WorldWideScience

Sample records for model tumor interfacial

  1. Interfacial properties in a discrete model for tumor growth

    Science.gov (United States)

    Moglia, Belén; Guisoni, Nara; Albano, Ezequiel V.

    2013-03-01

    We propose and study, by means of Monte Carlo numerical simulations, a minimal discrete model for avascular tumor growth, which can also be applied for the description of cell cultures in vitro. The interface of the tumor is self-affine and its width can be characterized by the following exponents: (i) the growth exponent β=0.32(2) that governs the early time regime, (ii) the roughness exponent α=0.49(2) related to the fluctuations in the stationary regime, and (iii) the dynamic exponent z=α/β≃1.49(2), which measures the propagation of correlations in the direction parallel to the interface, e.g., ξ∝t1/z, where ξ is the parallel correlation length. Therefore, the interface belongs to the Kardar-Parisi-Zhang universality class, in agreement with recent experiments of cell cultures in vitro. Furthermore, density profiles of the growing cells are rationalized in terms of traveling waves that are solutions of the Fisher-Kolmogorov equation. In this way, we achieved excellent agreement between the simulation results of the discrete model and the continuous description of the growth front of the culture or tumor.

  2. Model of interfacial melting

    DEFF Research Database (Denmark)

    Mouritsen, Ole G.; Zuckermann, Martin J.

    1987-01-01

    A two-dimensional model is proposed to describe systems with phase transitions which take place in terms of crystalline as well as internal degrees of freedom. Computer simulation of the model shows that the interplay between the two sets of degrees of freedom permits observation of grain-boundar......-boundary formation and interfacial melting, a nonequilibrium process by which the system melts at the boundaries of a polycrystalline domain structure. Lipid membranes are candidates for systems with pronounced interfacial melting behavior....

  3. Dynamic modeling of interfacial structures via interfacial area transport equation

    International Nuclear Information System (INIS)

    Seungjin, Kim; Mamoru, Ishii

    2004-01-01

    Full text of publication follows:In the current thermal-hydraulic system analysis codes using the two-fluid model, the empirical correlations that are based on the two-phase flow regimes and regime transition criteria are being employed as closure relations for the interfacial transfer terms. Due to its inherent shortcomings, however, such static correlations are inaccurate and present serious problems in the numerical analysis. In view of this, a new dynamic approach employing the interfacial area transport equation has been studied. The interfacial area transport equation dynamically models the two-phase flow regime transitions and predicts continuous change of the interfacial area concentration along the flow field. Hence, when employed in the thermal-hydraulic system analysis codes, it eliminates artificial bifurcations stemming from the use of the static flow regime transition criteria. Therefore, the interfacial area transport equation can make a leapfrog improvement in the current capability of the two-fluid model from both scientific and practical point of view. Accounting for the substantial differences in the transport phenomena of various sizes of bubbles, the two-group interfacial area transport equations have been developed. The group 1 equation describes the transport of small-dispersed bubbles that are either distorted or spherical in shapes, and the group 2 equation describes the transport of large cap, slug or churn-turbulent bubbles. The source and sink terms in the right hand-side of the transport equations have been established by mechanistically modeling the creation and destruction of bubbles due to major bubble interaction mechanisms. The coalescence mechanisms include the random collision driven by turbulence, and the entrainment of trailing bubbles in the wake region of the preceding bubble. The disintegration mechanisms include the break-up by turbulence impact, shearing-off at the rim of large cap bubbles and the break-up of large cap

  4. Dynamic modeling of interfacial structures via interfacial area transport equation

    International Nuclear Information System (INIS)

    Seungjin, Kim; Mamoru, Ishii

    2005-01-01

    The interfacial area transport equation dynamically models the two-phase flow regime transitions and predicts continuous change of the interfacial area concentration along the flow field. Hence, when employed in the numerical thermal-hydraulic system analysis codes, it eliminates artificial bifurcations stemming from the use of the static flow regime transition criteria. Accounting for the substantial differences in the transport phenomena of various sizes of bubbles, the two-group interfacial area transport equations have been developed. The group 1 equation describes the transport of small-dispersed bubbles that are either distorted or spherical in shapes, and the group 2 equation describes the transport of large cap, slug or churn-turbulent bubbles. The source and sink terms in the right-hand-side of the transport equations have been established by mechanistically modeling the creation and destruction of bubbles due to major bubble interaction mechanisms. In the present paper, the interfacial area transport equations currently available are reviewed to address the feasibility and reliability of the model along with extensive experimental results. These include the data from adiabatic upward air-water two-phase flow in round tubes of various sizes, from a rectangular duct, and from adiabatic co-current downward air-water two-phase flow in round pipes of two sizes. (authors)

  5. Modeling interfacial fracture in Sierra.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Arthur A.; Ohashi, Yuki; Lu, Wei-Yang; Nelson, Stacy A. C.; Foulk, James W.,; Reedy, Earl David,; Austin, Kevin N.; Margolis, Stephen B.

    2013-09-01

    This report summarizes computational efforts to model interfacial fracture using cohesive zone models in the SIERRA/SolidMechanics (SIERRA/SM) finite element code. Cohesive surface elements were used to model crack initiation and propagation along predefined paths. Mesh convergence was observed with SIERRA/SM for numerous geometries. As the funding for this project came from the Advanced Simulation and Computing Verification and Validation (ASC V&V) focus area, considerable effort was spent performing verification and validation. Code verification was performed to compare code predictions to analytical solutions for simple three-element simulations as well as a higher-fidelity simulation of a double-cantilever beam. Parameter identification was conducted with Dakota using experimental results on asymmetric double-cantilever beam (ADCB) and end-notched-flexure (ENF) experiments conducted under Campaign-6 funding. Discretization convergence studies were also performed with respect to mesh size and time step and an optimization study was completed for mode II delamination using the ENF geometry. Throughout this verification process, numerous SIERRA/SM bugs were found and reported, all of which have been fixed, leading to over a 10-fold increase in convergence rates. Finally, mixed-mode flexure experiments were performed for validation. One of the unexplained issues encountered was material property variability for ostensibly the same composite material. Since the variability is not fully understood, it is difficult to accurately assess uncertainty when performing predictions.

  6. Incorporating interfacial phenomena in solidification models

    Science.gov (United States)

    Beckermann, Christoph; Wang, Chao Yang

    1994-01-01

    A general methodology is available for the incorporation of microscopic interfacial phenomena in macroscopic solidification models that include diffusion and convection. The method is derived from a formal averaging procedure and a multiphase approach, and relies on the presence of interfacial integrals in the macroscopic transport equations. In a wider engineering context, these techniques are not new, but their application in the analysis and modeling of solidification processes has largely been overlooked. This article describes the techniques and demonstrates their utility in two examples in which microscopic interfacial phenomena are of great importance.

  7. Interfacial Fluid Mechanics A Mathematical Modeling Approach

    CERN Document Server

    Ajaev, Vladimir S

    2012-01-01

    Interfacial Fluid Mechanics: A Mathematical Modeling Approach provides an introduction to mathematical models of viscous flow used in rapidly developing fields of microfluidics and microscale heat transfer. The basic physical effects are first introduced in the context of simple configurations and their relative importance in typical microscale applications is discussed. Then,several configurations of importance to microfluidics, most notably thin films/droplets on substrates and confined bubbles, are discussed in detail.  Topics from current research on electrokinetic phenomena, liquid flow near structured solid surfaces, evaporation/condensation, and surfactant phenomena are discussed in the later chapters. This book also:  Discusses mathematical models in the context of actual applications such as electrowetting Includes unique material on fluid flow near structured surfaces and phase change phenomena Shows readers how to solve modeling problems related to microscale multiphase flows Interfacial Fluid Me...

  8. An improved interfacial bonding model for material interface modeling

    Science.gov (United States)

    Lin, Liqiang; Wang, Xiaodu; Zeng, Xiaowei

    2016-01-01

    An improved interfacial bonding model was proposed from potential function point of view to investigate interfacial interactions in polycrystalline materials. It characterizes both attractive and repulsive interfacial interactions and can be applied to model different material interfaces. The path dependence of work-of-separation study indicates that the transformation of separation work is smooth in normal and tangential direction and the proposed model guarantees the consistency of the cohesive constitutive model. The improved interfacial bonding model was verified through a simple compression test in a standard hexagonal structure. The error between analytical solutions and numerical results from the proposed model is reasonable in linear elastic region. Ultimately, we investigated the mechanical behavior of extrafibrillar matrix in bone and the simulation results agreed well with experimental observations of bone fracture. PMID:28584343

  9. Multiscale Modeling of Mesoscale and Interfacial Phenomena

    Science.gov (United States)

    Petsev, Nikolai Dimitrov

    With rapidly emerging technologies that feature interfaces modified at the nanoscale, traditional macroscopic models are pushed to their limits to explain phenomena where molecular processes can play a key role. Often, such problems appear to defy explanation when treated with coarse-grained continuum models alone, yet remain prohibitively expensive from a molecular simulation perspective. A prominent example is surface nanobubbles: nanoscopic gaseous domains typically found on hydrophobic surfaces that have puzzled researchers for over two decades due to their unusually long lifetimes. We show how an entirely macroscopic, non-equilibrium model explains many of their anomalous properties, including their stability and abnormally small gas-side contact angles. From this purely transport perspective, we investigate how factors such as temperature and saturation affect nanobubbles, providing numerous experimentally testable predictions. However, recent work also emphasizes the relevance of molecular-scale phenomena that cannot be described in terms of bulk phases or pristine interfaces. This is true for nanobubbles as well, whose nanoscale heights may require molecular detail to capture the relevant physics, in particular near the bubble three-phase contact line. Therefore, there is a clear need for general ways to link molecular granularity and behavior with large-scale continuum models in the treatment of many interfacial problems. In light of this, we have developed a general set of simulation strategies that couple mesoscale particle-based continuum models to molecular regions simulated through conventional molecular dynamics (MD). In addition, we derived a transport model for binary mixtures that opens the possibility for a wide range of applications in biological and drug delivery problems, and is readily reconciled with our hybrid MD-continuum techniques. Approaches that couple multiple length scales for fluid mixtures are largely absent in the literature, and

  10. Interfacial Micromechanics in Fibrous Composites: Design, Evaluation, and Models

    Science.gov (United States)

    Lei, Zhenkun; Li, Xuan; Qin, Fuyong; Qiu, Wei

    2014-01-01

    Recent advances of interfacial micromechanics in fiber reinforced composites using micro-Raman spectroscopy are given. The faced mechanical problems for interface design in fibrous composites are elaborated from three optimization ways: material, interface, and computation. Some reasons are depicted that the interfacial evaluation methods are difficult to guarantee the integrity, repeatability, and consistency. Micro-Raman study on the fiber interface failure behavior and the main interface mechanical problems in fibrous composites are summarized, including interfacial stress transfer, strength criterion of interface debonding and failure, fiber bridging, frictional slip, slip transition, and friction reloading. The theoretical models of above interface mechanical problems are given. PMID:24977189

  11. Interfacial Thermal Transport via One-Dimensional Atomic Junction Model

    Directory of Open Access Journals (Sweden)

    Guohuan Xiong

    2018-03-01

    Full Text Available In modern information technology, as integration density increases rapidly and the dimension of materials reduces to nanoscale, interfacial thermal transport (ITT has attracted widespread attention of scientists. This review introduces the latest theoretical development in ITT through one-dimensional (1D atomic junction model to address the thermal transport across an interface. With full consideration of the atomic structures in interfaces, people can apply the 1D atomic junction model to investigate many properties of ITT, such as interfacial (Kapitza resistance, nonlinear interface, interfacial rectification, and phonon interference, and so on. For the ballistic ITT, both the scattering boundary method (SBM and the non-equilibrium Green’s function (NEGF method can be applied, which are exact since atomic details of actual interfaces are considered. For interfacial coupling case, explicit analytical expression of transmission coefficient can be obtained and it is found that the thermal conductance maximizes at certain interfacial coupling (harmonic mean of the spring constants of the two leads and the transmission coefficient is not a monotonic decreasing function of phonon frequency. With nonlinear interaction—phonon–phonon interaction or electron–phonon interaction at interface, the NEGF method provides an efficient way to study the ITT. It is found that at weak linear interfacial coupling, the nonlinearity can improve the ITT, but it depresses the ITT in the case of strong-linear coupling. In addition, the nonlinear interfacial coupling can induce thermal rectification effect. For interfacial materials case which can be simulated by a two-junction atomic chain, phonons show interference effect, and an optimized thermal coupler can be obtained by tuning its spring constant and atomic mass.

  12. Modeling interfacial area transport in multi-fluid systems

    Energy Technology Data Exchange (ETDEWEB)

    Yarbro, Stephen Lee [Univ. of California, Berkeley, CA (United States)

    1996-11-01

    Many typical chemical engineering operations are multi-fluid systems. They are carried out in distillation columns (vapor/liquid), liquid-liquid contactors (liquid/liquid) and other similar devices. An important parameter is interfacial area concentration, which determines the rate of interfluid heat, mass and momentum transfer and ultimately, the overall performance of the equipment. In many cases, the models for determining interfacial area concentration are empirical and can only describe the cases for which there is experimental data. In an effort to understand multiphase reactors and the mixing process better, a multi-fluid model has been developed as part of a research effort to calculate interfacial area transport in several different types of in-line static mixers. For this work, the ensemble-averaged property conservation equations have been derived for each fluid and for the mixture. These equations were then combined to derive a transport equation for the interfacial area concentration. The final, one-dimensional model was compared to interfacial area concentration data from two sizes of Kenics in-line mixer, two sizes of concurrent jet and a Tee mixer. In all cases, the calculated and experimental data compared well with the highest scatter being with the Tee mixer comparison.

  13. Interfacial Healing and Transport Phenomena Modeling ff Biopolymers

    Science.gov (United States)

    Lebron, Karla

    This research focuses on the characterization of bioplastics joined using ultrasonic welding and modeling of temperature distributions and interfacial healing. Polylactic acid (PLA), which is typically derived from starch-rich crops such as corn, was studied. While the measurement of activation energy for interfacial healing at weld interfaces of PLA films has been reported, here, this information is used to predict the weld strength of rigid PLA samples welded by ultrasonics. A characterization of the mechanical properties was completed with a tensile test to determine the effects of amplitude, melt velocity and collapse distance on weld strength. From previous interfacial healing activation energy measurements based on an impulse welding method, it was also possible to predict weld strength. It was found that the most influential parameters were weld time, collapse distance and weld velocity. In general, the model predicted weld strength reasonably well with r2 values between 0.77 and 0.78.

  14. Tissue engineered tumor models.

    Science.gov (United States)

    Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

    2010-08-01

    Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

  15. Molecular Modeling of Interfacial Behaviors of Nanomaterials

    Science.gov (United States)

    2007-05-01

    potential was originally designed for the modeling of mixed covalent- ionic bonding and was successfully used to describe oxides in crystalline, glassy, and...is separates from the bulk liquid polymer, i.e., the structure of this layer, as influenced by that of the meatal surface, is significantly more...Striolo, J. Kieffer, and P. Cummings, ’Evaluation of Force- fields for molecular simulation of polyhedral oligomeric silsesquioxanes,’ J. Phys. Chem

  16. Interfacial and Wall Transport Models for SPACE-CAP Code

    International Nuclear Information System (INIS)

    Hong, Soon Joon; Choo, Yeon Joon; Han, Tae Young; Hwang, Su Hyun; Lee, Byung Chul; Choi, Hoon; Ha, Sang Jun

    2009-01-01

    The development project for the domestic design code was launched to be used for the safety and performance analysis of pressurized light water reactors. And CAP (Containment Analysis Package) code has been also developed for the containment safety and performance analysis side by side with SPACE. The CAP code treats three fields (gas, continuous liquid, and dispersed drop) for the assessment of containment specific phenomena, and is featured by its multidimensional assessment capabilities. Thermal hydraulics solver was already developed and now under testing of its stability and soundness. As a next step, interfacial and wall transport models was setup. In order to develop the best model and correlation package for the CAP code, various models currently used in major containment analysis codes, which are GOTHIC, CONTAIN2.0, and CONTEMPT-LT, have been reviewed. The origins of the selected models used in these codes have also been examined to find out if the models have not conflict with a proprietary right. In addition, a literature survey of the recent studies has been performed in order to incorporate the better models for the CAP code. The models and correlations of SPACE were also reviewed. CAP models and correlations are composed of interfacial heat/mass, and momentum transport models, and wall heat/mass, and momentum transport models. This paper discusses on those transport models in the CAP code

  17. Interfacial and Wall Transport Models for SPACE-CAP Code

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Soon Joon; Choo, Yeon Joon; Han, Tae Young; Hwang, Su Hyun; Lee, Byung Chul [FNC Tech., Seoul (Korea, Republic of); Choi, Hoon; Ha, Sang Jun [Korea Electric Power Research Institute, Daejeon (Korea, Republic of)

    2009-10-15

    The development project for the domestic design code was launched to be used for the safety and performance analysis of pressurized light water reactors. And CAP (Containment Analysis Package) code has been also developed for the containment safety and performance analysis side by side with SPACE. The CAP code treats three fields (gas, continuous liquid, and dispersed drop) for the assessment of containment specific phenomena, and is featured by its multidimensional assessment capabilities. Thermal hydraulics solver was already developed and now under testing of its stability and soundness. As a next step, interfacial and wall transport models was setup. In order to develop the best model and correlation package for the CAP code, various models currently used in major containment analysis codes, which are GOTHIC, CONTAIN2.0, and CONTEMPT-LT, have been reviewed. The origins of the selected models used in these codes have also been examined to find out if the models have not conflict with a proprietary right. In addition, a literature survey of the recent studies has been performed in order to incorporate the better models for the CAP code. The models and correlations of SPACE were also reviewed. CAP models and correlations are composed of interfacial heat/mass, and momentum transport models, and wall heat/mass, and momentum transport models. This paper discusses on those transport models in the CAP code.

  18. Modeling and measurement of interfacial area concentration in two-phase flow

    International Nuclear Information System (INIS)

    Paranjape, Sidharth; Ishii, Mamoru; Hibiki, Takashi

    2010-01-01

    This paper presents experimental and modeling approaches in characterizing interfacial structures in gas-liquid two-phase flow. For the modeling of the interfacial structure characterization, the interfacial area transport equation proposed earlier has been studied to provide a dynamic and mechanistic prediction tool for two-phase flow analysis. A state-of-the-art four-sensor conductivity probe technique has been developed to obtain detailed local interfacial structure information in a wide range of flow regimes spanning from bubbly to churn-turbulent flows. Newly obtained interfacial area data in 8 x 8 rod-bundle test section are also presented. This paper also reviews available models of the interfacial area sink and source terms and existing databases. The interfacial area transport equation has been benchmarked using condensation bubbly flow data.

  19. Fundamental study on interfacial area transport model (I) (contract research)

    International Nuclear Information System (INIS)

    Mishima, Kaichiro; Nakamura, Hideo

    2001-03-01

    Recently, improvement in the best-estimate (BE) code predictive capability is attempted by incorporating the interfacial area transport model (IATM) into a one-dimensional two-fluid model to represent gas-liquid two-phase flows in detail with less uncertainty in the flow predictions. Internationally, the nuclear regulatory commission (NRC) and Purdue University in the U.S.A. and CEA in France have promoted the renewal of their BE codes such as TRAC, RELAP5 and CATHARE, by introducing the IATM in cooperative manner. In Japan, JAERI is underway to develop a one-dimensional code based primarily on the IATM against the licensing procedures of next-generation nuclear reactors. The IATM has a possibility to correctly predict flow transient along flow path for such flows as developing flows, multi-dimensional flows, transitional flows, boiling flows, which are difficult to accurately predict by the two-fluid models employed in the current BE codes. The newly developed code with the IATM would dramatically improve the accuracy in the flow prediction. The model, however, is under development and needs great effort to overcome many difficulties with plenty of theoretical considerations based on much of data bases to be acquired further. This study attempts to measure interfacial area in air-water two-phase flows in a large-diameter tube to understand the characteristic of multi-dimensional flows that usually appear in large-diameter tube flows, and provide data bases, to contribute the development of the IATM. The results obtained by such institutes as Purdue University and CEA France were reviewed first. Clarified are the current status and problems of the IATM, basics and practical methods to measure the interfacial area using multi-sensor miniature local probes; metal needle electro-resistance probe and fiber-optic probe. It was found that the applicability of the IATM is limited mostly to a one-dimensional bubbly flow, and is far from satisfactory for multi

  20. Interfacial shear modeling in two-phase annular flow

    International Nuclear Information System (INIS)

    Kumar, R.; Edwards, D.P.

    1996-11-01

    A new interfacial shear stress model called the law of the interface model, based on the law of the wall approach in turbulent flows, has been developed and locally applied in a fully developed, adiabatic, two-phase annular flow in a duct. Numerical results have been obtained using this model in conjunction with other models available in the literature that are required for the closure of the continuity and momentum equations. These results have been compared with droplet velocity data (using laser Doppler velocimetry and hot film anemometry), void fraction data (using gamma densitometry) and pressure drop data obtained in a R-134A refrigerant test facility. Droplet velocity results match the experimental data well, however, the prediction of the void fraction is less accurate. The poor prediction of void fraction, especially for the low void fraction cases, appears to be due to the lack of a good mechanistic model for entrainment

  1. Interfacial shear modeling in two-phase annular flow

    International Nuclear Information System (INIS)

    Kumar, R.; Edwards, D.P.

    1996-07-01

    A new interfacial shear stress model called the law of the interface model, based on the law of the wall approach in turbulent flows, has been developed and locally applied in a fully developed, adiabatic, two-phase annular flow in a duct. Numerical results have been obtained using this model in conjunction with other models available in the literature that are required for the closure of the continuity and momentum equations. These results have been compared with droplet velocity data (using laser Doppler velocimetry and hot film anemometry), void fraction data (using gamma densitometry) and pressure drop data obtained in a R-134A refrigerant test facility. Droplet velocity results match the experimental data well, however, the prediction of the void fraction is less accurate. The poor prediction of void fraction, especially for the low void fraction cases, appears to be due to the lack of a good mechanistic model for entrainment

  2. A Summary of Interfacial Heat Transfer Models and Correlations

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sung Won; Cho, Hyung Kyu; Lee, Young Jin; Kim, Hee Chul; Jung, Young Jong; Kim, K. D. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2007-10-15

    A long term project has been launched in October 2006 to develop a plant safety analysis code. 5 organizations are joining together for the harmonious coworking to build up the code. In this project, KAERI takes the charge of the building up the physical models and correlations about the transport phenomena. The momentum and energy transfer terms as well as the mass are surveyed from the RELAP5/MOD3, RELAP5-3D, CATHARE, and TRAC-M does. Also the recent papers are surveyed. Among these resources, most of the CATHARE models are based on their own experiment and test results. Thus, the CATHARE models are only used as the comparison purposes. In this paper, a summary of the models and the correlations about the interfacial heat transfer are represented. These surveyed models and correlations will be tested numerically and one correlation is selected finally.

