Theoretical Analysis for Using Pulsed Heating Power in Magnetic Hyperthermia Therapy of Breast Cancer

In magnetic hyperthermia, magnetic nanoparticles (MNPs) are used to generate heat in an alternating magnetic field to destroy cancerous cells. This field can be continuous or pulsed. Although a large amount of research has been devoted to studying the efficiency and side effects of continuous fields, little attention has been paid to the use of pulsed fields. In this simulation study, Fourier’s law and COMSOL software have been utilized to identify the heating power necessary for treating breast cancer under blood flow and metabolism to obtain the optimized condition among the pulsed powers for thermal ablation. The results showed that for small source diameters (not larger than 4 mm), pulsed powers with high duties were more effective than continuous power. Although by increasing the source domain the fraction of damage caused by continuous power reached the damage caused by the pulsed powers, it affected the healthy tissues more (at least two times greater) than the pulsed powers. Pulsed powers with high duty (0.8 and 0.9) showed the optimized condition and the results have been explained based on the Arrhenius equation. Utilizing the pulsed powers for breast cancer treatment can potentially be an efficient approach for treating breast tumors due to requiring lower heating power and minimizing side effects to the healthy tissues.     

Study on radiation performances of dipole antenna with diamond‐structure EBG substrate fabricated by 3D printing technique

In order to improve antenna radiation performances, a dipole antenna with 3D diamond‐structure electromagnetic band‐gap (EBG) substrate is analyzed and its transmission performances are investigated. The diamond‐structure EBG substrate was fabricated with aluminum oxide ceramic by 3D printing technique and sintering process, and its band‐gap measured by a transmission‐reflection method was between 9 and 11.5 GHz, with a maximal loss of ?50 dB at 9.9 GHz. The radiation frequency of designed dipole antenna corresponded to the frequency of strongest reflection of the EBGs. Comparison of E‐plane radiation patterns of dipole antenna without substrate, dipole antenna with a common ceramic substrate and dipole antenna with EBGs showed that gain of dipole antenna with EBGs was 3 dB higher than that of dipole antenna with a common ceramic substrate and 5 dB higher than that of dipole antenna without substrate, thus the gain was improved by 3.2 times. Moreover, the radiation pattern of dipole antenna with EBGs was smoother, which showed that EBGs can effectively suppress propagation of surface waves. In addition, the main lobe width was reduced, thus antenna directivity was improved.     

可溶性Fas与VEGF及TIMP-1表达在乳腺癌淋巴结转移中的相互关系

目的通过对乳腺癌可溶性Fas浓度与血管内皮生长因子(VEGF)及金属蛋白酶抑制物(TIMP-1)表达之间关系的分析,探讨患者血清中sFas浓度改变对乳腺癌细胞生长、浸润和转移的影响。方法通过S-P免疫组化法和ELISA法,分别检测乳腺癌细胞VEGF和TIMP-1表达及血清sFas浓度,结合VEGF、TIMP-1与乳腺癌临床病理参数,分析浸润、淋巴结转移乳腺癌中VEGF、TIMP-1表达失衡与血清sFas浓度之间的关系。结果①VEGF阳性表达与乳腺癌淋巴结转移呈显著相关,VEGF阳性的肿瘤有淋巴结转移率为56%,明显高于VEGF阳性的肿瘤无淋巴结转移率(7%)。随着乳腺癌TNM分期和组织学分级的进展,VEGF阳性表达率逐渐增加,呈正相关。TIMP-1阳性表达与肿瘤淋巴结转移明显相关。随着TNM分期和组织学分级的进展,TIMP-1阳性表达率逐渐降低,呈负相关。②VEGF阳性表达而TIMP-1阴性表达组发生乳腺癌浸润和淋巴结转移率及血清sFas浓度最高,VEGF阴性表达而TIMP-1阳性表达组发生淋巴结转移率及血清sFas浓度最低,两组比较差异有极显著意义。结论sFas与VEGF及TIMP-1表达之间存在着反馈机理以及相互激活的密切关系。sFas浓度可以间接地反映基质金属蛋白酶(MMPs)和VEGF的表达情况,sFas在乳腺癌中的浓度变化可以反映乳腺癌的生长、局部浸润和转移。     

Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

Compared to conventional hyperthermia that is limited by low selectivity and severe side effects,nano-enabled hyperthermia yields great potentials to tackle these limitations for cancer treatment.Another major advance is the observation of immunological responses associated with nano-enabled hyperthermia,which introduces a new avenue,allowing a potential paradigm shift from the acutely effective and cytotoxicity-centric response to the next-phase discovery,i.e.,long-lasting and/or systemic anti-tumor immunity.This perspective first discusses the temperature-gradient and the spatially-structured immunological landscape in solid tumors receiving nano-enabled hyperthermia.This includes the discussion about underlying mechanism such as immunogenic cell death,which initiates a profound immunological chain reaction.In order to propagate the immune activation as a viable therapeutic principle,we further discussed the tumor type-specific complexity in the immunological tumor microenvironment,including the creative design of nano-enabled combination therapy to synergize with nano-enabled hyperthermia.     

Distribution of mono‐ and di‐methacrylic monomers in SBS block copolymer and its influence on the photopolymerization process

Persoz hardness measurements and the analysis of the temperature dependence of the storage modulus (E′) for SBS di‐ and tetrafunctional methacrylic monomer systems were carried out to determine the distribution of the monomers in the domains or phases of the SBS block copolymer, as well as the aggregation state of each system. The forces of attraction between the monomer and the phases or domains in the matrix (similar solubility parameters with appreciable dipole‐dipole and hydrogen bonding interactions) were determinant as for the monomer distribution. The influence of these structural factors on the kinetic parameters of the photoinitiated polymerization of di‐ and tetrafunctional methacrylic monomers in the SBS matrix was studied. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 163–168, 2005     

Simulations of Bubble Column Reactors Using a Volume of Fluid Approach: Effect of Air Distributor

Two‐ and three‐dimensional numerical simulations have been performed on a laboratory scale bubble column reactor using a volume‐of‐fluid approach. The effect of hole‐size and superficial gas velocity on the bubble size distribution and their trajectories has been investigated on a 20 cm diameter and 1 m high cylindrical reactor. All simulations were performed in a transient manner using a FLUENT solver. Surface tension between two phases has been modelled as a body force with a constant value. Turbulence was modelled using the k‐? turbulence approach. A comparison between simulation predictions and the reported experimental studies has shown a good agreement.     

Prediction of orthotropic mechanical properties of plain‐weave composites with matrix voids using unit cells at multi‐scales

A numerical procedure for predicting the orthotropic mechanical properties of plain‐weave composites with matrix voids through a combined approach of the representative volume element method and finite element analyses is presented. The representative volume element method was implemented using two unit cells established at different length scales with equation boundary conditions. By considering the presence of randomly scattered voids throughout the matrix induced during the manufacturing process, it was assumed in the simulation that the spatial distribution of matrix voids is completely random. The procedure was exemplified with a glass fiber‐reinforced (plain‐weave fabric) epoxy composite with matrix voids. Sensitivity studies were conducted to quantify the influence of fiber volume fraction and mechanical properties of the constituent phases on the orthotropic mechanical properties of the composite. The numerical procedure, which can be implemented in ABAQUS, is an efficient tool for guiding the design of plain‐weave composites at materials level and also provides effective properties of such composites for the design optimization of engineering structures made of such composite materials. © 2012 Society of Chemical Industry     

A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

Chemical exchange saturation transfer (CEST) MRI is a promising molecular imaging tool which allows the specific detection of metabolites that contain exchangeable amide, amine, and hydroxyl protons. Decades of development have progressed CEST imaging from an initial concept to a clinical imaging tool that is used to assess tumor metabolism. The first translation efforts involved brain imaging, but this has now progressed to imaging other body tissues. In this review, we summarize studies using CEST MRI to image a range of tumor types, including breast cancer, pelvic tumors, digestive tumors, and lung cancer. Approximately two thirds of the published studies involved breast or pelvic tumors which are sites that are less affected by body motion. Most studies conclude that CEST shows good potential for the differentiation of malignant from benign lesions with a number of reports now extending to compare different histological classifications along with the effects of anti-cancer treatments. Despite CEST being a unique ‘label-free’ approach with a higher sensitivity than MR spectroscopy, there are still some obstacles for implementing its clinical use. Future research is now focused on overcoming these challenges. Vigorous ongoing development and further clinical trials are expected to see CEST technology become more widely implemented as a mainstream imaging technology.     

