Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma

AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carcinoma(HCC).METHODS:Patients with advanced primary HCC were included in this study.CIK cells were perfused intraperitoneal twice a week,using 3.2 × 10 9 to 3.6 × 10 9 cells each session.Local RF hyperthermia was performed 2 h after intraperitoneal perfusion.Following an interval of one month,the next course of treatment was administered.Patients received treatment until disease progression.Tumor size,immune indices(CD3 +,CD4 +,CD3 + CD8 +,CD3 + CD56 +),alpha-fetoprotein(AFP) level,abdominal circumference and adverse events were recorded.Time to progression and overall survival(OS) were calculated.RESULTS:From June 2010 to July 2011,31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study.Patients received an average of 4.2 ± 0.6 treatment courses(range,1-8 courses).Patients were followed up for 8.3 ± 0.7 mo(range,2-12 mo).Following combination treatment,CD4 +,CD3 + CD8 + and CD3 + CD56 + cells increased from 35.78% ± 3.51%,24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48%(P = 0.016),39.67% ± 3.38%(P = 0.008) and 10.72% ± 0.67%(P = 0.001),respectively.AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL(P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm(P = 0.002).The disease control rate was 67.7%.The most common adverse events were low fever and slight abdominal erubescence,which resolved without treatment.The median time to progression was 6.1 mo.The 3-,6-and 9-mo and 1-year survival rates were 93.5%,77.4%,41.9% and 17.4%,respectively.The median OS was 8.5 mo.CONCLUSION:Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe,can efficiently improve immunological status,and may prolong survival in HCC patients.

Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent magnetic nanoparticles(FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods: Human i PS cells were prepared and cultured for 72 h. The culture medium was collected, and then was coincubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human i PS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iP S cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iP S cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion: FMNP-labeled human i PS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.

Effect of Tirapazamine and Mild Temperature Hyperthermia on the Recovery from Radiation-Induced Damage in Pimonidazole-Unlabeled Quiescent Tumor Cell Population

The aim in this study is to examine the effect of tirapazamine (TPZ) and mild temperature hyperthermia (MTH) on the repair of radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells. Labeling of proliferating (P) cells in C57BL/6J mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after the administration of pimonidazole followed by TPZ treatment or MTH. Twenty-four hours later, assessment of the responses of Q and total (= P + Q) cells were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. With γ-rays only, the pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using a delayed assay, was more clearly observed in Q cells than total cells. Post-irradiation MTH more remarkably repressed the decrease in radio-sensitivity in the Q cell than the total cells. Post-irradiation TPZ administration produced a large radio-sensitizing effect on both total and Q cells, especially on Q cells. On the other hand, in pimonidazole-unlabeled cell fractions in both total and Q cells, TPZ suppressed the reduction in sensitivity due to delayed assay much more efficiently than MTH, whereas no radio-sensitizing effect was produced. Not only through suppressing the recovery from radiation-induced damage but also through radio-sensitizing effect, post-irradiation TPZ administration is very useful for repressing the increase in the difference in radio-sensitivity due to the delayed assay not only between total and Q tumor cells but also between the pimonidazole-unlabeled and the whole cell fractions within the total and Q tumor cells.

Calculation of Electromagnetic Field and SAR Dis- tributions of Two Antenna Structures for Bone Tu- mors Microwave Hyperthermia

Objective: To investigate the electromagnetic field and specific absorptionrate (SAR) distribution of different structure applicators with different depths for treating bonetumors using microwave hyperthermia. Methods: The finite element method (FEM) was used to calculate,electromagnetic field and SAR distribution. Two different structure applicators were simulated. Theone is simple coaxial antenna, which has been successfully used in clinic treating bone tumors inTangdu hospital of the Forth Military Medical University several years. It was formed by a coaxialcable peeled off the out copper at end. The other applicator was coaxial- slot antenna, which waswidely used in microwave hyperthermia. The applicator inserted into the cylindrical bone withdifferent depths, and worked at the frequency of 2 450 MHz. Results: The electric field and SARgenerated by the simple coaxial applicator were mainly concentrated out the tissues, and were notuniform in the tissues, while the coaxial- slot applicator well transmits the electric field and SARinto the tissues, and can easily treat different position by adjusting the slat position.Conclusion: The results calculated by EFM, were well accordant with the experimental and clinicalresulls, and will be important for improving the clinical effects of microwave hyperthermia.