  3. Unsteady interfacial coupling of two-phase flow models

    International Nuclear Information System (INIS)

    Hurisse, O.

    2006-01-01

    The primary coolant circuit in a nuclear power plant contains several distinct components (vessel, core, pipes,...). For all components, specific codes based on the discretization of partial differential equations have already been developed. In order to obtain simulations for the whole circuit, the interfacial coupling of these codes is required. The approach examined within this work consists in coupling codes by providing unsteady information through the coupling interface. The numerical technique relies on the use of an interface model, which is combined with the basic strategy that was introduced by Greenberg and Leroux in order to compute approximations of steady solutions of non-homogeneous hyperbolic systems. Three different coupling cases have been examined: (i) the coupling of a one-dimensional Euler system with a two-dimensional Euler system; (ii) the coupling of two distinct homogeneous two-phase flow models; (iii) the coupling of a four-equation homogeneous model with the standard two-fluid model. (author)

  4. Physical Basis for Interfacial Traction-Separation Models

    International Nuclear Information System (INIS)

    Neville R. Moody

    2002-01-01

    Many weapon components contain interfaces between dissimilar materials where cracks can initiate and cause failure. In recent years many researchers in the fracture community have adopted a cohesive zone model for simulating crack propagation (based upon traction-separation relations) Sandia is implementing this model in its ASCI codes. There is, however, one important obstacle to using a cohesive zone modeling approach. At the present time traction-separation relations are chosen in an ad hoc manner. The goal of the present work is to determine a physical basis for Traction-Separation (T-U) relations. This report presents results of a program aimed at determining the dependence of such relations on adhesive and bulk properties. The work focused on epoxy/solid interfaces, although the approach is applicable to a broad range of materials. Asymmetric double cantilevered beam and free surface film nanoindentation fracture toughness tests were used to generate a unique set of data spanning length scales, applied mode mixities, and yield (plastic) zone constraint. The crucial roles of crack tip plastic zone size and interfacial adhesion were defined by varying epoxy layer thickness and using coupling agents or special self-assembled monolayers in preparing the samples. The nature of the yield zone was probed in collaborative experiments run at the Advanced Photon Source. This work provides an understanding of the major phenomena governing polymer/solid interfacial fracture and identifies the essential features that must be incorporated in a T-U based cohesive zone failure model. We believe that models using physically based T-U relations provide a more accurate and widely applicable description of interface cracking than models using ad hoc relations. Furthermore, these T-U relations provide an essential tool for using models to tailor interface properties to meet design needs

  5. Assessment of interfacial heat transfer models under subcooled flow boiling

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Guilherme B.; Braz Filho, Francisco A., E-mail: gbribeiro@ieav.cta.br, E-mail: fbraz@ieav.cta.br [Instituto de Estudos Avançados (DCTA/IEAv), São José dos Campos, SP (Brazil). Div. de Energia Nuclear

    2017-07-01

    The present study concerns a detailed analysis of subcooled flow boiling characteristics under high pressure systems using a two-fluid Eulerian approach provided by a Computational Fluid Dynamics (CFD) solver. For this purpose, a vertical heated pipe made of stainless steel with an internal diameter of 15.4 mm was considered as the modeled domain. An uniform heat flux of 570 kW/m2 and saturation pressure of 4.5 MPa were applied to the channel wall, whereas water mass flux of 900 kg/m2s was considered for all simulation cases. The model was validated against a set of experimental data and results have indicated a promising use of CFD technique for the estimation of wall temperature, the liquid bulk temperature and the location of the departure of nucleate boiling. Different sub-models of interfacial heat transfer coefficient were applied and compared, allowing a better prediction of void fraction along the heated channel. (author)

  6. Modelling CO2-Brine Interfacial Tension using Density Gradient Theory

    KAUST Repository

    Ruslan, Mohd Fuad Anwari Che

    2018-03-01

    Knowledge regarding carbon dioxide (CO2)-brine interfacial tension (IFT) is important for petroleum industry and Carbon Capture and Storage (CCS) strategies. In petroleum industry, CO2-brine IFT is especially importance for CO2 – based enhanced oil recovery strategy as it affects phase behavior and fluid transport in porous media. CCS which involves storing CO2 in geological storage sites also requires understanding regarding CO2-brine IFT as this parameter affects CO2 quantity that could be securely stored in the storage site. Several methods have been used to compute CO2-brine interfacial tension. One of the methods employed is by using Density Gradient Theory (DGT) approach. In DGT model, IFT is computed based on the component density distribution across the interface. However, current model is only applicable for modelling low to medium ionic strength solution. This limitation is due to the model only considers the increase of IFT due to the changes of bulk phases properties and does not account for ion distribution at interface. In this study, a new modelling strategy to compute CO2-brine IFT based on DGT was proposed. In the proposed model, ion distribution across interface was accounted for by separating the interface to two sections. The saddle point of tangent plane distance where ( ) was defined as the boundary separating the two sections of the interface. Electrolyte is assumed to be present only in the second section which is connected to the bulk liquid phase side. Numerical simulations were performed using the proposed approach for single and mixed salt solutions for three salts (NaCl, KCl, and CaCl2), for temperature (298 K to 443 K), pressure (2 MPa to 70 MPa), and ionic strength (0.085 mol·kg-1 to 15 mol·kg-1). The simulation result shows that the tuned model was able to predict with good accuracy CO2-brine IFT for all studied cases. Comparison with current DGT model showed that the proposed approach yields better match with the experiment data

  7. Stochastic models for tumoral growth

    Science.gov (United States)

    Escudero, Carlos

    2006-02-01

    Strong experimental evidence has indicated that tumor growth belongs to the molecular beam epitaxy universality class. This type of growth is characterized by the constraint of cell proliferation to the tumor border and the surface diffusion of cells at the growing edge. Tumor growth is thus conceived as a competition for space between the tumor and the host, and cell diffusion at the tumor border is an optimal strategy adopted for minimizing the pressure and helping tumor development. Two stochastic partial differential equations are reported in this paper in order to correctly model the physical properties of tumoral growth in (1+1) and (2+1) dimensions. The advantage of these models is that they reproduce the correct geometry of the tumor and are defined in terms of polar variables. An analysis of these models allows us to quantitatively estimate the response of the tumor to an unfavorable perturbation during growth.

  8. Skull base tumor model.

    Science.gov (United States)

    Gragnaniello, Cristian; Nader, Remi; van Doormaal, Tristan; Kamel, Mahmoud; Voormolen, Eduard H J; Lasio, Giovanni; Aboud, Emad; Regli, Luca; Tulleken, Cornelius A F; Al-Mefty, Ossama

    2010-11-01

    Resident duty-hours restrictions have now been instituted in many countries worldwide. Shortened training times and increased public scrutiny of surgical competency have led to a move away from the traditional apprenticeship model of training. The development of educational models for brain anatomy is a fascinating innovation allowing neurosurgeons to train without the need to practice on real patients and it may be a solution to achieve competency within a shortened training period. The authors describe the use of Stratathane resin ST-504 polymer (SRSP), which is inserted at different intracranial locations to closely mimic meningiomas and other pathological entities of the skull base, in a cadaveric model, for use in neurosurgical training. Silicone-injected and pressurized cadaveric heads were used for studying the SRSP model. The SRSP presents unique intrinsic metamorphic characteristics: liquid at first, it expands and foams when injected into the desired area of the brain, forming a solid tumorlike structure. The authors injected SRSP via different passages that did not influence routes used for the surgical approach for resection of the simulated lesion. For example, SRSP injection routes included endonasal transsphenoidal or transoral approaches if lesions were to be removed through standard skull base approach, or, alternatively, SRSP was injected via a cranial approach if the removal was planned to be via the transsphenoidal or transoral route. The model was set in place in 3 countries (US, Italy, and The Netherlands), and a pool of 13 physicians from 4 different institutions (all surgeons and surgeons in training) participated in evaluating it and provided feedback. All 13 evaluating physicians had overall positive impressions of the model. The overall score on 9 components evaluated--including comparison between the tumor model and real tumor cases, perioperative requirements, general impression, and applicability--was 88% (100% being the best possible

  9. Cold welding of organic light emitting diode: Interfacial and contact models

    Directory of Open Access Journals (Sweden)

    J. Asare

    2016-06-01

    Full Text Available This paper presents the results of an analytical and computational study of the contacts and interfacial fracture associated with the cold welding of Organic Light Emitting diodes (OLEDs. The effects of impurities (within the possible interfaces are explored for contacts and interfacial fracture between layers that are relevant to model OLEDs. The models are used to study the effects of adhesion, pressure, thin film layer thickness and dust particle modulus (between the contacting surfaces on contact profiles around impurities between cold-welded thin films. The lift-off stage of thin films (during cold welding is then modeled as an interfacial fracture process. A combination of adhesion and interfacial fracture theories is used to provide new insights for the design of improved contact and interfacial separation during cold welding. The implications of the results are discussed for the design and fabrication of cold welded OLED structures.

  10. Coupled Interfacial Tension and Phase Behavior Model Based on Micellar Curvatures

    KAUST Repository

    Torrealba, V. A.; Johns, R. T.

    2017-01-01

    This article introduces a consistent and robust model that predicts interfacial tensions for all microemulsion Winsor types and overall compositions. The model incorporates film bending arguments and Huh's equation and is coupled to phase behavior

  11. Models and Correlations of Interfacial and Wall Frictions for the SPACE code

    International Nuclear Information System (INIS)

    Kim, Soo Hyung; Hwang, Moon Kyu; Chung, Bub Dong

    2010-04-01

    This report describes models and correlations for the interfacial and wall frictions implemented in the SPACE code which has the capability to predict thermal-hydraulic behavior of nuclear power plants. The interfacial and wall frictions are essential to solve the momentum conservation equations of gas, continuous liquid and droplet. The interfacial and wall frictions are dealt in the Chapter 2 and 3, respectively. In Chapter 4, selection criteria for models and correlations are explained. In Chapter 5, the origins of the selected models and correlations used in this code are examined to check whether they are in confliction with intellectual proprietary rights

  12. Phase field modelling of precipitate morphologies in systems with tetragonal interfacial free energy anisotropy

    OpenAIRE

    Roy, Arijit; Gururajan, M P

    2017-01-01

    A wide variety of morphologies arise due to the tetragonal anisotropy in interfacial free energy. In this paper, we report on a family of Extended Cahn-Hilliard (ECH) models for incorporating tetragonal anisotropy in interfacial free energy. We list the non-zero and independent parameters that are introduced in our model and list the constraints on them. For appropriate choice of these parameters, our model can produce a many of the morphologies seen in tetragonal systems such as di-pyramids,...

  13. State-of-the-art report on the theoretical modeling of interfacial area concentration

    International Nuclear Information System (INIS)

    Lee, Won Jae; Euh, Dong Jin

    1998-03-01

    Classical approaches based on experimental correlations and the mechanistic approaches based on the interfacial area concentration were reviewed. The study focuses on the state-of-the-art researches based on the mechanistic modeling of the interfacial area concentration. The investigation is performed by classifying the mechanistic modeling approaches into those using the number density transport equations supported with a simple algebraic relation for obtaining interfacial area concentration and those using the direct interfacial area transport equations. The modeling approaches are subdivided into one group and multi-group models. The state-of-the-art source terms of transport equations are also investigated for their applicability and limitations. (author). 62 refs., 6 tabs., 49 figs

  14. Coupled Interfacial Tension and Phase Behavior Model Based on Micellar Curvatures

    KAUST Repository

    Torrealba, V. A.

    2017-11-08

    This article introduces a consistent and robust model that predicts interfacial tensions for all microemulsion Winsor types and overall compositions. The model incorporates film bending arguments and Huh\\'s equation and is coupled to phase behavior so that simultaneous tuning of both interfacial tension (IFT) and phase behavior is possible. The oil-water interfacial tension and characteristic length are shown to be related to each other through the hydrophilic-lipophilic deviation (HLD). The phase behavior is tied to the micelle curvatures, without the need for using the net average curvature (NAC). The interfacial tension model is related to solubilization ratios in order to introduce a coupled interfacial tension-phase behavior model for all phase environments. The approach predicts two- and three-phase interfacial tensions and phase behavior (i.e., tie lines and tie triangles) for changes in composition and HLD input parameters, such as temperature, pressure, surfactant structure, and oil equivalent alkane carbon number. Comparisons to experimental data show excellent fits and predictive capability.

  15. Two-group modeling of interfacial area transport in large diameter channels

    Energy Technology Data Exchange (ETDEWEB)

    Schlegel, J.P., E-mail: schlegelj@mst.edu [Department of Mining and Nuclear Engineering, Missouri University of Science and Technology, 301 W 14th St., Rolla, MO 65409 (United States); Hibiki, T.; Ishii, M. [School of Nuclear Engineering, Purdue University, 400 Central Dr., West Lafayette, IN 47907 (United States)

    2015-11-15

    Highlights: • Implemented updated constitutive models and benchmarking method for IATE in large pipes. • New model and method with new data improved the overall IATE prediction for large pipes. • Not all conditions well predicted shows that further development is still required. - Abstract: A comparison of the existing two-group interfacial area transport equation source and sink terms for large diameter channels with recently collected interfacial area concentration measurements (Schlegel et al., 2012, 2014. Int. J. Heat Fluid Flow 47, 42) has indicated that the model does not perform well in predicting interfacial area transport outside of the range of flow conditions used in the original benchmarking effort. In order to reduce the error in the prediction of interfacial area concentration by the interfacial area transport equation, several constitutive relations have been updated including the turbulence model and relative velocity correlation. The transport equation utilizing these updated models has been modified by updating the inter-group transfer and Group 2 coalescence and disintegration kernels using an expanded range of experimental conditions extending to pipe sizes of 0.304 m [12 in.], gas velocities of up to nearly 11 m/s [36.1 ft/s] and liquid velocities of up to 2 m/s [6.56 ft/s], as well as conditions with both bubbly flow and cap-bubbly flow injection (Schlegel et al., 2012, 2014). The modifications to the transport equation have resulted in a decrease in the RMS error for void fraction and interfacial area concentration from 17.32% to 12.3% and 21.26% to 19.6%. The combined RMS error, for both void fraction and interfacial area concentration, is below 15% for most of the experiments used in the comparison, a distinct improvement over the previous version of the model.

  16. Experimental study of interfacial shear stress for an analogy model of evaporative heat transfer

    International Nuclear Information System (INIS)

    Kwon, Hyuk; Park, GoonCherl; Min, ByungJoo

    2008-01-01

    In this study, we conducted measurements of an evaporative interfacial shear stress in a passive containment cooling system (PCCS). An interfacial shear stress for a counter-current flow was measured from a momentum balance equation and the interfacial friction factor for evaporation was evaluated by using experimental data. A model for the evaporative heat transfer coefficient of a vertical evaporative flat surface was developed based on an analogy between heat and momentum transfer. It was found that the interfacial shear stress increases with the Jacob number, which incorporates the evaporation rate, and the air and water Reynolds numbers. The relationship between the evaporative heat transfer and the interfacial shear stress was evaluated by using the experimental results. This relationship was used to develop a model for an evaporative heat transfer coefficient by using an analogy between heat and mass transfer. The prediction of this model were found to be in good agreement with the experimental data obtained for evaporative heat transfer by Kang and Park. (author)

  17. A phenomenological model of coating/substrate adhesion and interfacial bimetallic peeling stress in composite mirrors

    Science.gov (United States)

    Mcelroy, Paul M.; Lawson, Daniel D.

    1990-01-01

    Adhesion and interfacial stress between metal films and structural composite material substrates is discussed. A theoretical and conceptual basis for selecting coating materials for composite mirror substrates is described. A phenomenological model that interrelates cohesive tensile strength of thin film coatings and interfacial peeling stresses is presented. The model serves as a basis in determining gradiated materials response and compatibility of composite substrate and coating combinations. Parametric evaluation of material properties and geometrical factors such as coating thickness are used to determine the threshold stress levels for maintaining adhesion at the different interfaces.

  18. Modeling the Effects of Interfacial Characteristics on Gas Permeation Behavior of Nanotube-Mixed Matrix Membranes.

    Science.gov (United States)

    Chehrazi, Ehsan; Sharif, Alireza; Omidkhah, Mohammadreza; Karimi, Mohammad

    2017-10-25

    Theoretical approaches that accurately predict the gas permeation behavior of nanotube-containing mixed matrix membranes (nanotube-MMMs) are scarce. This is mainly due to ignoring the effects of nanotube/matrix interfacial characteristics in the existing theories. In this paper, based on the analogy of thermal conduction in polymer composites containing nanotubes, we develop a model to describe gas permeation through nanotube-MMMs. Two new parameters, "interfacial thickness" (a int ) and "interfacial permeation resistance" (R int ), are introduced to account for the role of nanotube/matrix interfacial interactions in the proposed model. The obtained values of a int , independent of the nature of the permeate gas, increased by increasing both the nanotubes aspect ratio and polymer-nanotube interfacial strength. An excellent correlation between the values of a int and polymer-nanotube interaction parameters, χ, helped to accurately reproduce the existing experimental data from the literature without the need to resort to any adjustable parameter. The data includes 10 sets of CO 2 /CH 4 permeation, 12 sets of CO 2 /N 2 permeation, 3 sets of CO 2 /O 2 permeation, and 2 sets of CO 2 /H 2 permeation through different nanotube-MMMs. Moreover, the average absolute relative errors between the experimental data and the predicted values of the proposed model are very small (less than 5%) in comparison with those of the existing models in the literature. To the best of our knowledge, this is the first study where such a systematic comparison between model predictions and such extensive experimental data is presented. Finally, the new way of assessing gas permeation data presented in the current work would be a simple alternative to complex approaches that are usually utilized to estimate interfacial thickness in polymer composites.

  19. A thermal conductivity model for nanofluids including effect of the temperature-dependent interfacial layer

    International Nuclear Information System (INIS)

    Sitprasert, Chatcharin; Dechaumphai, Pramote; Juntasaro, Varangrat

    2009-01-01

    The interfacial layer of nanoparticles has been recently shown to have an effect on the thermal conductivity of nanofluids. There is, however, still no thermal conductivity model that includes the effects of temperature and nanoparticle size variations on the thickness and consequently on the thermal conductivity of the interfacial layer. In the present work, the stationary model developed by Leong et al. (J Nanopart Res 8:245-254, 2006) is initially modified to include the thermal dispersion effect due to the Brownian motion of nanoparticles. This model is called the 'Leong et al.'s dynamic model'. However, the Leong et al.'s dynamic model over-predicts the thermal conductivity of nanofluids in the case of the flowing fluid. This suggests that the enhancement in the thermal conductivity of the flowing nanofluids due to the increase in temperature does not come from the thermal dispersion effect. It is more likely that the enhancement in heat transfer of the flowing nanofluids comes from the temperature-dependent interfacial layer effect. Therefore, the Leong et al.'s stationary model is again modified to include the effect of temperature variation on the thermal conductivity of the interfacial layer for different sizes of nanoparticles. This present model is then evaluated and compared with the other thermal conductivity models for the turbulent convective heat transfer in nanofluids along a uniformly heated tube. The results show that the present model is more general than the other models in the sense that it can predict both the temperature and the volume fraction dependence of the thermal conductivity of nanofluids for both non-flowing and flowing fluids. Also, it is found to be more accurate than the other models due to the inclusion of the effect of the temperature-dependent interfacial layer. In conclusion, the present model can accurately predict the changes in thermal conductivity of nanofluids due to the changes in volume fraction and temperature for

  20. Implementation of a new interfacial mass and energy transfer model in RETRAN-3D

    International Nuclear Information System (INIS)

    Macian, R.; Cebulh, P.; Coddington, P.; Paulsen, M.

    1999-01-01

    The RETRAN-3D MOD002.0 best estimate code includes a five-equation flow field model developed to deal with situations in which thermodynamic non-equilibrium phenomena are important. Several applications of this model to depressurization and pressurization transients showed serious convergence problems. An analysis of the causes for the numerical instabilities identified the models for interfacial heat and mass transfer as the source of the problems. A new interfacial mass and energy transfer model has thus been developed and implemented in RETRAN-3D. The heat transfer for each phase is equal to the product of the interfacial area density, a heat transfer coefficient and the temperature difference between the interface at saturation and the bulk temperature of the respective phase. However, in the context of RETRAN-3D, the vapor remains saturated in a two-phase volume, and no vapor heat transfer is thus calculated. The values of interfacial area density and heat transfer coefficient are obtained based on correlations appropriate for different flow regimes. A flow regime map, based on the work of Taitel and Dukler, with void fraction and mixture mass flux as map coordinates, is used to identify the flow regime present in a given volume. The new model has performed well when assessed against data from four experimental facilities covering depressurization, condensation and steady state void distribution. The results also demonstrate the viability of the approach followed to develop the new model for a five-equation based code. (author)

  1. Modeling of Pressure Dependence of Interfacial Tension Behaviors of Supercritical CO2 + Crude Oil Systems Using a Basic Parachor Expression

    International Nuclear Information System (INIS)

    Dayanand, S.

    2017-01-01

    Parachor based expressions (basic and mechanistic) are often used to model the experimentally observed pressure dependence of interfacial tension behaviors of complex supercritical carbon dioxide (sc-CO 2 ) and crude oil mixtures at elevated temperatures. However, such modeling requires various input data (e.g. compositions and densities of the equilibrium liquid and vapor phases, and molecular weights and diffusion coefficients for various components present in the system). In the absence of measured data, often phase behavior packages are used for obtaining these input data for performing calculations. Very few researchers have used experimentally measured input data for performing parachor based modeling of the experimental interfacial tension behaviors of sc-CO 2 and crude oil systems that are of particular interest to CO 2 injection in porous media based enhanced oil recovery operations. This study presents the results of parachor based modeling performed to predict pressure dependence of interfacial tension behaviors of a complex sc-CO 2 and crude oil system for which experimentally measured data is available in public domain. Though parachor model based on calculated interfacial tension behaviors shows significant deviation from the measured behaviors in high interfacial tension region, difference between the calculated and the experimental behaviors appears to vanish in low interfacial tension region. These observations suggest that basic parachor expression based calculated interfacial tension behaviors in low interfacial tension region follow the experimental interfacial tension behaviors more closely. An analysis of published studies (basic and mechanistic parachor expressions based on modeling of pressure dependence of interfacial tension behaviors of both standard and complex sc-CO 2 and crude oil systems) and the results of this study reinforce the need of better description of gas-oil interactions for robust modeling of pressure dependence of

  2. Comparison for the interfacial and wall friction models in thermal-hydraulic system analysis codes

    International Nuclear Information System (INIS)

    Hwang, Moon Kyu; Park, Jee Won; Chung, Bub Dong; Kim, Soo Hyung; Kim, See Dal

    2007-07-01

    The average equations employed in the current thermal hydraulic analysis codes need to be closed with the appropriate models and correlations to specify the interphase phenomena along with fluid/structure interactions. This includes both thermal and mechanical interactions. Among the closure laws, an interfacial and wall frictions, which are included in the momentum equations, not only affect pressure drops along the fluid flow, but also have great effects for the numerical stability of the codes. In this study, the interfacial and wall frictions are reviewed for the commonly applied thermal-hydraulic system analysis codes, i.e. RELAP5-3D, MARS-3D, TRAC-M, and CATHARE

  3. Development of two-group interfacial area transport equation for confined flow-2. Model evaluation

    International Nuclear Information System (INIS)

    Sun, Xiaodong; Kim, Seungjin; Ishii, Mamoru; Beus, Stephen G.

