b˜ 0.2 (h^{-1}Mpc)^{-1} and fit a two-parameter power-law at k > k b . This allows for an unbiased fit in the linear regime. Tests using improved mock catalogs demonstrate a reduced bias and a better fit. We find for the Mark III and SFI data Ω_m = 0.35± 0.09 with σ_8Ω_m^{0.6} = 0.55± 0.10 (90% errors). When allowing deviations from ΛCDM, we find an indication for a wiggle in the power spectrum in the form of an excess near k ˜ 0.05 and a deficiency at k ˜ 0.1 (h^{-1}Mpc)^{-1} - a "cold flow" which may be related to a feature indicated from redshift surveys and the second peak in the CMB anisotropy. A χ^2 test applied to principal modes demonstrates that the nonlinear procedure improves the goodness of fit. The Principal Component Analysis (PCA) helps identifying spatial features of the data and fine-tuning the theoretical and error models. We address the potential for optimal data compression using PCA.

Comprehensive characterization of measurement data gathered by the pressure tube to calandria tube gap probe

NASA Astrophysics Data System (ADS)

Shokralla, Shaddy Samir Zaki

Multi-frequency eddy current measurements are employed in estimating pressure tube (PT) to calandria tube (CT) gap in CANDU fuel channels, a critical inspection activity required to ensure fitness for service of fuel channels. In this thesis, a comprehensive characterization of eddy current gap data is laid out, in order to extract further information on fuel channel condition, and to identify generalized applications for multi-frequency eddy current data. A surface profiling technique, generalizable to multiple probe and conductive material configurations has been developed. This technique has allowed for identification of various pressure tube artefacts, has been independently validated (using ultrasonic measurements), and has been deployed and commissioned at Ontario Power Generation. Dodd and Deeds solutions to the electromagnetic boundary value problem associated with the PT to CT gap probe configuration were experimentally validated for amplitude response to changes in gap. Using the validated Dodd and Deeds solutions, principal components analysis (PCA) has been employed to identify independence and redundancies in multi-frequency eddy current data. This has allowed for an enhanced visualization of factors affecting gap measurement. Results of the PCA of simulation data are consistent with the skin depth equation, and are validated against PCA of physical experiments. Finally, compressed data acquisition has been realized, allowing faster data acquisition for multi-frequency eddy current systems with hardware limitations, and is generalizable to other applications where real time acquisition of large data sets is prohibitive.

Recursive approach of EEG-segment-based principal component analysis substantially reduces cryogenic pump artifacts in simultaneous EEG-fMRI data.

PubMed

Kim, Hyun-Chul; Yoo, Seung-Schik; Lee, Jong-Hwan

2015-01-01

Electroencephalography (EEG) data simultaneously acquired with functional magnetic resonance imaging (fMRI) data are preprocessed to remove gradient artifacts (GAs) and ballistocardiographic artifacts (BCAs). Nonetheless, these data, especially in the gamma frequency range, can be contaminated by residual artifacts produced by mechanical vibrations in the MRI system, in particular the cryogenic pump that compresses and transports the helium that chills the magnet (the helium-pump). However, few options are available for the removal of helium-pump artifacts. In this study, we propose a recursive approach of EEG-segment-based principal component analysis (rsPCA) that enables the removal of these helium-pump artifacts. Using the rsPCA method, feature vectors representing helium-pump artifacts were successfully extracted as eigenvectors, and the reconstructed signals of the feature vectors were subsequently removed. A test using simultaneous EEG-fMRI data acquired from left-hand (LH) and right-hand (RH) clenching tasks performed by volunteers found that the proposed rsPCA method substantially reduced helium-pump artifacts in the EEG data and significantly enhanced task-related gamma band activity levels (p=0.0038 and 0.0363 for LH and RH tasks, respectively) in EEG data that have had GAs and BCAs removed. The spatial patterns of the fMRI data were estimated using a hemodynamic response function (HRF) modeled from the estimated gamma band activity in a general linear model (GLM) framework. Active voxel clusters were identified in the post-/pre-central gyri of motor area, only from the rsPCA method (uncorrected p<0.001 for both LH/RH tasks). In addition, the superior temporal pole areas were consistently observed (uncorrected p<0.001 for the LH task and uncorrected p<0.05 for the RH task) in the spatial patterns of the HRF model for gamma band activity when the task paradigm and movement were also included in the GLM. Copyright © 2014 Elsevier Inc. All rights reserved.

Separation of polysaccharides from rice husk and wheat bran using solvent system consisting of BMIMOAc and DMI.

PubMed

Hou, Qidong; Li, Weizun; Ju, Meiting; Liu, Le; Chen, Yu; Yang, Qian; Wang, Jingyu

2015-11-20

A solvent system consisting of 1,3-dimethyl-2-imidazolidinone (DMI), and ionic liquid 1-butyl-3-methylimidazolium acetate (BMIMOAc) was used to separate polysaccharides from rice husk and wheat bran. The effects of the DMI/BMIMOAc ratios, temperature, and time on the dissolution of rice husk and wheat bran were investigated, and the influence of anti-solvents on the regeneration of polysaccharides-rich material was evaluated. We found that the solvent system is more powerful to dissolve rice husk and wheat bran than pure BMIMOAc, and that polysaccharides-rich material can be effectively separated from the biomass solution. The polysaccharides content of regenerated material from wheat bran can reach as high as 94.4% when ethanol was used as anti-solvents. Under optimized conditions, the extraction rate of polysaccharides for wheat bran can reach as high as 71.8% at merely 50°C. The recycled solvent system exhibited constant ability to separate polysaccharides from rice husk and wheat bran. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural characterization, formation mechanism and stability of curcumin in zein-lecithin composite nanoparticles fabricated by antisolvent co-precipitation.

PubMed

Dai, Lei; Sun, Cuixia; Li, Ruirui; Mao, Like; Liu, Fuguo; Gao, Yanxiang

2017-12-15

Curcumin (Cur) exhibits a range of bioactive properties, but its application is restrained due to its poor water solubility and sensitivity to environmental stresses. In this study, zein-lecithin composite nanoparticles were fabricated by antisolvent co-precipitation technique for delivery of Cur. The result showed that the encapsulation efficiency of Cur was significantly enhanced from 42.03% in zein nanoparticles to 99.83% in zein-lecithin composite nanoparticles. The Cur entrapped in the nanoparticles was in an amorphous state confirmed by differential scanning calorimetry and X-ray diffraction. Fourier transform infrared analysis revealed that hydrogen bonding, electrostatic interaction and hydrophobic attraction were the main interactions among zein, lecithin, and Cur. Compared with single zein and lecithin nanoparticles, zein-lecithin composite nanoparticles significantly improved the stability of Cur against thermal treatment, UV irradiation and high ionic strength. Therefore, zein-lecithin composite nanoparticles could be a potential delivery system for water-insoluble bioactive compounds with enhanced encapsulation efficiency and chemical stability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Maillard Conjugates on the Physical Stability of Zein Nanoparticles Prepared by Liquid Antisolvent Coprecipitation.

PubMed

Davidov-Pardo, Gabriel; Joye, Iris J; Espinal-Ruiz, Mauricio; McClements, David Julian

2015-09-30

Protein nanoparticles are often not very stable in a complex food matrix because they are primarily stabilized by electrostatic repulsion. In this study, we envisaged the stabilization of zein nanoparticles through Maillard conjugation reactions with polysaccharides of different molecular mass. Zein nanoparticles (0.5% w/v) containing resveratrol (0.025% w/v grape skin extract) were produced by liquid antisolvent precipitation and coated with Maillard conjugates (MC) of sodium caseinate and different molecular mass carbohydrates during particle production. Zein nanoparticles coated with conjugated polysaccharides of 2.8, 37, and 150 kDa had diameters of 198 ± 5, 176 ± 6, and 180 ± 3 nm, respectively. The encapsulation efficiency (∼83%) was not affected by conjugation, but the conjugates significantly improved particle stability against changes in pH (2.0-9.0), CaCl2 addition (up to 100 mM), and heat treatment (30-90 °C, 30 min). Zein nanoparticles coated by MC may therefore be suitable delivery systems for hydrophobic bioactive molecules in a wide range of commercial products.

Preparation and characterization of uniform nanosized cephradine by combination of reactive precipitation and liquid anti-solvent precipitation under high gravity environment.

PubMed

Zhong, Jie; Shen, Zhigang; Yang, Yan; Chen, Jianfeng

2005-09-14

In this work, a novel direct method, which was combined with reactive precipitation and liquid anti-solvent precipitation under high gravity environment, had been developed to prepare nanosized cephradine with narrow particle size distribution. Compared with commercial crude cephradine, the prepared cephradine showed a significant decrease in particle size, a significant increase in the specific surface area and shorter dissolving time when used for injection. The characteristic particle size was between 200-400 nm. The specific surface area increased from 2.95 to 10.87 m2/g after micronization. When the amount of L-arginin decreased from 0.25 to 0.18 g, the mixture of nanosized cephradine and L-arginine could still dissolve in 1 min. The X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) analysis indicated that the physical characteristics and molecular states remained unchanged after the recrystallization process. This method had potential application in industrial fields because of its low cost, efficient processing and the ease of scaling-up.

Supercritical antisolvent versus coevaporation: preparation and characterization of solid dispersions.

PubMed

Majerik, Viktor; Horváth, Géza; Szokonya, László; Charbit, Gérard; Badens, Elisabeth; Bosc, Nathalie; Teillaud, Eric

2007-09-01

The objective of this work was to improve the dissolution rate and aqueous solubility of oxeglitazar. Solid dispersions of oxeglitazar in PVP K17 (polyvinilpyrrolidone) and poloxamer 407 (polyoxyethylene-polyoxypropylene block copolymer) were prepared by supercritical antisolvent (SAS) and coevaporation (CoE) methods. Drug-carrier formulations were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography, UV/VIS spectroscopy and in vitro dissolution tests. The highest dissolution rate (nearly 3-fold higher than raw drug) was achieved by preparation of drug/PVP K17 coevaporate. Oxeglitazar/PVP K17 solid dispersions were stabilized by hydrogen bonding but contained higher amount of residual dichloromethane (DCM) than poloxamer 407 formulations regardless of the method of preparation. SAS prepared oxeglitazar/poloxamer 407 dissolved more than two times faster than raw drug. However, unlike PVP K17, poloxamer 407 did not form a single phase amorphous solid solution with oxeglitazar which has been manifested in higher degrees of crystallinity, too. Among the two techniques, evaluated in this work, conventional coevaporation resulted in higher amorphous content but SAS reduced residual solvent content more efficiently.

The effect of illumination on the formation of metal halide perovskite films

NASA Astrophysics Data System (ADS)

Ummadisingu, Amita; Steier, Ludmilla; Seo, Ji-Youn; Matsui, Taisuke; Abate, Antonio; Tress, Wolfgang; Grätzel, Michael

2017-04-01

Optimizing the morphology of metal halide perovskite films is an important way to improve the performance of solar cells when these materials are used as light harvesters, because film homogeneity is correlated with photovoltaic performance. Many device architectures and processing techniques have been explored with the aim of achieving high-performance devices, including single-step deposition, sequential deposition and anti-solvent methods. Earlier studies have looked at the influence of reaction conditions on film quality, such as the concentration of the reactants and the reaction temperature. However, the precise mechanism of the reaction and the main factors that govern it are poorly understood. The consequent lack of control is the main reason for the large variability observed in perovskite morphology and the related solar-cell performance. Here we show that light has a strong influence on the rate of perovskite formation and on film morphology in both of the main deposition methods currently used: sequential deposition and the anti-solvent method. We study the reaction of a metal halide (lead iodide) with an organic compound (methylammonium iodide) using confocal laser scanning fluorescence microscopy and scanning electron microscopy. The lead iodide crystallizes before the intercalation of methylammonium iodide commences, producing the methylammonium lead iodide perovskite. We find that the formation of perovskite via such a sequential deposition is much accelerated by light. The influence of light on morphology is reflected in a doubling of solar-cell efficiency. Conversely, using the anti-solvent method to form methyl ammonium lead iodide perovskite in a single step from the same starting materials, we find that the best photovoltaic performance is obtained when films are produced in the dark. The discovery of light-activated crystallization not only identifies a previously unknown source of variability in opto-electronic properties, but also opens up new ways of tuning morphology and structuring perovskites for various applications.

A facile green antisolvent approach to Cu2+-doped ZnO nanocrystals with visible-light-responsive photoactivities.

PubMed

Lu, Yi-Hsuan; Lin, Wei-Hao; Yang, Chao-Yao; Chiu, Yi-Hsuan; Pu, Ying-Chih; Lee, Min-Han; Tseng, Yuan-Chieh; Hsu, Yung-Jung

2014-08-07

An environmentally benign antisolvent method has been developed to prepare Cu(2+)-doped ZnO nanocrystals with controllable dopant concentrations. A room temperature ionic liquid, known as a deep eutectic solvent (DES), was used as the solvent to dissolve ZnO powders. Upon the introduction of the ZnO-containing DES into a bad solvent which shows no solvation to ZnO, ZnO was precipitated and grown due to the dramatic decrease of solubility. By adding Cu(2+) ions to the bad solvent, the growth of ZnO from the antisolvent process was accompanied by Cu(2+) introduction, resulting in the formation of Cu(2+)-doped ZnO nanocrystals. The as-prepared Cu(2+)-doped ZnO showed an additional absorption band in the visible range (400-800 nm), which conduced to an improvement in the overall photon harvesting efficiency. Time-resolved photoluminescence spectra, together with the photovoltage information, suggested that the doped Cu(2+) may otherwise trap photoexcited electrons during the charge transfer process, inevitably depressing the photoconversion efficiency. The photoactivity of Cu(2+)-doped ZnO nanocrystals for photoelectrochemical water oxidation was effectively enhanced in the visible region, which achieved the highest at 2.0 at% of Cu(2+). A further increase in the Cu(2+) concentration however led to a decrease in the photocatalytic performance, which was ascribed to the significant carrier trapping caused by the increased states given by excessive Cu(2+). The photocurrent action spectra illustrated that the enhanced photoactivity of the Cu(2+)-doped ZnO nanocrystals was mainly due to the improved visible photon harvesting achieved by Cu(2+) doping. These results may facilitate the use of transition metal ion-doped ZnO in other photoconversion applications, such as ZnO based dye-sensitized solar cells and magnetism-assisted photocatalytic systems.

Applications of supercritical fluids to enhance the dissolution behaviors of Furosemide by generation of microparticles and solid dispersions.

PubMed

De Zordi, Nicola; Moneghini, Mariarosa; Kikic, Ireneo; Grassi, Mario; Del Rio Castillo, Antonio Esau; Solinas, Dario; Bolger, Michael B

2012-05-01

The 'classical' loop diuretic drug Furosemide has been used as a model compound to investigate the possibility of enhancing the dissolution rate of poorly water-soluble drugs using supercritical anti-solvent techniques (SASs). In the present study we report upon the in vitro bioavailability improvement of Furosemide through particle size reduction as well as formation of solid dispersions (SDs) using the hydrophilic polymer Crospovidone. Supercritical carbon dioxide was used as the processing medium for these experiments. In order to successfully design a CO(2) antisolvent process, preliminary studies of Furosemide microparticles generation were conducted using Peng Robinson's Equation of State. These preliminary studies indicated using acetone as a solvent with pressures of 100 and 200bar and a temperature of 313K would yield optimum results. These operative conditions were then adopted for the SDs. Micronization by means of SAS at 200bar resulted in a significant reduction of crystallites, particle size, as well as improved dissolution rate in comparison with untreated drug. Furosemide recrystallized by SAS at 100bar and using traditional solvent evaporation. Moreover, changes in polymorphic form were observed in the 200bar samples. The physicochemical characterization of Furosemide:crospovidone SDs (1:1 and 1:2 w/w, respectively) generated by SAS revealed the presence of the drug amorphously dispersed in the 1:2 w/w sample at 100bar still remaining stable after 6months. This sample exhibits the best in vitro dissolution performance in the simulated gastric fluid (pH 1.2), in comparison with the same SD obtained by traditional method. No interactions between drug and polymer were observed. These results, together with the presence of the selected carrier, confirm that the use of Supercritical fluids antisolvent technology is a valid mean to increase the dissolution rate of poorly soluble drugs. Theoretical in vivo-in vitro relation was predicted by means of a pharmacokinetics mathematical model. Copyright © 2012 Elsevier B.V. All rights reserved.

ROI-Based On-Board Compression for Hyperspectral Remote Sensing Images on GPU.

PubMed

Giordano, Rossella; Guccione, Pietro

2017-05-19

In recent years, hyperspectral sensors for Earth remote sensing have become very popular. Such systems are able to provide the user with images having both spectral and spatial information. The current hyperspectral spaceborne sensors are able to capture large areas with increased spatial and spectral resolution. For this reason, the volume of acquired data needs to be reduced on board in order to avoid a low orbital duty cycle due to limited storage space. Recently, literature has focused the attention on efficient ways for on-board data compression. This topic is a challenging task due to the difficult environment (outer space) and due to the limited time, power and computing resources. Often, the hardware properties of Graphic Processing Units (GPU) have been adopted to reduce the processing time using parallel computing. The current work proposes a framework for on-board operation on a GPU, using NVIDIA's CUDA (Compute Unified Device Architecture) architecture. The algorithm aims at performing on-board compression using the target's related strategy. In detail, the main operations are: the automatic recognition of land cover types or detection of events in near real time in regions of interest (this is a user related choice) with an unsupervised classifier; the compression of specific regions with space-variant different bit rates including Principal Component Analysis (PCA), wavelet and arithmetic coding; and data volume management to the Ground Station. Experiments are provided using a real dataset taken from an AVIRIS (Airborne Visible/Infrared Imaging Spectrometer) airborne sensor in a harbor area.

Rotationally Invariant Image Representation for Viewing Direction Classification in Cryo-EM

PubMed Central

Zhao, Zhizhen; Singer, Amit

2014-01-01

We introduce a new rotationally invariant viewing angle classification method for identifying, among a large number of cryo-EM projection images, similar views without prior knowledge of the molecule. Our rotationally invariant features are based on the bispectrum. Each image is denoised and compressed using steerable principal component analysis (PCA) such that rotating an image is equivalent to phase shifting the expansion coefficients. Thus we are able to extend the theory of bispectrum of 1D periodic signals to 2D images. The randomized PCA algorithm is then used to efficiently reduce the dimensionality of the bispectrum coefficients, enabling fast computation of the similarity between any pair of images. The nearest neighbors provide an initial classification of similar viewing angles. In this way, rotational alignment is only performed for images with their nearest neighbors. The initial nearest neighbor classification and alignment are further improved by a new classification method called vector diffusion maps. Our pipeline for viewing angle classification and alignment is experimentally shown to be faster and more accurate than reference-free alignment with rotationally invariant K-means clustering, MSA/MRA 2D classification, and their modern approximations. PMID:24631969

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

PubMed Central

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-01-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant. PMID:28368030

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation.

PubMed

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-03

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

NASA Astrophysics Data System (ADS)

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

The Effect of Converting to a U.S. Hydrogen Fuel Cell Vehicle Fleet on Emissions and Energy Use

NASA Astrophysics Data System (ADS)

Colella, W. G.; Jacobson, M. Z.; Golden, D. M.

2004-12-01

This study analyzes the potential change in emissions and energy use from replacing fossil-fuel based vehicles with hydrogen fuel cell vehicles. This study examines three different hydrogen production scenarios to determine their resultant emissions and energy usage: hydrogen produced via 1) steam reforming of methane, 2) coal gasification, or 3) wind electrolysis. The atmospheric model simulations require two primary sets of data: the actual emissions associated with hydrogen fuel production and use, and the corresponding reduction in emissions associated with reducing fossil fuel use. The net change in emissions is derived using 1) the U.S. EPA's National Emission Inventory (NEI) that incorporates several hundred categories of on-road vehicles and 2) a Process Chain Analysis (PCA) for the different hydrogen production scenarios. NEI: The quantity of hydrogen-related emission is ultimately a function of the projected hydrogen consumption in on-road vehicles. Data for hydrogen consumption from on-road vehicles was derived from the number of miles driven in each U.S. county based on 1999 NEI data, the average fleet mileage of all on-road vehicles, the average gasoline vehicle efficiency, and the efficiency of advanced 2004 fuel cell vehicles. PCA: PCA involves energy and mass balance calculations around the fuel extraction, production, transport, storage, and delivery processes. PCA was used to examine three different hydrogen production scenarios: In the first scenario, hydrogen is derived from natural gas, which is extracted from gas fields, stored, chemically processed, and transmitted through pipelines to distributed fuel processing units. The fuel processing units, situated in similar locations as gasoline refueling stations, convert natural gas to hydrogen via a combination of steam reforming and fuel oxidation. Purified hydrogen is compressed for use onboard fuel cell vehicles. In the second scenario, hydrogen is derived from coal, which is extracted from mines and chemically processed into a hydrogen rich gas. Hydrogen is transmitted through pipelines to refueling stations. In the third scenario, hydrogen is derived via electrolysis powered by wind-generated electricity that has been transmitted across the country to electrolyzers at distributed hydrogen refueling stations. If hydrogen is produced via the first scenario, total annual U.S. production of carbon dioxide (CO2) could be expected to decrease by approximately 900 million metric tons, or 16 percent of annual U.S. CO2 production from all anthropogenic sources. Under this scenario, compared with the conventional vehicle fleet, a fuel cell vehicle fleet would produce some additional CO2 emissions due to the electric power required for the compression of hydrogen, but less CO2 emissions on the road during vehicle operation. This scenario results in an additional methane leakage of approximately one million metric tons per year, or 4 percent of annual U.S. methane emissions from all anthropogenic sources.

Fabrication and evaluation of valsartan–polymer– surfactant composite nanoparticles by using the supercritical antisolvent process

PubMed Central

Kim, Min-Soo; Baek, In-hwan

2014-01-01

The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan–hydroxypropyl methylcellulose–poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan–hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability. PMID:25404856

Recrystallization of puerarin using the supercritical fluid antisolvent process

NASA Astrophysics Data System (ADS)

Li, Y.; Yang, D. J.; Zhou, W.; Chen, S. B.; Chen, S. L.

2012-02-01

The purpose of this study was to investigate the influence of supercritical fluid (SCF) processing on the polymorphism of puerarin (Pur), a poorly soluble drug. The gas anti-solvent (GAS) technique was used to crystalize the drug in different conditions. The samples were analyzed by scanning electron microscopy and laser granulometry for changes in the habitus and particle size. The solid state was studied by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and melting point determination. Finally, the dissolution and solubility tests were carried out. It was attested that compared with the commercial Pur in Crystal form I, at the optimum and most of conditions, Pur changed into crystal form II with more orderly and pure appearances. At the concentration of 60 mg/ml and at the solvent of methanol, two other new crystal forms (named form III and form IV) were produced. It was demonstrated that the particles mean diameter, size distribution and morphology can be strongly controlled through the manipulation of the process parameters and more importantly, Pur in the new crystal forms, which were not reported before with better physico-chemical properties could be produced by recrystalization by GAS.

Principal component analysis-based anatomical motion models for use in adaptive radiation therapy of head and neck cancer patients

NASA Astrophysics Data System (ADS)

Chetvertkov, Mikhail A.

Purpose: To develop standard and regularized principal component analysis (PCA) models of anatomical changes from daily cone beam CTs (CBCTs) of head and neck (H&N) patients, assess their potential use in adaptive radiation therapy (ART), and to extract quantitative information for treatment response assessment. Methods: Planning CT (pCT) images of H&N patients were artificially deformed to create "digital phantom" images, which modeled systematic anatomical changes during Radiation Therapy (RT). Artificial deformations closely mirrored patients' actual deformations, and were interpolated to generate 35 synthetic CBCTs, representing evolving anatomy over 35 fractions. Deformation vector fields (DVFs) were acquired between pCT and synthetic CBCTs (i.e., digital phantoms), and between pCT and clinical CBCTs. Patient-specific standard PCA (SPCA) and regularized PCA (RPCA) models were built from these synthetic and clinical DVF sets. Eigenvectors, or eigenDVFs (EDVFs), having the largest eigenvalues were hypothesized to capture the major anatomical deformations during treatment. Modeled anatomies were used to assess the dose deviations with respect to the planned dose distribution. Results: PCA models achieve variable results, depending on the size and location of anatomical change. Random changes prevent or degrade SPCA's ability to detect underlying systematic change. RPCA is able to detect smaller systematic changes against the background of random fraction-to-fraction changes, and is therefore more successful than SPCA at capturing systematic changes early in treatment. SPCA models were less successful at modeling systematic changes in clinical patient images, which contain a wider range of random motion than synthetic CBCTs, while the regularized approach was able to extract major modes of motion. For dose assessment it has been shown that the modeled dose distribution was different from the planned dose for the parotid glands due to their shrinkage and shift into the higher dose volumes during the radiotherapy course. Modeled DVHs still underestimated the effect of parotid shrinkage due to the large compression factor (CF) used to acquire DVFs. Conclusion: Leading EDVFs from both PCA approaches have the potential to capture systematic anatomical changes during H&N radiotherapy when systematic changes are large enough with respect to random fraction-to-fraction changes. In all cases the RPCA approach appears to be more reliable than SPCA at capturing systematic changes, enabling dosimetric consequences to be projected to the future treatment fractions based on trends established early in a treatment course, or, potentially, based on population models. This work showed that PCA has a potential in identifying the major mode of anatomical changes during the radiotherapy course and subsequent use of this information in future dose predictions is feasible. Use of smaller CF values for DVFs is preferred, otherwise anatomical motion will be underestimated.

Evaluation of non-negative matrix factorization of grey matter in age prediction.

PubMed

Varikuti, Deepthi P; Genon, Sarah; Sotiras, Aristeidis; Schwender, Holger; Hoffstaedter, Felix; Patil, Kaustubh R; Jockwitz, Christiane; Caspers, Svenja; Moebus, Susanne; Amunts, Katrin; Davatzikos, Christos; Eickhoff, Simon B

2018-06-01

The relationship between grey matter volume (GMV) patterns and age can be captured by multivariate pattern analysis, allowing prediction of individuals' age based on structural imaging. Raw data, voxel-wise GMV and non-sparse factorization (with Principal Component Analysis, PCA) show good performance but do not promote relatively localized brain components for post-hoc examinations. Here we evaluated a non-negative matrix factorization (NNMF) approach to provide a reduced, but also interpretable representation of GMV data in age prediction frameworks in healthy and clinical populations. This examination was performed using three datasets: a multi-site cohort of life-span healthy adults, a single site cohort of older adults and clinical samples from the ADNI dataset with healthy subjects, participants with Mild Cognitive Impairment and patients with Alzheimer's disease (AD) subsamples. T1-weighted images were preprocessed with VBM8 standard settings to compute GMV values after normalization, segmentation and modulation for non-linear transformations only. Non-negative matrix factorization was computed on the GM voxel-wise values for a range of granularities (50-690 components) and LASSO (Least Absolute Shrinkage and Selection Operator) regression were used for age prediction. First, we compared the performance of our data compression procedure (i.e., NNMF) to various other approaches (i.e., uncompressed VBM data, PCA-based factorization and parcellation-based compression). We then investigated the impact of the granularity on the accuracy of age prediction, as well as the transferability of the factorization and model generalization across datasets. We finally validated our framework by examining age prediction in ADNI samples. Our results showed that our framework favorably compares with other approaches. They also demonstrated that the NNMF based factorization derived from one dataset could be efficiently applied to compress VBM data of another dataset and that granularities between 300 and 500 components give an optimal representation for age prediction. In addition to the good performance in healthy subjects our framework provided relatively localized brain regions as the features contributing to the prediction, thereby offering further insights into structural changes due to brain aging. Finally, our validation in clinical populations showed that our framework is sensitive to deviance from normal structural variations in pathological aging. Copyright © 2018 Elsevier Inc. All rights reserved.

Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia.

PubMed

Morote, Juan; Rigau, Marina; Garcia, Marta; Mir, Carmen; Ballesteros, Carlos; Planas, Jacques; Raventós, Carles X; Placer, José; de Torres, Inés M; Reventós, Jaume; Doll, Andreas

2010-12-01

An ideal marker for the early detection of prostate cancer (PCa) should also differentiate between men with isolated high grade prostatic intraepithelial neoplasia (HGPIN) and those with PCa. Prostate Cancer Gene 3 (PCA3) is a highly specific PCa gene and its score, in relation to the PSA gene in post-prostate massage urine (PMU-PCA3), seems to be useful in ruling out PCa, especially after a negative prostate biopsy. Because PCA3 is also expressed in the HGPIN lesion, the aim of this study was to determine the efficacy of PMU-PCA3 scores for ruling out PCa in men with previous HGPIN. The PMU-PCA3 score was assessed by quantitative PCR (multiplex research assay) in 244 men subjected to prostate biopsy: 64 men with an isolated HGPIN (no cancer detected after two or more repeated biopsies), 83 men with PCa and 97 men with benign pathology findings (BP: no PCa, HGPIN or ASAP). The median PMU-PCA3 score was 1.56 in men with BP, 2.01 in men with HGPIN (p = 0.128) and 9.06 in men with PCa (p = 0.008). The AUC in the ROC analysis was 0.705 in the subset of men with BP and PCa, while it decreased to 0.629 when only men with isolated HGPIN and PCa were included in the analysis. Fixing the sensitivity of the PMU-PCA3 score at 90%, its specificity was 79% in men with BP and 69% in men with isolated HGPIN. The efficacy of the PMU-PCA3 score to rule out PCa in men with HGPIN is lower than in men with BP.

Characterization of the lateral distribution of fluorescent lipid in binary-constituent lipid monolayers by principal component analysis.

PubMed

Sugár, István P; Zhai, Xiuhong; Boldyrev, Ivan A; Molotkovsky, Julian G; Brockman, Howard L; Brown, Rhoderick E

2010-01-01

Lipid lateral organization in binary-constituent monolayers consisting of fluorescent and nonfluorescent lipids has been investigated by acquiring multiple emission spectra during measurement of each force-area isotherm. The emission spectra reflect BODIPY-labeled lipid surface concentration and lateral mixing with different nonfluorescent lipid species. Using principal component analysis (PCA) each spectrum could be approximated as the linear combination of only two principal vectors. One point on a plane could be associated with each spectrum, where the coordinates of the point are the coefficients of the linear combination. Points belonging to the same lipid constituents and experimental conditions form a curve on the plane, where each point belongs to a different mole fraction. The location and shape of the curve reflects the lateral organization of the fluorescent lipid mixed with a specific nonfluorescent lipid. The method provides massive data compression that preserves and emphasizes key information pertaining to lipid distribution in different lipid monolayer phases. Collectively, the capacity of PCA for handling large spectral data sets, the nanoscale resolution afforded by the fluorescence signal, and the inherent versatility of monolayers for characterization of lipid lateral interactions enable significantly enhanced resolution of lipid lateral organizational changes induced by different lipid compositions.

Fast dictionary-based reconstruction for diffusion spectrum imaging.

PubMed

Bilgic, Berkin; Chatnuntawech, Itthi; Setsompop, Kawin; Cauley, Stephen F; Yendiki, Anastasia; Wald, Lawrence L; Adalsteinsson, Elfar

2013-11-01

Diffusion spectrum imaging reveals detailed local diffusion properties at the expense of substantially long imaging times. It is possible to accelerate acquisition by undersampling in q-space, followed by image reconstruction that exploits prior knowledge on the diffusion probability density functions (pdfs). Previously proposed methods impose this prior in the form of sparsity under wavelet and total variation transforms, or under adaptive dictionaries that are trained on example datasets to maximize the sparsity of the representation. These compressed sensing (CS) methods require full-brain processing times on the order of hours using MATLAB running on a workstation. This work presents two dictionary-based reconstruction techniques that use analytical solutions, and are two orders of magnitude faster than the previously proposed dictionary-based CS approach. The first method generates a dictionary from the training data using principal component analysis (PCA), and performs the reconstruction in the PCA space. The second proposed method applies reconstruction using pseudoinverse with Tikhonov regularization with respect to a dictionary. This dictionary can either be obtained using the K-SVD algorithm, or it can simply be the training dataset of pdfs without any training. All of the proposed methods achieve reconstruction times on the order of seconds per imaging slice, and have reconstruction quality comparable to that of dictionary-based CS algorithm.

Fast Dictionary-Based Reconstruction for Diffusion Spectrum Imaging

PubMed Central

Bilgic, Berkin; Chatnuntawech, Itthi; Setsompop, Kawin; Cauley, Stephen F.; Yendiki, Anastasia; Wald, Lawrence L.; Adalsteinsson, Elfar

2015-01-01

Diffusion Spectrum Imaging (DSI) reveals detailed local diffusion properties at the expense of substantially long imaging times. It is possible to accelerate acquisition by undersampling in q-space, followed by image reconstruction that exploits prior knowledge on the diffusion probability density functions (pdfs). Previously proposed methods impose this prior in the form of sparsity under wavelet and total variation (TV) transforms, or under adaptive dictionaries that are trained on example datasets to maximize the sparsity of the representation. These compressed sensing (CS) methods require full-brain processing times on the order of hours using Matlab running on a workstation. This work presents two dictionary-based reconstruction techniques that use analytical solutions, and are two orders of magnitude faster than the previously proposed dictionary-based CS approach. The first method generates a dictionary from the training data using Principal Component Analysis (PCA), and performs the reconstruction in the PCA space. The second proposed method applies reconstruction using pseudoinverse with Tikhonov regularization with respect to a dictionary. This dictionary can either be obtained using the K-SVD algorithm, or it can simply be the training dataset of pdfs without any training. All of the proposed methods achieve reconstruction times on the order of seconds per imaging slice, and have reconstruction quality comparable to that of dictionary-based CS algorithm. PMID:23846466

[Research on discrimination of cabbage and weeds based on visible and near-infrared spectrum analysis].

PubMed

Zu, Qin; Zhao, Chun-Jiang; Deng, Wei; Wang, Xiu

2013-05-01

The automatic identification of weeds forms the basis for precision spraying of crops infest. The canopy spectral reflectance within the 350-2 500 nm band of two strains of cabbages and five kinds of weeds such as barnyard grass, setaria, crabgrass, goosegrass and pigweed was acquired by ASD spectrometer. According to the spectral curve characteristics, the data in different bands were compressed with different levels to improve the operation efficiency. Firstly, the spectrum was denoised in accordance with the different order of multiple scattering correction (MSC) method and Savitzky-Golay (SG) convolution smoothing method set by different parameters, then the model was built by combining the principal component analysis (PCA) method to extract principal components, finally all kinds of plants were classified by using the soft independent modeling of class analogy (SIMCA) taxonomy and the classification results were compared. The tests results indicate that after the pretreatment of the spectral data with the method of the combination of MSC and SG set with 3rd order, 5th degree polynomial, 21 smoothing points, and the top 10 principal components extraction using PCA as a classification model input variable, 100% correct classification rate was achieved, and it is able to identify cabbage and several kinds of common weeds quickly and nondestructively.

Experimental investigation and oral bioavailability enhancement of nano-sized curcumin by using supercritical anti-solvent process.

PubMed

Anwar, Mohammed; Ahmad, Iqbal; Warsi, Musarrat H; Mohapatra, Sharmistha; Ahmad, Niyaz; Akhter, Sohail; Ali, Asgar; Ahmad, Farhan J

2015-10-01

The biomedical applications of curcumin (CUR) are limited due to its poor oral bioavailability. In this work, CUR nanoparticles were successfully prepared by combining the supercritical anti-solvent (SAS) process with Tween 80 as a solubilizing agent and permeation enhancer. Different processing parameters that can govern the mean particle size and size distribution of nanoparticles were well investigated by manipulating the types of solvents, mixing vessel pressure, mixing vessel temperature, CO2 flow rate, solution flow rate and solution concentration. Solid state characterization was done by Fourier Transform infrared spectroscopy, differential scanning calorimetry, dynamic light scattering, scanning electron microscopy, and powder X-ray diffraction study. Solubility and dissolution profile of SAS-processed CUR were found to be significantly increased in comparison with native CUR. Further, a validated ultra-performance liquid chromatographic method with quadrupole-time of flight-mass spectrometry was developed to investigate the pharmacokinetic parameters after a single oral dose (100mg/kg) administration of CUR (before/after SAS-processed) in male Wistar rats. From the plasma concentration vs. time profile graph, oral bioavailability of SAS-processed CUR was found to be increased approximately 11.6-fold (p<0.001) as compared to native CUR. Copyright © 2015 Elsevier B.V. All rights reserved.

Operation condition for continuous anti-solvent crystallization of CBZ-SAC cocrystal considering deposition risk of undesired crystals

NASA Astrophysics Data System (ADS)

Nishimaru, Momoko; Nakasa, Miku; Kudo, Shoji; Takiyama, Hiroshi

2017-07-01

Crystallization operation of cocrystal production has deposition risk of undesired crystals. Simultaneously, continuous manufacturing processes are focused on. In this study, conditions for continuous cocrystallization considering risk reduction of undesired crystals deposition were investigated on the view point of thermodynamics and kinetics. The anti-solvent cocrystallization was carried out in four-component system of carbamazepine, saccharin, methanol and water. From the preliminary batch experiment, the relationships among undesired crystal deposition, solution composition decided by mixing ratio of solutions, and residence time for the crystals were considered, and then the conditions of continuous experiment were decided. Under these conditions, the continuous experiment was carried out. The XRD patterns of obtained crystals in the continuous experiment showed that desired cocrystals were obtained without undesired crystals. This experimental result was evaluated by using multi-component phase diagrams from the view point of the operation point's movement. From the evaluation, it was found that there is a certain operation condition which the operation point is fixed with time in the specific domain without the deposition risk of undesired single component crystals. It means the possibility of continuous production of cocrystals without deposition risk of undesired crystals was confirmed by using multi-component phase diagrams.

Switchable ionic liquids as delignification solvents for lignocellulosic materials.

PubMed

Anugwom, Ikenna; Eta, Valerie; Virtanen, Pasi; Mäki-Arvela, Päivi; Hedenström, Mattias; Hummel, Michael; Sixta, Herbert; Mikkola, Jyri-Pekka

2014-04-01

The transformation of lignocellulosic materials into potentially valuable resources is compromised by their complicated structure. Consequently, new economical and feasible conversion/fractionation techniques that render value-added products are intensely investigated. Herein an unorthodox and feasible fractionation method of birch chips (B. pendula) using a switchable ionic liquid (SIL) derived from an alkanol amine (monoethanol amine, MEA) and an organic super base (1,8-diazabicyclo-[5.4.0]-undec-7-ene, DBU) with two different trigger acid gases (CO2 and SO2 ) is studied. After SIL treatment, the dissolved fractions were selectively separated by a step-wise method using an antisolvent to induce precipitation. The SIL was recycled after concentration and evaporation of anti-solvent. The composition of undissolved wood after MEA-SO2 -SIL treatment resulted in 80 wt % cellulose, 10 wt % hemicelluloses, and 3 wt % lignin, whereas MEA-CO2 -SIL treatment resulted in 66 wt % cellulose, 12 wt % hemicelluloses and 11 wt % lignin. Thus, the MEA-SO2 -SIL proved more efficient than the MEA-CO2 -SIL, and a better solvent for lignin removal. All fractions were analyzed by gas chromatography (GC), Fourier transform infrared spectroscopy (FT-IR), (13) C nuclear magnetic resonance spectroscopy (NMR) and Gel permeation chromatography (GPC). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of particle size on oral absorption of carvedilol nanosuspensions: in vitro and in vivo evaluation

PubMed Central

Liu, Dandan; Pan, Hao; He, Fengwei; Wang, Xiaoyu; Li, Jinyu; Yang, Xinggang; Pan, Weisan

2015-01-01

The purpose of this work was to explore the particle size reduction effect of carvedilol on dissolution and absorption. Three suspensions containing different sized particles were prepared by antisolvent precipitation method or in combination with an ultrasonication process. The suspensions were characterized for particle size, surface morphology, and crystalline state. The crystalline form of carvedilol was changed into amorphous form after antisolvent precipitation. The dissolution rate of carvedilol was significantly accelerated by a reduction in particle size. The intestinal absorption of carvedilol nanosuspensions was greatly improved in comparison with microsuspensions and solution in the in situ single-pass perfusion experiment. The in vivo evaluation demonstrated that carvedilol nanosuspensions and microsuspensions exhibited markedly increased Cmax (2.09- and 1.48-fold) and AUC0−t (2.11- and 1.51-fold), and decreased Tmax (0.34- and 0.48-fold) in contrast with carvedilol coarse suspensions. Moreover, carvedilol nanosuspensions showed good biocompatibility with the rat gastric mucosa in in vivo gastrointestinal irritation test. The entire results implicated that the dissolution rate and the oral absorption of carvedilol were significantly affected by the particle size. Particle size reduction to form nanosized particles was found to be an efficient method for improving the oral bioavailability of carvedilol. PMID:26508852

Preparation, characterization and in vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent (SAS) process.

PubMed

Kim, Min-Soo; Jin, Shun-Ji; Kim, Jeong-Soo; Park, Hee Jun; Song, Ha-Seung; Neubert, Reinhard H H; Hwang, Sung-Joo

2008-06-01

In this work, amorphous atorvastatin calcium nanoparticles were successfully prepared using the supercritical antisolvent (SAS) process. The effect of process variables on particle size and distribution of atorvastatin calcium during particle formation was investigated. Solid state characterization, solubility, intrinsic dissolution, powder dissolution studies and pharmacokinetic study in rats were performed. Spherical particles with mean particle size ranging between 152 and 863 nm were obtained by varying process parameters such as precipitation vessel pressure and temperature, drug solution concentration and feed rate ratio of CO2/drug solution. XRD, TGA, FT-IR, FT-Raman, NMR and HPLC analysis indicated that atorvastatin calcium existed as anhydrous amorphous form and no degradation occurred after SAS process. When compared with crystalline form (unprocessed drug), amorphous atorvastatin calcium nanoparticles were of better performance in solubility and intrinsic dissolution rate, resulting in higher solubility and faster dissolution rate. In addition, intrinsic dissolution rate showed a good correlation with the solubility. The dissolution rates of amorphous atorvastatin calcium nanoparticles were highly increased in comparison with unprocessed drug by the enhancement of intrinsic dissolution rate and the reduction of particle size resulting in an increased specific surface area. The absorption of atorvastatin calcium after oral administration of amorphous atorvastatin calcium nanoparticles to rats was markedly increased.

Fundamental Insights into the Dissolution and Precipitation of Cellulosic Biomass from Ionic Liquid Mixtures

NASA Astrophysics Data System (ADS)

Minnick, David L.

Lignocellulose is the most abundant biopolymer on earth making it a promising feedstock for the production of renewable chemicals and fuels. However, utilization of biomass remains a challenge as recalcitrance of cellulose and hemicellulose hinder separation and conversion of these carbohydrates. For instance, the complex inter- and intra- molecular hydrogen bonding network of cellulose renders it insoluble in nearly all aqueous and organic solvents. Alternatively, select ionic liquids (ILs) dissolve significant quantities. Through an ionic liquid mediated dissolution and precipitation process cellulose crystallinity is significantly reduced consequently enhancing subsequent chemical and biochemical reaction processes. Therefore, understanding the thermodynamics of ionic liquid - cellulose mixtures is imperative to developing an IL based biomass processing system. This dissertation illustrates solid-liquid phase equilibrium results for the dissolution and precipitation of cellulose in various IL/cosolvent, IL/antisolvent, and IL/mixed solvent systems with the ionic liquid 1-ethyl-3-methylimidazolium diethyl phosphate ([EMIm][DEP]). Molecular interactions between the ionic liquid, organic solvents, and cellulose are assessed by spectroscopic techniques including Kamlet-Taft solvatochromic analysis, FTIR, and NMR. Additionally, this dissertation discusses how preferential solvation of the IL cation and anion by co- and anti-solvents impact the ability of IL ions to interact with cellulose thus affecting the cellulose dissolution capacity of the various IL-solvent mixtures.

Size-controlled fabrication of zein nano/microparticles by modified anti-solvent precipitation with/without sodium caseinate

PubMed Central

Li, Feng; Chen, Yan; Liu, Shubo; Qi, Jian; Wang, Weiying; Wang, Chenhua; Zhong, Ruiyue; Chen, Zhijun; Li, Xiaoming; Guan, Yuanzhou; Kong, Wei; Zhang, Yong

2017-01-01

Zein-based nano/microparticles have been demonstrated to be promising carrier systems for both the food industry and biomedical applications. However, the fabrication of size-controlled zein particles has been a challenging issue. In this study, a modified anti-solvent precipitation method was developed, and the effects of various factors, such as mixing method, solvent/anti-solvent ratio, temperature, zein concentrations and the presence of sodium caseinate (SC) on properties of zein particles were investigated. Evidence is presented that, among the previously mentioned factors, the mixing method, especially mixing rate, could be used as an effective parameter to control the size of zein particles without changing other parameters. Moreover, through fine-tuning the mixing rate together with zein concentration, particles with sizes ranging from nanometers to micrometers and low polydispersity index values could be easily obtained. Based on the size-controlled fabrication method, SC-coated zein nanoparticles could also be obtained in a size-controlled manner by incubation of the coating material with the already-formed zein particles. The resultant nanoparticles showed better performance in both drug loading and controlled release, compared with zein/SC hybrid nanoparticles fabricated by adding aqueous ethanol solution to SC solution. The possible mechanisms of the nanoprecipitation process and self-assembly formation of these nanoparticles are discussed. PMID:29184408

Size-controlled fabrication of zein nano/microparticles by modified anti-solvent precipitation with/without sodium caseinate.

PubMed

Li, Feng; Chen, Yan; Liu, Shubo; Qi, Jian; Wang, Weiying; Wang, Chenhua; Zhong, Ruiyue; Chen, Zhijun; Li, Xiaoming; Guan, Yuanzhou; Kong, Wei; Zhang, Yong

2017-01-01

Zein-based nano/microparticles have been demonstrated to be promising carrier systems for both the food industry and biomedical applications. However, the fabrication of size-controlled zein particles has been a challenging issue. In this study, a modified anti-solvent precipitation method was developed, and the effects of various factors, such as mixing method, solvent/anti-solvent ratio, temperature, zein concentrations and the presence of sodium caseinate (SC) on properties of zein particles were investigated. Evidence is presented that, among the previously mentioned factors, the mixing method, especially mixing rate, could be used as an effective parameter to control the size of zein particles without changing other parameters. Moreover, through fine-tuning the mixing rate together with zein concentration, particles with sizes ranging from nanometers to micrometers and low polydispersity index values could be easily obtained. Based on the size-controlled fabrication method, SC-coated zein nanoparticles could also be obtained in a size-controlled manner by incubation of the coating material with the already-formed zein particles. The resultant nanoparticles showed better performance in both drug loading and controlled release, compared with zein/SC hybrid nanoparticles fabricated by adding aqueous ethanol solution to SC solution. The possible mechanisms of the nanoprecipitation process and self-assembly formation of these nanoparticles are discussed.

Process parameters and morphology in puerarin, phospholipids and their complex microparticles generation by supercritical antisolvent precipitation.

PubMed

Li, Ying; Yang, Da-Jian; Chen, Shi-Lin; Chen, Si-Bao; Chan, Albert Sun-Chi

2008-07-09

The aim of the study was to develop and evaluate a new method for the production of puerarin phospholipids complex (PPC) microparticles. The advanced particle formation method, solution enhanced dispersion by supercritical fluids (SEDS), was used for the preparation of puerarin (Pur), phospholipids (PC) and their complex particles for the first time. Evaluation of the processing variables on PPC particle characteristics was also conducted. The processing variables included temperature, pressure, solution concentration, the flow rate of supercritical carbon dioxide (SC-CO2) and the relative flow rate of drug solution to CO2. The morphology, particle size and size distribution of the particles were determined. Meanwhile Pur and phospholipids were separately prepared by gas antisolvent precipitation (GAS) method and solid characterization of particles by the two supercritical methods was also compared. Pur formed by GAS was more orderly, purer crystal, whereas amorphous Pur particles between 0.5 and 1microm were formed by SEDS. The complex was successfully obtained by SEDS exhibiting amorphous, partially agglomerated spheres comprised of particles sized only about 1microm. SEDS method may be useful for the processing of other pharmaceutical preparations besides phospholipids complex particles. Furthermore adopting a GAS process to recrystallize pharmaceuticals will provide a highly versatile methodology to generate new polymorphs of drugs in addition to conventional techniques.

Single-step preparation and deagglomeration of itraconazole microflakes by supercritical antisolvent method for dissolution enhancement.

PubMed

Sathigari, Sateesh Kumar; Ober, Courtney A; Sanganwar, Ganesh P; Gupta, Ram B; Babu, R Jayachandra

2011-07-01

Itraconazole (ITZ) microflakes were produced by supercritical antisolvent (SAS) method and simultaneously mixed with pharmaceutical excipients in a single step to prevent drug agglomeration. Simultaneous ITZ particle formation and mixing with fast-flo lactose (FFL) was performed in a high-pressure stirred vessel at 116 bar and 40 °C by the SAS-drug excipient mixing (SAS-DEM) method. The effects of stabilizers, such as sodium dodecyl sulfate and poloxamer 407 (PLX), on particle formation and drug dissolution were studied. Drug-excipient formulations were characterized for surface morphology, crystallinity, drug-excipient interactions, drug content uniformity, and drug dissolution rate. Mixture of drug microflakes and FFL formed by the SAS-DEM process shows that the process was successful in overcoming drug-drug agglomeration. PLX produced crystalline drug flakes in loose agglomerates with superior dissolution and flow properties even at higher drug loadings. Characterization studies confirmed the crystallinity of the drug and absence of chemical interactions during the SAS process. The dissolution of ITZ was substantially higher due to SAS and SAS-DEM processes; this improvement can be attributed to the microflake particle structures, effective deagglomeration, and wetting of the drug flakes with the excipients. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

Preparation of coenzyme Q10 liposomes using supercritical anti-solvent technique.

PubMed

Xia, Fei; Jin, Heyang; Zhao, Yaping; Guo, Xinqiu

2012-01-01

Coenzyme Q(10) (CoQ(10)) proliposomes were prepared using the supercritical anti-solvent (SAS) technique to encapsulate CoQ(10). The mixture of cholesterol and soya bean phosphatidylcholine (PC) was chosen as wall materials. The effects of operation conditions (temperature, pressure and components) on the recovery of CoQ(10) and the CoQ(10) loading in CoQ(10) proliposomes were studied. At the optimum conditions of pressure of 8.0 MPa, temperature of 35°C, the weight ratio of 1/10 between CoQ(10) and PC, and the weight ratio of 1/3 between cholesterol and PC, the CoQ(10) loading reached 8.92%. CoQ(10) liposomes were obtained by hydrating CoQ(10) proliposomes and the entrapment efficiency of CoQ(10) reached 82.28%. The morphologies of CoQ(10) proliposomes were characterized by scanning electron microscope, and their solid states were characterized by X-ray diffractometer. The structures of CoQ(10) liposomes were characterized by transmission electron microscope. The particle size distribution of CoQ(10) liposomes was determined by dynamic light scattering instrument. The results indicate that CoQ(10) liposomes with particle sizes about 50 nm can be easily obtained from hydrating CoQ(10) proliposomes prepared by SAS technique.

Compression strategies for LiDAR waveform cube

NASA Astrophysics Data System (ADS)

Jóźków, Grzegorz; Toth, Charles; Quirk, Mihaela; Grejner-Brzezinska, Dorota

2015-01-01

Full-waveform LiDAR data (FWD) provide a wealth of information about the shape and materials of the surveyed areas. Unlike discrete data that retains only a few strong returns, FWD generally keeps the whole signal, at all times, regardless of the signal intensity. Hence, FWD will have an increasingly well-deserved role in mapping and beyond, in the much desired classification in the raw data format. Full-waveform systems currently perform only the recording of the waveform data at the acquisition stage; the return extraction is mostly deferred to post-processing. Although the full waveform preserves most of the details of the real data, it presents a serious practical challenge for a wide use: much larger datasets compared to those from the classical discrete return systems. Atop the need for more storage space, the acquisition speed of the FWD may also limit the pulse rate on most systems that cannot store data fast enough, and thus, reduces the perceived system performance. This work introduces a waveform cube model to compress waveforms in selected subsets of the cube, aimed at achieving decreased storage while maintaining the maximum pulse rate of FWD systems. In our experiments, the waveform cube is compressed using classical methods for 2D imagery that are further tested to assess the feasibility of the proposed solution. The spatial distribution of airborne waveform data is irregular; however, the manner of the FWD acquisition allows the organization of the waveforms in a regular 3D structure similar to familiar multi-component imagery, as those of hyper-spectral cubes or 3D volumetric tomography scans. This study presents the performance analysis of several lossy compression methods applied to the LiDAR waveform cube, including JPEG-1, JPEG-2000, and PCA-based techniques. Wide ranges of tests performed on real airborne datasets have demonstrated the benefits of the JPEG-2000 Standard where high compression rates incur fairly small data degradation. In addition, the JPEG-2000 Standard-compliant compression implementation can be fast and, thus, used in real-time systems, as compressed data sequences can be formed progressively during the waveform data collection. We conclude from our experiments that 2D image compression strategies are feasible and efficient approaches, thus they might be applied during the acquisition of the FWD sensors.

PCA3 Silencing Sensitizes Prostate Cancer Cells to Enzalutamide-mediated Androgen Receptor Blockade.

PubMed

Özgür, Emre; Celik, Ayca Iribas; Darendeliler, Emin; Gezer, Ugur

2017-07-01

Prostate cancer (PCa) is an androgen-dependent disease. Novel anti-androgens (i.e. enzalutamide) have recently been developed for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Evidence is accumulating that prostate cancer antigen 3 (PCA3) is involved in androgen receptor (AR) signaling. Here, in combination with enzalutamide-mediated AR blockade, we investigated the effect of PCA3 targeting on the viability of PCa cells. In hormone-sensitive LNCaP cells, AR-overexpressing LNCaP-AR + cells and VCaP cells (representing CRPC), PCA3 was silenced using siRNA oligonucleotides. Gene expression and cell viability was assessed in PCA3-silenced and/or AR-blocked cells. PCA3 targeting reduced the expression of AR-related genes (i.e. prostate-specific antigen (PSA) and prostate-specific transcript 1 (non-protein coding) (PCGEM1)) and potentiated the effect of enzalutamide. Proliferation of PCa cells was suppressed upon PCA3 silencing with a greater effect in LNCaP-AR + cells. Furthermore, PCA3 silencing sensitized PCa cells to enzalutamide-induced loss of cell growth. PCA3, as a therapeutic target in PCa, might be used to potentiate AR antagonists. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy.

PubMed

Perdonà, Sisto; Bruzzese, Dario; Ferro, Matteo; Autorino, Riccardo; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; Longo, Michele; Spinelli, Rosa; Di Lorenzo, Giuseppe; Oliva, Andrea; De Sio, Marco; Damiano, Rocco; Altieri, Vincenzo; Terracciano, Daniela

2013-02-15

Prostate health index (phi) and prostate cancer antigen 3 (PCA3) have been recently proposed as novel biomarkers for prostate cancer (PCa). We assessed the diagnostic performance of these biomarkers, alone or in combination, in men undergoing first prostate biopsy for suspicion of PCa. One hundred sixty male subjects were enrolled in this prospective observational study. PSA molecular forms, phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay), and other established biomarkers (tPSA, fPSA, and %fPSA) were assessed before patients underwent a 18-core first prostate biopsy. The discriminating ability between PCa-negative and PCa-positive biopsies of Beckman coulter phi and PCA3 score and other used biomarkers were determined. One hundred sixty patients met inclusion criteria. %p2PSA (p2PSA/fPSA × 100), phi and PCA3 were significantly higher in patients with PCa compared to PCa-negative group (median values: 1.92 vs. 1.55, 49.97 vs. 36.84, and 50 vs. 32, respectively, P ≤ 0.001). ROC curve analysis showed that %p2PSA, phi, and PCA3 are good indicator of malignancy (AUCs = 0.68, 0.71, and 0.66, respectively). A multivariable logistic regression model consisting of both the phi index and PCA3 score allowed to reach an overall diagnostic accuracy of 0.77. Decision curve analysis revealed that this "combined" marker achieved the highest net benefit over the examined range of the threshold probability. phi and PCA3 showed no significant difference in the ability to predict PCa diagnosis in men undergoing first prostate biopsy. However, diagnostic performance is significantly improved by combining phi and PCA3. Copyright © 2012 Wiley Periodicals, Inc.

A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer.

PubMed

Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

2017-09-01

We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa -high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa -low PSA and non PCa -high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa.

A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer

PubMed Central

Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

2017-01-01

Objective We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). Material and methods We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. Results The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa –high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa –low PSA and non PCa –high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. Conclusion According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa. PMID:28861298

Accuracy of the prostate health index versus the urinary prostate cancer antigen 3 score to predict overall and significant prostate cancer at initial biopsy.

PubMed

Seisen, Thomas; Rouprêt, Morgan; Brault, Didier; Léon, Priscilla; Cancel-Tassin, Géraldine; Compérat, Eva; Renard-Penna, Raphaële; Mozer, Pierre; Guechot, Jérome; Cussenot, Olivier

2015-01-01

It remains unclear whether the Prostate Health Index (PHI) or the urinary Prostate-Cancer Antigen 3 (PCA-3) score is more accurate at screening for prostate cancer (PCa). The aim of this study was to prospectively compare the accuracy of PHI and PCA-3 scores to predict overall and significant PCa in men undergoing an initial prostate biopsy. Double-blind assessments of PHI and PCA-3 were conducted by referent physicians in 138 patients who subsequently underwent trans-rectal ultrasound-guided prostate biopsy according to a 12-core scheme. Predictive accuracies of PHI and PCA-3 were assessed using AUC and compared according to the DeLong method. Diagnostic performances with usual cut-off values for positivity (i.e., PHI >40 and PCA-3 >35) were calculated, and odds ratios associated with predicting PCa overall and significant PCa as defined by pathological updated Epstein criteria (i.e., Gleason score ≥7, more than three positive cores, or >50% cancer involvement in any core) were estimated using logistic regression. Prevalences of overall and significant PCa were 44.9% and 28.3%, respectively. PCA-3 (AUC = 0.71) was the most accurate predictor of PCa overall, and significantly outperformed PHI (AUC = 0.65; P = 0.03). However, PHI (AUC = 0.80) remained the most accurate predictor when screening exclusively for significant PCa and significantly outperformed PCA-3 (AUC = 0.55; P = 0.03). Furthermore, PCA-3 >35 had the best accuracy, and positive or negative predictive values when screening for PCa overall whereas these diagnostic performances were greater for PHI >40 when exclusively screening for significant PCa. PHI > 40 combined with PCA-3 > 35 was more specific in both cases. In multivariate analyses, PCA-3 >35 (OR = 5.68; 95%CI = [2.21-14.59]; P < 0.001) was significantly correlated with the presence of PCa overall, but PHI >40 (OR = 9.60; 95%CI = [1.72-91.32]; P = 0.001) was the only independent predictor for detecting significant PCa. Although PCA-3 score is the best predictor for PCa overall at initial biopsy, our findings strongly indicate that PHI should be used for population-based screening to avoid over-diagnosis of indolent tumors that are unlikely to cause death. © 2014 Wiley Periodicals, Inc.

Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers.

PubMed

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Marino, Ada; Sorrentino, Alessandra; Di Carlo, Angelina; Autorino, Riccardo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Altieri, Vincenzo; Mariano, Angela; Macchia, Vincenzo; Terracciano, Daniela

2012-08-16

Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3. The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard. Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy. Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (p<0.001) and also compared with high grade prostatic intraepithelial neoplasia (HGPIN) (p<0.001). PCA3 score values were significantly higher in PCa compared with PCa-negative subjects (p<0.001) and in HGPIN vs PCa-negative patients (p<0.001). ROC curve analysis showed that %p2PSA, phi and PCA3 are predictive of malignancy. In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

Consensus classification of posterior cortical atrophy

PubMed Central

Crutch, Sebastian J.; Schott, Jonathan M.; Rabinovici, Gil D.; Murray, Melissa; Snowden, Julie S.; van der Flier, Wiesje M.; Dickerson, Bradford C.; Vandenberghe, Rik; Ahmed, Samrah; Bak, Thomas H.; Boeve, Bradley F.; Butler, Christopher; Cappa, Stefano F.; Ceccaldi, Mathieu; de Souza, Leonardo Cruz; Dubois, Bruno; Felician, Olivier; Galasko, Douglas; Graff-Radford, Jonathan; Graff-Radford, Neill R.; Hof, Patrick R.; Krolak-Salmon, Pierre; Lehmann, Manja; Magnin, Eloi; Mendez, Mario F.; Nestor, Peter J.; Onyike, Chiadi U.; Pelak, Victoria S.; Pijnenburg, Yolande; Primativo, Silvia; Rossor, Martin N.; Ryan, Natalie S.; Scheltens, Philip; Shakespeare, Timothy J.; González, Aida Suárez; Tang-Wai, David F.; Yong, Keir X. X.; Carrillo, Maria; Fox, Nick C.