Integrated interpretation of dual frequency induced polarization measurement based on wavelet analysis and metal factor methods

In mineral exploration, the apparent resistivity and apparent frequency （or apparent polarizability） parameters of induced polarization method are commonly utilized to describe the induced polarization anomaly. When the target geology structure is significantly complicated, these parameters would fail to reflect the nature of the anomaly source, and wrong conclusions may be obtained. A wavelet approach and a metal factor method were used to comprehensively interpret the induced polarization anomaly of complex geologic bodies in the Adi Bladia mine. Db5 wavelet basis was used to conduct two-scale decomposition and reconstruction, which effectively suppress the noise interference of greenschist facies regional metamorphism and magma intrusion, making energy concentrated and boundary problem unobservable. On the basis of that, the ore-induced anomaly was effectively extracted by the metal factor method.

A DYNAMIC STUDY OF THE CYTOTOXIC EFFECTS OF HYPERTHERMIA COMBINED WITH CIS-DIAMINE DICHLOROLPLATINUM(DDP) ON HUMAN GASTRIC CANCER CELL LINES MKN_(28) AND MKN_(45) IN VITRO

Cytotoxic effects of hyperthermia combined with DDP on MKN28 and MKN45 cells were studied by MTT assay according to a nested design. The results showed:hyperthermia alone above 43℃ for 30 mins was cytotoxic;hyperthermia at temperature lower than 43℃ for 30 mins could increase sensitivity of cancer cells to DDP. The cytotoxic effect of simultaneous use of hyperthermia and DDP was more marked than that of sequential use of the 2 treatments. Hyperthermia combined with DDP could inhibit growth of human gastric adenocarcinoma cells regardless of their degree of differentiation.

Effect of hyperthermia in combination with cryotherapy on sarcoma 180 in mice

The significant decrease in tumor recurrence caused by combined hyperthermia (local water bath) with cryotherapy has previously been shown. This study demonstrated an in vivo additive interaction of local microwave diathermy (hyperthermia, 42±0.5℃, 20 min. ) and liquid nitrogen treatment (cryotherapy,-180℃, 3 min. ) against intraperitoneally implanted sarcoma 180 in ICR mice. Local hyperthermia was produced by applicating 2450 MHz microwave to the region of the tumor without induction of significant whole body hyperthermia.Both hyperthermia and cryotherapy were delivered as a single dose individually on day 1 and day 2. The analysis of the tumor size curves showed that all of the treatments had more significant effect on sarcoma 180 than on the control group (P < 0. 0001 ). The optimal sequence of the combined therapies found in the experiment was cryotherapy→hyperthermia (CH) (P<0. 0001). Weights of the tumors excised from the mice on day 11 showed that the combined therapies (cryotherapy→hyperthermia or hyperthermia→cryotherapy) were more effective on sarcoma 180 than hyperthermia or cryotherapy used alone(P<0.01).

Methods to produce induced pluripotent stem cell-derived mesenchymal stem cells: Mesenchymal stem cells from induced pluripotent stem cells

Mesenchymal stem cells(MSCs)have received significant attention in recent years due to their large potential for cell therapy.Indeed,they secrete a wide variety of immunomodulatory factors of interest for the treatment of immune-related disorders and inflammatory diseases.MSCs can be extracted from multiple tissues of the human body.However,several factors may restrict their use for clinical applications:the requirement of invasive procedures for their isolation,their limited numbers,and their heterogeneity according to the tissue of origin or donor.In addition,MSCs often present early signs of replicative senescence limiting their expansion in vitro,and their therapeutic capacity in vivo.Due to the clinical potential of MSCs,a considerable number of methods to differentiate induced pluripotent stem cells(iPSCs)into MSCs have emerged.iPSCs represent a new reliable,unlimited source to generate MSCs(MSCs derived from iPSC,iMSCs)from homogeneous and well-characterized cell lines,which would relieve many of the above mentioned technical and biological limitations.Additionally,the use of iPSCs prevents some of the ethical concerns surrounding the use of human embryonic stem cells.In this review,we analyze the main current protocols used to differentiate human iPSCs into MSCs,which we classify into five different categories:MSC Switch,Embryoid Body Formation,Specific Differentiation,Pathway Inhibitor,and Platelet Lysate.We also evaluate common and method-specific culture components and provide a list of positive and negative markers for MSC characterization.Further guidance on material requirements to produce iMSCs with these methods and on the phenotypic features of the iMSCs obtained is added.The information may help researchers identify protocol options to design and/or refine standardized procedures for large-scale production of iMSCs fitting clinical demands.

Generation of Transgene-free Induced Pluripotent Stem Cells with Non-viral Methods

Induced pluripotent stem （iPS） cells were originally generated from mouse fibroblasts by enforced expression of Yamanaka factors （Oct3/4, Sox2, Klf4, and c-Myc）. The technique was quickly re- produced with human fibroblasts or mesenchymal stem cells. Although having been showed therapeutic po- tential in animal models of sickle ceil anemia and Parkinson＇s disease, iPS cells generated by viral methods do not suit all the clinical applications. Various non-viral methods have appeared in recent years for application of iPS cells in cell transplantation therapy. These methods mainly include DNA vector-based approaches, transfection of mRNA, and transduction of reprogramming proteins. This review summarized these non-viral methods and compare the advantages, disadvantages, efficiency, and safety of these methods.