    2003-01-01

    The bubble interaction mechanisms have been analytically modeled in the first paper of this series to provide mechanistic constitutive relations for the two-group interfacial area transport equation (IATE), which was proposed to dynamically solve the interfacial area concentration in the two-fluid model. This paper presents the evaluation approach and results of the two-group IATE based on available experimental data obtained in confined flow, namely, 11 data sets in or near bubbly flow and 13 sets in cap-turbulent and churn-turbulent flow. The two-group IATE is evaluated in steady state, one-dimensional form. Also, since the experiments were performed under adiabatic, air-water two-phase flow conditions, the phase change effect is omitted in the evaluation. To account for the inter-group bubble transport, the void fraction transport equation for Group-2 bubbles is also used to predict the void fraction for Group-2 bubbles. Agreement between the data and the model predictions is reasonably good and the average relative difference for the total interfacial area concentration between the 24 data sets and predictions is within 7%. The model evaluation demonstrates the capability of the two-group IATE focused on the current confined flow to predict the interfacial area concentration over a wide range of flow regimes. (author)

  4. Interfacial tension and wettability in water-carbon dioxide systems: Experiments and self-consistent field modeling

    NARCIS (Netherlands)

    Banerjee, S.; Hassenklover, E.; Kleijn, J.M.; Cohen Stuart, M.A.; Leermakers, F.A.M.

    2013-01-01

    This paper presents experimental and modeling results on water–CO2 interfacial tension (IFT) together with wettability studies of water on both hydrophilic and hydrophobic surfaces immersed in CO2. CO2–water interfacial tension (IFT) measurements showed that the IFT decreased with increasing

  5. Experimental rat lung tumor model with intrabronchial tumor cell implantation.

    Science.gov (United States)

    Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

    2008-01-01

    The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

  6. Interfacial rheology of model particles at liquid interfaces and its relation to (bicontinuous) Pickering emulsions

    Science.gov (United States)

    Thijssen, J. H. J.; Vermant, J.

    2018-01-01

    Interface-dominated materials are commonly encountered in both science and technology, and typical examples include foams and emulsions. Conventionally stabilised by surfactants, emulsions can also be stabilised by micron-sized particles. These so-called Pickering-Ramsden (PR) emulsions have received substantial interest, as they are model arrested systems, rather ubiquitous in industry and promising templates for advanced materials. The mechanical properties of the particle-laden liquid-liquid interface, probed via interfacial rheology, have been shown to play an important role in the formation and stability of PR emulsions. However, the morphological processes which control the formation of emulsions and foams in mixing devices, such as deformation, break-up, and coalescence, are complex and diverse, making it difficult to identify the precise role of the interfacial rheological properties. Interestingly, the role of interfacial rheology in the stability of bicontinuous PR emulsions (bijels) has been virtually unexplored, even though the phase separation process which leads to the formation of these systems is relatively simple and the interfacial deformation processes can be better conceptualised. Hence, the aims of this topical review are twofold. First, we review the existing literature on the interfacial rheology of particle-laden liquid interfaces in rheometrical flows, focussing mainly on model latex suspensions consisting of polystyrene particles carrying sulfate groups, which have been most extensively studied to date. The goal of this part of the review is to identify the generic features of the rheology of such systems. Secondly, we will discuss the relevance of these results to the formation and stability of PR emulsions and bijels.

  7. Modelling CO2-Brine Interfacial Tension using Density Gradient Theory

    KAUST Repository

    Ruslan, Mohd Fuad Anwari Che

    2018-01-01

    In this study, a new modelling strategy to compute CO2-brine IFT based on DGT was proposed. In the proposed model, ion distribution across interface was accounted for by separating the interface to two sections

  8. Modeling Delamination of Interfacial Corner Cracks in Multilayered Structures

    DEFF Research Database (Denmark)

    Veluri, Badrinath (Badri); Jensen, Henrik Myhre

    2013-01-01

    Multilayered electronic components, typically of heterogeneous materials, delaminate under thermal and mechanical loading. A phenomenological model focused on modeling the shape of such interface cracks close to corners in layered interconnect structures for calculating the critical stress...

  9. Stochastic models for tumoral growth

    OpenAIRE

    Escudero, Carlos

    2006-01-01

    Strong experimental evidence has indicated that tumor growth belongs to the molecular beam epitaxy universality class. This type of growth is characterized by the constraint of cell proliferation to the tumor border, and surface diffusion of cells at the growing edge. Tumor growth is thus conceived as a competition for space between the tumor and the host, and cell diffusion at the tumor border is an optimal strategy adopted for minimizing the pressure and helping tumor development. Two stoch...

  10. Modified two-fluid model for the two-group interfacial area transport equation

    International Nuclear Information System (INIS)

    Sun Xiaodong; Ishii, Mamoru; Kelly, Joseph M.

    2003-01-01

    This paper presents a modified two-fluid model that is ready to be applied in the approach of the two-group interfacial area transport equation. The two-group interfacial area transport equation was developed to provide a mechanistic constitutive relation for the interfacial area concentration in the two-fluid model. In the two-group transport equation, bubbles are categorized into two groups: spherical/distorted bubbles as Group 1 while cap/slug/churn-turbulent bubbles as Group 2. Therefore, this transport equation can be employed in the flow regimes spanning from bubbly, cap bubbly, slug to churn-turbulent flows. However, the introduction of the two groups of bubbles requires two gas velocity fields. Yet it is not practical to solve two momentum equations for the gas phase alone. In the current modified two-fluid model, a simplified approach is proposed. The momentum equation for the averaged velocity of both Group-1 and Group-2 bubbles is retained. By doing so, the velocity difference between Group-1 and Group-2 bubbles needs to be determined. This may be made either based on simplified momentum equations for both Group-1 and Group-2 bubbles or by a modified drift-flux model

  11. New modeling and experimental approaches for characterization of two-phase flow interfacial structure

    International Nuclear Information System (INIS)

    Ishii, Mamoru; Sun, Xiaodong

    2004-01-01

    This paper presents new experimental and modeling approaches in characterizing interfacial structures in gas-liquid two-phase flow. For the experiments, two objective approaches are developed to identify flow regimes and to obtain local interfacial structure data. First, a global measurement technique using a non-intrusive ring-type impedance void-meter and a self-organizing neural network is presented to identify the one-dimensional'' flow regimes. In the application of this measurement technique, two methods are discussed, namely, one based on the probability density function of the impedance probe measurement (PDF input method) and the other based on the sorted impedance signals, which is essentially the cumulative probability distribution function of the impedance signals (instantaneous direct signal input method). In the latter method, the identification can be made close to instantaneously since the required signals can be acquired over a very short time period. In addition, a double-sensor conductivity probe can also be used to obtain ''local'' flow regimes by using the instantaneous direct signal input method with the bubble chord length information. Furthermore, a newly designed conductivity probe with multiple double-sensor heads is proposed to obtain ''two-dimensional'' flow regimes across the flow channel. Secondly, a state-of-the-art four-sensor conductivity probe technique has been developed to obtain detailed local interfacial structure information. The four-sensor conductivity probe accommodates the double-sensor probe capability and can be applied in a wide range of flow regimes spanning from bubbly to churn-turbulent flows. The signal processing scheme is developed such that it categorizes the acquired parameters into two groups based on bubble cord length information. Furthermore, for the modeling of the interfacial structure characterization, the interfacial area transport equation proposed earlier has been studied to provide a dynamic and

  12. Computational modeling for fluid flow and interfacial transport

    CERN Document Server

    Shyy, Wei

    2006-01-01

    Practical applications and examples highlight this treatment of computational modeling for handling complex flowfields. A reference for researchers and graduate students of many different backgrounds, it also functions as a text for learning essential computation elements.Drawing upon his own research, the author addresses both macroscopic and microscopic features. He begins his three-part treatment with a survey of the basic concepts of finite difference schemes for solving parabolic, elliptic, and hyperbolic partial differential equations. The second part concerns issues related to computati

  13. Mathematical model for self-propelled droplets driven by interfacial tension

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, Ken H. [School of Materials Science, Japan Advanced Institute of Science and Technology, Nomi, Ishikawa 923-1292 (Japan); Tachibana, Kunihito; Tobe, Yuta; Kazama, Masaki [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Kitahata, Hiroyuki [Department of Physics, Graduate School of Science, Chiba University, Chiba 263-8522 (Japan); Omata, Seiro [Faculty of Mathematics and Physics, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Nagayama, Masaharu, E-mail: nagayama@es.hokudai.ac.jp [Research Institute for Electronic Science, Hokkaido University, Hokkaido 060-0812 (Japan); CREST, Japan Science and Technology Agency, Tokyo 102-0076 (Japan)

    2016-03-21

    We propose a model for the spontaneous motion of a droplet induced by inhomogeneity in interfacial tension. The model is derived from a variation of the Lagrangian of the system and we use a time-discretized Morse flow scheme to perform its numerical simulations. Our model can naturally simulate the dynamics of a single droplet, as well as that of multiple droplets, where the volume of each droplet is conserved. We reproduced the ballistic motion and fission of a droplet, and the collision of two droplets was also examined numerically.

  14. Modeling Insight into Battery Electrolyte Electrochemical Stability and Interfacial Structure.

    Science.gov (United States)

    Borodin, Oleg; Ren, Xiaoming; Vatamanu, Jenel; von Wald Cresce, Arthur; Knap, Jaroslaw; Xu, Kang

    2017-12-19

    spectroscopy. The proton transfer (H-transfer) reactions between solvent molecules on the cathode surface coupled with solvent oxidation were found to be ubiquitous for common Li-ion electrolyte components and dependent on the local molecular environment. Quantum chemistry (QC) calculations on the representative clusters showed that the majority of solvents such as carbonates, phosphates, sulfones, and ethers have significantly lower oxidation potential when oxidation is coupled with H-transfer, while without H-transfer their oxidation potentials reside well beyond battery operating potentials. Thus, screening of the solvent oxidation limits without considering H-transfer reactions is unlikely to be relevant, except for solvents containing unsaturated functionalities (such as C═C) that oxidize without H-transfer. On the anode, the F-transfer reaction and LiF formation during anion and fluorinated solvent reduction could be enhanced or diminished depending on salt and solvent partitioning in the double layer, again giving an additional tool to manipulate the order of reductive decompositions and interphase chemistry. Combined with experimental efforts, modeling results highlight the promise of interphasial compositional control by either bringing the desired components closer to the electrode surface to facilitate redox reaction or expelling them so that they are kinetically shielded from the potential of the electrode.

  15. Current induced torques and interfacial spin-orbit coupling: Semiclassical modeling

    KAUST Repository

    Haney, Paul M.

    2013-05-07

    In bilayer nanowires consisting of a ferromagnetic layer and a nonmagnetic layer with strong spin-orbit coupling, currents create torques on the magnetization beyond those found in simple ferromagnetic nanowires. The resulting magnetic dynamics appear to require torques that can be separated into two terms, dampinglike and fieldlike. The dampinglike torque is typically derived from models describing the bulk spin Hall effect and the spin transfer torque, and the fieldlike torque is typically derived from a Rashba model describing interfacial spin-orbit coupling. We derive a model based on the Boltzmann equation that unifies these approaches. We also consider an approximation to the Boltzmann equation, the drift-diffusion model, that qualitatively reproduces the behavior, but quantitatively differs in some regimes. We show that the Boltzmann equation with physically reasonable parameters can match the torques for any particular sample, but in some cases, it fails to describe the experimentally observed thickness dependencies.

  16. Modeling of the interfacial separation work in relation to impurity concentration in adjoining materials

    Science.gov (United States)

    Alekseev, Ilia M.; Makhviladze, Tariel M.; Minushev, Airat Kh.; Sarychev, Mikhail E.

    2010-02-01

    On the basis of the general thermodynamic approach developed in a model describing the influence of point defects on the separation work at an interface of solid materials is developed. The kinetic equations describing the defect exchange between the interface and the material bulks are formulated. The model have been applied to the case when joined materials contain such point defects as impurity atoms (interstitial and substitutional), concretized the main characteristic parameters required for a numerical modeling as well as clarified their domains of variability. The results of the numerical modeling concerning the dependences on impurity concentrations and the temperature dependences are obtained and analyzed. Particularly, the effects of interfacial strengthening and adhesion incompatibility predicted analytically for the case of impurity atoms are verified and analyzed.

  17. Modeling strategy of the source and sink terms in the two-group interfacial area transport equation

    International Nuclear Information System (INIS)

    Ishii, Mamoru; Sun Xiaodong; Kim, Seungjin

    2003-01-01

    This paper presents the general strategy for modeling the source and sink terms in the two-group interfacial area transport equation. The two-group transport equation is applicable in bubbly, cap bubbly, slug, and churn-turbulent flow regimes to predict the change of the interfacial area concentration. This dynamic approach has an advantage of flow regime-independence over the conventional empirical correlation approach for the interfacial area concentration in the applications with the two-fluid model. In the two-group interfacial area transport equation, bubbles are categorized into two groups: spherical/distorted bubbles as Group 1 and cap/slug/churn-turbulent bubbles as Group 2. Thus, two sets of equations are used to describe the generation and destruction rates of bubble number density, void fraction, and interfacial area concentration for the two groups of bubbles due to bubble expansion and compression, coalescence and disintegration, and phase change. Based upon a detailed literature review of the research on the bubble interactions, five major bubble interaction mechanisms are identified for the gas-liquid two-phase flow of interest. A systematic integral approach, in which the significant variations of bubble volume and shape are accounted for, is suggested for the modeling of two-group bubble interactions. To obtain analytical forms for the various bubble interactions, a simplification is made for the bubble number density distribution function

  18. Model compounds for heavy crude oil components and tetrameric acids: Characterization and interfacial behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Nordgaard, Erland Loeken

    2009-07-01

    The tendency during the past decades in the quality of oil reserves shows that conventional crude oil is gradually being depleted and the demand being replaced by heavy crude oils. These oils contain more of a class high-molecular weight components termed asphaltenes. This class is mainly responsible for stable water-in-crude oil emulsions. Both heavy and lighter crude oils in addition contain substantial amounts of naphthenic acids creating naphthenate deposits in topside facilities. The asphaltene class is defined by solubility and consists of several thousand different structures which may behave differently in oil-water systems. The nature of possible sub fractions of the asphaltene has been received more attention lately, but still the properties and composition of such is not completely understood. In this work, the problem has been addressed by synthesizing model compounds for the asphaltenes, on the basis that an acidic function incorporated could be crucial. Such acidic, poly aromatic surfactants turned out to be highly inter facially active as studied by the pendant drop technique. Langmuir monolayer compressions combined with fluorescence of deposited films indicated that the interfacial activity was a result of an efficient packing of the aromatic cores in the molecules, giving stabilizing interactions at the o/w interface. Droplet size distributions of emulsions studied by PFG NMR and adsorption onto hydrophilic silica particles demonstrated the high affinity to o/w interfaces and that the efficient packing gave higher emulsion stability. Comparing to a model compound lacking the acidic group, it was obvious that sub fractions of asphaltenes that contain an acidic, or maybe similar hydrogen bonding functions, could be responsible for stable w/o emulsions. Indigenous tetrameric acids are the main constituent of calcium naphthenate deposits. Several synthetic model tetra acids have been prepared and their properties have been compared to the indigenous

  19. Assessment of some interfacial shear correlations in a model of ECC bypass flow in PWR reactor downcomer

    International Nuclear Information System (INIS)

    Popov, N.K.; Rohatgi, U.S.

    1987-01-01

    The bypass/refill process in the PWR reactor downcomer, following a large rupture of a cold leg coolant supply pipe, is a complicated thermo-hydraulic two-phase flow phenomenon. Mathematical modeling of such phenomena is always accompanied with a difficult task of selection of suitable constitutive correlations. In a typically hydrodynamic phenomenon, like ECC refill process of the reactor lower plenum is considered, the phasic interfacial friction is the most influential constitutive correlation. Therefore, assessment of the well-known widely-used interfacial friction constitutive correlations in the model of ECC bypass/refill process, is the subject of this paper

  20. Comparison of Interfacial and Wall Friction Models in Thermal-Hydraulic System Analysis Codes (Rev1.0)

    International Nuclear Information System (INIS)

    Hwang, Moon Kyu; Kim, Soo Hyung; Kim, Byung Jae; Chung, Bub Dong; Kim, Hee Cheol

    2010-04-01

    This reports is a literature survey on models and correlations for interfacial and wall friction models that are used to simulate thermal-hydraulics in nuclear reactors. The interfacial and wall frictions are needed to solve the momentum equations of gas, continuous liquid and droplet. Not only existing system codes, such as RELAP5-3D, TRAC-M, MARS, TRACE, CATHARE) but also up-to-date researches were reviewed. This report is a revised version of the previous technical report(KAERI/TR-3437/2007)

  1. Sensitivity Analysis of Interfacial Tension on Saturation and Relative Permeability Model Predictions

    KAUST Repository

    Abdallah, Wael; Zhao, Weishu; Gmira, Ahmed; Negara, Ardiansyah; Buiting, Jan

    2011-01-01

    Interfacial tension (IFT) measurements of Dodecane/brine systems at different concentrations and Dodecane/deionized water subject to different Dodecane purification cycles were taken over extended durations at room temperature and pressure to investigate the impact of aging. When a fresh droplet was formed, a sharp drop in IFT was observed assumed to be a result of intrinsic impurity adsorption at the interface. The subsequent measurements exhibited a prolonged equilibration period consistent with diffusion from the bulk phase to the interface. Our results indicate that minute amounts of impurities present in experimental chemical fluids "used as received" have a drastic impact on the properties of the interface. Initial and equilibrium IFT are shown to be dramatically different, therefore it is important to be cautious of utilizing IFT values in numerical models. The study demonstrates the impact these variations in IFT have on relative permeability relationships by adopting a simple pore network model simulation.

  2. Sensitivity Analysis of Interfacial Tension on Saturation and Relative Permeability Model Predictions

    KAUST Repository

    Abdallah, Wael

    2011-05-18

    Interfacial tension (IFT) measurements of Dodecane/brine systems at different concentrations and Dodecane/deionized water subject to different Dodecane purification cycles were taken over extended durations at room temperature and pressure to investigate the impact of aging. When a fresh droplet was formed, a sharp drop in IFT was observed assumed to be a result of intrinsic impurity adsorption at the interface. The subsequent measurements exhibited a prolonged equilibration period consistent with diffusion from the bulk phase to the interface. Our results indicate that minute amounts of impurities present in experimental chemical fluids "used as received" have a drastic impact on the properties of the interface. Initial and equilibrium IFT are shown to be dramatically different, therefore it is important to be cautious of utilizing IFT values in numerical models. The study demonstrates the impact these variations in IFT have on relative permeability relationships by adopting a simple pore network model simulation.

  3. Impact of Interfacial Characteristics on Foam Structure: Study on Model Fluids and at Pilot Scale

    Directory of Open Access Journals (Sweden)

    Mezdour Samir

    2017-03-01

    Full Text Available Foams represent an important area of research because of their relevance to many industrial processes. In continuous foaming operations, foaming ability depends on the process parameters and the characteristics of the raw materials used for foamed products. The effects of fluid viscosity and equilibrium surface tension on foam structure have been studied extensively. Furthermore, as surface active agents diffuse to the interface, they can modify other interface properties through their adsorption, such as interfacial rheology and surface tension kinetics. In order to better understand how these two interfacial properties influence foam structuring, we formulated model foaming solutions with different interface viscoelasticity levels and adsorption rates, but all with the same equilibrium surface tension and viscosity. The solutions were made up of a surface active agent and glucose syrup, so as to maintain a Newtonian behaviour. Five surface active agents were used: Whey Protein Isolate (WPI, sodium caseinate, saponin, cetyl phosphate and Sodium Dodecyl Sulphate (SDS, at concentrations ranging from 0.1% to 1%. Their molecular characteristics, and their interaction with the glucose syrup, made it possible to obtain a range of interface viscoelasticities and surface tension kinetics for these model solutions. The solutions were whipped in a continuously-operating industrial foaming device in order to control process parameters such as shearing and overrun, and to ensure that the experiment was representative of industrial production. The structure of the foams thus obtained foams was then determined by characterising bubble size using image analysis. For all the model solutions, both the viscoelastic moduli and apparent diffusion coefficient were linked to foam structure. The results showed that both high interface viscoelasticity and rapid diffusion kinetics induced a foam structure containing small bubbles. Both effects, as well as the impact of

  4. Modelling of AlAs/GaAs interfacial structures using high-angle annular dark field (HAADF) image simulations.

    Science.gov (United States)

    Robb, Paul D; Finnie, Michael; Craven, Alan J

    2012-07-01

    High angle annular dark field (HAADF) image simulations were performed on a series of AlAs/GaAs interfacial models using the frozen-phonon multislice method. Three general types of models were considered-perfect, vicinal/sawtooth and diffusion. These were chosen to demonstrate how HAADF image measurements are influenced by different interfacial structures in the technologically important III-V semiconductor system. For each model, interfacial sharpness was calculated as a function of depth and compared to aberration-corrected HAADF experiments of two types of AlAs/GaAs interfaces. The results show that the sharpness measured from HAADF imaging changes in a complicated manner with thickness for complex interfacial structures. For vicinal structures, it was revealed that the type of material that the probe projects through first of all has a significant effect on the measured sharpness. An increase in the vicinal angle was also shown to generate a wider interface in the random step model. The Moison diffusion model produced an increase in the interface width with depth which closely matched the experimental results of the AlAs-on-GaAs interface. In contrast, the interface width decreased as a function of depth in the linear diffusion model. Only in the case of the perfect model was it possible to ascertain the underlying structure directly from HAADF image analysis. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Application of stability enhancing minimum interfacial pressure force model for MARS

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Jae; Lim, Ho Gon; Kim, Kyung Doo; Ha, Kwi Seok

    2001-04-01

    For thermal-hydraulic modeling of two-phase flow systems, two-fluid model, which assumes that the pressures of liquid, vapor and interface are identical, a so-called single-pressure model, is commonly used in codes for nuclear reactor safety analyses. Typical two-phase model with single pressure assumption possesses complex characteristics that result in system being ill-posed. As a result, typical single pressure model may cause the unbounded growth of instabilities. In order to overcome the ill-posedness of single-pressure two-fluid model, a hyperbolic equation system has been developed by introducing an interfacial pressure force into single pressure two-fluid model. The potential impact of the present model on the stability of finite difference solution has been examined by Von-Neumann stability analysis. The obvious improvement in numerical stability has been found when a semi-implicit time advancement scheme is used. Numerical experiments using the pilot code were also performed for the conceptual problems. It was found that the result was consistent with numerical stability test. The new model was implemented to MARS using Two-step approach. Through the conceptual stability test problems and benchmark problems, the applicability of the new model was verified.