2017-01-01

Introduction A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Methods Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. Results A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. Discussion There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work. PMID:28259709

Consensus classification of posterior cortical atrophy.

PubMed

Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Murray, Melissa; Snowden, Julie S; van der Flier, Wiesje M; Dickerson, Bradford C; Vandenberghe, Rik; Ahmed, Samrah; Bak, Thomas H; Boeve, Bradley F; Butler, Christopher; Cappa, Stefano F; Ceccaldi, Mathieu; de Souza, Leonardo Cruz; Dubois, Bruno; Felician, Olivier; Galasko, Douglas; Graff-Radford, Jonathan; Graff-Radford, Neill R; Hof, Patrick R; Krolak-Salmon, Pierre; Lehmann, Manja; Magnin, Eloi; Mendez, Mario F; Nestor, Peter J; Onyike, Chiadi U; Pelak, Victoria S; Pijnenburg, Yolande; Primativo, Silvia; Rossor, Martin N; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Timothy J; Suárez González, Aida; Tang-Wai, David F; Yong, Keir X X; Carrillo, Maria; Fox, Nick C

2017-08-01

A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Genetic Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer.

PubMed

Jung, Seung-Hyun; Shin, Sun; Kim, Min Sung; Baek, In-Pyo; Lee, Ji Youl; Lee, Sung Hak; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

2016-05-01

Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown. Identification of the genomic landscape of HGPIN and the genomic differences between HGPIN and PCA that may drive the progression to PCA. We analyzed 20 regions of paired HGPIN and PCA from six patients using whole-exome sequencing and array-comparative genomic hybridization. Somatic mutation and copy number alteration (CNA) profiles of paired HGPIN and PCA were measured and compared. The number of total mutations and CNAs of HGPINs were significantly fewer than those of PCAs. Mutations in FOXA1 and CNAs (1q and 8q gains) were detected in both HGPIN and PCA ('common'), suggesting their roles in early PCA development. Mutations in SPOP, KDM6A, and KMT2D were 'PCA-specific', suggesting their roles in HGPIN progression to PCA. The 8p loss was either 'common' or 'PCA-specific'. In-silico estimation of evolutionary ages predicted that HGPIN genomes were much younger than PCA genomes. Our data show that PCAs are direct descendants of HGPINs in most cases that require more genomic alterations to progress to PCA. The nature of heterogeneous HGPIN population that might attenuate genomic signals should further be studied. HGPIN genomes harbor relatively fewer mutations and CNAs than PCA but require additional hits for the progression. In this study, we suggest a systemic diagram from high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PCA). Our results provide a clue to explain the long latency from HGPIN to PCA and provide useful information for the genetic diagnosis of HGPIN and PCA. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Occipital-posterior cerebral artery bypass via the occipital interhemispheric approach

PubMed Central

Kazumata, Ken; Yokoyama, Yuka; Sugiyama, Taku; Asaoka, Katsuyuki

2013-01-01

Background: The unavailability of the superficial temporal artery (STA) and the location of lesions pose a more technically demanding challenge when compared with conventional STA-superior cerebellar or posterior cerebral artery (PCA) bypass in vascular reconstruction procedures. To describe a case series of patients with cerebrovascular lesions who were treated using an occipital artery (OA) to PCA bypass via the occipital interhemispheric approach. Methods: We retrospectively reviewed three consecutive cases of patients with cerebrovascular lesions who were treated using OA-PCA bypass. Results: OA-PCA bypass was performed via the occipital interhemispheric approach. This procedure included: (1) OA-PCA bypass (n = 1), and combined OA-posterior inferior cerebellar artery and OA-PCA saphenous vein interposition graft bypass (n = 1) in patients with vertebrobasilar ischemia; (2) OA-PCA radial artery interposition graft bypass in one patient with residual PCA aneurysm. Conclusions: OA-PCA bypass represents a useful alternative to conventional STA-SCA or PCA bypass. PMID:23956933

Diagnostic and predictive value of urine PCA3 gene expression for the clinical management of patients with altered prostatic specific antigen.

PubMed

Rodón, N; Trías, I; Verdú, M; Román, R; Domínguez, A; Calvo, M; Banus, J M; Ballesta, A M; Maestro, M L; Puig, X

2014-04-01

Analyze the impact of the introduction of the study of PCA3 gene in post-prostatic massage urine in the clinical management of patients with PSA altered, evaluating its diagnostic ability and predictive value of tumor aggressiveness. Observational, prospective, multicenter study of patients with suspected prostate cancer (PC) candidates for biopsy. We present a series of 670 consecutive samples of urine collected post-prostatic massage for three years in which we determined the "PCA3 score" (s-PCA3). Biopsy was only indicated in cases with s-positive PCA3. The s-PCA3 was positive in 43.7% of samples. In the 124 biopsies performed, the incidence of PC or atypical small acinar proliferation was 54%, reaching 68,6% in s-PCA3≥100. Statistically significant relationship between the s-PCA3 and tumor grade was demonstrated. In cases with s-PCA3 between 35 and 50 only 23% of PC were high grade (Gleason≥7), compared to 76.7% in cases with s-PCA3 over 50. There was a statistically significant correlation between s-PCA3 and cylinders affected. Both relationships were confirmed by applying a log-linear model. The incorporation of PCA3 can avoid the need for biopsies in 54% of patients. s-PCA3 positivity increases the likelihood of a positive biopsy, especially in higher s-PCA3 100 (68.6%). s-PCA3 is also an indicator of tumor aggressiveness and provides essential information in making treatment decisions. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Comparative evaluation of the powder and compression properties of various grades and brands of microcrystalline cellulose by multivariate methods.

PubMed

Haware, Rahul V; Bauer-Brandl, Annette; Tho, Ingunn

2010-01-01

The present work challenges a newly developed approach to tablet formulation development by using chemically identical materials (grades and brands of microcrystalline cellulose). Tablet properties with respect to process and formulation parameters (e.g. compression speed, added lubricant and Emcompress fractions) were evaluated by 2(3)-factorial designs. Tablets of constant true volume were prepared on a compaction simulator at constant pressure (approx. 100 MPa). The highly repeatable and accurate force-displacement data obtained was evaluated by simple 'in-die' Heckel method and work descriptors. Relationships and interactions between formulation, process and tablet parameters were identified and quantified by multivariate analysis techniques; principal component analysis (PCA) and partial least square regressions (PLS). The method proved to be able to distinguish between different grades of MCC and even between two different brands of the same grade (Avicel PH 101 and Vivapur 101). One example of interaction was studied in more detail by mixed level design: The interaction effect of lubricant and Emcompress on elastic recovery of Avicel PH 102 was demonstrated to be complex and non-linear using the development tool under investigation.

PCA-LBG-based algorithms for VQ codebook generation

NASA Astrophysics Data System (ADS)

Tsai, Jinn-Tsong; Yang, Po-Yuan

2015-04-01

Vector quantisation (VQ) codebooks are generated by combining principal component analysis (PCA) algorithms with Linde-Buzo-Gray (LBG) algorithms. All training vectors are grouped according to the projected values of the principal components. The PCA-LBG-based algorithms include (1) PCA-LBG-Median, which selects the median vector of each group, (2) PCA-LBG-Centroid, which adopts the centroid vector of each group, and (3) PCA-LBG-Random, which randomly selects a vector of each group. The LBG algorithm finds a codebook based on the better vectors sent to an initial codebook by the PCA. The PCA performs an orthogonal transformation to convert a set of potentially correlated variables into a set of variables that are not linearly correlated. Because the orthogonal transformation efficiently distinguishes test image vectors, the proposed PCA-LBG-based algorithm is expected to outperform conventional algorithms in designing VQ codebooks. The experimental results confirm that the proposed PCA-LBG-based algorithms indeed obtain better results compared to existing methods reported in the literature.

Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.

PubMed

Alfaro, Clint M; Jarmusch, Alan K; Pirro, Valentina; Kerian, Kevin S; Masterson, Timothy A; Cheng, Liang; Cooks, R Graham

2016-08-01

Touch spray-mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (∼1-5 cm(3)), within 1 h of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700-1000) data provided the separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA-compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98 and 95 %, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization-MS imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700-1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100 and 89 %, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1 + Cl](-) and 844 [PC 38:4 + Cl](-) for TS vs. m/z 788 [PS 36:1 - H](-) and 810 [PS 38:4 - H](-) for DESI), while m/z 885 ([PI 38:4 - H](-)) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis are discussed. Graphical abstract Touch spray-mass spectrometry used for lipid profiling of fresh human renal cell carcinoma. Left) Photograph of the touch spray probe pointed at the MS inlet. Right) Average mass spectra of healthy renal tissue (blue) and RCC (red).

Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

PubMed Central

Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Li, Yang; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L.; Zhau, Haiyen E.; Shih, Jean C.; Chung, Leland W.K.

2014-01-01

Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines. Despite the association between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression. Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition (EMT) and stabilize the transcription factor HIF1α, which mediates hypoxia through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines indicated that MAOA induces EMT through activation of VEGF and its coreceptor neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1 signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA activity also reduced PCa xenograft growth in mice. Moreover, high MAOA expression in PCa tissues correlated with worse clinical outcomes in PCa patients. These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa. PMID:24865426

Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis.

PubMed

Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Li, Yang; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L; Zhau, Haiyen E; Shih, Jean C; Chung, Leland W K

2014-07-01

Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines. Despite the association between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression. Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition (EMT) and stabilize the transcription factor HIF1α, which mediates hypoxia through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines indicated that MAOA induces EMT through activation of VEGF and its coreceptor neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1 signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA activity also reduced PCa xenograft growth in mice. Moreover, high MAOA expression in PCa tissues correlated with worse clinical outcomes in PCa patients. These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa.

MD-11 PCA - Research flight team photo

NASA Technical Reports Server (NTRS)

1995-01-01

On Aug. 30, 1995, a the McDonnell Douglas MD-11 transport aircraft landed equipped with a computer-assisted engine control system that has the potential to increase flight safety. In landings at NASA Dryden Flight Research Center, Edwards, California, on August 29 and 30, the aircraft demonstrated software used in the aircraft's flight control computer that essentially landed the MD-11 without a need for the pilot to manipulate the flight controls significantly. In partnership with McDonnell Douglas Aerospace (MDA), with Pratt & Whitney and Honeywell helping to design the software, NASA developed this propulsion-controlled aircraft (PCA) system following a series of incidents in which hydraulic failures resulted in the loss of flight controls. This new system enables a pilot to operate and land the aircraft safely when its normal, hydraulically-activated control surfaces are disabled. This August 29, 1995, photo shows the MD-11 team. Back row, left to right: Tim Dingen, MDA pilot; John Miller, MD-11 Chief pilot (MDA); Wayne Anselmo, MD-11 Flight Test Engineer (MDA); Gordon Fullerton, PCA Project pilot; Bill Burcham, PCA Chief Engineer; Rudey Duran, PCA Controls Engineer (MDA); John Feather, PCA Controls Engineer (MDA); Daryl Townsend, Crew Chief; Henry Hernandez, aircraft mechanic; Bob Baron, PCA Project Manager; Don Hermann, aircraft mechanic; Jerry Cousins, aircraft mechanic; Eric Petersen, PCA Manager (Honeywell); Trindel Maine, PCA Data Engineer; Jeff Kahler, PCA Software Engineer (Honeywell); Steve Goldthorpe, PCA Controls Engineer (MDA). Front row, left to right: Teresa Hass, Senior Project Management Analyst; Hollie Allingham (Aguilera), Senior Project Management Analyst; Taher Zeglum, PCA Data Engineer (MDA); Drew Pappas, PCA Project Manager (MDA); John Burken, PCA Control Engineer.

Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa)

PubMed Central

Rittenhouse, Harry; Hu, Xinhai; Cammann, Henning; Jung, Klaus

2014-01-01

Abstract PSA screening reduces PCa-mortality but the disadvantages overdiagnosis and overtreatment require multivariable risk-prediction tools to select appropriate treatment or active surveillance. This review explains the differences between the two largest screening trials and discusses the drawbacks of screening and its meta-analysisxs. The current American and European screening strategies are described. Nonetheless, PSA is one of the most widely used tumor markers and strongly correlates with the risk of harboring PCa. However, while PSA has limitations for PCa detection with its low specificity there are several potential biomarkers presented in this review with utility for PCa currently being studied. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA-approved prostate health index (phi) shows improved specificity over percent free and total PSA. Another kallikrein panel, 4K, which includes KLK2 has recently shown promise in clinical research studies but has not yet undergone formal validation studies. In urine, prostate cancer gene 3 (PCA3) has also been validated and approved by the FDA for its utility to detect PCa. The potential correlation of PCA3 with cancer aggressiveness requires more clinical studies. The detection of the fusion of androgen-regulated genes with genes of the regulatory transcription factors in tissue of ~50% of all PCa-patients is a milestone in PCa research. A combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 shows an improved accuracy for PCa detection. Overall, the field of PCa biomarker discovery is very exciting and prospective. PMID:27683457

Target oriented dimensionality reduction of hyperspectral data by Kernel Fukunaga-Koontz Transform

NASA Astrophysics Data System (ADS)

Binol, Hamidullah; Ochilov, Shuhrat; Alam, Mohammad S.; Bal, Abdullah

2017-02-01

Principal component analysis (PCA) is a popular technique in remote sensing for dimensionality reduction. While PCA is suitable for data compression, it is not necessarily an optimal technique for feature extraction, particularly when the features are exploited in supervised learning applications (Cheriyadat and Bruce, 2003) [1]. Preserving features belonging to the target is very crucial to the performance of target detection/recognition techniques. Fukunaga-Koontz Transform (FKT) based supervised band reduction technique can be used to provide this requirement. FKT achieves feature selection by transforming into a new space in where feature classes have complimentary eigenvectors. Analysis of these eigenvectors under two classes, target and background clutter, can be utilized for target oriented band reduction since each basis functions best represent target class while carrying least information of the background class. By selecting few eigenvectors which are the most relevant to the target class, dimension of hyperspectral data can be reduced and thus, it presents significant advantages for near real time target detection applications. The nonlinear properties of the data can be extracted by kernel approach which provides better target features. Thus, we propose constructing kernel FKT (KFKT) to present target oriented band reduction. The performance of the proposed KFKT based target oriented dimensionality reduction algorithm has been tested employing two real-world hyperspectral data and results have been reported consequently.

Inversion using a new low-dimensional representation of complex binary geological media based on a deep neural network

NASA Astrophysics Data System (ADS)

Laloy, Eric; Hérault, Romain; Lee, John; Jacques, Diederik; Linde, Niklas

2017-12-01

Efficient and high-fidelity prior sampling and inversion for complex geological media is still a largely unsolved challenge. Here, we use a deep neural network of the variational autoencoder type to construct a parametric low-dimensional base model parameterization of complex binary geological media. For inversion purposes, it has the attractive feature that random draws from an uncorrelated standard normal distribution yield model realizations with spatial characteristics that are in agreement with the training set. In comparison with the most commonly used parametric representations in probabilistic inversion, we find that our dimensionality reduction (DR) approach outperforms principle component analysis (PCA), optimization-PCA (OPCA) and discrete cosine transform (DCT) DR techniques for unconditional geostatistical simulation of a channelized prior model. For the considered examples, important compression ratios (200-500) are achieved. Given that the construction of our parameterization requires a training set of several tens of thousands of prior model realizations, our DR approach is more suited for probabilistic (or deterministic) inversion than for unconditional (or point-conditioned) geostatistical simulation. Probabilistic inversions of 2D steady-state and 3D transient hydraulic tomography data are used to demonstrate the DR-based inversion. For the 2D case study, the performance is superior compared to current state-of-the-art multiple-point statistics inversion by sequential geostatistical resampling (SGR). Inversion results for the 3D application are also encouraging.

Magnetic Flux Leakage and Principal Component Analysis for metal loss approximation in a pipeline

NASA Astrophysics Data System (ADS)

Ruiz, M.; Mujica, L. E.; Quintero, M.; Florez, J.; Quintero, S.

2015-07-01

Safety and reliability of hydrocarbon transportation pipelines represent a critical aspect for the Oil an Gas industry. Pipeline failures caused by corrosion, external agents, among others, can develop leaks or even rupture, which can negatively impact on population, natural environment, infrastructure and economy. It is imperative to have accurate inspection tools traveling through the pipeline to diagnose the integrity. In this way, over the last few years, different techniques under the concept of structural health monitoring (SHM) have continuously been in development. This work is based on a hybrid methodology that combines the Magnetic Flux Leakage (MFL) and Principal Components Analysis (PCA) approaches. The MFL technique induces a magnetic field in the pipeline's walls. The data are recorded by sensors measuring leakage magnetic field in segments with loss of metal, such as cracking, corrosion, among others. The data provide information of a pipeline with 15 years of operation approximately, which transports gas, has a diameter of 20 inches and a total length of 110 km (with several changes in the topography). On the other hand, PCA is a well-known technique that compresses the information and extracts the most relevant information facilitating the detection of damage in several structures. At this point, the goal of this work is to detect and localize critical loss of metal of a pipeline that are currently working.

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

PubMed Central

Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

2011-01-01

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

Evaluation of Vitronectin Expression in Prostate Cancer and the Clinical Significance of the Association of Vitronectin Expression with Prostate Specific Antigen in Detecting Prostate Cancer.

PubMed

Niu, Yue; Zhang, Ling; Bi, Xing; Yuan, Shuai; Chen, Peng

2016-03-05

To detect the expression of vitronectin (VTN) in the tissues and blood serum of prostate cancer (PCa) patients, and evaluate its clinical significance and to evaluate the significance of the combined assay of VTN and prostate specific antigens (PSA) in PCa diagnosis. To detect the expression of VTN as a potential marker for PCa diagnosis and prognosis, immunohistochemistry was performed on the tissues of 32 patients with metastatic PCa (PCaM), 34 patients with PCa without metastasis (PCa), and 41 patients with benign prostatic hyperplasia (BPH). The sera were then subjected to Western blot analysis. All cases were subsequently examined to determine the concentrations of PSA and VTN in the sera. The collected data were collated and analyzed. The positive expression rates of VTN in the tissues of the BPH and PCa groups (including PCa and PCaM groups) were 75.61% and 45.45%, respectively (P = .005). VTN was more highly expressed in the sera of the BPH patients (0.83 ± 0.07) than in the sera of the PCa patients (0.65 ± 0.06) (P < .05). It was also more highly expressed in the sera of the PCa patients than in the sera of the PCaM patients (0.35 ± 0.08) (P < .05). In the diagnosis of BPH and PCa, the Youden indexes of PSA detection, VTN detection, and combined detection were 0.2620, 0.3468, and 0.5635; the kappa values were 0.338, 0.304, and 0.448, respectively, and the areas under the receiver operating characteristic curve were 0.625, 0.673, and 0.703 (P < .05), respectively. VTN levels in sera may be used as a potential marker of PCa for the diagnosis and assessment of disease progression and metastasis. The combined detection of VTN and PSA in sera can be clinically applied in PCa diagnosis. .

Phenazine-1-carboxylic acid and soil moisture influence biofilm development and turnover of rhizobacterial biomass on wheat root surfaces.

PubMed

LeTourneau, Melissa K; Marshall, Matthew J; Cliff, John B; Bonsall, Robert F; Dohnalkova, Alice C; Mavrodi, Dmitri V; Devi, S Indira; Mavrodi, Olga V; Harsh, James B; Weller, David M; Thomashow, Linda S

2018-04-24

Phenazine-1-carboxylic acid (PCA) is produced by rhizobacteria in dryland but not in irrigated wheat fields of the Pacific Northwest, USA. PCA promotes biofilm development in bacterial cultures and bacterial colonization of wheat rhizospheres. However, its impact upon biofilm development has not been demonstrated in the rhizosphere, where biofilms influence terrestrial carbon and nitrogen cycles with ramifications for crop and soil health. Furthermore, the relationships between soil moisture and the rates of PCA biosynthesis and degradation have not been established. In this study, expression of PCA biosynthesis genes was up-regulated relative to background transcription, and persistence of PCA was slightly decreased in dryland relative to irrigated wheat rhizospheres. Biofilms in dryland rhizospheres inoculated with the PCA-producing (PCA + ) strain Pseudomonas synxantha 2-79RN 10 were more robust than those in rhizospheres inoculated with an isogenic PCA-deficient (PCA - ) mutant strain. This trend was reversed in irrigated rhizospheres. In dryland PCA + rhizospheres, the turnover of 15 N-labelled rhizobacterial biomass was slower than in the PCA - and irrigated PCA + treatments, and incorporation of bacterial 15 N into root cell walls was observed in multiple treatments. These results indicate that PCA promotes biofilm development in dryland rhizospheres, and likely influences crop nutrition and soil health in dryland wheat fields. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Incidental prostate cancer in radical cystoprostatectomy specimens.

PubMed

Jin, Xiao-Dong; Chen, Zhao-Dian; Wang, Bo; Cai, Song-Liang; Yao, Xiao-Lin; Jin, Bai-Ye

2008-09-01

To investigate the rates of prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens for bladder cancer in mainland China. To determine the follow-up outcome of patients with two concurrent cancers and identify whether prostate-specific antigen (PSA) is a useful tool for the detection of PCa prior to surgery. From January 2002 to January 2007, 264 male patients with bladder cancer underwent RCP at our center. All patients underwent digital rectal examination (DRE) and B ultrasound. Serum PSA levels were tested in 168 patients. None of the patients had any evidence of PCa before RCP. Entire prostates were embedded and sectioned at 5 mm intervals. Incidental PCa was observed in 37 of 264 (14.0%) RCP specimens. Of these, 12 (32.4%) were clinically significant according to an accepted definition. The PSA levels were not significantly different between patients with PCa and those without PCa, nor between patients with significant PCa and those with insignificant PCa. Thirty-four patients with incidental PCa were followed up. During a mean follow-up period of 26 months, two patients with PSA > 4 ng/mL underwent castration. None of the patients died of PCa. The incidence of PCa in RCP specimens in mainland China is lower than that in most developed countries. PSA cannot identify asymptomatic PCa prior to RCP. In line with published reports, incidental PCa does not impact the prognosis of bladder cancer patients undergoing RCP. (c) 2008, Asian Journal of Andrology, SIMM and SJTU. All rights reserved.

Impact of phenazine-1-carboxylic acid upon iron speciation and microbial biomass in the rhizosphere of wheat

NASA Astrophysics Data System (ADS)

LeTourneau, M.; Marshall, M.; Grant, M.; Freeze, P.; Cliff, J. B.; Lai, B.; Strawn, D. G.; Thomashow, L. S.; Weller, D. M.; Harsh, J. B.

2015-12-01

Phenazine-1-carboxylic acid (PCA) is a redox-active antibiotic produced by diverse bacterial taxa, and has been shown to facilitate interactions between biofilms and iron (hydr)oxides in culture systems (Wang et al. 2011, J Bacteriol 192: 365). Because rhizobacterial biofilms are a major sink for plant-derived carbon and source for soil organic matter (SOM), and Fe (hydr)oxides have reactive surfaces that influence the stability of microbial biomass and SOM, PCA-producing rhizobacteria could influence soil carbon fluxes. Large populations of Pseudomonas fluorescens strains producing PCA in concentrations up to 1 μg/g root have been observed in the rhizosphere of non-irrigated wheat fields covering 1.56 million hectares of central Washington state. This is one of the highest concentrations ever reported for a natural antibiotic in a terrestrial ecosystem (Mavrodi et al. 2012, Appl Environ Microb 78: 804). Microscopic comparisons of PCA-producing (PCA+) and non-PCA-producing (PCA-) rhizobacterial colony morphologies, and comparisons of Fe extractions from rhizosphere soil inoculated with PCA+ and PCA- strains suggest that PCA promotes biofilm development as well as dramatic Fe transformations throughout the rhizosphere (unpublished data). In order to illustrate PCA-mediated interactions between biofilms and Fe (hydr)oxides in the rhizosphere, identify the specific Fe phases favored by PCA, and establish the ramifications for stability and distribution of microbial biomass and SOM, we have collected electron micrographs, X-ray fluorescence images, X-ray absorption near-edge spectra, and secondary-ion mass spectrometry images of wheat root sections inoculated with 15N-labelled PCA+ or PCA- rhizobacteria. These images and spectra allow us to assess the accumulation, turnover, and distribution of microbial biomass, the associations between Fe and other nutrients such as phosphorus, and the redox status and speciation of iron in the presence and absence of PCA. This information provides a starting point to model the impact of PCA upon carbon fluxes in Columbia Basin agro-ecosystems and other environments where PCA-producing bacteria are prevalent.

Exploratory Development on a New Process to Produce Improved RDX crystals: Supercritical Fluid Anti-Solvent Recrystallization

DTIC Science & Technology

1988-05-02

G. and J. Chiovini. Decaffeination Process . U.S. Patent 4,251.559; 17 February 1981. 43. Friedrich, J.P.. G.R. List, and A.J. Leakin. Petroleum...0 CONTRACT REPORT BRL-CR-606 EXPLORATORY DEVELOPMENT ON A NEW PROCESS TO PRODUCE IMPROVED RDX CRYSTALS: SUPERCRITICAL FLUID ANTI-SOLVENT...CCESSION NO. 11. TITLE (icnude Sun• y Uasuihcanon) I . • EXPLORATORY DEVELOPMENT ON A NEW PROCESS TO PRODUCE IMPROVED RDX CRYSTALS: SUPERCRITICAL

Enhanced photovoltaic performance of CH3NH3PbBrXI3-X-based perovskite solar cells via anti-solvent extraction

NASA Astrophysics Data System (ADS)

Jiang, Zhaoyi; Zhang, Weijia; Lu, Chaoqun; Ma, Denghao; Liu, Haixu; Yu, Wei; Zhang, Yu; Ma, Qiang; Zhang, Yulong

2018-06-01

In this paper, the two-step sequential deposition method was used to prepare the CH3NH3PbBrXI3-X films by introducing CH3NH3Br in the precursors. The surface morphology of the PbI2 films was controlled by anti-solvent extraction (ASE) to improve the microstructure and photo-physical properties of the perovskite films. It was noteworthy that, compared to the compact PbI2 films, the porous PbI2 films facilitated the growth of crystals and bromine incorporation in films, and the prepared perovskite films exhibited enlarged grain size, increased light absorption, enhanced Br incorporation and prolonged carrier lifetime, which resulted in excellent photo-electrical properties of the CH3NH3PbBrXI3-X films. With porous PbI2 templates, the inverted planar perovskite solar cells based on films with appropriate Br incorporation (CH3NH3Br/CH3NH3I mole ratio = 3/7) showed a photovoltaic conversion efficiency (PCE) of 14.9%, and the stability of the devices in air was elevated. Consequently, the high-quality CH3NH3PbBrXI3-X films can be obtained with porous PbI2 templates for improving the performance of the perovskite solar cells.

New polymorphs of 9-nitro-camptothecin prepared using a supercritical anti-solvent process.

PubMed

Huang, Yinxia; Wang, Hongdi; Liu, Guijin; Jiang, Yanbin

2015-12-30

Recrystallization and micronization of 9-nitro-camptothecin (9-NC) has been investigated using the supercritical anti-solvent (SAS) technology in this study. Five operating factors, i.e., the type of organic solvent, the concentration of 9-NC in the solution, the flow rate of 9-NC solution, the precipitation pressure and the temperature, were optimized using a selected OA16 (4(5)) orthogonal array design and a series of characterizations were performed for all samples. The results showed that the processed 9-NC particles exhibited smaller particle size and narrower particle size distribution as compared with 9-NC raw material (Form I), and the optimum micronization conditions for preparing 9-NC with minimum particle size were determined by variance analysis, where the solvent plays the most important role in the formation and transformation of polymorphs. Three new polymorphic forms (Form II, III and IV) of 9-NC, which present different physicochemical properties, were generated after the SAS process. The predicted structures of the 9-NC crystals, which were consistent with the experiments, were performed from their experimental XRD data by the direct space approach using the Reflex module of Materials Studio. Meanwhile, the optimal sample (Form III) was proved to have higher cytotoxicity against the cancer cells, which suggested the therapeutic efficacy of 9-NC is polymorph-dependent. Copyright © 2015 Elsevier B.V. All rights reserved.

Anti-solvent crystallization of L-threonine in Taylor crystallizers and MSMPR crystallizer: Effect of fluid dynamic motions on crystal size, shape, and recovery

NASA Astrophysics Data System (ADS)

Lee, Sooyun; Lee, Choul-Ho; Kim, Woo-Sik

2017-07-01

The influence of the fluid dynamic motions of a periodic Taylor vortex and random turbulent eddy on the anti-solvent crystallization of L-threonine was investigated. The Taylor vortex flow and random turbulent eddy flow were generated by the inner cylinder rotation in a Couette-Taylor (CT) crystallizer and the impeller agitation in a mixed-suspension mixed product removal (MSMPR) crystallizer, respectively. Furthermore, the circumferentially sinusoidal fluctuation of a Taylor vortex was induced in an elliptical Couette-Taylor (ECT) crystallizer . The periodic Taylor vortex flows in the CT and ECT crystallizers resulted in a smaller crystal size and higher crystal recovery ratio of L-threonine than the random turbulent flow in the MSMPR crystallizer due to induction of a higher supersaturation, resulting in a higher nucleation in the CT and ECT crystallizers than in the MSMPR crystallizer. Thus, the crystal size was reduced and the crystal recovery ratio enhanced when increasing the rotation/agitation speed and feed flow rate in the CT, ECT, and MSMPR crystallizers. When increasing the temperature, the crystal size and crystal recovery ratio were both increased due an enhanced mass transfer for crystal growth. The crystal morphology changes according to the fluid dynamic motion with various crystallization conditions were well correlated in terms of the supersaturation.

Enhanced Solubility and Dissolution Rate of Lacidipine Nanosuspension: Formulation Via Antisolvent Sonoprecipitation Technique and Optimization Using Box-Behnken Design.

PubMed

Kassem, Mohamed A A; ElMeshad, Aliaa N; Fares, Ahmed R

2017-05-01

Lacidipine (LCDP) is a highly lipophilic calcium channel blocker of poor aqueous solubility leading to poor oral absorption. This study aims to prepare and optimize LCDP nanosuspensions using antisolvent sonoprecipitation technique to enhance the solubility and dissolution of LCDP. A three-factor, three-level Box-Behnken design was employed to optimize the formulation variables to obtain LCDP nanosuspension of small and uniform particle size. Formulation variables were as follows: stabilizer to drug ratio (A), sodium deoxycholate percentage (B), and sonication time (C). LCDP nanosuspensions were assessed for particle size, zeta potential, and polydispersity index. The formula with the highest desirability (0.969) was chosen as the optimized formula. The values of the formulation variables (A, B, and C) in the optimized nanosuspension were 1.5, 100%, and 8 min, respectively. Optimal LCDP nanosuspension had particle size (PS) of 273.21 nm, zeta potential (ZP) of -32.68 mV and polydispersity index (PDI) of 0.098. LCDP nanosuspension was characterized using x-ray powder diffraction, differential scanning calorimetry, and transmission electron microscopy. LCDP nanosuspension showed saturation solubility 70 times that of raw LCDP in addition to significantly enhanced dissolution rate due to particle size reduction and decreased crystallinity. These results suggest that the optimized LCDP nanosuspension could be promising to improve oral absorption of LCDP.

Stable and Efficient Organo-Metal Halide Hybrid Perovskite Solar Cells via π-Conjugated Lewis Base Polymer Induced Trap Passivation and Charge Extraction.

PubMed

Qin, Ping-Li; Yang, Guang; Ren, Zhi-Wei; Cheung, Sin Hang; So, Shu Kong; Chen, Li; Hao, Jianhua; Hou, Jianhui; Li, Gang

2018-03-01

High-quality pinhole-free perovskite film with optimal crystalline morphology is critical for achieving high-efficiency and high-stability perovskite solar cells (PSCs). In this study, a p-type π-conjugated polymer poly[(2,6-(4,8-bis(5-(2-ethylhexyl) thiophen-2-yl)-benzo[1,2-b:4,5-b'] dithiophene))-alt-(5,5-(1',3'-di-2-thienyl-5',7'-bis(2-ethylhexyl) benzo[1',2'-c:4',5'-c'] dithiophene-4,8-dione))] (PBDB-T) is introduced into chlorobenzene to form a facile and effective template-agent during the anti-solvent process of perovskite film formation. The π-conjugated polymer PBDB-T is found to trigger a heterogeneous nucleation over the perovskite precursor film and passivate the trap states of the mixed perovskite film through the formation of Lewis adducts between lead and oxygen atom in PBDB-T. The p-type semiconducting and hydrophobic PBDB-T polymer fills in the perovskite grain boundaries to improve charge transfer for better conductivity and prevent moisture invasion into the perovskite active layers. Consequently, the PSCs with PBDB-T modified anti-solvent processing leads to a high-efficiency close to 20%, and the devices show excellent stability, retaining about 90% of the initial power conversion efficiency after 150 d storage in dry air. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mesophase and size manipulation of itraconazole liquid crystalline nanoparticles produced via quasi nanoemulsion precipitation.

PubMed

Mugheirbi, Naila A; Tajber, Lidia

2015-10-01

The fabrication of drug nanoparticles (NPs) with process-mediated tunable properties and performances continues to grow rapidly during the last decades. This study investigates the synthesis and phase tuning of nanoparticulate itraconazole (ITR) mesophases using quasi nanoemulsion precipitation from acetone/water systems to seek out an alternative pathway to the nucleation-based NP formation. ITR liquid crystalline (LC) phases were formed and nematic-smectic mesomorphism was achieved via controlling solvent:antisolvent temperature difference (ΔTS:AS). The use of ΔTS:AS=49.5°C was associated with a nematic assembly, while intercalated smectic A layering was observed at ΔTS:AS=0°C, with both phases confined in the nanospheres at room temperature. The quasi emulsion system has not been investigated at the nanoscale to date and in contrary to the microscale, quasi nanoemulsion was observed over the solvent:antisolvent viscosity ratios of 1:7-1:1.4. Poly(acrylic acid) in the solvent phase exhibited a concentration dependent interaction when ITR formed NPs. This nanodroplet-based approach enabled the preparation of a stable ITR nanodispersion using Poloxamer 407 at 80°C, which was unachievable before using precipitation via nucleation. Findings of this work lay groundwork in terms of rationalised molecular assembly as a tool in designing pharmaceutical LC NPs with tailored properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Supercritical antisolvent precipitation of nimesulide: preliminary experiments.

PubMed

Moneghini, M; Perissutti, B; Vecchione, F; Kikic, I; Alessi, P; Cortesi, A; Princivalle, F

2007-07-01

The purpose of this preliminary study was to investigate the physico-chemical properties of nimesulide precipitated by continuous supercritical antisolvent (SAS) from different organic solvents like acetone, chloroform and dichloromethane at 40 degrees C and 80, 85 and 88 bar, respectively. Scanning electron microscopy, differential scanning calorimetry, X-Ray diffractometry and in vitro dissolution tests were employed to study how the technological process and the solvent nature would affect the final product. SAS-processed nimesulide particles showed dramatic morphological change in crystalline structure if compared to native nimesulide, resulting in needle and thin rods shaped crystals. The solid state analysis showed that using chloroform or dichloromethane as a solvent the drug solid state remained substantially unchanged, whilst if using acetone the applied method caused a transition from the starting form I to the meta-stable form II. So as to identify which process was responsible for this result, nimesulide was further precipitated from the same solvent by conventional evaporation method (RV-sample). On the basis of this comparison, the solvent was found to be responsible for the re-organization into the different polymorphic form and the potential of the SAS process to produce micronic needle shaped particles, with an enhanced dissolution rate if compared to the to the pure drug, was ascertained. Finally, the stability of the nimesulide form II, checked by DSC analysis, was ruled on over a period of 15 months.

Physicochemical stability, pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process.

PubMed

Shanmugam, Srinivasan; Park, Jae-Hyun; Chi, Sang-Cheol; Yong, Chul Soon; Choi, Han-Gon; Woo, Jong Soo

2011-06-01

To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process. Physicochemical stability was performed in accelerated (40°C 70 ± 5% RH) and stress (60°C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.v. administration of PTX equivalent to 6 and 12 mg/kg formulations. Physical stability of PSD showed excellent stability with no recrystallization of the amorphous form. Chemical stability of PSD in terms of % PTX remaining was 98.2 ± 0.6% at 6 months and 97.9 ± 0.3% at 4 weeks of accelerated and stress conditions, respectively. The PK study showed a nonlinear increase in AUC with increasing dose, that is, 100% increase in dose (from 6 to 12 mg/kg) resulted in 405.90% increase in AUC. Unlike PK study, the organ distribution study of PTX from PSD showed linear relationship with dose escalation. The order of organ distribution of PTX from highest to lowest for both PSD and Taxol® was liver>kidney>lung>brain. This study demonstrated excellent physicochemical stability with insight information on the PK and biodistribution of PTX from PSD prepared by SAS process.

Formation of inhalable rifampicin-poly(L-lactide) microparticles by supercritical anti-solvent process.

PubMed

Patomchaiviwat, Vipaluk; Paeratakul, Ornlaksana; Kulvanich, Poj

2008-01-01

Formation of inhalable microparticles containing rifampicin and poly(L-lactide) (L-PLA) by using supercritical anti-solvent process (SAS) was investigated. The solutions of drug and polymer in methylene chloride were sprayed into supercritical carbon dioxide. The effect of polymer content and operating conditions, temperature, pressure, carbon dioxide molar fraction, and concentration of solution, on product characteristics were studied. The prepared microparticles were characterized with respect to their morphology, particle size and size distribution, drug content, drug loading efficiency, and drug release characteristic. Discrete, spherical microparticles were obtained at high polymer:drug ratios of 7:3, 8:2, and 9:1. The shape of L-PLA microparticles became more irregular and agglomerated with decreasing polymer content. Microparticles with polymer content higher than 60% exhibited volumetric mean diameter less than 5 microm, but percent drug loading efficiency was relatively low. Drug-loaded microparticles containing 70% and 80% L-PLA showed a sustainable drug release property without initial burst release. Operating temperature level influenced on mean size and size distribution of microparticles. The operating pressure and carbon dioxide molar fraction in the range investigated were unlikely to have an effect on microparticle formation. An increasing concentration of feed solution provided larger size microparticles. Rifampicin-loaded L-PLA microparticles could be produced by SAS in a size range suitable for dry powder inhaler formulation.

Self-built supercritical CO2 anti-solvent unit design, construction and operation using carbamazepine.

PubMed

Meng, Dan; Falconer, James; Krauel-Goellner, Karen; Chen, John J J J; Farid, Mohammed; Alany, Raid G

2008-01-01

The purpose of this study was to design and build a supercritical CO(2) anti-solvent (SAS) unit and use it to produce microparticles of the class II drug carbamazepine. The operation conditions of the constructed unit affected the carbamazepine yield. Optimal conditions were: organic solution flow rate of 0.15 mL/min, CO(2) flow rate of 7.5 mL/min, pressure of 4,200 psi, over 3,000 s and at 33 degrees C. The drug solid-state characteristics, morphology and size distribution were examined before and after processing using X-ray powder diffraction and differential scanning calorimetry, scanning electron microscopy and laser diffraction particle size analysis, respectively. The in vitro dissolution of the treated particles was investigated and compared to that of untreated particles. Results revealed a change in the crystalline structure of carbamazepine with different polymorphs co-existing under various operation conditions. Scanning electron micrographs showed a change in the crystalline habit from the prismatic into bundled whiskers, fibers and filaments. The volume weighted diameter was reduced from 209 to 29 mum. Furthermore, the SAS CO(2) process yielded particles with significantly improved in vitro dissolution. Further research is needed to optimize the operation conditions of the self-built unit to maximize the production yield and produce a uniform polymorphic form of carbamazepine.

A comprehensive evaluation of CHEK2 germline mutations in men with prostate cancer.

PubMed

Wu, Yishuo; Yu, Hongjie; Zheng, S Lilly; Na, Rong; Mamawala, Mufaddal; Landis, Tricia; Wiley, Kathleen; Petkewicz, Jacqueline; Shah, Sameep; Shi, Zhuqing; Novakovic, Kristian; McGuire, Michael; Brendler, Charles B; Ding, Qiang; Helfand, Brian T; Carter, H Ballentine; Cooney, Kathleen A; Isaacs, William B; Xu, Jianfeng

2018-06-01

Germline mutations in CHEK2 have been associated with prostate cancer (PCa) risk. Our objective is to examine whether germline pathogenic CHEK2 mutations can differentiate risk of lethal from indolent PCa. A case-case study of 703 lethal PCa patients and 1455 patients with low-risk localized PCa of European, African, and Chinese origin was performed. Germline DNA samples from these patients were sequenced for CHEK2. Mutation carrier rates and their association with lethal PCa were analyzed using the Fisher exact test and Kaplan-Meier survival analysis. In the entire study population, 40 (1.85%) patients were identified as carrying one of 15 different germline CHEK2 pathogenic or likely pathogenic mutations. CHEK2 mutations were detected in 16 (2.28%) of 703 lethal PCa patients compared with 24 (1.65%) of 1455 low-risk PCa patients (P = 0.31). No association was found between CHEK2 mutation status and early-diagnosis or PCa-specific survival time. However, the most common mutation in CHEK2, c.1100delC (p.T367 fs), had a significantly higher carrier rate (1.28%) in lethal PCa patients than low-risk PCa patients of European American origin (0.16%), P = 0.0038. The estimated Odds Ratio of this mutation for lethal PCa was 7.86. The carrier rate in lethal PCa was also significantly higher than that (0.46%) in 32 461 non-Finnish European subjects from the Exome Aggregation Consortium (ExAC) (P = 0.01). While overall CHEK2 mutations were not significantly more common in men with lethal compared to low-risk PCa, the specific CHEK2 mutation, c.1100delC, appears to contribute to an increased risk of lethal PCa in European American men. © 2018 Wiley Periodicals, Inc.

Bone-induced c-kit expression in prostate cancer: a driver of intraosseous tumor growth

PubMed Central

Mainetti, Leandro E.; Zhe, Xiaoning; Diedrich, Jonathan; Saliganan, Allen D.; Cho, Won Jin; Cher, Michael L.; Heath, Elisabeth; Fridman, Rafael; Kim, Hyeong-Reh Choi; Bonfil, R. Daniel

2014-01-01

Loss of BRCA2 function stimulates prostate cancer (PCa) cell invasion and is associated with more aggressive and metastatic tumors in PCa patients. Concurrently, the receptor tyrosine kinase c-kit is highly expressed in skeletal metastases of PCa patients and induced in PCa cells placed into the bone microenvironment in experimental models. However, the precise requirement of c-kit for intraosseous growth of PCa and its relation to BRCA2 expression remain unexplored. Here, we show that c-kit expression promotes migration and invasion of PCa cells. Alongside, we found that c-kit expression in PCa cells parallels BRCA2 downregulation. Gene rescue experiments with human BRCA2 transgene in c-kit-transfected PCa cells resulted in reduction of c-kit protein expression and migration and invasion, suggesting a functional significance of BRCA2 downregulation by c-kit. The inverse association between c-kit and BRCA2 gene expressions in PCa cells was confirmed using laser capture microdissection in experimental intraosseous tumors and bone metastases of PCa patients. Inhibition of bone-induced c-kit expression in PCa cells transduced with lentiviral short hairpin RNA reduced intraosseous tumor incidence and growth. Overall, our results provide evidence of a novel pathway that links bone-induced c-kit expression in PCa cells to BRCA2 downregulation and supports bone metastasis. PMID:24798488

The impact of sexual orientation on body image, self-esteem, urinary and sexual functions in the experience of prostate cancer.

PubMed

Thomas, C; Wootten, A C; Robinson, P; Law, P C F; McKenzie, D P

2018-03-01

Prostate cancer (PCa) poses a large health burden globally. Research indicates that men experience a range of psychological challenges associated with PCa including changes to identity, self-esteem and body image. The ways in which sexual orientation plays a role in the experience of PCa, and the subsequent impact on quality of life (QoL), body image and self-esteem have only recently been addressed. By addressing treatment modality, where participant numbers were sufficient, we also sought to explore whether gay (homosexual) men diagnosed with PCa (PCaDx) and with a primary treatment modality of surgery would report differences in body image and self-esteem compared with straight (heterosexual) men with PCaDx with a primary treatment modality of surgery, compared with gay and straight men without PCaDx. The results of our study identified overall differences with respect to PCaDx (related to urinary function, sexual function and health evaluation), and sexual orientation (related to self-esteem), rather than interactions between sexual orientation and PCaDx. Gay men with PCaDx exhibited higher levels of urinary functioning than straight men with PCaDx, the difference being reversed for gay and straight men without PCaDx; but this result narrowly failed to achieve statistical significance, suggesting a need for further research, with larger samples. © 2018 John Wiley & Sons Ltd.

Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Bollito, Enrico; Manfredi, Matteo; Scarpa, Roberto Mario; Sottile, Antonino; Randone, Donato Franco; Porpiglia, Francesco

2014-12-01

To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Distal radius: anatomical morphometric gender characteristics. Do anatomical pre-shaped plates pay attention on it?

PubMed

Oppermann, Johannes; Bredow, Jan; Beyer, Frank; Neiss, Wolfram Friedrich; Spies, Christian K; Eysel, Peer; Dargel, Jens; Wacker, Max

2015-01-01

The purpose of the study was to investigate differences in the osseous structure anatomy of male and female distal radii. Morphometric data were obtained of 49 distal human cadaveric radii. An imprint of the distal edge was attained using silicone mass and the palmar cortical angle (PCA) of the lateral and intermediate column, here declared as medial, according to the concept of Rikli and Rigazzoni. The lateral and medial length and five widths were digitally measured by three observers. In order to compare the measurements an unpaired t test was used. To prove the reliability of the measurements an intraclass correlation analyses was done. Overall mean medial PCA was 148.25° (SD ± 6.83) and mean lateral PCA 156.07° (SD ± 7.00). In male specimens, the mean medial PCA was 147.38° (SD ± 6.01) and mean lateral PCA was 153.6° (SD ± 6.20) whereas in female specimens, the mean medial PCA was 149.41° (SD ± 7.79) and the mean lateral PCA 159.37° (SD ± 6.78), with statistical significance for the female lateral PCA. No gender significant difference for the medial PCA and no significant side difference for the PCA's could be found. The ICC of the observers was r = 0.936 and 0.976 for the medial and for lateral PCA 0.957-0.984. The palmar cortical length of the distal radius was significantly longer in male specimens. For all widths, larger values for male radii were measured, being statistically significant in all cases. Male dimensions concerning the wide were significantly larger when compared with females. Regarding the PCA at the medial and lateral column, we found significant difference for lateral PCA concerning the gender. Overall, study results demonstrated an angle of 148.25° ± 6.83 for the medial PCA and 156.07° ± 7.00 for the lateral PCA.

Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Jin Boo; Lee, Seong-Ho, E-mail: slee2000@umd.edu

Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment ofmore » PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.« less

Prostate cancer antigen 3 gene expression in peripheral blood and urine sediments from prostate cancer and benign prostatic hyperplasia patients versus healthy individuals.

PubMed

Moradi Sardareh, Hemen; Goodarzi, Mohammad Taghi; Yadegar-Azari, Reza; Poorolajal, Jalal; Mousavi-Bahar, Seyed Habibollah; Saidijam, Massoud

2014-11-30

To determine the expression of prostate cancer antigen 3 (PCA3) gene in peripheral blood and urine sediments from patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and normal subjects. A total number of 48 patients [24 with biopsy proven prostate cancer (PCa) and 24 with benign prostate hyperplasia (BPH)] were studied. Twenty-four healthy individuals were also recruited as control group. After blood and urine sampling, total RNA was extracted and cDNA was synthesized. Expression of PCA3 gene was assessed by quantitative reverse transcription polymerase chain reaction. Comparison of PCA3 gene expression between control and BPH groups indicated no statistically significant differences in both urine and blood samples. Patients with PCa demonstrated an increased PCA3 gene expression rate compared to control and BPH groups (10.64 and 7.17 folds, respectively). The rate of fold increased PCA3 gene expression in urine was 20.90, 20.90, and 20.35 in patients with PCa, BPH and normal subjects, respectively. Evaluation of PCA3 gene expression can be considered as a reliable marker for detection of PCa. Increased level of this marker in urine sediments is more sensitive than blood for distinguishing between cancerous and non-cancerous groups. 

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml

PubMed Central

Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D’Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K.; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA. PMID:23861782

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2-10 ng/ml.

PubMed

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D'Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.

Identification of an IL-1-induced gene expression pattern in AR+ PCa cells that mimics the molecular phenotype of AR- PCa cells.

PubMed

Thomas-Jardin, Shayna E; Kanchwala, Mohammed S; Jacob, Joan; Merchant, Sana; Meade, Rachel K; Gahnim, Nagham M; Nawas, Afshan F; Xing, Chao; Delk, Nikki A

2018-06-01

In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance. Furthermore, IL-1 and AR protein levels negatively correlate in PCa tumor cells. Taken together, we hypothesize that IL-1 reprograms AR positive (AR + ) PCa cells into AR negative (AR - ) PCa cells that co-opt IL-1 signaling to ensure AR-independent survival and tumor progression in the inflammatory tumor microenvironment. LNCaP and PC3 PCa cells were treated with IL-1β or HS-5 bone marrow stromal cell (BMSC) conditioned medium and analyzed by RNA sequencing and RT-QPCR. To verify genes identified by RNA sequencing, LNCaP, MDA-PCa-2b, PC3, and DU145 PCa cell lines were treated with the IL-1 family members, IL-1α or IL-1β, or exposed to HS-5 BMSC in the presence or absence of Interleukin-1 Receptor Antagonist (IL-1RA). Treated cells were analyzed by western blot and/or RT-QPCR. Comparative analysis of sequencing data from the AR + LNCaP PCa cell line versus the AR - PC3 PCa cell line reveals an IL-1-conferred gene suite in LNCaP cells that is constitutive in PC3 cells. Bioinformatics analysis of the IL-1 regulated gene suite revealed that inflammatory and immune response pathways are primarily elicited; likely facilitating PCa cell survival and tumorigenicity in an inflammatory tumor microenvironment. Our data supports that IL-1 reprograms AR + PCa cells to mimic AR - PCa gene expression patterns that favor AR-targeted treatment resistance and cell survival. © 2018 Wiley Periodicals, Inc.

Multilevel principal component analysis (mPCA) in shape analysis: A feasibility study in medical and dental imaging.

PubMed

Farnell, D J J; Popat, H; Richmond, S

2016-06-01

Methods used in image processing should reflect any multilevel structures inherent in the image dataset or they run the risk of functioning inadequately. We wish to test the feasibility of multilevel principal components analysis (PCA) to build active shape models (ASMs) for cases relevant to medical and dental imaging. Multilevel PCA was used to carry out model fitting to sets of landmark points and it was compared to the results of "standard" (single-level) PCA. Proof of principle was tested by applying mPCA to model basic peri-oral expressions (happy, neutral, sad) approximated to the junction between the mouth/lips. Monte Carlo simulations were used to create this data which allowed exploration of practical implementation issues such as the number of landmark points, number of images, and number of groups (i.e., "expressions" for this example). To further test the robustness of the method, mPCA was subsequently applied to a dental imaging dataset utilising landmark points (placed by different clinicians) along the boundary of mandibular cortical bone in panoramic radiographs of the face. Changes of expression that varied between groups were modelled correctly at one level of the model and changes in lip width that varied within groups at another for the Monte Carlo dataset. Extreme cases in the test dataset were modelled adequately by mPCA but not by standard PCA. Similarly, variations in the shape of the cortical bone were modelled by one level of mPCA and variations between the experts at another for the panoramic radiographs dataset. Results for mPCA were found to be comparable to those of standard PCA for point-to-point errors via miss-one-out testing for this dataset. These errors reduce with increasing number of eigenvectors/values retained, as expected. We have shown that mPCA can be used in shape models for dental and medical image processing. mPCA was found to provide more control and flexibility when compared to standard "single-level" PCA. Specifically, mPCA is preferable to "standard" PCA when multiple levels occur naturally in the dataset. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling

PubMed Central

2012-01-01

Background PCA3 is a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, but its functional role is unknown. To investigate its putative function in PCa biology, we used gene expression knockdown by small interference RNA, and also analyzed its involvement in androgen receptor (AR) signaling. Methods LNCaP and PC3 cells were used as in vitro models for these functional assays, and three different siRNA sequences were specifically designed to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and cell growth, viability, and apoptosis assays. Associations between PCA3 and the androgen-receptor (AR) signaling pathway were investigated by treating LNCaP cells with 100 nM dihydrotestosterone (DHT) and with its antagonist (flutamide), and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1, PSA, AR, FGF8, CdK1, CdK2 and PMEPA1). PCA3 expression levels were investigated in different cell compartments by using differential centrifugation and qRT-PCR. Results LNCaP siPCA3-transfected cells significantly inhibited cell growth and viability, and increased the proportion of cells in the sub G0/G1 phase of the cell cycle and the percentage of pyknotic nuclei, compared to those transfected with scramble siRNA (siSCr)-transfected cells. DHT-treated LNCaP cells induced a significant upregulation of PCA3 expression, which was reversed by flutamide. In siPCA3/LNCaP-transfected cells, the expression of AR target genes was downregulated compared to siSCr-transfected cells. The siPCA3 transfection also counteracted DHT stimulatory effects on the AR signaling cascade, significantly downregulating expression of the AR target gene. Analysis of PCA3 expression in different cell compartments provided evidence that the main functional roles of PCA3 occur in the nuclei and microsomal cell fractions. Conclusions Our findings suggest that the ncRNA PCA3 is involved in the control of PCa cell survival, in part through modulating AR signaling, which may raise new possibilities of using PCA3 knockdown as an additional therapeutic strategy for PCa control. PMID:23130941

Curcumin Suppresses In Vitro Proliferation and Invasion of Human Prostate Cancer Stem Cells by Modulating DLK1-DIO3 Imprinted Gene Cluster MicroRNAs.

PubMed

Zhang, Hu; Zheng, Jiajia; Shen, Hongliang; Huang, Yongyi; Liu, Te; Xi, Hao; Chen, Chuan

2018-01-01

Curcumin can suppress human prostate cancer (HuPCa) cell proliferation and invasion. However, it is not known whether curcumin can inhibit HuPCa stem cell (HuPCaSC) proliferation and invasion. We used methyl thiazolyl tetrazolium and Transwell assays to examine the proliferation and invasion of the HuPCaSC lines DU145 and 22Rv1 following curcumin or dimethyl sulfoxide (control) treatment. The microRNA (miRNA) expression levels in the DLK1-DIO3 imprinted genomic region in the cells and in tumor tissues from patients with PCa were examined using microarray and quantitative PCR. The median inhibitory concentration of curcumin for HuPCa cells significantly inhibited HuPCaSC proliferation and invasion in vitro. The miR-770-5p and miR-1247 expression levels in the DLK1-DIO3 imprinted gene cluster were significantly different between the curcumin-treated and control HuPCaSCs. Overexpression of these positive miRNAs significantly increased the inhibition rates of miR-770-5p- and miR-1247-transfected HuPCaSCs compared to the control miR-Mut-transfected HuPCaSCs. Lastly, low-tumor grade PCa tissues had higher miR-770-5p and miR-1247 expression levels than high-grade tumor tissues. Curcumin can suppress HuPCaSC proliferation and invasion in vitro by modulating specific miRNAs in the DLK1-DIO3 imprinted gene cluster.

Beyond textbook neuroanatomy: The syndrome of malignant PCA infarction.

PubMed

Gogela, Steven L; Gozal, Yair M; Rahme, Ralph; Zuccarello, Mario; Ringer, Andrew J

2015-01-01

Given its limited vascular territory, occlusion of the posterior cerebral artery (PCA) usually does not result in malignant infarction. Challenging this concept, we present 3 cases of unilateral PCA infarction with secondary malignant progression, resulting from extension into what would classically be considered the posterior middle cerebral artery (MCA) territory. Interestingly, these were true PCA infarctions, not "MCA plus" strokes, since the underlying occlusive lesion was in the PCA. We hypothesize that congenital and/or acquired variability in the distribution and extent of territory supplied by the PCA may underlie this rare clinical entity. Patients with a PCA infarction should thus be followed closely and offered early surgical decompression in the event of malignant progression.

Androgen Receptor Expression in Epithelial and Stromal Cells of Prostatic Carcinoma and Benign Prostatic Hyperplasia.

PubMed

Filipovski, Vanja; Kubelka-Sabit, Katerina; Jasar, Dzengis; Janevska, Vesna

2017-08-15

Prostatic carcinoma (PCa) derives from prostatic epithelial cells. However stromal microenvironment, associated with malignant epithelium, also plays a role in prostatic carcinogenesis. Alterations in prostatic stromal cells contribute to the loss of growth control in epithelial cells that lead to progression of PCa. To analyse the differences between Androgen Receptor (AR) expression in both epithelial and stromal cells in PCa and the surrounding benign prostatic hyperplasia (BPH) and to compare the results with tumour grade. Samples from 70 cases of radical prostatectomy specimens were used. The expression and intensity of the signal for AR was analysed in the epithelial and stromal cells of PCa and BPH, and the data was quantified using histological score (H-score). AR showed significantly lower expression in both epithelial and stromal cells of PCa compared to BPH. In PCa a significant positive correlation of AR expression was found between stromal and epithelial cells of PCa. AR expression showed a correlation between the stromal cells of PCa and tumour grade. AR expression is reduced in epithelial and stromal cells of PCa. Expression of AR in stromal cells of PCa significantly correlates with tumour grade.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Dibash K.; The Graduate Center Departments of Biology and Biochemistry, The City University of New York, New York, NY 10016; Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065

Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of microRNA-1207-3p in PCa is unclear. We discovered that microRNA-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells. Increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of FNDC1, a protein which contains a conserved protein domain of fibronectin (FN1). FNDC1, FN1, and themore » androgen receptor (AR) are significantly overexpressed in PCa cell lines and human PCa, and positively correlate with aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa-specific death is significantly higher than in patients that remained alive. Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa. Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa. - Graphical abstract: miR-1207-3p/FNDC1/FN1/AR is a novel regulatory pathway in prostate cancer. - Highlights: • Expression of microRNA-1207-3p is significantly lost in prostate cancer (PCa) cells. • MicroRNA-1207-3p regulates proliferation, apoptosis, and migration via direct molecular targeting of the 3′UTR of FNDC1. • MicroRNA-1207-3p regulates proliferation, apoptosis, and migration via direct molecular targeting of the 3′UTR of FNDC1. • FNDC1, FN1, and AR are concurrently overexpressed in metastatic PCa.« less

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

PubMed

Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M; Aleixandre, Rosa N; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2016-01-01

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes

PubMed Central

Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M.; Aleixandre, Rosa N.; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2016-01-01

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic. PMID:27279911

Testing the impact of a multimedia video CD of patient-controlled analgesia on pain knowledge and pain relief in patients receiving surgery.

PubMed

Chen, Hsing-Hsia; Yeh, Mei-Ling; Yang, Hui-Ju

2005-07-01

This study aimed to develop a multimedia video CD (VCD) of patient-controlled analgesia (PCA) and test its effects on pain knowledge and pain relief in patients receiving surgery. This multimedia VCD of PCA was created to convey fundamental knowledge to both patients and their family members and help patients properly utilize PCA devices to relieve pain and improve recovery. The content of multimedia VCD of PCA included pre-admission pain education, introduction of PCA, nursing care procedures, and questions and answers. This study used a quasi-experimental research design to test effects of the multimedia education program in the experimental group of 30 subjects compared to the control subjects of equal number (without the multimedia VCD of PCA). (1) The intervention of multimedia VCD of PCA resulted in a statistically significant difference in pain knowledge between the experimental and control groups. (2) Subjects in the experimental group obtained a better outcome of pain relief compared to control subjects. (3) Subjects in the experimental group indicated that the multimedia VCD of PCA indeed helped them effectively operate their PCA devices to relieve surgery pain. The clinical application of the multimedia VCD of PCA could help patients improve knowledge on pain, learn how to use PCA devices, achieve proper pain relief, and increase effectiveness of recovery activities.