Numerical Calculation Methods for Wavemaking Response Induced by Explosion in Harbour

Using the axial symmetry results of marker and cell (MAC) method as initial value in this paper, two numerical calculating methods are presented for the late wavemaking response induced by explosion in harbour. One of the methods is the superposition method of the vibration mode based on fluid slosh in container. Another one is the joining method of the MAC results with the shallow wave theory calculation in time domain. As a practical example, it is conducted to the numerical calculation about 1000 ton TNT equivalent explosion within touch of water surface. The results show that it can be rationally described with the methods to the wavemaking progress and character. The numerical results are identical with the observed scene on the spot experiment. The methods are simple and applicable in the engineering design.

Laser-induced plasma electron number density:Stark broadening method versus the Saha-Boltzmann equation

We report spectroscopic studies on plasma electron number density of laser-induced plasma produced by ns-Nd：YAG laser light pulses on an aluminum sample in air at atmospheric pressure. The effect of different laser energy and the effect of different laser wavelengths were compared. The experimentally observed line profiles of neutral aluminum have been used to extract the excitation temperature using the Boltzmann plot method, whereas the electron number density has been determined from the Stark broadened as well as using the Saha-Boltzmann equation （SBE）. Each approach was also carried out by using the AI emission line and Mg emission lines. It was observed that the,SBE method generated a little higher electron number density value than the Stark broadening, method, but within the experimental uncertainty range. Comparisons of Ne determined by the two methods show the presence of a linear relation which is independent of laser energy or laser wavelength. These results show the applicability of the SBE method for Are determination, especially when the system does not have any pure emission lines whose electron impact factor is known, Also use of Mg lines gives superior results than Al lines.

Synthesis of Hierarchically Porous FAU/γ-Al2O3 Composites with Different Morphologies via Directing Agent Induced Method

Zeolite FAU composites with a macro/meso-microporous hierarchical structure were hydrothermally synthesized using macro-mesoporous γ-Al_2O_3 monolith as the substrate by means of the liquid crystallization directing agent(LCDA) induced method. No template was needed throughout the synthesis processes. The structure and porosity of zeolite composites were analyzed by means of X-ray powder diffraction(XRD), scanning electron microscopy(SEM) and N_2adsorption-desorption isotherms. The results showed that the supported zeolite composites with varied zeolitic crystalline phases and different morphologies can be obtained by adjusting the crystallization parameters, such as the crystallization temperature, the composition and the alkalinity of the precursor solution. The presence of LCDA was defined as a determinant for synthesizing the zeolite composites. The mechanisms for formation of the hierarchically porous FAU zeolite composites in the LCDA induced synthesis process were discussed. The resulting monolithic zeolite with a trimodal-porous hierarchical structure shows potential applicability where facile diffusion is required.

Study on Free Surface and Channel Flow Induced by Low Temperature Plasma via Lattice Boltzmann Method

Active boundary layer flow control and boundary layer manipulation in the channel flow that was based on low temperature plasma were studied by means of a lattice Boltzmann method. Two plasma actuators were placed in a row to obtain the influence rule of their separation distance on the velocity profile at three locations and maximum velocity in the flow field. Two plasma actuators were placed symmetrically inside a channel to examine the effect of channel height and voltage on the velocity profile and flow rate. It was found that the channel height controls the distribution of flow velocity, which affected the flow rate and its direction. Increasing plasma voltage had a negative effect on the flow rate due to the generation of a larger and stronger flow vortex.

A numerical method of combined SPF-MEM-LBM on the rockfall-induced surge and its application

Rockfalls in reservoirs are prone to induce surges, posing a severe threat to passing vessels and facilities. A scheme combined Single-phase freesurface method(SPF), momentum exchange method(MEM), and Lattice Boltzmann method(LBM) is proposed to predict the impact of rockfall-induced surges. First, the LBM-SPF model is used to simulate the motion of the free surface, and the MEM model is used to calculate the hydrodynamic force acting on rock mass. To address the incompatibility issue arising from the coupling of LBM-SPF model and MEM model, a correction scheme inside the solid is induced. The simulation results of the single particle and double particle sedimentation in cavity show the feasibility and accuracy of the method designed in this paper. Moreover, the validation experiments of Scott Russel’s wave generator show that the proposed scheme can simulate wave profile stably. The simulation results emphasize that the waves induced by rockfalls have a significant impact on the safe operation of the Laxiwa dam and the passing vessels in the reservoir.

