Role of human nucleoside transporters in pancreatic cancer and chemoresistance

The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5%changing minimally over the past decades and future projections predicting it developing into the second leading cause of cancer related mortality within the next decade.Investigations into the mechanisms of pancreatic cancer development,progression and acquired chemoresistance have been constant for the past few decades,thus resulting in the identification of human nucleoside transporters and factors affecting cytotoxic uptake via said transporters.This review summaries the aberrant expression and role of human nucleoside transports in pancreatic cancer,more specifically human equilibrative nucleoside transporter 1/2(hENT1,hENT2),and human concentrative nucleoside transporter 1/3(hCNT1,hCNT3),while briefly discussing the connection and importance between these nucleoside transporters and mucins that have also been identified as being aberrantly expressed in pancreatic cancer.The review also discusses the incidence,current diagnostic techniques as well as the current therapeutic treatments for pancreatic cancer.Furthermore,we address the importance of chemoresistance in nucleoside analogue drugs,in particular,gemcitabine and we discuss prospective therapeutic treatments and strategies for overcoming acquired chemoresistance in pancreatic cancer by the enhancement of human nucleoside transporters as well as the potential targeting of mucins using a combination of mucolytic compounds with cytotoxic agents.

THE RESEARCH OF RHEOLOGICAL PROPERTIES OF STOWING SLURRY WITH HIGH-WATER MATERIALSOLIDIFYING TAILINGS

High-water material, tailings from goldmine and water are mixed into a new slurry.Testing of rheological properties of stowing slurries A and B is made to determine type and rheological parameters of the slurry. The main factors influencing rheological properties of the slurry are analyzed and the rational concentration and empirical resistance calculating formula of pipe line transportation are presented.

Analysis of High Concentration Spikes Appearing in Mass Plume in Nearly Homogeneous Turbulent Flow Based on the PDF Transport Equation

To evaluate the pollutant dispersion in background turbulent flows, most researches focus on statistical variation of concentrations or its fluctuations. However, those time-averaged quantities may be insufficient for risk assessment, because there emerge many high-intensity pollutant areas in the instantaneous concentration field. In this study, we tried to estimate the frequency of appearance of the high concentration areas in a turbulent flow based on the Probability Density Function (PDF) of concentration. The high concentration area was recognized by two conditions based on the concentration and the concentration gradient values. We considered that the estimation equation for the frequency of appearance of the recognized areas consisted of two terms based on each condition. In order to represent the two terms with physical quantities of velocity and concentration fields, simultaneous PIV (Particle Image Velocimetry) and PLIF (Planar Laser-Induced Fluorescence) measurement and PLIF time-serial measurement were performed in a quasi-homogeneous turbulent flow. According to the experimental results, one of the terms, related to the condition of the concentration, was found to be represented by the concentration PDF, while the other term, by the streamwise mean velocity and the integral length scale of the turbulent flow. Based on the results, we developed an estimation equation including the concentration PDF and the flow features of mean velocity and integral scale of turbulence. In the area where the concentration PDF was a Gaussian one, the difference between the frequencies of appearance estimated by the equation and calculated from the experimental data was within 25%, which showed good accuracy of our proposed estimation equation. Therefore, our proposed equation is feasible for estimating the frequency of appearance of high concentration areas in a limited area in turbulent mass diffusion.

A simulation study of airborne wear particles from laboratory wheel-rail contacts

Laboratory measurements of airborne particles from sliding contacts are often performed using a tri- bometer located in a ventilation chamber. Although knowledge of particle transport behavior inside the chamber is required because it can influence the analysis of measurements, this knowledge is lacking. A numerical model was built based on the same geometry as a pin-on-disc measurement system to explain particle transport behavior inside the chamber and to determine the deviation between real amounts of generated and measured particles at the outlet. The effect of controlled flow conditions on the airflow pattern and particle transport inside the chamber was studied for different experimental conditions. Cal- culations show that a complex airflow pattern is formed by the spinning disc, and that it differs for each rotational speed. Simulation results reveal that particle transport in the chamber is governed mainly by the airflow pattern. The deposition velocity in the chamber was estimated and the possibility that part of the generated particles would remain in the chamber was studied. This led to an approximate estima- tion of particle loss rate. A comparison between experimental and simulated results with respect to the particle mass flow rate close to the outlet yields a reference factor of 0.7, which provides an indication of the difference between measured and real values.

Development of gemcitabine-resistant patient-derived xenograft models of pancreatic ductal adenocarcinoma

Aim:Gemcitabine is a frontline agent for locally-advanced and metastatic pancreatic ductal adenocarcinoma(PDAC),but neither gemcitabine alone nor in combination produces durable remissions of this tumor type.We developed three PDAC patient-derived xenograft(PDX)models with gemcitabine resistance(gemR)acquired in vivo,with which to identify mechanisms of resistance relevant to drug exposure in vivo and to evaluate novel therapies.Methods:Mice bearing independently-derived PDXs received 100 mg/kg gemcitabine once or twice weekly.Tumors initially responded,but regrew on treatment and were designated gemR.We used immunohistochemistry to compare expression of proteins previously associated with gemcitabine resistance[ribonucleotide reductase subunit M1(RRM1),RRM2,human concentrative nucleoside transporter 1(hCNT1),human equilibrative nucleoside transporter 1(hENT1),cytidine deaminase(CDA),and deoxycytidine kinase(dCK)]in gemR and respective gemcitabine-naïve parental tumors.Results:Parental and gemR tumors did not differ in tumor cell morphology,amount of tumor-associated stroma,or expression of stem cell markers.No consistent pattern of expression of the six gemR marker proteins was observed among the models.Increases in RRM1 and CDA were consistent with in vitro-derived gemR models.However,rather than the expected decreases of hCNT1,hENT1,and dCK,gemR tumors expressed no change in or higher levels of these gemR marker proteins than parental tumors.Conclusion:These models are the first PDAC PDX models with gemcitabine resistance acquired in vivo.The data indicate that mechanisms identified in models with resistance acquired in vitro are unlikely to be the predominant mechanisms when resistance is acquired in vivo.Ongoing work focuses on characterizing unidentified mechanisms of gemR and on identifying agents with anti-tumor efficacy in these gemR models。

Analysis of minimum specific energy consumption and optimal transport concentration of slurry pipeline transport systems

Slurry pipeline transport is widely used in several industrial processes.Calculating the specific power consumption(SPC)and determining the best working conditions are important for the design and operation of transportation systems.Based on the Shanghai Jiao Tong University high-concentration multi-sized slurry pressure drop(SJTU-HMSPD)pipeline-resistance-calculation model,the SJTU-SPC model for calculating the power required to transport a unit volume of solid materials over a unit pipeline length is established for a slurry transport system.The said system demonstrates a uniformity coefficient in the 1.26–7.98 range,median particle size of 0.075–4 mm,particle volume concentration of 10–60%,and pipeline diameter of 0.203–0.8 m.The results obtained were successfully verified against existing experimental data.The influence of parameters,such as particle-gradation uniformity coefficient,median particle size,pipe diameter,and particle volume concentration,on the SPC were analysed.The results revealed that the greater is the uniformity coefficient,the smaller is the minimum specific energy consumption and the larger the optimal transport concentration for a constant,median particle size slurry.As observed,the optimal transport concentration for broad-graded sand equalled approximately 48%.These results supplement the conclusions of existing research,indicating that the optimal transport concentration is approximately 30%and provides theoretical support for high concentration transportation of broad graded slurry.