Circular RNA Myosin Light Chain Kinase (MYLK) Promotes Prostate Cancer Progression through Modulating Mir-29a Expression.

PubMed

Dai, Yuanqing; Li, Dongjie; Chen, Xiong; Tan, Xinji; Gu, Jie; Chen, Mingquan; Zhang, Xiaobo

2018-05-25

BACKGROUND In developed countries, prostate cancer (PCa) is a frequently diagnosed cancer with the second highest fatality rate. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) stably expressed in cells and involved in a series of carcinomas. However, few research studies have reported on the role of circRNAs in PCa. MATERIAL AND METHODS We used qRT-PCR to detect the expression of circMYLK (circRNA ID: hsa_circ_0141940) and miR-29a in PCa tissues and cell lines. MTT, colony formation, and TUNEL assays were performed to analysis the cell viability of PCa cells. Transwell and wound scratch assays were performed to investigate the cell invasion and migration of PCa cells. RESULTS In the present study, we confirmed that circMYLK expression level was significantly higher in PCa samples and PCa cells than in normal tissues and normal prostatic cells. The upregulated circRNA-MYLK promoted PCa cells proliferation, invasion, and migration; however, si-circRNA-MYLK significantly accelerated the PCa cell apoptosis. We also observed that the aforementioned function of circRNA-MYLK on PCa cells was affected through targeting miR-29a. CONCLUSIONS We confirmed circRNA-MYLK was an oncogene in PCa and revealed a novel mechanism underlying circRNA-MYLK in PC progression.

The theoretical and experimental study on dicalcium phosphate dehydrate loading with protocatechuic aldehyde.

PubMed

Guo, Yuehua; Qu, Shuxin; Lu, Xiong; Xie, Haodong; Zhang, Hongping; Weng, Jie

2010-07-01

The aim of this study is to investigate the interaction between dicalcium phosphate dihydrate (CaHPO(4) x 2H(2)O, DCPD) and Protocatechuic aldehyde (C(7)H(6)O(3), Pca), which is the water-soluble constituents of Chinese Medicine, Salvia Miltiorrhiza Bunge (SMB), by calculating the absorption energy through molecular dynamics simulation. Furthermore, the effects of functional groups of Pca and temperature on Pca adsorbed by DCPD are calculated respectively. DCPD/Pca and DCPD were analyzed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TG). The simulation results showed that Pca mostly absorbed on the (0 2 0) surface of DCPD. The aldehyde group of Pca played a moren important role on the adsorption of Pca on DCPD than hydroxyl did, while temperature had no distinct effects on the adsorption. XRD results indicated that Pca induced the preferential growth of (0 2 0) crystal surface in DCPC/Pca whereas it had no influence on the crystal structure, the crystallinity and grain size of DCPD. FTIR and TG results showed that the characteristic peak of Pca was at 1295 cm(-1) and the content of Pca in DCPD was 16%, respectively. The present results show that molecular dynamics simulation is a very effective and complementary method to study the interaction between materials and medicine.

Applying robust variant of Principal Component Analysis as a damage detector in the presence of outliers

NASA Astrophysics Data System (ADS)

Gharibnezhad, Fahit; Mujica, Luis E.; Rodellar, José

2015-01-01

Using Principal Component Analysis (PCA) for Structural Health Monitoring (SHM) has received considerable attention over the past few years. PCA has been used not only as a direct method to identify, classify and localize damages but also as a significant primary step for other methods. Despite several positive specifications that PCA conveys, it is very sensitive to outliers. Outliers are anomalous observations that can affect the variance and the covariance as vital parts of PCA method. Therefore, the results based on PCA in the presence of outliers are not fully satisfactory. As a main contribution, this work suggests the use of robust variant of PCA not sensitive to outliers, as an effective way to deal with this problem in SHM field. In addition, the robust PCA is compared with the classical PCA in the sense of detecting probable damages. The comparison between the results shows that robust PCA can distinguish the damages much better than using classical one, and even in many cases allows the detection where classic PCA is not able to discern between damaged and non-damaged structures. Moreover, different types of robust PCA are compared with each other as well as with classical counterpart in the term of damage detection. All the results are obtained through experiments with an aircraft turbine blade using piezoelectric transducers as sensors and actuators and adding simulated damages.

Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.

PubMed

Rubio-Briones, Jose; Borque, Angel; Esteban, Luis M; Casanova, Juan; Fernandez-Serra, Antonio; Rubio, Luis; Casanova-Salas, Irene; Sanz, Gerardo; Domínguez-Escrig, Jose; Collado, Argimiro; Gómez-Ferrer, Alvaro; Iborra, Inmaculada; Ramírez-Backhaus, Miguel; Martínez, Francisco; Calatrava, Ana; Lopez-Guerrero, Jose A

2015-09-11

PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.

Pain Levels Within 24 Hours After UFE: A Comparison of Morphine and Fentanyl Patient-Controlled Analgesia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hyun S., E-mail: sikhkim@jhmi.edu; Czuczman, Gregory J.; Nicholson, Wanda K.

The purpose of this study was to assess the presence and severity of pain levels during 24 h after uterine fibroid embolization (UFE) for symptomatic leiomyomata and compare the effectiveness and adverse effects of morphine patient-controlled analgesia (PCA) versus fentanyl PCA. We carried out a prospective, nonrandomized study of 200 consecutive women who received UFE and morphine or fentanyl PCA after UFE. Pain perception levels were obtained on a 0-10 scale for the 24-h period after UFE. Linear regression methods were used to determine pain trends and differences in pain trends between two groups and the association between pain scoresmore » and patient covariates. One hundred eighty-five patients (92.5%) reported greater-than-baseline pain after UFE, and 198 patients (99%) required IV opioid PCA. One hundred thirty-six patients (68.0%) developed nausea during the 24-h period. Seventy-two patients (36%) received morphine PCA and 128 (64%) received fentanyl PCA, without demographic differences. The mean dose of morphine used was 33.8 {+-} 26.7 mg, while the mean dose of fentanyl was 698.7 {+-} 537.4 {mu}g. Using this regimen, patients who received morphine PCA had significantly lower pain levels than those who received fentanyl PCA (p < 0.0001). We conclude that patients develop pain requiring IV opioid PCA within 24 h after UFE. Morphine PCA is more effective in reducing post-uterine artery embolization pain than fentanyl PCA. Nausea is a significant adverse effect from opioid PCA.« less

Flight test of a propulsion controlled aircraft system on the NASA F-15 airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.

1995-01-01

Flight tests of the propulsion controlled aircraft (PCA) system on the NASA F-15 airplane evolved as a result of a long series of simulation and flight tests. Initially, the simulation results were very optimistic. Early flight tests showed that manual throttles-only control was much more difficult than the simulation, and a flight investigation was flown to acquire data to resolve this discrepancy. The PCA system designed and developed by MDA evolved as these discrepancies were found and resolved, requiring redesign of the PCA software and modification of the flight test plan. Small throttle step inputs were flown to provide data for analysis, simulation update, and control logic modification. The PCA flight tests quickly revealed less than desired performance, but the extensive flexibility built into the flight PCA software allowed rapid evaluation of alternate gains, filters, and control logic, and within 2 weeks, the PCA system was functioning well. The initial objective of achieving adequate control for up-and-away flying and approaches was satisfied, and the option to continue to actual landings was achieved. After the PCA landings were accomplished, other PCA features were added, and additional maneuvers beyond those originally planned were flown. The PCA system was used to recover from extreme upset conditions, descend, and make approaches to landing. A heading mode was added, and a single engine plus rudder PCA mode was also added and flown. The PCA flight envelope was expanded far beyond that originally designed for. Guest pilots from the USAF, USN, NASA, and the contractor also flew the PCA system and were favorably impressed.

An In Vitro Spectroscopic Analysis to Determine Whether para-Chloroaniline is Produced from Mixing Sodium Hypochlorite and Chlorhexidine

PubMed Central

Thomas, John E.; Sem, Daniel S.

2009-01-01

Introduction The purpose of this in vitro study was to determine whether para-chloroaniline (PCA) is formed through the reaction of mixing sodium hypochlorite (NaOCl) and chlorhexidine (CHX). Methods Initially commercially available samples of chlorhexidine acetate (CHXa) and PCA were analyzed with 1H NMR spectroscopy. Two solutions, NaOCl and CHXa, were warmed to 37°C and when mixed they produced a brown precipitate. This precipitate was separated in half and pure PCA was added to one of the samples for comparison before they were each analyzed with 1H NMR spectroscopy. Results The peaks in the 1H NMR spectra of CHXa and PCA were assigned to specific protons of the molecules, and the location of the aromatic peaks in the PCA spectrum defined the PCA doublet region. While the spectrum of the precipitate alone resulted in a complex combination of peaks, upon magnification there were no peaks in the PCA doublet region which were intense enough to be quantified. In the spectrum of the precipitate, to which PCA was added, two peaks do appear in the PCA doublet region. Comparing this spectrum to that of precipitate alone, the peaks in the PCA doublet region are not visible prior to the addition of PCA. Conclusions Based on this in vitro study, the reaction mixture of NaOCl and CHXa does not produce PCA at any measurable quantity and further investigation is needed to determine the chemical composition of the brown precipitate. PMID:20113799

External validation of a PCA-3-based nomogram for predicting prostate cancer and high-grade cancer on initial prostate biopsy.

PubMed

Greene, Daniel J; Elshafei, Ahmed; Nyame, Yaw A; Kara, Onder; Malkoc, Ercan; Gao, Tianming; Jones, J Stephen

2016-08-01

The aim of this study was to externally validate a previously developed PCA3-based nomogram for the prediction of prostate cancer (PCa) and high-grade (intermediate and/or high-grade) prostate cancer (HGPCa) at the time of initial prostate biopsy. A retrospective review was performed on a cohort of 336 men from a large urban academic medical center. All men had serum PSA <20 ng/ml and underwent initial transrectal ultrasound-guided prostate biopsy with at least 10 cores sampling for suspicious exam and/or elevated PSA. Covariates were collected for the nomogram and included age, ethnicity, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and abnormal finding on digital rectal exam (DRE). These variables were used to test the accuracy (concordance index) and calibration of a previously published PCA3 nomogram. Biopsy confirms PCa and HGPCa in 51.0% and 30.4% of validation patients, respectively. This differed from the original cohort in that it had significantly more PCa and HGPCA (51% vs. 44%, P = 0.019; and 30.4% vs. 19.1%, P < 0.001). Despite the differences in PCa detection the concordance index was 75% and 77% for overall PCa and HGPCa, respectively. Calibration for overall PCa was good. This represents the first external validation of a PCA3-based prostate cancer predictive nomogram in a North American population. Prostate 76:1019-1023, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain?

PubMed

Mathews, Timothy J; Churchhouse, Antonia M D; Housden, Tessa; Dunning, Joel

2012-02-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'is the addition of ketamine to morphine patient-controlled analgesia (PCA) following thoracic surgery superior to morphine alone'. Altogether 201 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This consisted of one systematic review of PCA morphine with ketamine (PCA-MK) trials, one meta-analysis of PCA-MK trials, four randomized controlled trials of PCA-MK, one meta-analysis of trials using a variety of peri-operative ketamine regimes and two cohort studies of PCA-MK. Main outcomes measured included pain score rated on visual analogue scale, morphine consumption and incidence of psychotomimetic side effects/hallucination. Two papers reported the measurements of respiratory function. This evidence shows that adding ketamine to morphine PCA is safe, with a reported incidence of hallucination requiring intervention of 2.9%, and a meta-analysis finding an incidence of all central nervous system side effects of 18% compared with 15% with morphine alone, P = 0.31, RR 1.27 with 95% CI (0.8-2.01). All randomized controlled trials of its use following thoracic surgery found no hallucination or psychological side effect. All five studies in thoracic surgery (n = 243) found reduced morphine requirements with PCA-MK. Pain scores were significantly lower in PCA-MK patients in thoracic surgery papers, with one paper additionally reporting increased patient satisfaction. However, no significant improvement was found in a meta-analysis of five papers studying PCA-MK in a variety of surgical settings. Both papers reporting respiratory outcomes found improved oxygen saturations and PaCO(2) levels in PCA-MK patients following thoracic surgery. We conclude that adding low-dose ketamine to morphine PCA is safe and post-thoracotomy may provide better pain control than PCA with morphine alone (PCA-MO), with reduced morphine consumption and possible improvement in respiratory function. These studies thus support the routine use of PCA-MK instead of PCA-MO to improve post-thoracotomy pain control.

Using Serological Proteome Analysis to Identify Serum Anti-Nucleophosmin 1 Autoantibody as a Potential Biomarker in European-American and African-American Patients With Prostate Cancer.

PubMed

Dai, Liping; Li, Jitian; Xing, Mengtao; Sanchez, Tino W; Casiano, Carlos A; Zhang, Jian-Ying

2016-11-01

The prostate-specific antigen (PSA) testing has been widely implemented for the early detection and management of prostate cancer (PCa). However, the lack of specificity has led to overdiagnosis, resulting in many possibly unnecessary biopsies and overtreatment. Therefore, novel serological biomarkers with high sensitivity and specificity are of vital importance needed to complement PSA testing in the early diagnosis and effective management of PCa. This is particularly critical in the context of PCa health disparities, where early detection and management could help reduce the disproportionately high PCa mortality observed in African-American men. Previous studies have demonstrated that sera from patients with PCa contain autoantibodies that react with tumor-associated antigens (TAAs). The serological proteome analysis (SERPA) approach was used to identify tumor-associated antigens (TAAs) of PCa. In evaluation study, the level of anti-NPM1 antibody was examined in sera from test cohort, validation cohort, as well as European-American (EA) and African-American (AA) men with PCa by using immunoassay. Nucleophosmin 1 (NPM1) as a 33 kDa TAA in PCa was identified and characterized by SERPA approach. Anti-NPM1 antibody level in PCa was higher than in benign prostatic hyperplasia (BPH) patients and healthy individuals. Receiver operating characteristic (ROC) curve analysis showed similar high diagnostic value for PCa in the test cohort (area under the curve (AUC):0.860) and validation cohort (AUC: 0.822) to differentiate from normal individuals and BPH. Interestingly, AUC values were significantly higher for AA PCa patients. When considering concurrent serum measurements of anti-NPM1 antibody and PSA, 97.1% PCa patients at early stage were identified correctly, while 69.2% BPH patients who had elevated PSA levels were found to be anti-NPM1 negative. Additionally, anti-NPM1 antibody levels in PCa patients at early stage significantly increased after surgery treatment. This intriguing data suggested that NPM1 can elicit autoantibody response in PCa and might be a potential biomarker for the immunodiagnosis and prognosis of PCa, and for supplementing PSA testing in distinguishing PCa from BPH. Prostate 76:1375-1386, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neuropsychiatric Symptoms in Posterior Cortical Atrophy and Alzheimer Disease

PubMed Central

Crutch, Sebastian J.; Franco-Macías, Emilio; Gil-Néciga, Eulogio

2016-01-01

Background: Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterized by early progressive visual dysfunction in the context of relative preservation of memory and a pattern of atrophy mainly involving the posterior cortex. The aim of the present study is to characterize the neuropsychiatric profile of PCA. Methods: The Neuropsychiatric Inventory was used to assess 12 neuropsychiatric symptoms (NPS) in 28 patients with PCA and 34 patients with typical Alzheimer disease (AD) matched by age, disease duration, and illness severity. Results: The most commonly reported NPS in both groups were depression, anxiety, apathy, and irritability. However, aside from a trend toward lower rates of apathy in patients with PCA, there were no differences in the percentage of NPS presented in each group. All those patients presenting visual hallucinations in the PCA group also met diagnostic criteria for dementia with Lewy bodies (DLB). Auditory hallucinations were only present in patients meeting diagnosis criteria for DLB. Conclusion: Prevalence of the 12 NPS examined was similar between patients with PCA and AD. Hallucinations in PCA may be helpful in the differential diagnosis between PCA-AD and PCA-DLB. PMID:26404166

The function of oxytocin: a potential biomarker for prostate cancer diagnosis and promoter of prostate cancer.

PubMed

Xu, Huan; Fu, Shi; Chen, Qi; Gu, Meng; Zhou, Juan; Liu, Chong; Chen, Yanbo; Wang, Zhong

2017-05-09

To measure the level of oxytocin in serum and prostate cancer (PCa) tissue and study its effect on the proliferation of PCa cells. Oxytocin level in serum was significantly increased in PCa patients compared with the no-carcinoma individuals. Additionally, the levels of oxytocin and its receptor were also elevated in the PCa tissue. However, no significant difference existed among the PCa of various Gleason grades. Western blot analysis confirmed the previous results and revealed an increased expression level of APPL1. The level of oxytocin in serum was measured by ELISA analysis. The expression of oxytocin and its receptor in prostate was analyzed by immunohistochemistry. The proliferation and apoptosis of PCa cells were assessed by the Cell Counting Kit 8 (CCK8) assay, cell cycle analysis and caspase3 activity analysis, respectively. Western blot analysis was used for the detection of PCNA, Caspase3 and APPL1 protein levels. Serum and prostatic oxytocin levels are increased in the PCa subjects. Serum oxytocin level may be a biomarker for PCa in the future. Oxytocin increases PCa growth and APPL1 expression.

Effect of deep-fat frying on sensory and textural attributes of pellet snacks.

PubMed

BahramParvar, Maryam; Mohammadi Moghaddam, Toktam; Razavi, Seyed M A

2014-12-01

In this paper, the effects of several frying parameters on the quality of indirect expanded snacks were studied. Pellets, in two colors of yellow and green, were deep-fat fried at 150, 170, and 190 °C for 0.5, 1.5, 2.5, 3.5, and 4.5 min; then, subjected to uniaxial compression test and sensory analysis. The results showed that hardness, fracture force and apparent modulus of elasticity reduced with increase in frying time and temperature due to puffing samples and decrease in crust thickness. In contrast, higher frying temperature improved the crispness of samples. Panelists preferred the flavor, color, and total acceptance of yellow samples to the green ones. Moreover, principal component analysis (PCA) of instrumental and sensory data provided important information for the correlation of objective and sensory properties.

Association between age-related reductions in testosterone and risk of prostate cancer-An analysis of patients' data with prostatic diseases.

PubMed

Wang, Kai; Chen, Xinguang; Bird, Victoria Y; Gerke, Travis A; Manini, Todd M; Prosperi, Mattia

2017-11-01

The relationship between serum total testosterone and prostate cancer (PCa) risk is controversial. The hypothesis that faster age-related reduction in testosterone is linked with increased PCa risk remains untested. We conducted our study at a tertiary-level hospital in southeast of the USA, and derived data from the Medical Registry Database of individuals that were diagnosed of any prostate-related disease from 2001 to 2015. Cases were those diagnosed of PCa and had one or more measurements of testosterone prior to PCa diagnosis. Controls were those without PCa and had one or more testosterone measurements. Multivariable logistic regression models for PCa risk of absolute levels (one-time measure and 5-year average) and annual change in testosterone were respectively constructed. Among a total of 1,559 patients, 217 were PCa cases, and neither one-time measure nor 5-year average of testosterone was found to be significantly associated with PCa risk. Among the 379 patients with two or more testosterone measurements, 27 were PCa cases. For every 10 ng/dL increment in annual reduction of testosterone, the risk of PCa would increase by 14% [adjusted odds ratio, 1.14; 95% confidence interval (CI), 1.03-1.25]. Compared to patients with a relatively stable testosterone, patients with an annual testosterone reduction of more than 30 ng/dL had 5.03 [95% CI: 1.53, 16.55] fold increase in PCa risk. This implies a faster age-related reduction in, but not absolute level of serum total testosterone as a risk factor for PCa. Further longitudinal studies are needed to confirm this finding. © 2017 UICC.

European Randomized Study of Screening for Prostate Cancer Risk Calculator: External Validation, Variability, and Clinical Significance.

PubMed

Gómez-Gómez, Enrique; Carrasco-Valiente, Julia; Blanca-Pedregosa, Ana; Barco-Sánchez, Beatriz; Fernandez-Rueda, Jose Luis; Molina-Abril, Helena; Valero-Rosa, Jose; Font-Ugalde, Pilar; Requena-Tapia, Maria José

2017-04-01

To externally validate the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) and to evaluate its variability between 2 consecutive prostate-specific antigen (PSA) values. We prospectively catalogued 1021 consecutive patients before prostate biopsy for suspicion of prostate cancer (PCa). The risk of PCa and significant PCa (Gleason score ≥7) from 749 patients was calculated according to ERSPC-RC (digital rectal examination-based version 3 of 4) for 2 consecutive PSA tests per patient. The calculators' predictions were analyzed using calibration plots and the area under the receiver operating characteristic curve (area under the curve). Cohen kappa coefficient was used to compare the ability and variability. Of 749 patients, PCa was detected in 251 (33.5%) and significant PCa was detected in 133 (17.8%). Calibration plots showed an acceptable parallelism and similar discrimination ability for both PSA levels with an area under the curve of 0.69 for PCa and 0.74 for significant PCa. The ERSPC showed 226 (30.2%) unnecessary biopsies with the loss of 10 significant PCa. The variability of the RC was 16% for PCa and 20% for significant PCa, and a higher variability was associated with a reduced risk of significant PCa. We can conclude that the performance of the ERSPC-RC in the present cohort shows a high similitude between the 2 PSA levels; however, the RC variability value is associated with a decreased risk of significant PCa. The use of the ERSPC in our cohort detects a high number of unnecessary biopsies. Thus, the incorporation of ERSPC-RC could help the clinical decision to carry out a prostate biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Substantial Family History of Prostate Cancer in Black Men Recruited for Prostate Cancer Screening

PubMed Central

Mastalski, Kathleen; Coups, Elliot J.; Ruth, Karen; Raysor, Susan; Giri, Veda N.

2008-01-01

Background Black men are at increased risk for prostate cancer (PCA), particularly with a family history (FH) of the disease. Previous reports have raised concern for suboptimal screening of Black men with a FH of PCA. We report on the extent of FH of PCA from a prospective, longitudinal PCA screening program for high-risk men. Methods Black men ages 35-69 are eligible for PCA screening through the Prostate Cancer Risk Assessment Program (PRAP) regardless of FH. Rates of self-reported FH of PCA, breast, and colon cancer at baseline were compared with an age-matched sample of Black men from the 2005 National Health Interview Survey (NHIS) using standard statistical methods. Results As of January 2007, 332 Black men with pedigree information were enrolled in PRAP and FH of PCA was compared to 838 Black men from the 2005 NHIS. Black men in PRAP reported significantly more first-degree relatives with PCA compared to Black men in the 2005 NHIS (34.3%, 95% CI 29.2-39.7 vs. 5.7%, 95% CI 3.9-7.4). Black men in PRAP also had more FH of breast cancer compared to the 2005 NHIS (11.5%, 95% CI 8.2-15.4 vs 6.3%, 95% CI 4.6-8.0). Conclusions FH of PCA appears to be a motivating factor for Black men seeking PCA screening. Targeted recruitment and education among Black families should improve PCA screening rates. Efforts to recruit Black men without a FH of PCA are also needed. Condensed Abstract Black men seeking prostate cancer screening have a substantial burden of family history of prostate cancer. Targeted education and enhancing discussion in Black families should increase prostate cancer screening and adherence. PMID:18816608

Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories.

PubMed

Arthur, Rhonda; Møller, Henrik; Garmo, Hans; Holmberg, Lars; Stattin, Pår; Malmstrom, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Robinson, David; Jungner, Ingmar; Hemelrijck, Mieke Van

2016-06-01

Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 μg/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 μg/L compared to PSA 4.0-9.9 μg/L. Hypertriglyceridemia was also positively associated with PSA>20 μg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

[Interest of evaluation of professional practice for the improvement of the management of postoperative pain with patient controlled analgesia (PCA)].

PubMed

Baumann, A; Cuignet-Royer, E; Cornet, C; Trueck, S; Heck, M; Taron, F; Peignier, C; Chastel, A; Gervais, P; Bouaziz, H; Audibert, G; Mertes, P-M

2010-10-01

To evaluate the daily practice of postoperative PCA in Nancy University Hospital, in continuity with a quality program of postoperative pain (POP) care conducted in 2003. A retrospective audit of patient medical records. A review of all the medical records of consecutive surgical patients managed by PCA over a 5-week period in six surgical services. Criteria studied: Evaluation of hospital means (eight criteria) and of medical and nursing staff practice (16 criteria). A second audit was conducted 6 months after the implementation of quality improvement measures. Assessment of the hospital means: temperature chart including pain scores and PCA drug consumption, patient information leaflet, PCA protocol, postoperative pre-filled prescription form (PFPF) for post-anaesthesia care including PCA, and optional training of nurses in postoperative pain management. EVALUATION OF PRACTICES: One hundred and fifty-nine files of a total of 176 patients were analyzed (88%). Improvements noted after 6 months: trace of POP evaluation progressed from 73 to 87%, advance prescription of PCA adjustment increased from 56 to 68% and of the treatment of adverse effects from 54 to 68%, trace of PCA adaptation by attending nurse from 15 to 43%, trace of the administration of the treatment of adverse effects by attending nurse from 24% to 64%, as did the use of PFPF from 59 to 70%. The usefulness of a pre-filled prescription form for post-anaesthesia care including PCA prescription is demonstrated. Quality improvement measures include: poster information and pocket guides on PCA for nurses, training of 3 nurses per service to act as "PCA advisers" who will in turn train their ward colleagues in PCA management and the use of equipment until an acute pain team is established. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Innovative Comparison of Transient Ignition Temperature at the Booster Interface, New Stainless Steel Pyrovalve Primer Chamber Assembly "V" (PCA) Design Versus the Current Aluminum "Y" PCA Design

NASA Technical Reports Server (NTRS)

Saulsberry, Regor L.; McDougle, Stephen H.; Garcia,Roberto; Johnson, Kenneth L.; Sipes, William; Rickman, Steven; Hosangadi, Ashvin

2011-01-01

An assessment of four spacecraft pyrovalve anomalies that occurred during ground testing was conducted by the NASA Engineering & Safety Center (NESC) in 2008. In all four cases, a common aluminum (Al) primer chamber assembly (PCA) was used with dual NASA Standard Initiators (NSIs) and the nearly simultaneous (separated by less than 80 microseconds) firing of both initiators failed to ignite the booster charge. The results of the assessment and associated test program were reported in AIAA Paper AIAA-2008-4798, NESC Independent Assessment of Pyrovalve Ground Test Anomalies. As a result of the four Al PCA anomalies, and the test results and findings of the NESC assessment, the Mars Science Laboratory (MSL) project team decided to make changes to the PCA. The material for the PCA body was changed from aluminum (Al) to stainless steel (SS) to avoid melting, distortion, and potential leakage of the NSI flow passages when the device functioned. The flow passages, which were interconnected in a Y-shaped configuration (Y-PCA) in the original design, were changed to a V-shaped configuration (V-PCA). The V-shape was used to more efficiently transfer energy from the NSIs to the booster. Development and qualification testing of the new design clearly demonstrated faster booster ignition times compared to the legacy AL Y-PCA design. However, the final NESC assessment report recommended that the SS V-PCA be experimentally characterized and quantitatively compared to the Al Y-PCA design. This data was deemed important for properly evaluating the design options for future NASA projects. This test program has successfully quantified the improvement of the SS V-PCA over the Al Y-PCA. A phase B of the project was also conducted and evaluated the effect of firing command skew and enlargement of flame channels to further assist spacecraft applications.

Epileptic seizure detection in EEG signal with GModPCA and support vector machine.

PubMed

Jaiswal, Abeg Kumar; Banka, Haider

2017-01-01

Epilepsy is one of the most common neurological disorders caused by recurrent seizures. Electroencephalograms (EEGs) record neural activity and can detect epilepsy. Visual inspection of an EEG signal for epileptic seizure detection is a time-consuming process and may lead to human error; therefore, recently, a number of automated seizure detection frameworks were proposed to replace these traditional methods. Feature extraction and classification are two important steps in these procedures. Feature extraction focuses on finding the informative features that could be used for classification and correct decision-making. Therefore, proposing effective feature extraction techniques for seizure detection is of great significance. Principal Component Analysis (PCA) is a dimensionality reduction technique used in different fields of pattern recognition including EEG signal classification. Global modular PCA (GModPCA) is a variation of PCA. In this paper, an effective framework with GModPCA and Support Vector Machine (SVM) is presented for epileptic seizure detection in EEG signals. The feature extraction is performed with GModPCA, whereas SVM trained with radial basis function kernel performed the classification between seizure and nonseizure EEG signals. Seven different experimental cases were conducted on the benchmark epilepsy EEG dataset. The system performance was evaluated using 10-fold cross-validation. In addition, we prove analytically that GModPCA has less time and space complexities as compared to PCA. The experimental results show that EEG signals have strong inter-sub-pattern correlations. GModPCA and SVM have been able to achieve 100% accuracy for the classification between normal and epileptic signals. Along with this, seven different experimental cases were tested. The classification results of the proposed approach were better than were compared the results of some of the existing methods proposed in literature. It is also found that the time and space complexities of GModPCA are less as compared to PCA. This study suggests that GModPCA and SVM could be used for automated epileptic seizure detection in EEG signal.

Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins*

PubMed Central

Sanchez, Tino W.; Zhang, Guangyu; Li, Jitian; Dai, Liping; Mirshahidi, Saied; Wall, Nathan R.; Yates, Clayton; Wilson, Colwick; Montgomery, Susanne; Zhang, Jian-Ying; Casiano, Carlos A.

2016-01-01

African American (AA) men suffer from a disproportionately high incidence and mortality of prostate cancer (PCa) compared with other racial/ethnic groups. Despite these disparities, African American men are underrepresented in clinical trials and in studies on PCa biology and biomarker discovery. We used immunoseroproteomics to profile antitumor autoantibody responses in AA and European American (EA) men with PCa, and explored differences in these responses. This minimally invasive approach detects autoantibodies to tumor-associated antigens that could serve as clinical biomarkers and immunotherapeutic agents. Sera from AA and EA men with PCa were probed by immunoblotting against PC3 cell proteins, with AA sera showing stronger immunoreactivity. Mass spectrometry analysis of immunoreactive protein spots revealed that several AA sera contained autoantibodies to a number of proteins associated with both the glycolysis and plasminogen pathways, particularly to alpha-enolase (ENO1). The proteomic data is deposited in ProteomeXchange with identifier PXD003968. Analysis of sera from 340 racially diverse men by enzyme-linked immunosorbent assays (ELISA) showed higher frequency of anti-ENO1 autoantibodies in PCa sera compared with control sera. We observed differences between AA-PCa and EA-PCa patients in their immunoreactivity against ENO1. Although EA-PCa sera reacted with higher frequency against purified ENO1 in ELISA and recognized by immunoblotting the endogenous cellular ENO1 across a panel of prostate cell lines, AA-PCa sera reacted weakly against this protein by ELISA but recognized it by immunoblotting preferentially in metastatic cell lines. These race-related differences in immunoreactivity to ENO1 could not be accounted by differential autoantibody recognition of phosphoepitopes within this antigen. Proteomic analysis revealed differences in the posttranslational modification profiles of ENO1 variants differentially recognized by AA-PCa and EA-PCa sera. These intriguing results suggest the possibility of race-related differences in the antitumor autoantibody response in PCa, and have implications for defining novel biological determinants of PCa health disparities. PMID:27742740

Gabor-based kernel PCA with fractional power polynomial models for face recognition.

PubMed

Liu, Chengjun

2004-05-01

This paper presents a novel Gabor-based kernel Principal Component Analysis (PCA) method by integrating the Gabor wavelet representation of face images and the kernel PCA method for face recognition. Gabor wavelets first derive desirable facial features characterized by spatial frequency, spatial locality, and orientation selectivity to cope with the variations due to illumination and facial expression changes. The kernel PCA method is then extended to include fractional power polynomial models for enhanced face recognition performance. A fractional power polynomial, however, does not necessarily define a kernel function, as it might not define a positive semidefinite Gram matrix. Note that the sigmoid kernels, one of the three classes of widely used kernel functions (polynomial kernels, Gaussian kernels, and sigmoid kernels), do not actually define a positive semidefinite Gram matrix either. Nevertheless, the sigmoid kernels have been successfully used in practice, such as in building support vector machines. In order to derive real kernel PCA features, we apply only those kernel PCA eigenvectors that are associated with positive eigenvalues. The feasibility of the Gabor-based kernel PCA method with fractional power polynomial models has been successfully tested on both frontal and pose-angled face recognition, using two data sets from the FERET database and the CMU PIE database, respectively. The FERET data set contains 600 frontal face images of 200 subjects, while the PIE data set consists of 680 images across five poses (left and right profiles, left and right half profiles, and frontal view) with two different facial expressions (neutral and smiling) of 68 subjects. The effectiveness of the Gabor-based kernel PCA method with fractional power polynomial models is shown in terms of both absolute performance indices and comparative performance against the PCA method, the kernel PCA method with polynomial kernels, the kernel PCA method with fractional power polynomial models, the Gabor wavelet-based PCA method, and the Gabor wavelet-based kernel PCA method with polynomial kernels.

PCA3-based nomogram for predicting prostate cancer and high grade cancer on initial transrectal guided biopsy.

PubMed

Elshafei, Ahmed; Chevli, K Kent; Moussa, Ayman S; Kara, Onder; Chueh, Shih-Chieh; Walter, Peter; Hatem, Asmaa; Gao, Tianming; Jones, J Stephen; Duff, Michael

2015-12-01

To develop a validated prostate cancer antigen 3 (PCA3) based nomogram that predicts likelihood of overall prostate cancer (PCa) and intermediate/high grade prostate cancer (HGPCa) in men pursuing initial transrectal prostate biopsy (TRUS-PBx). Data were collected on 3,675 men with serum prostate specific antigen level (PSA) ≤ 20 ng/ml who underwent initial prostate biopsy with at least 10 cores sampling at time of the biopsy. Two logistic regression models were constructed to predict overall PCa and HGPCa incorporating age, race, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and digital rectal exam (DRE). One thousand six hundred twenty (44%) patients had biopsy confirmed PCa with 701 men (19.1%) showing HGPCa. Statistically significant predictors of overall PCa were age (P < 0.0001, OR. 1.51), PSA at diagnosis (P < 0.0001, OR.1.95), PCA3 (P < 0.0001, OR.3.06), TPV (P < 0.0001, OR.0.47), FH (P = 0.003, OR.1.32), and abnormal DRE (P = 0.001, OR. 1.32). While for HGPCa, predictors were age (P < 0.0001, OR.1.77), PSA (P < 0.0001, OR.2.73), PCA3 (P < 0.0001, OR.2.26), TPV (P < 0.0001, OR.0.4), and DRE (P < 0.0001, OR.1.53). Two nomograms were reconstructed for predicted overall PCa probability at time of initial biopsy with a concordance index of 0.742 (Fig. 1), and HGPCa with a concordance index of 0.768 (Fig. 2). Our internally validated initial biopsy PCA3 based nomogram is reconstructed based on a large dataset. The c-index indicates high predictive accuracy, especially for high grade PCa and improves the ability to predict biopsy outcomes. © 2015 Wiley Periodicals, Inc.

Application of time series discretization using evolutionary programming for classification of precancerous cervical lesions.

PubMed

Acosta-Mesa, Héctor-Gabriel; Rechy-Ramírez, Fernando; Mezura-Montes, Efrén; Cruz-Ramírez, Nicandro; Hernández Jiménez, Rodolfo

2014-06-01

In this work, we present a novel application of time series discretization using evolutionary programming for the classification of precancerous cervical lesions. The approach optimizes the number of intervals in which the length and amplitude of the time series should be compressed, preserving the important information for classification purposes. Using evolutionary programming, the search for a good discretization scheme is guided by a cost function which considers three criteria: the entropy regarding the classification, the complexity measured as the number of different strings needed to represent the complete data set, and the compression rate assessed as the length of the discrete representation. This discretization approach is evaluated using a time series data based on temporal patterns observed during a classical test used in cervical cancer detection; the classification accuracy reached by our method is compared with the well-known times series discretization algorithm SAX and the dimensionality reduction method PCA. Statistical analysis of the classification accuracy shows that the discrete representation is as efficient as the complete raw representation for the present application, reducing the dimensionality of the time series length by 97%. This representation is also very competitive in terms of classification accuracy when compared with similar approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA).

PubMed

Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P; Kovács, Tünde; Bai, Péter; Trencsényi, György

2017-01-01

The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68 Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 ( 68 Ga-NODAGA-PCA). The melanin specificity of 68 Ga-NODAGA-PCA was tested in vitro , ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68 Ga-NODAGA-PCA and 18 FDG tracers. 68 Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that 68 Ga-NODAGA-PCA uptake of B16-F10 cells was significantly ( p ≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly ( p ≤0.01) higher 68 Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18 FDG and 68 Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly ( p ≤0.05 and p ≤0.01) higher using 68 Ga-NODAGA-PCA than the 18 FDG accumulation. Our novel radiotracer 68 Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68 Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo .

In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA)

PubMed Central

Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P.; Kovács, Tünde; Bai, Péter; Trencsényi, György

2017-01-01

Purpose: The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Methods: Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 (68Ga-NODAGA-PCA). The melanin specificity of 68Ga-NODAGA-PCA was tested in vitro, ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68Ga-NODAGA-PCA and 18FDG tracers. Results: 68Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that 68Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly (p≤0.01) higher 68Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18FDG and 68Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly (p≤0.05 and p≤0.01) higher using 68Ga-NODAGA-PCA than the 18FDG accumulation. Conclusion: Our novel radiotracer 68Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo. PMID:28382139

Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

PubMed

Jansson, Keith H; Castillo, Deborah G; Morris, Joseph W; Boggs, Mary E; Czymmek, Kirk J; Adams, Elizabeth L; Schramm, Lawrence P; Sikes, Robert A

2014-01-01

Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated. Voltage sensitive sodium channels (VSSC) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two auxiliary beta (β) subunits with inherent cell adhesion molecule (CAM) functions. The beta-2 isoform (gene SCN2B) interacts with several neural CAMs, while interacting putatively with other prominent neural CAMs. Furthermore, beta-2 exhibits elevated mRNA and protein levels in highly metastatic and castrate-resistant PCa. When overexpressed in weakly aggressive LNCaP cells (2BECFP), beta-2 alters LNCaP cell morphology and enhances LNCaP cell metastasis associated behavior in vitro. We hypothesize that PCa cells use beta-2 as a CAM during PNI and subsequent PCa metastasis. The objective of this study was to determine the effect of beta-2 expression on PCa cell neurotropic metastasis associated behavior. We overexpressed beta-2 as a fusion protein with enhanced cyan fluorescence protein (ECFP) in weakly aggressive LNCaP cells and observed neurotropic effects utilizing our novel ex vivo organotypic spinal cord co-culture model, and performed functional assays with neural matrices and atomic force microscopy. With increased beta-2 expression, PCa cells display a trend of enhanced association with nerve axons. On laminin, a neural CAM, overexpression of beta-2 enhances PCa cell migration, invasion, and growth. 2BECFP cells exhibit marked binding affinity to laminin relative to LNECFP controls, and recombinant beta-2 ectodomain elicits more binding events to laminin than BSA control. Functional overexpression of VSSC beta subunits in PCa may mediate PCa metastatic behavior through association with neural matrices.

E-selectin ligand-1 controls circulating prostate cancer cell rolling/adhesion and metastasis

PubMed Central

Yasmin-Karim, Sayeda; King, Michael R.; Messing, Edward M.; Lee, Yi-Fen

2014-01-01

Circulating prostate cancer (PCa) cells preferentially roll and adhere on bone marrow vascular endothelial cells, where abundant E-selectin and stromal cell-derived factor 1 (SDF-1) are expressed, subsequently initiating a cascade of activation events that eventually lead to the development of metastases. To elucidate the roles of circulating PCa cells' rolling and adhesion behaviors in cancer metastases, we applied a dynamic cylindrical flow-based microchannel device that is coated with E-selectin and SDF-1, mimicking capillary endothelium. Using this device we captured a small fraction of rolling PCa cells. These rolling cells display higher static adhesion ability, more aggressive cancer phenotypes and stem-like properties. Importantly, mice received rolling PCa cells, but not floating PCa cells, developed cancer metastases. Genes coding for E-selectin ligands and genes associated with cancer stem cells and metastasis were elevated in rolling PCa cells. Knock down of E-selectin ligand 1(ESL-1), significantly impaired PCa cells' rolling capacity and reduced cancer aggressiveness. Moreover, ESL-1 activates RAS and MAP kinase signal cascade, consequently inducing the downstream targets. In summary, circulating PCa cells' rolling capacity contributes to PCa metastasis, and that is in part controlled by ESL-1. PMID:25301730

Hsp70 and gama-Semino protein as possible prognostic marker of prostate cancer.

PubMed

Kumar, Sanjay; Gurshaney, Sanjeev; Adagunodo, Yori; Gage, Erica; Qadri, Shezreen; Sharma, Mahak; Malik, Shalie; Manne, Upender; Singh, Udai P; Singh, Rajesh; Mishra, Manoj K

2018-06-01

In the United States, Prostate Cancer (PCa) is the leading cause of cancer-related mortality in men. PCa resulted in abnormal growth and function of prostate gland such as secretion of high level of gamma-seminoprotein (gama-SM)/Prostate-Specific Antigen (PSA) which could be detected in the blood. Beside gama-SM protein, the levels of heat shock proteins (Hsp70) were also observed significantly high. Therefore, gama-SM and Hsp70 are unique proteins with high potential for PCa therapeutics and diagnostics. High level of Hsp70 suppresses apoptosis, thus allowing PCa cells to exist; however, depletion of Hsp70 induces apoptosis in PCa cells. Gama-SM is the most prominent biomarker for PCa screening; however, its accuracy is still questionable. Thus, a more suitable streamline biomarker for PCa screening is urgently needed. Hsp70 and gama-SM proteins could be used as a revolutionary biomarker for PCa, and could help to identify possible therapeutic target(s). In this review article we will discuss the relationship between the Hsp70 and gama-SM proteins with PCa, their potential as a dual biomarker, and the possibility for both proteins being used as therapeutic targets.

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer.

PubMed

Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

2015-07-14

Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice.

Knockdown of Mediator Complex Subunit 19 Suppresses the Growth and Invasion of Prostate Cancer Cells

PubMed Central

Zhao, Hongwei; Lv, Wei; Chen, Jian; Wan, Fengchun; Liu, Dongfu; Gao, Zhenli; Wu, Jitao

2017-01-01

Prostate cancer (PCa) is one of the most common cancers in elderly men. Mediator Complex Subunit 19 (Med19) is overexpressed and plays promotional roles in many cancers. However, the roles of Med19 in PCa are still obscure. In this study, by using immunohistochemical staining, we found higher expression level of Med19 in PCa tissues than in adjacent benign prostate tissues. We then knocked down the Med19 expression in PCa cell lines LNCaP and PC3 by using lentivirus siRNA. Cell proliferation, anchor-independent growth, migration, and invasion were suppressed in Med19 knockdown PCa cells. In nude mice xenograft model, we found that Med19 knockdown PCa cells formed smaller tumors with lower proliferation index than did control cells. In the mechanism study, we found that Med19 could regulate genes involved in cell proliferation, cell cycle, and epithelial-mesenchymal transition, including P27, pAKT, pPI3K, IGF1R, E-Cadherin, N-Cadherin, Vimentin, ZEB2, Snail-1 and Snail-2. Targeting Med19 in PCa cells could inhibit the PCa growth and metastasis, and might be a therapeutic option for PCa in the future. PMID:28125713

Physical activity in relation to risk of prostate cancer: a systematic review and meta-analysis.

PubMed

Benke, I N; Leitzmann, M F; Behrens, G; Schmid, D

2018-05-01

Prostate cancer (PCa) is one of the most common cancers among men, yet little is known about its modifiable risk and protective factors. This study aims to quantitatively summarize observational studies relating physical activity (PA) to PCa incidence and mortality. Published articles pertaining to PA and PCa incidence and mortality were retrieved in July 2017 using the Medline and EMBASE databases. The literature review yielded 48 cohort studies and 24 case-control studies with a total of 151 748 PCa cases. The mean age of the study participants at baseline was 61 years. In random-effects models, comparing the highest versus the lowest level of overall PA showed a summary relative risk (RR) estimate for total PCa incidence close to the null [RR = 0.99, 95% confidence interval (CI) = 0.94-1.04]. The corresponding RRs for advanced and non-advanced PCa were 0.92 (95% CI = 0.80-1.06) and 0.95 (95% CI = 0.85-1.07), respectively. We noted a statistically significant inverse association between long-term occupational activity and total PCa (RR = 0.83, 95% CI = 0.71-0.98, n studies = 13), although that finding became statistically non-significant when individual studies were removed from the analysis. When evaluated by cancer subtype, an inverse association with long-term occupational activity was noted for non-advanced/non-aggressive PCa (RR = 0.51, 95% CI = 0.37-0.71, n studies = 2) and regular recreational activity was inversely related to advanced/aggressive PCa (RR = 0.75, 95% CI = 0.60-0.95, n studies = 2), although these observations are based on a low number of studies. Moreover, PA after diagnosis was related to reduced risk of PCa mortality among survivors of PCa (summary RR based on four studies = 0.69, 95% CI = 0.55-0.85). Whether PA protects against PCa remains elusive. Further investigation taking into account the complex clinical and pathologic nature of PCa is needed to clarify the PA and PCa incidence relation. Moreover, future studies are needed to confirm whether PA after diagnosis reduces risk of PCa mortality.

Characterizing the molecular features of ERG-positive tumors in primary and castration resistant prostate cancer

PubMed Central

Roudier, Martine P; Winters, Brian R; Coleman, Ilsa; Lam, Hung-Ming; Zhang, Xiaotun; Coleman, Roger; Chéry, Lisly; True, Lawrence D.; Higano, Celestia S.; Montgomery, Bruce; Lange, Paul H.; Snyder, Linda A.; Srivistava, Shiv; Corey, Eva; Vessella, Robert L.; Nelson, Peter S.; Üren, Aykut; Morrissey, Colm

2017-01-01

Background The TMPRSS2-ERG gene fusion is detected in approximately half of primary prostate cancers (PCa) yet the prognostic significance remains unclear. We hypothesized that ERG promotes the expression of common genes in primary PCa and metastatic castration-resistant PCa (CRPC), with the objective of identifying ERG-associated pathways, which may promote the transition from primary PCa to CRPC. Methods We constructed tissue microarrays (TMA) from 127 radical prostatectomy specimens, 20 LuCaP patient-derived xenografts (PDX), and 152 CRPC metastases obtained immediately at time of death. Nuclear ERG was assessed by immunohistochemistry (IHC). To characterize the molecular features of ERG-expressing PCa, a subset of IHC confirmed ERG+ or ERG-specimens including 11 radical prostatectomies, 20 LuCaP PDXs, and 45 CRPC metastases underwent gene expression analysis. Genes were ranked based on expression in primary PCa and CRPC. Common genes of interest were targeted for IHC analysis and expression compared with biochemical recurrence (BCR) status. Results IHC revealed that 43% of primary PCa, 35% of the LuCaP PDXs, and 18% of the CRPC metastases were ERG+ (12 of 48 patients [25%] had at least 1 ERG+ metastasis). Based on gene expression data and previous literature, two proteins involved in calcium signaling (NCALD, CACNA1D), a protein involved in inflammation (HLA-DMB), CD3 positive immune cells, and a novel ERG-associated protein, DCLK1 were evaluated in primary PCa and CRPC metastases. In ERG+ primary PCa, a weak association was seen with NCALD and CACNA1D protein expression. HLA-DMB expression and the presence of CD3 positive immune cells were decreased in CRPC metastases compared to primary PCa. DCLK1 was upregulated at the protein level in unpaired ERG+ primary PCa and CRPC metastases (p=0.0013 and p<0.0001, respectively). In primary PCa, ERG status or expression of targeted proteins was not associated with BCR-free survival. However for primary PCa, ERG+DCLK1+ patients exhibited shorter time to BCR (p=0.06) compared with ERG+DCLK1- patients. Conclusions This study examined ERG expression in primary PCa and CRPC. We have identified altered levels of inflammatory mediators associated with ERG expression. We determined expression of DCLK1 correlates with ERG expression and may play a role in primary PCa progression to metastatic CPRC. PMID:26990456

Differentiation of neuropsychological features between posterior cortical atrophy and early onset Alzheimer's disease.

PubMed

Li, Jieying; Wu, Liyong; Tang, Yi; Zhou, Aihong; Wang, Fen; Xing, Yi; Jia, Jianping

2018-05-10

Posterior cortical atrophy (PCA) is a group of clinical syndromes characterized by visuospatial and visuoperceptual impairment, with memory relatively preserved. Although PCA is pathologically almost identical to Alzheimer's disease (AD), they have different cognitive features. Those differences have only rarely been reported in any Chinese population. The purpose of the study is to establish neuropsychological tests that distinguish the clinical features of PCA from early onset AD (EOAD). Twenty-one PCA patients, 20 EOAD patients, and 20 healthy controls participated in this study. Patients had disease duration of ≤4 years. All participants completed a series of neuropsychological tests to evaluate their visuospatial, visuoperceptual, visuo-constructive, language, executive function, memory, calculation, writing, and reading abilities. The cognitive features of PCA and EOAD were compared. All the neuropsychological test scores showed that both the PCA and EOAD patients were significantly more impaired than people in the control group. However, PCA patients were significantly more impaired than EOAD patients in visuospatial, visuoperceptual, and visuo-constructive function, as well as in handwriting, and reading Chinese characters. The profile of neuropsychological test results highlights cognitive features that differ between PCA and EOAD. One surprising result is that the two syndromes could be distinguished by patients' ability to read and write Chinese characters. Tests based on these characteristics could therefore form a brief PCA neuropsychological examination that would improve the diagnosis of PCA.

The role of serum neuron-specific enolase in patients with prostate cancer: a systematic review of the recent literature.

PubMed

Muoio, Barbara; Pascale, Mariarosa; Roggero, Enrico

2018-01-01

In this systematic review, we evaluated the value of serum concentrations of neuron-specific enolase (NSE) in patients with prostate cancer (PCa) in order to clarify the possible role of NSE in the diagnosis, management, treatment and monitoring of PCa. A comprehensive search of the recent literature was conducted to find relevant data on the role of NSE in PCa. Two hundred and eighty-two records were revealed, and 19 articles including 1,772 patients with PCa (either confirmed or suspected) were selected. After reviewing the articles, the major result was that elevated serum NSE appears to correlate with prognosis in advanced PCa, particularly in patients with progressive and metastatic castration-resistant PCa. Based on the existing literature, the role of serum NSE in PCa patients should be further evaluated.

The preparation of large surface area lanthanum based perovskite supports for AuPt nanoparticles: tuning the glycerol oxidation reaction pathway by switching the perovskite B site

PubMed Central

Evans, Christopher D.; Smith, Paul J.; Manning, Troy D.; Miedziak, Peter J.; Brett, Gemma L.; Armstrong, Robert D.; Bartley, Jonathan K.; Taylor, Stuart H.; Rosseinsky, Matthew J.; Hutchings, Graham J.

2016-01-01

Gold and gold alloys, in the form of supported nanoparticles, have been shown over the last three decades to be highly effective oxidation catalysts. Mixed metal oxide perovskites, with their high structural tolerance, are ideal for investigating how changes in the chemical composition of supports affect the catalysts' properties, while retaining similar surface areas, morphologies and metal co-ordinations. However, a significant disadvantage of using perovskites as supports is their high crystallinity and small surface area. We report the use of a supercritical carbon dioxide anti-solvent precipitation methodology to prepare large surface area lanthanum based perovskites, making the deposition of 1 wt% AuPt nanoparticles feasible. These catalysts were used for the selective oxidation of glycerol. By changing the elemental composition of the perovskite B site, we dramatically altered the reaction pathway between a sequential oxidation route to glyceric or tartronic acid and a dehydration reaction pathway to lactic acid. Selectivity profiles were correlated to reported oxygen adsorption capacities of the perovskite supports and also to changes in the AuPt nanoparticle morphologies. Extended time on line analysis using the best oxidation catalyst (AuPt/LaMnO3) produced an exceptionally high tartronic acid yield. LaMnO3 produced from alternative preparation methods was found to have lower activities, but gave comparable selectivity profiles to that produced using the supercritical carbon dioxide anti-solvent precipitation methodology. PMID:27074316

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathias, Paul M.; Afshar, Kash; Zheng, Feng

This paper describes an unusual solvent regeneration method unique to CO₂BOLs and other switchable ionic liquids; utilizing changes in polarity to shift the free energy of the system. The degree of CO₂ loading in CO₂BOLs is known to control the polarity of the solvent; conversely, polarity could be exploited as a means to control CO₂ loading. In this process, a chemically inert non-polar “antisolvent” is added to aid in de-complexing CO₂ from a CO₂-rich CO₂BOL. The addition of this polarity assist reduces temperatures required for regeneration of CO₂BOLs by as much as 76 °C. The lower regeneration temperatures realized withmore » this polarity change allow for reduced solvent attrition and thermal degradation. Furthermore, the polarity assist shows considerable promise for reducing regeneration energy of CO₂BOL solvents, and separation of the CO₂BOL from the antisolvent is as simple as cooling the mixture below the upper critical solution temperature. Vapour-liquid equilibrium and liquid-liquid equilibrium measurements of a candidate CO₂BOL with CO₂ with and without an antisolvent were completed. From this data, we present the evidence and impacts of a polarity change on a CO₂BOL. Thermodynamic models and analysis of the system were constructed using ASPEN Plus, and forecasts preliminary process configurations and feasibility are also presented. Lastly, projections of solvent performance for removing CO₂ from a sub-critical coal fired power plant (total net power and parasitic load) are presented with and without this polarity assist and compared to DOE’s Case 10 MEA baseline.« less

Continuous API-crystal coating via coacervation in a tubular reactor.

PubMed

Besenhard, M O; Thurnberger, A; Hohl, R; Faulhammer, E; Rattenberger, J; Khinast, J G

2014-11-20

We present a proof-of-concept study of a continuous coating process of single API crystals in a tubular reactor using coacervation as a microencapsulation technique. Continuous API crystal coating can have several advantages, as in a single step (following crystallization) individual crystals can be prepared with a functional coating, either to change the release behavior, to protect the API from gastric juice or to modify the surface energetics of the API (i.e., to tailor the hydrophobic/hydrophilic characteristics, flowability or agglomeration tendency, etc.). The coating process was developed for the microencapsulation of a lipophilic core material (ibuprofen crystals of 20 μm- to 100 μm-size), with either hypromellose phthalate (HPMCP) or Eudragit L100-55. The core material was suspended in an aqueous solution containing one of these enteric polymers, fed into the tubing and mixed continuously with a sodium sulfate solution as an antisolvent to induce coacervation. A subsequent temperature treatment was applied to optimize the microencapsulation of crystals via the polymer-rich coacervate phase. Cross-linking of the coating shell was achieved by mixing the processed material with an acidic solution (pH<3). Flow rates, temperature profiles and polymer-to-antisolvent ratios had to be tightly controlled to avoid excessive aggregation, leading to pipe plugging. This work demonstrates the potential of a tubular reactor design for continuous coating applications and is the basis for future work, combining continuous crystallization and coating. Copyright © 2014 Elsevier B.V. All rights reserved.

Isoxyl aerosols for tuberculosis treatment: preparation and characterization of particles.

PubMed

Wang, Chenchen; Hickey, Anthony J

2010-06-01

Isoxyl is a potent antituberculosis drug effective in treating various multidrug-resistant strains in the absence of known side effects. Isoxyl has been used exclusively, but infrequently, via the oral route and has exhibited very poor and highly variable bioavailability due to its sparing solubility in water. These properties resulted in failure of some clinical trials and, consequently, isoxyl's use has been limited. Delivery of isoxyl to the lungs, a major site of Mycobacterium tuberculosis infection, is an attractive alternative route of administration that may rescue this abandoned drug for a disease that urgently requires new therapies. Particles for pulmonary delivery were prepared by antisolvent precipitation. Nanofibers with a width of 200 nm were obtained by injecting isoxyl solution in ethanol to water at a volume ratio of solvent to antisolvent of 1:5. Based on this preliminary result, a well-controlled method, involving nozzle mixing, was employed to prepare isoxyl particles. All the particles were 200 to 400 nm in width but had different lengths depending on properties of the solvents. However, generating these nanoparticles by simultaneous spray drying produced isoxyl microparticles (Feret's diameter, 1.19-1.77 microm) with no discernible nanoparticle substructure. The bulking agent, mannitol, helped to prevent these nanoparticles from agglomeration during process and resulted in nanoparticle aggregates in micron-sized superstructures. Future studies will focus on understanding difference of these isoxyl microparticles and nanoparticles/nanoparticle aggregates in terms of in vivo disposition and efficacy.

Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process

PubMed Central

Kim, Min-Soo; Kim, Jeong-Soo; Park, Hee Jun; Cho, Won Kyung; Cha, Kwang-Ho; Hwang, Sung-Joo

2011-01-01

Background The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS) process. Methods First, excipients for enhancing the stability and solubility of sirolimus were screened. Second, using the SAS process, solid dispersions of sirolimus-polyvinylpyrrolidone (PVP) K30 nanoparticles were prepared with or without surfactants such as sodium lauryl sulfate (SLS), tocopheryl propylene glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52. A mean particle size of approximately 250 nm was obtained for PVP K30-sirolimus nanoparticles. Solid state characterization, kinetic solubility, powder dissolution, stability, and pharmacokinetics were analyzed in rats. Results X-ray diffraction, differential scanning calorimetry, and high-pressure liquid chromatography indicated that sirolimus existed in an anhydrous amorphous form within a solid dispersion of nanoparticles and that no degradation occurred after SAS processing. The improved supersaturation and dissolution of sirolimus as a solid dispersion of nanoparticles appeared to be well correlated with enhanced bioavailability of oral sirolimus in rats. With oral administration of a solid dispersion of PVP K30-SLS-sirolimus nanoparticles, the peak concentration and AUC0→12h of sirolimus were increased by approximately 18.3-fold and 15.2-fold, respectively. Conclusion The results of this study suggest that preparation of PVP K30-sirolimus-surfactant nanoparticles using the SAS process may be a promising approach for improving the bioavailability of sirolimus. PMID:22162657

Formation of nanoparticles of a hydrophilic drug using supercritical carbon dioxide and microencapsulation for sustained release.

PubMed

Thote, Amol J; Gupta, Ram B

2005-03-01

Our purpose was to produce nanoparticles of a hydrophilic drug with use of supercritical carbon dioxide (CO2), encapsulate the obtained nanoparticles into polymer microparticles with use of an anhydrous method and study their sustained in vitro drug release. The hydrophilic drug, dexamethasone phosphate, is dissolved in methanol and injected in supercritical CO2 with an ultrasonic field for enhanced molecular mixing (supercritical antisolvent technique with enhanced mass transfer [SAS-EM]). Supercritical CO2 rapidly extracts methanol leading to instantaneous precipitation of drug nanoparticles. The nanoparticles are then encapsulated in poly(lactide-co-glycolide) (PLGA) polymer by use of the anhydrous solid-oil-oil-oil technique. This results in a well-dispersed encapsulation of drug nanoparticles in polymer microspheres. In vitro drug release from these microparticles is studied. With supercritical CO2 used as an antisolvent, nanoparticles of dexamethasone phosphate were obtained in the range of 150 to 200 nm. On encapsulation in polylactide coglycolide, composite microspheres of approximately 70 microm were obtained. The in vitro drug release of these nanoparticles/microparticles composites shows sustained release of dexamethasone phosphate over a period of 700 hours with almost no initial burst release. Nanoparticles of dexamethasone phosphate can be produced with the SAS-EM technique. When microencapsulated, these particles can provide sustained drug release without initial burst release. Because the complete process is anhydrous, it can be easily extended to produce sustained release formulations of other hydrophilic drugs.

A three step supercritical process to improve the dissolution rate of eflucimibe.