  6. Application of stability enhancing minimum interfacial pressure force model for MARS

    International Nuclear Information System (INIS)

    Lee, Won Jae; Lim, Ho Gon; Kim, Kyung Doo; Ha, Kwi Seok

    2001-04-01

    For thermal-hydraulic modeling of two-phase flow systems, two-fluid model, which assumes that the pressures of liquid, vapor and interface are identical, a so-called single-pressure model, is commonly used in codes for nuclear reactor safety analyses. Typical two-phase model with single pressure assumption possesses complex characteristics that result in system being ill-posed. As a result, typical single pressure model may cause the unbounded growth of instabilities. In order to overcome the ill-posedness of single-pressure two-fluid model, a hyperbolic equation system has been developed by introducing an interfacial pressure force into single pressure two-fluid model. The potential impact of the present model on the stability of finite difference solution has been examined by Von-Neumann stability analysis. The obvious improvement in numerical stability has been found when a semi-implicit time advancement scheme is used. Numerical experiments using the pilot code were also performed for the conceptual problems. It was found that the result was consistent with numerical stability test. The new model was implemented to MARS using Two-step approach. Through the conceptual stability test problems and benchmark problems, the applicability of the new model was verified

  7. Modeling of isothermal bubbly flow with interfacial area transport equation and bubble number density approach

    Energy Technology Data Exchange (ETDEWEB)

    Sari, Salih [Hacettepe University, Department of Nuclear Engineering, Beytepe, 06800 Ankara (Turkey); Erguen, Sule [Hacettepe University, Department of Nuclear Engineering, Beytepe, 06800 Ankara (Turkey); Barik, Muhammet; Kocar, Cemil; Soekmen, Cemal Niyazi [Hacettepe University, Department of Nuclear Engineering, Beytepe, 06800 Ankara (Turkey)

    2009-03-15

    In this study, isothermal turbulent bubbly flow is mechanistically modeled. For the modeling, Fluent version 6.3.26 is used as the computational fluid dynamics solver. First, the mechanistic models that simulate the interphase momentum transfer between the gas (bubbles) and liquid (continuous) phases are investigated, and proper models for the known flow conditions are selected. Second, an interfacial area transport equation (IATE) solution is added to Fluent's solution scheme in order to model the interphase momentum transfer mechanisms. In addition to solving IATE, bubble number density (BND) approach is also added to Fluent and this approach is also used in the simulations. Different source/sink models derived for the IATE and BND models are also investigated. The simulations of experiments based on the available data in literature are performed by using IATE and BND models in two and three-dimensions. The results show that the simulations performed by using IATE and BND models agree with each other and with the experimental data. The simulations performed in three-dimensions give better agreement with the experimental data.

  8. Modeling of isothermal bubbly flow with interfacial area transport equation and bubble number density approach

    International Nuclear Information System (INIS)

    Sari, Salih; Erguen, Sule; Barik, Muhammet; Kocar, Cemil; Soekmen, Cemal Niyazi

    2009-01-01

    In this study, isothermal turbulent bubbly flow is mechanistically modeled. For the modeling, Fluent version 6.3.26 is used as the computational fluid dynamics solver. First, the mechanistic models that simulate the interphase momentum transfer between the gas (bubbles) and liquid (continuous) phases are investigated, and proper models for the known flow conditions are selected. Second, an interfacial area transport equation (IATE) solution is added to Fluent's solution scheme in order to model the interphase momentum transfer mechanisms. In addition to solving IATE, bubble number density (BND) approach is also added to Fluent and this approach is also used in the simulations. Different source/sink models derived for the IATE and BND models are also investigated. The simulations of experiments based on the available data in literature are performed by using IATE and BND models in two and three-dimensions. The results show that the simulations performed by using IATE and BND models agree with each other and with the experimental data. The simulations performed in three-dimensions give better agreement with the experimental data

  9. On interfacial properties of tetrahydrofuran: Atomistic and coarse-grained models from molecular dynamics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Garrido, J. M. [Departamento de Ingeniería Química, Universidad de Concepción, POB 160-C Concepción (Chile); Algaba, J.; Blas, F. J., E-mail: felipe@uhu.es [Laboratorio de Simulación Molecular y Química Computacional, CIQSO-Centro de Investigación en Química Sostenible and Departamento de Física Aplicada, Universidad de Huelva, 21007 Huelva (Spain); Míguez, J. M. [Laboratoire des Fluides Complexes et Leurs Reservoirs, Université de Pau et des Pays de l’Adour, CNRS, TOTAL–UMR 5150, Avenue de l’Université, B.P. 1155, Pau F-64013 (France); Departamento de Física Aplicada, Universidade de Vigo, E36310 Vigo (Spain); Mendiboure, B. [Laboratoire des Fluides Complexes et Leurs Reservoirs, Université de Pau et des Pays de l’Adour, CNRS, TOTAL–UMR 5150, Avenue de l’Université, B.P. 1155, Pau F-64013 (France); Moreno-Ventas Bravo, A. I. [Laboratorio de Simulación Molecular y Química Computacional, CIQSO-Centro de Investigación en Química Sostenible and Departamento de Geología, Universidad de Huelva, 21007 Huelva (Spain); Piñeiro, M. M. [Departamento de Física Aplicada, Universidade de Vigo, E36310 Vigo (Spain)

    2016-04-14

    We have determined the interfacial properties of tetrahydrofuran (THF) from direct simulation of the vapor-liquid interface. The molecules are modeled using six different molecular models, three of them based on the united-atom approach and the other three based on a coarse-grained (CG) approach. In the first case, THF is modeled using the transferable parameters potential functions approach proposed by Chandrasekhar and Jorgensen [J. Chem. Phys. 77, 5073 (1982)] and a new parametrization of the TraPPE force fields for cyclic alkanes and ethers [S. J. Keasler et al., J. Phys. Chem. B 115, 11234 (2012)]. In both cases, dispersive and coulombic intermolecular interactions are explicitly taken into account. In the second case, THF is modeled as a single sphere, a diatomic molecule, and a ring formed from three Mie monomers according to the SAFT-γ Mie top-down approach [V. Papaioannou et al., J. Chem. Phys. 140, 054107 (2014)]. Simulations were performed in the molecular dynamics canonical ensemble and the vapor-liquid surface tension is evaluated from the normal and tangential components of the pressure tensor along the simulation box. In addition to the surface tension, we have also obtained density profiles, coexistence densities, critical temperature, density, and pressure, and interfacial thickness as functions of temperature, paying special attention to the comparison between the estimations obtained from different models and literature experimental data. The simulation results obtained from the three CG models as described by the SAFT-γ Mie approach are able to predict accurately the vapor-liquid phase envelope of THF, in excellent agreement with estimations obtained from TraPPE model and experimental data in the whole range of coexistence. However, Chandrasekhar and Jorgensen model presents significant deviations from experimental results. We also compare the predictions for surface tension as obtained from simulation results for all the models with

  10. On interfacial properties of tetrahydrofuran: Atomistic and coarse-grained models from molecular dynamics simulation

    International Nuclear Information System (INIS)

    Garrido, J. M.; Algaba, J.; Blas, F. J.; Míguez, J. M.; Mendiboure, B.; Moreno-Ventas Bravo, A. I.; Piñeiro, M. M.

    2016-01-01

    We have determined the interfacial properties of tetrahydrofuran (THF) from direct simulation of the vapor-liquid interface. The molecules are modeled using six different molecular models, three of them based on the united-atom approach and the other three based on a coarse-grained (CG) approach. In the first case, THF is modeled using the transferable parameters potential functions approach proposed by Chandrasekhar and Jorgensen [J. Chem. Phys. 77, 5073 (1982)] and a new parametrization of the TraPPE force fields for cyclic alkanes and ethers [S. J. Keasler et al., J. Phys. Chem. B 115, 11234 (2012)]. In both cases, dispersive and coulombic intermolecular interactions are explicitly taken into account. In the second case, THF is modeled as a single sphere, a diatomic molecule, and a ring formed from three Mie monomers according to the SAFT-γ Mie top-down approach [V. Papaioannou et al., J. Chem. Phys. 140, 054107 (2014)]. Simulations were performed in the molecular dynamics canonical ensemble and the vapor-liquid surface tension is evaluated from the normal and tangential components of the pressure tensor along the simulation box. In addition to the surface tension, we have also obtained density profiles, coexistence densities, critical temperature, density, and pressure, and interfacial thickness as functions of temperature, paying special attention to the comparison between the estimations obtained from different models and literature experimental data. The simulation results obtained from the three CG models as described by the SAFT-γ Mie approach are able to predict accurately the vapor-liquid phase envelope of THF, in excellent agreement with estimations obtained from TraPPE model and experimental data in the whole range of coexistence. However, Chandrasekhar and Jorgensen model presents significant deviations from experimental results. We also compare the predictions for surface tension as obtained from simulation results for all the models with

  11. Dividing phases in two-phase flow and modeling of interfacial drag

    Energy Technology Data Exchange (ETDEWEB)

    Narumo, T.; Rajamaeki, M. [VTT Energy (Finland)

    1997-07-01

    Different models intended to describe one-dimensional two-phase flow are considered in this paper. The following models are introduced: conventional six-equation model, conventional model equipped with terms taking into account nonuniform transverse velocity distribution of the phases, several virtual mass models and a model in which the momentum equations have been derived by using the principles of Separation of the Flow According to Velocity (SFAV). The dynamics of the models have been tested by comparing their characteristic velocities to each other and against experimental data. The results show that the SFAV-model makes a hyperbolic system and predicts the propagation velocities of disturbances with the same order of accuracy as the best tested virtual mass models. Furthermore, the momentum interaction terms for the SFAV-model are considered. These consist of the wall friction terms and the interfacial friction term. The authors model wall friction with two independent terms describing the effect of each fluid on the wall separately. In the steady state, a relationship between the slip velocity and friction coefficients can be derived. Hence, the friction coefficients for the SFAV-model can be calculated from existing correlations, viz. from a drift-flux correlation and a wall friction correlation. The friction model was tested by searching steady-state distributions in a partial BWR fuel channel and comparing the relaxed values with the drift-flux correlation, which agreed very well with each other. In addition, response of the flow to a sine-wave disturbance in the water inlet flux was calculated as function of frequency. The results of the models differed from each other already with frequency of order 5 Hz, while the time constant for the relaxation, obtained from steady-state distribution calculation, would have implied significant differences appear not until with frequency of order 50 Hz.

  12. Dividing phases in two-phase flow and modeling of interfacial drag

    International Nuclear Information System (INIS)

    Narumo, T.; Rajamaeki, M.

    1997-01-01

    Different models intended to describe one-dimensional two-phase flow are considered in this paper. The following models are introduced: conventional six-equation model, conventional model equipped with terms taking into account nonuniform transverse velocity distribution of the phases, several virtual mass models and a model in which the momentum equations have been derived by using the principles of Separation of the Flow According to Velocity (SFAV). The dynamics of the models have been tested by comparing their characteristic velocities to each other and against experimental data. The results show that the SFAV-model makes a hyperbolic system and predicts the propagation velocities of disturbances with the same order of accuracy as the best tested virtual mass models. Furthermore, the momentum interaction terms for the SFAV-model are considered. These consist of the wall friction terms and the interfacial friction term. The authors model wall friction with two independent terms describing the effect of each fluid on the wall separately. In the steady state, a relationship between the slip velocity and friction coefficients can be derived. Hence, the friction coefficients for the SFAV-model can be calculated from existing correlations, viz. from a drift-flux correlation and a wall friction correlation. The friction model was tested by searching steady-state distributions in a partial BWR fuel channel and comparing the relaxed values with the drift-flux correlation, which agreed very well with each other. In addition, response of the flow to a sine-wave disturbance in the water inlet flux was calculated as function of frequency. The results of the models differed from each other already with frequency of order 5 Hz, while the time constant for the relaxation, obtained from steady-state distribution calculation, would have implied significant differences appear not until with frequency of order 50 Hz

  13. In silico modeling for tumor growth visualization.

    Science.gov (United States)

    Jeanquartier, Fleur; Jean-Quartier, Claire; Cemernek, David; Holzinger, Andreas

    2016-08-08

    Cancer is a complex disease. Fundamental cellular based studies as well as modeling provides insight into cancer biology and strategies to treatment of the disease. In silico models complement in vivo models. Research on tumor growth involves a plethora of models each emphasizing isolated aspects of benign and malignant neoplasms. Biologists and clinical scientists are often overwhelmed by the mathematical background knowledge necessary to grasp and to apply a model to their own research. We aim to provide a comprehensive and expandable simulation tool to visualizing tumor growth. This novel Web-based application offers the advantage of a user-friendly graphical interface with several manipulable input variables to correlate different aspects of tumor growth. By refining model parameters we highlight the significance of heterogeneous intercellular interactions on tumor progression. Within this paper we present the implementation of the Cellular Potts Model graphically presented through Cytoscape.js within a Web application. The tool is available under the MIT license at https://github.com/davcem/cpm-cytoscape and http://styx.cgv.tugraz.at:8080/cpm-cytoscape/ . In-silico methods overcome the lack of wet experimental possibilities and as dry method succeed in terms of reduction, refinement and replacement of animal experimentation, also known as the 3R principles. Our visualization approach to simulation allows for more flexible usage and easy extension to facilitate understanding and gain novel insight. We believe that biomedical research in general and research on tumor growth in particular will benefit from the systems biology perspective.

  14. Interfacial separation of a mature biofilm from a glass surface - A combined experimental and cohesive zone modelling approach.

    Science.gov (United States)

    Safari, Ashkan; Tukovic, Zeljko; Cardiff, Philip; Walter, Maik; Casey, Eoin; Ivankovic, Alojz

    2016-02-01

    A good understanding of the mechanical stability of biofilms is essential for biofouling management, particularly when mechanical forces are used. Previous biofilm studies lack a damage-based theoretical model to describe the biofilm separation from a surface. The purpose of the current study was to investigate the interfacial separation of a mature biofilm from a rigid glass substrate using a combined experimental and numerical modelling approach. In the current work, the biofilm-glass interfacial separation process was investigated under tensile and shear stresses at the macroscale level, known as modes I and II failure mechanisms respectively. The numerical simulations were performed using a Finite Volume (FV)-based simulation package (OpenFOAM®) to predict the separation initiation using the cohesive zone model (CZM). Atomic force microscopy (AFM)-based retraction curve was used to obtain the separation properties between the biofilm and glass colloid at microscale level, where the CZM parameters were estimated using the Johnson-Kendall-Roberts (JKR) model. In this study CZM is introduced as a reliable method for the investigation of interfacial separation between a biofilm and rigid substrate, in which a high local stress at the interface edge acts as an ultimate stress at the crack tip.This study demonstrated that the total interfacial failure energy measured at the macroscale, was significantly higher than the pure interfacial separation energy obtained by AFM at the microscale, indicating a highly ductile deformation behaviour within the bulk biofilm matrix. The results of this study can significantly contribute to the understanding of biofilm detachments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Development and validation of bubble breakup and coalescence constitutive models for the one-group interfacial area transport equation

    International Nuclear Information System (INIS)

    Pellacani, Filippo

    2012-01-01

    A local mechanistic model for bubble coalescence and breakup for the one-group interfacial area transport equation has been developed, in agreement and within the limits of the current understanding, based on an exhaustive survey of the theory and of the state of the art models for bubble dynamics simulation. The new model has been tested using the commercial 3D CFD code ANSYS CFX. Upward adiabatic turbulent air-water bubbly flow has been simulated and the results have been compared with the data obtained in the experimental facility PUMA. The range of the experimental data available spans between 0.5 to 2 m/s liquid velocity and 5 to 15 % volume fraction. For the implementation of the models, both the monodispersed and the interfacial area transport equation approaches have been used. The first one to perform a detailed analysis of the forces and models to reproduce the dynamic of the dispersed phase adequately and to be used in the next phases of the work. Also two different bubble induced turbulence models have been tested to consider the effect of the presence of the gas phase on the turbulence of the liquid phase. The interfacial area transport equation has been successfully implemented into the CFD code and the state of the art breakup and coalescence models have been used for simulation. The limitations of the actual theory have been shown and a new bubble interactions model has been developed. The simulations showed that a considerable improvement is achieved if compared to the state of the art closure models. Limits in the implementation derive from the actual understanding and formulation of the bubbly dynamics. A strong dependency on the interfacial non-drag force models and coefficients have been shown. More experimental and theory work needs to be done in this field to increase the prediction capability of the simulation tools regarding the distribution of the phases along the pipe radius.

  16. Augmented reality in a tumor resection model.

    Science.gov (United States)

    Chauvet, Pauline; Collins, Toby; Debize, Clement; Novais-Gameiro, Lorraine; Pereira, Bruno; Bartoli, Adrien; Canis, Michel; Bourdel, Nicolas

    2018-03-01

    Augmented Reality (AR) guidance is a technology that allows a surgeon to see sub-surface structures, by overlaying pre-operative imaging data on a live laparoscopic video. Our objectives were to evaluate a state-of-the-art AR guidance system in a tumor surgical resection model, comparing the accuracy of the resection with and without the system. Our system has three phases. Phase 1: using the MRI images, the kidney's and pseudotumor's surfaces are segmented to construct a 3D model. Phase 2: the intra-operative 3D model of the kidney is computed. Phase 3: the pre-operative and intra-operative models are registered, and the laparoscopic view is augmented with the pre-operative data. We performed a prospective experimental study on ex vivo porcine kidneys. Alginate was injected into the parenchyma to create pseudotumors measuring 4-10 mm. The kidneys were then analyzed by MRI. Next, the kidneys were placed into pelvictrainers, and the pseudotumors were laparoscopically resected. The AR guidance system allows the surgeon to see tumors and margins using classical laparoscopic instruments, and a classical screen. The resection margins were measured microscopically to evaluate the accuracy of resection. Ninety tumors were segmented: 28 were used to optimize the AR software, and 62 were used to randomly compare surgical resection: 29 tumors were resected using AR and 33 without AR. The analysis of our pathological results showed 4 failures (tumor with positive margins) (13.8%) in the AR group, and 10 (30.3%) in the Non-AR group. There was no complete miss in the AR group, while there were 4 complete misses in the non-AR group. In total, 14 (42.4%) tumors were completely missed or had a positive margin in the non-AR group. Our AR system enhances the accuracy of surgical resection, particularly for small tumors. Crucial information such as resection margins and vascularization could also be displayed.

  17. Two-phase interfacial area and flow regime modeling in FLOWTRAN-TF code

    International Nuclear Information System (INIS)

    Smith, F.G. III; Lee, S.Y.; Flach, G.P.; Hamm, L.L.

    1992-01-01

    FLOWTRAN-TF is a new two-component, two-phase thermal-hydraulics code to capture the detailed assembly behavior associated with loss-of-coolant accident analyses in multichannel assemblies of the SRS reactors. The local interfacial area of the two-phase mixture is computed by summing the interfacial areas contributed by each of three flow regimes. For smooth flow regime transitions, the code uses an interpolation technique in terms of component void fraction for each basic flow regime

  18. A model for the interfacial shear in vertical, adiabatic, annular-mist flow

    International Nuclear Information System (INIS)

    Cappiello, M.W.

    1992-01-01

    A model is developed for the interfacial shear in upward, vertical, adiabatic, annular-mist flow. The model accounts for the momentum of both the droplet and film components and is applicable to the two-fluid approximation. Three computer programs are developed to evaluate the sensitivity of the droplet drag coefficient on the droplet velocity calculation, to solve the two-fluid set of equations by iteration, and to evaluate the required film friction factor from the data. The results of the sensitivity calculation show that a constant drag coefficient of 0.44 for the droplet is sufficient for estimating the droplet velocity over a typical range of gas velocities. Several film friction factor correlations from the literature were tested against the existing data of Hossfeld and Barathan. It was found that a modified effective roughness correlation proposed by Wallis performs the best overall in predicting the data for both small- and large-diameter pipes. The Electrical Power Research Institute drift-flux correlation and the Barathan correlation consistently underpredict the data. The use of the Henstock and Hanratty correlation predicts an incorrect trend. A new correlation is developed that better predicts the data over the entire range of gas injection rates. 17 refs

  19. Analytical Model for Diffusive Evaporation of Sessile Droplets Coupled with Interfacial Cooling Effect.

    Science.gov (United States)

    Nguyen, Tuan A H; Biggs, Simon R; Nguyen, Anh V

    2018-05-30

    Current analytical models for sessile droplet evaporation do not consider the nonuniform temperature field within the droplet and can overpredict the evaporation by 20%. This deviation can be attributed to a significant temperature drop due to the release of the latent heat of evaporation along the air-liquid interface. We report, for the first time, an analytical solution of the sessile droplet evaporation coupled with this interfacial cooling effect. The two-way coupling model of the quasi-steady thermal diffusion within the droplet and the quasi-steady diffusion-controlled droplet evaporation is conveniently solved in the toroidal coordinate system by applying the method of separation of variables. Our new analytical model for the coupled vapor concentration and temperature fields is in the closed form and is applicable for a full range of spherical-cap shape droplets of different contact angles and types of fluids. Our analytical results are uniquely quantified by a dimensionless evaporative cooling number E o whose magnitude is determined only by the thermophysical properties of the liquid and the atmosphere. Accordingly, the larger the magnitude of E o , the more significant the effect of the evaporative cooling, which results in stronger suppression on the evaporation rate. The classical isothermal model is recovered if the temperature gradient along the air-liquid interface is negligible ( E o = 0). For substrates with very high thermal conductivities (isothermal substrates), our analytical model predicts a reversal of temperature gradient along the droplet-free surface at a contact angle of 119°. Our findings pose interesting challenges but also guidance for experimental investigations.