Development of a Solvent Extraction Model for Process Tests in Short Residence Time Centrifugal Contactors

A computer program has been developed for optimization and modelling of counter–current solvent extraction processes. The distribution between the phases is calculated by either D-ratio functions or by a novel kinetic model for the transfer between the phases. The kinetic model is important to use when slow extraction kinetics yields D-ratios far from equilibrium. Transfer rate data was investigated in a single stage centrifugal contactor, modified for internal recirculation of the phases. Using this methodology a demonstration process for the recovery of minor actinides in a counter–current centrifugal contactor system using CyMe₄-BTBP was modelled with excellent agreement towards the experimental values.     

Optimization of sub-ambient separation systems with embedded cubic equation of state thermodynamic models and complementarity constraints

A previously developed equation-based flowsheet optimization framework is extended and applied to design sub-ambient separation systems for oxy-fired coal power systems with carbon capture. Unlike most commercial flowsheet design and optimization tools, the proposed methods use exact derivatives and large-scale nonlinear programming algorithms to solve large flowsheet design problems with many degrees of freedom, including the simultaneous design of air separation units (ASUs) and their accompanying multistream heat exchangers. Emphasis is placed on additional model improvements regarding thermodynamic calculations. In order to maintain differentiability, complementarity constraints are used to model switches, including vanishing and reappearing phases. Nevertheless, these complementarity constraints may construct trivial phase equilibrium solutions, and a procedure based on embedded bubble and dew points calculations is proposed to avoid them. Furthermore, additional complementarity constraints for the cubic equation of state model are proposed to ensure correct phase identification in the supercritical region. Finally, the efficacy of these new models are demonstrated by optimization of the CO₂ processing unit and compression train for an oxy-fired power plant.     

Studies on anti-tumor and antimetastatic activities of fullerenol in a mouse breast cancer model

The purpose was to examine the anti-tumor and antimetastatic activities of fullerenol and their related mechanisms. Thirty EMT-6 tumor-bearing mice were injected intraperitoneally with 0.1 ml saline or 0.1 ml saline containing fullerenol C₆₀(OH)₂₀ (0.08 and 0.4 mg/ml) daily for 16 days. Using tumor tissues, we investigated imbalances in the oxidative defense system and the expression of several angiogenesis factors. C₆₀(OH)₂₀ exhibits anti-tumor and antimetastatic activities in EMT-6 breast cancer metastasis model. Treatment with C₆₀(OH)₂₀ was found to modulate oxidative stress significantly. The expression of several angiogenesis factors was reduced in tumor tissues after treatment with fullerenol. Importantly, CD31 (also known as PECAM-1, platelet endothelial cell adhesion molecule) expression and vessel density were markedly reduced in tumors from fullerenol-treated mice compared with controls. Modulation of oxidative stress in tumor tissues, inhibition of the formation of angiogenesis factors, and subsequent reduction in tumor vessel density and the nutrient supply to tumor cells could be important mechanisms by which fullerenol aggregates inhibit tumor growth and suppress carcinoma metastasis in vivo.     

Fluorescent magnetic nanoparticle-labeled mesenchymal stem cells for targeted imaging and hyperthermia therapy of in vivo gastric cancer

How to find early gastric cancer cells in vivo is a great challenge for the diagnosis and therapy of gastric cancer. This study is aimed at investigating the feasibility of using fluorescent magnetic nanoparticle (FMNP)-labeled mesenchymal stem cells (MSCs) to realize targeted imaging and hyperthermia therapy of in vivo gastric cancer. The primary cultured mouse marrow MSCs were labeled with amino-modified FMNPs then intravenously injected into mouse model with subcutaneous gastric tumor, and then, the in vivo distribution of FMNP-labeled MSCs was observed by using fluorescence imaging system and magnetic resonance imaging system. After FMNP-labeled MSCs arrived in local tumor tissues, subcutaneous tumor tissues in nude mice were treated under external alternating magnetic field. The possible mechanism of MSCs targeting gastric cancer was investigated by using a micro-multiwell chemotaxis chamber assay. Results show that MSCs were labeled with FMNPs efficiently and kept stable fluorescent signal and magnetic properties within 14 days, FMNP-labeled MSCs could target and image in vivo gastric cancer cells after being intravenously injected for 14 days, FMNP-labeled MSCs could significantly inhibit the growth of in vivo gastric cancer because of hyperthermia effects, and CCL19/CCR7 and CXCL12/CXCR4 axis loops may play key roles in the targeting of MSCs to in vivo gastric cancer. In conclusion, FMNP-labeled MSCs could target in vivo gastric cancer cells and have great potential in applications such as imaging, diagnosis, and hyperthermia therapy of early gastric cancer in the near future.     