PubMed

Rodier, Elisabeth; Lochard, Hubert; Sauceau, Martial; Letourneau, Jean-Jacques; Freiss, Bernard; Fages, Jacques

2005-10-01

The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.

Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

PubMed Central

Kalantarian, Pardis; Najafabadi, Abdolhosein Rouholamini; Haririan, Ismaeil; Vatanara, Alireza; Yamini, Yadollah; Darabi, Majid; Gilani, Kambiz

2010-01-01

This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction. PMID:21042422

Study of the solid state of carbamazepine after processing with gas anti-solvent technique.

PubMed

Moneghini, M; Kikic, I; Voinovich, D; Perissutti, B; Alessi, P; Cortesi, A; Princivalle, F; Solinas, D

2003-09-01

The purpose of this study was to investigate the influence of supercritical CO2 processing on the physico-chemical properties of carbamazepine, a poorly soluble drug. The gas anti-solvent (GAS) technique was used to precipitate the drug from three different solvents (acetone, ethylacetate and dichloromethane) to study how they would affect the final product. The samples were analysed before and after treatment by scanning electron microscopy analysis and laser granulometry for possible changes in the habitus of the crystals. In addition, the solid state of the samples was studied by means of X-ray powder diffraction, differential scanning calorimetry, diffuse reflectance Fourier-transform infrared spectroscopy and hot stage microscopy. Finally, the in vitro dissolution tests were carried out. The solid state analysis of both samples untreated and treated with CO2, showed that the applied method caused a transition from the starting form III to the form I as well as determined a dramatic change of crystal morphology, resulting in needle-shaped crystals, regardless of the chosen solvent. In order to identify which process was responsible for the above results, carbamazepine was further precipitated from the same three solvents by traditional evaporation method (RV-samples). On the basis of this cross-testing, the solvents were found to be responsible for the reorganisation into a different polymorphic form, and the potential of the GAS process to produce micronic needle shaped particles, with an enhanced dissolution rate compared to the RV-carbamazepine, was ascertained.

Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process.

PubMed

Won, Dong-Han; Kim, Min-Soo; Lee, Sibeum; Park, Jeong-Sook; Hwang, Sung-Joo

2005-09-14

Solid dispersions of felodipine were formulated with HPMC and surfactants by the conventional solvent evaporation (CSE) and supercritical anti-solvent precipitation (SAS) methods. The solid dispersion particles were characterized by particle size, zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), solubility and dissolution studies. The effects of the drug/polymer ratio and surfactants on the solubility of felodipine were also studied. The mean particle size of the solid dispersions was 200-250 nm; these had a relatively regular spherical shape with a narrow size distribution. The particle size of the solid dispersions from the CSE method increased at 1 h after dispersed in distilled water. However, the particle sizes of solid dispersions from the SAS process were maintained for 6 h due to the increased solubility of felodipine. The physical state of felodipine changed from crystalline to amorphous during the CSE and SAS processes, confirmed by DSC/XRD data. The equilibrium solubility of the felodipine solid dispersion prepared by the SAS process was 1.5-20 microg/ml, while the maximum solubility was 35-110 microg/ml. Moreover, the solubility of felodipine increased with decreasing drug/polymer ratio or increasing HCO-60 content. The solid dispersions from the SAS process showed a high dissolution rate of over 90% within 2 h. The SAS process system may be used to enhance solubility or to produce oral dosage forms with high dissolution rate.

Supercritical Fluid Technologies to Fabricate Proliposomes.

PubMed

Falconer, James R; Svirskis, Darren; Adil, Ali A; Wu, Zimei

2015-01-01

Proliposomes are stable drug carrier systems designed to form liposomes upon addition of an aqueous phase. In this review, current trends in the use of supercritical fluid (SCF) technologies to prepare proliposomes are discussed. SCF methods are used in pharmaceutical research and industry to address limitations associated with conventional methods of pro/liposome fabrication. The SCF solvent methods of proliposome preparation are eco-friendly (known as green technology) and, along with the SCF anti-solvent methods, could be advantageous over conventional methods; enabling better design of particle morphology (size and shape). The major hurdles of SCF methods include poor scalability to industrial manufacturing which may result in variable particle characteristics. In the case of SCF anti-solvent methods, another hurdle is the reliance on organic solvents. However, the amount of solvent required is typically less than that used by the conventional methods. Another hurdle is that most of the SCF methods used have complicated manufacturing processes, although once the setup has been completed, SCF technologies offer a single-step process in the preparation of proliposomes compared to the multiple steps required by many other methods. Furthermore, there is limited research into how proliposomes will be converted into liposomes for the end-user, and how such a product can be prepared reproducibly in terms of vesicle size and drug loading. These hurdles must be overcome and with more research, SCF methods, especially where the SCF acts as a solvent, have the potential to offer a strong alternative to the conventional methods to prepare proliposomes.

The preparation of large surface area lanthanum based perovskite supports for AuPt nanoparticles: tuning the glycerol oxidation reaction pathway by switching the perovskite B site.

PubMed

Evans, Christopher D; Kondrat, Simon A; Smith, Paul J; Manning, Troy D; Miedziak, Peter J; Brett, Gemma L; Armstrong, Robert D; Bartley, Jonathan K; Taylor, Stuart H; Rosseinsky, Matthew J; Hutchings, Graham J

2016-07-04

Gold and gold alloys, in the form of supported nanoparticles, have been shown over the last three decades to be highly effective oxidation catalysts. Mixed metal oxide perovskites, with their high structural tolerance, are ideal for investigating how changes in the chemical composition of supports affect the catalysts' properties, while retaining similar surface areas, morphologies and metal co-ordinations. However, a significant disadvantage of using perovskites as supports is their high crystallinity and small surface area. We report the use of a supercritical carbon dioxide anti-solvent precipitation methodology to prepare large surface area lanthanum based perovskites, making the deposition of 1 wt% AuPt nanoparticles feasible. These catalysts were used for the selective oxidation of glycerol. By changing the elemental composition of the perovskite B site, we dramatically altered the reaction pathway between a sequential oxidation route to glyceric or tartronic acid and a dehydration reaction pathway to lactic acid. Selectivity profiles were correlated to reported oxygen adsorption capacities of the perovskite supports and also to changes in the AuPt nanoparticle morphologies. Extended time on line analysis using the best oxidation catalyst (AuPt/LaMnO3) produced an exceptionally high tartronic acid yield. LaMnO3 produced from alternative preparation methods was found to have lower activities, but gave comparable selectivity profiles to that produced using the supercritical carbon dioxide anti-solvent precipitation methodology.

Prostate Cancer Predictive Simulation Modelling, Assessing the Risk Technique (PCP-SMART): Introduction and Initial Clinical Efficacy Evaluation Data Presentation of a Simple Novel Mathematical Simulation Modelling Method, Devised to Predict the Outcome of Prostate Biopsy on an Individual Basis.

PubMed

Spyropoulos, Evangelos; Kotsiris, Dimitrios; Spyropoulos, Katherine; Panagopoulos, Aggelos; Galanakis, Ioannis; Mavrikos, Stamatios

2017-02-01

We developed a mathematical "prostate cancer (PCa) conditions simulating" predictive model (PCP-SMART), from which we derived a novel PCa predictor (prostate cancer risk determinator [PCRD] index) and a PCa risk equation. We used these to estimate the probability of finding PCa on prostate biopsy, on an individual basis. A total of 371 men who had undergone transrectal ultrasound-guided prostate biopsy were enrolled in the present study. Given that PCa risk relates to the total prostate-specific antigen (tPSA) level, age, prostate volume, free PSA (fPSA), fPSA/tPSA ratio, and PSA density and that tPSA ≥ 50 ng/mL has a 98.5% positive predictive value for a PCa diagnosis, we hypothesized that correlating 2 variables composed of 3 ratios (1, tPSA/age; 2, tPSA/prostate volume; and 3, fPSA/tPSA; 1 variable including the patient's tPSA and the other, a tPSA value of 50 ng/mL) could operate as a PCa conditions imitating/simulating model. Linear regression analysis was used to derive the coefficient of determination (R 2 ), termed the PCRD index. To estimate the PCRD index's predictive validity, we used the χ 2 test, multiple logistic regression analysis with PCa risk equation formation, calculation of test performance characteristics, and area under the receiver operating characteristic curve analysis using SPSS, version 22 (P < .05). The biopsy findings were positive for PCa in 167 patients (45.1%) and negative in 164 (44.2%). The PCRD index was positively signed in 89.82% positive PCa cases and negative in 91.46% negative PCa cases (χ 2 test; P < .001; relative risk, 8.98). The sensitivity was 89.8%, specificity was 91.5%, positive predictive value was 91.5%, negative predictive value was 89.8%, positive likelihood ratio was 10.5, negative likelihood ratio was 0.11, and accuracy was 90.6%. Multiple logistic regression revealed the PCRD index as an independent PCa predictor, and the formulated risk equation was 91% accurate in predicting the probability of finding PCa. On the receiver operating characteristic analysis, the PCRD index (area under the curve, 0.926) significantly (P < .001) outperformed other, established PCa predictors. The PCRD index effectively predicted the prostate biopsy outcome, correctly identifying 9 of 10 men who were eventually diagnosed with PCa and correctly ruling out PCa for 9 of 10 men who did not have PCa. Its predictive power significantly outperformed established PCa predictors, and the formulated risk equation accurately calculated the probability of finding cancer on biopsy, on an individual patient basis. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison between a disposable and an electronic PCA device for labor epidural analgesia.

PubMed

Sumikura, Hiroyuki; van de Velde, Marc; Tateda, Takeshi

2004-01-01

The aims of the present study were (1) to investigate if a disposable patient-controlled analgesia (PCA) device can be used for labor analgesia and (2) to evaluate the device by midwives and parturients. Forty healthy parturients were divided into two groups and received combined spinal epidural analgesia for labor pain relief. Following intrathecal administration of 3 mg ropivacaine and 1.5 microg sufentanil, either a disposable PCA device (Coopdech Syrinjector; Daiken Medical, Osaka, Japan) or an electronic PCA device (IVAC PCAM PCA Syringe Pump; Alaris, Basingstoke, UK) was connected to the epidural catheter, and 0.15% ropivacaine with sufentanil 0.75 microg/ml was used for continuous infusion and PCA. For an electronic PCA device, continuous infusion rate, bolus dose, lockout time, and hourly limit were set at 4 ml/h, 3 ml, 15 min, and 16 ml, respectively. For a disposable PCA device, continuous infusion rate, bolus dose, and an hourly limit were set at 4 ml/h, 3 ml, and 16 ml, respectively, but lockout function was not available. No differences were observed between the groups concerning demographic data, obstetric data, and outcome of labor. Anesthetic requirements (disposable, 9.7 +/- 4.7 ml/h; electronic, 8.2 +/- 4.0 ml/h) and VAS score during the delivery (disposable, 26 +/- 25; electronic, 21 +/- 22) were similar between the groups. Midwives praised the disposable PCA device as well as the electronic one. The present results imply that the disposable PCA device can be an alternative to the electronic PCA device for labor analgesia.

The Association Between Calcium Channel Blocker Use and Prostate Cancer Outcome

PubMed Central

Poch, Michael A.; Mehedint, Diana; Green, Dawn J.; Payne-Ondracek, Rochelle; Fontham, Elizabeth T.H.; Bensen, Jeannette T.; Attwood, Kristopher; Wilding, Gregory E.; Guru, Khurshid A.; Underwood, Willie; Mohler, James L.; Heemers, Hannelore V.

2018-01-01

BACKGROUND Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined. METHODS Medication use, PCa aggressiveness and post-RP outcome were retrieved from a prospectively populated database that contains clinical and outcome for RP patients at Roswell Park Cancer Institute (RPCI) from 1993 to 2010. The database was queried for anti-hypertensive medication use at diagnosis for patients with ≥1 year follow-up. Recurrence was defined using NCCN guidelines. Chi-Square tests assessed the relationship between CCB use and PCa aggressiveness. Cox regression models compared the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Results for association between CCB usage and PCa aggressiveness were validated using data from the population-based North Carolina-Louisiana Prostate Cancer Project (PCaP). RESULTS 48%, 37%, and 15% of RPCI’s RP patients (n = 875) had low, intermediate, and high aggressive PCa, respectively. 104 (11%) had a history of CCB use. Patients taking CCBs were more likely to be older, have a higher BMI and use additional anti-hypertensive medications. Diagnostic PSA levels, PCa aggressiveness, and margin status were similar for CCB users and non-users. PFS and OS did not differ between the two groups. Tumor aggressiveness was associated with PFS. CCB use in the PCaP study population was not associated with PCa aggressiveness. CONCLUSIONS CCB use is not associated with PCa aggressiveness at diagnosis, PFS or OS. PMID:23280547

Testosterone inhibits the growth of prostate cancer xenografts in nude mice.

PubMed

Song, Weitao; Soni, Vikram; Soni, Samit; Khera, Mohit

2017-09-07

Traditional beliefs of androgen's stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice. Different serum testosterone levels were manipulated in male nude/nude athymic mice by orchiectomy or inserting different dosages of T pellets subcutaneously. PCa cells were injected subcutaneously to nude mice and tumor incidence rate and tumor growth rate of PCa xenografts were tested. The data demonstrated that low levels of serum T resulted in the highest PCa incidence rate (50%). This PCa incidence rate in mice with low T levels was significantly higher than that in mice treated with higher doses of T (24%, P < 0.01) and mice that underwent orchiectomy (8%, P < 0.001). Mice that had low serum T levels had the shortest tumor volume doubling time (112 h). This doubling time was significantly shorter than that in the high dose 5 mg T arm (158 h, P < 0.001) and in the orchiectomy arm (468 h, P < 0.001). These results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth.

PSMA PET and radionuclide therapy in prostate cancer

PubMed Central

Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter L.

2016-01-01

Prostate cancer (Pca) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical recurrence, and for therapy of PCa patients. Since no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. In order to optimize treatment outcome, especially in high risk PCa patients, therapy of PCa is moving rapidly towards personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CT), plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, since it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guiding focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low PSA values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa, and is an area of active investigation. The “Image and treat” strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of PCa patients, and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy of PCa. PMID:27825432

Sugarcane bagasse pretreatment using three imidazolium-based ionic liquids; mass balances and enzyme kinetics

PubMed Central

2012-01-01

Background Effective pretreatment is key to achieving high enzymatic saccharification efficiency in processing lignocellulosic biomass to fermentable sugars, biofuels and value-added products. Ionic liquids (ILs), still relatively new class of solvents, are attractive for biomass pretreatment because some demonstrate the rare ability to dissolve all components of lignocellulosic biomass including highly ordered (crystalline) cellulose. In the present study, three ILs, 1-butyl-3-methylimidazolium chloride ([C4mim]Cl), 1-ethyl-3-methylimidazolium chloride ([C2mim]Cl), 1-ethyl-3-methylimidazolium acetate ([C2mim]OAc) are used to dissolve/pretreat and fractionate sugarcane bagasse. In these IL-based pretreatments the biomass is completely or partially dissolved in ILs at temperatures greater than 130°C and then precipitated by the addition of an antisolvent to the IL biomass mixture. For the first time mass balances of IL-based pretreatments are reported. Such mass balances, along with kinetics data, can be used in process modelling and design. Results Lignin removals of 10% mass of lignin in bagasse with [C4mim]Cl, 50% mass with [C2mim]Cl and 60% mass with [C2mim]OAc, are achieved by limiting the amount of water added as antisolvent to 0.5 water:IL mass ratio thus minimising lignin precipitation. Enzyme saccharification (24 h, 15FPU) yields (% cellulose mass in starting bagasse) from the recovered solids rank as: [C2mim]OAc(83%) > >[C2mim]Cl(53%) = [C4mim]Cl(53%). Composition of [C2mim]OAc-treated solids such as low lignin, low acetyl group content and preservation of arabinosyl groups are characteristic of aqueous alkali pretreatments while those of chloride IL-treated solids resemble aqueous acid pretreatments. All ILs are fully recovered after use (100% mass as determined by ion chromatography). Conclusions In all three ILs regulated addition of water as an antisolvent effected a polysaccharide enriched precipitate since some of the lignin remained dissolved in the aqueous IL solution. Of the three IL studied [C2mim]OAc gave the best saccharification yield, material recovery and delignification. The effects of [C2mim]OAc pretreatment resemble those of aqueous alkali pretreatments while those of [C2mim]Cl and [C4mim]Cl resemble aqueous acid pretreatments. The use of imidazolium IL solvents with shorter alkyl chains results in accelerated dissolution, pretreatment and degradation. PMID:22920045

Exploring patterns enriched in a dataset with contrastive principal component analysis.

PubMed

Abid, Abubakar; Zhang, Martin J; Bagaria, Vivek K; Zou, James

2018-05-30

Visualization and exploration of high-dimensional data is a ubiquitous challenge across disciplines. Widely used techniques such as principal component analysis (PCA) aim to identify dominant trends in one dataset. However, in many settings we have datasets collected under different conditions, e.g., a treatment and a control experiment, and we are interested in visualizing and exploring patterns that are specific to one dataset. This paper proposes a method, contrastive principal component analysis (cPCA), which identifies low-dimensional structures that are enriched in a dataset relative to comparison data. In a wide variety of experiments, we demonstrate that cPCA with a background dataset enables us to visualize dataset-specific patterns missed by PCA and other standard methods. We further provide a geometric interpretation of cPCA and strong mathematical guarantees. An implementation of cPCA is publicly available, and can be used for exploratory data analysis in many applications where PCA is currently used.

Physicochemical and mechanical properties of paracetamol cocrystal with 5-nitroisophthalic acid.

PubMed

Hiendrawan, Stevanus; Veriansyah, Bambang; Widjojokusumo, Edward; Soewandhi, Sundani Nurono; Wikarsa, Saleh; Tjandrawinata, Raymond R

2016-01-30

We report novel pharmaceutical cocrystal of a popular antipyretic drug paracetamol (PCA) with coformer 5-nitroisophhthalic acid (5NIP) to improve its tabletability. The cocrystal (PCA-5NIP at molar ratio of 1:1) was synthesized by solvent evaporation technique using methanol as solvent. The physicochemical properties of cocrystal were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), fourier transform infrared spectroscopy (FTIR), hot stage polarized microscopy (HSPM) and scanning electron microscopy (SEM). Stability of the cocrystal was assessed by storing them at 40°C/75% RH for one month. Compared to PCA, the cocrystal displayed superior tableting performance. PCA-5NIP cocrystal showed a similar dissolution profile as compared to PCA and exhibited good stability. This study showed the utility of PCA-5NIP cocrystal for improving mechanical properties of PCA. Copyright © 2015 Elsevier B.V. All rights reserved.

PEM-PCA: a parallel expectation-maximization PCA face recognition architecture.

PubMed

Rujirakul, Kanokmon; So-In, Chakchai; Arnonkijpanich, Banchar

2014-01-01

Principal component analysis or PCA has been traditionally used as one of the feature extraction techniques in face recognition systems yielding high accuracy when requiring a small number of features. However, the covariance matrix and eigenvalue decomposition stages cause high computational complexity, especially for a large database. Thus, this research presents an alternative approach utilizing an Expectation-Maximization algorithm to reduce the determinant matrix manipulation resulting in the reduction of the stages' complexity. To improve the computational time, a novel parallel architecture was employed to utilize the benefits of parallelization of matrix computation during feature extraction and classification stages including parallel preprocessing, and their combinations, so-called a Parallel Expectation-Maximization PCA architecture. Comparing to a traditional PCA and its derivatives, the results indicate lower complexity with an insignificant difference in recognition precision leading to high speed face recognition systems, that is, the speed-up over nine and three times over PCA and Parallel PCA.

The influence of stigma on the quality of life for prostate cancer survivors.

PubMed

Wood, Andrew W; Barden, Sejal; Terk, Mitchell; Cesaretti, Jamie

2017-01-01

The purpose of the present study was to investigate the influence of stigma on prostate cancer (PCa) survivors' quality of life. Stigma for lung cancer survivors has been the focus of considerable research (Else-Quest & Jackson, 2014); however, gaps remain in understanding the experience of PCa stigma. A cross-sectional correlational study was designed to assess the incidence of PCa stigma and its influence on the quality of life of survivors. Eighty-five PCa survivors were administered survey packets consisting of a stigma measure, a PCa-specific quality of life measure, and a demographic survey during treatment of their disease. A linear regression analysis was conducted with the data received from PCa survivors. Results indicated that PCa stigma has a significant, negative influence on the quality of life for survivors (R 2 = 0.33, F(4, 80) = 11.53, p < 0.001). There were no statistically significant differences in PCa stigma based on demographic variables (e.g., race and age). Implications for physical and mental health practitioners and researchers are discussed.

Motor features in posterior cortical atrophy and their imaging correlates☆

PubMed Central

Ryan, Natalie S.; Shakespeare, Timothy J.; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M.; Leung, Kelvin K.; Fox, Nick C.; Crutch, Sebastian J.

2014-01-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. PMID:25086839

Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii

PubMed Central

Wright, Terry W.; Malone, Jane E.; Haidaris, Constantine G.; Harber, Martha; Sant, Andrea J.; Nayak, Jennifer L.

2016-01-01

ABSTRACT Pneumocystis pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse Pneumocystis surface protein, designated Pneumocystis cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4+ T cells were depleted, and the mice were exposed to Pneumocystis murina. Pca1 immunization completely protected nearly all mice, similar to immunization with whole Pneumocystis organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized Pneumocystis jirovecii and Pneumocystis carinii. Potential orthologs of Pca1 have been identified in P. jirovecii. Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation. PMID:28031260

Fatty acid binding protein 4 enhances prostate cancer progression by upregulating matrix metalloproteinases and stromal cell cytokine production

PubMed Central

Huang, Mingguo; Narita, Shintaro; Inoue, Takamitsu; Koizumi, Atsushi; Saito, Mitsuru; Tsuruta, Hiroshi; Numakura, Kazuyuki; Satoh, Shigeru; Nanjo, Hiroshi; Sasaki, Takehiko; Habuchi, Tomonori

2017-01-01

Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and its production is influenced by high-fat diet (HFD) or obesity. The prostate stromal microenvironment induces proinflammatory cytokine production, which is key for the development and progression of prostate cancer (PCa). Here, we show that high FABP4 expression and its secretion by PCa cells directly stimulated PCa cell invasiveness by upregulating matrix metalloproteinases through phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4 and interleukin-8. Clinically, the serum level of FABP4 was significantly associated with an aggressive type of PCa rather than obesity. Taken together, FABP4 may enhance PCa progression and invasiveness by upregulating matrix metalloproteinases and cytokine production in the PCa stromal microenvironment, especially under HFD or obesity. PMID:29340091

Novel targets for prostate cancer chemoprevention

PubMed Central

Sarkar, Fazlul H; Li, Yiwei; Wang, Zhiwei; Kong, Dejuan

2010-01-01

Among many endocrine-related cancers, prostate cancer (PCa) is the most frequent male malignancy, and it is the second most common cause of cancer-related death in men in the United States. Therefore, this review focuses on summarizing the knowledge of molecular signaling pathways in PCa because, in order to better design new preventive strategies for the fight against PCa, documentation of the knowledge on the pathogenesis of PCa at the molecular level is very important. Cancer cells are known to have alterations in multiple cellular signaling pathways; indeed, the development and the progression of PCa are known to be caused by the deregulation of several selective signaling pathways such as the androgen receptor, Akt, nuclear factor-κB, Wnt, Hedgehog, and Notch. Therefore, strategies targeting these important pathways and their upstream and downstream signaling could be promising for the prevention of PCa progression. In this review, we summarize the current knowledge regarding the alterations in cell signaling pathways during the development and progression of PCa, and document compelling evidence showing that these are the targets of several natural agents against PCa progression and its metastases. PMID:20576802

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer

PubMed Central

Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

2015-01-01

Background: Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. Methods: We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. Results: Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. Conclusions: There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice. PMID:26103574

Hypoxia induces triglycerides accumulation in prostate cancer cells and extracellular vesicles supporting growth and invasiveness following reoxygenation

PubMed Central

Kumar, Rahul; Dhar, Deepanshi; Agarwal, Chapla; Bergman, Bryan; Graner, Michael; Maroni, Paul; Singh, Rana P.; Agarwal, Rajesh; Deep, Gagan

2015-01-01

Hypoxia is an independent prognostic indicator of poor outcome in several malignancies. However, precise mechanism through which hypoxia promotes disease aggressiveness is still unclear. Here, we report that under hypoxia (1% O2), human prostate cancer (PCA) cells, and extracellular vesicles (EVs) released by these cells, are significantly enriched in triglycerides due to the activation of lipogenesis-related enzymes and signaling molecules. This is likely a survival response to hypoxic stress as accumulated lipids could support growth following reoxygenation. Consistent with this, significantly higher proliferation was observed in hypoxic PCA cells following reoxygenation associated with rapid use of accumulated lipids. Importantly, lipid utilization inhibition by CPT1 inhibitor etomoxir and shRNA-mediated CPT1-knockdown significantly compromised hypoxic PCA cell proliferation following reoxygenation. Furthermore, COX2 inhibitor celecoxib strongly reduced growth and invasiveness following hypoxic PCA cells reoxygenation, and inhibited invasiveness induced by hypoxic PCA EVs. This establishes a role for COX2 enzymatic products in the enhanced PCA growth and invasiveness. Importantly, concentration and loading of EVs secreted by PCA cells were significantly compromised under delipidized serum condition and by lipogenesis inhibitors (fatostatin and silibinin). Overall, present study highlights the biological significance of lipid accumulation in hypoxic PCA cells and its therapeutic relevance in PCA. PMID:26087400

Prostate cancer characterization by optical contrast enhanced photoacoustics

NASA Astrophysics Data System (ADS)

Xu, Guan; Qin, Ming; Mukundan, Ananya; Siddiqui, Javed; Takada, Marilia; Vilar-Saavedra, Paulo; Tomlins, Scott A.; Kopelman, Raoul; Wang, Xueding

2016-03-01

During the past decades, prostate cancer (PCa), with an annual incident rate much higher than any other cancer, is the most commonly diagnosed cancer in American men. PCa has a relatively low progression rate yet the survival percentage decreases dramatically once the cancer has metastasized. Identifying aggressive from indolent PCa to prevent metastasis and death is critical to improving outcomes for patients with PCa. Standard procedure for assessing the aggressiveness of PCa involves the removal of tumor tissues by transrectal (TR) ultrasound (US) guided needle biopsy. The microscopic architecture of the biopsied tissue is visualized by histological or immunohistochemical staining procedures. The heterogeneity of the microscopic architecture is characterized by a Gleason score, a quantitative description of the aggressiveness of PCa. Due to the inability to identify the cancer cells, most noninvasive imaging modalities can only provide diagnosis of PCa at limited accuracy. This study investigates the feasibility of identifying PCa tumors and characterizing the aggressiveness of PCa by photoacoustic imaging assisted by cancer targeting polyacrylamide (PAA) nanoparticles (NPs). PAA is a biocompatible material used in clinics for the past 20 years. PAA NPs can protect capsulated optical contrast agents from interference by enzymes and enable prolonged systematic circulation in the living biological environment. The cancer targeting mechanism is achieved by conjugating the NPs to F3 peptides, which trace nucleolin overexpressed on the surface of cancer cells. Preliminary studies have shown that the NPs are capable of staining the PCa cells in vivo.

Facilitating text reading in posterior cortical atrophy.

PubMed

Yong, Keir X X; Rajdev, Kishan; Shakespeare, Timothy J; Leff, Alexander P; Crutch, Sebastian J

2015-07-28

We report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA. Reading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2). Mean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%-270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA. These findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. This study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy. © 2015 American Academy of Neurology.

Facilitating text reading in posterior cortical atrophy

PubMed Central

Rajdev, Kishan; Shakespeare, Timothy J.; Leff, Alexander P.; Crutch, Sebastian J.

2015-01-01

Objective: We report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA. Methods: Reading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2). Results: Mean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%–270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA. Conclusions: These findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. Classification of evidence: This study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy. PMID:26138948

AMACR polymorphisms, dietary intake of red meat and dairy and prostate cancer risk.

PubMed

Wright, Jonathan L; Neuhouser, Marian L; Lin, Daniel W; Kwon, Erika M; Feng, Ziding; Ostrander, Elaine A; Stanford, Janet L

2011-04-01

Alpha-methylacyl CoA racemase (AMACR) is an enzyme involved in fatty acids metabolism. One of AMACRs primary substrates, phytanic acid, is principally obtained from dietary red meat/dairy, which are associated with prostate cancer (PCa) risk. AMACR is also a tumor tissue biomarker over-expressed in PCa. In this study, we explored the potential relationship between AMACR polymorphisms, red meat/dairy intake, and PCa risk. Caucasian participants from two population-based PCa case-control studies were included. AMACR single nucleotide polymorphisms (SNPs) were selected to capture variation across the gene and regulatory regions. Red meat and dairy intake was determined from food frequency questionnaires. The odds ratio (OR) of PCa (overall and by disease aggressiveness) was estimated by logistic and polytomous regression. Potential interactions between genotypes and dietary exposures were evaluated. Data from 1,309 cases and 1,267 controls were analyzed. Carriers of the variant T allele (rs2287939) had an OR of 0.81 (95% CI 0.68-0.97) for less aggressive PCa, but no alteration in risk for more aggressive PCa. Red meat consumption was positively associated with PCa risk, and the association was stronger for more aggressive disease (lowest vs. highest tertile OR=1.55, 95% CI 1.10-2.20). No effect modification of AMACR polymorphisms by either dietary red meat or dairy intake on PCa risk was observed. PCa risk varied by level of red meat intake and by one AMACR SNP, but there was no evidence for gene-environment interaction. These findings suggest that the effects of AMACR polymorphisms and red meat and dairy on PCa risk are independent. Copyright © 2010 Wiley-Liss, Inc.

Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells

PubMed Central

Jeet, Varinder; Tevz, Gregor; Lehman, Melanie; Hollier, Brett; Nelson, Colleen

2014-01-01

Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa. PMID:24981110

Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells.

PubMed

Jeet, Varinder; Tevz, Gregor; Lehman, Melanie; Hollier, Brett; Nelson, Colleen

2014-10-01

Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa. © 2014 The authors.

DWI-associated entire-tumor histogram analysis for the differentiation of low-grade prostate cancer from intermediate-high-grade prostate cancer.

PubMed

Wu, Chen-Jiang; Wang, Qing; Li, Hai; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin; Zhang, Yu-Dong

2015-10-01

To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate-high-grade (HG) PCa in comparison with conventional ROI-based measurement. DW images (b of 0-1400 s/mm(2)) from 126 pathology-confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI-based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS ≤ 6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar's test. There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (ρ = -0.225 to -0.406, p < 0.05). All above imaging indices reflected significant difference between LG-PCa and HG-PCa (all p values <0.01). Histogram 10th ADCs had dominantly high Az (0.738), Youden index (0.415), and positive likelihood ratio (LR+, 2.45) in stratifying tumor GS against mean, median and 90th ADCs, and ROI-based ADCs. Histogram mean, median, and 10th ADCs showed higher specificity (65.3%-74.1% vs. 44.9%, p < 0.01), but lower sensitivity (57.1%-71.3% vs. 84.4%, p < 0.05) than ROI-based ADCs in differentiating LG-PCa from HG-PCa. DWI-associated histogram analysis had higher specificity, Az, Youden index, and LR+ for differentiation of PCa Gleason grade than ROI-based approach.

Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

PubMed

Giri, Veda N; Knudsen, Karen E; Kelly, William K; Abida, Wassim; Andriole, Gerald L; Bangma, Chris H; Bekelman, Justin E; Benson, Mitchell C; Blanco, Amie; Burnett, Arthur; Catalona, William J; Cooney, Kathleen A; Cooperberg, Matthew; Crawford, David E; Den, Robert B; Dicker, Adam P; Eggener, Scott; Fleshner, Neil; Freedman, Matthew L; Hamdy, Freddie C; Hoffman-Censits, Jean; Hurwitz, Mark D; Hyatt, Colette; Isaacs, William B; Kane, Christopher J; Kantoff, Philip; Karnes, R Jeffrey; Karsh, Lawrence I; Klein, Eric A; Lin, Daniel W; Loughlin, Kevin R; Lu-Yao, Grace; Malkowicz, S Bruce; Mann, Mark J; Mark, James R; McCue, Peter A; Miner, Martin M; Morgan, Todd; Moul, Judd W; Myers, Ronald E; Nielsen, Sarah M; Obeid, Elias; Pavlovich, Christian P; Peiper, Stephen C; Penson, David F; Petrylak, Daniel; Pettaway, Curtis A; Pilarski, Robert; Pinto, Peter A; Poage, Wendy; Raj, Ganesh V; Rebbeck, Timothy R; Robson, Mark E; Rosenberg, Matt T; Sandler, Howard; Sartor, Oliver; Schaeffer, Edward; Schwartz, Gordon F; Shahin, Mark S; Shore, Neal D; Shuch, Brian; Soule, Howard R; Tomlins, Scott A; Trabulsi, Edouard J; Uzzo, Robert; Vander Griend, Donald J; Walsh, Patrick C; Weil, Carol J; Wender, Richard; Gomella, Leonard G

2018-02-01

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

The impact of socioeconomic status on stage specific prostate cancer survival and mortality before and after introduction of PSA test in Finland.

PubMed

Seikkula, Heikki A; Kaipia, Antti J; Ryynänen, Heidi; Seppä, Karri; Pitkäniemi, Janne M; Malila, Nea K; Boström, Peter J

2018-03-01

Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men with high SES have higher incidence and lower mortality of PCa versus lower SES males. PCa cases diagnosed in Finland in 1985-2014 (N = 95,076) were identified from the Finnish Cancer Registry. Information on education level (EL) was obtained from Statistics Finland. EL was assessed with three-tiered scale: basic, upper secondary and higher education. PCa stage at diagnosis was defined as localized, metastatic or unknown. Years of diagnosis 1985-1994 were defined as pre-PSA period and thereafter as post-PSA period. We report PCa-specific survival (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer cases in Finland, where healthcare is 100% publicly reimbursed and inequality in healthcare services low. Men with higher EL had markedly better 10-year PCSS: 68 versus 63% in 1985-1994 and 90 versus 85% in 1995-2004 compared to basic EL in localized PCa. The RR for PCSM among men with localized PCa and higher EL compared to basic EL was 0.76(95%confidence interval (CI) 0.66-0.88) in 1985-1994 and 0.61(95%CI 0.53-0.70) in 1995-2004. Variation in PCSS and PCSM between EL categories was evident in metastatic PCa, too. The difference in PCSM between EL categories was larger in the first 10-year post-PSA period than before that but decreased thereafter in localized PCa, suggesting PSA testing became earlier popular among men with high EL. In summary, higher SES/EL benefit PCa survival both in local and disseminated disease and the effect of EL was more pronounced in early post-PSA period. © 2017 UICC.

Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth muscle cells and intravascular thrombosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moon, Chang Yoon; Endocrinology, Brain Korea 21 Project for Medical Science, Institute of Endocrine Research, and Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University College of Medicine, Seoul; Ku, Cheol Ryong

2012-06-22

Highlights: Black-Right-Pointing-Pointer Protocatechuic aldehyde (PCA) inhibits ROS production in VSMCs. Black-Right-Pointing-Pointer PCA inhibits proliferation and migration in PDGF-induced VSMCs. Black-Right-Pointing-Pointer PCA has anti-platelet effects in ex vivo rat whole blood. Black-Right-Pointing-Pointer We report the potential therapeutic role of PCA in atherosclerosis. -- Abstract: The migration and proliferation of vascular smooth muscle cells (VSMCs) and formation of intravascular thrombosis play crucial roles in the development of atherosclerotic lesions. This study examined the effects of protocatechuic aldehyde (PCA), a compound isolated from the aqueous extract of the root of Salvia miltiorrhiza, an herb used in traditional Chinese medicine to treat a varietymore » of vascular diseases, on the migration and proliferation of VSMCs and platelets due to platelet-derived growth factor (PDGF). DNA 5-bromo-2 Prime -deoxy-uridine (BrdU) incorporation and wound-healing assays indicated that PCA significantly attenuated PDGF-induced proliferation and migration of VSMCs at a pharmacologically relevant concentration (100 {mu}M). On a molecular level, we observed down-regulation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the mitogen-activated protein kinase (MAPK) pathways, both of which regulate key enzymes associated with migration and proliferation. We also found that PCA induced S-phase arrest of the VSMC cell cycle and suppressed cyclin D2 expression. In addition, PCA inhibited PDGF-BB-stimulated reactive oxygen species production in VSMCs, indicating that PCA's antioxidant properties may contribute to its suppression of PDGF-induced migration and proliferation in VSMCs. Finally, PCA exhibited an anti-thrombotic effect related to its inhibition of platelet aggregation, confirmed with an aggregometer. Together, these findings suggest a potential therapeutic role of PCA in the treatment of atherosclerosis and angioplasty-induced vascular restenosis.« less

Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians.

PubMed

Song, Yan; Chavarro, Jorge E; Cao, Yin; Qiu, Weiliang; Mucci, Lorelei; Sesso, Howard D; Stampfer, Meir J; Giovannucci, Edward; Pollak, Michael; Liu, Simin; Ma, Jing

2013-02-01

Previous studies have associated higher milk intake with greater prostate cancer (PCa) incidence, but little data are available concerning milk types and the relation between milk intake and risk of fatal PCa. We investigated the association between intake of dairy products and the incidence and survival of PCa during a 28-y follow-up. We conducted a cohort study in the Physicians' Health Study (n = 21,660) and a survival analysis among the incident PCa cases (n = 2806). Information on dairy product consumption was collected at baseline. PCa cases and deaths (n = 305) were confirmed during follow-up. The intake of total dairy products was associated with increased PCa incidence [HR = 1.12 (95% CI: 0.93, 1.35); >2.5 servings/d vs. ≤0.5 servings/d]. Skim/low-fat milk intake was positively associated with risk of low-grade, early stage, and screen-detected cancers, whereas whole milk intake was associated only with fatal PCa [HR = 1.49 (95% CI: 0.97, 2.28); ≥237 mL/d (1 serving/d) vs. rarely consumed]. In the survival analysis, whole milk intake remained associated with risk of progression to fatal disease after diagnosis [HR = 2.17 (95% CI: 1.34, 3.51)]. In this prospective cohort, higher intake of skim/low-fat milk was associated with a greater risk of nonaggressive PCa. Most importantly, only whole milk was consistently associated with higher incidence of fatal PCa in the entire cohort and higher PCa-specific mortality among cases. These findings add further evidence to suggest the potential role of dairy products in the development and prognosis of PCa.

Activation of Beta-Catenin Signaling in Androgen Receptor–Negative Prostate Cancer Cells

PubMed Central

Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S.; Troncoso, Patricia; Maity, Sankar N.; Navone, Nora M.

2012-01-01

Purpose To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction. Experimental Design We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. Results Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling. Conclusion We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients. PMID:22298898

Increasing patient knowledge on the proper usage of a PCA machine with the use of a post-operative instructional card.

PubMed

Shovel, Louisa; Max, Bryan; Correll, Darin J

2016-01-01

The purpose of this study was to see if an instructional card, attached to the PCA machine following total hip arthroplasty describing proper use of the device, would positively affect subjects' understanding of device usage, pain scores, pain medication consumption and satisfaction. Eighty adults undergoing total hip replacements who had been prescribed PCA were randomized into two study groups. Forty participants received the standard post-operative instruction on PCA device usage at our institution. The other 40 participants received the standard of care in addition to being given a typed instructional card immediately post-operatively, describing proper PCA device use. This card was attached to the PCA device during their recovery period. On post-operative day one, each patient completed a questionnaire on PCA usage, pain scores and satisfaction scores. The pain scores in the Instructional Card group were significantly lower than the Control group (p = 0.024). Subjects' understanding of PCA usage was also improved in the Instructional Card group for six of the seven questions asked. The findings from this study strongly support that postoperative patient information on proper PCA use by means of an instructional card improves pain control and hence the overall recovery for patients undergoing surgery. In addition, through improved understanding it adds an important safety feature in that patients and potentially their family members and/or friends may refrain from PCA-by-proxy. This article demonstrates that the simple intervention of adding an instructional card to a PCA machine is an effective method to improve patients' knowledge as well as pain control and potentially increase the safety of the device use.

Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells

PubMed Central

Chao, Hsueh-Ping; Deng, Qu; Jeter, Collene; Liu, Can; Honorio, Sofia; Li, Hangwen; Davis, Tammy; Suraneni, Mahipal; Laffin, Brian; Qin, Jichao; Li, Qiuhui; Yang, Tao; Whitney, Pamela; Shen, Jianjun; Huang, Jiaoti; Tang, Dean G.

2015-01-01

Human cancers are heterogeneous containing stem-like cancer cells operationally defined as cancer stem cells (CSCs) that possess great tumor-initiating and long-term tumor-propagating properties. In this study, we systematically dissect the phenotypic, functional and tumorigenic heterogeneity in human prostate cancer (PCa) using xenograft models and >70 patient tumor samples. In the first part, we further investigate the PSA−/lo PCa cell population, which we have recently shown to harbor self-renewing long-term tumor-propagating cells and present several novel findings. We show that discordant AR and PSA expression in both untreated and castration-resistant PCa (CRPC) results in AR+PSA+, AR+PSA−, AR−PSA−, and AR−PSA+ subtypes of PCa cells that manifest differential sensitivities to therapeutics. We further demonstrate that castration leads to a great enrichment of PSA−/lo PCa cells in both xenograft tumors and CRPC samples and systemic androgen levels dynamically regulate the relative abundance of PSA+ versus PSA−/lo PCa cells that impacts the kinetics of tumor growth. We also present evidence that the PSA−/lo PCa cells possess distinct epigenetic profiles. As the PSA−/lo PCa cell population is heterogeneous, in the second part, we employ two PSA− (Du145 and PC3) and two PSA+ (LAPC9 and LAPC4) PCa models as well as patient tumor cells to further dissect the clonogenic and tumorigenic subsets. We report that different PCa models possess distinct tumorigenic subpopulations that both commonly and uniquely express important signaling pathways that could represent therapeutic targets. Our results have important implications in understanding PCa cell heterogeneity, response to clinical therapeutics, and cellular mechanisms underlying CRPC. PMID:26246472

Evidence for Masturbation and Prostate Cancer Risk: Do We Have a Verdict?

PubMed

Aboul-Enein, Basil H; Bernstein, Joshua; Ross, Michael W

2016-07-01

Prostate cancer (PCa) is one of the leading causes of cancer death in men and remains one of the most diagnosed malignancies worldwide. Ongoing public health efforts continue to promote protective factors, such as diet, physical activity, and other lifestyle modifications, against PCa development. Masturbation is a nearly universal safe sexual activity that transcends societal boundaries and geography yet continues to be met with stigma and controversy in contemporary society. Although previous studies have examined associations between sexual activity and PCa risk, anecdotal relations have been suggested regarding masturbation practice and PCa risk. To provide a summary of the published literature and examine the contemporary evidence for relations between masturbation practice and PCa risk. A survey of the current literature using seven academic electronic databases was conducted using search terms and key words associated with masturbation practice and PCa risk. The practice of masturbation and its relation to PCa risk. The literature search identified study samples (n = 16) published before October 2015. Sample inclusions varied by study type, sample size, and primary objective. Protective relations (n = 7) between ejaculation through masturbation and PCa risk were reported by 44% of the study sample. Age range emerged as a significant variable in the relation between masturbation and PCa. Findings included relations among masturbation, ejaculation frequency, and age range as individual factors of PCa risk. No universally accepted themes were identified across the study sample. Throughout the sample, there was insufficient agreement in survey design and data reporting. Potential avenues for new research include frequency of ejaculation and age range as covarying factors that could lead to more definitive statements about masturbation practice and PCa risk. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Biotransformation of ferulic acid to protocatechuic acid by Corynebacterium glutamicum ATCC 21420 engineered to express vanillate O-demethylase.

PubMed

Okai, Naoko; Masuda, Takaya; Takeshima, Yasunobu; Tanaka, Kosei; Yoshida, Ken-Ichi; Miyamoto, Masanori; Ogino, Chiaki; Kondo, Akihiko

2017-12-01

Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a lignin-derived phenolic compound abundant in plant biomass. The utilization of FA and its conversion to valuable compounds is desired. Protocatechuic acid (3,4-dihydroxybenzoic acid, PCA) is a precursor of polymers and plastics and a constituent of food. A microbial conversion system to produce PCA from FA was developed in this study using a PCA-producing strain of Corynebacterium glutamicum F (ATCC 21420). C. glutamicum strain F grown at 30 °C for 48 h utilized 2 mM each of FA and vanillic acid (4-hydroxy-3-methoxybenzoic acid, VA) to produce PCA, which was secreted into the medium. FA may be catabolized by C. glutamicum through proposed (I) non-β-oxidative, CoA-dependent or (II) β-oxidative, CoA-dependent phenylpropanoid pathways. The conversion of VA to PCA is the last step in each pathway. Therefore, the vanillate O-demethylase gene (vanAB) from Corynebacterium efficiens NBRC 100395 was expressed in C. glutamicum F (designated strain FVan) cultured at 30 °C in AF medium containing FA. Strain C. glutamicum FVan converted 4.57 ± 0.07 mM of FA into 2.87 ± 0.01 mM PCA after 48 h with yields of 62.8% (mol/mol), and 6.91 mM (1064 mg/L) of PCA was produced from 16.0 mM of FA after 12 h of fed-batch biotransformation. Genomic analysis of C. glutamicum ATCC 21420 revealed that the PCA-utilization genes (pca cluster) were conserved in strain ATCC 21420 and that mutations were present in the PCA importer gene pcaK.

Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

PubMed

Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

2015-02-01

Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry.

PubMed

Biggs, Colleen N; Siddiqui, Khurram M; Al-Zahrani, Ali A; Pardhan, Siddika; Brett, Sabine I; Guo, Qiu Q; Yang, Jun; Wolf, Philipp; Power, Nicholas E; Durfee, Paul N; MacMillan, Connor D; Townson, Jason L; Brinker, Jeffrey C; Fleshner, Neil E; Izawa, Jonathan I; Chambers, Ann F; Chin, Joseph L; Leong, Hon S

2016-02-23

Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

A novel-type phosphatidylinositol phosphate-interactive, Ca-binding protein PCaP1 in Arabidopsis thaliana: stable association with plasma membrane and partial involvement in stomata closure.

PubMed

Nagata, Chisako; Miwa, Chika; Tanaka, Natsuki; Kato, Mariko; Suito, Momoe; Tsuchihira, Ayako; Sato, Yori; Segami, Shoji; Maeshima, Masayoshi

2016-05-01

The Ca(2+)-binding protein-1 (PCaP1) of Arabidopsis thaliana is a new type protein that binds to phosphatidylinositol phosphates and Ca(2+)-calmodulin complex as well as free Ca(2+). Although biochemical properties, such as binding to ligands and N-myristoylation, have been revealed, the intracellular localization, tissue and cell specificity, integrity of membrane association and physiological roles of PCaP1 are unknown. We investigated the tissue and intracellular distribution of PCaP1 by using transgenic lines expressing PCaP1 linked with a green fluorescence protein (GFP) at the carboxyl terminus of PCaP1. GFP fluorescence was obviously detected in most tissues including root, stem, leaf and flower. In these tissues, PCaP1-GFP signal was observed predominantly in the plasma membrane even under physiological stress conditions but not in other organelles. The fluorescence was detected in the cytosol when the 25-residue N-terminal sequence was deleted from PCaP1 indicating essential contribution of N-myristoylation to the plasma membrane anchoring. Fluorescence intensity of PCaP1-GFP in roots was slightly decreased in seedlings grown in medium supplemented with high concentrations of iron for 1 week and increased in those grown with copper. In stomatal guard cells, PCaP1-GFP was strictly, specifically localized to the plasma membrane at the epidermal-cell side but not at the pore side. A T-DNA insertion mutant line of PCaP1 did not show marked phenotype in a life cycle except for well growth under high CO2 conditions. However, stomata of the mutant line did not close entirely even in high osmolarity, which usually induces stomata closure. These results suggest that PCaP1 is involved in the stomatal movement, especially closure process, in leaves and response to excessive copper in root and leaf as a mineral nutrient as a physiological role.

Calcium channel blocker use and risk of prostate cancer by TMPRSS2:ERG gene fusion status

PubMed Central

Geybels, Milan S.; McCloskey, Karen D.; Mills, Ian G.; Stanford, Janet L.

2017-01-01

Background Calcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen-regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status. Methods Participants were residents of King County, Washington, recruited for population-based case–control studies (1993–1996 or 2002–2005). Tumor T2E status was determined by fluorescence in situ hybridization using tumor tissue specimens from radical prostatectomy. Detailed information on use of CCBs and other variables was obtained through in-person interviews. Binomial and polytomous logistic regression were used to generate odds ratios (ORs) and 95% confidence intervals (CIs). Results The study includes 1,747 PCa patients and 1,635 age-matched controls. A subset of 563 patients treated with radical prostatectomy had T2E status determined, of which 295 were T2E positive (52%). Use of CCBs (ever vs. never) was not associated with overall PCa risk. However, among European-American men, users had a reduced risk of higher-grade PCa (Gleason scores ≥7: adjusted OR = 0.64; 95% CI: 0.44–0.95). Further, use of CCBs was associated with a reduced risk of T2E positive PCa (adjusted OR = 0.38; 95% CI: 0.19–0.78), but was not associated with T2E negative PCa. Conclusions This study found suggestive evidence that use of CCBs is associated with reduced relative risks for higher Gleason score and T2E positive PCa. Future studies of PCa etiology should consider etiologic heterogeneity as PCa subtypes may develop through different causal pathways. PMID:27753122

G Protein-Coupled Estrogen Receptor-1 Is Involved in the Protective Effect of Protocatechuic Aldehyde against Endothelial Dysfunction

PubMed Central

Kong, Byung Soo; Cho, Yoon Hee; Lee, Eun Jig

2014-01-01

Protocatechuic aldehyde (PCA), a phenolic aldehyde, has therapeutic potency against atherosclerosis. Although PCA is known to inhibit the migration and proliferation of vascular smooth muscle cells and intravascular thrombosis, the underlying mechanism remains unclear. In this study, we investigated the protective effect of PCA on endothelial cells and injured vessels in vivo in association with G protein-coupled estrogen receptor-1 (GPER-1). With PCA treatment, cAMP production was increased in HUVECs, while GPER-1 expression was increased in both HUVECs and a rat aortic explant. PCA and G1, a GPER-1 agonist, reduced H2O2 stimulated ROS production in HUVECs, whereas, G15, a GPER-1 antagonist, increased ROS production further. These elevations were inhibited by co-treatment with PCA or G1. TNFα stimulated the expression of inflammatory markers (VCAM-1, ICAM-1 and CD40), phospho-NF-κB, phospho-p38 and HIF-1α; however, co-treatment with PCA or G1 down-regulated this expression significantly. Likewise, increased expression of inflammatory markers by treatment with G15 was inhibited by co-treatment with PCA. In re-endothelization, aortic ring sprouting and neointima formation assay, rat aortas treated with PCA or G1 showed accelerated re-endothelization of the endothelium and reduced sprouting and neointima formation. However, aortas from G15-treated rats showed decelerated re-endothelization and increased sprouting and neointima formation. The effects of G15 were restored by co-treatment with PCA or G1. Also, in the endothelia of these aortas, PCA and G1 increased CD31 and GPER-1 and decreased VCAM-1 and CD40 expression. In contrast, the opposite effect was observed in G15-treated endothelium. These results suggest that GPER-1 might mediate the protective effect of PCA on the endothelium. PMID:25411835

G protein-coupled estrogen receptor-1 is involved in the protective effect of protocatechuic aldehyde against endothelial dysfunction.

PubMed

Kong, Byung Soo; Cho, Yoon Hee; Lee, Eun Jig

2014-01-01

Protocatechuic aldehyde (PCA), a phenolic aldehyde, has therapeutic potency against atherosclerosis. Although PCA is known to inhibit the migration and proliferation of vascular smooth muscle cells and intravascular thrombosis, the underlying mechanism remains unclear. In this study, we investigated the protective effect of PCA on endothelial cells and injured vessels in vivo in association with G protein-coupled estrogen receptor-1 (GPER-1). With PCA treatment, cAMP production was increased in HUVECs, while GPER-1 expression was increased in both HUVECs and a rat aortic explant. PCA and G1, a GPER-1 agonist, reduced H2O2 stimulated ROS production in HUVECs, whereas, G15, a GPER-1 antagonist, increased ROS production further. These elevations were inhibited by co-treatment with PCA or G1. TNFα stimulated the expression of inflammatory markers (VCAM-1, ICAM-1 and CD40), phospho-NF-κB, phospho-p38 and HIF-1α; however, co-treatment with PCA or G1 down-regulated this expression significantly. Likewise, increased expression of inflammatory markers by treatment with G15 was inhibited by co-treatment with PCA. In re-endothelization, aortic ring sprouting and neointima formation assay, rat aortas treated with PCA or G1 showed accelerated re-endothelization of the endothelium and reduced sprouting and neointima formation. However, aortas from G15-treated rats showed decelerated re-endothelization and increased sprouting and neointima formation. The effects of G15 were restored by co-treatment with PCA or G1. Also, in the endothelia of these aortas, PCA and G1 increased CD31 and GPER-1 and decreased VCAM-1 and CD40 expression. In contrast, the opposite effect was observed in G15-treated endothelium. These results suggest that GPER-1 might mediate the protective effect of PCA on the endothelium.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry

PubMed Central

Al-Zahrani, Ali A.; Pardhan, Siddika; Brett, Sabine I.; Guo, Qiu Q.; Yang, Jun; Wolf, Philipp; Power, Nicholas E.; Durfee, Paul N.; MacMillan, Connor D.; Townson, Jason L.; Brinker, Jeffrey C.; Fleshner, Neil E.; Izawa, Jonathan I.; Chambers, Ann F.; Chin, Joseph L.; Leong, Hon S.

2016-01-01

Background Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/μL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer. PMID:26814433

Inflammation: an important parameter in the search of prostate cancer biomarkers

PubMed Central

2014-01-01

Background A more specific and early diagnostics for prostate cancer (PCa) is highly desirable. In this study, being inflammation the focus of our effort, serum protein profiles were analyzed in order to investigate if this parameter could interfere with the search of discriminating proteins between PCa and benign prostatic hyperplasia (BPH). Methods Patients with clinical suspect of PCa and candidates for trans-rectal ultrasound guided prostate biopsy (TRUS) were enrolled. Histological specimens were examined in order to grade and classify the tumor, identify BPH and detect inflammation. Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (SELDI-ToF-MS) and two-dimensional gel electrophoresis (2-DE) coupled with Liquid Chromatography-MS/MS (LC-MS/MS) were used to analyze immuno-depleted serum samples from patients with PCa and BPH. Results The comparison between PCa (with and without inflammation) and BPH (with and without inflammation) serum samples by SELDI-ToF-MS analysis did not show differences in protein expression, while changes were only observed when the concomitant presence of inflammation was taken into consideration. In fact, when samples with histological sign of inflammation were excluded, 20 significantly different protein peaks were detected. Subsequent comparisons (PCa with inflammation vs PCa without inflammation, and BPH with inflammation vs BPH without inflammation) showed that 16 proteins appeared to be modified in the presence of inflammation, while 4 protein peaks were not modified. With 2-DE analysis, comparing PCa without inflammation vs PCa with inflammation, and BPH without inflammation vs the same condition in the presence of inflammation, were identified 29 and 25 differentially expressed protein spots, respectively. Excluding samples with inflammation the comparison between PCa vs BPH showed 9 unique PCa proteins, 4 of which overlapped with those previously identified in the presence of inflammation, while other 2 were new proteins, not identified in our previous comparisons. Conclusions The present study indicates that inflammation might be a confounding parameter during the proteomic research of candidate biomarkers of PCa. These results indicate that some possible biomarker-candidate proteins are strongly influenced by the presence of inflammation, hence only a well-selected protein pattern should be considered for potential marker of PCa. PMID:24944525

Can Prostate Imaging Reporting and Data System Version 2 reduce unnecessary prostate biopsies in men with PSA levels of 4-10 ng/ml?

PubMed

Xu, Ning; Wu, Yu-Peng; Chen, Dong-Ning; Ke, Zhi-Bin; Cai, Hai; Wei, Yong; Zheng, Qing-Shui; Huang, Jin-Bei; Li, Xiao-Dong; Xue, Xue-Yi

2018-05-01

To explore the value of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) for predicting prostate biopsy results in patients with prostate specific antigen (PSA) levels of 4-10 ng/ml. We retrospectively reviewed multi-parameter magnetic resonance images from 528 patients with PSA levels of 4-10 ng/ml who underwent transrectal ultrasound-guided prostate biopsies between May 2015 and May 2017. Among them, 137 were diagnosed with prostate cancer (PCa), and we further subdivided them according to pathological results into the significant PCa (S-PCa) and insignificant significant PCa (Ins-PCa) groups (121 cases were defined by surgical pathological specimen and 16 by biopsy). Age, PSA, percent free PSA, PSA density (PSAD), prostate volume (PV), and PI-RADS score were collected. Logistic regression analysis was performed to determine predictors of pathological results. Receiver operating characteristic curves were constructed to analyze the diagnostic value of PI-RADS v2 in PCa. Multivariate analysis indicated that age, PV, percent free PSA, and PI-RADS score were independent predictors of biopsy findings, while only PI-RADS score was an independent predictor of S-PCa (P < 0.05). The areas under the receiver operating characteristic curve for diagnosing PCa with respect to age, PV, percent free PSA, and PI-RADS score were 0.570, 0.430, 0.589 and 0.836, respectively. The area under the curve for diagnosing S-PCa with respect to PI-RADS score was 0.732. A PI-RADS score of 3 was the best cutoff for predicting PCa, and 4 was the best cutoff for predicting S-PCa. Thus, 92.8% of patients with PI-RADS scores of 1-2 would have avoided biopsy, but at the cost of missing 2.2% of the potential PCa cases. Similarly, 83.82% of patients with a PI-RADS score ≤ 3 would have avoided biopsy, but at the cost of missing 3.3% of the potential S-PCa cases. PI-RADS v2 could be used to reduce unnecessary prostate biopsies in patients with PSA levels of 4-10 ng/ml.

Risk of prostate cancer in African-American men: Evidence of mixed effects of dietary quercetin by serum vitamin D status.

PubMed

Paller, C J; Kanaan, Y M; Beyene, D A; Naab, T J; Copeland, R L; Tsai, H L; Kanarek, N F; Hudson, T S

2015-09-01

African-American (AA) men experience higher rates of prostate cancer (PCa) and vitamin D (vitD) deficiency than white men. VitD is promoted for PCa prevention, but there is conflicting data on the association between vitD and PCa. We examined the association between serum vitD and dietary quercetin and their interaction with PCa risk in AA men. Participants included 90 AA men with PCa undergoing treatment at Howard University Hospital (HUH) and 62 controls participating in HUH's free PCa screening program. We measured serum 25-hydroxy vitD [25(OH)D] and used the 98.2 item Block Brief 2000 Food Frequency Questionnaires to measure dietary intake of quercetin and other nutrients. Case and control groups were compared using a two-sample t-test for continuous risk factors and a Fisher exact test for categorical factors. Associations between risk factors and PCa risk were examined via age-adjusted logistic regression models. Interaction effects of dietary quercetin and serum vitD on PCa status were observed. AA men (age 40-70) with normal levels of serum vitD (>30 ng/ml) had a 71% lower risk of PCa compared to AA men with vitD deficiency (OR = 0.29, 95%CI: 0.08-1.03; P = 0.055). In individuals with vitD deficiency, increased dietary quercetin showed a tendency toward lower risk of PCa (OR = 0.91, 95%CI: 0.82-1.00; P = 0.054, age-adjusted) while men with normal vitD were at elevated risk (OR = 1.23, 95%CI: 1.04-1.45). These findings suggest that AA men who are at a higher risk of PCa may benefit more from vitD intake, and supplementation with dietary quercetin may increase the risk of PCa in AA men with normal vitD levels. Further studies with larger populations are needed to better understand the impact of the interaction between sera vitD levels and supplementation with quercetin on PCa in AA men. © 2015 Wiley Periodicals, Inc.