  20. Probing the role of interfacial waters in protein-DNA recognition using a hybrid implicit/explicit solvation model

    Science.gov (United States)

    Li, Shen; Bradley, Philip

    2013-01-01

    When proteins bind to their DNA target sites, ordered water molecules are often present at the protein-DNA interface bridging protein and DNA through hydrogen bonds. What is the role of these ordered interfacial waters? Are they important determinants of the specificity of DNA sequence recognition, or do they act in binding in a primarily non-specific manner, by improving packing of the interface, shielding unfavorable electrostatic interactions, and solvating unsatisfied polar groups that are inaccessible to bulk solvent? When modeling details of structure and binding preferences, can fully implicit solvent models be fruitfully applied to protein-DNA interfaces, or must the individualistic properties of these interfacial waters be accounted for? To address these questions, we have developed a hybrid implicit/explicit solvation model that specifically accounts for the locations and orientations of small numbers of DNA-bound water molecules while treating the majority of the solvent implicitly. Comparing the performance of this model to its fully implicit counterpart, we find that explicit treatment of interfacial waters results in a modest but significant improvement in protein sidechain placement and DNA sequence recovery. Base-by-base comparison of the performance of the two models highlights DNA sequence positions whose recognition may be dependent on interfacial water. Our study offers large-scale statistical evidence for the role of ordered water for protein DNA recognition, together with detailed examination of several well-characterized systems. In addition, our approach provides a template for modeling explicit water molecules at interfaces that should be extensible to other systems. PMID:23444044

  1. Spherical Cancer Models in Tumor Biology

    Directory of Open Access Journals (Sweden)

    Louis-Bastien Weiswald

    2015-01-01

    Full Text Available Three-dimensional (3D in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.

  2. A modified two-fluid model for the application of two-group interfacial area transport equation

    International Nuclear Information System (INIS)

    Sun, X.; Ishii, M.; Kelly, J.

    2003-01-01

    This paper presents the modified two-fluid model that is ready to be applied in the approach of the two-group interfacial area transport equation. The two-group interfacial area transport equation was developed to provide a mechanistic constitutive relation for the interfacial area concentration in the two-fluid model. In the two-group transport equation, bubbles are categorized into two groups: spherical/distorted bubbles as Group 1 while cap/slug/churn-turbulent bubbles as Group 2. Therefore, this transport equation can be employed in the flow regimes spanning from bubbly, cap bubbly, slug to churn-turbulent flows. However, the introduction of the two groups of bubbles requires two gas velocity fields. Yet it is not desirable to solve two momentum equations for the gas phase alone. In the current modified two-fluid model, a simplified approach is proposed. The momentum equation for the averaged velocity of both Group-1 and Group-2 bubbles is retained. By doing so, the velocity difference between Group-1 and Group-2 bubbles needs to be determined. This may be made either based on simplified momentum equations for both Group-1 and Group-2 bubbles or by a modified drift-flux model

  3. Tumor cell culture on collagen–chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies

    Directory of Open Access Journals (Sweden)

    Aziz Mahmoudzadeh

    2016-07-01

    Full Text Available Tumor cells naturally live in three-dimensional (3D microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen–chitosan scaffold compared with 2D plate cultures. Collagen–chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen–chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies.

  4. Tumor cell culture on collagen-chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies.

    Science.gov (United States)

    Mahmoudzadeh, Aziz; Mohammadpour, Hemn

    2016-07-01

    Tumor cells naturally live in three-dimensional (3D) microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D) plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen-chitosan scaffold compared with 2D plate cultures. Collagen-chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen-chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies. Copyright © 2016. Published by Elsevier B.V.

  5. Predicting the mixed-mode I/II spatial damage propagation along 3D-printed soft interfacial layer via a hyperelastic softening model

    Science.gov (United States)

    Liu, Lei; Li, Yaning

    2018-07-01

    A methodology was developed to use a hyperelastic softening model to predict the constitutive behavior and the spatial damage propagation of nonlinear materials with damage-induced softening under mixed-mode loading. A user subroutine (ABAQUS/VUMAT) was developed for numerical implementation of the model. 3D-printed wavy soft rubbery interfacial layer was used as a material system to verify and validate the methodology. The Arruda - Boyce hyperelastic model is incorporated with the softening model to capture the nonlinear pre-and post- damage behavior of the interfacial layer under mixed Mode I/II loads. To characterize model parameters of the 3D-printed rubbery interfacial layer, a series of scarf-joint specimens were designed, which enabled systematic variation of stress triaxiality via a single geometric parameter, the slant angle. It was found that the important model parameter m is exponentially related to the stress triaxiality. Compact tension specimens of the sinusoidal wavy interfacial layer with different waviness were designed and fabricated via multi-material 3D printing. Finite element (FE) simulations were conducted to predict the spatial damage propagation of the material within the wavy interfacial layer. Compact tension experiments were performed to verify the model prediction. The results show that the model developed is able to accurately predict the damage propagation of the 3D-printed rubbery interfacial layer under complicated stress-state without pre-defined failure criteria.

  6. A new ODE tumor growth modeling based on tumor population dynamics

    International Nuclear Information System (INIS)

    Oroji, Amin; Omar, Mohd bin; Yarahmadian, Shantia

    2015-01-01

    In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan

  7. A new ODE tumor growth modeling based on tumor population dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Oroji, Amin; Omar, Mohd bin [Institute of Mathematical Sciences, Faculty of Science University of Malaya, 50603 Kuala Lumpur, Malaysia amin.oroji@siswa.um.edu.my, mohd@um.edu.my (Malaysia); Yarahmadian, Shantia [Mathematics Department Mississippi State University, USA Syarahmadian@math.msstate.edu (United States)

    2015-10-22

    In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan.

  8. A Linear Gradient Theory Model for Calculating Interfacial Tensions of Mixtures

    DEFF Research Database (Denmark)

    Zou, You-Xiang; Stenby, Erling Halfdan

    1996-01-01

    excellent agreement between the predicted and experimental IFTs at high and moderate levels of IFTs, while the agreement is reasonably accurate in the near-critical region as the used equations of state reveal classical scaling behavior. To predict accurately low IFTs (sigma ... with proper scaling behavior at the critical point is at least required.Key words: linear gradient theory; interfacial tension; equation of state; influence parameter; density profile....

  9. The role of interfacial layers in the enhanced thermal conductivity of nanofluids: A renovated Hamilton-Crosser model

    International Nuclear Information System (INIS)

    Yu, W; Choi, S.U.S.

    2004-01-01

    We previously developed a renovated Maxwell model for the effective thermal conductivity of nanofluids and determined that the solid/liquid interfacial layers play an important role in the enhanced thermal conductivity of nanofluids. However, this renovated Maxwell model is limited to suspensions with spherical particles. Here, we extend the Hamilton--Crosser model for suspensions of nonspherical particles to include the effect of a solid/liquid interface. The solid/liquid interface is described as a confocal ellipsoid with a solid particle. The new model for the three-phase suspensions is mathematically expressed in terms of the equivalent thermal conductivity and equivalent volume fraction of anisotropic complex ellipsoids, as well as an empirical shape factor. With a generalized empirical shape factor, the renovated Hamilton--Crosser model correctly predicts the magnitude of the thermal conductivity of nanotube-in-oil nanofluids. At present, this new model is not able to predict the nonlinear behavior of the nanofluid thermal conductivity

  10. Development of two-group interfacial area transport equation for confined flow-1. Modeling of bubble interactions

    International Nuclear Information System (INIS)

    Sun, Xiaodong; Kim, Seungjin; Ishii, Mamoru; Beus, Stephen G.

    2003-01-01

    This paper presents the modeling of bubble interaction mechanisms in the two-group interfacial area transport equation (IATE) for confined gas-liquid two-phase flow. The transport equation is applicable to bubbly, cap-turbulent, and churn-turbulent flow regimes. In the two-group IATE, bubbles are categorized into two groups: spherical/distorted bubbles as Group 1 and cap/slug/churn-turbulent bubbles as Group 2. Thus, two sets of equations are used to describe the generation and destruction rates of bubble number density, void fraction, and interfacial area concentration for the two groups of bubbles due to bubble expansion and compression, coalescence and disintegration, and phase change. Five major bubble interaction mechanisms are identified for the gas-liquid two-phase flow of interest, and are analytically modeled as the source/sink terms for the transport equations based on certain assumptions for the confined flow. These models include both intra-group (within a certain group) and inter-group (between two groups) bubble interactions. The comparisons of the prediction by the one-dimensional two-group IATE with experimental data are presented in the second paper of this series. (author)

  11. FEM Modeling of In-Plane Stress Distribution in Thick Brittle Coatings/Films on Ductile Substrates Subjected to Tensile Stress to Determine Interfacial Strength

    Directory of Open Access Journals (Sweden)

    Kaishi Wang

    2018-03-01

    Full Text Available The ceramic-metal interface is present in various material structures and devices that are vulnerable to failures, like cracking, which are typically due to their incompatible properties, e.g., thermal expansion mismatch. In failure of these multilayer systems, interfacial shear strength is a good measure of the robustness of interfaces, especially for planar films. There is a widely-used shear lag model and method by Agrawal and Raj to analyse and measure the interfacial shear strength of thin brittle film on ductile substrates. The use of this classical model for a type of polymer derived ceramic coatings (thickness ~18 μm on steel substrate leads to high values of interfacial shear strength. Here, we present finite element simulations for such a coating system when it is subjected to in-plane tension. Results show that the in-plane stresses in the coating are non-uniform, i.e., varying across the thickness of the film. Therefore, they do not meet one of the basic assumptions of the classical model: uniform in-plane stress. Furthermore, effects of three significant parameters, film thickness, crack spacing, and Young’s modulus, on the in-plane stress distribution have also been investigated. ‘Thickness-averaged In-plane Stress’ (TIS, a new failure criterion, is proposed for estimating the interfacial shear strength, which leads to a more realistic estimation of the tensile strength and interfacial shear strength of thick brittle films/coatings on ductile substrates.

  12. FEM Modeling of In-Plane Stress Distribution in Thick Brittle Coatings/Films on Ductile Substrates Subjected to Tensile Stress to Determine Interfacial Strength.

    Science.gov (United States)

    Wang, Kaishi; Zhang, Fangzhou; Bordia, Rajendra K

    2018-03-27

    The ceramic-metal interface is present in various material structures and devices that are vulnerable to failures, like cracking, which are typically due to their incompatible properties, e.g., thermal expansion mismatch. In failure of these multilayer systems, interfacial shear strength is a good measure of the robustness of interfaces, especially for planar films. There is a widely-used shear lag model and method by Agrawal and Raj to analyse and measure the interfacial shear strength of thin brittle film on ductile substrates. The use of this classical model for a type of polymer derived ceramic coatings (thickness ~18 μm) on steel substrate leads to high values of interfacial shear strength. Here, we present finite element simulations for such a coating system when it is subjected to in-plane tension. Results show that the in-plane stresses in the coating are non-uniform, i.e., varying across the thickness of the film. Therefore, they do not meet one of the basic assumptions of the classical model: uniform in-plane stress. Furthermore, effects of three significant parameters, film thickness, crack spacing, and Young's modulus, on the in-plane stress distribution have also been investigated. 'Thickness-averaged In-plane Stress' (TIS), a new failure criterion, is proposed for estimating the interfacial shear strength, which leads to a more realistic estimation of the tensile strength and interfacial shear strength of thick brittle films/coatings on ductile substrates.

  13. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

    Directory of Open Access Journals (Sweden)

    Yingjen Jeffrey Wu

    2009-02-01

    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  14. Mathematical models of tumor growth: translating absorbed dose to tumor control probability

    International Nuclear Information System (INIS)

    Sgouros, G.

    1996-01-01

    Full text: The dose-rate in internal emitter therapy is low and time-dependent as compared to external beam radiotherapy. Once the total absorbed dose delivered to a target tissue is calculated, however, most dosimetric analyses of radiopharmaceuticals are considered complete. To translate absorbed dose estimates obtained for internal emitter therapy to biologic effect, the growth characteristics, repair capacity, and radiosensitivity of the tumor must be considered. Tumor growth may be represented by the Gompertz equation in which tumor cells increase at an exponential growth rate that is itself decreasing at an exponential rate; as the tumor increases in size, the growth rate diminishes. The empirical Gompertz expression for tumor growth may be derived from a mechanistic model in which growth is represented by a balance between tumor-cell birth and loss. The birth rate is assumed to be fixed, while the cell loss rate is time-dependent and increases with tumor size. The birth rate of the tumors may be related to their potential doubling time. Multiple biopsies of individual tumors have demonstrated a heterogeneity in the potential doubling time of tumors. By extending the mechanistic model described above to allow for sub-populations of tumor cells with different birth rates, the effect of kinetic heterogeneity within a tumor may be examined. Model simulations demonstrate that the cell kinetic parameters of a tumor are predicted to change over time and measurements obtained using a biopsy are unlikely to reflect the kinetics of the tumor throughout its growth history. A decrease in overall tumor mass, in which each sub-population is reduced in proportion to its cell number, i.e., the log-kill assumption, leads to re-growth of a tumor that has a greater proliferation rate. Therapy that is linked to the potential doubling time or to the effective proliferation rate of the tumor may lead to re-growth of a tumor that is kinetically unchanged. The simplest model of

  15. Modelling of high temperature interfacial reactions in continuously reinforced Ti/SiC metal matrix composites (MMCs)

    International Nuclear Information System (INIS)

    Fox, K.M.

    1993-01-01

    Previous experimental work by Gundel and Wawner showed that the matrix alloy has a strong effect on reaction layer growth in Ti alloy/SCS-6 composite systems. A finite difference technique was used to model the reaction layer growth, which predicts the same trends as those exhibited by the experimental data. Matrix alloying elements such as Mo and Cr in metastable β alloys will affect the equilibrium compositions and diffusivities in the matrix, but matrix diffusion is not found to be rate controlling. Regular solution thermodynamic models indicate that the main affect of matrix composition is in controlling carbon-flux through the reaction layer by altering equilibrium C-TiC-Ti interfacial compositions. (orig.)

  16. Therapeutic Implications from Sensitivity Analysis of Tumor Angiogenesis Models

    Science.gov (United States)

    Poleszczuk, Jan; Hahnfeldt, Philip; Enderling, Heiko

    2015-01-01

    Anti-angiogenic cancer treatments induce tumor starvation and regression by targeting the tumor vasculature that delivers oxygen and nutrients. Mathematical models prove valuable tools to study the proof-of-concept, efficacy and underlying mechanisms of such treatment approaches. The effects of parameter value uncertainties for two models of tumor development under angiogenic signaling and anti-angiogenic treatment are studied. Data fitting is performed to compare predictions of both models and to obtain nominal parameter values for sensitivity analysis. Sensitivity analysis reveals that the success of different cancer treatments depends on tumor size and tumor intrinsic parameters. In particular, we show that tumors with ample vascular support can be successfully targeted with conventional cytotoxic treatments. On the other hand, tumors with curtailed vascular support are not limited by their growth rate and therefore interruption of neovascularization emerges as the most promising treatment target. PMID:25785600

  17. Theoretical modeling of CHF for near-saturated pool boiling and flow boiling from short heaters using the interfacial lift-off criterion

    International Nuclear Information System (INIS)

    Mudawar, I.; Galloway, J.E.; Gersey, C.O.

    1995-01-01

    Pool boiling and flow boiling were examined for near-saturated bulk conditions in order to determine the critical heat flux (CHF) trigger mechanism for each. Photographic studies of the wall region revealed features common to both situations. At fluxes below CHF, the vapor coalesces into a wavy layer which permits wetting only in wetting fronts, the portions of the liquid-vapor interface which contact the wall as a result of the interfacial waviness. Close examination of the interfacial features revealed the waves are generated from the lower edge of the heater in pool boiling and the heater's upstream region in flow boiling. Wavelengths follow predictions based upon the Kelvin-Helmholtz instability criterion. Critical heat flux in both cases occurs when the pressure force exerted upon the interface due to interfacial curvature, which tends to preserve interfacial contact with the wall prior to CHF, is overcome by the momentum of vapor at the site of the first wetting front, causing the interface to lift away from the wall. It is shown this interfacial lift-off criterion facilitates accurate theoretical modeling of CHF in pool boiling and in flow boiling in both straight and curved channels

  18. Theoretical modeling of CHF for near-saturated pool boiling and flow boiling from short heaters using the interfacial lift-off criterion

    Energy Technology Data Exchange (ETDEWEB)

    Mudawar, I.; Galloway, J.E.; Gersey, C.O. [Purdue Univ., West Lafayette, IN (United States)] [and others

    1995-12-31

    Pool boiling and flow boiling were examined for near-saturated bulk conditions in order to determine the critical heat flux (CHF) trigger mechanism for each. Photographic studies of the wall region revealed features common to both situations. At fluxes below CHF, the vapor coalesces into a wavy layer which permits wetting only in wetting fronts, the portions of the liquid-vapor interface which contact the wall as a result of the interfacial waviness. Close examination of the interfacial features revealed the waves are generated from the lower edge of the heater in pool boiling and the heater`s upstream region in flow boiling. Wavelengths follow predictions based upon the Kelvin-Helmholtz instability criterion. Critical heat flux in both cases occurs when the pressure force exerted upon the interface due to interfacial curvature, which tends to preserve interfacial contact with the wall prior to CHF, is overcome by the momentum of vapor at the site of the first wetting front, causing the interface to lift away from the wall. It is shown this interfacial lift-off criterion facilitates accurate theoretical modeling of CHF in pool boiling and in flow boiling in both straight and curved channels.

  19. Mathematical modeling of liquid/liquid hollow fiber membrane contactor accounting for interfacial transport phenomena: Extraction of lanthanides as a surrogate for actinides

    International Nuclear Information System (INIS)

    Rogers, J.D.

    1994-01-01

    This report is divided into two parts. The second part is divided into the following sections: experimental protocol; modeling the hollow fiber extractor using film theory; Graetz model of the hollow fiber membrane process; fundamental diffusive-kinetic model; and diffusive liquid membrane device-a rigorous model. The first part is divided into: membrane and membrane process-a concept; metal extraction; kinetics of metal extraction; modeling the membrane contactor; and interfacial phenomenon-boundary conditions-applied to membrane transport

  20. Brain Tumor Segmentation Using a Generative Model with an RBM Prior on Tumor Shape

    DEFF Research Database (Denmark)

    Agn, Mikael; Puonti, Oula; Rosenschöld, Per Munck af

    2016-01-01

    In this paper, we present a fully automated generative method for brain tumor segmentation in multi-modal magnetic resonance images. The method is based on the type of generative model often used for segmenting healthy brain tissues, where tissues are modeled by Gaussian mixture models combined...... the use of the intensity information in the training images. Experiments on public benchmark data of patients suffering from low- and high-grade gliomas show that the method performs well compared to current state-of-the-art methods, while not being tied to any specific imaging protocol....... with a spatial atlas-based tissue prior. We extend this basic model with a tumor prior, which uses convolutional restricted Boltzmann machines (cRBMs) to model the shape of both tumor core and complete tumor, which includes edema and core. The cRBMs are trained on expert segmentations of training images, without...

  1. Structure, viscoelasticity, and interfacial dynamics of a model polymeric bicontinuous microemulsion

    Energy Technology Data Exchange (ETDEWEB)

    Hickey, Robert J.; Gillard, Timothy M.; Irwin, Matthew T.; Lodge, Timothy P.; Bates, Frank S. (UMM)

    2016-01-01

    We have systematically studied the equilibrium structure and dynamics of a polymeric bicontinuous microemulsion (BμE) composed of poly(cyclohexylethylene) (PCHE), poly(ethylene) (PE), and a volumetrically symmetric PCHE–PE diblock copolymer, using dynamic mechanical spectroscopy, small angle X-ray and neutron scattering, and transmission electron microscopy. The BμE was investigated over an 80 °C temperature range, revealing a structural evolution and a rheological response not previously recognized in such systems. As the temperature is reduced below the point associated with the lamellar-disorder transition at compositions adjacent to the microemulsion channel, the interfacial area per chain of the BμE approaches that of the neat (undiluted) lamellar diblock copolymer. With increasing temperature, the diblock-rich interface swells through homopolymer infiltration. Time–temperature-superposed linear dynamic data obtained as a function of frequency show that the viscoelastic response of the BμE is strikingly similar to that of the fluctuating pure diblock copolymer in the disordered state, which we associate with membrane undulations and the breaking and reforming of interfaces. This work provides new insights into the structure and dynamics that characterize thermodynamically stable BμEs in the limits of relatively weak and strong segregation.

  2. Modelling Nanoparticle Diffusion into Cancer Tumors

    Science.gov (United States)

    Podduturi, Vishwa Priya; Derosa, Pedro

    2011-03-01

    Cancer is one of the major, potentially deadly diseases and has been for years. Non-specific delivery of the drug can damage healthy tissue seriously affecting in many cases the patient's living condition. Nanoparticles are being used for a targeted drug delivery thereby reducing the dose. In addition, metallic nanoparticles are being used in thermal treatment of cancer cells where nanoparticles help concentrate heat in the tumor and away from living tissue. We proposed a model that combines random walk with diffusion principles. The particle drift velocity is taken from the Hagen-Poiseuille equation and the velocity profile of the particle at the pores in the capillary wall is obtained using the Coventorware software. Pressure gradient and concentration gradient through the capillary wall are considered. Simulations are performed in Matlab using the Monte Carlo technique. Number of particles leaving the blood vessel through a pore is obtained as a function of blood pressure, the osmotic pressure, temperature, particle concentration, blood vessel radius, and pore size, and the relative effect of each of the parameters is discussed.