Superparamagnetic Hyperthermia Study with Cobalt Ferrite Nanoparticles Covered with γ-Cyclodextrins by Computer Simulation for Application in Alternative Cancer Therapy

In this paper, we present a study by computer simulation on superparamagnetic hyperthermia with CoFe₂O₄ ferrimagnetic nanoparticles coated with biocompatible gamma-cyclodextrins (γ-CDs) to be used in alternative cancer therapy with increased efficacy and non-toxicity. The specific loss power that leads to the heating of nanoparticles in superparamagnetic hyperthermia using CoFe₂O₄–γ-CDs was analyzed in detail depending on the size of the nanoparticles, the thickness of the γ-CDs layer on the nanoparticle surface, the amplitude and frequency of the alternating magnetic field, and the packing fraction of nanoparticles, in order to find the proper conditions in which the specific loss power is maximal. We found that the maximum specific loss power was determined by the Brown magnetic relaxation processes, and the maximum power obtained was significantly higher than that which would be obtained by the Néel relaxation processes under the same conditions. Moreover, increasing the amplitude of the magnetic field led to a significant decrease in the optimal diameter at which the maximum specific loss power is obtained (e.g., for 500 kHz frequency the optimal diameter decreased from 13.6 nm to 9.8 nm when the field increased from 10 kA/m to 50 kA/m), constituting a major advantage in magnetic hyperthermia for its optimization, in contrast to the known results in the absence of cyclodextrins from the surface of immobilized nanoparticles of CoFe₂O₄, where the optimal diameter remained practically unchanged at ~6.2 nm.     

Coal combustion modelling of large power plant, for NOx abatement

This paper presents the comparison of experimental results and computational fluid dynamics (CFD) simulations for a 600 MWe industrial pulverised coal power station. The power station measurements were made in a normal combustion mode and in an overfire air (OFA) mode. The agreement between the model and the data collected in the chimney is good; the NO_x reduction modelled is in agreement with the measured one, but data taken in the flame show that the flame structure is imperfectly represented.     

Atovaquone Suppresses Triple-Negative Breast Tumor Growth by Reducing Immune-Suppressive Cells

A major contributing factor in triple-negative breast cancer progression is its ability to evade immune surveillance. One mechanism for this immunosuppression is through ribosomal protein S19 (RPS19), which facilitates myeloid-derived suppressor cells (MDSCs) recruitment in tumors, which generate cytokines TGF-β and IL-10 and induce regulatory T cells (Tregs), all of which are immunosuppressive and enhance tumor progression. Hence, enhancing the immune system in breast tumors could be a strategy for anticancer therapeutics. The present study evaluated the immune response of atovaquone, an antiprotozoal drug, in three independent breast-tumor models. Our results demonstrated that oral administration of atovaquone reduced HCC1806, CI66 and 4T1 paclitaxel-resistant (4T1-PR) breast-tumor growth by 45%, 70% and 42%, respectively. MDSCs, TGF-β, IL-10 and Tregs of blood and tumors were analyzed from all of these in vivo models. Our results demonstrated that atovaquone treatment in mice bearing HCC1806 tumors reduced MDSCs from tumor and blood by 70% and 30%, respectively. We also observed a 25% reduction in tumor MDSCs in atovaquone-treated mice bearing CI66 and 4T1-PR tumors. In addition, a decrease in TGF-β and IL-10 in tumor lysates was observed in atovaquone-treated mice with a reduction in tumor Tregs. Moreover, a significant reduction in the expression of RPS19 was found in tumors treated with atovaquone.     