Lycopene and Risk of Prostate Cancer

PubMed Central

Chen, Ping; Zhang, Wenhao; Wang, Xiao; Zhao, Keke; Negi, Devendra Singh; Zhuo, Li; Qi, Mao; Wang, Xinghuan; Zhang, Xinhua

2015-01-01

Abstract Prostate cancer (PCa) is a common illness for aging males. Lycopene has been identified as an antioxidant agent with potential anticancer properties. Studies investigating the relation between lycopene and PCa risk have produced inconsistent results. This study aims to determine dietary lycopene consumption/circulating concentration and any potential dose–response associations with the risk of PCa. Eligible studies published in English up to April 10, 2014, were searched and identified from Pubmed, Sciencedirect Online, Wiley online library databases and hand searching. The STATA (version 12.0) was applied to process the dose–response meta-analysis. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) and to incorporate variation between studies. The linear and nonlinear dose–response relations were evaluated with data from categories of lycopene consumption/circulating concentrations. Twenty-six studies were included with 17,517 cases of PCa reported from 563,299 participants. Although inverse association between lycopene consumption and PCa risk was not found in all studies, there was a trend that with higher lycopene intake, there was reduced incidence of PCa (P = 0.078). Removal of one Chinese study in sensitivity analysis, or recalculation using data from only high-quality studies for subgroup analysis, indicated that higher lycopene consumption significantly lowered PCa risk. Furthermore, our dose–response meta-analysis demonstrated that higher lycopene consumption was linearly associated with a reduced risk of PCa with a threshold between 9 and 21 mg/day. Consistently, higher circulating lycopene levels significantly reduced the risk of PCa. Interestingly, the concentration of circulating lycopene between 2.17 and 85 μg/dL was linearly inversed with PCa risk whereas there was no linear association >85 μg/dL. In addition, greater efficacy for the circulating lycopene concentration on preventing PCa was found for studies with high quality, follow-up >10 years and where results were adjusted by the age or the body mass index. In conclusion, our novel data demonstrates that higher lycopene consumption/circulating concentration is associated with a lower risk of PCa. However, further studies are required to determine the mechanism by which lycopene reduces the risk of PCa and if there are other factors in tomato products that might potentially decrease PCa risk and progression. PMID:26287411

Characterizing the molecular features of ERG-positive tumors in primary and castration resistant prostate cancer.

PubMed

Roudier, Martine P; Winters, Brian R; Coleman, Ilsa; Lam, Hung-Ming; Zhang, Xiaotun; Coleman, Roger; Chéry, Lisly; True, Lawrence D; Higano, Celestia S; Montgomery, Bruce; Lange, Paul H; Snyder, Linda A; Srivastava, Shiv; Corey, Eva; Vessella, Robert L; Nelson, Peter S; Üren, Aykut; Morrissey, Colm

2016-06-01

The TMPRSS2-ERG gene fusion is detected in approximately half of primary prostate cancers (PCa) yet the prognostic significance remains unclear. We hypothesized that ERG promotes the expression of common genes in primary PCa and metastatic castration-resistant PCa (CRPC), with the objective of identifying ERG-associated pathways, which may promote the transition from primary PCa to CRPC. We constructed tissue microarrays (TMA) from 127 radical prostatectomy specimens, 20 LuCaP patient-derived xenografts (PDX), and 152 CRPC metastases obtained immediately at time of death. Nuclear ERG was assessed by immunohistochemistry (IHC). To characterize the molecular features of ERG-expressing PCa, a subset of IHC confirmed ERG+ or ERG- specimens including 11 radical prostatectomies, 20 LuCaP PDXs, and 45 CRPC metastases underwent gene expression analysis. Genes were ranked based on expression in primary PCa and CRPC. Common genes of interest were targeted for IHC analysis and expression compared with biochemical recurrence (BCR) status. IHC revealed that 43% of primary PCa, 35% of the LuCaP PDXs, and 18% of the CRPC metastases were ERG+ (12 of 48 patients [25%] had at least one ERG+ metastasis). Based on gene expression data and previous literature, two proteins involved in calcium signaling (NCALD, CACNA1D), a protein involved in inflammation (HLA-DMB), CD3 positive immune cells, and a novel ERG-associated protein, DCLK1 were evaluated in primary PCa and CRPC metastases. In ERG+ primary PCa, a weak association was seen with NCALD and CACNA1D protein expression. HLA-DMB association with ERG was decreased and CD3 cell number association with ERG was changed from positive to negative in CRPC metastases compared to primary PCa. DCLK1 was upregulated at the protein level in unpaired ERG+ primary PCa and CRPC metastases (P = 0.0013 and P < 0.0001, respectively). In primary PCa, ERG status or expression of targeted proteins was not associated with BCR-free survival. However, for primary PCa, ERG+DCLK1+ patients exhibited shorter time to BCR (P = 0.06) compared with ERG+DCLK1- patients. This study examined ERG expression in primary PCa and CRPC. We have identified altered levels of inflammatory mediators associated with ERG expression. We determined expression of DCLK1 correlates with ERG expression and may play a role in primary PCa progression to metastatic CPRC. Prostate 76:810-822, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Spinal anaesthesia for a caesarean section in a patient with paraneoplastic cerebellar ataxia

PubMed Central

Tuna, Ayca Tas; Sahin, Fatih; Kotan, Dilcan; Erdem, Ali Fuat; Baykara, Meltem; Duzcan, Tuba

2017-01-01

Paraneoplastic cerebellar ataxia (PCA) is most frequently observed in gynaecological cancers, small cell lung cancer, breast cancer, Hodgkin's lymphoma, cancer testis or malignant thymoma. In the literature, there is no data related to the effects of PCA during pregnancy or reports on the effects of anaesthesia in patients with PCA. We present management of a pregnant woman with PCA who was suddenly unable to walk with PCA and for whom effective spinal anaesthesia was performed for an elective caesarean section with no complications. PMID:28515524

Structural design approaches for creating fat droplet and starch granule mimetics.

PubMed

McClements, David Julian; Chung, Cheryl; Wu, Bi-Cheng

2017-02-22

This article focuses on hydrogel-based strategies for creating reduced calorie foods with desirable physicochemical, sensory, and nutritional properties. Initially, the role of fat droplets and starch granules in foods is discussed, and then different methods for fabricating hydrogel beads are reviewed, including phase separation, antisolvent precipitation, injection, and emulsion template methods. Finally, the potential application of hydrogel beads as fat droplet and starch granule replacements is discussed. There is still a need for large-scale, high-throughout, and economical methods of fabricating hydrogel beads suitable for utilization within the food industry.

Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluids (SEDS).

PubMed

Edwards, A D; Shekunov, B Y; Kordikowski, A; Forbes, R T; York, P

2001-08-01

Pure anhydrous polymorphs of carbamazepine were prepared by solution-enhanced dispersion with supercritical fluids (SEDS). Crystallization of the polymorphs was studied. Mechanisms are proposed that consider the thermodynamics of carbamazepine, supersaturation in the SEDS process, and the binary phase equilibria of organic solvents and the carbon dioxide antisolvent. alpha-Carbamazepine was crystallized at high supersaturations and low temperatures, beta-carbamazepine crystallized from a methanol-carbon dioxide phase split, and gamma-carbamazepine crystallized via nucleation at high temperatures and low supersaturation. Copyright 2001 Wiley-Liss, Inc.

EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.

PubMed

Kim, Yong-June; Yoon, Hyung-Yoon; Kim, Seon-Kyu; Kim, Young-Won; Kim, Eun-Jung; Kim, Isaac Yi; Kim, Wun-Jae

2011-07-01

Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells. Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out. Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH. Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa.

Development and Flight Test of an Emergency Flight Control System Using Only Engine Thrust on an MD-11 Transport Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Burken, John J.; Maine, Trindel A.; Fullerton, C. Gordon

1997-01-01

An emergency flight control system that uses only engine thrust, called the propulsion-controlled aircraft (PCA) system, was developed and flight tested on an MD-11 airplane. The PCA system is a thrust-only control system, which augments pilot flightpath and track commands with aircraft feedback parameters to control engine thrust. The PCA system was implemented on the MD-11 airplane using only software modifications to existing computers. Results of a 25-hr flight test show that the PCA system can be used to fly to an airport and safely land a transport airplane with an inoperative flight control system. In up-and-away operation, the PCA system served as an acceptable autopilot capable of extended flight over a range of speeds, altitudes, and configurations. PCA approaches, go-arounds, and three landings without the use of any normal flight controls were demonstrated, including ILS-coupled hands-off landings. PCA operation was used to recover from an upset condition. The PCA system was also tested at altitude with all three hydraulic systems turned off. This paper reviews the principles of throttles-only flight control, a history of accidents or incidents in which some or all flight controls were lost, the MD-11 airplane and its systems, PCA system development, operation, flight testing, and pilot comments.

Opioid Patient Controlled Analgesia (PCA) use during the Initial Experience with the IMPROVE PCA Trial: A Phase III Analgesic Trial for Hospitalized Sickle Cell Patients with Painful Episodes

PubMed Central

Dampier, Carlton D.; Smith, Wally R.; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C.; Minniti, Caterina P.; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A. Kyle; McClish, Donna; McKinlay, Sonja M.; Miller, Scott T.; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J.; Weiner, Debra L.

2015-01-01

Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents, mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI and in the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI 0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage. PMID:21953763

Degradation of 1,1,2,2-tetrachloroethane in a freshwater tidal wetland: Field and laboratory evidence

USGS Publications Warehouse

Lorah, M.M.; Olsen, L.D.

1999-01-01

Degradation reactions controlling the fate of 1,1,2,2-tetrachloroethane (PCA) in a freshwater tidal wetland that is a discharge area for a contaminated aquifer were investigated by a combined field and laboratory study. Samples from nested piezometers and porous-membrane sampling devices (peepers) showed that PCA concentrations decreased and that less chlorinated daughter products formed as the groundwater became increasingly reducing along upward flow paths through the wetland sediments. The cis and trans isomers of 1,2-dichloroethylene (12DCE) and vinyl chloride (VC) were the predominant daughter products detected from degradation of PCA in the field and in microcosms constructed under methanogenic conditions. Significantly lower ratios of cis-12DCE to trans-12DCE were produced by PCA degradation than by degradation of trichloroethylene, a common co-contaminant with PCA. 1,1,2-Trichloroethane (112TCA) and 1,2-dichloroethane (12DCA) occurred simultaneously with 12DCE, indicating simultaneous hydrogenolysis and dichloroelimination of PCA. From an initial PCA concentration of about 1.5 ??mol/L, concentrations of PCA and its daughter products decreased to below detection within a 1.0-m vertical distance in the wetland sediments and within 34 days in the microcosms. The results indicate that natural attenuation of PCA through complete anaerobic biodegradation can occur in wetlands before sensitive surface water receptors are reached.

Integration of lipidomics and transcriptomics unravels aberrant lipid metabolism and defines cholesteryl oleate as potential biomarker of prostate cancer

NASA Astrophysics Data System (ADS)

Li, Jia; Ren, Shancheng; Piao, Hai-Long; Wang, Fubo; Yin, Peiyuan; Xu, Chuanliang; Lu, Xin; Ye, Guozhu; Shao, Yaping; Yan, Min; Zhao, Xinjie; Sun, Yinghao; Xu, Guowang

2016-02-01

In-depth delineation of lipid metabolism in prostate cancer (PCa) is significant to open new insights into prostate tumorigenesis and progression, and provide potential biomarkers with greater accuracy for improved diagnosis. Here, we performed lipidomics and transcriptomics in paired prostate cancer tumor (PCT) and adjacent nontumor (ANT) tissues, followed by external validation of biomarker candidates. We identified major dysregulated pathways involving lipogenesis, lipid uptake and phospholipids remodeling, correlated with widespread lipid accumulation and lipid compositional reprogramming in PCa. Specifically, cholesteryl esters (CEs) were most prominently accumulated in PCa, and significantly associated with cancer progression and metastasis. We showed that overexpressed scavenger receptor class B type I (SR-BI) may contribute to CEs accumulation. In discovery set, CEs robustly differentiated PCa from nontumor (area under curve (AUC) of receiver operating characteristics (ROC), 0.90-0.94). In validation set, CEs potently distinguished PCa and non-malignance (AUC, 0.84-0.91), and discriminated PCa and benign prostatic hyperplasia (BPH) (AUC, 0.90-0.96), superior to serum prostate-specific antigen (PSA) (AUC = 0.83). Cholesteryl oleate showed highest AUCs in distinguishing PCa from non-malignance or BPH (AUC = 0.91 and 0.96). Collectively, our results unravel the major lipid metabolic aberrations in PCa and imply the potential role of CEs, particularly, cholesteryl oleate, as molecular biomarker for PCa detection.

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines.

PubMed

Haddad, A Q; Venkateswaran, V; Viswanathan, L; Teahan, S J; Fleshner, N E; Klotz, L H

2006-01-01

Epidemiologic studies have demonstrated an inverse association between flavonoid intake and prostate cancer (PCa) risk. The East Asian diet is very high in flavonoids and, correspondingly, men in China and Japan have the lowest incidence of PCa worldwide. There are thousands of different naturally occurring and synthetic flavonoids. However, only a few have been studied in PCa. Our aim was to identify novel flavonoids with antiproliferative effect in PCa cell lines, as well as determine their effects on cell cycle. We have screened a representative subgroup of 26 flavonoids for antiproliferative effect on the human PCa (LNCaP and PC3), breast cancer (MCF-7), and normal prostate stromal cell lines (PrSC). Using a fluorescence-based cell proliferation assay (Cyquant), we have identified five flavonoids, including the novel compounds 2,2'-dihydroxychalcone and fisetin, with antiproliferative and cell cycle arresting properties in human PCa in vitro. Most of the flavonoids tested exerted antiproliferative effect at lower doses in the PCa cell lines compared to the non-PCa cells. Flow cytometry was used as a means to determine the effects on cell cycle. PC3 cells were arrested in G2/M phase by flavonoids. LNCaP cells demonstrated different cell cycle profiles. Further studies are warranted to determine the molecular mechanism of action of 2,2'-DHC and fisetin in PCa, and to establish their effectiveness in vivo.

Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer

PubMed Central

Narizhneva, Natalia V.; Tararova, Natalia D.; Ryabokon, Petro; Shyshynova, Inna; Prokvolit, Anatoly; Komarov, Pavel G.; Purmal, Andrei A.; Gudkov, Andrei V.; Gurova, Katerina V.

2010-01-01

In prostate cancer (PCa) patients, initial responsiveness to androgen deprivation therapy is frequently followed by relapse due to development of treatment-resistant androgen-independent PCa. This is typically associated with acquisition of mutations in AR that allow activity as a transcription factor in the absence of ligand, indicating that androgen-independent PCa remains dependent on AR function. Our strategy to effectively target AR in androgen-independent PCa involved using a cell-based readout to isolate small molecules that inhibit AR transactivation function through mechanisms other than modulation of ligand binding. A number of the identified inhibitors were toxic to AR-expressing PCa cells regardless of their androgen dependence. Among these, some only suppressed PCa cell growth (ARTIS), while others induced cell death (ARTIK). ARTIK, but not ARTIS, compounds caused disappearance of AR protein from treated cells. siRNA against AR behaved like ARTIK compounds, while a dominant negative AR mutant that prevents AR-mediated transactivation but does not eliminate the protein showed only a growth suppressive effect. These observations reveal a transcription-independent function of AR that is essential for PCa cell viability and, therefore, is an ideal target for anti-PCa treatment. Indeed, several of the identified AR inhibitors demonstrated in vivo efficacy in mouse models of PCa and are candidates for pharmacologic optimization. PMID:19946220

Development and Flight Test of an Augmented Thrust-Only Flight Control System on an MD-11 Transport Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.; Burken, John J.; Pappas, Drew

1996-01-01

An emergency flight control system using only engine thrust, called Propulsion-Controlled Aircraft (PCA), has been developed and flight tested on an MD-11 airplane. In this thrust-only control system, pilot flight path and track commands and aircraft feedback parameters are used to control the throttles. The PCA system was installed on the MD-11 airplane using software modifications to existing computers. Flight test results show that the PCA system can be used to fly to an airport and safely land a transport airplane with an inoperative flight control system. In up-and-away operation, the PCA system served as an acceptable autopilot capable of extended flight over a range of speeds and altitudes. The PCA approaches, go-arounds, and three landings without the use of any non-nal flight controls have been demonstrated, including instrument landing system-coupled hands-off landings. The PCA operation was used to recover from an upset condition. In addition, PCA was tested at altitude with all three hydraulic systems turned off. This paper reviews the principles of throttles-only flight control; describes the MD-11 airplane and systems; and discusses PCA system development, operation, flight testing, and pilot comments.

Isolation of candidate genes for apomictic development in buffelgrass (Pennisetum ciliare).

PubMed

Singh, Manjit; Burson, Byron L; Finlayson, Scott A

2007-08-01

Asexual reproduction through seeds, or apomixis, is a process that holds much promise for agricultural advances. However, the molecular mechanisms underlying apomixis are currently poorly understood. To identify genes related to female gametophyte development in apomictic ovaries of buffelgrass (Pennisetum ciliare (L.) Link), Suppression Subtractive Hybridization of ovary cDNA with leaf cDNA was performed. Through macroarray screening of subtracted cDNAs two genes were identified, Pca21 and Pca24, that showed differential expression between apomictic and sexual ovaries. Sequence analysis showed that both Pca21 and Pca24 are novel genes not previously characterized in plants. Pca21 shows homology to two wheat genes that are also expressed during reproductive development. Pca24 has similarity to coiled-coil-helix-coiled-coil-helix (CHCH) domain containing proteins from maize and sugarcane. Northern blot analysis revealed that both of these genes are expressed throughout female gametophyte development in apomictic ovaries. In situ hybridizations localized the transcript of these two genes to the developing embryo sacs in the apomictic ovaries. Based on the expression patterns it was concluded that Pca21 and Pca24 likely play a role during apomictic development in buffelgrass.

Personal and couple level risk factors: Maternal and paternal parent-child aggression risk.

PubMed

Tucker, Meagan C; Rodriguez, Christina M; Baker, Levi R

2017-07-01

Previous literature examining parent-child aggression (PCA) risk has relied heavily upon mothers, limiting our understanding of paternal risk factors. Moreover, the extent to which factors in the couple relationship work in tandem with personal vulnerabilities to impact PCA risk is unclear. The current study examined whether personal stress and distress predicted PCA risk (child abuse potential, over-reactive discipline style, harsh discipline practices) for fathers as well as mothers and whether couple functioning mediated versus moderated the relation between personal stress and PCA risk in a sample of 81 couples. Additionally, the potential for risk factors in one partner to cross over and affect their partner's PCA risk was considered. Findings indicated higher personal stress predicted elevated maternal and paternal PCA risk. Better couple functioning did not moderate this relationship but partially mediated stress and PCA risk for both mothers and fathers. In addition, maternal stress evidenced a cross-over effect, wherein mothers' personal stress linked to fathers' couple functioning. Findings support the role of stress and couple functioning in maternal and paternal PCA risk, including potential cross-over effects that warrant further inquiry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Motor features in posterior cortical atrophy and their imaging correlates.

PubMed

Ryan, Natalie S; Shakespeare, Timothy J; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M; Leung, Kelvin K; Fox, Nick C; Crutch, Sebastian J

2014-12-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia

PubMed Central

Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-01-01

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa. PMID:29100363

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia.

PubMed

Jia, Gaozhen; Dong, Zhenyang; Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-09-29

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii.

PubMed

Tesini, Brenda L; Wright, Terry W; Malone, Jane E; Haidaris, Constantine G; Harber, Martha; Sant, Andrea J; Nayak, Jennifer L; Gigliotti, Francis

2017-04-01

Pneumocystis pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse Pneumocystis surface protein, designated Pneumocystis cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4 + T cells were depleted, and the mice were exposed to Pneumocystis murina Pca1 immunization completely protected nearly all mice, similar to immunization with whole Pneumocystis organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized Pneumocystis jirovecii and Pneumocystis carinii Potential orthologs of Pca1 have been identified in P. jirovecii Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation. Copyright © 2017 American Society for Microbiology.

Comparison of water extraction methods in Tibet based on GF-1 data

NASA Astrophysics Data System (ADS)

Jia, Lingjun; Shang, Kun; Liu, Jing; Sun, Zhongqing

2018-03-01

In this study, we compared four different water extraction methods with GF-1 data according to different water types in Tibet, including Support Vector Machine (SVM), Principal Component Analysis (PCA), Decision Tree Classifier based on False Normalized Difference Water Index (FNDWI-DTC), and PCA-SVM. The results show that all of the four methods can extract large area water body, but only SVM and PCA-SVM can obtain satisfying extraction results for small size water body. The methods were evaluated by both overall accuracy (OAA) and Kappa coefficient (KC). The OAA of PCA-SVM, SVM, FNDWI-DTC, PCA are 96.68%, 94.23%, 93.99%, 93.01%, and the KCs are 0.9308, 0.8995, 0.8962, 0.8842, respectively, in consistent with visual inspection. In summary, SVM is better for narrow rivers extraction and PCA-SVM is suitable for water extraction of various types. As for dark blue lakes, the methods using PCA can extract more quickly and accurately.

Hemispheric Asymmetry of Visual Cortical Response by Means of Functional Transcranial Doppler

PubMed Central

Roje-Bedeković, Marina; Lovrenčić-Huzjan, Arijana; Bosnar-Puretić, Marijana; Šerić, Vesna; Demarin, Vida

2012-01-01

We assessed the visual evoked response and investigated side-to-side differences in mean blood flow velocities (MBFVs) by means of functional transcranial Doppler (fTCD) in 49 right-handed patients with severe internal carotid artery (ICA) stenosis and 30 healthy volunteers, simultaneously in both posterior cerebral arteries (PCAs) using 2 MHz probes, successively in the dark and during the white light stimulation. Statistically significant correlation (P = 0.001) was shown in healthy and in patients (P < 0.05) between MBFV in right PCA in physiological conditions and MBFV in right PCA during the white light stimulation and in the dark. The correlation between MBVF in right PCA and contralateral left PCA was not statistically significant (P > 0.05). The correlation between ipsilateral left PCA was significantly higher than the one with contralateral right PCA (P < 0.05). There is a clear trend towards the lateralisation of the visual evoked response in the right PCA. PMID:22135771

Modelling Nonlinear Dynamic Textures using Hybrid DWT-DCT and Kernel PCA with GPU

NASA Astrophysics Data System (ADS)

Ghadekar, Premanand Pralhad; Chopade, Nilkanth Bhikaji

2016-12-01

Most of the real-world dynamic textures are nonlinear, non-stationary, and irregular. Nonlinear motion also has some repetition of motion, but it exhibits high variation, stochasticity, and randomness. Hybrid DWT-DCT and Kernel Principal Component Analysis (KPCA) with YCbCr/YIQ colour coding using the Dynamic Texture Unit (DTU) approach is proposed to model a nonlinear dynamic texture, which provides better results than state-of-art methods in terms of PSNR, compression ratio, model coefficients, and model size. Dynamic texture is decomposed into DTUs as they help to extract temporal self-similarity. Hybrid DWT-DCT is used to extract spatial redundancy. YCbCr/YIQ colour encoding is performed to capture chromatic correlation. KPCA is applied to capture nonlinear motion. Further, the proposed algorithm is implemented on Graphics Processing Unit (GPU), which comprise of hundreds of small processors to decrease time complexity and to achieve parallelism.

Asymmetric distances for binary embeddings.

PubMed

Gordo, Albert; Perronnin, Florent; Gong, Yunchao; Lazebnik, Svetlana

2014-01-01

In large-scale query-by-example retrieval, embedding image signatures in a binary space offers two benefits: data compression and search efficiency. While most embedding algorithms binarize both query and database signatures, it has been noted that this is not strictly a requirement. Indeed, asymmetric schemes that binarize the database signatures but not the query still enjoy the same two benefits but may provide superior accuracy. In this work, we propose two general asymmetric distances that are applicable to a wide variety of embedding techniques including locality sensitive hashing (LSH), locality sensitive binary codes (LSBC), spectral hashing (SH), PCA embedding (PCAE), PCAE with random rotations (PCAE-RR), and PCAE with iterative quantization (PCAE-ITQ). We experiment on four public benchmarks containing up to 1M images and show that the proposed asymmetric distances consistently lead to large improvements over the symmetric Hamming distance for all binary embedding techniques.

Energy-Discriminative Performance of a Spectral Micro-CT System

PubMed Central

He, Peng; Yu, Hengyong; Bennett, James; Ronaldson, Paul; Zainon, Rafidah; Butler, Anthony; Butler, Phil; Wei, Biao; Wang, Ge

2013-01-01

Experiments were performed to evaluate the energy-discriminative performance of a spectral (multi-energy) micro-CT system. The system, designed by MARS (Medipix All Resolution System) Bio-Imaging Ltd. (Christchurch, New Zealand), employs a photon-counting energy-discriminative detector technology developed by CERN (European Organization for Nuclear Research). We used the K-edge attenuation characteristic of some known materials to calibrate the detector’s photon energy discrimination. For tomographic analysis, we used the compressed sensing (CS) based ordered-subset simultaneous algebraic reconstruction techniques (OS-SART) to reconstruct sample images, which is effective to reduce noise and suppress artifacts. Unlike conventional CT, the principal component analysis (PCA) method can be applied to extract and quantify additional attenuation information from a spectral CT dataset. Our results show that the spectral CT has a good energy-discriminative performance and provides more attenuation information than the conventional CT. PMID:24004864

PCA Tomography: how to extract information from data cubes

NASA Astrophysics Data System (ADS)

Steiner, J. E.; Menezes, R. B.; Ricci, T. V.; Oliveira, A. S.

2009-05-01

Astronomy has evolved almost exclusively by the use of spectroscopic and imaging techniques, operated separately. With the development of modern technologies, it is possible to obtain data cubes in which one combines both techniques simultaneously, producing images with spectral resolution. To extract information from them can be quite complex, and hence the development of new methods of data analysis is desirable. We present a method of analysis of data cube (data from single field observations, containing two spatial and one spectral dimension) that uses Principal Component Analysis (PCA) to express the data in the form of reduced dimensionality, facilitating efficient information extraction from very large data sets. PCA transforms the system of correlated coordinates into a system of uncorrelated coordinates ordered by principal components of decreasing variance. The new coordinates are referred to as eigenvectors, and the projections of the data on to these coordinates produce images we will call tomograms. The association of the tomograms (images) to eigenvectors (spectra) is important for the interpretation of both. The eigenvectors are mutually orthogonal, and this information is fundamental for their handling and interpretation. When the data cube shows objects that present uncorrelated physical phenomena, the eigenvector's orthogonality may be instrumental in separating and identifying them. By handling eigenvectors and tomograms, one can enhance features, extract noise, compress data, extract spectra, etc. We applied the method, for illustration purpose only, to the central region of the low ionization nuclear emission region (LINER) galaxy NGC 4736, and demonstrate that it has a type 1 active nucleus, not known before. Furthermore, we show that it is displaced from the centre of its stellar bulge. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the National Science Foundation on behalf of the Gemini partnership: the National Science Foundation (United States), the Science and Technology Facilities Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência e Tecnologia (Brazil) and SECYT (Argentina). E-mail: steiner@astro.iag.usp.br

[Patient-controlled Analgesia (PCA): an Overview About Methods, Handling and New Modalities].

PubMed

Abrolat, Marie; Eberhart, Leopold H J; Kalmus, Gerald; Koch, Tilo; Nardi-Hiebl, Stefan

2018-04-01

Patient-controlled analgesia (PCA) is one of the well established methods for the treatment of postoperative pain. A cochrane-review concluded that PCA is associated with better postoperative pain ratings and improved patient-satifaction compared to traditional way of administering opioids. Some prerequisites concerning patient selection, education of the patient and the medical staff, and supervision during PCA therapy are mandatory for a safe use of PCA. Current PCA modalities (intravenous and epidural routes of application) are expanded by newer, less invasive routes of drug administration, e.g. by the iontophoretic transdermal and the sublingual route. Their role in improving safety and the quality of pain therapy on the one hand side, and costs on the other hand side are discussion. Georg Thieme Verlag KG Stuttgart · New York.

Comparative preclinical evaluation of 68Ga-NODAGA and 68Ga-HBED-CC conjugated procainamide in melanoma imaging.

PubMed

Trencsényi, György; Dénes, Noémi; Nagy, Gábor; Kis, Adrienn; Vida, András; Farkas, Flóra; Szabó, Judit P; Kovács, Tünde; Berényi, Ervin; Garai, Ildikó; Bai, Péter; Hunyadi, János; Kertész, István

2017-05-30

Malignant melanoma is the most aggressive form of skin cancer. The early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of this disease. Previous studies have shown that benzamide derivatives (e.g. procainamide) conjugated with PET radionuclides specifically bind to melanin pigment of melanoma tumors. 68 Ga chelating agents can have high influence on physiological properties of 68 Ga labeled bioactive molecules, as was experienced during the application of HBED-CC on PSMA ligand. The aim of this study was to assess this concept in the case of the melanin specific procaindamide (PCA) and to compare the melanin specificity of 68 Ga-labeled PCA using HBED-CC and NODAGA chelators under in vitro and in vivo conditions. Procainamide (PCA) was conjugated with HBED-CC and NODAGA chelators and was labeled with Ga-68. The melanin specificity of 68 Ga-HBED-CC-PCA and 68 Ga-NODAGA-PCA was investigated in vitro and in vivo using amelanotic (MELUR and A375) and melanin containing (B16-F10) melanoma cell lines. Tumor-bearing mice were prepared by subcutaneous injection of B16-F10, MELUR and A375 melanoma cells into C57BL/6 and SCID mice. 21±2days after tumor cell inoculation and 90min after intravenous injection of the 68 Ga-labelledlabeled radiopharmacons whole body PET/MRI scans were performed. 68 Ga-NODAGA-PCA and 68 Ga-HBED-CC-PCA were produced with excellent radiochemical purity (98%). In vitro experiments demonstrated that after 30 and 90min incubation time 68 Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than the 68 Ga-HBED-CC-conjugated PCA accumulation in the same cell line. Furthermore, significant difference (p≤0.01 and 0.05) was found between the uptake of melanin negative and positive cell lines using 68 Ga-NODAGA-PCA and 68 Ga-HBED-CC-PCA. In vivo PET/MRI studies using tumor models revealed significantly (p≤0.01) higher 68 Ga-NODAGA-PCA uptake (SUVmean: 0.46±0.05, SUVmax: 1.96±0.25,T/M ratio: 40.7±4.23) in B16-F10 tumors in contrast to 68 Ga-HBED-CC-PCA where the SUVmean, SUVmax and T/M ratio were 0.13±0.01, 0.56±0.11 and 11.43±1.24, respectively. Melanin specific PCA conjugated with NODAGA chelator showed higher specific binding properties than conjugated with HBED-CC. The chemical properties of the bifunctional chelators used for 68 Ga-labeling of PCA determine the biological behaviour of the probes. Due to the high specificity and sensitivity 68 Ga-labeled PCA molecules are promising radiotracers in melanoma imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of THADA, FOXP4, GPRC6A/RFX6 genes and 8q24 risk alleles with prostate cancer in Northern Chinese men.

PubMed

Li, Xing-Hui; Xu, Yong; Yang, Kuo; Shi, Jian-Jian; Zhang, Xiao; Yang, Fang; Yuan, Huiping; Zhu, Xiaoquan; Zhang, Yu-Hong; Wang, Jian-Ye; Yang, Ze

2015-01-01

Prostate cancer (PCa) is one of the most common malignancies in males, and multiple genetic studies have confirmed association with susceptibility to PCa. However, the risk conferred in men living in China is unkown. We selected 6 previously identified variants as candidates to define their association with PCa in Chinese men. We genotyped 6 single nucleotide polymorphisms (SNPs) (rs1465618, rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) using high resolution melting (HRM) analysis and assessed their association with PCa risk in a case-control study of 481 patients and 480 controls in a Chinese population. In addition, the individual and cumulative contribution for the risk of PCa and clinical covariates were analysed. We found that 5 of the 6 genetic variants were associated with PCa risk. The T allele of rs339331 and the G allele of rs16901966 showed a significant association with PCa susceptibility: OR (95%CI)= 0.78 (0.64-0.94), p<0.009 and OR (95%CI)= 0.66 (0.54-0.81), p<0.0001, as well as A allele of rs1447295 (OR [95%CI]=1.46 (1.17-1.84), p<0.001) and T allele of rs10090154 (OR [95%CI]= 0.58 (0.46-0.74), p<0.0001). rs339331(T) was associated with a 0.71-fold and 1.42-fold increase of PCa risk by dominant model (p=0.007) and recessive model (p=0.007). rs16901966 (G) was associated with a 0.51-fold and 1.98-fold increase of PCa risk by dominant model (p=0.006) and recessive model (p=0.0058). rs10090154 (T) was associated with a 1.89-fold and 0.53-fold increase of PCa risk by dominant model (p=0.000006) and recessive model (p=0.000006). And, rs1983891(C) was associated with a 0.77-fold increase of PCa risk by recessive model (p=0.045). rs1447295 was associated with a 1.57-fold increase of PCa risk by dominant model (p=0.008). rs1465618 showed no significant association with PCa. The cumulative effects test of risk alleles (rs rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) showed an increasing risk to PCa in a frequency-dependent manner (ptrend=0.001), and men with more than 3 risk alleles had the most significant susceptibility to PCa (OR=1.99, p=0.001), compared with those who had one risk allele (OR=1.17, p=0.486). Our results provide further support for association of the THADA, FOXP4, GPRC6A/RFX6 and 8q24 genes with Pca in Asian populations. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.

The added value of percentage of free to total prostate-specific antigen, PCA3, and a kallikrein panel to the ERSPC risk calculator for prostate cancer in prescreened men.

PubMed

Vedder, Moniek M; de Bekker-Grob, Esther W; Lilja, Hans G; Vickers, Andrew J; van Leenders, Geert J L H; Steyerberg, Ewout W; Roobol, Monique J

2014-12-01

Prostate-specific antigen (PSA) testing has limited accuracy for the early detection of prostate cancer (PCa). To assess the value added by percentage of free to total PSA (%fPSA), prostate cancer antigen 3 (PCA3), and a kallikrein panel (4k-panel) to the European Randomised Study of Screening for Prostate Cancer (ERSPC) multivariable prediction models: risk calculator (RC) 4, including transrectal ultrasound, and RC 4 plus digital rectal examination (4+DRE) for prescreened men. Participants were invited for rescreening between October 2007 and February 2009 within the Dutch part of the ERSPC study. Biopsies were taken in men with a PSA level ≥3.0 ng/ml or a PCA3 score ≥10. Additional analyses of the 4k-panel were done on serum samples. Outcome was defined as PCa detectable by sextant biopsy. Receiver operating characteristic curve and decision curve analyses were performed to compare the predictive capabilities of %fPSA, PCA3, 4k-panel, the ERSPC RCs, and their combinations in logistic regression models. PCa was detected in 119 of 708 men. The %fPSA did not perform better univariately or added to the RCs compared with the RCs alone. In 202 men with an elevated PSA, the 4k-panel discriminated better than PCA3 when modelled univariately (area under the curve [AUC]: 0.78 vs. 0.62; p=0.01). The multivariable models with PCA3 or the 4k-panel were equivalent (AUC: 0.80 for RC 4+DRE). In the total population, PCA3 discriminated better than the 4k-panel (univariate AUC: 0.63 vs. 0.56; p=0.05). There was no statistically significant difference between the multivariable model with PCA3 (AUC: 0.73) versus the model with the 4k-panel (AUC: 0.71; p=0.18). The multivariable model with PCA3 performed better than the reference model (0.73 vs. 0.70; p=0.02). Decision curves confirmed these patterns, although numbers were small. Both PCA3 and, to a lesser extent, a 4k-panel have added value to the DRE-based ERSPC RC in detecting PCa in prescreened men. We studied the added value of novel biomarkers to previously developed risk prediction models for prostate cancer. We found that inclusion of these biomarkers resulted in an increase in predictive ability. Copyright © 2014. Published by Elsevier B.V.

External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome.

PubMed

Auprich, Marco; Haese, Alexander; Walz, Jochen; Pummer, Karl; de la Taille, Alexandre; Graefen, Markus; de Reijke, Theo; Fisch, Margit; Kil, Paul; Gontero, Paolo; Irani, Jacques; Chun, Felix K-H

2010-11-01

Prior to safely adopting risk stratification tools, their performance must be tested in an external patient cohort. To assess accuracy and generalizability of previously reported, internally validated, prebiopsy prostate cancer antigen 3 (PCA3) gene-based nomograms when applied to a large, external, European cohort of men at risk of prostate cancer (PCa). Biopsy data, including urinary PCA3 score, were available for 621 men at risk of PCa who were participating in a European multi-institutional study. All patients underwent a ≥10-core prostate biopsy. Biopsy indication was based on suspicious digital rectal examination, persistently elevated prostate-specific antigen level (2.5-10 ng/ml) and/or suspicious histology (atypical small acinar proliferation of the prostate, >/= two cores affected by high-grade prostatic intraepithelial neoplasia in first set of biopsies). PCA3 scores were assessed using the Progensa assay (Gen-Probe Inc, San Diego, CA, USA). According to the previously reported nomograms, different PCA3 score codings were used. The probability of a positive biopsy was calculated using previously published logistic regression coefficients. Predicted outcomes were compared to the actual biopsy results. Accuracy was calculated using the area under the curve as a measure of discrimination; calibration was explored graphically. Biopsy-confirmed PCa was detected in 255 (41.1%) men. Median PCA3 score of biopsy-negative versus biopsy-positive men was 20 versus 48 in the total cohort, 17 versus 47 at initial biopsy, and 37 versus 53 at repeat biopsy (all p≤0.002). External validation of all four previously reported PCA3-based nomograms demonstrated equally high accuracy (0.73-0.75) and excellent calibration. The main limitations of the study reside in its early detection setting, referral scenario, and participation of only tertiary-care centers. In accordance with the original publication, previously developed PCA3-based nomograms achieved high accuracy and sufficient calibration. These novel nomograms represent robust tools and are thus generalizable to European men at risk of harboring PCa. Consequently, in presence of a PCA3 score, these nomograms may be safely used to assist clinicians when prostate biopsy is contemplated. Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naïve Patients with Suspected Prostate Cancer.

PubMed

Porpiglia, Francesco; Manfredi, Matteo; Mele, Fabrizio; Cossu, Marco; Bollito, Enrico; Veltri, Andrea; Cirillo, Stefano; Regge, Daniele; Faletti, Riccardo; Passera, Roberto; Fiori, Cristian; De Luca, Stefano

2017-08-01

An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa). To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa. Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial. Patients were randomized into a prebiopsy mpMRI group (arm A, n=107) or a standard biopsy (SB) group (arm B, n=105). In arm A, patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy (TB) (n=81). The remaining patients in arm A (n=26) with negative mpMRI results and patients in arm B underwent 12-core SB. The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study; the secondary end point was comparison of the DR between TB and SB. The overall DRs were higher in arm A versus arm B for PCa (50.5% vs 29.5%, respectively; p=0.002) and csPCa (43.9% vs 18.1%, respectively; p<0.001). Concerning the biopsy approach, that is, TB in arm A, SB in arm A, and SB in arm B, the overall DRs were significantly different for PCa (60.5% vs 19.2% vs 29.5%, respectively; p<0.001) and for csPCa (56.8% vs 3.8% vs 18.1%, respectively; p<0.001). The reproducibility of the study could have been affected by the single-center nature. A diagnostic pathway based on mpMRI had a higher DR than the standard pathway in both PCa and csPCa. In this randomized trial, a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) was compared with the standard pathway based on random biopsy. The mpMRI-based pathway had better performance than the standard pathway. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Fiori, Cristian; Bollito, Enrico; Cappia, Susanna; Mario Scarpa, Roberto; Sottile, Antonino; Franco Randone, Donato; Porpiglia, Francesco

2015-10-01

To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4-10ng/ml) cohort (171 individuals). Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, P<0.001), as for the PCA3 score (24 vs. 54, P<0.001) and %fPSA (11.8% vs. 15.8%, P = 0.012). The net benefit of using PCA3 and PHI to differentiate prostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40%-100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN. Copyright © 2015 Elsevier Inc. All rights reserved.

Erratum: Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment.

PubMed

Kong, D; Heath, E; Chen, W; Cher, M; Powell, I; Heilbrun, L; Li, Y; Ali, S; Sethi, S; Hassan, O; Hwang, C; Gupta, N; Chitale, D; Sakr, Wa; Menon, M; Sarkar, Fh

2013-01-01

Androgen Receptor (AR) signaling is critically important during the development and progression of prostate cancer (PCa). The AR signaling is also important in the development of castrate resistant prostate cancer (CRPC) where AR is functional even after androgen deprivation therapy (ADT); however, little is known regarding the transcriptional and functional regulation of AR in PCa. Moreover, treatment options for primary PCa for preventing the occurrence of CRPC is limited; therefore, novel strategy for direct inactivation of AR is urgently needed. In this study, we found loss of miR-34a, which targets AR, in PCa tissue specimens, especially in patients with higher Gleason grade tumors, consistent with increased expression of AR. Forced over-expression of miR-34a in PCa cell lines led to decreased expression of AR and prostate specific antigen (PSA) as well as the expression of Notch-1, another important target of miR-34a. Most importantly, BR-DIM intervention in PCa patients prior to radical prostatectomy showed reexpression of miR-34a, which was consistent with decreased expression of AR, PSA and Notch-1 in PCa tissue specimens. Moreover, BR-DIM intervention led to nuclear exclusion both in PCa cell lines and in tumor tissues. PCa cells treated with BR-DIM and 5-aza-dC resulted in the demethylation of miR-34a promoter concomitant with inhibition of AR and PSA expression in LNCaP and C4-2B cells. These results suggest, for the first time, epigenetic silencing of miR-34a in PCa, which could be reversed by BR-DIM treatment and, thus BR-DIM could be useful for the inactivation of AR in the treatment of PCa.[This corrects the article on p. 14 in vol. 4.].

Kernel Principal Component Analysis for dimensionality reduction in fMRI-based diagnosis of ADHD.

PubMed

Sidhu, Gagan S; Asgarian, Nasimeh; Greiner, Russell; Brown, Matthew R G

2012-01-01

This study explored various feature extraction methods for use in automated diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD) from functional Magnetic Resonance Image (fMRI) data. Each participant's data consisted of a resting state fMRI scan as well as phenotypic data (age, gender, handedness, IQ, and site of scanning) from the ADHD-200 dataset. We used machine learning techniques to produce support vector machine (SVM) classifiers that attempted to differentiate between (1) all ADHD patients vs. healthy controls and (2) ADHD combined (ADHD-c) type vs. ADHD inattentive (ADHD-i) type vs. controls. In different tests, we used only the phenotypic data, only the imaging data, or else both the phenotypic and imaging data. For feature extraction on fMRI data, we tested the Fast Fourier Transform (FFT), different variants of Principal Component Analysis (PCA), and combinations of FFT and PCA. PCA variants included PCA over time (PCA-t), PCA over space and time (PCA-st), and kernelized PCA (kPCA-st). Baseline chance accuracy was 64.2% produced by guessing healthy control (the majority class) for all participants. Using only phenotypic data produced 72.9% accuracy on two class diagnosis and 66.8% on three class diagnosis. Diagnosis using only imaging data did not perform as well as phenotypic-only approaches. Using both phenotypic and imaging data with combined FFT and kPCA-st feature extraction yielded accuracies of 76.0% on two class diagnosis and 68.6% on three class diagnosis-better than phenotypic-only approaches. Our results demonstrate the potential of using FFT and kPCA-st with resting-state fMRI data as well as phenotypic data for automated diagnosis of ADHD. These results are encouraging given known challenges of learning ADHD diagnostic classifiers using the ADHD-200 dataset (see Brown et al., 2012).

Monitoring of the posterior cricoarytenoid muscle represents another option for neural monitoring during thyroid surgery: Normative vagal and recurrent laryngeal nerve posterior cricoarytenoid muscle electromyographic data.

PubMed

Liddy, Whitney; Barber, Samuel R; Lin, Brian M; Kamani, Dipti; Kyriazidis, Natalia; Lawson, Bradley; Randolph, Gregory W

2018-01-01

Intraoperative neural monitoring (IONM) of laryngeal nerves using electromyography (EMG) is routinely performed using endotracheal tube surface electrodes adjacent to the vocalis muscles. Other laryngeal muscles such as the posterior cricoarytenoid muscle (PCA) are indirectly monitored. The PCA may be directly and reliably monitored through an electrode placed in the postcricoid region. Herein, we describe the method and normative data for IONM using PCA EMG. Retrospective review. Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of laryngeal nerves from January to August 2016. Recordings of vocalis and PCA EMG amplitudes and latencies with stimulation of laryngeal nerves were obtained using endotracheal (ET) tube-based and postcricoid surface electrodes. Data comprised EMG responses in vocalis and PCA recording channels with stimulation of the vagus, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve from 20 subjects (11 left, 9 right), as well as PCA EMG threshold data with RLN stimulation from 17 subjects. Mean EMG amplitude was 725.69 ± 108.58 microvolts (µV) for the ipsilateral vocalis and 329.44 ± 34.12 µV for the PCA with vagal stimulation, and 1,059.75 ± 140.40 µV for the ipsilateral vocalis and 563.88 ± 116.08 µV for the PCA with RLN stimulation. There were no statistically significant differences in mean latency. For threshold cutoffs of the PCA with RLN stimulation, mean minimum and maximum threshold intensities were 0.37 milliamperes (mA) and 0.84 mA, respectively. This study shows robust and reliable PCA EMG waveforms with direct nerve stimulation. Further studies will evaluate feasibility and application of the PCA electrode as a complementary quantitative tool in IONM. 4. Laryngoscope, 128:283-289, 2018. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Using the prostate imaging reporting and data system version 2 (PI-RIDS v2) to detect prostate cancer can prevent unnecessary biopsies and invasive treatment.

PubMed

Liu, Chang; Liu, Shi-Liang; Wang, Zhi-Xian; Yu, Kai; Feng, Chun-Xiang; Ke, Zan; Wang, Liang; Zeng, Xiao-Yong

2018-04-13

Prostate cancer (PCa) is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) to classify men with PCa, clinically significant PCa (CSPCa), or no PCa, especially among those with serum total prostate-specific antigen (tPSA) levels in the "gray zone" (4-10 ng ml -1 ). A total of 308 patients (355 lesions) were enrolled in this study. Diagnostic efficiency was determined. Univariate and multivariate analyses, receiver operating characteristic curve analysis, and decision curve analysis were performed to determine and compare the predictors of PCa and CSPCa. The results suggested that PI-RADS v2, tPSA, and prostate-specific antigen density (PSAD) were independent predictors of PCa and CSPCa. A PI-RADS v2 score ≥4 provided high negative predictive values (91.39% for PCa and 95.69% for CSPCa). A model of PI-RADS combined with PSA and PSAD helped to define a high-risk group (PI-RADS score = 5 and PSAD ≥0.15 ng ml -1 cm -3 , with tPSA in the gray zone, or PI-RADS score ≥4 with high tPSA level) with a detection rate of 96.1% for PCa and 93.0% for CSPCa while a low-risk group with a detection rate of 6.1% for PCa and 2.2% for CSPCa. It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa. The combination of PI-RADS v2 score with PSA and PSAD could be helpful in the prediction and diagnosis of PCa and CSPCa and, thus, may help in preventing unnecessary invasive procedures.

Silibinin inhibits prostate cancer cells- and RANKL-induced osteoclastogenesis by targeting NFATc1, NF-κB, and AP-1 activation in RAW264.7 cells.

PubMed

Kavitha, Chandagirikoppal V; Deep, Gagan; Gangar, Subhash C; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

2014-03-01

Currently, there are limited therapeutic options against bone metastatic prostate cancer (PCA), which is primarily responsible for high mortality and morbidity in PCA patients. Enhanced osteoclastogenesis is an essential feature associated with metastatic PCA in the bone microenvironment. Silibinin, an effective chemopreventive agent, is in phase II clinical trials in PCA patients but its efficacy against PCA cells-induced osteoclastogenesis is largely unknown. Accordingly, here we examined silibinin effect on PCA cells-induced osteoclastogenesis employing human PCA (PC3MM2, PC3, and C4-2B) and murine macrophage RAW264.7 cells. We also assessed silibinin effect on receptor activator of nuclear factor κB ligand (RANKL)-induced signaling associated with osteoclast differentiation in RAW264.7 cells. Further, we analyzed silibinin effect on osteomimicry biomarkers in PCA cells. Results revealed that silibinin (30-90 μM) inhibits PCA cells-induced osteoclast activity and differentiation in RAW264.7 cells via modulating expression of several cytokines (IGF-1, TGF-β, TNF-α, I-TAC, M-CSF, G-CSF, GM-CSF, etc.) that are important in osteoclastogenesis. Additionally, in RAW264.7 cells, silibinin decreased the RANKL-induced expression and nuclear localization of NFATc1, which is considered the master regulator of osteoclastogenesis. Furthermore, silibinin decreased the RANKL-induced DNA binding activity of NFATc1 and its regulators NF-κB and AP1, and the protein expression of osteoclast specific markers (TRAP, OSCAR, and cathepsin K). Importantly, silibinin also decreased the expression of osteomimicry biomarkers (RANKL, Runx2, osteocalcin, and PTHrP) in cell culture (PC3 and C4-2B cells) and/or in PC3 tumors. Together, our findings showing that silibinin inhibits PCA cells-induced osteoclastogenesis, suggest that silibinin could be useful clinically against bone metastatic PCA. © 2013 Wiley Periodicals, Inc.

SU-F-R-41: Regularized PCA Can Model Treatment-Related Changes in Head and Neck Patients Using Daily CBCTs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chetvertkov, M; Henry Ford Health System, Detroit, MI; Siddiqui, F

2016-06-15

Purpose: To use daily cone beam CTs (CBCTs) to develop regularized principal component analysis (PCA) models of anatomical changes in head and neck (H&N) patients, to guide replanning decisions in adaptive radiation therapy (ART). Methods: Known deformations were applied to planning CT (pCT) images of 10 H&N patients to model several different systematic anatomical changes. A Pinnacle plugin was used to interpolate systematic changes over 35 fractions, generating a set of 35 synthetic CTs for each patient. Deformation vector fields (DVFs) were acquired between the pCT and synthetic CTs and random fraction-to-fraction changes were superimposed on the DVFs. Standard non-regularizedmore » and regularized patient-specific PCA models were built using the DVFs. The ability of PCA to extract the known deformations was quantified. PCA models were also generated from clinical CBCTs, for which the deformations and DVFs were not known. It was hypothesized that resulting eigenvectors/eigenfunctions with largest eigenvalues represent the major anatomical deformations during the course of treatment. Results: As demonstrated with quantitative results in the supporting document regularized PCA is more successful than standard PCA at capturing systematic changes early in the treatment. Regularized PCA is able to detect smaller systematic changes against the background of random fraction-to-fraction changes. To be successful at guiding ART, regularized PCA should be coupled with models of when anatomical changes occur: early, late or throughout the treatment course. Conclusion: The leading eigenvector/eigenfunction from the both PCA approaches can tentatively be identified as a major systematic change during radiotherapy course when systematic changes are large enough with respect to random fraction-to-fraction changes. In all cases the regularized PCA approach appears to be more reliable at capturing systematic changes, enabling dosimetric consequences to be projected once trends are established early in the treatment course. This work is supported in part by a grant from Varian Medical Systems, Palo Alto, CA.« less

National economic and development indicators and international variation in prostate cancer incidence and mortality: an ecological analysis.

PubMed

Neupane, Subas; Bray, Freddie; Auvinen, Anssi

2017-06-01

Macroeconomic indicators are likely associated with prostate cancer (PCa) incidence and mortality globally, but have rarely been assessed. Data on PCa incidence in 2003-2007 for 49 countries with either nationwide cancer registry or at least two regional registries were obtained from Cancer Incidence in Five Continents Vol X and national PCa mortality for 2012 from GLOBOCAN 2012. We compared PCa incidence and mortality rates with various population-level indicators of health, economy and development in 2000. Poisson and linear regression methods were used to quantify the associations. PCa incidence varied more than 15-fold, being highest in high-income countries. PCa mortality exhibited less variation, with higher rates in many low- and middle-income countries. Healthcare expenditure (rate ratio, RR 1.46, 95 % CI 1.45-1.47) and population growth (RR 1.15, 95 % CI 1.14-1.16), as well as computer and mobile phone density, were associated with a higher PCa incidence, while gross domestic product, GDP (RR 0.94, 95 % CI 0.93-0.95) and overall mortality (RR 0.72, 95 % CI 0.71-0.73) were associated with a low incidence. GDP (RR 0.55, 95 % CI 0.46-0.66) was also associated with a low PCa mortality, while life expectancy (RR 3.93, 95 % CI 3.22-4.79) and healthcare expenditure (RR 1.20, 95 % CI 1.09-1.32) were associated with an elevated mortality. Our results show that healthcare expenditure and, thus, the availability of medical resources are an important contributor to the patterns of international variation in PCa incidence. This suggests that there is an iatrogenic component in the current global epidemic of PCa. On the other hand, higher healthcare expenditure is associated with lower PCa death rates.

Epigenetics-related genes in prostate cancer: expression profile in prostate cancer tissues, androgen-sensitive and -insensitive cell lines.

PubMed

Shaikhibrahim, Zaki; Lindstrot, Andreas; Ochsenfahrt, Jacqueline; Fuchs, Kerstin; Wernert, Nicolas

2013-01-01

Epigenetic changes have been suggested to drive prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to identify novel epigenetics-related genes in PCa tissues, and to examine their expression in metastatic PCa cell lines. We analyzed the expression of epigenetics-related genes via a clustering analysis based on gene function in moderately and poorly differentiated PCa glands compared to normal glands of the peripheral zone (prostate proper) from PCa patients using Whole Human Genome Oligo Microarrays. Our analysis identified 12 epigenetics-related genes with a more than 2-fold increase or decrease in expression and a p-value <0.01. In modera-tely differentiated tumors compared to normal glands of the peripheral zone, we found the genes, TDRD1, IGF2, DICER1, ADARB1, HILS1, GLMN and TRIM27, to be upregulated, whereas TNRC6A and DGCR8 were found to be downregulated. In poorly differentiated tumors, we found TDRD1, ADARB and RBM3 to be upregulated, whereas DGCR8, PIWIL2 and BC069781 were downregulated. Our analysis of the expression level for each gene in the metastatic androgen-sensitive VCaP and LNCaP, and -insensitive PC3 and DU-145 PCa cell lines revealed differences in expression among the cell lines which may reflect the different biological properties of each cell line, and the potential role of each gene at different metastatic sites. The novel epigenetics-related genes that we identified in primary PCa tissues may provide further insight into the role that epigenetic changes play in PCa. Moreover, some of the genes that we identified may play important roles in primary PCa and metastasis, in primary PCa only, or in metastasis only. Follow-up studies are required to investigate the functional role and the role that the expression of these genes play in the outcome and progression of PCa using tissue microarrays.

Testosterone therapy for men at risk for or with history of prostate cancer.

PubMed

Morgentaler, Abraham

2006-09-01

Since the early 1940s when Huggins showed that severe reductions in serum testosterone by castration or estrogen therapy caused regression of prostate cancer (PCa), it has been assumed that higher testosterone levels cause enhanced growth of PCa. For this reason, it has been considered taboo to offer testosterone replacement therapy (TRT) to any man with a prior history of PCa, even if all objective evidence suggests he has been cured. The fear has been that higher testosterone levels would "awaken" dormant cells and cause a recurrence. Thus, US Food and Drug Administration-mandated language in all testosterone package inserts states that testosterone is contraindicated in men with a history of, or suspected of having, PCa. Although there is little modern experience with administration of testosterone in men with known history of PCa, there is a varied and extensive literature indicating that TRT does not pose any increased risk of PCa growth in men with or without prior treatment. For instance, the cancer rate in TRT trials is only approximately 1%, similar to detection rates in screening programs, yet biopsy-detectable PCa is found in one of seven hypogonadal men. Moreover, PCa is almost never seen in the peak testosterone years of the early 20s, despite autopsy evidence that men in this age group already harbor microfoci of PCa in substantial numbers. The growing number of PCa survivors who happen to be hypogonadal and request treatment has spurred a change in attitude toward this topic, with increasing numbers of physicians now offering TRT to men who appear cured of their disease. Publications have now reported no prostate-specific antigen (PSA) recurrence with TRT in small numbers of men who had undetectable PSA values after radical prostatectomy. Although still controversial, there appears to be little reason to withhold TRT from men with favorable outcomes after definitive treatment for PCa. Monitoring with PSA and digital rectal examination at regular intervals is recommended.

Causes of Death in Men With Prevalent Diabetes and Newly Diagnosed High- Versus Favorable-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Amico, Anthony V., E-mail: adamico@partners.or; Braccioforte, Michelle H.; Moran, Brian J.

2010-08-01

Purpose: To determine whether prevalent diabetes mellitus (pDM) affects the presentation, extent of radiotherapy, or prostate cancer (PCa)-specific mortality (PCSM) and whether PCa aggressiveness affects the risk of non-PCSM, DM-related mortality, and all-cause mortality in men with pDM. Methods: Between October 1997 and July 2907, 5,279 men treated at the Chicago Prostate Cancer Center with radiotherapy for PCa were included in the study. Logistic and competing risk regression analyses were performed to assess whether pDM was associated with high-grade PCa, less aggressive radiotherapy, and an increased risk of PCSM. Competing risks and Cox regression analyses were performed to assess whethermore » PCa aggressiveness described by risk group in men with pDM was associated with the risk of non-PCSM, DM-related mortality, and all-cause mortality. Analyses were adjusted for predictors of high-grade PCa and factors that could affect treatment extent and mortality. Results: Men with pDM were more likely (adjusted hazard ratio [AHR], 1.9; 95% confidence interval [CI], 1.3-2.7; p = .002) to present with high-grade PCa but were not treated less aggressively (p = .33) and did not have an increased risk of PCSM (p = .58) compared to men without pDM. Among the men with pDM, high-risk PCa was associated with a greater risk of non-PCSM (AHR, 2.2; 95% CI, 1.1-4.5; p = .035), DM-related mortality (AHR, 5.2; 95% CI, 2.0-14.0; p = .001), and all-cause mortality (AHR, 2.4; 95% CI, 1.2-4.7; p = .01) compared to favorable-risk PCa. Conclusion: Aggressive management of pDM is warranted in men with high-risk PCa.« less

PHI and PCA3 improve the prognostic performance of PRIAS and Epstein criteria in predicting insignificant prostate cancer in men eligible for active surveillance.

PubMed

Cantiello, Francesco; Russo, Giorgio Ivan; Cicione, Antonio; Ferro, Matteo; Cimino, Sebastiano; Favilla, Vincenzo; Perdonà, Sisto; De Cobelli, Ottavio; Magno, Carlo; Morgia, Giuseppe; Damiano, Rocco

2016-04-01

To assess the performance of prostate health index (PHI) and prostate cancer antigen 3 (PCA3) when added to the PRIAS or Epstein criteria in predicting the presence of pathologically insignificant prostate cancer (IPCa) in patients who underwent radical prostatectomy (RP) but eligible for active surveillance (AS). An observational retrospective study was performed in 188 PCa patients treated with laparoscopic or robot-assisted RP but eligible for AS according to Epstein or PRIAS criteria. Blood and urinary specimens were collected before initial prostate biopsy for PHI and PCA3 measurements. Multivariate logistic regression analyses and decision curve analysis were carried out to identify predictors of IPCa using the updated ERSPC definition. At the multivariate analyses, the inclusion of both PCA3 and PHI significantly increased the accuracy of the Epstein multivariate model in predicting IPCa with an increase of 17 % (AUC = 0.77) and of 32 % (AUC = 0.92), respectively. The inclusion of both PCA3 and PHI also increased the predictive accuracy of the PRIAS multivariate model with an increase of 29 % (AUC = 0.87) and of 39 % (AUC = 0.97), respectively. DCA revealed that the multivariable models with the addition of PHI or PCA3 showed a greater net benefit and performed better than the reference models. In a direct comparison, PHI outperformed PCA3 performance resulting in higher net benefit. In a same cohort of patients eligible for AS, the addition of PHI and PCA3 to Epstein or PRIAS models improved their prognostic performance. PHI resulted in greater net benefit in predicting IPCa compared to PCA3.