  3. Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model

    International Nuclear Information System (INIS)

    Yoshimoto, Mitsuyoshi; Kinuya, Seigo; Kawashima, Atsuhiro; Nishii, Ryuichi; Yokoyama, Kunihiko; Kawai, Keiichi

    2006-01-01

    Introduction: Angiogenesis is essential for tumor growth or metastasis. A method involving noninvasive detection of angiogenic activity in vivo would provide diagnostic information regarding antiangiogenic therapy targeting vascular endothelial cells as well as important insight into the role of vascular endothelial growth factor (VEGF) and its receptor (flt-1 and KDR) system in tumor biology. We evaluated radioiodinated VEGF 121 , which displays high binding affinity for KDR, and VEGF 165 , which possesses high binding affinity for flt-1 and low affinity for KDR, as angiogenesis imaging agents using the LS180 tumor xenograft model. Methods: VEGF 121 and VEGF 165 were labeled with 125 I by the chloramine-T method. Biodistribution was observed in an LS180 human colon cancer xenograft model. Additionally, autoradiographic imaging and immunohistochemical staining of tumors were performed with 125 I-VEGF 121 . Results: 125 I-VEGF 121 and 125 I-VEGF 165 exhibited strong, continuous uptake by tumors and the uterus, an organ characterized by angiogenesis. 125 I-VEGF 121 uptake in tumors was twofold higher than that of 125 I-VEGF 165 (9.12±98 and 4.79±1.08 %ID/g at 2 h, respectively). 125 I-VEGF 121 displayed higher tumor to nontumor (T/N) ratios in most normal organs in comparison with 125 I-VEGF 165 . 125 I-VEGF 121 accumulation in tumors decreased with increasing tumor volume. Autoradiographic and immunohistochemical analyses confirmed that the difference in 125 I-VEGF 121 tumor accumulation correlated with degree of tumor vascularity. Conclusion: Radioiodinated VEGF 121 is a promising tracer for noninvasive delineation of angiogenesis in vivo

  4. Model construction of nursing service satisfaction in hospitalized tumor patients.

    Science.gov (United States)

    Chen, Yongyi; Liu, Jingshi; Xiao, Shuiyuan; Liu, Xiangyu; Tang, Xinhui; Zhou, Yujuan

    2014-01-01

    This study aims to construct a satisfaction model on nursing service in hospitalized tumor patients. Using questionnaires, data about hospitalized tumor patients' expectation, quality perception and satisfaction of hospital nursing service were obtained. A satisfaction model of nursing service in hospitalized tumor patients was established through empirical study and by structural equation method. This model was suitable for tumor specialized hospital, with reliability and validity. Patient satisfaction was significantly affected by quality perception and patient expectation. Patient satisfaction and patient loyalty was also affected by disease pressure. Hospital brand was positively correlated with patient satisfaction and patient loyalty, negatively correlated with patient complaint. Patient satisfaction was positively correlated with patient loyalty, patient complaints, and quality perception, and negatively correlated with disease pressure and patient expectation. The satisfaction model on nursing service in hospitalized tumor patients fits well. By this model, the quality of hospital nursing care may be improved.

  5. Tumor heterogeneity and progression: conceptual foundations for modeling.

    Science.gov (United States)

    Greller, L D; Tobin, F L; Poste, G

    1996-01-01

    A conceptual foundation for modeling tumor progression, growth, and heterogeneity is presented. The purpose of such models is to aid understanding, test ideas, formulate experiments, and to model cancer 'in machina' to address the dynamic features of tumor cell heterogeneity, progression, and growth. The descriptive capabilities of such an approach provides a consistent language for qualitatively reasoning about tumor behavior. This approach provides a schema for building conceptual models that combine three key phenomenological driving elements: growth, progression, and genetic instability. The growth element encompasses processes contributing to changes in tumor bulk and is distinct from progression per se. The progression element subsumes a broad collection of processes underlying phenotypic progression. The genetics elements represents heritable changes which potentially affect tumor character and behavior. Models, conceptual and mathematical, can be built for different tumor situations by drawing upon the interaction of these three distinct driving elements. These models can be used as tools to explore a diversity of hypotheses concerning dynamic changes in cellular populations during tumor progression, including the generation of intratumor heterogeneity. Such models can also serve to guide experimentation and to gain insight into dynamic aspects of complex tumor behavior.

  6. Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

    International Nuclear Information System (INIS)

    Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

    1995-01-01

    , the rank-order correlation coefficient between the single dose hypoxic versus fractionated dose TCD50s under hypoxic or aerobic conditions was 1.0. For all 5 tumors examined, a trend for rank correlation was observed between the single dose and the fractionated dose TCD50s performed under normal or clamp hypoxic conditions (r=0.7, p=0.16 in both cases). The linear correlation coefficients were 0.83, p=0.08 and 0.72, p=0.17, respectively. Failure to attain a rank correlation of 1.0 was due to one tumor exhibiting an insignificant fractionation effect. The rank correlation between the TCD50s for fractionated treatments under normal versus the extrapolated TCD50s under clamp hypoxic conditions was 1.00; the linear correlation coefficient was 0.97 (p=0.01). Conclusions: In the tumor models examined, factors controlling the single fraction tumor control dose, also impact the response to fractionated treatments. These results suggest that laboratory estimates of intrinsic radiosensitivity and tumor clonogen number at the onset of treatment, will be of use in predicting radiocurability for fractionated treatments, as has been observed for single dose treatments

  7. Angiogenic Signaling in Living Breast Tumor Models

    National Research Council Canada - National Science Library

    Brown, Edward

    2006-01-01

    .... Progress to date includes the recruitment of personnel to the new laboratory, the development and testing of a novel method for the measurement of convective flow in tumors in vivo, the investigation...

  8. Measurement and modelling of high pressure density and interfacial tension of (gas + n-alkane) binary mixtures

    International Nuclear Information System (INIS)

    Pereira, Luís M.C.; Chapoy, Antonin; Burgass, Rod; Tohidi, Bahman

    2016-01-01

    Highlights: • (Density + IFT) measurements are performed in synthetic reservoir fluids. • Measured systems include CO_2, CH_4 and N_2 with n-decane. • Novel data are reported for temperatures up to 443 K and pressures up to 69 MPa. • Predictive models are tested in 16 (gas + n-alkane) systems. • Best modelling results are achieved with the Density Gradient Theory. - Abstract: The deployment of more efficient and economical extraction methods and processing facilities of oil and gas requires the accurate knowledge of the interfacial tension (IFT) of fluid phases in contact. In this work, the capillary constant a of binary mixtures containing n-decane and common gases such as carbon dioxide, methane and nitrogen was measured. Experimental measurements were carried at four temperatures (313, 343, 393 and 442 K) and pressures up to 69 MPa, or near the complete vaporisation of the organic phase into the gas-rich phase. To determine accurate IFT values, the capillary constants were combined with saturated phase density data measured with an Anton Paar densitometer and correlated with a model based on the Peng–Robinson 1978 equation of state (PR78 EoS). Correlated density showed an overall percentage absolute deviation (%AAD) to measured data of (0.2 to 0.5)% for the liquid phase and (1.5 to 2.5)% for the vapour phase of the studied systems and P–T conditions. The predictive capability of models to accurately describe both the temperature and pressure dependence of the saturated phase density and IFT of 16 (gas + n-alkane) binary mixtures was assessed in this work by comparison with data gathered from the literature and measured in this work. The IFT models considered include the Parachor, the Linear Gradient Theory (LGT) and the Density Gradient Theory (DGT) approaches combined with the Volume-Translated Predictive Peng–Robinson 1978 EoS (VT-PPR78 EoS). With no adjustable parameters, the VT-PPR78 EoS allowed a good description of both solubility and

  9. An interfacial shear term evaluation study for adiabatic dispersed air–water two-phase flow with the two-fluid model using CFD

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, S.L., E-mail: sharma55@purdue.edu [School of Nuclear Engineering, Purdue University, West Lafayette, IN (United States); Hibiki, T.; Ishii, M. [School of Nuclear Engineering, Purdue University, West Lafayette, IN (United States); Schlegel, J.P. [Department of Mining and Nuclear Engineering, Missouri University of Science and Technology, Rolla, MO (United States); Buchanan, J.R.; Hogan, K.J. [Bettis Laboratory, Naval Nuclear Laboratory, West Mifflin, PA (United States); Guilbert, P.W. [ANSYS UK Ltd, Oxfordshire (United Kingdom)

    2017-02-15

    Highlights: • Closure form of the interfacial shear term in three-dimensional form is investigated. • Assessment against adiabatic upward bubbly air–water flow data using CFD. • Effect of addition of the interfacial shear term on the phase distribution. - Abstract: In commercially available Computational Fluid Dynamics (CFD) codes such as ANSYS CFX and Fluent, the interfacial shear term is missing in the field momentum equations. The derivation of the two-fluid model (Ishii and Hibiki, 2011) indicates the presence of this term as a momentum source in the right hand side of the field momentum equation. The inclusion of this term is considered important for proper modeling of the interfacial momentum coupling between phases. For separated flows, such as annular flow, the importance of the shear term is understood in the one-dimensional (1-D) form as the major mechanism by which the wall shear is transferred to the gas phase (Ishii and Mishima, 1984). For gas dispersed two-phase flow CFD simulations, it is important to assess the significance of this term in the prediction of phase distributions. In the first part of this work, the closure of this term in three-dimensional (3-D) form in a CFD code is investigated. For dispersed gas–liquid flow, such as bubbly or churn-turbulent flow, bubbles are dispersed in the shear layer of the continuous phase. The continuous phase shear stress is mainly due to the presence of the wall and the modeling of turbulence through the Boussinesq hypothesis. In a 3-D simulation, the continuous phase shear stress can be calculated from the continuous fluid velocity gradient, so that the interfacial shear term can be closed using the local values of the volume fraction and the total stress of liquid phase. This form also assures that the term acts as an action-reaction force for multiple phases. In the second part of this work, the effect of this term on the volume fraction distribution is investigated. For testing the model two

  10. A model of tumor architecture and spatial interactions with tumor microenvironment in breast carcinoma

    Science.gov (United States)

    Ben Cheikh, Bassem; Bor-Angelier, Catherine; Racoceanu, Daniel

    2017-03-01

    Breast carcinomas are cancers that arise from the epithelial cells of the breast, which are the cells that line the lobules and the lactiferous ducts. Breast carcinoma is the most common type of breast cancer and can be divided into different subtypes based on architectural features and growth patterns, recognized during a histopathological examination. Tumor microenvironment (TME) is the cellular environment in which tumor cells develop. Being composed of various cell types having different biological roles, TME is recognized as playing an important role in the progression of the disease. The architectural heterogeneity in breast carcinomas and the spatial interactions with TME are, to date, not well understood. Developing a spatial model of tumor architecture and spatial interactions with TME can advance our understanding of tumor heterogeneity. Furthermore, generating histological synthetic datasets can contribute to validating, and comparing analytical methods that are used in digital pathology. In this work, we propose a modeling method that applies to different breast carcinoma subtypes and TME spatial distributions based on mathematical morphology. The model is based on a few morphological parameters that give access to a large spectrum of breast tumor architectures and are able to differentiate in-situ ductal carcinomas (DCIS) and histological subtypes of invasive carcinomas such as ductal (IDC) and lobular carcinoma (ILC). In addition, a part of the parameters of the model controls the spatial distribution of TME relative to the tumor. The validation of the model has been performed by comparing morphological features between real and simulated images.

  11. A Big Bang model of human colorectal tumor growth.

    Science.gov (United States)

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

  12. Interfacial phenomenon theory

    International Nuclear Information System (INIS)

    Kim, Jong Deuk

    2000-02-01

    This book is composed of 8 chapters. It tells what interfacial phenomenon is by showing interfacial energy, characteristic of interface and system of interface from chapter 1. It also introduces interfacial energy and structure theory, molecular structure and orientation theory, and interfacial electricity phenomenon theory in the following 3 chapters. It still goes on by introducing super molecule cluster, disequilibrium dispersion, and surface and film through 3 chapters. And the last chapter is about colloid and application of interface.

  13. Scaling of interfacial jump conditions

    International Nuclear Information System (INIS)

    Quezada G, S.; Vazquez R, A.; Espinosa P, G.

    2015-09-01

    To model the behavior of a nuclear reactor accurately is needed to have balance models that take into account the different phenomena occurring in the reactor. These balances have to be coupled together through boundary conditions. The boundary conditions have been studied and different treatments have been given to the interface. In this paper is a brief description of some of the interfacial jump conditions that have been proposed in recent years. Also, the scaling of an interfacial jump condition is proposed, for coupling the different materials that are in contact within a nuclear reactor. (Author)

  14. Cyclosporin safety in a simplified rat brain tumor implantation model

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

    Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

  15. Hedgehog pathway activity in the LADY prostate tumor model

    Directory of Open Access Journals (Sweden)

    Kasper Susan

    2007-03-01

    Full Text Available Abstract Background Robust Hedgehog (Hh signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate cancer model has never been examined. Results We analyzed expression of Hh pathway components and conserved Hh target genes along with progenitor cell markers and selected markers of epithelial differentiation during tumor development in the LADY transgenic mouse model. Tumor development was associated with a selective increase in Ihh expression. In contrast Shh expression was decreased. Expression of the Hh target Patched (Ptc was significantly decreased while Gli1 expression was not significantly altered. A survey of other relevant genes revealed significant increases in expression of Notch-1 and Nestin together with decreased expression of HNF3a/FoxA1, NPDC-1 and probasin. Conclusion Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development.

  16. Development of DPD coarse-grained models: From bulk to interfacial properties

    Energy Technology Data Exchange (ETDEWEB)

    Solano Canchaya, José G.; Dequidt, Alain, E-mail: alain.dequidt@univ-bpclermont.fr; Goujon, Florent; Malfreyt, Patrice [Institut de Chimie de Clermont-Ferrand, Université Blaise Pascal, Université Clermont Auvergne, BP 10448, F-63000 Clermont-Ferrand (France); CNRS, UMR 6296, ICCF, F-63178 Aubiere (France)

    2016-08-07

    A new Bayesian method was recently introduced for developing coarse-grain (CG) force fields for molecular dynamics. The CG models designed for dissipative particle dynamics (DPD) are optimized based on trajectory matching. Here we extend this method to improve transferability across thermodynamic conditions. We demonstrate the capability of the method by developing a CG model of n-pentane from constant-NPT atomistic simulations of bulk liquid phases and we apply the CG-DPD model to the calculation of the surface tension of the liquid-vapor interface over a large range of temperatures. The coexisting densities, vapor pressures, and surface tensions calculated with different CG and atomistic models are compared to experiments. Depending on the database used for the development of the potentials, it is possible to build a CG model which performs very well in the reproduction of the surface tension on the orthobaric curve.

  17. Mathematical and Computational Modeling for Tumor Virotherapy with Mediated Immunity.

    Science.gov (United States)

    Timalsina, Asim; Tian, Jianjun Paul; Wang, Jin

    2017-08-01

    We propose a new mathematical modeling framework based on partial differential equations to study tumor virotherapy with mediated immunity. The model incorporates both innate and adaptive immune responses and represents the complex interaction among tumor cells, oncolytic viruses, and immune systems on a domain with a moving boundary. Using carefully designed computational methods, we conduct extensive numerical simulation to the model. The results allow us to examine tumor development under a wide range of settings and provide insight into several important aspects of the virotherapy, including the dependence of the efficacy on a few key parameters and the delay in the adaptive immunity. Our findings also suggest possible ways to improve the virotherapy for tumor treatment.

  18. Bifurcation analysis of a delayed mathematical model for tumor growth

    International Nuclear Information System (INIS)

    Khajanchi, Subhas

    2015-01-01

    In this study, we present a modified mathematical model of tumor growth by introducing discrete time delay in interaction terms. The model describes the interaction between tumor cells, healthy tissue cells (host cells) and immune effector cells. The goal of this study is to obtain a better compatibility with reality for which we introduced the discrete time delay in the interaction between tumor cells and host cells. We investigate the local stability of the non-negative equilibria and the existence of Hopf-bifurcation by considering the discrete time delay as a bifurcation parameter. We estimate the length of delay to preserve the stability of bifurcating periodic solutions, which gives an idea about the mode of action for controlling oscillations in the tumor growth. Numerical simulations of the model confirm the analytical findings

  19. Interfacial mixing in high-energy-density matter with a multiphysics kinetic model

    Science.gov (United States)

    Haack, Jeffrey R.; Hauck, Cory D.; Murillo, Michael S.

    2017-12-01

    We have extended a recently developed multispecies, multitemperature Bhatnagar-Gross-Krook model [Haack et al., J. Stat. Phys. 168, 822 (2017), 10.1007/s10955-017-1824-9], to include multiphysics capabilities that enable modeling of a wider range of physical conditions. In terms of geometry, we have extended from the spatially homogeneous setting to one spatial dimension. In terms of the physics, we have included an atomic ionization model, accurate collision physics across coupling regimes, self-consistent electric fields, and degeneracy in the electronic screening. We apply the model to a warm dense matter scenario in which the ablator-fuel interface of an inertial confinement fusion target is heated, but for larger length and time scales and for much higher temperatures than can be simulated using molecular dynamics. Relative to molecular dynamics, the kinetic model greatly extends the temperature regime and the spatiotemporal scales over which we are able to model. In our numerical results we observe hydrogen from the ablator material jetting into the fuel during the early stages of the implosion and compare the relative size of various diffusion components (Fickean diffusion, electrodiffusion, and barodiffusion) that drive this process. We also examine kinetic effects, such as anisotropic distributions and velocity separation, in order to determine when this problem can be described with a hydrodynamic model.

  20. Selection, calibration, and validation of models of tumor growth.

    Science.gov (United States)

    Lima, E A B F; Oden, J T; Hormuth, D A; Yankeelov, T E; Almeida, R C

    2016-11-01

    This paper presents general approaches for addressing some of the most important issues in predictive computational oncology concerned with developing classes of predictive models of tumor growth. First, the process of developing mathematical models of vascular tumors evolving in the complex, heterogeneous, macroenvironment of living tissue; second, the selection of the most plausible models among these classes, given relevant observational data; third, the statistical calibration and validation of models in these classes, and finally, the prediction of key Quantities of Interest (QOIs) relevant to patient survival and the effect of various therapies. The most challenging aspects of this endeavor is that all of these issues often involve confounding uncertainties: in observational data, in model parameters, in model selection, and in the features targeted in the prediction. Our approach can be referred to as "model agnostic" in that no single model is advocated; rather, a general approach that explores powerful mixture-theory representations of tissue behavior while accounting for a range of relevant biological factors is presented, which leads to many potentially predictive models. Then representative classes are identified which provide a starting point for the implementation of OPAL, the Occam Plausibility Algorithm (OPAL) which enables the modeler to select the most plausible models (for given data) and to determine if the model is a valid tool for predicting tumor growth and morphology ( in vivo ). All of these approaches account for uncertainties in the model, the observational data, the model parameters, and the target QOI. We demonstrate these processes by comparing a list of models for tumor growth, including reaction-diffusion models, phase-fields models, and models with and without mechanical deformation effects, for glioma growth measured in murine experiments. Examples are provided that exhibit quite acceptable predictions of tumor growth in laboratory

  1. A multiphase interfacial model for the dissolution of spent nuclear fuel

    Science.gov (United States)

    Jerden, James L.; Frey, Kurt; Ebert, William

    2015-07-01

    The Fuel Matrix Dissolution Model (FMDM) is an electrochemical reaction/diffusion model for the dissolution of spent uranium oxide fuel. The model was developed to provide radionuclide source terms for use in performance assessment calculations for various types of geologic repositories. It is based on mixed potential theory and consists of a two-phase fuel surface made up of UO2 and a noble metal bearing fission product phase in contact with groundwater. The corrosion potential at the surface of the dissolving fuel is calculated by balancing cathodic and anodic reactions occurring at the solution interfaces with UO2 and NMP surfaces. Dissolved oxygen and hydrogen peroxide generated by radiolysis of the groundwater are the major oxidizing agents that promote fuel dissolution. Several reactions occurring on noble metal alloy surfaces are electrically coupled to the UO2 and can catalyze or inhibit oxidative dissolution of the fuel. The most important of these is the oxidation of hydrogen, which counteracts the effects of oxidants (primarily H2O2 and O2). Inclusion of this reaction greatly decreases the oxidation of U(IV) and slows fuel dissolution significantly. In addition to radiolytic hydrogen, large quantities of hydrogen can be produced by the anoxic corrosion of steel structures within and near the fuel waste package. The model accurately predicts key experimental trends seen in literature data, the most important being the dramatic depression of the fuel dissolution rate by the presence of dissolved hydrogen at even relatively low concentrations (e.g., less than 1 mM). This hydrogen effect counteracts oxidation reactions and can limit fuel degradation to chemical dissolution, which results in radionuclide source term values that are four or five orders of magnitude lower than when oxidative dissolution processes are operative. This paper presents the scientific basis of the model, the approach for modeling used fuel in a disposal system, and preliminary

  2. A multiphase interfacial model for the dissolution of spent nuclear fuel

    Energy Technology Data Exchange (ETDEWEB)

    Jerden, James L., E-mail: jerden@anl.gov [Argonne National Laboratory, 9700 South Cass Ave., Argonne, IL 60439 (United States); Frey, Kurt [University of Notre Dame, Notre Dame, IN 46556 (United States); Ebert, William [Argonne National Laboratory, 9700 South Cass Ave., Argonne, IL 60439 (United States)

    2015-07-15

    Highlights: • This model accounts for chemistry, temperature, radiolysis, U(VI) minerals, and hydrogen effect. • The hydrogen effect dominates processes determining spent fuel dissolution rate. • The hydrogen effect protects uranium oxide spent fuel from oxidative dissolution. - Abstract: The Fuel Matrix Dissolution Model (FMDM) is an electrochemical reaction/diffusion model for the dissolution of spent uranium oxide fuel. The model was developed to provide radionuclide source terms for use in performance assessment calculations for various types of geologic repositories. It is based on mixed potential theory and consists of a two-phase fuel surface made up of UO{sub 2} and a noble metal bearing fission product phase in contact with groundwater. The corrosion potential at the surface of the dissolving fuel is calculated by balancing cathodic and anodic reactions occurring at the solution interfaces with UO{sub 2} and NMP surfaces. Dissolved oxygen and hydrogen peroxide generated by radiolysis of the groundwater are the major oxidizing agents that promote fuel dissolution. Several reactions occurring on noble metal alloy surfaces are electrically coupled to the UO{sub 2} and can catalyze or inhibit oxidative dissolution of the fuel. The most important of these is the oxidation of hydrogen, which counteracts the effects of oxidants (primarily H{sub 2}O{sub 2} and O{sub 2}). Inclusion of this reaction greatly decreases the oxidation of U(IV) and slows fuel dissolution significantly. In addition to radiolytic hydrogen, large quantities of hydrogen can be produced by the anoxic corrosion of steel structures within and near the fuel waste package. The model accurately predicts key experimental trends seen in literature data, the most important being the dramatic depression of the fuel dissolution rate by the presence of dissolved hydrogen at even relatively low concentrations (e.g., less than 1 mM). This hydrogen effect counteracts oxidation reactions and can limit

  3. Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

    Directory of Open Access Journals (Sweden)

    Felicia Leccia

    2016-07-01

    Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

  4. Modeling interfacial glass-water reactions: recent advances and current limitations

    International Nuclear Information System (INIS)

    Pierce, Eric M.; Frugier, Pierre; Criscenti, Louise J.; Kwon, Kideok D.; Kerisit, Sebastien N.