Turbulence modelling of multiphase flow in high-pressure trickle-bed reactors

Computational fluid dynamics (CFD) has been used as a successful tool for single-phase reactors. However, fixed-bed reactors design depends overly in empirical correlations for the prediction of heat and mass transfer phenomena. Therefore, the aim of this work is to present the application of CFD to the simulation of three-dimensional interstitial flow in a multiphase reactor. A case study comprising a high-pressure trickle-bed reactor (30 bar) was modelled by means of an Euler-Euler CFD model. The numerical simulations were evaluated quantitatively by experimental data from the literature. During grid optimization and validation, the effects of mesh size, time step and convergence criteria were evaluated plotting the hydrodynamic predictions as a function of liquid flow rate. Among the discretization methods for the momentum equation, a monotonic upwind scheme for conservation laws was found to give better computed results for either liquid holdup or two-phase pressure drop since it reduces effectively the numerical dispersion in convective terms of transport equation.After the parametric optimization of numerical solution parameters, four RANS multiphase turbulence models were investigated in the whole range of simulated gas and liquid flow rates. During RANS turbulence modelling, standard k-ε dispersed turbulence model gave the better compromise between computer expense and numerical accuracy in comparison with both realizable, renormalization group and Reynolds stress based models. Finally, several computational runs were performed at different temperatures for the evaluation of either axial averaged velocity and turbulent kinetic energy profiles for gas and liquid phases. Flow disequilibrium and strong heterogeneities detected along the packed bed demonstrated liquid distribution issues with slighter impact at high temperatures.     

Kinetic model development and simulation of simultaneous hydrodenitrogenation and hydrodemetallization of crude oil in trickle bed reactor

One of the more difficult tasks in the petroleum refining industries that have not been considered largely in the literature is hydrotreating (HDT) of crude oil. The accurate calculations of kinetic models of the relevant reaction scheme are required for obtaining helpful models for HDT reactions, which can be confidently used for reactor design, operating and control. In this work, an optimization technique is employed to evaluate the best kinetic models of a trickle bed reactor (TBR) process utilized for hydrodenitrogenation (HDN) and hydrodemetallization (HDM) that includes hydrodevanadization (HDV) and hydrodenickelation (HDNi) of crude oil based on pilot plant experiments. The minimization of the sum of the squared errors (SSE) between the experimental and estimated concentrations of nitrogen (N), vanadium (V) and nickel (Ni) compounds in the products is used as an objective function in the optimization problem to determine the kinetic parameters.A series of experimental work was conducted in a continuous flow isothermal trickle bed reactor, using crude oil as a feedstock and the commercial cobalt-molybdenum on alumina (Co-Mo/γ-Al₂O₃) as a catalyst.A three-phase heterogeneous model based on two-film theory is developed to describe the behaviour of crude oil hydroprocessing in a pilot-plant trickle bed reactor (TBR) system. The hydroprocessing reactions have been modelled by power law kinetics with respect to nitrogen, vanadium and nickel compounds, and with respect to hydrogen. In this work, the gPROMS (general PROcess Modelling System) package has been used for modelling, simulation and parameter estimation via optimization. The model simulations results were found to agree well with the experiments carried out in a wide range of the studied operating conditions. The model is employed to predict the concentration profiles of hydrogen, nitrogen, vanadium and nickel along the catalyst bed length in three phases.     

Differential Expression of Peroxisomal Proteins in Distinct Types of Parotid Gland Tumors

Salivary gland cancers are rare but aggressive tumors that have poor prognosis and lack effective cure. Of those, parotid tumors constitute the majority. Functioning as metabolic machinery contributing to cellular redox balance, peroxisomes have emerged as crucial players in tumorigenesis. Studies on murine and human cells have examined the role of peroxisomes in carcinogenesis with conflicting results. These studies either examined the consequences of altered peroxisomal proliferators or compared their expression in healthy and neoplastic tissues. None, however, examined such differences exclusively in human parotid tissue or extended comparison to peroxisomal proteins and their associated gene expressions. Therefore, we examined differences in peroxisomal dynamics in parotid tumors of different morphologies. Using immunofluorescence and quantitative PCR, we compared the expression levels of key peroxisomal enzymes and proliferators in healthy and neoplastic parotid tissue samples. Three parotid tumor subtypes were examined: pleomorphic adenoma, mucoepidermoid carcinoma and acinic cell carcinoma. We observed higher expression of peroxisomal matrix proteins in neoplastic samples with exceptional down regulation of certain enzymes; however, the degree of expression varied between tumor subtypes. Our findings confirm previous experimental results on other organ tissues and suggest peroxisomes as possible therapeutic targets or markers in all or certain subtypes of parotid neoplasms.