The fractal characteristic of facial anthropometric data for developing PCA fit test panels for youth born in central China.

PubMed

Yang, Lei; Wei, Ran; Shen, Henggen

2017-01-01

New principal component analysis (PCA) respirator fit test panels had been developed for current American and Chinese civilian workers based on anthropometric surveys. The PCA panels used the first two principal components (PCs) obtained from a set of 10 facial dimensions. Although the PCA panels for American and Chinese subjects adopted the bivairate framework with two PCs, the number of the PCs retained in the PCA analysis was different between Chinese subjects and Americans. For the Chinese youth group, the third PC should be retained in the PCA analysis for developing new fit test panels. In this article, an additional number label (ANL) is used to explain the third PC in PCA analysis when the first two PCs are used to construct the PCA half-facepiece respirator fit test panel for Chinese group. The three-dimensional box-counting method is proposed to estimate the ANLs by calculating fractal dimensions of the facial anthropometric data of the Chinese youth. The linear regression coefficients of scale-free range R 2 are all over 0.960, which demonstrates that the facial anthropometric data of the Chinese youth has fractal characteristic. The youth subjects born in Henan province has an ANL of 2.002, which is lower than the composite facial anthropometric data of Chinese subjects born in many provinces. Hence, Henan youth subjects have the self-similar facial anthropometric characteristic and should use the particular ANL (2.002) as the important tool along with using the PCA panel. The ANL method proposed in this article not only provides a new methodology in quantifying the characteristics of facial anthropometric dimensions for any ethnic/racial group, but also extends the scope of PCA panel studies to higher dimensions.

Racial Differences in Prediction of Time to Prostate Cancer Diagnosis in a Prospective Screening Cohort of High-Risk Men: Effect of TMPRSS2 Met160Val

PubMed Central

Giri, Veda N.; Ruth, Karen; Hughes, Lucinda; Uzzo, Robert G.; Chen, David Y.T.; Boorjian, Stephen A.; Viterbo, Rosalia; Rebbeck, Timothy R.

2011-01-01

Introduction The TMPRSS2-ERG gene fusion occurs in >50% of prostate tumors and has been associated with poor outcomes. The T-allele (Valine) of the Met160Val (rs12329760) in TMPRSS2 has been associated with this fusion. We evaluated this polymorphism with respect to self-identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high-risk men. Patients and Methods 631 men ages 35-69 years were studied. “High-risk” was defined as ≥ one first degree or two second degree relatives with PCA, any African American (AA) man regardless of familial PCA, and men with BRCA1/2 mutations. Men with elevated PSA or other indications for PCA underwent biopsy. Men were followed from time of study entry to PCA diagnosis. Cox models were used to evaluate time to PCA diagnosis by genotype. Results Genotype distribution differed significantly by SIRE (CT/TT vs. CC, p<0.0001). Among 183 Caucasian men with at least one follow-up visit, PCA was more than doubled in men carrying CT/TT vs CC genotypes (HR= 2.55, 95% CI=1.14-5.70) after controlling for age and PSA. No association was seen among AA men by TMPRSS2 genotype. Conclusions The T-allele of the Met160Val variant in TMPRSS2, which has been associated with the TMPRSS2-ERG fusion, may be informative of time to PCA diagnosis for a subset of high-risk Caucasian men who are undergoing regular PCA screening. This variant along with other genetic markers warrant further study for personalizing PCA screening. PMID:20735386

A new statistic for identifying batch effects in high-throughput genomic data that uses guided principal component analysis.

PubMed

Reese, Sarah E; Archer, Kellie J; Therneau, Terry M; Atkinson, Elizabeth J; Vachon, Celine M; de Andrade, Mariza; Kocher, Jean-Pierre A; Eckel-Passow, Jeanette E

2013-11-15

Batch effects are due to probe-specific systematic variation between groups of samples (batches) resulting from experimental features that are not of biological interest. Principal component analysis (PCA) is commonly used as a visual tool to determine whether batch effects exist after applying a global normalization method. However, PCA yields linear combinations of the variables that contribute maximum variance and thus will not necessarily detect batch effects if they are not the largest source of variability in the data. We present an extension of PCA to quantify the existence of batch effects, called guided PCA (gPCA). We describe a test statistic that uses gPCA to test whether a batch effect exists. We apply our proposed test statistic derived using gPCA to simulated data and to two copy number variation case studies: the first study consisted of 614 samples from a breast cancer family study using Illumina Human 660 bead-chip arrays, whereas the second case study consisted of 703 samples from a family blood pressure study that used Affymetrix SNP Array 6.0. We demonstrate that our statistic has good statistical properties and is able to identify significant batch effects in two copy number variation case studies. We developed a new statistic that uses gPCA to identify whether batch effects exist in high-throughput genomic data. Although our examples pertain to copy number data, gPCA is general and can be used on other data types as well. The gPCA R package (Available via CRAN) provides functionality and data to perform the methods in this article. reesese@vcu.edu

Strain Transient Detection Techniques: A Comparison of Source Parameter Inversions of Signals Isolated through Principal Component Analysis (PCA), Non-Linear PCA, and Rotated PCA

NASA Astrophysics Data System (ADS)

Lipovsky, B.; Funning, G. J.

2009-12-01

We compare several techniques for the analysis of geodetic time series with the ultimate aim to characterize the physical processes which are represented therein. We compare three methods for the analysis of these data: Principal Component Analysis (PCA), Non-Linear PCA (NLPCA), and Rotated PCA (RPCA). We evaluate each method by its ability to isolate signals which may be any combination of low amplitude (near noise level), temporally transient, unaccompanied by seismic emissions, and small scale with respect to the spatial domain. PCA is a powerful tool for extracting structure from large datasets which is traditionally realized through either the solution of an eigenvalue problem or through iterative methods. PCA is an transformation of the coordinate system of our data such that the new "principal" data axes retain maximal variance and minimal reconstruction error (Pearson, 1901; Hotelling, 1933). RPCA is achieved by an orthogonal transformation of the principal axes determined in PCA. In the analysis of meteorological data sets, RPCA has been seen to overcome domain shape dependencies, correct for sampling errors, and to determine principal axes which more closely represent physical processes (e.g., Richman, 1986). NLPCA generalizes PCA such that principal axes are replaced by principal curves (e.g., Hsieh 2004). We achieve NLPCA through an auto-associative feed-forward neural network (Scholz, 2005). We show the geophysical relevance of these techniques by application of each to a synthetic data set. Results are compared by inverting principal axes to determine deformation source parameters. Temporal variability in source parameters, estimated by each method, are also compared.

Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer.

PubMed

Gershman, Boris; Shui, Irene M; Stampfer, Meir; Platz, Elizabeth A; Gann, Peter H; Sesso, Howard L; DuPre, Natalie; Giovannucci, Edward; Mucci, Lorelei A

2014-04-01

Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa). To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS). We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed. The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality. PCa cases were followed for a mean of 12.0±4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile. We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Patient-controlled analgesia versus intramuscular analgesic therapy.

PubMed

Smythe, M; Loughlin, K; Schad, R F; Lucarroti, R L

1994-06-01

The pharmacy and nursing time requirements, quality of postoperative pain control, and cost of patient-controlled analgesia (PCA) and intramuscular (i.m.) analgesic therapy were studied. All timings were conducted with a stopwatch on a single nursing unit that primarily receives gynecologic surgery patients. The various work elements involved in each type of therapy were timed individually. Both quality of analgesia and cost were evaluated in a prospective, randomized study in hysterectomy patients. I.M. patients received meperidine hydrochloride 75-100 mg every three to four hours as needed. PCA patients had access to morphine sulfate 1 mg or meperidine hydrochloride 10 mg, with a six-minute lockout period. The patients scored their pain every four hours. Direct costs for PCA were calculated as drug cost plus tubing cost plus form cost plus maintenance cost plus depreciation cost. Direct costs for i.m. therapy consisted of the cost of drugs. The total mean nursing time per patient was 16.9 minutes for PCA and 10.7 minutes for i.m. therapy. Pharmacy time per patient was 5.1 minutes longer for PCA than for i.m. therapy. Thirty-six hysterectomy patients (17 i.m. and 19 PCA) were enrolled in the study of pain control and cost. Among i.m. patients, 64% of the pain scores were mild or worse, compared with 40% for PCA patients. The median pain scores were moderate for i.m. patients and mild for PCA patients. Scores tended to be lower for PCA patients at 16 and 20 hours. Although equal numbers of patients in the two groups experienced nausea, i.m. patients needed more doses of antiemetics than PCA patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of Localized and Advanced Prostate Cancer Among Immigrants Versus Native-Born Swedish Men: A nation-wide, population-based study

PubMed Central

Loeb, Stacy; Drevin, Linda; Robinson, David; Holmberg, Erik; Carlsson, Sigrid; Lambe, Mats; Stattin, Pär

2016-01-01

Purpose Prostate cancer (PCa) incidence and prognosis vary geographically. We examined possible differences in PCa risk by clinical risk category between native-born and immigrant populations in Sweden. Our hypothesis was that lower PSA-testing uptake among foreign-born men would result in lower rates of localized disease, and similar or higher risk of metastatic disease. Methods Using the Prostate Cancer database Sweden (PCBaSe), we identified 117,328 men with PCa diagnosed from 1991–2008, of which 8,332 were foreign-born. For each case, 5 cancer-free matched controls were randomly selected from the population register. Conditional logistic regression was used to compare low-risk, intermediate-risk, high-risk, regionally metastatic, and distant metastatic PCa based upon region of origin. Results Across all risk categories, immigrants had significantly lower PCa risk than native-born Swedish men, except North Americans and Northern Europeans. The lowest PCa risk was observed in men from the Middle East, Southern Europe and Asia. Multivariable adjustment for socioeconomic factors and comorbidities did not materially change risk estimates. Older age at immigration and more recent arrival in Sweden were associated with lower PCa risk. Non-native men were less likely to be diagnosed with PCa through PSA-testing during a health check-up. Conclusions The risk for all stages of PCa was lower among first-generation immigrants to Sweden compared to native-born men. Older age at immigration and more recent immigration were associated with particularly low risks. Patterns of PSA testing appeared to only partly explain the differences in PCa risk, since immigrant men also had a lower risk of metastatic disease. PMID:23266834

[The role of a single PCA3 test before a first negative prostate biopsy: 5-year follow-up].

PubMed

Bernardeau, S; Charles, T; Fromont-Hankard, G; Irani, J

2017-04-01

We report a 5-year follow-up of a cohort of patients who underwent a first prostate biopsy following a prostate cancer antigen 3 (PCA3) test. We reviewed consecutive patients who had in 2008 a single urinary PCA3 test using the Gen-Probe ® assay before a first prostate biopsy for a prostate-specific antigen (PSA) between 3 and 20ng/mL and/or a suspicious digital rectal examination. PCA3 performances were analyzed in 2008 and then in 2013 after taking into account the results of repeat biopsies. At initial biopsy in 2008, among the 125 patients study cohort, prostate cancer was diagnosed in 47 patients (37.6%). Abnormal digital rectal exam, PSA density, prostate volume and PCA3 score were significantly associated with prostate cancer diagnosis. PCA3 area under the curve of the receiver operating curve was 0.67 [95%CI: 0.57-0.76] with an optimal threshold of PCA3 in this sample of 24 units. During the 5-year follow-up, among the 78 patients with a negative prostate biopsy in 2008, 23 (29.5%) had a repeat prostate biopsy of whom 14 were diagnosed with prostate cancer. PCA3 score measured in 2008 was associated with prostate cancer diagnosis (P=0.002). All 9 patients with a negative repeat prostate biopsy had a PCA3 score below the cut-off while this was the case in only 2 patients among the 14 with a positive repeat prostate biopsy. The results of a single PCA3 test before a first prostate biopsy seems to be a useful aid in deciding whether to perform a repeat biopsy. 4. Copyright © 2017. Published by Elsevier Masson SAS.

Expression of spermidine/spermine N(1) -acetyl transferase (SSAT) in human prostate tissues is related to prostate cancer progression and metastasis.

PubMed

Huang, Wei; Eickhoff, Jens C; Mehraein-Ghomi, Farideh; Church, Dawn R; Wilding, George; Basu, Hirak S

2015-08-01

Prostate cancer (PCa) in many patients remains indolent for the rest of their lives, but in some patients, it progresses to lethal metastatic disease. Gleason score is the current clinical method for PCa prognosis. It cannot reliably identify aggressive PCa, when GS is ≤ 7. It is shown that oxidative stress plays a key role in PCa progression. We have shown that in cultured human PCa cells, an activation of spermidine/spermine N(1) -acetyl transferase (SSAT; EC 2.3.1.57) enzyme initiates a polyamine oxidation pathway and generates copious amounts of reactive oxygen species in polyamine-rich PCa cells. We used RNA in situ hybridization and immunohistochemistry methods to detect SSAT mRNA and protein expression in two tissue microarrays (TMA) created from patient's prostate tissues. We analyzed 423 patient's prostate tissues in the two TMAs. Our data show that there is a significant increase in both SSAT mRNA and the enzyme protein in the PCa cells as compared to their benign counterpart. This increase is even more pronounced in metastatic PCa tissues as compared to the PCa localized in the prostate. In the prostatectomy tissues from early-stage patients, the SSAT protein level is also high in the tissues obtained from the patients who ultimately progress to advanced metastatic disease. Based on these results combined with published data from our and other laboratories, we propose an activation of an autocrine feed-forward loop of PCa cell proliferation in the absence of androgen as a possible mechanism of castrate-resistant prostate cancer growth. © 2015 Wiley Periodicals, Inc.

Long non-coding RNA HOTTIP promotes prostate cancer cells proliferation and migration by sponging miR-216a-5p.

PubMed

Yang, Bin; Gao, Ge; Wang, Zhixin; Sun, Daju; Wei, Xin; Ma, Yanan; Ding, Youpeng

2018-06-08

Long non-coding RNAs (lncRNAs) are a class of ncRNAs with > 200 nucleotides in length that regulate gene expression. The HOXA transcript at the distal tip (HOTTIP) lncRNA plays an important role in carcinogenesis, however, the underlying role of HOTTIP in prostate cancer (PCa) remain unknown. The aim of the present study was to evaluate the expression and function of HOTTIP in PCa. In the present study, we analyzed HOTTIP expression levels of 86 PCa patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown or overexpression of HOTTIP was performed to explore its roles in cell proliferation, migration, invasion, and cell cycle. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOTTIP and miR-216a-5p in PCa cells. Our results found that HOTTIP was up-regulated in human primary PCa tissues with lymph node metastasis. Knockdown of HOTTIP inhibited PCa cell proliferation, migration and invasion. Overexpression of HOTTIP promoted cell proliferation, migration and invasion of PCa cells. Bioinformatics online programs predicted that HOTTIP sponge miR-216a-5p at 3'-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOTTIP could negatively regulate the expression of miR-216a-5p in PCa cells. Above all, knockdown of HOTTIP could represent a rational therapeutic strategy for PCa. ©2018 The Author(s).

The willingness of patients to pay for intravenous patient-controlled analgesia in Korea.

PubMed

Lim, Hyungsun; Lee, Duck-Hyoung; Lee, Jeongwoo; Han, Young Jin; Choe, Huhn; Son, Ji-Seon

2012-06-01

The use of intravenous patient-controlled analgesia (IV-PCA) has been increasing because it has advantages such as improved pain relief, greater patient satisfaction, and fewer postoperative complications. However, current research has not considered the patients' thoughts about IV-PCA's cost-effectiveness. The purpose of this study was to investigate the willingness to pay (WTP) for IV-PCA and the relationship between patients' characteristics and WTP in Korea. We enrolled 400 adult patients who were scheduled for elective surgery. The patient was requested to indicate a series of predefined amounts of money (Korean won; 30,000/50,000/100,000/150,000/200,000/300,000/500,000). We also recorded patient characteristics, such as age, sex, type of surgery, IV-PCA history, education level, the person responsible for medical expenses, type of insurance, net annual income, and residential area. Three days after surgery, we asked about the degree of satisfaction and the WTP for IV-PCA. For IV-PCA, the median WTP was 100,000 won (25-75%; 50,000-200,000 won: US$1 = W1078.04; July 19, 2011) before surgery. All patients' characteristics were not related to preoperative WTP for IV-PCA, whereas the increase in WTP after surgery showed a tendency correlated to higher IV-PCA satisfaction. The median WTP was 100,000 won. The satisfaction of IV-PCA increased patients' WTP after surgery, but the WTP may be independent of patient characteristics in Korea.

A case-control study of lower urinary-tract infections, associated antibiotics and the risk of developing prostate cancer using PCBaSe 3.0.

PubMed

Russell, Beth; Garmo, Hans; Beckmann, Kerri; Stattin, Pär; Adolfsson, Jan; Van Hemelrijck, Mieke

2018-01-01

To investigate the association between lower urinary-tract infections, their associated antibiotics and the subsequent risk of developing PCa. Using data from the Swedish PCBaSe 3.0, we performed a matched case-control study (8762 cases and 43806 controls). Conditional logistic regression analysis was used to assess the association between lower urinary-tract infections, related antibiotics and PCa, whilst adjusting for civil status, education, Charlson Comorbidity Index and time between lower urinary-tract infection and PCa diagnosis. It was found that lower urinary-tract infections did not affect PCa risk, however, having a lower urinary-tract infection or a first antibiotic prescription 6-12 months before PCa were both associated with an increased risk of PCa (OR: 1.50, 95% CI: 1.23-1.82 and 1.96, 1.71-2.25, respectively), as compared to men without lower urinary-tract infections. Compared to men with no prescriptions for antibiotics, men who were prescribed ≥10 antibiotics, were 15% less likely to develop PCa (OR: 0.85, 95% CI: 0.78-0.91). PCa was not found to be associated with diagnosis of a urinary-tract infection or frequency, but was positively associated with short time since diagnoses of lower urinary-tract infection or receiving prescriptions for antibiotics. These observations can likely be explained by detection bias, which highlights the importance of data on the diagnostic work-up when studying potential risk factors for PCa.

Adaptive online monitoring for ICU patients by combining just-in-time learning and principal component analysis.

PubMed

Li, Xuejian; Wang, Youqing

2016-12-01

Offline general-type models are widely used for patients' monitoring in intensive care units (ICUs), which are developed by using past collected datasets consisting of thousands of patients. However, these models may fail to adapt to the changing states of ICU patients. Thus, to be more robust and effective, the monitoring models should be adaptable to individual patients. A novel combination of just-in-time learning (JITL) and principal component analysis (PCA), referred to learning-type PCA (L-PCA), was proposed for adaptive online monitoring of patients in ICUs. JITL was used to gather the most relevant data samples for adaptive modeling of complex physiological processes. PCA was used to build an online individual-type model and calculate monitoring statistics, and then to judge whether the patient's status is normal or not. The adaptability of L-PCA lies in the usage of individual data and the continuous updating of the training dataset. Twelve subjects were selected from the Physiobank's Multi-parameter Intelligent Monitoring for Intensive Care II (MIMIC II) database, and five vital signs of each subject were chosen. The proposed method was compared with the traditional PCA and fast moving-window PCA (Fast MWPCA). The experimental results demonstrated that the fault detection rates respectively increased by 20 % and 47 % compared with PCA and Fast MWPCA. L-PCA is first introduced into ICU patients monitoring and achieves the best monitoring performance in terms of adaptability to changes in patient status and sensitivity for abnormality detection.

Mutational Landscape of Candidate Genes in Familial Prostate Cancer

PubMed Central

Johnson, Anna M.; Zuhlke, Kimberly A.; Plotts, Chris; McDonnell, Shannon K.; Middha, Sumit; Riska, Shaun M.; Thibodeau, Stephen N.; Douglas, Julie A.; Cooney, Kathleen A.

2014-01-01

Background Family history is a major risk factor for prostate cancer (PCa), suggesting a genetic component to the disease. However, traditional linkage and association studies have failed to fully elucidate the underlying genetic basis of familial PCa. Methods Here we use a candidate gene approach to identify potential PCa susceptibility variants in whole exome sequencing data from familial PCa cases. Six hundred ninety-seven candidate genes were identified based on function, location near a known chromosome 17 linkage signal, and/or previous association with prostate or other cancers. Single nucleotide variants (SNVs) in these candidate genes were identified in whole exome sequence data from 33 PCa cases from 11 multiplex PCa families (3 cases/family). Results Overall, 4856 candidate gene SNVs were identified, including 1052 missense and 10 nonsense variants. Twenty missense variants were shared by all 3 family members in each family in which they were observed. Additionally, 15 missense variants were shared by 2 of 3 family members and predicted to be deleterious by 5 different algorithms. Four missense variants, BLM Gln123Arg, PARP2 Arg283Gln, LRCC46 Ala295Thr and KIF2B Pro91Leu, and 1 nonsense variant, CYP3A43 Arg441Ter, showed complete co-segregation with PCa status. Twelve additional variants displayed partial co-segregation with PCa. Conclusions Forty-three nonsense and shared, missense variants were identified in our candidate genes. Further research is needed to determine the contribution of these variants to PCa susceptibility. PMID:25111073

GO-PCA: An Unsupervised Method to Explore Gene Expression Data Using Prior Knowledge

PubMed Central

Wagner, Florian

2015-01-01

Method Genome-wide expression profiling is a widely used approach for characterizing heterogeneous populations of cells, tissues, biopsies, or other biological specimen. The exploratory analysis of such data typically relies on generic unsupervised methods, e.g. principal component analysis (PCA) or hierarchical clustering. However, generic methods fail to exploit prior knowledge about the molecular functions of genes. Here, I introduce GO-PCA, an unsupervised method that combines PCA with nonparametric GO enrichment analysis, in order to systematically search for sets of genes that are both strongly correlated and closely functionally related. These gene sets are then used to automatically generate expression signatures with functional labels, which collectively aim to provide a readily interpretable representation of biologically relevant similarities and differences. The robustness of the results obtained can be assessed by bootstrapping. Results I first applied GO-PCA to datasets containing diverse hematopoietic cell types from human and mouse, respectively. In both cases, GO-PCA generated a small number of signatures that represented the majority of lineages present, and whose labels reflected their respective biological characteristics. I then applied GO-PCA to human glioblastoma (GBM) data, and recovered signatures associated with four out of five previously defined GBM subtypes. My results demonstrate that GO-PCA is a powerful and versatile exploratory method that reduces an expression matrix containing thousands of genes to a much smaller set of interpretable signatures. In this way, GO-PCA aims to facilitate hypothesis generation, design of further analyses, and functional comparisons across datasets. PMID:26575370

GO-PCA: An Unsupervised Method to Explore Gene Expression Data Using Prior Knowledge.

PubMed

Wagner, Florian

2015-01-01

Genome-wide expression profiling is a widely used approach for characterizing heterogeneous populations of cells, tissues, biopsies, or other biological specimen. The exploratory analysis of such data typically relies on generic unsupervised methods, e.g. principal component analysis (PCA) or hierarchical clustering. However, generic methods fail to exploit prior knowledge about the molecular functions of genes. Here, I introduce GO-PCA, an unsupervised method that combines PCA with nonparametric GO enrichment analysis, in order to systematically search for sets of genes that are both strongly correlated and closely functionally related. These gene sets are then used to automatically generate expression signatures with functional labels, which collectively aim to provide a readily interpretable representation of biologically relevant similarities and differences. The robustness of the results obtained can be assessed by bootstrapping. I first applied GO-PCA to datasets containing diverse hematopoietic cell types from human and mouse, respectively. In both cases, GO-PCA generated a small number of signatures that represented the majority of lineages present, and whose labels reflected their respective biological characteristics. I then applied GO-PCA to human glioblastoma (GBM) data, and recovered signatures associated with four out of five previously defined GBM subtypes. My results demonstrate that GO-PCA is a powerful and versatile exploratory method that reduces an expression matrix containing thousands of genes to a much smaller set of interpretable signatures. In this way, GO-PCA aims to facilitate hypothesis generation, design of further analyses, and functional comparisons across datasets.

Trichomonas vaginalis infection and risk of prostate cancer: associations by disease aggressiveness and race/ethnicity in the PLCO Trial.

PubMed

Marous, Miguelle; Huang, Wen-Yi; Rabkin, Charles S; Hayes, Richard B; Alderete, John F; Rosner, Bernard; Grubb, Robert L; Winter, Anke C; Sutcliffe, Siobhan

2017-08-01

Results from previous sero-epidemiologic studies of Trichomonas vaginalis infection and prostate cancer (PCa) support a positive association between this sexually transmitted infection and aggressive PCa. However, findings from previous studies are not entirely consistent, and only one has investigated the possible relation between T. vaginalis seropositivity and PCa in African-American men who are at highest risk of both infection and PCa. Therefore, we examined this possible relation in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, including separate analyses for aggressive PCa and African-American men. We included a sample of participants from a previous nested case-control study of PCa, as well as all additional Caucasian, aggressive, and African-American cases diagnosed since the previous study (total n = 438 Gleason 7 Caucasian cases, 487 more advanced Caucasian cases (≥Gleason 8 or stage III/IV), 201 African-American cases, and 1216 controls). We tested baseline sera for T. vaginalis antibodies. No associations were observed for risk of Gleason 7 (odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.55-1.37) or more advanced (OR = 0.90, 95% CI 0.58-1.38) PCa in Caucasian men, or for risk of any PCa (OR = 1.06, 95% CI 0.67-1.68) in African-American men. Our findings do not support an association between T. vaginalis infection and PCa.

Effects of Interscalene Nerve Block for Postoperative Pain Management in Patients after Shoulder Surgery.

PubMed

Chen, Hsiu-Pin; Shen, Shih-Jyun; Tsai, Hsin-I; Kao, Sheng-Chin; Yu, Huang-Ping

2015-01-01

Shoulder surgery can produce severe postoperative pain and movement limitations. Evidence has shown that regional nerve block is an effective management for postoperative shoulder pain. The purpose of this study was to investigate the postoperative analgesic effect of intravenous patient-controlled analgesia (PCA) combined with interscalene nerve block in comparison to PCA alone after shoulder surgery. In this study, 103 patients receiving PCA combined with interscalene nerve block (PCAIB) and 48 patients receiving PCA alone after shoulder surgery were included. Patients' characteristics, preoperative shoulder score and range of motion, surgical and anesthetic condition in addition to visual analog scale (VAS) pain score, postoperative PCA consumption, and adverse outcomes were evaluated. The results showed that PCA combined with interscalene nerve block (PCAIB) group required less volume of analgesics than PCA alone group in 24 hours (57.76 ± 23.29 mL versus 87.29 ± 33.73 mL, p < 0.001) and 48 hours (114.86 ± 40.97 mL versus 183.63 ± 44.83 mL, p < 0.001) postoperatively. The incidence of dizziness in PCAIB group was significantly lower than PCA group (resp., 1.9% and 14.6%, p = 0.005). VAS, nausea, and vomiting were less in group PCAIB, but in the absence of significant statistical correlation. Interscalene nerve block is effective postoperatively in reducing the demand for PCA analgesics and decreasing opioids-induced adverse events following shoulder surgery.

Patient-controlled hospital admission for patients with severe mental disorders: a nationwide prospective multicentre study.

PubMed

Thomsen, C T; Benros, M E; Maltesen, T; Hastrup, L H; Andersen, P K; Giacco, D; Nordentoft, M

2018-04-01

To assess whether implementing patient-controlled admission (PCA) can reduce coercion and improve other clinical outcomes for psychiatric in-patients. During 2013-2016, 422 patients in the PCA group were propensity score matched 1:5 with a control group (n = 2110) that received treatment as usual (TAU). Patients were followed up for at least one year using the intention to treat principle utilising nationwide registers. In a paired design, the outcomes of PCA patients during the year after signing a contract were compared with the year before. No reduction in coercion (risk difference = 0.001; 95% CI: -0.038; 0.040) or self-harming behaviour (risk difference = 0.005; 95% CI: -0.008; 0.018) was observed in the PCA group compared with the TAU group. The PCA group had more in-patient bed days (mean difference = 28.4; 95% CI: 21.3; 35.5) and more medication use (P < 0.0001) than the TAU group. Before and after analyses showed reduction in coercion (P = 0.0001) and in-patient bed days (P = 0.0003). Implementing PCA did not reduce coercion, service use or self-harm behaviour when compared with TAU. Beneficial effects of PCA were observed only in the before and after PCA comparisons. Further research should investigate whether PCA affects other outcomes to better establish its clinical value. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spherical agglomerates of pure drug nanoparticles for improved pulmonary delivery in dry powder inhalers

NASA Astrophysics Data System (ADS)

Hu, Jun; Dong, Yuancai; Pastorin, Giorgia; Ng, Wai Kiong; Tan, Reginald B. H.

2013-04-01

The aim of this study was to produce micron-sized spherical agglomerates of pure drug nanoparticles to achieve improved aerosol performance in dry powder inhalers (DPIs). Sodium cromoglicate was chosen as the model drug. Pure drug nanoparticles were prepared through a bottom-up particle formation process, liquid antisolvent precipitation, and then rapidly agglomerated into porous spherical microparticles by immediate (on-line) spray drying. Nonporous spherical drug microparticles with similar geometric size distribution were prepared by conventional spray drying of the aqueous drug solution, which together with the mechanically micronized drug particles were used as the control samples. The three samples were characterized by field emission scanning electron microscopy, laser diffraction, Brunauer-Emmett-Teller analysis, density measurement, powder X-ray diffraction, and in vitro aerosol deposition measurement with a multistage liquid impinger. It was found that drug nanoparticles with a diameter of 100 nm were precipitated and agglomerated into highly porous spherical microparticles with a volume median diameter ( D 50 %) of 2.25 ± 0.08 μm and a specific surface area of 158.63 ± 3.27 m2/g. In vitro aerosol deposition studies showed the fine particle fraction of such spherical agglomerates of drug nanoparticles was increased by more than 50 % in comparison with the control samples, demonstrating significant improvements in aerosol performance. The results of this study indicated the potential of the combined particle engineering process of liquid antisolvent precipitation followed by immediate (on-line) spray drying in the development of novel DPI drug products with improved aerosol performance.

Inkjet printing of single-crystal films.

PubMed

Minemawari, Hiromi; Yamada, Toshikazu; Matsui, Hiroyuki; Tsutsumi, Jun'ya; Haas, Simon; Chiba, Ryosuke; Kumai, Reiji; Hasegawa, Tatsuo

2011-07-13

The use of single crystals has been fundamental to the development of semiconductor microelectronics and solid-state science. Whether based on inorganic or organic materials, the devices that show the highest performance rely on single-crystal interfaces, with their nearly perfect translational symmetry and exceptionally high chemical purity. Attention has recently been focused on developing simple ways of producing electronic devices by means of printing technologies. 'Printed electronics' is being explored for the manufacture of large-area and flexible electronic devices by the patterned application of functional inks containing soluble or dispersed semiconducting materials. However, because of the strong self-organizing tendency of the deposited materials, the production of semiconducting thin films of high crystallinity (indispensable for realizing high carrier mobility) may be incompatible with conventional printing processes. Here we develop a method that combines the technique of antisolvent crystallization with inkjet printing to produce organic semiconducting thin films of high crystallinity. Specifically, we show that mixing fine droplets of an antisolvent and a solution of an active semiconducting component within a confined area on an amorphous substrate can trigger the controlled formation of exceptionally uniform single-crystal or polycrystalline thin films that grow at the liquid-air interfaces. Using this approach, we have printed single crystals of the organic semiconductor 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C(8)-BTBT) (ref. 15), yielding thin-film transistors with average carrier mobilities as high as 16.4 cm(2) V(-1) s(-1). This printing technique constitutes a major step towards the use of high-performance single-crystal semiconductor devices for large-area and flexible electronics applications.

Design of gefitinib-loaded poly (l-lactic acid) microspheres via a supercritical anti-solvent process for dry powder inhalation.

PubMed

Lin, Qing; Liu, Guijin; Zhao, Ziyi; Wei, Dongwei; Pang, Jiafeng; Jiang, Yanbin

2017-10-30

To develop a safer, more stable and potent formulation of gefitinib (GFB), micro-spheres of GFB encapsulated into poly (l-lactic acid) (PLLA) have been prepared by supercritical anti-solvent (SAS) technology in this study. Operating factors were optimized using a selected OA 16 (4 5 ) orthogonal array design, and the properties of the raw material and SAS processed samples were characterized by different methods The results show that the GFB-loaded PLLA particles prepared were spherical, having a smaller and narrower particle size compared with raw GFB. The optimal GFB-loaded PLLA sample was prepared with less aggregation, highest GFB loading (15.82%) and smaller size (D 50 =2.48μm, which meets the size of dry powder inhalers). The results of XRD and DSC indicate that GFB is encapsulated into PLLA matrix in a polymorphic form different from raw GFB. FT-IR results show that the chemical structure of GFB does not change after the SAS process. The results of in vitro release show that the optimal sample release was slower compared with raw GFB particles. Moreover, the results of in vitro anti-cancer trials show that the optimal sample had a higher cytotoxicity than raw GFB. After blending with sieved lactose, the flowability and aerosolization performance of the optimal sample for DPI were improved, with angle of repose, emitted dose and fine particles fractions from 38.4° to 23°, 63.21% to >90%, 23.37% to >30%, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug recrystallization using supercritical anti-solvent (SAS) process with impinging jets: Effect of process parameters

NASA Astrophysics Data System (ADS)

Careno, Stéphanie; Boutin, Olivier; Badens, Elisabeth

2012-03-01

The aim of this study is to improve mixing in supercritical anti-solvent process (SAS) with impinging jets in order to form finer particles of sulfathiazole, a poorly water-soluble drug. The influence of several process parameters upon the powder characteristics is studied. Parameters are jets' velocity (0.25 m s-1 to 25.92 m s-1), molar ratio solvent/CO2 (2.5% to 20%), temperature (313 K to 343 K), pressure (10 MPa to 20 MPa) and sulfathiazole concentration in the organic solution (0.5% to 1.8%). Two solvents are used: acetone and methanol. Smaller particles with a more homogeneous morphology are obtained from acetone solutions. For the smallest jets' velocity, corresponding to a non-atomized jet, the stable polymorphic form is obtained, pure or in mixture. At this velocity, pressure is the most influential parameter controlling the polymorphic nature of the powder formed. The pure stable polymorph is formed at 20 MPa. Concerning the particle size, the most influential parameters are temperature and sulfathiazole concentration. The use of impinging jets with different process parameters allows the crystallization of four polymorphs among the five known, and particle sizes are varied. This work demonstrates the studied device ability of the polymorph and the size control. A comparison with the classical SAS process shows that particle size, size distribution and morphology of particles crystallized with impinging jets are different from the ones obtained with classical SAS introduction device in similar operating conditions. Mean particle sizes are significantly smaller and size distributions are narrower with impinging jets device.

Supercritical anti-solvent technique assisted synthesis of thymoquinone liposomes for radioprotection: Formulation optimization, in-vitro and in-vivo studies.

PubMed

Ahmad, Iqbal; Akhter, Sohail; Anwar, Mohammed; Zafar, Sobiya; Sharma, Rakesh Kumar; Ali, Asgar; Ahmad, Farhan Jalees

2017-05-15

The aim of this study was to develop Thymoquinone (TQ) loaded PEGylated liposomes using supercritical anti-solvent (SAS) process for enhanced blood circulation, and greater radioprotection. The SAS process of PEGylated liposomes synthesis was optimized by Box-Behnken design. Spherical liposomes with a particle size of 195.6±5.56nm and entrapment efficiency (%EE) of 89.4±3.69% were obtained. Optimized SAS process parameters; temperature, pressure and solution flow rate were 35°C, 140bar and 0.18mL/min, respectively, while 7.5mmol phospholipid, 0.75mmol of cholesterol, and 1mmol TQ were optimized formulation ingredients. Incorporation of MPEG-2000-DSPE (5% w/w) provided the PEGylated liposomes (FV-17B; particle size=231.3±6.74nm, %EE=91.9±3.45%, maximum TQ release >70% in 24h). Pharmacokinetics of FV-17B in mice demonstrated distinctly superior systemic circulation time for TQ in plasma. Effectiveness of radioprotection by FV-17B in mice model was demonstrated by non-significant body weight change, normal vital blood components (WBCs, RBCs, and Platelets), micronuclei and spleen index and increased survival probability in post irradiation animal group as compared to controls (plain TQ and marketed formulation). Altogether, the results anticipated that the SAS process could serve as a single step environmental friendly technique for the development of stable long circulating TQ loaded liposomes for effective radioprotection. Copyright © 2017 Elsevier B.V. All rights reserved.

Minireview: The Molecular and Genomic Basis for Prostate Cancer Health Disparities

PubMed Central

Bollig-Fischer, Aliccia

2013-01-01

Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, race disparities persist. For African American men (AAM), PCa is more often an aggressive disease showing increased metastases and greater PCa-related mortality compared with European American men. The earliest research points to how distinctions are likely the result of a combination of factors, including ancestry genetics and lifestyle variables. More recent research considers that cancer, although influenced by external forces, is ultimately a disease primarily driven by aberrations observed in the molecular genetics of the tumor. Research studying PCa predominantly from European American men shows that indolent and advanced or metastatic prostate tumors have distinguishing molecular genomic make-ups. Early yet increasing evidence suggests that clinically distinct PCa from AAM also display molecular distinctions. It is reasonable to predict that further study will reveal molecular subtypes and various frequencies for PCa subtypes among diverse patient groups, thereby providing insight as to the genomic lesions and gene signatures that are functionally implicated in carcinogenesis or aggressive PCa in AAM. That knowledge will prove useful in developing strategies to predict who will develop advanced PCa among AAM and will provide the rationale to develop effective individualized treatment strategies to overcome disparities. PMID:23608645

Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis

PubMed Central

Ranard, Katherine M.; Jeon, Sookyoung; Erdman, John W.

2018-01-01

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, accounting for 15% of all cancers in men worldwide. Asian populations consume soy foods as part of a regular diet, which may contribute to the lower PCa incidence observed in these countries. This meta-analysis provides a comprehensive updated analysis that builds on previously published meta-analyses, demonstrating that soy foods and their isoflavones (genistein and daidzein) are associated with a lower risk of prostate carcinogenesis. Thirty articles were included for analysis of the potential impacts of soy food intake, isoflavone intake, and circulating isoflavone levels, on both primary and advanced PCa. Total soy food (p < 0.001), genistein (p = 0.008), daidzein (p = 0.018), and unfermented soy food (p < 0.001) intakes were significantly associated with a reduced risk of PCa. Fermented soy food intake, total isoflavone intake, and circulating isoflavones were not associated with PCa risk. Neither soy food intake nor circulating isoflavones were associated with advanced PCa risk, although very few studies currently exist to examine potential associations. Combined, this evidence from observational studies shows a statistically significant association between soy consumption and decreased PCa risk. Further studies are required to support soy consumption as a prophylactic dietary approach to reduce PCa carcinogenesis. PMID:29300347

Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers

PubMed Central

Filella, Xavier; Foj, Laura

2016-01-01

Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis. PMID:27792187

An in vitro investigation on friction generated by ceramic brackets.

PubMed

Tecco, Simona; Teté, Stefano; Festa, Mario; Festa, Felice

2010-01-01

To compare friction (F) of conventional and ceramic brackets (0.022-inch slot) using a model that tests the sliding of the archwire through 10 aligned brackets. Polycrystalline alumina brackets (PCAs), PCA brackets with a stainless steel slot (PCA-M), and monocrystalline sapphire brackets (MCS) were tested under elastic ligatures using various archwires in dry and wet (saliva) states. Conventional stainless steel brackets were used as controls. In both dry and wet states, PCA and MCS brackets expressed a statistically significant higher F value with respect to stainless steel and PCA-M brackets when combined with the rectangular archwires (P<.01). PCA brackets showed significantly higher friction than MCS brackets (P<.01) when coupled with 0.014 x 0.025-inch nickel-titanium (Ni-Ti) archwire. SEM analysis showed differences in the surfaces among stainless steel, MCS, PCA-M, and PCA brackets. In the wet state, the mean F values were generally higher than in the dry state. PCA brackets showed significantly higher F than MCS brackets only when combined with 0.014 x 0.025-inch Ni-Ti archwires. Thus, in this study, a 10 aligned-brackets study model showed similar results when compared to a single bracket system except for friction level with 0.014 × 0.025-inch Ni-Ti archwires. © 2011 BY QUINTESSENCE PUBLISHING CO, INC.

The long non-coding RNA PCSEAT exhibits an oncogenic property in prostate cancer and functions as a competing endogenous RNA that associates with EZH2.

PubMed

Yang, Xiaohui; Wang, Liang; Li, Rong; Zhao, Yuhui; Gu, Yinmin; Liu, Siying; Cheng, Tianyou; Huang, Kuohsiang; Yuan, Yi; Song, Dalong; Gao, Shan

2018-07-12

Prostate cancer (PCa) is the most common malignancy and the leading cause of cancer deaths in males. Recent studies demonstrate that long non-coding RNAs (lncRNAs) are involved in many aspects of PCa. However, their biological roles in PCa remain imperfectly understood. Here,wecharacterized anlncRNA, PCaspecific expression and EZH2-associatedtranscript (PCSEAT, annotated as PRCAT38), which is specifically overexpressedin PCa. We further demonstrated that knockdown of PCSEAT results in the reduction of PCa cell growth and motility, and overexpression of PCSEAT reverses these phenotypes. Furthermore, bioactive PCSEAT is incorporated into exosomes and transmitted to adjacent cells, thus promoting cell proliferation and motility. Mechanistically, we found that PCSEAT promotes cell proliferation, at least in part by affecting miR-143-3p- and miR-24-2-5p-mediated regulation of EZH2, suggesting that PCSEAT and EZH2 competitively 'sponge' miR-143-3p and miR-24-2-5p.Overall, ourresultsrevealthat PCSEAT is specifically overexpressed in PCa patients and a potential oncogene in PCa cells via mediating EZH2 activity, indicating that PCSEAT may be a potential therapeutic target in PCa. Copyright © 2018 Elsevier Inc. All rights reserved.

Clonazepam treatment of pathologic childhood aerophagia with psychological stresses.

PubMed

Hwang, Jin Bok; Kim, Jun Sik; Ahn, Byung Hoon; Jung, Chul Ho; Lee, Young Hwan; Kam, Sin

2007-04-01

The treatment of pathologic aerophagia has rarely been discussed in the literature. In this retrospective study, the authors investigated the effects of clonazepam on the management of pathologic childhood aerophagia (PCA) with psychological stresses (PS), but not with mental retardation. Data from 22 consecutive PCA patients with PS (aged 2 to 10 yr), who had been followed up for over 1 yr, were reviewed. On the basis of videolaryngoscopic views, the authors observed that the pathology of aerophagia was the result of reflex-induced swallowing with paroxysmal openings of the upper esophageal sphincter due to unknown factors and also observed that these reflex-induced openings were subsided after intravenous low dose benzodiazepine administration. Hence, clonazepam was administered to treat paroxysmal openings in these PCA patients with PS. Remission positivity was defined as symptom-free for a consecutive 1 month within 6 months of treatment. The results of treatment in 22 PCA patients with PS were analyzed. A remission positive state was documented in 14.3% of PCA patients managed by reassurance, and in 66.7% of PCA patients treated with clonazepam (p=0.032). Thus, clonazepam may produce positive results in PCA with PS. Future studies by randomized and placebo-controlled trials are needed to confirm the favorable effect of clonazepam in PCA.

Clonazepam Treatment of Pathologic Childhood Aerophagia with Psychological Stresses

PubMed Central

Kim, Jun Sik; Ahn, Byung Hoon; Jung, Chul-Ho; Lee, Young Hwan; Kam, Sin

2007-01-01

The treatment of pathologic aerophagia has rarely been discussed in the literature. In this retrospective study, the authors investigated the effects of clonazepam on the management of pathologic childhood aerophagia (PCA) with psychological stresses (PS), but not with mental retardation. Data from 22 consecutive PCA patients with PS (aged 2 to 10 yr), who had been followed up for over 1 yr, were reviewed. On the basis of videolaryngoscopic views, the authors observed that the pathologyof aerophagia was the result of reflex-induced swallowing with paroxysmal openings of the upper esophageal sphincter due to unknown factors and also observed that these reflex-induced openings were subsided after intravenous low dose benzodiazepine administration. Hence, clonazepam was administered to treat paroxysmal openings in these PCA patients with PS. Remission positivity was defined as symptom-free for a consecutive 1 month within 6 months of treatment. The results of treatment in 22 PCA patients with PS were analyzed. A remission positive state was documented in 14.3% of PCA patients managed by reassurance, and in 66.7% of PCA patients treated with clonazepam (p=0.032). Thus, clonazepam may produce positive results in PCA with PS. Future studies by randomized and placebo-controlled trials are needed to confirm the favorable effect of clonazepam in PCA. PMID:17449924

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

PubMed Central

Rao, S R; Snaith, A E; Marino, D; Cheng, X; Lwin, S T; Orriss, I R; Hamdy, F C; Edwards, C M

2017-01-01

Background: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. Methods: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. Results: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. Conclusions: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression. PMID:28006818

Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers.

PubMed

Filella, Xavier; Foj, Laura

2016-10-26

Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis.

Pronounced impairment of everyday skills and self-care in posterior cortical atrophy.

PubMed

Shakespeare, Timothy J; Yong, Keir X X; Foxe, David; Hodges, John; Crutch, Sebastian J

2015-01-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and self-care while the tAD group showed greater impairment in aspects of memory and orientation, and motivation. We suggest that PCA poses specific challenges for those caring for people affected by the condition.

The monoamine oxidase A gene promoter repeat and prostate cancer risk.

PubMed

White, Thomas A; Kwon, Erika M; Fu, Rong; Lucas, Jared M; Ostrander, Elaine A; Stanford, Janet L; Nelson, Peter S

2012-11-01

Amine catabolism by monoamine oxidase A (MAOA) contributes to oxidative stress, which plays a role in prostate cancer (PCa) development and progression. An upstream variable-number tandem repeat (uVNTR) in the MAOA promoter influences gene expression and activity, and may thereby affect PCa susceptibility. Caucasian (n = 2,572) men from two population-based case-control studies of PCa were genotyped for the MAOA-VNTR. Logistic regression was used to assess PCa risk in relation to genotype. Common alleles of the MAOA-VNTR were not associated with the relative risk of PCa, nor did the relationship differ by clinical features of the disease. The rare 5-copy variant (frequency: 0.5% in cases; 1.8% in controls), however, was associated with a reduced PCa risk (odds ratio, OR = 0.30, 95% CI 0.13-0.71). A rare polymorphism of the MAOA promoter previously shown to confer low expression was associated with a reduced risk of developing PCa. This novel finding awaits confirmation in other study populations. Copyright © 2012 Wiley Periodicals, Inc.

The role of DAB2IP in androgen receptor activation during prostate cancer progression.

PubMed

Wu, K; Liu, J; Tseng, S-F; Gore, C; Ning, Z; Sharifi, N; Fazli, L; Gleave, M; Kapur, P; Xiao, G; Sun, X; Oz, O K; Min, W; Alexandrakis, G; Yang, C-R; Hsieh, C-L; Wu, H-C; He, D; Xie, D; Hsieh, J-T

2014-04-10

Altered androgen-receptor (AR) expression and/or constitutively active AR are commonly associated with prostate cancer (PCa) progression. Targeting AR remains a focal point for designing new strategy of PCa therapy. Here, we have shown that DAB2IP, a novel tumor suppressor in PCa, can inhibit AR-mediated cell growth and gene activation in PCa cells via distinct mechanisms. DAB2IP inhibits the genomic pathway by preventing AR nuclear translocation or phosphorylation and suppresses the non-genomic pathway via its unique functional domain to inactivate c-Src. Also, DAB2IP is capable of suppressing AR activation in an androgen-independent manner. In addition, DAB2IP can inhibit several AR splice variants showing constitutive activity in PCa cells. In DAB2IP(-/-) mice, the prostate gland exhibits hyperplastic epithelia, in which AR becomes more active. Consistently, DAB2IP expression inversely correlates with AR activation status particularly in recurrent or metastatic PCa patients. Taken together, DAB2IP is a unique intrinsic AR modulator in normal cells, and likely can be further developed into a therapeutic agent for PCa.

The PSA−/lo prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration

PubMed Central

Qin, Jichao; Liu, Xin; Laffin, Brian; Chen, Xin; Choy, Grace; Jeter, Collene; Calhoun-Davis, Tammy; Li, Hangwen; Palapattu, Ganesh S.; Pang, Shen; Lin, Kevin; Huang, Jiaoti; Ivanov, Ivan; Li, Wei; Suraneni, Mahipal V.; Tang, Dean G.

2012-01-01

SUMMARY Prostate cancer (PCa) is heterogeneous and contains both differentiated and undifferentiated tumor cells, but the relative functional contribution of these two cell populations remains unclear. Here we report distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (PSA+) and low (PSA−/lo) levels of the differentiation marker PSA. PSA−/lo PCa cells are quiescent and refractory to stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity. They preferentially express stem cell genes and can undergo asymmetric cell division generating PSA+ cells. Importantly, PSA−/lo PCa cells can initiate robust tumor development and resist androgen ablation in castrated hosts, and harbor highly tumorigenic castration-resistant PCa cells that can be prospectively enriched using ALDH+CD44+α2β1+ phenotype. In contrast, PSA+ PCa cells possess more limited tumor-propagating capacity, undergo symmetric division and are sensitive to castration. Together, our study suggests PSA−/lo cells may represent a critical source of castration-resistant PCa cells. PMID:22560078

Time-dependent analysis of dosage delivery information for patient-controlled analgesia services.

PubMed

Kuo, I-Ting; Chang, Kuang-Yi; Juan, De-Fong; Hsu, Steen J; Chan, Chia-Tai; Tsou, Mei-Yung

2018-01-01

Pain relief always plays the essential part of perioperative care and an important role of medical quality improvement. Patient-controlled analgesia (PCA) is a method that allows a patient to self-administer small boluses of analgesic to relieve the subjective pain. PCA logs from the infusion pump consisted of a lot of text messages which record all events during the therapies. The dosage information can be extracted from PCA logs to provide easily understanding features. The analysis of dosage information with time has great help to figure out the variance of a patient's pain relief condition. To explore the trend of pain relief requirement, we developed a PCA dosage information generator (PCA DIG) to extract meaningful messages from PCA logs during the first 48 hours of therapies. PCA dosage information including consumption, delivery, infusion rate, and the ratio between demand and delivery is presented with corresponding values in 4 successive time frames. Time-dependent statistical analysis demonstrated the trends of analgesia requirements decreased gradually along with time. These findings are compatible with clinical observations and further provide valuable information about the strategy to customize postoperative pain management.

STAMP2 increases oxidative stress and is critical for prostate cancer

PubMed Central

Jin, Yang; Wang, Ling; Qu, Su; Sheng, Xia; Kristian, Alexandr; Mælandsmo, Gunhild M; Pällmann, Nora; Yuca, Erkan; Tekedereli, Ibrahim; Gorgulu, Kivanc; Alpay, Neslihan; Sood, Anil; Lopez-Berestein, Gabriel; Fazli, Ladan; Rennie, Paul; Risberg, Bjørn; Wæhre, Håkon; Danielsen, Håvard E; Ozpolat, Bulent; Saatcioglu, Fahri

2015-01-01

The six transmembrane protein of prostate 2 (STAMP2) is an androgen-regulated gene whose mRNA expression is increased in prostate cancer (PCa). Here, we show that STAMP2 protein expression is increased in human PCa compared with benign prostate that is also correlated with tumor grade and treatment response. We also show that STAMP2 significantly increased reactive oxygen species (ROS) in PCa cells through its iron reductase activity which also depleted NADPH levels. Knockdown of STAMP2 expression in PCa cells inhibited proliferation, colony formation, and anchorage-independent growth, and significantly increased apoptosis. Furthermore, STAMP2 effects were, at least in part, mediated by activating transcription factor 4 (ATF4), whose expression is regulated by ROS. Consistent with in vitro findings, silencing STAMP2 significantly inhibited PCa xenograft growth in mice. Finally, therapeutic silencing of STAMP2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in two established preclinical PCa models in mice. These data suggest that STAMP2 is required for PCa progression and thus may serve as a novel therapeutic target. PMID:25680860

Discrimination of Geographical Origin of Asian Garlic Using Isotopic and Chemical Datasets under Stepwise Principal Component Analysis.

PubMed

Liu, Tsang-Sen; Lin, Jhen-Nan; Peng, Tsung-Ren

2018-01-16

Isotopic compositions of δ 2 H, δ 18 O, δ 13 C, and δ 15 N and concentrations of 22 trace elements from garlic samples were analyzed and processed with stepwise principal component analysis (PCA) to discriminate garlic's country of origin among Asian regions including South Korea, Vietnam, Taiwan, and China. Results indicate that there is no single trace-element concentration or isotopic composition that can accomplish the study's purpose and the stepwise PCA approach proposed does allow for discrimination between countries on a regional basis. Sequentially, Step-1 PCA distinguishes garlic's country of origin among Taiwanese, South Korean, and Vietnamese samples; Step-2 PCA discriminates Chinese garlic from South Korean garlic; and Step-3 and Step-4 PCA, Chinese garlic from Vietnamese garlic. In model tests, countries of origin of all audit samples were correctly discriminated by stepwise PCA. Consequently, this study demonstrates that stepwise PCA as applied is a simple and effective approach to discriminating country of origin among Asian garlics. © 2018 American Academy of Forensic Sciences.

Long-term surface EMG monitoring using K-means clustering and compressive sensing

NASA Astrophysics Data System (ADS)

Balouchestani, Mohammadreza; Krishnan, Sridhar

2015-05-01

In this work, we present an advanced K-means clustering algorithm based on Compressed Sensing theory (CS) in combination with the K-Singular Value Decomposition (K-SVD) method for Clustering of long-term recording of surface Electromyography (sEMG) signals. The long-term monitoring of sEMG signals aims at recording of the electrical activity produced by muscles which are very useful procedure for treatment and diagnostic purposes as well as for detection of various pathologies. The proposed algorithm is examined for three scenarios of sEMG signals including healthy person (sEMG-Healthy), a patient with myopathy (sEMG-Myopathy), and a patient with neuropathy (sEMG-Neuropathr), respectively. The proposed algorithm can easily scan large sEMG datasets of long-term sEMG recording. We test the proposed algorithm with Principal Component Analysis (PCA) and Linear Correlation Coefficient (LCC) dimensionality reduction methods. Then, the output of the proposed algorithm is fed to K-Nearest Neighbours (K-NN) and Probabilistic Neural Network (PNN) classifiers in order to calclute the clustering performance. The proposed algorithm achieves a classification accuracy of 99.22%. This ability allows reducing 17% of Average Classification Error (ACE), 9% of Training Error (TE), and 18% of Root Mean Square Error (RMSE). The proposed algorithm also reduces 14% clustering energy consumption compared to the existing K-Means clustering algorithm.

Electric Power Engineering Cost Predicting Model Based on the PCA-GA-BP

NASA Astrophysics Data System (ADS)

Wen, Lei; Yu, Jiake; Zhao, Xin

2017-10-01

In this paper a hybrid prediction algorithm: PCA-GA-BP model is proposed. PCA algorithm is established to reduce the correlation between indicators of original data and decrease difficulty of BP neural network in complex dimensional calculation. The BP neural network is established to estimate the cost of power transmission project. The results show that PCA-GA-BP algorithm can improve result of prediction of electric power engineering cost.

Chylous ascites after resection of giant adrenocortical carcinoma.

PubMed

Habibi, Mani; Karakoyun, Rojbin; Demirci, Erkan; Alikanoglu, Arsenal Sezgin

2016-12-01

Postoperative chylous ascites (PCA) is a rare clinical state that occurs during abdominal surgery. Despite its rarity, the need to diagnose and treat PCA is increasing in importance with the increased number of wide resections and lymph node dissections being performed and the serious consequences of treatment. Here we describe the PCA complications we observed after resection for treating a case of giant adrenocortical carcinoma and we have the brief review of the PCA complication.

Posterior cortical atrophy variant of Alzheimer's dementia-A case report.

PubMed

Mukku, Shiva Shanker Reddy; Chintala, Haripriya; Nagaraj, Chandana; Mangalore, Sandhya; Sivakumar, Palanimuthu T; Varghese, Mathew

2018-05-17

Alzheimer's dementia (AD) is the commonest type of dementia presenting with initial episodic memory decline followed by involvement of other cognitive domains. Posterior cortical atrophy (PCA) is one of the variants of Alzheimer's dementia (AD) characterized by the atypical presentation of relatively persevered memory in the initial stage. PCA is an uncommon early onset dementia affecting adults between 50 and 65 years. It presents predominantly with visuo-spatial and visuo-perceptual deficits. PCA is a phenotype with varied etiology most common being Alzheimer's disease. The complex and atypical presentation with preserved memory and insight in patients with PCA poses challenge to clinicians in diagnosing at initial stages. There is also paucity of research on prevalence, course, prognosis and management of PCA. In this article we describe a middle aged gentlemen presenting with clinical features suggestive of PCA. We also discussed relevant literature. Copyright © 2018 Elsevier B.V. All rights reserved.

The Present and Future of Prostate Cancer Urine Biomarkers

PubMed Central

Rigau, Marina; Olivan, Mireia; Garcia, Marta; Sequeiros, Tamara; Montes, Melania; Colás, Eva; Llauradó, Marta; Planas, Jacques; de Torres, Inés; Morote, Juan; Cooper, Colin; Reventós, Jaume; Clark, Jeremy; Doll, Andreas

2013-01-01

In order to successfully cure patients with prostate cancer (PCa), it is important to detect the disease at an early stage. The existing clinical biomarkers for PCa are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid over-treatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two thirds of the biopsies performed are still unnecessary. Thus the discovery of non-invasive PCa biomarkers remains urgent. In recent years, the utilization of urine has emerged as an attractive option for the non-invasive detection of PCa. Moreover, a great improvement in high-throughput “omic” techniques has presented considerable opportunities for the identification of new biomarkers. Herein, we will review the most significant urine biomarkers described in recent years, as well as some future prospects in that field. PMID:23774836

Picture agnosia as a characteristic of posterior cortical atrophy.

PubMed

Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Hieda, Sotaro; Kawamura, Mitsuru

2012-01-01

Posterior cortical atrophy (PCA) is a degenerative disease characterized by progressive visual agnosia with posterior cerebral atrophy. We examine the role of the picture naming test and make a number of suggestions with regard to diagnosing PCA as atypical dementia. We investigated 3 cases of early-stage PCA with 7 control cases of Alzheimer disease (AD). The patients and controls underwent a naming test with real objects and colored photographs of familiar objects. We then compared rates of correct answers. Patients with early-stage PCA showed significant inability to recognize photographs compared to real objects (F = 196.284, p = 0.0000) as measured by analysis of variants. This difficulty was also significant to AD controls (F = 58.717, p = 0.0000). Picture agnosia is a characteristic symptom of early-stage PCA, and the picture naming test is useful for the diagnosis of PCA as atypical dementia at an early stage. Copyright © 2012 S. Karger AG, Basel.

[Glucose tolerance and insulinemia in patients with hepatic cirrhosis and portal hypertension treated by portacaval anastomosis].

PubMed

Postiglione, A; Casaretti, B; Masciariello, S; Riccardi, G; Perrotti, N; Lamenza, F; Porcellini, M; Mattioli, P L

1979-02-28

Development of diabetes mellitus is a common complication of side to side porta-caval anastomosis (PCA). Five patients with liver cirrhosis and portal hypertension have been studied with intravehous (IVGTT, 0,5 g/Kg B.W.) and oral (OGTT, 1 g/Kg B.W.) glucose tolerance tests before and three weeks after PCA. Fasting plasma glucose was 84 +/- 7 before and 87 +/- 3 mg/dl after PCA. Fasting IRI increased from 17 +/- 3 to 31 +/- 6 microU/ml. The pattern of plasma glucose and IRI response to IVGTT did not change after PCA. Plasma glucose resonse to OGTT after PCA showed only an earlier rise at 60 instead of 90 minutes, whereas IRI resonse (area under the insulin curve) was significantly enhanced (from 12.4 to 19.8 U/l, p < 0.05). These data suggest a role of gut polipeptides in determining hyperinsulinemia and insulin resistence in PCA patients.

Priority of VHS Development Based in Potential Area using Principal Component Analysis

NASA Astrophysics Data System (ADS)

Meirawan, D.; Ana, A.; Saripudin, S.