Evaluation of gases'molecular abundance ratio by fiber-optic laser-induced breakdown spectroscopy with a metal-assisted method

A metal-assisted method is proposed for the evaluation of gases’molecular abundance ratio in fiber-optic laser-induced breakdown spectroscopy(FO-LIBS).This method can reduce the laser ablation energy and make gas composition identification possible.The principle comes from the collision between the detected gases and the plasma produced by the laser ablation of the metal substrate.The interparticle collision in the plasma plume leads to gas molecules dissociating and sparking,which can be used to determine the gas composition.The quantitative relationship between spectral line intensity and molecular abundance ratio was developed over a large molecular abundance ratio range.The influence of laser ablation energy and substrate material on gas quantitative calibration measurement is also analyzed.The proposed metal-assisted method makes the measurement of gases’molecular abundance ratios possible with an FO-LIBS system.

Fully coupled flow-induced vibration of structures under small deformation with GMRES method

Lagrangian-Eulerian formulations based on a generalized variational principle of fluid-solid coupling dynamics are established to describe flow-induced vibration of a structure under small deformation in an incompressible viscous fluid flow. The spatial discretization of the formulations is based on the multi-linear interpolating functions by using the finite element method for both the fluid and solid structures. The generalized trapezoidal rule is used to obtain apparently non-symmetric linear equations in an incremental form for the variables of the flow and vibration. The nonlinear convective term and time factors are contained in the non-symmetric coefficient matrix of the equations. The generalized minimum residual （GMRES） method is used to solve the incremental equations. A new stable algorithm of GMRES-Hughes-Newmark is developed to deal with the flow-induced vibration with dynamical fluid-structure interaction in complex geometries. Good agreement between the simulations and laboratory measurements of the pressure and blade vibration accelerations in a hydro turbine passage was obtained, indicating that the GiViRES-Hughes-Newmark algorithm presented in this paper is suitable for dealing with the flow-induced vibration of structures under small deformation.

Numerical Investigation on Vortex-Induced Rotations of A Triangular Cylinder Using An Immersed Boundary Method

A numerical study of vortex-induced rotations(VIRs) of an equivalent triangular cylinder, which is free to rotate in the azimuthal direction in a uniform flow, is presented. Based on an immersed boundary method, the numerical model is established, and is verified through the benchmark problem of flow past a freely rotating rectangular body.The computation is performed for a fixed reduced mass of m~*=2.0 and the structural stiffness and damping ratio are set to zero. The effects of Reynolds number(Re=25-180) on the characteristics of VIR are studied. It is found that the dynamic response of the triangular cylinder exhibits four distinct modes with increasing Re: a rest position,periodic rotational oscillation, random rotation and autorotation. For the rotational oscillation mode, the cylinder undergoes a periodic vibration around an equilibrium position with one side facing the incoming flow. Since the rotation effect, the outset of vortex shedding from cylinder shifts to a much lower Reynolds number. Further increase in Re leads to 2 P and P+S vortex shedding modes besides the typical 2 S pattern. Our simulation results also elucidate that the free rotation significantly changes the drag and lift forces. Inspired by these facts, the effect of free rotation on flow-induced vibration of a triangular cylinder in the in-line and transverse directions is investigated. The results show that when the translational vibration is coupled with rotation, the triangular cylinder presents a galloping response instead of vortex-induced vibration(VIV).

Preparation of AZ91D magnesium alloy semi-solid billet by new strain induced melt activated method

New strain induced melt activated (new SIMA) method for preparing AZ91D magnesium alloy semi-solid billet is introduced by applying equal channel angular extrusion into strain induced step in SIMA method, by which semi-solid billet with fine spheroidal grains and average grain size of 18 μm can be prepared. Furthermore, average grain size of semi-solid billet is reduced with increasing extrusion pass of AZ91D magnesium alloy obtained in ECAE process. By using semi-solid billet prepared by new SIMA, thixoforged magazine plates component with high mechanical properties such as yield strength of 201.4 MPa, ultimate tensile strength of 321.8 MPa and elongation of 15.3%, can be obtained.

Simulation of shock-induced instability using an essentially conservative adaptive CE/SE method

An essentially conservative adaptive space time conservation element and solution element （CE/SE） method is pro- posed for the effective simulation of shock-induced instability with low computational cost. Its implementation is based on redefined conservation elements （CEs） and solution elements （SEs）, optimized interpolations and a Courant number insensitive CE/SE scheme. This approach is used in two applications, the Woodward double Mach reflection and a two- component Richtmyer-Meshkov instability experiment. This scheme reveals the essential features of the investigated cases, captures small unstable structures, and yields a solution that is consistent with the results from experiments or other high order methods.

MEASURING PRECISION OF INDUCED POLARIZATION METHOD

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