    2014-01-01

    Describing the reactions that occur at the glass-water interface and control the development of the altered layer constitutes one of the main scientific challenges impeding existing models from providing accurate radionuclide release estimates. Radionuclide release estimates are a critical component of the safety basis for geologic repositories. The altered layer (i.e., amorphous hydrated surface layer and crystalline reaction products) represents a complex region, both physically and chemically, sandwiched between two distinct boundaries-pristine glass surface at the inner most interface and aqueous solution at the outer most interface. Computational models, spanning different length and timescales, are currently being developed to improve our understanding of this complex and dynamic process with the goal of accurately describing the mesoscale changes that occur as the system evolves. These modeling approaches include geochemical simulations (i.e., classical reaction path simulations and glass reactivity in allowance for alteration layer simulations), Monte Carlo simulations, and molecular dynamics methods. Discussed in this manuscript are the advances and limitations of each modeling approach placed in the context of the glass-water reaction and how collectively these approaches provide insights into the mechanisms that control the formation and evolution of altered layers. New results are presented as examples of each approach. (authors)

  5. International Workshop on Mathematical Modeling of Tumor-Immune Dynamics

    CERN Document Server

    Kim, Peter; Mallet, Dann

    2014-01-01

    This collection of papers offers a broad synopsis of state-of-the-art mathematical methods used in modeling the interaction between tumors and the immune system. These papers were presented at the four-day workshop on Mathematical Models of Tumor-Immune System Dynamics held in Sydney, Australia from January 7th to January 10th, 2013. The workshop brought together applied mathematicians, biologists, and clinicians actively working in the field of cancer immunology to share their current research and to increase awareness of the innovative mathematical tools that are applicable to the growing field of cancer immunology. Recent progress in cancer immunology and advances in immunotherapy suggest that the immune system plays a fundamental role in host defense against tumors and could be utilized to prevent or cure cancer. Although theoretical and experimental studies of tumor-immune system dynamics have a long history, there are still many unanswered questions about the mechanisms that govern the interaction betwe...

  6. A numerical insight into elastomer normally closed micro valve actuation with cohesive interfacial cracking modelling

    Science.gov (United States)

    Wang, Dongyang; Ba, Dechun; Hao, Ming; Duan, Qihui; Liu, Kun; Mei, Qi

    2018-05-01

    Pneumatic NC (normally closed) valves are widely used in high density microfluidics systems. To improve actuation reliability, the actuation pressure needs to be reduced. In this work, we utilize 3D FEM (finite element method) modelling to get an insight into the valve actuation process numerically. Specifically, the progressive debonding process at the elastomer interface is simulated with CZM (cohesive zone model) method. To minimize the actuation pressure, the V-shape design has been investigated and compared with a normal straight design. The geometrical effects of valve shape has been elaborated, in terms of valve actuation pressure. Based on our simulated results, we formulate the main concerns for micro valve design and fabrication, which is significant for minimizing actuation pressures and ensuring reliable operation.

  7. Evaluation of Interfacial Heat Transfer Models for Flashing Flow with Two-Fluid CFD

    Directory of Open Access Journals (Sweden)

    Yixiang Liao

    2018-06-01

    Full Text Available The complexity of flashing flows is increased vastly by the interphase heat transfer as well as its coupling with mass and momentum transfers. A reliable heat transfer coefficient is the key in the modelling of such kinds of flows with the two-fluid model. An extensive literature survey on computational modelling of flashing flows has been given in previous work. The present work is aimed at giving a brief review on available theories and correlations for the estimation of interphase heat transfer coefficient, and evaluating them quantitatively based on computational fluid dynamics simulations of bubble growth in superheated liquid. The comparison of predictions for bubble growth rate obtained by using different correlations with the experimental as well as direct numerical simulation data reveals that the performance of the correlations is dependent on the Jakob number and Reynolds number. No generally applicable correlations are available. Both conduction and convection are important in cases of bubble rising and translating in stagnant liquid at high Jakob numbers. The correlations combining the analytical solution for heat diffusion and the theoretical relation for potential flow give the best agreement.

  8. Cell Competition Drives the Formation of Metastatic Tumors in a Drosophila Model of Epithelial Tumor Formation

    DEFF Research Database (Denmark)

    Eichenlaub, Teresa; Cohen, Stephen M; Herranz, Héctor

    2016-01-01

    . The mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis. However, direct evidence supporting this hypothesis has been lacking. Here, we provide evidence that cell competition drives tumor formation in a Drosophila model of epithelial cancer. Cells...

  9. Interfacial heat transfer - State of the art

    International Nuclear Information System (INIS)

    Yadigaroglu, G.

    1987-01-01

    Interfacial heat exchanges control the interfacial mass exchange rate, depend on the interfacial area, and are tied to the prediction of thermal nonequilibrium. The nature of the problem usually requires the formulation of mechanistic laws and precludes the general use of universal correlations. This is partly due to the fact that the length scale controlling the interfacial exchanges varies widely from one situation to another and has a strong influence on the exchange coefficients. Within the framework of the ''two-fluid models'', the exchanges occurring at the interfaces are explicitly taken into consideration by the jump condition linking the volumetric mass exchange (evaporation) rate between the phases, to the interfacial energy transfer rates

  10. Predictive modeling of interfacial damage in substructured steels: application to martensitic microstructures

    International Nuclear Information System (INIS)

    Maresca, F; Kouznetsova, V G; Geers, M G D

    2016-01-01

    Metallic composite phases, like martensite present in conventional steels and new generation high strength steels exhibit microscale, locally lamellar microstructures characterized by alternating layers of phases or crystallographic variants. The layers can be sub-micron down to a few nanometers thick, and they are often characterized by high contrasts in plastic properties. As a consequence, fracture in these lamellar microstructures generally occurs along the layer interfaces or within one of the layers, typically parallel to the interface. This paper presents a computational framework that addresses the lamellar nature of these microstructures, by homogenizing the plastic deformation at the mesoscale by using the microscale response of the laminates. Failure is accounted for by introducing a family of damaging planes that are parallel to the layer interface. Mode I, mode II and mixed-mode opening are incorporated. The planes along which failure occurs are captured using a smeared damage approach. Coupling of damage with isotropic or anisotropic plasticity models, like crystal plasticity, is straightforward. The damaging planes and directions do not need to correspond to crystalline slip planes, and normal opening is also included. Focus is given on rate-dependent formulations of plasticity and damage, i.e. converged results can be obtained without further regularization techniques. The validation of the model using experimental observations in martensite-austenite lamellar microstructures in steels reveals that the model correctly predicts the main features of the onset of failure, e.g. the necking point, the failure initiation region and the failure mode. Finally, based on the qualitative results obtained, some material design guidelines are provided for martensitic and multi-phase steels. (paper)

  11. Chemical, spectroscopic, and ab initio modelling approach to interfacial reactivity applied to anion retention by siderite

    International Nuclear Information System (INIS)

    Badaut, V.

    2010-07-01

    Among the many radionuclides contained in high-level nuclear waste, 79 Se was identified as a potential threat to the safety of long term underground storage. However, siderite (FeCO 3 ) is known to form upon corrosion of the waste container, and the impact of this mineral on the fate of selenium was not accounted for. In this work, the interactions between selenium oxyanions - selenate and selenite - and siderite were investigated. To this end, both experimental characterizations (solution chemistry, X-ray Absorption Spectroscopy - XAS) and theoretical studies (ab initio modelling using Density Functional Theory - DFT ) were performed. Selenite and selenate (≤ 10 3 M) retention experiments by siderite suspensions (75 g/L ) at neutral pH in reducing glovebox (5 % H 2 ) showed that selenite is quantitatively immobilized by siderite after 48 h of reaction time, when selenate is only partly immobilized after 10 days. In the selenite case, XAS showed that immobilized selenium is initially present as Se(IV) probably sorbed on siderite surface. After 10 days of reaction, selenite ions are quantitatively reduced and form poorly crystalline elementary selenium. Selenite retention and reduction kinetics are therefore distinct. On the other hand, the fraction of immobilized selenate retained in the solid fraction does not appear to be significantly reduced over the probed timescale (10 days). For a better understanding of the reduction mechanism of selenite ions by siderite, the properties of bulk and perfect surfaces of siderite were modelled using DFT. We suggest that the properties of the valence electrons can be correctly described only if the symmetry of the fundamental state electronic density is lower than the experimental crystallographic symmetry. We then show that the retention of simple molecules as O 2 or H 2 O on siderite and magnesite (10 -14 ) perfect surfaces (perfect cleavage plane, whose surface energy is the lowest according to DFT) can be modelled with

  12. Interfacial effects in multilayers

    International Nuclear Information System (INIS)

    Barbee, T.W. Jr.

    1998-01-01

    Interfacial structure and the atomic interactions between atoms at interfaces in multilayers or nano-laminates have significant impact on the physical properties of these materials. A technique for the experimental evaluation of interfacial structure and interfacial structure effects is presented and compared to experiment. In this paper the impact of interfacial structure on the performance of x-ray, soft x-ray and extreme ultra-violet multilayer optic structures is emphasized. The paper is concluded with summary of these results and an assessment of their implications relative to multilayer development and the study of buried interfaces in solids in general

  13. Cellular Interaction and Tumoral Penetration Properties of Cyclodextrin Nanoparticles on 3D Breast Tumor Model

    Directory of Open Access Journals (Sweden)

    Gamze Varan

    2018-01-01

    Full Text Available Amphiphilic cyclodextrins are biocompatible oligosaccharides that can be used for drug delivery especially for the delivery of drugs with solubility problems thanks to their unique molecular structures. In this paper, Paclitaxel was used as a model anticancer drug to determine the inclusion complex properties of amphiphilic cyclodextrins with different surface charge. Paclitaxel-loaded cyclodextrin nanoparticles were characterized in terms of mean particle diameter, zeta potential, encapsulation efficacy, drug release profile and cell culture studies. It was determined that the nanoparticles prepared from the inclusion complex according to characterization studies have a longer release profile than the conventionally prepared nanoparticles. In order to mimic the tumor microenvironment, breast cancer cells and healthy fibroblast cells were used in 3-dimensional (3D cell culture studies. It was determined that the activities of nanoparticles prepared by conventional methods behave differently in 2-dimensional (2D and 3D cell cultures. In addition, it was observed that the nanoparticles prepared from the inclusion complex have a stronger anti-tumoral activity in the 3D multicellular tumor model than the drug solution. Furthermore, polycationic amphiphilic cyclodextrin nanoparticles can diffuse and penetrate through multilayer cells in a 3D tumor model, which is crucial for an eventual antitumor effect.

  14. Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors.

    Directory of Open Access Journals (Sweden)

    Andrea Sottoriva

    2011-05-01

    Full Text Available The cancer stem cell (CSC concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult to interpret. An important reason for this is that most experimental data that support this model rely on transplantation studies. In this study we use a novel cellular Potts model to elucidate the dynamics of established malignancies that are driven by a small subset of CSCs. Our results demonstrate that epigenetic mutations that occur during mitosis display highly altered dynamics in CSC-driven malignancies compared to a classical, non-hierarchical model of growth. In particular, the heterogeneity observed in CSC-driven tumors is considerably higher. We speculate that this feature could be used in combination with epigenetic (methylation sequencing studies of human malignancies to prove or refute the CSC hypothesis in established tumors without the need for transplantation. Moreover our tumor growth simulations indicate that CSC-driven tumors display evolutionary features that can be considered beneficial during tumor progression. Besides an increased heterogeneity they also exhibit properties that allow the escape of clones from local fitness peaks. This leads to more aggressive phenotypes in the long run and makes the neoplasm more adaptable to stringent selective forces such as cancer treatment. Indeed when therapy is applied the clone landscape of the regrown tumor is more aggressive with respect to the primary tumor, whereas the classical model demonstrated similar patterns before and after therapy. Understanding these often counter-intuitive fundamental properties of (non-hierarchically organized malignancies is a crucial step in validating the CSC concept as well as providing insight into the therapeutical consequences of this model.

  15. Modelo experimental de tumor de Walker Walker’s tumoral experimental model

    Directory of Open Access Journals (Sweden)

    Sandra Pedroso de Moraes

    2000-12-01

    Full Text Available Com o objetivo de padronizar normas técnicas para obtenção de modelo animal com tumor de Walker 256 e de estabelecer o número de células tumorais necessárias para que esse tumor tenha grande porcentagem de pega e longevidade, possibilitando o desenvolvimento de pesquisas em várias áreas da saúde, foi realizado trabalho em duas etapas. Na primeira foram utilizados 120 ratos para treinamento e definição da técnica. Na segunda etapa foram utilizados 84 ratos, sendo estes separados em 7 grupos (G de 12 animais cada. O tumor, na forma ascítica, foi inoculado no tecido celular subcutâneo do dorso dos ratos com os seguintes números de células: GI, 1 x 10(7; GII, 5 x 10(6; GIII, 2,5 x 10(6; GIV, 1 x 10(6; GV, 5 x 10(5; GVI, 3 x 10(5 e GVII, 2 x 10(5. Foram avaliadas a porcentagem de pega e a longevidade nos grupos. Os animais dos GI, GII, GIII e GIV obtiveram 100% de desenvolvimento tumoral, porém baixa longevidade. Os dos GV e GVI obtiveram desenvolvimento tumoral em frequência maior que 90% e longevidade satisfatória. Os do GVII não apresentaram desenvolvimento tumoral. Concluiu-se que todos os procedimentos devem ser exaustivamente treinados e que o número de células tumorais viáveis para inoculação, em tecido celular subcutâneo de ratos, deve estar na faixa entre 5 x 10(5 e 3 x 10(5.The aim of this work was standardize technical norms to obtain a model of Walker 256 tumor in animals and get the tumorous cells number needed to increase the tumorous join percentage and longevity, it makes possible the research development in several health areas. The work was realized in two stages. In first were used 120 rats to crew’s training and technicals definitions. In second stage were used 84 rats, these separated in 7 groups (G with 12 animals each one. The tumor, in ascitic form was inoculated on subcutaneous cellular tissue on dorsal of rats with the follow number of cells : GI, 1 x 10(7; GII, 5 x 10(6; GIII, 2,5 x 10(6; GIV, 1

  16. Evaluation of the interfacial shear strength and residual stress of TiAlN coating on ZIRLO™ fuel cladding using a modified shear-lag model approach

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Y., E-mail: troy.liu@manchester.ac.uk [Materials Performance Centre, School of Materials, The University of Manchester, M13 9PL (United Kingdom); Bhamji, I., E-mail: imran.bhamji@manchester.ac.uk [Materials Performance Centre, School of Materials, The University of Manchester, M13 9PL (United Kingdom); Withers, P.J., E-mail: p.j.withers@manchester.ac.uk [Materials Performance Centre, School of Materials, The University of Manchester, M13 9PL (United Kingdom); Wolfe, D.E., E-mail: dew125@arl.psu.edu [The Pennsylvania State University, University Park, State College, PA 16801 (United States); Motta, A.T., E-mail: atmnuc@engr.psu.edu [The Pennsylvania State University, University Park, State College, PA 16801 (United States); Preuss, M., E-mail: michael.preuss@manchester.ac.uk [Materials Performance Centre, School of Materials, The University of Manchester, M13 9PL (United Kingdom)

    2015-11-15

    This paper investigates the residual stresses and interfacial shear strength of a TiAlN coating on Zr–Nb–Sn–Fe alloy (ZIRLO™) substrate designed to improve corrosion resistance of fuel cladding used in water-cooled nuclear reactors, both during normal and exceptional conditions, e.g. a loss of coolant event (LOCA). The distribution and maximum value of the interfacial shear strength has been estimated using a modified shear-lag model. The parameters critical to this analysis were determined experimentally. From these input parameters the interfacial shear strength between the TiAlN coating and ZIRLO™ substrate was inferred to be around 120 MPa. It is worth noting that the apparent strength of the coating is high (∼3.4 GPa). However, this is predominantly due to the large compressive residuals stress (3 GPa in compression), which must be overcome for the coating to fail in tension, which happens at a load just 150 MPa in excess of this.

  17. Numerical simulations of counter-current two-phase flow experiments in a PWR hot leg model using an interfacial area density model

    Energy Technology Data Exchange (ETDEWEB)

    Hoehne, Thomas, E-mail: t.hoehne@hzdr.de [Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Safety Research, P.O. Box 510 119, D-01314 Dresden (Germany); Deendarlianto,; Lucas, Dirk [Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Safety Research, P.O. Box 510 119, D-01314 Dresden (Germany)

    2011-10-15

    In order to improve the understanding of counter-current two-phase flows and to validate new physical models, CFD simulations of 1/3rd scale model of the hot leg of a German Konvoi PWR with rectangular cross section was performed. Selected counter-current flow limitation (CCFL) experiments at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) were calculated with ANSYS CFX 12.1 using the multi-fluid Euler-Euler modeling approach. The transient calculations were carried out using a gas/liquid inhomogeneous multiphase flow model coupled with a k-{omega} turbulence model for each phase. In the simulation, the surface drag was approached by a new correlation inside the Algebraic Interfacial Area Density (AIAD) model. The AIAD model allows the detection of the morphological form of the two phase flow and the corresponding switching via a blending function of each correlation from one object pair to another. As a result this model can distinguish between bubbles, droplets and the free surface using the local liquid phase volume fraction value. A comparison with the high-speed video observations shows a good qualitative agreement. The results indicated that quantitative agreement of the CCFL characteristics between calculation and experimental data was obtained. The goal is to provide an easy usable AIAD framework for all Code users, with the possibility of the implementation of their own correlations.

  18. Numerical simulations of counter-current two-phase flow experiments in a PWR hot leg model using an interfacial area density model

    Energy Technology Data Exchange (ETDEWEB)

    Hohne, T.; Deendarlianto; Vallee, C.; Lucas, D.; Beyer, M., E-mail: t.hoehne@hzdr.de [Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Inst. of Safety Research, Dresden (Germany)

    2011-07-01

    In order to improve the understanding of counter-current two-phase flows and to validate new physical models, CFD simulations of 1/3rd scale model of the hot leg of a German Konvoi PWR with rectangular cross section was performed. Selected counter-current flow limitation (CCFL) experiments at the Helmholtz-Zentrum Dresden- Rossendorf (HZDR) were calculated with ANSYS CFX 12.1 using the multi-fluid Euler-Euler modeling approach. The transient calculations were carried out using a gas/liquid inhomogeneous multiphase flow model coupled with a SST turbulence model for each phase. In the simulation, the surface drag was approached by a new correlation inside the Algebraic Interfacial Area Density (AIAD) model. The AIAD model allows the detection of the morphological form of the two phase flow and the corresponding switching via a blending function of each correlation from one object pair to another. As a result this model can distinguish between bubbles, droplets and the free surface using the local liquid phase volume fraction value. A comparison with the high-speed video observations shows a good qualitative agreement. The results indicated that quantitative agreement of the CCFL characteristics between calculation and experimental data was obtained. The goal is to provide an easy usable AIAD framework for all ANSYS CFX users, with the possibility of the implementation of their own correlations. (author)

  19. Modeling the oxygen microheterogeneity of tumors for photodynamic therapy dosimetry

    Science.gov (United States)

    Pogue, Brian W.; Paulsen, Keith D.; O'Hara, Julia A.; Hoopes, P. Jack; Swartz, Harold

    2000-03-01

    Photodynamic theory of tumors uses optical excitation of a sensitizing drug within tissue to produce large deposits of singlet oxygen, which are thought to ultimately cause the tumor destruction. Predicting dose deposition of singlet oxygen in vivo is challenging because measurement of this species in vivo is not easily achieved. But it is possible to follow the concentration of oxygen in vivo, and so measuring the oxygen concentration transients during PDT may provide a viable method of estimating the delivered dose of singlet oxygen. However modeling the microscopic heterogeneity of the oxygen distribution within a tumor is non-trivial, and predicting the microscopic dose deposition requires further study, but this study present the framework and initial calibration needed or modeling oxygen transport in complex geometries. Computational modeling with finite elements provides a versatile structure within which oxygen diffusion and consumption can be modeled within realistic tissue geometries. This study develops the basic tools required to simulate a tumor region, and examines the role of (i) oxygen supply and consumption rates, (ii) inter- capillary spacing, (iii) photosensitizer distribution, and (iv) differences between simulated tumors and those derived directly from histology. The result of these calculations indicate that realistic tumor tissue capillary networks can be simulated using the finite element method, without excessive computational burden for 2D regions near 1 mm2, and 3D regions near 0.1mm3. These simulations can provide fundamental information about tissue and ways to implement appropriate oxygen measurements. These calculations suggest that photodynamic therapy produces the majority of singlet oxygen in and near the blood vessels, because these are the sites of highest oxygen tension. These calculations support the concept that tumor vascular regions are the major targets for PDT dose deposition.

  20. A murine model of targeted infusion for intracranial tumors.

    Science.gov (United States)

    Kim, Minhyung; Barone, Tara A; Fedtsova, Natalia; Gleiberman, Anatoli; Wilfong, Chandler D; Alosi, Julie A; Plunkett, Robert J; Gudkov, Andrei; Skitzki, Joseph J

    2016-01-01

    Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors.

  1. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

  2. A fractional motion diffusion model for grading pediatric brain tumors.

    Science.gov (United States)

    Karaman, M Muge; Wang, He; Sui, Yi; Engelhard, Herbert H; Li, Yuhua; Zhou, Xiaohong Joe

    2016-01-01

    To demonstrate the feasibility of a novel fractional motion (FM) diffusion model for distinguishing low- versus high-grade pediatric brain tumors; and to investigate its possible advantage over apparent diffusion coefficient (ADC) and/or a previously reported continuous-time random-walk (CTRW) diffusion model. With approval from the institutional review board and written informed consents from the legal guardians of all participating patients, this study involved 70 children with histopathologically-proven brain tumors (30 low-grade and 40 high-grade). Multi- b -value diffusion images were acquired and analyzed using the FM, CTRW, and mono-exponential diffusion models. The FM parameters, D fm , φ , ψ (non-Gaussian diffusion statistical measures), and the CTRW parameters, D m , α , β (non-Gaussian temporal and spatial diffusion heterogeneity measures) were compared between the low- and high-grade tumor groups by using a Mann-Whitney-Wilcoxon U test. The performance of the FM model for differentiating between low- and high-grade tumors was evaluated and compared with that of the CTRW and the mono-exponential models using a receiver operating characteristic (ROC) analysis. The FM parameters were significantly lower ( p  < 0.0001) in the high-grade ( D fm : 0.81 ± 0.26, φ : 1.40 ± 0.10, ψ : 0.42 ± 0.11) than in the low-grade ( D fm : 1.52 ± 0.52, φ : 1.64 ± 0.13, ψ : 0.67 ± 0.13) tumor groups. The ROC analysis showed that the FM parameters offered better specificity (88% versus 73%), sensitivity (90% versus 82%), accuracy (88% versus 78%), and area under the curve (AUC, 93% versus 80%) in discriminating tumor malignancy compared to the conventional ADC. The performance of the FM model was similar to that of the CTRW model. Similar to the CTRW model, the FM model can improve differentiation between low- and high-grade pediatric brain tumors over ADC.