2018-02-01

The current condition of VHS is still inadequate in quality, quantity and relevance. The purpose of this research is to analyse the development of VHS based on the development of regional potential by using principal component analysis (PCA) in Bandung, Indonesia. This study used descriptive qualitative data analysis using the principle of secondary data reduction component. The method used is Principal Component Analysis (PCA) analysis with Minitab Statistics Software tool. The results of this study indicate the value of the lowest requirement is a priority of the construction of development VHS with a program of majors in accordance with the development of regional potential. Based on the PCA score found that the main priority in the development of VHS in Bandung is in Saguling, which has the lowest PCA value of 416.92 in area 1, Cihampelas with the lowest PCA value in region 2 and Padalarang with the lowest PCA value.

PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status

PubMed Central

Lütje, Susanne; Heskamp, Sandra; Cornelissen, Alexander S.; Poeppel, Thorsten D.; van den Broek, Sebastiaan A. M. W.; Rosenbaum-Krumme, Sandra; Bockisch, Andreas; Gotthardt, Martin; Rijpkema, Mark; Boerman, Otto C.

2015-01-01

Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided. PMID:26681984

Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients.

PubMed

Kader, A Karim; Sun, Jielin; Isaacs, Sarah D; Wiley, Kathleen E; Yan, Guifang; Kim, Seong-Tae; Fedor, Helen; DeMarzo, Angelo M; Epstein, Jonathan I; Walsh, Patrick C; Partin, Alan W; Trock, Bruce; Zheng, S Lilly; Xu, Jianfeng; Isaacs, William

2009-08-01

More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome-wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive. Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol. For 18 of the 20 SNPs examined, no statistically significant differences (P > 0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason scores > or =4 + 3, or stage > or =T3b, or N+) or less aggressive disease (Gleason scores < or =3 + 4, and stage < or =T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P = 8.4 x 10(-7)) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA. The vast majority of PCa risk-associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa.

Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer.

PubMed

Kinnunen, Pete T T; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo L J; Auvinen, Anssi

2017-08-29

Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease. The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death. We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.

A case-control study of lower urinary-tract infections, associated antibiotics and the risk of developing prostate cancer using PCBaSe 3.0

PubMed Central

Garmo, Hans; Beckmann, Kerri; Stattin, Pär; Adolfsson, Jan; Van Hemelrijck, Mieke

2018-01-01

Objectives To investigate the association between lower urinary-tract infections, their associated antibiotics and the subsequent risk of developing PCa. Subjects/Patients (or materials) and methods Using data from the Swedish PCBaSe 3.0, we performed a matched case-control study (8762 cases and 43806 controls). Conditional logistic regression analysis was used to assess the association between lower urinary-tract infections, related antibiotics and PCa, whilst adjusting for civil status, education, Charlson Comorbidity Index and time between lower urinary-tract infection and PCa diagnosis. Results It was found that lower urinary-tract infections did not affect PCa risk, however, having a lower urinary-tract infection or a first antibiotic prescription 6–12 months before PCa were both associated with an increased risk of PCa (OR: 1.50, 95% CI: 1.23–1.82 and 1.96, 1.71–2.25, respectively), as compared to men without lower urinary-tract infections. Compared to men with no prescriptions for antibiotics, men who were prescribed ≥10 antibiotics, were 15% less likely to develop PCa (OR: 0.85, 95% CI: 0.78–0.91). Conclusion PCa was not found to be associated with diagnosis of a urinary-tract infection or frequency, but was positively associated with short time since diagnoses of lower urinary-tract infection or receiving prescriptions for antibiotics. These observations can likely be explained by detection bias, which highlights the importance of data on the diagnostic work-up when studying potential risk factors for PCa. PMID:29649268

AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth.

PubMed

Hu, Brian R; Fairey, Adrian S; Madhav, Anisha; Yang, Dongyun; Li, Meng; Groshen, Susan; Stephens, Craig; Kim, Philip H; Virk, Navneet; Wang, Lina; Martin, Sue Ellen; Erho, Nicholas; Davicioni, Elai; Jenkins, Robert B; Den, Robert B; Xu, Tong; Xu, Yucheng; Gill, Inderbir S; Quinn, David I; Goldkorn, Amir

2016-05-01

Treatment of prostate cancer (PCa) may be improved by identifying biological mechanisms of tumor growth that directly impact clinical disease progression. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor phenotype impact PCa biology and recurrence. Radical prostatectomy (RP) specimens (±disease recurrence, N = 276) were analyzed by qRT-PCR to quantify expression of genes associated with self-renewal, drug resistance, and tumorigenicity in prior studies. Associations between gene expression and PCa recurrence were confirmed by bootstrap internal validation and by external validation in independent cohorts (total N = 675) and in silico. siRNA knockdown and lentiviral overexpression were used to determine the effect of gene expression on PCa invasion, proliferation, and tumor growth. Four candidate genes were differentially expressed in PCa recurrence. Of these, low AXIN2 expression was internally validated in the discovery cohort. Validation in external cohorts and in silico demonstrated that low AXIN2 was independently associated with more aggressive PCa, biochemical recurrence, and metastasis-free survival after RP. Functionally, siRNA-mediated depletion of AXIN2 significantly increased invasiveness, proliferation, and tumor growth. Conversely, ectopic overexpression of AXIN2 significantly reduced invasiveness, proliferation, and tumor growth. Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts, and its expression levels in PCa cells significantly impacted invasiveness, proliferation, and tumor growth. Given these novel roles, further study of AXIN2 in PCa may yield promising new predictive and therapeutic strategies. © 2016 Wiley Periodicals, Inc.

Incidental prostate cancer in patients with muscle-invasive bladder cancer who underwent radical cystoprostatectomy.

PubMed

Tanaka, Toshikazu; Koie, Takuya; Ohyama, Chikara; Hashimoto, Yasuhiro; Imai, Atsushi; Tobisawa, Yuki; Hatakeyama, Shingo; Yamamoto, Hayato; Yoneyama, Tohru; Horiguchi, Hirotaka; Kodama, Hirotake; Yoneyama, Takahiro

2017-11-01

The aim of this study was to analyze the features of incidentally detected prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens to determine their pathological characteristics and clinical significance. In this retrospective study, we reviewed the clinical and pathological records of 431 consecutive patients with muscle-invasive bladder cancer who underwent RCP at Hirosaki University. Of these, we focused on 237 male patients with prostate-specific antigen (PSA) measurements and digital rectal examinations (DRE) that were recorded prior to the RCP. Significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, pathological T3 or higher stage, lymph node involvement or three or more multifocal lesions within the prostate specimen. We compared clinically significant and insignificant PCa. In this study, a total of 43 patients (18.1%) were diagnosed with incidental PCa via RCP specimens. Age, preoperative PSA levels and pathological T stage in patients with clinically significant PCa were considerably higher than in those with insignificant cancer. Apical involvement was found in 16 patients, including 11 of those with clinically significant PCa. By the end of the follow-up period, none of the enrolled patients had a biochemical recurrence after surgery or died from PCa. According to our findings, preoperative risk factors were not reliable enough to accurately predict clinically significant PCa. Although there was no biochemical relapse or clinical recurrence of PCa in this study, the potential oncologic risk of prostate-sparing RCP must be considered. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ghrelin O-acyltransferase (GOAT) enzyme is overexpressed in prostate cancer, and its levels are associated with patient's metabolic status: Potential value as a non-invasive biomarker.

PubMed

Hormaechea-Agulla, Daniel; Gómez-Gómez, Enrique; Ibáñez-Costa, Alejandro; Carrasco-Valiente, Julia; Rivero-Cortés, Esther; L-López, Fernando; Pedraza-Arevalo, Sergio; Valero-Rosa, José; Sánchez-Sánchez, Rafael; Ortega-Salas, Rosa; Moreno, María M; Gahete, Manuel D; López-Miranda, José; Requena, María J; Castaño, Justo P; Luque, Raúl M

2016-12-01

Ghrelin-O-acyltransferase (GOAT) is the key enzyme regulating ghrelin activity, and has been proposed as a potential therapeutic target for obesity/diabetes and as a biomarker in some endocrine-related cancers. However, GOAT presence and putative role in prostate-cancer (PCa) is largely unknown. Here, we demonstrate, for the first time, that GOAT is overexpressed (mRNA/protein-level) in prostatic tissues (n = 52) and plasma/urine-samples (n = 85) of PCa-patients, compared with matched controls [healthy prostate tissues (n = 12) and plasma/urine-samples from BMI-matched controls (n = 28), respectively]. Interestingly, GOAT levels in PCa-patients correlated with aggressiveness and metabolic conditions (i.e. diabetes). Actually, GOAT expression was regulated by metabolic inputs (i.e. In1-ghrelin, insulin/IGF-I) in cultured normal prostate cells and PCa-cell lines. Importantly, ROC-curve analysis unveiled a valuable diagnostic potential for GOAT to discriminate PCa at the tissue/plasma/urine-level with high sensitivity/specificity, particularly in non-diabetic individuals. Moreover, we discovered that GOAT is secreted by PCa-cells, and that its levels are higher in urine samples from a stimulated post-massage vs. pre-massage prostate-test. In conclusion, plasmatic GOAT levels exhibit high specificity/sensitivity to predict PCa-presence compared with other PCa-biomarkers, especially in non-diabetic individuals, suggesting that GOAT holds potential as a novel non-invasive PCa-biomarker. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The burden of prostate cancer in Asian nations

PubMed Central

Cullen, Jennifer; Elsamanoudi, Sally; Brassell, Stephen A.; Chen, Yongmei; Colombo, Monica; Srivastava, Amita; McLeod, David G.

2012-01-01

Introduction: In this review, the International Agency for Research on Cancer's cancer epidemiology databases were used to examine prostate cancer (PCa) age-standardized incidence rates (ASIR) in selected Asian nations, including Cancer Incidence in Five Continents (CI5) and GLOBOCAN databases, in an effort to determine whether ASIRs are rising in regions of the world with historically low risk of PCa development. Materials and Methods: Asian nations with adequate data quality were considered for this review. PCa ASIR estimates from CI5 and GLOBOCAN 2008 public use databases were examined in the four eligible countries: China, Japan, Korea and Singapore. Time trends in PCa ASIRs were examined using CI5 Volumes I-IX. Results: While PCa ASIRs remain much lower in the Asian nations examined than in North America, there is a clear trend of increasing PCa ASIRs in the four countries examined. Conclusion: Efforts to systematically collect cancer incidence data in Asian nations must be expanded. Current CI5 data indicate a rise in PCa ASIR in several populous Asian countries. If these rates continue to rise, it is uncertain whether there will be sufficient resources in place, in terms of trained personnel and infrastructure for medical treatment and continuum of care, to handle the increase in PCa patient volume. The recommendation by some experts to initiate PSA screening in Asian nations could compound a resource shortfall. Obtaining accurate estimates of PCa incidence in these countries is critically important for preparing for a potential shift in the public health burden posed by this disease. PMID:22529743

The language profile of Posterior Cortical Atrophy

PubMed Central

Crutch, Sebastian J.; Lehmann, Manja; Warren, Jason D.; Rohrer, Jonathan D.

2015-01-01

Background Posterior Cortical Atrophy (PCA) is typically considered to be a visual syndrome, primarily characterised by progressive impairment of visuoperceptual and visuospatial skills. However patients commonly describe early difficulties with word retrieval. This paper details the first systematic analysis of linguistic function in PCA. Characterising and quantifying the aphasia associated with PCA is important for clarifying diagnostic and selection criteria for clinical and research studies. Methods Fifteen patients with PCA, 7 patients with logopenic/phonological aphasia (LPA) and 18 age-matched healthy participants completed a detailed battery of linguistic tests evaluating auditory input processing, repetition and working memory, lexical and grammatical comprehension, single word retrieval and fluency, and spontaneous speech. Results Relative to healthy controls, PCA patients exhibited language impairments across all the domains examined, but with anomia, reduced phonemic fluency and slowed speech rate the most prominent deficits. PCA performance most closely resembled that of LPA patients on tests of auditory input processing, repetition and digit span, but was relatively stronger on tasks of comprehension and spontaneous speech. Conclusions The study demonstrates that in addition to the well-reported degradation of vision, literacy and numeracy, PCA is characterised by a progressive oral language dysfunction with prominent word retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which are both most commonly caused by Alzheimer’s disease, further emphasises the notion of a phenotypic continuum between typical and atypical manifestations of the disease. Clarifying the boundaries between AD phenotypes has important implications for diagnosis, clinical trial recruitment and investigations into biological factors driving phenotypic heterogeneity in AD. Rehabilitation strategies to ameliorate the phonological deficit in PCA are required. PMID:23138762

Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients

PubMed Central

Kader, A. Karim; Sun, Jielin; Isaacs, Sarah D.; Wiley, Kathleen E.; Yan, Guifang; Kim, Seong-Tae; Fedor, Helen; DeMarzo, Angelo M.; Epstein, Jonathan I.; Walsh, Patrick C.; Partin, Alan W.; Trock, Bruce; Zheng, S. Lilly; Xu, Jianfeng; Isaacs, William

2009-01-01

Background More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome-wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive. Methods Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol. Results For 18 of the 20 SNPs examined, no statistically significant differences (P > 0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason Scores ≥ 4+3, or stage ≥ T3b, or N+) or less aggressive disease (Gleason Scores ≤ 3+4, and stage ≤ T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease (rs2735839 in KLK3 (P = 8.4 × 10−7) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA. Conclusions The vast majority of PCa risk-associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa. PMID:19434657

Targeting monoamine oxidase A in advanced prostate cancer.

PubMed

Flamand, Vincent; Zhao, Hongjuan; Peehl, Donna M

2010-11-01

Inhibitors of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine, are commonly used to treat neurological conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostatic epithelium and high-grade primary prostate cancer (PCa). In contrast, MAOA is low in normal secretory prostatic epithelium and low-grade PCa. An irreversible inhibitor of MAOA, clorgyline, induced secretory differentiation in primary cultures of normal basal epithelial cells and high-grade PCa. Furthermore, clorgyline inhibited several oncogenic pathways in PCa cells, suggesting clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high-risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time polymerase chain reaction. Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa.

Epigenetics in prostate cancer: biologic and clinical relevance.

PubMed

Jerónimo, Carmen; Bastian, Patrick J; Bjartell, Anders; Carbone, Giuseppina M; Catto, James W F; Clark, Susan J; Henrique, Rui; Nelson, William G; Shariat, Shahrokh F

2011-10-01

Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge. PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications. Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance. Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth.

PubMed

Wan, Xinhai; Li, Zhi-Gang; Yingling, Jonathan M; Yang, Jun; Starbuck, Michael W; Ravoori, Murali K; Kundra, Vikas; Vazquez, Elba; Navone, Nora M

2012-03-01

Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with X-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1-induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p<0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor-bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth in bone. Thus, targeting TGF-β receptor I is a valuable intervention in men with advanced PCa. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth

PubMed Central

Wan, Xinhai; Li, Zhi-Gang; Yingling, Jonathan M.; Yang, Jun; Starbuck, Michael W.; Ravoori, Murali K.; Kundra, Vikas; Vazquez, Elba; Navone, Nora M.

2012-01-01

Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with x-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1–induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6 weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p < 0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor–bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth in bone. Thus, targeting TGF-β receptor I is a valuable intervention in men with advanced PCa. PMID:22173053

Chylous ascites after resection of giant adrenocortical carcinoma

PubMed Central

Karakoyun, Rojbin; Demirci, Erkan; Alikanoglu, Arsenal Sezgin

2016-01-01

Postoperative chylous ascites (PCA) is a rare clinical state that occurs during abdominal surgery. Despite its rarity, the need to diagnose and treat PCA is increasing in importance with the increased number of wide resections and lymph node dissections being performed and the serious consequences of treatment. Here we describe the PCA complications we observed after resection for treating a case of giant adrenocortical carcinoma and we have the brief review of the PCA complication. PMID:28149812

Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression.

PubMed

Kaulfuss, S; von Hardenberg, S; Schweyer, S; Herr, A M; Laccone, F; Wolf, S; Burfeind, P

2009-11-12

Recently, we could show that the focal adhesion protein leupaxin (LPXN) is expressed in human prostate carcinomas (PCa) and induces invasiveness of androgen-independent PCa cells. In this study we show that LPXN enhanced the progression of existing PCa in vivo by breeding transgenic mice with prostate-specific LPXN expression and TRAMP mice (transgenic adenocarcinoma of mouse prostate). Double transgenic LPXN/TRAMP mice showed a significant increase in poorly differentiated PCa and distant metastases as compared with control TRAMP mice. Additional studies on primary PCa cells generated from both transgenic backgrounds confirmed the connection regarding LPXN overexpression and increased motility and invasiveness of PCa cells. One mediator of LPXN-induced invasion was found to be the cell-cell adhesion protein p120catenin (p120CTN). Both in vitro and in vivo experiments revealed that p120CTN expression negatively correlates with LPXN expression, followed by a redistribution of beta-catenin. Downregulation of LPXN using small interfering RNAs (siRNAs) resulted in a membranous localization of beta-catenin, whereas strong nuclear accumulation of beta-catenin was observed in p120CTN knockdown cells leading to enhanced transcription of the beta-catenin target gene matrix metalloprotease-7. In conclusion, the present results indicate that LPXN enhances the progression of PCa through downregulation of p120CTN expression and that LPXN could function as a marker for aggressive PCa in the future.

Brachyury as a potential modulator of androgen receptor activity and a key player in therapy resistance in prostate cancer

PubMed Central

Pinto, Filipe; Pértega-Gomes, Nelma; Vizcaíno, José R.; Andrade, Raquel P.; Cárcano, Flavio M.; Reis, Rui Manuel

2016-01-01

Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related deaths in men. Acquisition of resistance to conventional therapy is a major problem for PCa patient management. Several mechanisms have been described to promote therapy resistance in PCa, such as androgen receptor (AR) activation, epithelial-to-mesenchymal transition (EMT), acquisition of stem cell properties and neuroendocrine transdifferentiation (NEtD). Recently, we identified Brachyury as a new biomarker of PCa aggressiveness and poor prognosis. In the present study we aimed to assess the role of Brachyury in PCa therapy resistance. We showed that Brachyury overexpression in prostate cancer cells lines increased resistance to docetaxel and cabazitaxel drugs, whereas Brachyury abrogation induced decrease in therapy resistance. Through ChiP-qPCR assays we further demonstrated that Brachyury is a direct regulator of AR expression as well as of the biomarker AMACR and the mesenchymal markers Snail and Fibronectin. Furthermore, in vitro Brachyury was also able to increase EMT and stem properties. By in silico analysis, clinically human Brachyury-positive PCa samples were associated with biomarkers of PCa aggressiveness and therapy resistance, including PTEN loss, and expression of NEtD markers, ERG and Bcl-2. Taken together, our results indicate that Brachyury contributes to tumor chemotherapy resistance, constituting an attractive target for advanced PCa patients. PMID:27049720

Fetal origin of the posterior cerebral artery produces left-right asymmetry on perfusion imaging.

PubMed

Wentland, A L; Rowley, H A; Vigen, K K; Field, A S

2010-03-01

Fetal origin of the PCA is a common anatomic variation of the circle of Willis. On perfusion imaging, patients with unilateral fetal-type PCA may demonstrate left-right asymmetry that could mimic cerebrovascular disease. The aim of this study was to characterize the relationship between a fetal-type PCA and asymmetry of hemodynamic parameters derived from MR perfusion imaging. We retrospectively reviewed MR perfusion studies of 36 patients to determine the relationship between hemodynamic and vascular asymmetries in the PCA territory. Perfusion asymmetry indices for the PCA territory were computed from maps of rCBF, rCBV, MTT, T(max), and FMT. Vascular asymmetry indices were derived from calibers of the PCA-P1 segments relative to the posterior communicating arteries. Asymmetrically smaller values of FMT and T(max) were observed with unilateral fetal-type PCA, and these were strongly correlated with the degree of vascular asymmetry (Spearman's rho = 0.76 and 0.74, respectively, P < 1 x 10(-6)). Asymmetries of rCBF, MTT, and rCBV were neither significant nor related to vascular asymmetry. Faster perfusion transit times are seen for parameters sensitive to macrovascular transit effects (eg, FMT and T(max)) ipsilateral to fetal origin of the PCA in proportion to the degree of arterial asymmetry. Knowledge of this normal variation is critical in the interpretation of perfusion studies because asymmetry could mimic cerebrovascular pathology.

Tau PET binding distinguishes patients with early-stage posterior cortical atrophy from amnestic Alzheimer disease dementia

PubMed Central

Day, Gregory S.; Gordon, Brian A.; Jackson, Kelley; Christensen, Jon J.; Ponisio, Maria Rosana; Su, Yi; Ances, Beau M; Benzinger, Tammie L.S.; Morris, John C.

2017-01-01

Background Flortaucipir (tau) PET binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Methods Flortaucipir and florbetapir (β-amyloid) PET-imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxel-wise level, controlling for age. Results PCA patients (median age-at-onset, 59 [51–61] years) were younger at symptom-onset than similarly-staged individuals with amnestic AD (75 [60–85] years) or CN controls (73 [61–90] years; p=0.002). Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Conclusions and Relevance Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype. PMID:28394771

[The value of PHI/PCA3 in the early diagnosis of prostate cancer].

PubMed

Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

2016-01-12

To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

Analysis of Zinc-Exporters Expression in Prostate Cancer.

PubMed

Singh, Chandra K; Malas, Kareem M; Tydrick, Caitlin; Siddiqui, Imtiaz A; Iczkowski, Kenneth A; Ahmad, Nihal

2016-11-11

Maintaining optimal intracellular zinc (Zn) concentration is crucial for critical cellular functions. Depleted Zn has been associated with prostate cancer (PCa) progression. Solute carrier family 30 (SLC30A) proteins maintain cytoplasmic Zn balance by exporting Zn out to the extracellular space or by sequestering cytoplasmic Zn into intracellular compartments. In this study, we determined the involvement of Zn-exporters, SLC30A 1-10 in PCa, in the context of racial health disparity in human PCa samples obtained from European-American (EA) and African-American (AA) populations. We also analyzed the levels of Zn-exporters in a panel of PCa cells derived from EA and AA populations. We further explored the expression profile of Zn-exporters in PCa using Oncomine database. Zn-exporters were found to be differentially expressed at the mRNA level, with a significant upregulation of SLC30A1, SLC30A9 and SLC30A10, and downregulation of SLC30A5 and SLC30A6 in PCa, compared to benign prostate. Moreover, Ingenuity Pathway analysis revealed several interactions of Zn-exporters with certain tumor suppressor and promoter proteins known to be modulated in PCa. Our study provides an insight regarding Zn-exporters in PCa, which may open new avenues for future studies aimed at enhancing the levels of Zn by modulating Zn-transporters via pharmacological means.

Analysis of Zinc-Exporters Expression in Prostate Cancer

PubMed Central

Singh, Chandra K.; Malas, Kareem M.; Tydrick, Caitlin; Siddiqui, Imtiaz A.; Iczkowski, Kenneth A.; Ahmad, Nihal

2016-01-01

Maintaining optimal intracellular zinc (Zn) concentration is crucial for critical cellular functions. Depleted Zn has been associated with prostate cancer (PCa) progression. Solute carrier family 30 (SLC30A) proteins maintain cytoplasmic Zn balance by exporting Zn out to the extracellular space or by sequestering cytoplasmic Zn into intracellular compartments. In this study, we determined the involvement of Zn-exporters, SLC30A 1–10 in PCa, in the context of racial health disparity in human PCa samples obtained from European-American (EA) and African-American (AA) populations. We also analyzed the levels of Zn-exporters in a panel of PCa cells derived from EA and AA populations. We further explored the expression profile of Zn-exporters in PCa using Oncomine database. Zn-exporters were found to be differentially expressed at the mRNA level, with a significant upregulation of SLC30A1, SLC30A9 and SLC30A10, and downregulation of SLC30A5 and SLC30A6 in PCa, compared to benign prostate. Moreover, Ingenuity Pathway analysis revealed several interactions of Zn-exporters with certain tumor suppressor and promoter proteins known to be modulated in PCa. Our study provides an insight regarding Zn-exporters in PCa, which may open new avenues for future studies aimed at enhancing the levels of Zn by modulating Zn-transporters via pharmacological means. PMID:27833104

Consensus statement on definition, diagnosis, and management of high-risk prostate cancer patients on behalf of the Spanish Groups of Uro-Oncology Societies URONCOR, GUO, and SOGUG.

PubMed

Henríquez, I; Rodríguez-Antolín, A; Cassinello, J; Gonzalez San Segundo, C; Unda, M; Gallardo, E; López-Torrecilla, J; Juarez, A; Arranz, J

2018-03-01

Prostate cancer (PCa) is the most prevalent malignancy in men and the second cause of mortality in industrialized countries. Based on Spanish Register of PCa, the incidence of high-risk PCa is 29%, approximately. In spite of the evidence-based beneficial effect of radiotherapy and androgen deprivation therapy in high-risk PCa, these patients (pts) are still a therapeutic challenge for all specialists involved, in part due to the absence of comparative studies to establish which of the present disposable treatments offer better results. Nowadays, high-risk PCa definition is not well consensual through the published oncology guides. Clinical stage, tumour grade, and number of risk factors are relevant to be considered on PCa prognosis. However, these factors are susceptible to change depending on when surgical or radiation therapy is considered to be the treatment of choice. Other factors, such as reference pathologist, different diagnosis biopsy schedules, surgical or radiotherapy techniques, adjuvant treatments, biochemical failures, and follow-up, make it difficult to compare the results between different therapeutic options. This article reviews important issues concerning high-risk PCa. URONCOR, GUO, and SOGUG on behalf of the Spanish Groups of Uro-Oncology Societies have reached a consensus addressing a practical recommendation on definition, diagnosis, and management of high-risk PCa.

Dietary protocatechuic acid ameliorates dextran sulphate sodium-induced ulcerative colitis and hepatotoxicity in rats.

PubMed

Farombi, Ebenezer O; Adedara, Isaac A; Awoyemi, Omolola V; Njoku, Chinonye R; Micah, Gabriel O; Esogwa, Cynthia U; Owumi, Solomon E; Olopade, James O

2016-02-01

The present study investigated the antioxidant and anti-inflammatory effects of dietary protocatechuic acid (PCA), a simple hydrophilic phenolic compound commonly found in many edible vegetables, on dextran sulphate sodium (DSS)-induced ulcerative colitis and its associated hepatotoxicity in rats. PCA was administered orally at 10 mg kg(-1) to dextran sulphate sodium exposed rats for five days. The result revealed that administration of PCA significantly (p < 0.05) prevented the incidence of diarrhea and bleeding, the decrease in the body weight gain, shortening of colon length and the increase in colon mass index in DSS-treated rats. Furthermore, PCA prevented the increase in the plasma levels of pro-inflammatory cytokines, markers of liver toxicity and markedly suppressed the DSS-mediated elevation in colonic nitric oxide concentration and myeloperoxidase activity in the treated rats. Administration of PCA significantly protected against colonic and hepatic oxidative damage by increasing the antioxidant status and concomitantly decreased hydrogen peroxide and lipid peroxidation levels in the DSS-treated rats. Moreover, histological examinations confirmed PCA chemoprotection against colon and liver damage. Immunohistochemical analysis showed that PCA significantly inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in the colon of DSS-treated rats. In conclusion, the effective chemoprotective role of PCA in colitis and the associated hepatotoxicity is related to its intrinsic anti-inflammatory and anti-oxidative properties.

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

PubMed

Day, Gregory S; Gordon, Brian A; Jackson, Kelley; Christensen, Jon J; Rosana Ponisio, Maria; Su, Yi; Ances, Beau M; Benzinger, Tammie L S; Morris, John C

2017-01-01

Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Flortaucipir and florbetapir (β-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age. PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

Osteopontin is a tumor autoantigen in prostate cancer patients

PubMed Central

TILLI, TATIANA M.; SILVA, ELOÍSIO A.; MATOS, LÍVIA C.; FAGET, DOUGLAS V.; DIAS, BIANCA F.P.; VASCONCELOS, JULIANA S.P.; YOKOSAKI, YASUYUKI; GIMBA, ETEL R.P.

2011-01-01

Anti-tumor antibodies act as biomarkers for the early diagnosis of prostate cancer (PCa). Osteopontin (OPN) is overexpressed in PCa cells and contributes to the progression of the disease. This study aimed to evaluate whether OPN evokes a humoral immune response in PCa patients and whether the reactivity levels of anti-OPN antibodies may be used to better differentiate PCa from benign and healthy donor plasma samples. Plasma samples from biopsy-proven PCa patients (29), benign prostate hyperplasia (BPH) (18) and control healthy donors (HD) (30) were tested by immunoblots using the recombinant human OPN. The frequency of anti-OPN antibodies was significantly higher in PCa (66%) plasma samples as compared to BPH (33%) and HD controls (10%). Anti-OPN antibodies were detected in a high proportion of plasma samples from patients with a Gleason score of less than 6 (57%), prostate-specific antigen levels lower than 10 ng/ml (67%) and pT2 organ-confined disease (70%), suggesting that anti-OPN antibodies may be used as an early serum marker for PCa. To the best of our knowledge, this is the first description of OPN as a tumor autoantigen and one of the most reactive individual autoantigens described thus far. These data support the inclusion of OPN in a multiplex of tumor antigens in order to perform antibody profiling in PCa as well as in other malignancies overexpressing OPN. PMID:22870138

Patient Preferences and Urologist Judgments on Prostate Cancer Therapy in Japan.

PubMed

Nakayama, Masahiko; Kobayashi, Hisanori; Okazaki, Masateru; Imanaka, Keiichiro; Yoshizawa, Kazutake; Mahlich, Jörg

2018-05-01

The purpose of the present study is to investigate the concordance of treatment preferences between patients and physicians in prostate cancer (PCa) in Japan. An internet-based discrete choice experiment was conducted. Patients and physicians were asked to select their preferred treatment from a pair of hypothetical treatments consisting of four attributes: quality of life (QOL), treatment effectiveness, side effects, and accessibility of treatment. The data were analyzed using a conditional logistic regression model to calculate coefficients and the relative importance (RI) of each attribute. A total of 103 PCa patients and 127 physicians responded. The study looked at 37 patients considered as advanced PCa and 66 who were non-advanced PCa. All of the physicians were urologists. Advanced PCa patients ranked the attributes as follows: treatment effectiveness (RI: 32%), accessibility of treatment (RI: 26%), QOL (RI: 23%), and side effects (RI: 19%). For physicians, the RI ranking was the same as for advanced PCa patients; treatment effectiveness (RI: 29%), accessibility of treatment (RI: 27%), QOL (RI: 26%), and side effects (RI: 18%). For non-advanced PCa patients, accessibility of treatment ranked the highest RI (27%) and treatment effectiveness ranked as the lowest RI (14%). Our study suggests that the ranking of the attributes was consistent between advanced PCa patients and physicians. The most influential attribute was treatment effectiveness. Treatment preferences also vary by disease stage.

Relevance of Occlusion Test in Endovascular Coiling of Posterior Cerebral Artery (P2 Segment) Aneurysms

PubMed Central

Jayakumar, P. N.; Desai, S.; Srikanth, S. G.; Ravishankar, S.; Kovoor, J. M. E.

2004-01-01

Summary P2 segment aneurysms are located on the posterior cerebral artery (PCA) between the junction of the posterior communicating artery with the PCA and the quadrigeminal cisternal part of the PCA. We reviewed our experience with endovascular coiling in such aneurysms. Clinical and pre-procedural data from four patients, referred for endovascular treatment of P2 segment aneurysms, were retrospectively studied for factors influencing post-interventional neurological deficits caused by ischemia of the PCA distal territory. Balloon occlusion was done in three patients and patient tolerance was assessed using clinical and anatomic criteria. Embryologic and anatomic features of the PCA were reviewed. Balloon occlusion test and endovascular coiling of aneurysms was possible in three patients. Control angiogram after embolization showed elimination of aneurysms from the circulation and the distal PCA filled through leptomeningeal anastomoses. One patient deteriorated due to aneurysmal rupture soon after the balloon occlusion test and coiling could not be done. In the other three patients post-intervention CT and MRI images showed PCA territory infarcts in spite of demonstration of good collateral circulation distal to the occluded PCA. In conclusion, P2 aneurysms can be effectively treated by endovascular coiling without a balloon occlusion test. While the balloon occlusion test does not contribute to clinical decision-making it may be associated with potential morbidity and mortality. PMID:20587236

Kinetic Studies of Calcium-Induced Calcium Release in Cardiac Sarcoplasmic Reticulum Vesicles

PubMed Central

Sánchez, Gina; Hidalgo, Cecilia; Donoso, Paulina

2003-01-01

Fast Ca2+ release kinetics were measured in cardiac sarcoplasmic reticulum vesicles actively loaded with Ca2+. Release was induced in solutions containing 1.2 mM free ATP and variable free [Ca2+] and [Mg2+]. Release rate constants (k) were 10-fold higher at pCa 6 than at pCa 5 whereas Ryanodine binding was highest at pCa ≤5. These results suggest that channels respond differently when exposed to sudden [Ca2+] changes than when exposed to Ca2+ for longer periods. Vesicles with severalfold different luminal calcium contents exhibited double exponential release kinetics at pCa 6, suggesting that channels undergo time-dependent activity changes. Addition of Mg2+ produced a marked inhibition of release kinetics at pCa 6 (K0.5 = 63 μM) but not at pCa 5. Coexistence of calcium activation and inhibition sites with equally fast binding kinetics is proposed to explain this behavior. Thimerosal activated release kinetics at pCa 5 at all [Mg2+] tested and increased at pCa 6 the K0.5 for Mg2+ inhibition, from 63 μM to 136 μM. We discuss the possible relevance of these results, which suggest release through RyR2 channels is subject to fast regulation by Ca2+ and Mg2+ followed by time-dependent regulation, to the physiological mechanisms of cardiac channel opening and closing. PMID:12668440

Leupaxin stimulates adhesion and migration of prostate cancer cells through modulation of the phosphorylation status of the actin-binding protein caldesmon

PubMed Central

Schmidt, Thomas; Bremmer, Felix; Burfeind, Peter; Kaulfuß, Silke

2015-01-01

The focal adhesion protein leupaxin (LPXN) is overexpressed in a subset of prostate cancers (PCa) and is involved in the progression of PCa. In the present study, we analyzed the LPXN-mediated adhesive and cytoskeletal changes during PCa progression. We identified an interaction between the actin-binding protein caldesmon (CaD) and LPXN and this interaction is increased during PCa cell migration. Furthermore, knockdown of LPXN did not affect CaD expression but reduced CaD phosphorylation. This is known to destabilize the affinity of CaD to F-actin, leading to dynamic cell structures that enable cell motility. Thus, downregulation of CaD increased migration and invasion of PCa cells. To identify the kinase responsible for the LPXN-mediated phosphorylation of CaD, we used data from an antibody array, which showed decreased expression of TGF-beta-activated kinase 1 (TAK1) after LPXN knockdown in PC-3 PCa cells. Subsequent analyses of the downstream kinases revealed the extracellular signal-regulated kinase (ERK) as an interaction partner of LPXN that facilitates CaD phosphorylation during LPXN-mediated PCa cell migration. In conclusion, we demonstrate that LPXN directly influences cytoskeletal dynamics via interaction with the actin-binding protein CaD and regulates CaD phosphorylation by recruiting ERK to highly dynamic structures within PCa cells. PMID:26079947

Common factor analysis versus principal component analysis: choice for symptom cluster research.

PubMed

Kim, Hee-Ju

2008-03-01

The purpose of this paper is to examine differences between two factor analytical methods and their relevance for symptom cluster research: common factor analysis (CFA) versus principal component analysis (PCA). Literature was critically reviewed to elucidate the differences between CFA and PCA. A secondary analysis (N = 84) was utilized to show the actual result differences from the two methods. CFA analyzes only the reliable common variance of data, while PCA analyzes all the variance of data. An underlying hypothetical process or construct is involved in CFA but not in PCA. PCA tends to increase factor loadings especially in a study with a small number of variables and/or low estimated communality. Thus, PCA is not appropriate for examining the structure of data. If the study purpose is to explain correlations among variables and to examine the structure of the data (this is usual for most cases in symptom cluster research), CFA provides a more accurate result. If the purpose of a study is to summarize data with a smaller number of variables, PCA is the choice. PCA can also be used as an initial step in CFA because it provides information regarding the maximum number and nature of factors. In using factor analysis for symptom cluster research, several issues need to be considered, including subjectivity of solution, sample size, symptom selection, and level of measure.

Waist-hip Ratio (WHR), a Better Predictor for Prostate Cancer than Body Mass Index (BMI): Results from a Chinese Hospital-based Biopsy Cohort.

PubMed

Tang, Bo; Han, Cheng-Tao; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Vidal, Adriana C; Freedland, Stephen J; Zhu, Yao; Ye, Ding-Wei

2017-03-08

To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03-1.11) and HGPCa (OR = 1.14 95%Cl 1.09-1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60-0.72) to 0.71 (95%Cl 0.65-0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection.

Waist-hip Ratio (WHR), a Better Predictor for Prostate Cancer than Body Mass Index (BMI): Results from a Chinese Hospital-based Biopsy Cohort

PubMed Central

Tang, Bo; Han, Cheng-Tao; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Vidal, Adriana C.; Freedland, Stephen J.; Zhu, Yao; Ye, Ding-Wei

2017-01-01

To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03–1.11) and HGPCa (OR = 1.14 95%Cl 1.09–1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60–0.72) to 0.71 (95%Cl 0.65–0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection. PMID:28272469

Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity

PubMed Central

Deep, Gagan; Kumar, Rahul; Jain, Anil K.; Dhar, Deepanshi; Panigrahi, Gati K.; Hussain, Anowar; Agarwal, Chapla; El-Elimat, Tamam; Sica, Vincent P.; Oberlies, Nicholas H.; Agarwal, Rajesh

2016-01-01

Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1–5 μg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47phox). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity. PMID:26979487

Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

PubMed

Dampier, Carlton D; Smith, Wally R; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C; Minniti, Caterina P; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A Kyle; McClish, Donna; McKinlay, Sonja M; Miller, Scott T; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J; Weiner, Debra L

2011-12-01

Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.

DCE-MRI of the prostate using shutter-speed vs. Tofts model for tumor characterization and assessment of aggressiveness.

PubMed

Hectors, Stefanie J; Besa, Cecilia; Wagner, Mathilde; Jajamovich, Guido H; Haines, George K; Lewis, Sara; Tewari, Ashutosh; Rastinehad, Ardeshir; Huang, Wei; Taouli, Bachir

2017-09-01

To quantify Tofts model (TM) and shutter-speed model (SSM) perfusion parameters in prostate cancer (PCa) and noncancerous peripheral zone (PZ) and to compare the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to Prostate Imaging and Reporting and Data System (PI-RADS) classification for the assessment of PCa aggressiveness. Fifty PCa patients (mean age 60 years old) who underwent MRI at 3.0T followed by prostatectomy were included in this Institutional Review Board-approved retrospective study. DCE-MRI parameters (K trans , v e , k ep [TM&SSM] and intracellular water molecule lifetime τ i [SSM]) were determined in PCa and PZ. Differences in DCE-MRI parameters between PCa and PZ, and between models were assessed using Wilcoxon signed-rank tests. Receiver operating characteristic (ROC) analysis for differentiation between PCa and PZ was performed for individual and combined DCE-MRI parameters. Diagnostic performance of DCE-MRI parameters for identification of aggressive PCa (Gleason ≥8, grade group [GG] ≥3 or pathology stage pT3) was assessed using ROC analysis and compared with PI-RADSv2 scores. DCE-MRI parameters were significantly different between TM and SSM and between PZ and PCa (P < 0.037). Diagnostic performances of TM and SSM for differentiation of PCa from PZ were similar (highest AUC TM: K trans +k ep 0.76, SSM: τ i +k ep 0.80). PI-RADS outperformed TM and SSM DCE-MRI for identification of Gleason ≥8 lesions (AUC PI-RADS: 0.91, highest AUC DCE-MRI: K trans +τ i SSM 0.61, P = 0.002). The diagnostic performance of PI-RADS and DCE-MRI for identification of GG ≥3 and pT3 PCa was not significantly different (P > 0.213). SSM DCE-MRI did not increase the diagnostic performance of DCE-MRI for PCa characterization. PI-RADS outperformed both TM and SSM DCE-MRI for identification of aggressive cancer. 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:837-849. © 2017 International Society for Magnetic Resonance in Medicine.

Tumor volume in insignificant prostate cancer: increasing threshold gains increasing risk.

PubMed

Schiffmann, Jonas; Connan, Judith; Salomon, Georg; Boehm, Katharina; Beyer, Burkhard; Schlomm, Thorsten; Tennstedt, Pierre; Sauter, Guido; Karakiewicz, Pierre I; Graefen, Markus; Huland, Hartwig

2015-01-01

An increased tumor volume threshold (<2.5 ml) is suggested to define insignificant prostate cancer (iPCa). We hypothesize that an increasing tumor volume within iPCa patients increases the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We relied on RP patients treated between 1992 and 2008. Multivariable Cox regression analyses predicting BCR within patients harboring favorable pathological characteristics (≤pT2, pN0/Nx, Gleason 3 + 3). Kaplan-Meier analysis was performed for BCR-free survival within iPCa patients (≤pT2, pN0/Nx, Gleason 3 + 3, tumor volume: <0.5 vs. 0.5-2.49 ml). From 1,829 patients, 141 (7.7%) and 310 (16.9%) harbored iPCa (tumor volume: <0.5 vs. 0.5-2.49 ml), respectively. Of those, 21 (14.9%) versus 31 (10.0%) had PSA >10 ng/ml. Tumor volume achieved independent predictor status for BCR. Specifically, iPCa patients with increasing tumor volume (0.5-2.49 ml) were at higher risk of BCR after RP than those with tumor volume <0.5 ml (HR: 8.8, 95% CI: 1.2-65.9, P = 0.04). Kaplan-Meier analysis recorded superior BCR-free survival in iPCa patients with lower tumor volume (<0.5 ml) (log-rank P = 0.009). The 10-year cancer-specific death rate was 0 versus 0.5%. Contemporary iPCa definition incorporates intermediate and high-risk patients (PSA: 10-20 and >20 ng/ml). Despite most favorable pathological characteristics, iPCa patients are not devoid of BCR after RP. Moreover, iPCa patients were at higher risk of BCR, when increasing tumor volume up to 2.49 ml was at play. Taken together the contemporary concept of iPCa is suboptimal. Especially, an increased tumor volume threshold for defining iPCa cannot be recommended according to our data. Clinicians might take these considerations into account during decision-making process. © 2014 Wiley Periodicals, Inc.

Cell Line Modeling to Study Biomarker Panel in Prostate Cancer

PubMed Central

NickKholgh, Bita; Fang, Xiaolan; Winters, Shira M.; Raina, Anvi; Pandya, Komal S.; Gyabaah, Kenneth; Fino, Nora; Balaji, K.C.

2016-01-01

BACKGROUND African–American men with prostate cancer (PCa) present with higher-grade and -stage tumors compared to Caucasians. While the disparity may result from multiple factors, a biological basis is often strongly suspected. Currently, few well-characterized experimental model systems are available to study the biological basis of racial disparity in PCa. We report a validated in vitro cell line model system that could be used for the purpose. METHODS We assembled a PCa cell line model that included currently available African–American PCa cell lines and LNCaP (androgen-dependent) and C4-2 (castration-resistant) Caucasian PCa cells. The utility of the cell lines in studying the biological basis of variance in a malignant phenotype was explored using a multiplex biomarker panel consisting of proteins that have been proven to play a role in the progression of PCa. The panel expression was evaluated by Western blot and RT-PCR in cell lines and validated in human PCa tissues by RT-PCR. As proof-of-principle to demonstrate the utility of our model in functional studies, we performed MTS viability assays and molecular studies. RESULTS The dysregulation of the multiplex biomarker panel in primary African–American cell line (E006AA) was similar to metastatic Caucasian cell lines, which would suggest that the cell line model could be used to study an inherent aggressive phenotype in African–American men with PCa. We had previously demonstrated that Protein kinase D1 (PKD1) is a novel kinase that is down regulated in advanced prostate cancer. We established the functional relevance by over expressing PKD1, which resulted in decreased proliferation and epithelial mesenchymal transition (EMT) in PCa cells. Moreover, we established the feasibility of studying the expression of the multiplex biomarker panel in archived human PCa tissue from African–Americans and Caucasians as a prelude to future translational studies. CONCLUSION We have characterized a novel in vitro cell line model that could be used to study the biological basis of disparity in PCa between African–Americans and Caucasians. PMID:26764245

Genome-wide copy number analysis reveals candidate gene loci that confer susceptibility to high-grade prostate cancer.

PubMed

Poniah, Prevathe; Mohd Zain, Shamsul; Abdul Razack, Azad Hassan; Kuppusamy, Shanggar; Karuppayah, Shankar; Sian Eng, Hooi; Mohamed, Zahurin

2017-09-01

Two key issues in prostate cancer (PCa) that demand attention currently are the need for a more precise and minimally invasive screening test owing to the inaccuracy of prostate-specific antigen and differential diagnosis to distinguish advanced vs. indolent cancers. This continues to pose a tremendous challenge in diagnosis and prognosis of PCa and could potentially lead to overdiagnosis and overtreatment complications. Copy number variations (CNVs) in the human genome have been linked to various carcinomas including PCa. Detection of these variants may improve clinical treatment as well as an understanding of the pathobiology underlying this complex disease. To this end, we undertook a pilot genome-wide CNV analysis approach in 36 subjects (18 patients with high-grade PCa and 18 controls that were matched by age and ethnicity) in search of more accurate biomarkers that could potentially explain susceptibility toward high-grade PCa. We conducted this study using the array comparative genomic hybridization technique. Array results were validated in 92 independent samples (46 high-grade PCa, 23 benign prostatic hyperplasia, and 23 healthy controls) using polymerase chain reaction-based copy number counting method. A total of 314 CNV regions were found to be unique to PCa subjects in this cohort (P<0.05). A log 2 ratio-based copy number analysis revealed 5 putative rare or novel CNV loci or both associated with susceptibility to PCa. The CNV gain regions were 1q21.3, 15q15, 7p12.1, and a novel CNV in PCa 12q23.1, harboring ARNT, THBS1, SLC5A8, and DDC genes that are crucial in the p53 and cancer pathways. A CNV loss and deletion event was observed at 8p11.21, which contains the SFRP1 gene from the Wnt signaling pathway. Cross-comparison analysis with genes associated to PCa revealed significant CNVs involved in biological processes that elicit cancer pathogenesis via cytokine production and endothelial cell proliferation. In conclusion, we postulated that the CNVs identified in this study could provide an insight into the development of advanced PCa. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of a robotic surgical system on treatment choice for men with clinically organ-confined prostate cancer.

PubMed

Kobayashi, Takashi; Kanao, Kent; Araki, Motoo; Terada, Naoki; Kobayashi, Yasuyuki; Sawada, Atsuro; Inoue, Takahiro; Ebara, Shin; Watanabe, Toyohiko; Kamba, Tomomi; Sumitomo, Makoto; Nasu, Yasutomo; Ogawa, Osamu

2018-04-01

Introducing a new surgical technology may affect behaviors and attitudes of patients and surgeons about clinical practice. Robot-assisted laparoscopic radical prostatectomy (RALP) was approved in 2012 in Japan. We investigated whether the introduction of this system affected the treatment of organ-confined prostate cancer (PCa) and the use of radical prostatectomy (RP). We conducted a retrospective multicenter study on 718 patients with clinically determined organ-confined PCa treated at one of three Japanese academic institutions in 2011 (n = 338) or 2013 (n = 380). Two patient groups formed according to the treatment year were compared regarding the clinical characteristics of PCa, whether referred or screened at our hospital, comorbidities and surgical risk, and choice of primary treatment. Distribution of PCa risk was not changed by the introduction of RALP. Use of RP increased by 70% (from 127 to 221 cases, p < 0.0001), whereas the number of those undergoing radiotherapy or androgen deprivation therapy decreased irrespective of the disease risk of PCa. Increased use of RP (from 34 to 100 cases) for intermediate- or high-risk PCa patients with mild perioperative risk (American Society of Anesthesiologists score 2) accounted for 70% of the total RP increase, whereas the number of low- or very low-risk PCa patients with high comorbidity scores (Charlson Index ≥ 4) increased from 8 to 25 cases, accounting for 18%. Use of expectant management (active surveillance, watchful waiting) in very low-risk PCa patients was 15% in 2011 and 12% in 2013 (p = 0.791). Introduction of a robotic surgical system had little effect on the risk distribution of PCa. Use of RP increased, apparently due to increased indications in patients who are candidates for RP but have mild perioperative risk. Although small, there was an increase in the number of RPs performed on patients with severe comorbidities but with low-risk or very low-risk PCa.

Reaction Kinetics for the Biocatalytic Conversion of Phenazine-1-Carboxylic Acid to 2-Hydroxyphenazine

PubMed Central

Chen, Mingmin; Cao, Hongxia; Peng, Huasong; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

2014-01-01

The phenazine derivative 2-hydroxyphenazine (2-OH-PHZ) plays an important role in the biocontrol of plant diseases, and exhibits stronger bacteriostatic and fungistatic activity than phenazine-1-carboxylic acid (PCA) toward some pathogens. PhzO has been shown to be responsible for the conversion of PCA to 2-OH-PHZ, however the kinetics of the reaction have not been systematically studied. Further, the yield of 2-OH-PHZ in fermentation culture is quite low and enhancement in our understanding of the reaction kinetics may contribute to improvements in large-scale, high-yield production of 2-OH-PHZ for biological control and other applications. In this study we confirmed previous reports that free PCA is converted to 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the action of a single enzyme PhzO, and particularly demonstrate that this reaction is dependent on NADP(H) and Fe3+. Fe3+ enhanced the conversion from PCA to 2-OH-PHZ and 28°C was a optimum temperature for the conversion. However, PCA added in excess to the culture inhibited the production of 2-OH-PHZ. 2-OH-PCA was extracted and purified from the broth, and it was confirmed that the decarboxylation of 2-OH-PCA could occur without the involvement of any enzyme. A kinetic analysis of the conversion of 2-OH-PCA to 2-OH-PHZ in the absence of enzyme and under different temperatures and pHs in vitro, revealed that the conversion followed first-order reaction kinetics. In the fermentation, the concentration of 2-OH-PCA increased to about 90 mg/L within a red precipitate fraction, as compared to 37 mg/L within the supernatant. The results of this study elucidate the reaction kinetics involved in the biosynthesis of 2-OH-PHZ and provide insights into in vitro methods to enhance yields of 2-OH-PHZ. PMID:24905009

Biomarker microRNAs for prostate cancer metastasis: screened with a network vulnerability analysis model.

PubMed

Lin, Yuxin; Chen, Feifei; Shen, Li; Tang, Xiaoyu; Du, Cui; Sun, Zhandong; Ding, Huijie; Chen, Jiajia; Shen, Bairong

2018-05-21

Prostate cancer (PCa) is a fatal malignant tumor among males in the world and the metastasis is a leading cause for PCa death. Biomarkers are therefore urgently needed to detect PCa metastatic signature at the early time. MicroRNAs are small non-coding RNAs with the potential to be biomarkers for disease prediction. In addition, computer-aided biomarker discovery is now becoming an attractive paradigm for precision diagnosis and prognosis of complex diseases. In this study, we identified key microRNAs as biomarkers for predicting PCa metastasis based on network vulnerability analysis. We first extracted microRNAs and mRNAs that were differentially expressed between primary PCa and metastatic PCa (MPCa) samples. Then we constructed the MPCa-specific microRNA-mRNA network and screened microRNA biomarkers by a novel bioinformatics model. The model emphasized the characterization of systems stability changes and the network vulnerability with three measurements, i.e. the structurally single-line regulation, the functional importance of microRNA targets and the percentage of transcription factor genes in microRNA unique targets. With this model, we identified five microRNAs as putative biomarkers for PCa metastasis. Among them, miR-101-3p and miR-145-5p have been previously reported as biomarkers for PCa metastasis and the remaining three, i.e. miR-204-5p, miR-198 and miR-152, were screened as novel biomarkers for PCa metastasis. The results were further confirmed by the assessment of their predictive power and biological function analysis. Five microRNAs were identified as candidate biomarkers for predicting PCa metastasis based on our network vulnerability analysis model. The prediction performance, literature exploration and functional enrichment analysis convinced our findings. This novel bioinformatics model could be applied to biomarker discovery for other complex diseases.

Effect of protocatechuic acid on insulin responsiveness and inflammation in visceral adipose tissue from obese individuals: possible role for PTP1B.

PubMed

Ormazabal, Paulina; Scazzocchio, Beatrice; Varì, Rosaria; Santangelo, Carmela; D'Archivio, Massimo; Silecchia, Gianfranco; Iacovelli, Annunziata; Giovannini, Claudio; Masella, Roberta

2018-05-16

The occurrence of chronic inflammation in visceral adipose tissue (VAT) in obese subjects precipitates the development of insulin resistance and type 2 diabetes (T2D). Anthocyanins and their main metabolite protocatechuic acid (PCA) have been demonstrated to stimulate insulin signaling in human adipocytes. The aim of this study was to investigate whether PCA is able to modulate insulin responsiveness and inflammation in VAT from obese (OB) and normal weight (NW) subjects. VATs obtained from NW and OB subjects were incubated or not (control) with 100 μM PCA for 24 h. After incubation, tissues untreated and treated with PCA were acutely stimulated with insulin (20 nM, 20 min). PTP1B, p65 NF-κB, phospho-p65 NF-κB, IRS-1, IRβ, Akt, GLUT4 as well as basal and insulin-stimulated Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting in NW- and OB-VAT. Samples were assessed for PTP1B activity and adipocytokine secretion. PCA restored insulin-induced phosphorylation in OB-VAT by increasing phospho-Tyr-IRS-1 and phospho-Ser-Akt after insulin stimulation as observed in NW-VAT (p < 0.05). PTP1B activity was lower in OB-VAT treated with PCA with respect to untreated (p < 0.05). Compared to non-treated tissues, PCA reduced phospho-p65 NF-κB and IL-6 in OB-VAT, and IL-1β in NW-VAT (p < 0.05); and increased adiponectin secretion in NW-VAT (p < 0.05). PCA restores the insulin responsiveness of OB-VAT by increasing IRS-1 and Akt phosphorylation which could be related with the lower PTP1B activity found in PCA-treated OB-VAT. Furthermore, PCA diminishes inflammation in VAT. These results support the beneficial role of an anthocyanin-rich diet against inflammation and insulin resistance in obesity.

Elevated hardness of peripheral gland on real-time elastography is an independent marker for high-risk prostate cancers.

PubMed

Zhang, Qi; Yao, Jing; Cai, Yehua; Zhang, Limin; Wu, Yishuo; Xiong, Jingyu; Shi, Jun; Wang, Yuanyuan; Wang, Yi

2017-12-01

To examine the role of quantitative real-time elastography (RTE) features on differentiation between high-risk prostate cancer (PCA) and non-high-risk prostatic diseases in the initial transperineal biopsy setting. We retrospectively included 103 patients with suspicious PCA who underwent both RTE and initial transperineal prostate biopsy. Patients were grouped into high-risk and non-high-risk categories according to the D'Amico's risk stratification. With computer assistance based on MATLAB programming, three features were extracted from RTE, i.e., the median hardness within peripheral gland (PG) (H med ), the ratio of the median hardness within PG to that outside PG (H ratio ), and the ratio of the hard area within PG to the total PG area (H ar ). A multiple regression model incorporating an RTE feature, age, transrectal ultrasound finding, and prostate volume was used to identify markers for high-risk PCA. Forty-seven patients (45.6%) were diagnosed with PCA and 34 (33.0%) were diagnosed with high-risk PCA. Three RTE features were all statistically higher in high-risk PCA than in non-high-risk diseases (p < 0.001), indicating that the PGs in high-risk PCA patients were harder than those in non-high-risk patients. A high H ratio , high age, and low prostate volume were found to be independent markers for PCAs (p < 0.05), among which the high H ratio was the only independent marker for high-risk PCAs (p = 0.012). When predicting high-risk PCAs, the multiple regression achieved an area under receiver operating characteristic curve of 0.755, sensitivity of 73.5%, and specificity of 71.0%. The elevated hardness of PG identified high-risk PCA and served as an independent marker of high-risk PCA. As a non-invasive imaging modality, the RTE could be potentially used in routine clinical practice for the detection of high-risk PCA to decrease unnecessary biopsies and reduce overtreatment.

Mortality among men with locally advanced prostate cancer managed with noncurative intent: a nationwide study in PCBaSe Sweden.

PubMed

Akre, Olof; Garmo, Hans; Adolfsson, Jan; Lambe, Mats; Bratt, Ola; Stattin, Pär

2011-09-01

There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment. To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent. We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis. We followed up the patient cohort in the Cause of Death Register for ≤ 11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics. The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25-32%) for Gleason score (GS) 2-6, 41% (95% CI, 38-44%) for GS 7, 52% (95% CI, 47-57%) for GS 8, and 64% (95% CI, 59-69%) for GS 9-10. Even for men aged >85 yr at diagnosis with GS 8-10, PCa was a major cause of death: 42% (95% CI, 37-47%). Men with locally advanced disease and a PSA<4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status. The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

BPH: a tell-tale sign of prostate cancer? Results from the Prostate Cancer and Environment Study (PROtEuS).

PubMed

Boehm, Katharina; Valdivieso, Roger; Meskawi, Malek; Larcher, Alessandro; Sun, Maxine; Sosa, José; Blanc-Lapierre, Audrey; Weiss, Deborah; Graefen, Markus; Saad, Fred; Parent, Marie-Élise; Karakiewicz, Pierre I

2015-12-01

In a population-based case-control study (PROtEuS), we examined the association between prostate cancer (PCa) and (1) benign prostatic hypertrophy (BPH) history at any time prior to PCa diagnosis, (2) BPH-history reported at least 1 year prior to interview/diagnosis (index date) and (3) exposure to BPH-medications. Cases were 1933 men with incident prostate cancer diagnosed across Montreal French hospitals between 2005 and 2009. Population controls were 1994 men from the same age distribution and residential area. In-person interviews collected socio-demographic characteristics and medical history, e.g., BPH diagnosis, duration and treatment, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. A BPH-history was associated with an increased risk of PCa (OR 1.37 [95 % CI 1.16-2.61]), more pronounced for low-grade PCa (Gleason ≤6: OR 1.54 [1.26-1.87]; Gleason ≥7: OR 1.05 [0.86-1.27]). The association was not significant when BPH-history diagnosis was more than 1 year prior to index date, except for low-grade PCa (OR 1.29 [1.05-1.60]). Exposure to 5α reductase inhibitors (5α-RI) resulted in a decreased risk of overall PCa (OR 0.62 [0.42-0.92]), particularly for intermediate- to high-grade PCa (Gleason ≤6: OR 0.70 [0.43-1.14]; Gleason ≥7: OR 0.43 [0.26-0.72]). Adjusting for PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. BPH-history was associated with an increased PCa risk, which disappeared, when BPH-history did not include BPH diagnosis within the previous year. Our results also suggest that 5α-RI exposure exerts a protective effect on intermediate and high-grade PCa.

Stability and precipitation of diverse nanoparticles

NASA Astrophysics Data System (ADS)

Desai, Chintal

Nanotechnology is a rapidly growing industry that is exploiting the novel characteristics of materials manufactured at the nanoscale. Carbon based nanomaterials such as Carbon Nanotubes (CNTs) and Detonation Nanodiamond (DND) possess unique properties and find a wide range of industrial applications. With the advent of mass production of such materials, there is a possibility of contamination of water resources. Depending on the surface properties and structures, they might aggregate and settle down, or be dispersed and transported by the water. Therefore, there is a need to develop an understanding of the fate of such materials in aqueous media. The understanding and effect of solution chemistry is a key to predicting their deposition, transport, reactivity, and bioavailability in aquatic environments. The colloidal behavior of organic dispersed CNTs and water dispersed DNDs is investigated. The aggregation behavior of these two colloidal systems is quite different from that of hydrophilic, water soluble functionalized CNTs (F-CNTs). The values of the Fuchs stability ratio or the critical coagulant concentration are determined experimentally using time-resolved dynamic light scattering and are used to predict the stability of such systems. It is found that the aggregation behavior of the organic dispersed, antisolvent precipitated system does not follow the conventional Derjaguin--Landau--Verwey-- Overbeek (DLVO) theory. But they stabilize in the long term, which is attributed to the supersaturation generated by different solubility of a solute in the solvent/antisolvent. Based on particle size distribution, zeta potential as well as the aggregation kinetics, the water dispersed DNDs are found to be relatively stable in aqueous solutions, but aggregate rapidly in presence of mono and divalent salts. Also, the formation of carboxylic groups on the DND surface does not alter colloidal behavior as dramatically as it does for other nanocarbons especially carbon nanotubes. Formation of colloidal dispersions via precipitation processes has been widely used in the chemical and pharmaceutical industries. The synthesis of micro- particles for hydrophobic drugs is effectively carried out via anti-solvent precipitation method. The formation of small particles in the precipitation method is strongly influenced by colloidal interactions, and therefore, dependent on the properties of the particles and the liquid. The effect of solvent on the colloidal stability of the micro-drug particles is studied in detail. It is found that the organic solvent plays an important role on particle formation, polymorphism and stability of micron scale drug particles in aqueous media. Also, the supersaturation can be varied by using different solvents and the physicochemical characteristics of the suspension can be altered, which affects stability. Understanding of the colloidal stability and the aggregation kinetics has great importance not only for fundamental researches, but also for their applications.

Non-invasive urinary metabolomic profiling discriminates prostate cancer from benign prostatic hyperplasia.

PubMed

Pérez-Rambla, Clara; Puchades-Carrasco, Leonor; García-Flores, María; Rubio-Briones, José; López-Guerrero, José Antonio; Pineda-Lucena, Antonio

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results. In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH. Urine samples from 64 PCa patients and 51 individuals diagnosed with BPH were analysed using 1 H nuclear magnetic resonance ( 1 H-NMR). Comparative analysis of urinary metabolomic profiles was carried out using multivariate and univariate statistical approaches. The urine metabolomic profile of PCa patients is characterised by increased concentrations of branched-chain amino acids (BCAA), glutamate and pseudouridine, and decreased concentrations of glycine, dimethylglycine, fumarate and 4-imidazole-acetate compared with individuals diagnosed with BPH. PCa patients have a specific urinary metabolomic profile. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be useful to discriminate PCa from BPH in a clinical context.

Multimethod Prediction of Physical Parent-Child Aggression Risk in Expectant Mothers and Fathers with Social Information Processing Theory

PubMed Central

Rodriguez, Christina M.; Smith, Tamika L.; Silvia, Paul J.

2015-01-01

The Social Information Processing (SIP) model postulates that parents undergo a series of stages in implementing physical discipline that can escalate into physical child abuse. The current study utilized a multimethod approach to investigate whether SIP factors can predict risk of parent-child aggression (PCA) in a diverse sample of expectant mothers and fathers. SIP factors of PCA attitudes, negative child attributions, reactivity, and empathy were considered as potential predictors of PCA risk; additionally, analyses considered whether personal history of PCA predicted participants’ own PCA risk through its influence on their attitudes and attributions. Findings indicate that, for both mothers and fathers, history influenced attitudes but not attributions in predicting PCA risk, and attitudes and attributions predicted PCA risk; empathy and reactivity predicted negative child attributions for expectant mothers, but only reactivity significantly predicted attributions for expectant fathers. Path models for expectant mothers and fathers were remarkably similar. Overall, the findings provide support for major aspects of the SIP model. Continued work is needed in studying the progression of these factors across time for both mothers and fathers as well as the inclusion of other relevant ecological factors to the SIP model. PMID:26631420

CatB is Critical for Total Catalase Activity and Reduces Bactericidal Effects of Phenazine-1-Carboxylic Acid on Xanthomonas oryzae pv. oryzae and X. oryzae pv. oryzicola.

PubMed

Pan, Xiayan; Wu, Jian; Xu, Shu; Duan, Yabing; Zhou, Mingguo

2017-02-01

Rice bacterial leaf blight, caused by Xanthomonas oryzae pv. oryzae, and rice bacterial leaf streak, caused by X. oryzae pv. oryzicola, are major diseases of rice. Phenazine-1-carboxylic acid (PCA) is a natural product that is isolated from Pseudomonas spp. and is used to control many important rice diseases in China. We previously reported that PCA disturbs the redox balance, which results in the accumulation of reactive oxygen species in X. oryzae pv. oryzae. In this study, we found that PCA significantly upregulated the transcript levels of catB and katE, which encode catalases, and that PCA sensitivity was reduced when X. oryzae pvs. oryzae and oryzicola were cultured with exogenous catalase. Furthermore, catB deletion mutants of X. oryzae pvs. oryzae and oryzicola showed dramatically decreased total catalase activity, increased sensitivity to PCA, and reduced virulence in rice. In contrast, deletion mutants of srpA and katG, which also encode catalases, exhibited little change in PCA sensitivity. The results indicate that catB in both X. oryzae pvs. oryzae and oryzicola encodes a catalase that helps protect the bacteria against PCA-induced stress.

Incorporating biological information in sparse principal component analysis with application to genomic data.

PubMed

Li, Ziyi; Safo, Sandra E; Long, Qi

2017-07-11

Sparse principal component analysis (PCA) is a popular tool for dimensionality reduction, pattern recognition, and visualization of high dimensional data. It has been recognized that complex biological mechanisms occur through concerted relationships of multiple genes working in networks that are often represented by graphs. Recent work has shown that incorporating such biological information improves feature selection and prediction performance in regression analysis, but there has been limited work on extending this approach to PCA. In this article, we propose two new sparse PCA methods called Fused and Grouped sparse PCA that enable incorporation of prior biological information in variable selection. Our simulation studies suggest that, compared to existing sparse PCA methods, the proposed methods achieve higher sensitivity and specificity when the graph structure is correctly specified, and are fairly robust to misspecified graph structures. Application to a glioblastoma gene expression dataset identified pathways that are suggested in the literature to be related with glioblastoma. The proposed sparse PCA methods Fused and Grouped sparse PCA can effectively incorporate prior biological information in variable selection, leading to improved feature selection and more interpretable principal component loadings and potentially providing insights on molecular underpinnings of complex diseases.

Developing a novel therapeutic strategy targeting Kallikrein-4 to inhibit prostate cancer growth and metastasis

DTIC Science & Technology

Kallikrein-related peptidase 4 (KLK4) is a rational therapeutic target for prostate cancer (PCa) as it is up-regulated in both localised and bone ...in PCa homing to bone . We therefore hypothesize that blockade of KLK4 activity will inhibit PCa growth and prevent metastasis to secondary sites like... bone . This project aims to develop a novel therapeutic strategy targeting KLK4 specifically in PCa. KLK4 siRNA is incorporated into a novel polymeric

Identification of Novel, Inherited Genetic Markers for Aggressive PCa in European and African Americans Using Whole Genome Sequencing

DTIC Science & Technology

2013-09-01

DATES COVERED (From - To) 22 August 2012 – 21 August 2013 4. TITLE AND SUBTITLE Identification of Novel, Inherited Genetic Markers for Aggressive... Inherited markers of aggressive PCa could be used for screening and diagnosis of aggressive PCa at an early stage while reducing over-diagnosis and...treatment for others. The overall hypothesis is that inherited sequence variants in the genome are associated with a lethal (aggressive) form of PCa but not

An incidence model of the cost of advanced prostate cancer in Spain.

PubMed

Hart, W M; Nazir, J; Baskin-Bey, E

2014-02-01

Prostate cancer (PCa) is the second leading cancer diagnosed among men. In Spain the incidence of PCa was 70.75 cases per 100,000 males. Advanced PCa has spread outside of the prostate capsule and may involve other parts of the body. The aim of this study was to estimate the lifetime costs of a cohort of advanced PCa patients diagnosed in Spain in 2012. A partitioned economic model was developed in EXCEL incorporating Spanish incidence, mortality, and cost data supplemented with data from the international literature. Progression from Stage III to Stage IV was permitted. Costs were discounted at the standard rate of 3%. Lifetime costs were presented on an individual basis and for the entire cohort of newly diagnosed Stage III and Stage IV PCa patients. Lifetime costs for advanced PCa were ∼€19,961 per patient (mean survival of 8.4 years). Using the projected incident cases for 2012 (3047), the total cost for the incident cohort of patients in 2012 would amount to €61 million. These results were more sensitive to changes in the ongoing costs (post-initial 12 months) of Stage III PCa, the rate of progression from Stage III to Stage IV, and the discount rate applied to costs. This study provides an estimate of the lifetime costs of advanced PCa in Spain and a framework for further research. The study is limited by the availability of long-term Spanish data and the need to make inferences from international studies. However, until long-term prospective or observational data do become available in Spain, based on the assumptions, the current results indicate that the burden of advanced PCa in Spain is substantial. Any treatments that could potentially reduce the economic burden of the disease should be of interest to healthcare decision makers.

Prostate cancer gene 3 and multiparametric magnetic resonance can reduce unnecessary biopsies: decision curve analysis to evaluate predictive models.

PubMed

Busetto, Gian Maria; De Berardinis, Ettore; Sciarra, Alessandro; Panebianco, Valeria; Giovannone, Riccardo; Rosato, Stefano; D'Errigo, Paola; Di Silverio, Franco; Gentile, Vincenzo; Salciccia, Stefano

2013-12-01

To overcome the well-known prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Copyright © 2013 Elsevier Inc. All rights reserved.

[Evaluation of the effectiveness of patient-controlled analgesia in children with sickle cell anemia from the perspective of healthcare professionals and parents].

PubMed

Turaç, Ayşegül; Rumeli Atıcı, Şebnem

2016-07-01

This study evaluated the efficacy of patient-controlled analgesia (PCA) used by children with sickle cell anemia (SCA) based on the attitudes of parents and healthcare professionals. A total of 86 individuals were involved in the study: 54 parents of children with SCA who were receiving treatment and 32 healthcare providers (doctors, nurses). To evaluate the effectiveness of the PCA method, a questionnaire was prepared to determine the level of knowledge of the participants about the PCA method and their perception of its advantages and disadvantages. According to 65.6% (n=21) of the healthcare providers, PCA should be used during acute phase of pain. The great majority of the participants (93%; n=80) thought that pain was effectively controlled both during the day and at night. PCA reduced the fear of unavailability of analgesic drugs in 83.3% (n=45) of parents and in 87.5% (n=28) of healthcare providers. More parents (37%) reported a reduction in the fear of return of pain than healthcare providers (9.4%) (p<0.05). Most parents (87%; n=47) reported that they preferred to wait until their child complained of severe pain to use on-demand doses of analgesic due to concerns about overdose and addiction. Resolving machine alarms (48%; n=26) and the length of time required to refill the machine (48%; n=26) were reported as disadvantages of PCA method. In this study, parents and healthcare professionals found PCA to be effective in relieving pain in children with SCA; however, fears and biased knowledge of users about the analgesic drug are thought to inhibit reaching sufficient dosage. Educational courses for users about PCA and the drugs used may increase the effectiveness of PCA method.

Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment

PubMed Central

Hosseini-Beheshti, Elham; Choi, Wendy; Weiswald, Louis-Bastien; Kharmate, Geetanjali; Ghaffari, Mazyar; Roshan-Moniri, Mani; Hassona, Mohamed D.; Chan, Leslie; Chin, Mei Yieng; Tai, Isabella T.; Rennie, Paul S.; Fazli, Ladan; Guns, Emma S. Tomlinson

2016-01-01

Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression. PMID:26840259

Antidiabetic and antihyperlipidemic activity of p-coumaric acid in diabetic rats, role of pancreatic GLUT 2: In vivo approach.

PubMed

Amalan, Venkatesan; Vijayakumar, Natesan; Indumathi, Dhananjayan; Ramakrishnan, Arumugam

2016-12-01

P-coumaric acid (p-CA, 3-[4-hydroxyphenyl]-2-propenoic acid), the major component widely found in nutritious plant foods, has various antioxidant, antiinflammatory and anticancer property. To evaluate the antidiabetic and antihyperlipidemic mechanisms, via the effects on carbohydrate, lipids and lipoproteins responses in adult male albino Wistar rats were examined by treated with p-CA. Rats were injected with streptozotocin (STZ, 40mg/kg b.w.) by intraperitonially (i.p.) 30days for the induction of experimental diabetes mellitus. Diabetic rats were treated with p-CA orally at a dose of 100mg/kg b.w. The potential defending character of p-CA against diabetic rats was evaluated by performing the various biochemical parameters and glucose transporter such as GLUT2 mRNA expression of pancreas. Administration of p-CA significantly lowers the blood glucose level, gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase whereas increases the activities of hexokinase, glucose-6 phosphatase dehydrogenase and GSH via by increasing level of insulin. p-CA reduces the total cholesterol and triglycerides in both plasma and tissues i.e. liver and kidney. p-CA also decreases the LDL-C, VLDL-C and it considerably increase the level of HDL-C. A significant decreased expression of GLUT 2 mRNA in the pancreas was recorded in the supplementation of p-CA treated groups. Taken together, these results suggest that p-CA modulates glucose and lipid metabolism via GLUT 2 activation in the pancreatic and has potentially beneficial effects in improving or treating metabolic disorders. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers.

PubMed

Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P V L N; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

2016-01-01

Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient's serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet's serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10-6 in Fischer's exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis.

Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers

PubMed Central

Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P. V. L. N.; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

2016-01-01

Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient’s serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet’s serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10−6 in Fischer’s exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis. PMID:26958841

Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguus of the rat.

PubMed

Hayakawa, T; Takanaga, A; Maeda, S; Ito, H; Seki, M

2000-11-01

The cricothyroid (CT) and the posterior cricoarytenoid (PCA) muscles in the larynx are activated by the laryngeal motoneurons located within the nucleus ambiguus; these motoneurons receive the laryngeal sensory information from the nucleus tractus solitarii (NTS) during respiration and swallowing. We investigated whether the neurons in the NTS projected directly to the laryngeal motoneurons, and what is the synaptic organization of their nerve terminals on the laryngeal motoneurons using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) was injected into the CT muscle or the PCA muscle, the anterogradely WGA-HRP-labeled terminals from the NTS were found to directly contact the retrogradely CT-HRP-labeled dendrites and soma of both the CT and the PCA motoneurons. The labeled NTS terminals comprised about 4% of the axosomatic terminals in a section through the CT motoneurons, and about 9% on both the small (PCA-A) and the large (PCA-B) PCA motoneurons. The number of labeled axosomatic terminals containing round vesicles and making asymmetric synaptic contacts (Gray's type I) was almost equal to that of the labeled terminals containing pleomorphic vesicles and making symmetric synaptic contacts (Gray's type II) on the CT motoneurons. The labeled axosomatic terminals were mostly Gray's type II on the PCA-A motoneurons, while the majority of them were Gray's type I on the PCA-B motoneurons. These results indicate that the laryngeal CT and PCA motoneurons receive a few direct excitatory and inhibitory inputs from the neurons in the NTS.

The effect of start and stop age at screening on the risk of being diagnosed with prostate cancer

PubMed Central

Arnsrud Godtman, Rebecka; Carlsson, Sigrid; Holmberg, Erik; Stranne, Johan; Hugosson, Jonas

2016-01-01

Purpose The aim of this study was to investigate the effect of age and number of screens on the risk of prostate cancer (PCa) diagnosis. Materials and Methods The Göteborg randomized population-based PCa screening trial has, since 1995, invited men biennially for prostate-specific antigen (PSA)-testing, until the upper age limit 70 years. Men with a PSA-level above the threshold ≥2.5 ng/ml were recommended further work-up including 10-core biopsy (sextant before 2009). The present study comprises 9,065 men born 1930–43 (1944 excluded due to different screening algorithm). Complete attendees were defined as men who accepted all screening invitations (maximum 3–9 invitations). Cumulative incidence of PCa was calculated using standard methods. Results Of the 3,488 (38%) complete attendees, 667 were diagnosed with PCa (follow-up 1995–30 Jun 2014). At the age 70, there was no significant difference in PCa risk between those who started screening at the age of 52 (9 screens), 55 (7 screens) or 60 (5 screens) years. However, the cumulative risk of PCa diagnosis increased dramatically with age and was 7.9% at age 60, 15% at age 65 and 21% at age 70, for men who had been screened ≥4 times. Conclusion There was no clear association between risk of PCa and the number of screens. Starting screening at an early age appears to advance the time of PCa diagnosis but does not seem to increase the risk of being diagnosed with the disease. Age at termination of screening is strongly associated with the risk of being diagnosed with PCa. PMID:26678954

Race, Genetic West African Ancestry, and Prostate Cancer Prediction by PSA in Prospectively Screened High-Risk Men

PubMed Central

Giri, Veda N.; Egleston, Brian; Ruth, Karen; Uzzo, Robert G.; Chen, David Y.T.; Buyyounouski, Mark; Raysor, Susan; Hooker, Stanley; Torres, Jada Benn; Ramike, Teniel; Mastalski, Kathleen; Kim, Taylor Y.; Kittles, Rick

2008-01-01

Introduction “Race-specific” PSA needs evaluation in men at high-risk for prostate cancer (PCA) for optimizing early detection. Baseline PSA and longitudinal prediction for PCA was examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Materials and Methods Eligibility criteria are age 35–69 years, FH of PCA, African American (AA) race, or BRCA1/2 mutations. Biopsies have been performed at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for PCA. Results 646 men (63% AA) were analyzed. Individual WA ancestry estimates varied widely among self-reported AA men. “Race-specific” differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with ≥ 1 follow-up visit (405 total, 54% AA), three-year prediction for PCA with a PSA of 1.5–4.0 ng/mL was higher in AA men with age in the model (p=0.025) compared to EA men. Hazard ratios of PSA for PCA were also higher by self-reported race (1.59 for AA vs. 1.32 for EA, p=0.04). There was a trend for increasing prediction for PCA with increasing genetic WA ancestry. Conclusions “Race-specific” PSA may need to be redefined as higher prediction for PCA at any given PSA in AA men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing PCA early detection. PMID:19240249

A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

PubMed

Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

2011-12-01

Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Copyright © 2011 Wiley Periodicals, Inc.

Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature.

PubMed

Mohamedali, Khalid A; Li, Zhi Gang; Starbuck, Michael W; Wan, Xinhai; Yang, Jun; Kim, Sehoon; Zhang, Wendy; Rosenblum, Michael G; Navone, Nora M

2011-04-15

A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF(121)/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting nontumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa. Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF(121)/rGel. VEGF(121)/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF(121)/rGel internalization into osteoblasts was VEGF(121) receptor driven. Furthermore, VEGF(121)/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF(121)/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomographic analysis revealed that VEGF(121)/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non-tumor-bearing) femurs. VEGF(121)/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF(121)/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF(121)/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation. Targeting VEGF receptor (VEGFR)-1- or VEGFR-2-expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. ©2011 AACR.

Androgen receptor (AR) degradation enhancer ASC-J9® in an FDA-approved formulated solution suppresses castration resistant prostate cancer cell growth.

PubMed

Cheng, Max A; Chou, Fu-Ju; Wang, Keliang; Yang, Rachel; Ding, Jie; Zhang, Qiaoxia; Li, Gonghui; Yeh, Shuyuan; Xu, Defeng; Chang, Chawnshang

2018-03-28

ASC-J9 ® is a recently-developed androgen receptor (AR)-degradation enhancer that effectively suppresses castration resistant prostate cancer (PCa) cell proliferation and invasion. The optimal half maximum inhibitory concentrations (IC 50 ) of ASC-J9 ® at various PCa cell confluences (20%, 50%, and 100%) were assessed via both short-term MTT growth assays and long-term clonogenic proliferation assays. Our results indicate that the IC 50 values for ASC-J9 ® increased with increasing cell confluency. The IC 50 values were significantly decreased in PCa AR-positive cells compared to PCa AR-negative cells or in normal prostate cells. This suggests that ASC-J9 ® may function mainly via targeting the AR-positive PCa cells with limited unwanted side-effects to suppress the surrounding normal prostate cells. Mechanism dissection indicated that ASC-J9 ® might function via altering the apoptosis signals to suppress the PCa AR-negative PC-3 cells. Preclinical studies using multiple in vitro PCa cell lines and an in vivo mouse model with xenografted castration-resistant PCa CWR22Rv1 cells demonstrated that ASC-J9 ® has similar AR degradation effects when dissolved in FDA-approved solvents, including DMSO, PEG-400:Tween-80 (95:5), DMA:Labrasol:Tween-80 (10:45:45), and DMA:Labrasol:Tween-20 (10:45:45). Together, results from preclinical studies suggest a potential new therapy with AR-degradation enhancer ASC-J9 ® may potentially be ready to be used in human clinical trials in order to better suppress PCa at later castration resistant stages. Copyright © 2017 Elsevier B.V. All rights reserved.

Silibinin prevents prostate cancer cell-mediated differentiation of naïve fibroblasts into cancer-associated fibroblast phenotype by targeting TGF β2.

PubMed

Ting, Harold J; Deep, Gagan; Jain, Anil K; Cimic, Adela; Sirintrapun, Joseph; Romero, Lina M; Cramer, Scott D; Agarwal, Chapla; Agarwal, Rajesh

2015-09-01

Tumor microenvironment (TM) is an essential element in prostate cancer (PCA), offering unique opportunities for its prevention. TM includes naïve fibroblasts that are recruited by nascent neoplastic lesion and altered into 'cancer-associated fibroblasts' (CAFs) that promote PCA. A better understanding and targeting of interaction between PCA cells and fibroblasts and inhibiting CAF phenotype through non-toxic agents are novel approaches to prevent PCA progression. One well-studied cancer chemopreventive agent is silibinin, and thus, we examined its efficacy against PCA cells-mediated differentiation of naïve fibroblasts into a myofibroblastic-phenotype similar to that found in CAFs. Silibinin's direct inhibitory effect on the phenotype of CAFs derived directly from PCA patients was also assessed. Human prostate stromal cells (PrSCs) exposed to control conditioned media (CCM) from human PCA PC3 cells showed more invasiveness, with increased alpha-smooth muscle actin (α-SMA) and vimentin expression, and differentiation into a phenotype we identified in CAFs. Importantly, silibinin (at physiologically achievable concentrations) inhibited α-SMA expression and invasiveness in differentiated fibroblasts and prostate CAFs directly, as well as indirectly by targeting PCA cells. The observed increase in α-SMA and CAF-like phenotype was transforming growth factor (TGF) β2 dependent, which was strongly inhibited by silibinin. Furthermore, induction of α-SMA and CAF phenotype by CCM were also strongly inhibited by a TGFβ2-neutralizing antibody. The inhibitory effect of silibinin on TGFβ2 expression and CAF-like biomarkers was also observed in PC3 tumors. Together, these findings highlight the potential usefulness of silibinin in PCA prevention through targeting the CAF phenotype in the prostate TM. © 2014 Wiley Periodicals, Inc.

Variants on 8q24 and prostate cancer risk in Chinese population: a meta-analysis.

PubMed

Ren, Xiao-Qiang; Zhang, Jian-Guo; Xin, Shi-Yong; Cheng, Tao; Li, Liang; Ren, Wei-Hua

2015-01-01

Previous studies have identified 8q24 as an important region to prostate cancer (PCa) susceptibility. The aim of this study was to investigate the role of six genetic variants on 8q24 (rs1447295, A; rs6983267, G; rs6983561, C; rs7837688, T; rs10090154, T and rs16901979, A) on PCa risk in Chinese population. Online electronic databases were searched to retrieve related articles concerning the association between 8q24 variants and PCa risk in men of Chinese population published between 2000 and 2014. Odds ratio (ORs) with its 95% correspondence interval (CI) were employed to assess the strength of association. Total eleven case-control studies were screened out, including 2624 PCa patients and 2438 healthy controls. Our results showed that three risk alleles of rs1447295 A (OR=1.35, 95% CI=1.19-1.53, P<0.00001), rs6983561 C (C vs. A: OR=1.41, 95% CI=1.21-1.63, P<0.00001) and rs10090154 T (T vs. C: OR=1.48, 95% CI=1.22-1.80, P<0.00001) on8q24 were significantly associated with PCa risk in Chinese population. Furthermore, genotypes of rs1447295, AA+AC; rs6983561, CC+AC and CC; rs10090154, TT+TC; and rs16901979, AA were associated with PCa as well (P<0.01). No association was found between rs6983267, rs7837688 and PCa risk. In conclusions, variants including rs1447295, rs6983561, rs10090154 and rs16901979 on 8q24 might be associated with PCa risk in Chinese population, indicating these four variations may contribute risk to this disease. This meta-analysis was the first study to assess the role of 8q24 variants on PCa risk in Chinese population.

MSMB gene variant alters the association between prostate cancer and number of sexual partners

PubMed Central

Stott-Miller, Marni; Wright, Jonathan L.; Stanford, Janet L.

2014-01-01

Background Recently, a genetic variant (rs10993994) in the MSMB gene associated with prostate cancer (PCa) risk was shown to correlate with reduced prostate secretory protein of 94 amino acids (PSP94) levels. Although the biological activity of PSP94 is unclear, one of its hypothesized functions is to protect prostatic cells from pathogens. Number of sexual partners and a history of sexually transmitted infections (STIs) have been positively associated with PCa risk, and these associations may be related to pathogen-induced chronic prostatic inflammation. Based on these observations, we investigated whether MSMB genotype modifies the PCa-sexual history association. Methods We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between number of sexual partners and PCa by fitting logistic regression models, stratified by MSMB genotype, and adjusted for age, family history of PCa, and PCa screening history among 1,239 incident cases and 1,232 controls. Results Compared with 1–4 female sexual partners, men with ≥15 such partners who carried the variant T allele of rs10993994 were at increased risk for PCa (OR=1.32; 95% CI, 1.03–1.71); no association was observed in men with the CC genotype (OR=1.03; 95% CI, 0.73–1.46; p=0.05 for interaction). Similar estimates were observed for total sexual partners (any T allele OR=1.37; 95% CI, 1.07–1.77; CC genotype OR=1.11; 95% CI, 0.79–1.55; p=0.06 for interaction). Conclusions The rs10993994 genotype in the MSMB gene modifies the association between number of sexual partners and PCa risk. These findings support a hypothesized biological mechanism whereby prostatic infection/inflammation may enhance risk of PCa. PMID:24037734

The relationship between nutrition and prostate cancer: is more always better?

PubMed

Masko, Elizabeth M; Allott, Emma H; Freedland, Stephen J

2013-05-01

Prostate cancer (PCa) remains one of the most diagnosed malignancies in the world, correlating with regions where men consume more of a so-called Western-style diet. As such, there is much interest in understanding the role of lifestyle and diet on the incidence and progression of PCa. To provide a summary of published literature with regard to dietary macro- and micronutrients and PCa incidence and progression. A literature search was completed using the PubMed database for all studies published on diet and PCa in June 2012 or earlier. Primary literature and meta-analyses were given preference over other review articles when possible. The literature was reviewed on seven dietary components: carbohydrates, protein, fat and cholesterol, vegetables, vitamins and minerals, and phytochemicals. Current literature linking these nutrients to PCa is limited at best, but trends in the published data suggest consumption of carbohydrates, saturated and ω-6 fats, and certain vitamin supplements may promote PCa risk and progression. Conversely, consumption of many plant phytochemicals and ω-3 fatty acids seem to slow the risk and progression of the disease. All other nutrients seem to have no effect or data are inconclusive. A brief summary about the clinical implications of dietary interventions with respect to PCa prevention, treatment, and survivorship is provided. Due to the number and heterogeneity of published studies investigating diet and PCa, it is difficult to determine what nutrients make up the perfect diet for the primary and secondary prevention of PCa. Because diets are made of multiple macro- and micronutrients, further prospective studies are warranted, particularly those investigating the relationship between whole foods instead of a single nutritional component. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

An Estimate of the Incidence of Prostate Cancer in Africa: A Systematic Review and Meta-Analysis

PubMed Central

Aderemi, Adewale Victor; Iseolorunkanmi, Alexander; Oyedokun, Ayo; Ayo, Charles K.

2016-01-01

Background Prostate cancer (PCa) is rated the second most common cancer and sixth leading cause of cancer deaths among men globally. Reports show that African men suffer disproportionately from PCa compared to men from other parts of the world. It is still quite difficult to accurately describe the burden of PCa in Africa due to poor cancer registration systems. We systematically reviewed the literature on prostate cancer in Africa and provided a continent-wide incidence rate of PCa based on available data in the region. Methods A systematic literature search of Medline, EMBASE and Global Health from January 1980 to June 2015 was conducted, with additional search of Google Scholar, International Association of Cancer Registries (IACR), International Agency for Research on Cancer (IARC), and WHO African region websites, for studies that estimated incidence rate of PCa in any African location. Having assessed quality and consistency across selected studies, we extracted incidence rates of PCa and conducted a random effects meta-analysis. Results Our search returned 9766 records, with 40 studies spreading across 16 African countries meeting our selection criteria. We estimated a pooled PCa incidence rate of 22.0 (95% CI: 19.93–23.97) per 100,000 population, and also reported a median incidence rate of 19.5 per 100,000 population. We observed an increasing trend in PCa incidence with advancing age, and over the main years covered. Conclusion Effective cancer registration and extensive research are vital to appropriately quantifying PCa burden in Africa. We hope our findings may further assist at identifying relevant gaps, and contribute to improving knowledge, research, and interventions targeted at prostate cancer in Africa. PMID:27073921

miR-503 suppresses tumor cell proliferation and metastasis by directly targeting RNF31 in prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Jia; Liu, Xiuheng, E-mail: l_xiuheng@163.com; Wang, Min

2015-09-04

Microarray data analyses were performed to search for metastasis-associated oncogenes in prostate cancer (PCa). RNF31 mRNA expressions in tumor tissues and benign prostate tissues were evaluated. The RNF31 protein expression levels were also analyzed by western blot and immunohistochemistry. Luciferase reporter assays were used to identify miRNAs that can regulate RNF31. The effect of RNF31 on PCa progression was studied in vitro and in vivo. We found that RNF31 was significantly increased in PCa and its expression level was highly correlated with seminal vesicle invasion, clinical stage, prostate specific antigen (PSA) level, Gleason score, and BCR. Silence of RNF31 suppressed PCa cellmore » proliferation and metastasis in vitro and in vivo. miR-503 can directly regulate RNF31. Enforced expression of miR-503 inhibited the expression of RNF31 significantly and the restoration of RNF31 expression reversed the inhibitory effects of miR-503 on PCa cell proliferation and metastasis. These findings collectively indicated an oncogene role of RNF31 in PCa progression which can be regulated by miR-503, suggesting that RNF31 could serve as a potential prognostic biomarker and therapeutic target for PCa. - Highlights: • RNF31 is a potential metastasis associated gene and is associated with prostate cancer progression. • Silence of RNF31 inhibits PCa cell colony formation, migration and invasion. • RNF31 as a direct target of miR-503. • miR-503 can regulate cell proliferation, invasion and migration by targeting RNF31. • RNF31 plays an important role in PCa growth and metastasis in vivo.« less

Investigation of probabilistic principal component analysis compared to proper orthogonal decomposition methods for basis extraction and missing data estimation

NASA Astrophysics Data System (ADS)

Lee, Kyunghoon

To evaluate the maximum likelihood estimates (MLEs) of probabilistic principal component analysis (PPCA) parameters such as a factor-loading, PPCA can invoke an expectation-maximization (EM) algorithm, yielding an EM algorithm for PPCA (EM-PCA). In order to examine the benefits of the EM-PCA for aerospace engineering applications, this thesis attempts to qualitatively and quantitatively scrutinize the EM-PCA alongside both POD and gappy POD using high-dimensional simulation data. In pursuing qualitative investigations, the theoretical relationship between POD and PPCA is transparent such that the factor-loading MLE of PPCA, evaluated by the EM-PCA, pertains to an orthogonal basis obtained by POD. By contrast, the analytical connection between gappy POD and the EM-PCA is nebulous because they distinctively approximate missing data due to their antithetical formulation perspectives: gappy POD solves a least-squares problem whereas the EM-PCA relies on the expectation of the observation probability model. To juxtapose both gappy POD and the EM-PCA, this research proposes a unifying least-squares perspective that embraces the two disparate algorithms within a generalized least-squares framework. As a result, the unifying perspective reveals that both methods address similar least-squares problems; however, their formulations contain dissimilar bases and norms. Furthermore, this research delves into the ramifications of the different bases and norms that will eventually characterize the traits of both methods. To this end, two hybrid algorithms of gappy POD and the EM-PCA are devised and compared to the original algorithms for a qualitative illustration of the different basis and norm effects. After all, a norm reflecting a curve-fitting method is found to more significantly affect estimation error reduction than a basis for two example test data sets: one is absent of data only at a single snapshot and the other misses data across all the snapshots. From a numerical performance aspect, the EM-PCA is computationally less efficient than POD for intact data since it suffers from slow convergence inherited from the EM algorithm. For incomplete data, this thesis quantitatively found that the number of data missing snapshots predetermines whether the EM-PCA or gappy POD outperforms the other because of the computational cost of a coefficient evaluation, resulting from a norm selection. For instance, gappy POD demands laborious computational effort in proportion to the number of data-missing snapshots as a consequence of the gappy norm. In contrast, the computational cost of the EM-PCA is invariant to the number of data-missing snapshots thanks to the L2 norm. In general, the higher the number of data-missing snapshots, the wider the gap between the computational cost of gappy POD and the EM-PCA. Based on the numerical experiments reported in this thesis, the following criterion is recommended regarding the selection between gappy POD and the EM-PCA for computational efficiency: gappy POD for an incomplete data set containing a few data-missing snapshots and the EM-PCA for an incomplete data set involving multiple data-missing snapshots. Last, the EM-PCA is applied to two aerospace applications in comparison to gappy POD as a proof of concept: one with an emphasis on basis extraction and the other with a focus on missing data reconstruction for a given incomplete data set with scattered missing data. The first application exploits the EM-PCA to efficiently construct reduced-order models of engine deck responses obtained by the numerical propulsion system simulation (NPSS), some of whose results are absent due to failed analyses caused by numerical instability. Model-prediction tests validate that engine performance metrics estimated by the reduced-order NPSS model exhibit considerably good agreement with those directly obtained by NPSS. Similarly, the second application illustrates that the EM-PCA is significantly more cost effective than gappy POD at repairing spurious PIV measurements obtained from acoustically-excited, bluff-body jet flow experiments. The EM-PCA reduces computational cost on factors 8 ˜ 19 compared to gappy POD while generating the same restoration results as those evaluated by gappy POD. All in all, through comprehensive theoretical and numerical investigation, this research establishes that the EM-PCA is an efficient alternative to gappy POD for an incomplete data set containing missing data over an entire data set. (Abstract shortened by UMI.)

Antidiabetic and Beta Cell-Protection Activities of Purple Corn Anthocyanins

PubMed Central

Hong, Su Hee; Heo, Jee-In; Kim, Jeong-Hyeon; Kwon, Sang-Oh; Yeo, Kyung-Mok; Bakowska-Barczak, Anna M.; Kolodziejczyk, Paul; Ryu, Ok-Hyun; Choi, Moon-Ki; Kang, Young-Hee; Lim, Soon Sung; Suh, Hong-Won; Huh, Sung-Oh; Lee, Jae-Yong

2013-01-01

Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice. In addition, PCA showed efficient protection activity of pancreatic beta cell from cell death in HIT-T15 cell culture and db/db mice. The result showed that PCA had antidiabetic and beta cell-protection activities in pancreatic beta cell culture and db/db mice. PMID:24244813

Development and Flight Evaluation of an Emergency Digital Flight Control System Using Only Engine Thrust on an F-15 Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.; Fullerton, C. Gordon; Webb, Lannie Dean

1996-01-01

A propulsion-controlled aircraft (PCA) system for emergency flight control of aircraft with no flight controls was developed and flight tested on an F-15 aircraft at the NASA Dryden Flight Research Center. The airplane has been flown in a throttles-only manual mode and with an augmented system called PCA in which pilot thumbwheel commands and aircraft feedback parameters were used to drive the throttles. Results from a 36-flight evaluation showed that the PCA system can be used to safety land an airplane that has suffered a major flight control system failure. The PCA system was used to recover from a severe upset condition, descend, and land. Guest pilots have also evaluated the PCA system. This paper describes the principles of throttles-only flight control; a history of loss-of-control accidents; a description of the F-15 aircraft; the PCA system operation, simulation, and flight testing; and the pilot comments.

Cysteine Inhibits Mercury Methylation by Geobacter sulfurreducens PCA Mutant Δ omcBESTZ

DOE PAGES

Lin, Hui; Lu, Xia; Liang, Liyuan; ...

2015-04-21

For cysteine enhances Hg uptake and methylation by Geobacter sulfurreducens PCA wild type (WT) strain in short-term assays. The prevalence of this enhancement in other strains remains poorly understood. We examined the influence of cysteine concentration on time-dependent Hg(II) reduction, sorption and methylation by PCA-WT and its c-type cytochrome-deficient mutant ( omcBESTZ) in phosphate buffered saline. Without cysteine, the mutant methylated twice as much Hg(II) as the PCA-WT, whereas addition of cysteine inhibited Hg methylation, regardless of the reaction time. PCA-WT, but, exhibited both time-dependent and cysteine concentration-dependent methylation. In 144 hour assay, nearly complete sorption of the Hg(II) bymore » PCA-WT occurred in the presence of 1 mM cysteine, resulting in our highest observed methylmercury production. Moreover, the chemical speciation modeling and experimental data suggest that uncharged Hg(II) species are more readily taken up, and that this uptake is kinetic limiting, thereby affecting Hg methylation by both mutant and WT.« less

On a PCA-based lung motion model

NASA Astrophysics Data System (ADS)

Li, Ruijiang; Lewis, John H.; Jia, Xun; Zhao, Tianyu; Liu, Weifeng; Wuenschel, Sara; Lamb, James; Yang, Deshan; Low, Daniel A.; Jiang, Steve B.

2011-09-01

Respiration-induced organ motion is one of the major uncertainties in lung cancer radiotherapy and is crucial to be able to accurately model the lung motion. Most work so far has focused on the study of the motion of a single point (usually the tumor center of mass), and much less work has been done to model the motion of the entire lung. Inspired by the work of Zhang et al (2007 Med. Phys. 34 4772-81), we believe that the spatiotemporal relationship of the entire lung motion can be accurately modeled based on principle component analysis (PCA) and then a sparse subset of the entire lung, such as an implanted marker, can be used to drive the motion of the entire lung (including the tumor). The goal of this work is twofold. First, we aim to understand the underlying reason why PCA is effective for modeling lung motion and find the optimal number of PCA coefficients for accurate lung motion modeling. We attempt to address the above important problems both in a theoretical framework and in the context of real clinical data. Second, we propose a new method to derive the entire lung motion using a single internal marker based on the PCA model. The main results of this work are as follows. We derived an important property which reveals the implicit regularization imposed by the PCA model. We then studied the model using two mathematical respiratory phantoms and 11 clinical 4DCT scans for eight lung cancer patients. For the mathematical phantoms with cosine and an even power (2n) of cosine motion, we proved that 2 and 2n PCA coefficients and eigenvectors will completely represent the lung motion, respectively. Moreover, for the cosine phantom, we derived the equivalence conditions for the PCA motion model and the physiological 5D lung motion model (Low et al 2005 Int. J. Radiat. Oncol. Biol. Phys. 63 921-9). For the clinical 4DCT data, we demonstrated the modeling power and generalization performance of the PCA model. The average 3D modeling error using PCA was within 1 mm (0.7 ± 0.1 mm). When a single artificial internal marker was used to derive the lung motion, the average 3D error was found to be within 2 mm (1.8 ± 0.3 mm) through comprehensive statistical analysis. The optimal number of PCA coefficients needs to be determined on a patient-by-patient basis and two PCA coefficients seem to be sufficient for accurate modeling of the lung motion for most patients. In conclusion, we have presented thorough theoretical analysis and clinical validation of the PCA lung motion model. The feasibility of deriving the entire lung motion using a single marker has also been demonstrated on clinical data using a simulation approach.

Free-energy landscape of RNA hairpins constructed via dihedral angle principal component analysis.

PubMed

Riccardi, Laura; Nguyen, Phuong H; Stock, Gerhard

2009-12-31

To systematically construct a low-dimensional free-energy landscape of RNA systems from a classical molecular dynamics simulation, various versions of the principal component analysis (PCA) are compared: the cPCA using the Cartesian coordinates of all atoms, the dPCA using the sine/cosine-transformed six backbone dihedral angles as well as the glycosidic torsional angle chi and the pseudorotational angle P, the aPCA which ignores the circularity of the 6 + 2 dihedral angles of the RNA, and the dPCA(etatheta), which approximates the 6 backbone dihedral angles by 2 pseudotorsional angles eta and theta. As representative examples, a 10-nucleotide UUCG hairpin and the 36-nucleotide segment SL1 of the Psi site of HIV-1 are studied by classical molecular dynamics simulation, using the Amber all-atom force field and explicit solvent. It is shown that the conformational heterogeneity of the RNA hairpins can only be resolved by an angular PCA such as the dPCA but not by the cPCA using Cartesian coordinates. Apart from possible artifacts due to the coupling of overall and internal motion, this is because the details of hydrogen bonding and stacking interactions but also of global structural rearrangements of the RNA are better discriminated by dihedral angles. In line with recent experiments, it is found that the free energy landscape of RNA hairpins is quite rugged and contains various metastable conformational states which may serve as an intermediate for unfolding.

Exercise and prostate cancer: From basic science to clinical applications.

PubMed

Campos, Christian; Sotomayor, Paula; Jerez, Daniel; González, Javier; Schmidt, Camila B; Schmidt, Katharina; Banzer, Winfried; Godoy, Alejandro S

2018-06-01

Prostate cancer (PCa) is a disease of increasing medical significance worldwide. In developed countries, PCa is the most common non-skin cancer in men, and one of the leading causes of cancer-related deaths. Exercise is one of the environmental factors that have been shown to influence cancer risk. Moreover, systemic reviews and meta-analysis have suggested that total physical activity is related to a decrease in the risk of developing PCa. In addition, epidemiological studies have shown that exercise, after diagnosis, has benefits regarding PCa development, and positive outcome in patients under treatment. The standard treatment for locally advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces diverse side effects, including loss of libido, changes in body composition (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of numerous research publications showed that aerobic and/or resistance training improve patient's physical condition, such us, cardiorespiratory fitness, muscle strength, physical function, body composition, and fatigue. Therefore, exercise might counteract several ADT treatment-induced side effects. In addition of the aforementioned benefits, epidemiological, and in vitro studies have shown that exercise might decrease PCa development. Thus, physical activity might attenuate the risk of PCa and supervised exercise intervention might improve deleterious effects of cancer treatment, such as ADT side effects. This review article provides evidence indicating that exercise could complement, and potentiate, the current standard treatments for advanced PCa, probably by creating an unfavorable microenvironment that can negatively affect tumor development, and progression. © 2018 Wiley Periodicals, Inc.

IL-10 -1082 G>A: a risk for prostate cancer but may be protective against progression of prostate cancer in North Indian cohort.

PubMed

Kesarwani, Pravin; Ahirwar, Dinesh Kumar; Mandhani, Anil; Singh, Anand Narayan; Dalela, Divakar; Srivastava, Anand Narain; Mittal, Rama D

2009-06-01

Chronic intraprostatic inflammation is suspected to play a major role in the pathogenesis of prostate cancer (PCa). Polymorphisms in interleukin-10 (IL-10), a key anti-inflammatory cytokine gene can influence immune response and immune evasion of tumor cells. Its role as an anti-metastatic molecule is also well documented. Gene promoter polymorphisms in IL-10 (-1082 G>A and -819 C>T) was analyzed in 159 PCa patients and 259 healthy controls to investigate their potential association with susceptibility for PCa. Our results indicated that the heterozygous (GA) and homozygous mutant (AA) genotypes of IL-10 -1082 to be more prevalent among PCa patients in comparison to controls (GA: OR - 2.8, p = 0.011; AA: OR - 2.3, p = 0.037). More patients (92.5%) than controls (82.7%) were positive for the A allele (GA + AA: OR - 2.6, p = 0.015). We observed lower frequency of T(-819)-G(-1082) haplotype in patients without bone metastasis (4.4%, OR - 0.30, p = 0.019) in comparison to PCa patients with bone metastasis (12.6%). Our results support the emerging hypothesis that genetically determined immune activity may play a role in the pathophysiology of PCa. Our findings of high producer of IL-10 -1082 variants suggest initiation of PCa. Future studies in large cohort of different ethnicity PCa groups are warranted to establish definite associations with other cytokine gene polymorphisms.

Cerebral blood flow regulation during cognitive tasks

PubMed Central

Sorond, Farzaneh A.; Schnyer, D.M.; Serrador, J.M.; Milberg, W.P.; Lipsitz, L.A.

2008-01-01

Aging is associated with frontal subcortical microangiopathy and executive cognitive dysfunction, suggesting that elderly individuals may have impaired metabolic activation of cerebral blood flow to the frontal lobes. We used transcranial Doppler (TCD) ultrasound to examine the cerebral blood flow response to executive control and visual tasks in the anterior and posterior cerebral circulations and to determine the effects of healthy aging on cerebral blood flow regulation during cognitive tasks. Continuous simultaneous anterior cerebral artery (ACA) and posterior cerebral artery (PCA) blood flow velocities (BFVs) and mean arterial pressure (MAP) were measured in response to word stem completion (WSC) and a visual search (VS) task in 29 healthy subjects (14 young, 30 ± 1.5 years; 15 old, 74 ± 1.4 years). We found that: (1) ACA and PCA blood flow velocities are both significantly increased during WSC and VS cognitive tasks, (2) ACA and PCA activations were task specific in our young volunteers, with ACA > PCA BFV during the WSC task and PCA > ACA BFV during the VS task, (3) while healthy elderly subjects also had PCA > ACA BFV during the VS task, they did not have ACA > PCA activation during the WSC task, and (4) healthy elderly subjects tend to have overall greater increases in BFV during both cognitive tasks. We conclude that TCD can be used to monitor cerebrovascular hemodynamics during the performance of cognitive tasks. Our data suggest that there is differential blood flow increase in the ACA and PCA in young versus elderly subjects during cognitive tasks. PMID:18387547

Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential

PubMed Central

Almeida, Mafalda; Costa, Vera L; Costa, Natália R; Ramalho-Carvalho, João; Baptista, Tiago; Ribeiro, Franclim R; Paulo, Paula; Teixeira, Manuel R; Oliveira, Jorge; Lothe, Ragnhild A; Lind, Guro E; Henrique, Rui; Jerónimo, Carmen

2014-01-01

Epigenetic alterations are common in prostate cancer (PCa) and seem to contribute decisively to its initiation and progression. Moreover, aberrant promoter methylation is a promising biomarker for non-invasive screening. Herein, we sought to characterize EFEMP1 as biomarker for PCa, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP1 was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by qMSP. Expression analysis of EFEMP1 and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on EFEMP1 transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of EFEMP1’s role in PCa development. EFEMP1 methylation assay discriminated PCa from normal prostate tissue (NPT; P < 0.001, Kruskall–Wallis test) and renal and bladder cancers (96% sensitivity and 98% specificity). EFEMP1 transcription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that EFEMP1 de novo expression reduces malignant phenotype of PCa cells. EFEMP1 promoter methylation is prevalent in PCa and accurately discriminates PCa from non-cancerous prostate tissues and other urological neoplasms. This epigenetic alteration occurs early in prostate carcinogenesis and, in association with histone deacetylation, progressively leads to gene down-regulation, fostering cell proliferation, invasion and evasion of apoptosis. PMID:25211630

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report.

PubMed

Francio, Vinicius T; Boesch, Ron; Tunning, Michael

2015-03-01

Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient's perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option.

Digital map of posterior cerebral artery infarcts associated with posterior cerebral artery trunk and branch occlusion.

PubMed

Phan, Thanh G; Fong, Ashley C; Donnan, Geoffrey; Reutens, David C

2007-06-01

Knowledge of the extent and distribution of infarcts of the posterior cerebral artery (PCA) may give insight into the limits of the arterial territory and infarct mechanism. We describe the creation of a digital atlas of PCA infarcts associated with PCA branch and trunk occlusion by magnetic resonance imaging techniques. Infarcts were manually segmented on T(2)-weighted magnetic resonance images obtained >24 hours after stroke onset. The images were linearly registered into a common stereotaxic coordinate space. The segmented images were averaged to yield the probability of involvement by infarction at each voxel. Comparisons were made with existing maps of the PCA territory. Thirty patients with a median age of 61 years (range, 22 to 86 years) were studied. In the digital atlas of the PCA, the highest frequency of infarction was within the medial temporal lobe and lingual gyrus (probability=0.60 to 0.70). The mean and maximal PCA infarct volumes were 55.1 and 128.9 cm(3), respectively. Comparison with published maps showed greater agreement in the anterior and medial boundaries of the PCA territory compared with its posterior and lateral boundaries. We have created a probabilistic digital atlas of the PCA based on subacute magnetic resonance scans. This approach is useful for establishing the spatial distribution of strokes in a given cerebral arterial territory and determining the regions within the arterial territory that are at greatest risk of infarction.

The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats.

PubMed

Ma, Feng-Wei; Deng, Qing-Fang; Zhou, Xin; Gong, Xiao-Jian; Zhao, Yang; Chen, Hua-Guo; Zhao, Chao

2016-03-24

In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study.

Determination of tumor cell procoagulant activity by Sonoclot analysis in whole blood.

PubMed

Amirkhosravi, A; Biggerstaff, J P; Warnes, G; Francis, D A; Francis, J L

1996-12-01

Coagulation activation in cancer may be due to expression of procoagulant activity (PCA) by tumor cells. Some PCA activate coagulation, while others influence platelet aggregation. Thus, clotting time assessments of PCA may not reflect the potential for hypercoagulability. We therefore studied the effect of various malignant and non-malignant cells on whole blood coagulation using the Sonoclot Analyzer. Five human (HT29 colon, J82 bladder, MCF-7 breast, BT-474 breast and A375 malignant melanoma) and three rodent (MC28, WEHI-164 and Neuro2a) cell lines were used. Rat thymocytes and peritoneal macrophages and human endotoxin-stimulated mononuclear cells and umbilical vein endothelial cells (HUVEC) were used as non-malignant controls. All tumor cells markedly shortened the recalcification time of citrated blood and the most potent (HT29 and J82) also increased clot rate (P < 0.01). The breast cancer cells MCF-7 and BT-474 expressed only weak PCA and did not affect clotting rate. None of the non-malignant cells significantly affected clotting time or rate in whole blood. J82 and HT29 cells grown in serum-rich media shortened the recalcification time of both normal and FVII-deficient plasmas. However, cells grown in serum-free conditions had significantly less PCA in FVII-deficient plasma. We conclude that the Sonoclot Analyzer is useful for determining cellular PCA; significant PCA is a feature of malignant cells and cells grown in medium containing serum supplements cannot be reliably evaluated for PCA.

Heterogeneity of DNA methylation in multifocal prostate cancer.

PubMed

Serenaite, Inga; Daniunaite, Kristina; Jankevicius, Feliksas; Laurinavicius, Arvydas; Petroska, Donatas; Lazutka, Juozas R; Jarmalaite, Sonata

2015-01-01

Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (≥75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p < 0.001). Hierarchical cluster analysis revealed a divergent methylation profile of paired PCa foci, while the foci from separate cases with biochemical recurrence showed similar methylation profile and the highest mean levels of DNA methylation. Our findings suggest that PCa tissue is heterogeneous, as between paired foci differences in DNA methylation status were found. Common epigenetic profile of recurrent tumors can be inferred from our data.

Decreased expression of serine protease inhibitor family G1 (SERPING1) in prostate cancer can help distinguish high-risk prostate cancer and predicts malignant progression.

PubMed

Peng, Shengmeng; Du, Tao; Wu, Wanhua; Chen, Xianju; Lai, Yiming; Zhu, Dingjun; Wang, Qiong; Ma, Xiaoming; Lin, Chunhao; Li, Zean; Guo, Zhenghui; Huang, Hai

2018-06-11

The aim of this study was to investigate the associations of serine proteinase inhibitor family G1 (SERPING1) down-regulation with poor prognosis in patients with prostate cancer (PCa). Furthermore, we aim to find more novel and effective PCa molecular markers to provide an early screening of PCa, distinguish patients with aggressive PCa, predict the prognosis, or reduce the economic burden of PCa. SERPING1 protein expression in both human PCa and normal prostate tissues was detected by immunohistochemical staining, which intensity was analyzed in association with clinical pathological parameters such Gleason score, pathological grade, clinical stage, tumor stage, lymph node metastasis, and distant metastasis. Moreover, we used The Cancer Genome Atlas (TCGA) Database, Taylor Database, and Oncomine dataset to validate our immunohistochemical results and investigated the value of SERPING1 in PCa at mRNA level. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the relationship between SERPING1 and prognosis of patients with PCa. The outcome showed that SERPING1 was expressed mainly in cytoplasm of grand cells of prostate tissue and was significantly expressed less in PCa (P<0.001). Furthermore, in the tissue microarray of our samples, decreasing expression of SERPING1 was correlated with the higher Gleason score (P = 0.004), the higher pathological grade (P = 0.01) and the advanced tumor stage (P = 0.005) at protein level. In TCGA dataset and Taylor Dataset, low-expressed SERPING1 was correlated with the younger patient (P = 0.02 in TCGA, P = 0.044 in Taylor) and the higher Gleason score (P = 0.019 in TCGA, P<0.001 in Taylor) at mRNA level. Kaplan-Meier analysis revealed that the lower mRNA of SERPING1 predicted lower overall survivals (P = 0.027 in TCGA), lower disease-free survival (P = 0.029) and lower biochemical recurrence-free survival (P = 0.011 in Taylor). Data from Oncomine database shown that SERPING1 low expression implying higher malignancy of prostate lesions. Using multivariate analysis, we also found that SERPING1 expression was independent prognostic marker of poor disease-free survival and biochemical recurrence-free survival. SERPING1 may play an important role in PCa and can be serve as a novel marker in diagnosis and prognostic prediction in PCa. In addition, levels of SERPING1 can help identify low-risk prostate to provide reference for patients with PCa to accept active surveillance and reduce overtreatment. Copyright © 2018 Elsevier Inc. All rights reserved.

The oncogenic role of the In1-ghrelin splicing variant in prostate cancer aggressiveness.

PubMed

Hormaechea-Agulla, Daniel; Gahete, Manuel D; Jiménez-Vacas, Juan M; Gómez-Gómez, Enrique; Ibáñez-Costa, Alejandro; L-López, Fernando; Rivero-Cortés, Esther; Sarmento-Cabral, André; Valero-Rosa, José; Carrasco-Valiente, Julia; Sánchez-Sánchez, Rafael; Ortega-Salas, Rosa; Moreno, María M; Tsomaia, Natia; Swanson, Steve M; Culler, Michael D; Requena, María J; Castaño, Justo P; Luque, Raúl M

2017-08-29

The Ghrelin-system is a complex, pleiotropic family composed of several peptides, including native-ghrelin and its In1-ghrelin splicing variant, and receptors (GHSR 1a/b), which are dysregulated in various endocrine-related tumors, where they associate to pathophysiological features, but the presence, functional role, and mechanisms of actions of In1-ghrelin splicing variant in prostate-cancer (PCa), is completely unexplored. Herein, we aimed to determine the presence of key ghrelin-system components (native-ghrelin, In1-ghrelin, GHSR1a/1b) and their potential pathophysiological role in prostate cancer (PCa). In1-ghrelin and native-ghrelin expression was evaluated by qPCR in prostate tissues from patients with high PCa-risk (n = 52; fresh-tumoral biopsies), and healthy-prostates (n = 12; from cystoprostatectomies) and correlated with clinical parameters using Spearman-test. In addition, In1-ghrelin and native-ghrelin was measured in plasma from an additional cohort of PCa-patients with different risk levels (n = 30) and control-healthy patients (n = 20). In vivo functional (proliferation/migration) and mechanistic (gene expression/signaling-pathways) assays were performed in PCa-cell lines in response to In1-ghrelin and native-ghrelin treatment, overexpression and/or silencing. Finally, tumor progression was monitored in nude-mice injected with PCa-cells overexpressing In1-ghrelin, native-ghrelin and empty vector (control). In1-ghrelin, but not native-ghrelin, was overexpressed in high-risk PCa-samples compared to normal-prostate (NP), and this expression correlated with that of PSA. Conversely, GHSR1a/1b expression was virtually absent. Remarkably, plasmatic In1-ghrelin, but not native-ghrelin, levels were also higher in PCa-patients compared to healthy-controls. Furthermore, In1-ghrelin treatment/overexpression, and to a much lesser extent native-ghrelin, increased aggressiveness features (cell-proliferation, migration and PSA secretion) of NP and PCa cells. Consistently, nude-mice injected with PC-3-cells stably-transfected with In1-ghrelin, but not native-ghrelin, presented larger tumors. These effects were likely mediated by ERK1/2-signaling activation and involved altered expression of key oncogenes/tumor suppressor genes. Finally, In1-ghrelin silencing reduced cell-proliferation and PSA secretion from PCa cells. Altogether, our results indicate that In1-ghrelin levels (in tissue) and circulating levels (in plasma) are increased in PCa where it can regulate key pathophysiological processes, thus suggesting that In1-ghrelin may represent a novel biomarker and a new therapeutic target in PCa.

Meta-analysis of CDKN2A methylation to find its role in prostate cancer development and progression, and also to find the effect of CDKN2A expression on disease-free survival (PRISMA).

PubMed

Cao, Zipei; Wei, Lijuan; Zhu, Weizhi; Yao, Xuping

2018-03-01

Reduction of cyclin-dependent kinase inhibitor 2A (CDKN2A) (p16 and p14) expression through DNA methylation has been reported in prostate cancer (PCa). This meta-analysis was conducted to assess the difference of p16 and p14 methylation between PCa and different histological types of nonmalignant controls and the correlation of p16 or p14 methylation with clinicopathological features of PCa. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, articles were searched in PubMed, Embase, EBSCO, Wanfang, and CNKI databases. The strength of correlation was calculated by the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Trial sequential analysis (TSA) was used to estimate the required population information for significant results. A total of 20 studies published from 1997 to 2017 were identified in this meta-analysis, including 1140 PCa patients and 530 cases without cancer. Only p16 methylation in PCa was significantly higher than in benign prostatic lesions (OR = 4.72, P = .011), but had a similar level in PCa and adjacent tissues or high-grade prostatic intraepithelial neoplasias (HGPIN). TSA revealed that this analysis on p16 methylation is a false positive result in cancer versus benign prostatic lesions (the estimated required information size of 5116 participants). p16 methylation was not correlated with PCa in the urine and blood. Besides, p16 methylation was not linked to clinical stage, prostate-specific antigen (PSA) level, and Gleason score (GS) of patients with PCa. p14 methylation was not correlated with PCa in tissue and urine samples. No correlation was observed between p14 methylation and clinical stage or GS. CDKN2A mutation and copy number alteration were not associated with prognosis of PCa in overall survival and disease-free survival. CDKN2A expression was not correlated with the prognosis of PCa in overall survival (492 cases) (P > .1), while CDKN2A expression was significantly associated with a poor disease-free survival (P < .01). CDKN2A methylation may not be significantly associated with the development, progression of PCa. Although CDKN2A expression had an unfavorable prognosis in disease-free survival. More studies are needed to confirm our results.

Analysis of the principal component algorithm in phase-shifting interferometry.

PubMed

Vargas, J; Quiroga, J Antonio; Belenguer, T

2011-06-15

We recently presented a new asynchronous demodulation method for phase-sampling interferometry. The method is based in the principal component analysis (PCA) technique. In the former work, the PCA method was derived heuristically. In this work, we present an in-depth analysis of the PCA demodulation method.

Nonlinear Principal Components Analysis: Introduction and Application

ERIC Educational Resources Information Center

Linting, Marielle; Meulman, Jacqueline J.; Groenen, Patrick J. F.; van der Koojj, Anita J.

2007-01-01

The authors provide a didactic treatment of nonlinear (categorical) principal components analysis (PCA). This method is the nonlinear equivalent of standard PCA and reduces the observed variables to a number of uncorrelated principal components. The most important advantages of nonlinear over linear PCA are that it incorporates nominal and ordinal…