  3. Modelling of interfacial transition zone effect on resistance to crack propagation in fine-grained cement-based composites

    Czech Academy of Sciences Publication Activity Database

    Šimonová, H.; Vyhlídal, M.; Kucharczyková, B.; Bayer, P.; Keršner, Z.; Malíková, Lucie; Klusák, Jan

    2017-01-01

    Roč. 11, č. 41 (2017), s. 211-219 ISSN 1971-8993 R&D Projects: GA ČR(CZ) GA16-18702S Institutional support: RVO:68081723 Keywords : Effective fracture toughness * Fine-grained concrete * Interfacial transition zone * Three-point bending fracture test * Scanning electron microscopy Subject RIV: JL - Materials Fatigue, Friction Mechanics OBOR OECD: Audio engineering, reliability analysis

  4. Interfacial area and interfacial transfer in two-phase systems. DOE final report

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Mamoru; Hibiki, T.; Revankar, S.T.; Kim, S.; Le Corre, J.M.

    2002-07-01

    In the two-fluid model, the field equations are expressed by the six conservation equations consisting of mass, momentum and energy equations for each phase. The existence of the interfacial transfer terms is one of the most important characteristics of the two-fluid model formulation. The interfacial transfer terms are strongly related to the interfacial area concentration and to the local transfer mechanisms such as the degree of turbulence near interfaces. This study focuses on the development of a closure relation for the interfacial area concentration. A brief summary of several problems of the current closure relation for the interfacial area concentration and a new concept to overcome the problem are given.

  5. Building Context with Tumor Growth Modeling Projects in Differential Equations

    Science.gov (United States)

    Beier, Julie C.; Gevertz, Jana L.; Howard, Keith E.

    2015-01-01

    The use of modeling projects serves to integrate, reinforce, and extend student knowledge. Here we present two projects related to tumor growth appropriate for a first course in differential equations. They illustrate the use of problem-based learning to reinforce and extend course content via a writing or research experience. Here we discuss…

  6. Linear-quadratic model predictions for tumor control probability

    International Nuclear Information System (INIS)

    Yaes, R.J.

    1987-01-01

    Sigmoid dose-response curves for tumor control are calculated from the linear-quadratic model parameters α and Β, obtained from human epidermoid carcinoma cell lines, and are much steeper than the clinical dose-response curves for head and neck cancers. One possible explanation is the presence of small radiation-resistant clones arising from mutations in an initially homogeneous tumor. Using the mutation theory of Delbruck and Luria and of Goldie and Coldman, the authors discuss the implications of such radiation-resistant clones for clinical radiation therapy

  7. Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

    Directory of Open Access Journals (Sweden)

    Ferrone Soldano

    2007-06-01

    Full Text Available Abstract Background The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs, has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed. Methods To address questions related to the in vivo interaction of human lung tumor cells and immune effector cells, we obtained an HLA class I + lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+ CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer. Results The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific manner in vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumors in vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumors in vivo without the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface. Conclusion These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, the in vivo model described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular

  8. A mechanistic compartmental model for total antibody uptake in tumors.

    Science.gov (United States)

    Thurber, Greg M; Dane Wittrup, K

    2012-12-07

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Gentamicin release from commercially-available gentamicin-loaded PMMA bone cements in a prosthesis-related interfacial gap model and their antibacterial efficacy

    Directory of Open Access Journals (Sweden)

    van der Mei Henny C

    2010-11-01

    Full Text Available Abstract Background Around about 1970, a gentamicin-loaded poly (methylmethacrylate (PMMA bone cement brand (Refobacin Palacos R was introduced to control infection in joint arthroplasties. In 2005, this brand was replaced by two gentamicin-loaded follow-up brands, Refobacin Bone Cement R and Palacos R + G. In addition, another gentamicin-loaded cement brand, SmartSet GHV, was introduced in Europe in 2003. In the present study, we investigated differences in gentamicin release and the antibacterial efficacy of the eluent between these four cement brands. Methods 200 μm-wide gaps were made in samples of each cement and filled with buffer in order to measure the gentamicin release. Release kinetics were related to bone cement powder particle characteristics and wettabilities of the cement surfaces. Gaps were also inoculated with bacteria isolated from infected prostheses for 24 h and their survival determined. Gentamicin release and bacterial survival were statistically analysed using the Student's t-test. Results All three Palacos variants showed equal burst releases but each of the successor Palacos cements showed significantly higher sustained releases. SmartSet GHV showed a significantly higher burst release, while its sustained release was comparable with original Palacos. A gentamicin-sensitive bacterium did not survive in the high gentamicin concentrations in the interfacial gaps, while a gentamicin-resistant strain did, regardless of the type of cement used. Survival was independent of the level of burst release by the bone cement. Conclusions Although marketed as the original gentamicin-loaded Palacos cement, orthopaedic surgeons should be aware that the successor cements do not appear to have the same release characteristics as the original one. Overall, high gentamicin concentrations were reached inside our prosthesis-related interfacial gap model. These concentrations may be expected to effectively decontaminate the prosthesis

  10. Combination radiotherapy in an orthotopic mouse brain tumor model.

    Science.gov (United States)

    Kramp, Tamalee R; Camphausen, Kevin

    2012-03-06

    Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 μl every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without

  11. The analysis of interfacial waves

    International Nuclear Information System (INIS)

    Galimov, Azat Yu.; Drew, Donald A.; Lahey, Richard T.; Moraga, Francisco J.

    2005-01-01

    We present analytical results for stable stratified wavy two-phase flow and functional forms for the various interfacial force densities in a two-fluid model. In particular, we have derived analytically the components of the non-drag interfacial force density [Drew, D.A., Passman, S.L., 1998. Theory of Multicomponent Fluids. Springer-Verlag, New York; Nigmatulin, T.R., Drew, D.A., Lahey, R.T., Jr., 2000. An analysis of wavy annular flow. In: International Conference on Multiphase Systems, ICMS'2000, Ufa, Russia, June 15-17], Reynolds stress tensor, and the term, (p-bar cl i -p-bar cl )-bar α cl , where p-bar cl i is interfacial average pressure, p-bar cl the average pressure, and α cl is the volume fraction of the continuous liquid phase. These functional forms should be useful for assessing two-fluid closure relations and Computational Multiphase Fluid Dynamics (CMFD) numerical models for stratified wavy flows. Moreover, it appears that this approach can be generalized to other flow regimes (e.g., annular flows)

  12. Monte Carlo estimates of interfacial tension in the two-dimensional Ising model from non-equilibrium methods

    International Nuclear Information System (INIS)

    Híjar, Humberto; Sutmann, Godehard

    2008-01-01

    Non-equilibrium methods for estimating free energy differences are used in order to calculate the interfacial tension between domains with opposite magnetizations in two-dimensional Ising lattices. Non-equilibrium processes are driven by changing the boundary conditions for two opposite sides of the lattice from periodic to antiperiodic and vice versa. This mechanism, which promotes the appearance and disappearance of the interface, is studied by means of Monte Carlo simulations performed at different rates and using different algorithms, thus allowing for testing the applicability of non-equilibrium methods for processes driven far from or close to equilibrium. Interfaces in lattices with different widths and heights are studied and the interface tension as a function of these quantities is obtained. It is found that the estimates of the interfacial tension from non-equilibrium procedures are in good agreement with previous reports as well as with exact results. The efficiency of the different procedures used is analyzed and the dynamics of the interface under these perturbations is briefly discussed. A method for determining the efficiency of non-equilibrium methods as regards thermodynamic perturbation is also presented. It is found that for all cases studied, the Crooks non-equilibrium method for estimating free energy differences is the most efficient one

  13. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

    Science.gov (United States)

    Jablonska, Jadwiga; Leschner, Sara; Westphal, Kathrin; Lienenklaus, Stefan; Weiss, Siegfried

    2010-04-01

    Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

  14. Tumor hypoxia - A confounding or exploitable factor in interstitial brachytherapy? Effects of tissue trauma in an experimental rat tumor model

    NARCIS (Netherlands)

    van den Berg, AP; van Geel, CAJF; van Hooije, CMC; van der Kleij, AJ; Visser, AG

    2000-01-01

    Purpose: To evaluate the potential effects of tumor hypoxia induced by afterloading catheter implantation on the effectiveness of brachytherapy in a rat tumor model. Methods and Materials: Afterloading catheters (4) Here implanted in subcutaneously growing R1M rhabdomyosarcoma in female Wag/Rij

  15. Evaluation of Tumor Angiogenesis with a Second-Generation US Contrast Medium in a Rat Breast Tumor Model

    International Nuclear Information System (INIS)

    Ko, Eun Young; Lee, Sang Hoon; Kim, Hak Hee; Kim, Sung Moon; Shin, Myung Jin; Kim, Nam Kug; Gong, Gyung Yub

    2008-01-01

    Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast enhanced ultrasound (US) examination with a second-generation US contrast agent. The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H and E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis. The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05). Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat

  16. A study of the dispersed flow interfacial heat transfer model of RELAP5/MOD2.5 and RELAP5/MOD3

    Energy Technology Data Exchange (ETDEWEB)

    Andreani, M. [Swiss Federal Institute of Technology, Zurich (Switzerland); Analytis, G.T.; Aksan, S.N. [Paul Scherrer Institute, Villigen (Switzerland)

    1995-09-01

    The model of interfacial heat transfer for the dispersed flow regime used in the RELAP5 computer codes is investigated in the present paper. Short-transient calculations of two low flooding rate tube reflooding experiments have been performed, where the hydraulic conditions and the heat input to the vapour in the post-dryout region were controlled for the predetermined position of the quench front. Both RELAP5/MOD2.5 and RELAP5/MOD3 substantially underpredicted the exit vapour temperature. The mass flow rate and quality, however, were correct and the heat input to the vapour was larger than the actual one. As the vapour superheat at the tube exit depends on the balance between the heat input from the wall and the heat exchange with the droplets, the discrepancy between the calculated and the measured exit vapour temperature suggested that the inability of both codes to predict the vapour superheat in the dispersed flow region is due to the overprediction of the interfacial heat transfer rate.

  17. Mean free path dependent phonon contributions to interfacial thermal conductance

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Yi; Liu, Chenhan; Chen, Weiyu; Cai, Shuang; Chen, Chen; Wei, Zhiyong; Bi, Kedong; Yang, Juekuan; Chen, Yunfei, E-mail: yunfeichen@seu.edu.cn

    2017-06-15

    Interfacial thermal conductance as an accumulation function of the phonon mean free path is rigorously derived from the thermal conductivity accumulation function. Based on our theoretical model, the interfacial thermal conductance accumulation function between Si/Ge is calculated. The results show that the range of mean free paths (MFPs) for phonons contributing to the interfacial thermal conductance is far narrower than that for phonons contributing to the thermal conductivity. The interfacial thermal conductance is mainly contributed by phonons with shorter MFPs, and the size effects can be observed only for an interface constructed by nanostructures with film thicknesses smaller than the MFPs of those phonons mainly contributing to the interfacial thermal conductance. This is why most experimental measurements cannot detect size effects on interfacial thermal conductance. A molecular dynamics simulation is employed to verify our proposed model. - Highlights: • A model to account for the interfacial thermal conductance as an accumulation function of phonon mean free path is proposed; • The model predicts that the range of mean free paths (MFPs) for phonons contributing to the interfacial thermal conductance is far narrower than that contributing to the thermal conductivity; • This model can be conveniently implemented to estimate the size effects on the interfacial thermal conductance for the interfaces formed by a nanostructure contacting a substrate.

  18. Qualitative and Computational Analysis of a Mathematical Model for Tumor-Immune Interactions

    Directory of Open Access Journals (Sweden)

    F. A. Rihan

    2012-01-01

    Full Text Available We provide a family of ordinary and delay differential equations to model the dynamics of tumor-growth and immunotherapy interactions. We explore the effects of adoptive cellular immunotherapy on the model and describe under what circumstances the tumor can be eliminated. The possibility of clearing the tumor, with a strategy, is based on two parameters in the model: the rate of influx of the effector cells and the rate of influx of IL-2. The critical tumor-growth rate, below which endemic tumor does not exist, has been found. One can use the model to make predictions about tumor dormancy.

  19. Stability of interfacial waves in two-phase flows

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W S [Ontario Hydro, Toronto, ON (Canada)

    1996-12-31

    The influence of the interfacial pressure and the flow distribution in the one-dimensional two-fluid model on the stability problems of interfacial waves is discussed. With a proper formulation of the interfacial pressure, the following two-phase phenomena can be predicted from the stability and stationary criteria of the interfacial waves: onset of slug flow, stationary hydraulic jump in a stratified flow, flooding in a vertical pipe, and the critical void fraction of a bubbly flow. It can be concluded that the interfacial pressure plays an important role in the interfacial wave propagation of the two-fluid model. The flow distribution parameter may enhance the flow stability range, but only plays a minor role in the two-phase characteristics. (author). 20 refs., 3 tabs., 4 figs.

  20. Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model

    International Nuclear Information System (INIS)

    Nagane, Masaki; Yasui, Hironobu; Yamamori, Tohru; Zhao, Songji; Kuge, Yuji; Tamaki, Nagara; Kameya, Hiromi; Nakamura, Hideo; Fujii, Hirotada; Inanami, Osamu

    2013-01-01

    Highlights: •IR-induced NO increased tissue perfusion and pO 2 . •IR increased NO production in tumors without changes in the mRNA and protein levels of NOS isoforms. •NOS activity assay showed that IR upregulated eNOS activity in tumors. •IR-induced NO decreased tumor hypoxia and altered tumor radiosensitivity. -- Abstract: Tumor hypoxia, which occurs mainly as a result of inadequate tissue perfusion in solid tumors, is a well-known challenge for successful radiotherapy. Recent evidence suggests that ionizing radiation (IR) upregulates nitric oxide (NO) production and that IR-induced NO has the potential to increase intratumoral circulation. However, the kinetics of NO production and the responsible isoforms for NO synthase in tumors exposed to IR remain unclear. In this study, we aimed to elucidate the mechanism by which IR stimulates NO production in tumors and the effect of IR-induced NO on tumor radiosensitivity. Hoechst33342 perfusion assay and electron spin resonance oxymetry showed that IR increased tissue perfusion and pO 2 in tumor tissue. Immunohistochemical analysis using two different hypoxic probes showed that IR decreased hypoxic regions in tumors; treatment with a nitric oxide synthase (NOS) inhibitor, L-NAME, abrogated the effects of IR. Moreover, IR increased endothelial NOS (eNOS) activity without affecting its mRNA or protein expression levels in SCCVII-transplanted tumors. Tumor growth delay assay showed that L-NAME decreased the anti-tumor effect of fractionated radiation (10 Gy × 2). These results suggested that IR increased eNOS activity and subsequent tissue perfusion in tumors. Increases in intratumoral circulation simultaneously decreased tumor hypoxia. As a result, IR-induced NO increased tumor radiosensitivity. Our study provides a new insight into the NO-dependent mechanism for efficient fractionated radiotherapy

  1. Simple biophysical model of tumor evasion from immune system control

    Science.gov (United States)

    D'Onofrio, Alberto; Ciancio, Armando

    2011-09-01

    The competitive nonlinear interplay between a tumor and the host's immune system is not only very complex but is also time-changing. A fundamental aspect of this issue is the ability of the tumor to slowly carry out processes that gradually allow it to become less harmed and less susceptible to recognition by the immune system effectors. Here we propose a simple epigenetic escape mechanism that adaptively depends on the interactions per time unit between cells of the two systems. From a biological point of view, our model is based on the concept that a tumor cell that has survived an encounter with a cytotoxic T-lymphocyte (CTL) has an information gain that it transmits to the other cells of the neoplasm. The consequence of this information increase is a decrease in both the probabilities of being killed and of being recognized by a CTL. We show that the mathematical model of this mechanism is formally equal to an evolutionary imitation game dynamics. Numerical simulations of transitory phases complement the theoretical analysis. Implications of the interplay between the above mechanisms and the delivery of immunotherapies are also illustrated.

  2. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    Science.gov (United States)

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  3. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    Directory of Open Access Journals (Sweden)

    Sejal Desai

    Full Text Available Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2 and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper

  4. Multimodality Tumor Delineation and Predictive Modelling via Fuzzy-Fusion Deformable Models and Biological Potential Functions

    Science.gov (United States)

    Wasserman, Richard Marc

    The radiation therapy treatment planning (RTTP) process may be subdivided into three planning stages: gross tumor delineation, clinical target delineation, and modality dependent target definition. The research presented will focus on the first two planning tasks. A gross tumor target delineation methodology is proposed which focuses on the integration of MRI, CT, and PET imaging data towards the generation of a mathematically optimal tumor boundary. The solution to this problem is formulated within a framework integrating concepts from the fields of deformable modelling, region growing, fuzzy logic, and data fusion. The resulting fuzzy fusion algorithm can integrate both edge and region information from multiple medical modalities to delineate optimal regions of pathological tissue content. The subclinical boundaries of an infiltrating neoplasm cannot be determined explicitly via traditional imaging methods and are often defined to extend a fixed distance from the gross tumor boundary. In order to improve the clinical target definition process an estimation technique is proposed via which tumor growth may be modelled and subclinical growth predicted. An in vivo, macroscopic primary brain tumor growth model is presented, which may be fit to each patient undergoing treatment, allowing for the prediction of future growth and consequently the ability to estimate subclinical local invasion. Additionally, the patient specific in vivo tumor model will be of significant utility in multiple diagnostic clinical applications.

  5. Stress, microstructure and evolution under ion irradiation in thin films grown by ion beam sputtering: modelling and application to interfacial effects in metallic multilayers

    International Nuclear Information System (INIS)

    Debelle, A.

    2006-09-01

    We have investigated the formation of the interfacial chemical mixing in Mo/Ni multilayers, and particularly the influence of ballistic effects during the growth. For this purpose, hetero-epitaxial b.c.c./f.c.c. Mo(110)/Ni(111) multilayers were grown by two deposition methods: thermal evaporation and direct ion beam sputtering. As a preliminary, an accurate description of the stress state in pure sputtered Mo thin films was required. Microstructural and stress state analyses were essentially carried out by X-ray diffraction, and ion irradiation was used as a powerful tool to control the stress level. We showed that thermal evaporated thin films exhibit a weak tensile growth stress (∼ 0.6 GPa) that can be accounted for by the grain boundary relaxation model, whereas sputtered thin films develop large compressive growth stress (- 2 to - 4 GPa). This latter results from the bombardment of the growing film by the energetic particles involved during the sputtering process (atomic peening phenomenon), which induces the formation of defects in the layers, generating volume distortions. We thus developed a stress model that includes a hydrostatic stress component to account for these volume strains. This model allowed us to determine the 'unstressed and free of defects lattice parameter' a 0 , solely linked to chemical effects. For epitaxial Mo layers, it was possible to separate coherency stress from growth stress due to their distinct kinetic evolution during ion irradiation. Therefore, the stress analysis enabled us to determine the a 0 values in Mo sub-layers of Mo/Ni superlattices. A tendency to the formation of an interfacial alloy is observed independently of the growth conditions, which suggests that thermodynamic forces favour the exchange mechanism. However, the extent of the intermixing effect is clearly enhanced by ballistic effects. (author)

  6. Simulation of glioblastoma multiforme (GBM) tumor cells using ising model on the Creutz Cellular Automaton

    Science.gov (United States)

    Züleyha, Artuç; Ziya, Merdan; Selçuk, Yeşiltaş; Kemal, Öztürk M.; Mesut, Tez

    2017-11-01

    Computational models for tumors have difficulties due to complexity of tumor nature and capacities of computational tools, however, these models provide visions to understand interactions between tumor and its micro environment. Moreover computational models have potential to develop strategies for individualized treatments for cancer. To observe a solid brain tumor, glioblastoma multiforme (GBM), we present a two dimensional Ising Model applied on Creutz cellular automaton (CCA). The aim of this study is to analyze avascular spherical solid tumor growth, considering transitions between non tumor cells and cancer cells are like phase transitions in physical system. Ising model on CCA algorithm provides a deterministic approach with discrete time steps and local interactions in position space to view tumor growth as a function of time. Our simulation results are given for fixed tumor radius and they are compatible with theoretical and clinic data.

  7. Repopulation of interacting tumor cells during fractionated radiotherapy: Stochastic modeling of the tumor control probability

    International Nuclear Information System (INIS)

    Fakir, Hatim; Hlatky, Lynn; Li, Huamin; Sachs, Rainer

    2013-01-01

    Purpose: Optimal treatment planning for fractionated external beam radiation therapy requires inputs from radiobiology based on recent thinking about the “five Rs” (repopulation, radiosensitivity, reoxygenation, redistribution, and repair). The need is especially acute for the newer, often individualized, protocols made feasible by progress in image guided radiation therapy and dose conformity. Current stochastic tumor control probability (TCP) models incorporating tumor repopulation effects consider “stem-like cancer cells” (SLCC) to be independent, but the authors here propose that SLCC-SLCC interactions may be significant. The authors present a new stochastic TCP model for repopulating SLCC interacting within microenvironmental niches. Our approach is meant mainly for comparing similar protocols. It aims at practical generalizations of previous mathematical models. Methods: The authors consider protocols with complete sublethal damage repair between fractions. The authors use customized open-source software and recent mathematical approaches from stochastic process theory for calculating the time-dependent SLCC number and thereby estimating SLCC eradication probabilities. As specific numerical examples, the authors consider predicted TCP results for a 2 Gy per fraction, 60 Gy protocol compared to 64 Gy protocols involving early or late boosts in a limited volume to some fractions. Results: In sample calculations with linear quadratic parameters α = 0.3 per Gy, α/β = 10 Gy, boosting is predicted to raise TCP from a dismal 14.5% observed in some older protocols for advanced NSCLC to above 70%. This prediction is robust as regards: (a) the assumed values of parameters other than α and (b) the choice of models for intraniche SLCC-SLCC interactions. However, α = 0.03 per Gy leads to a prediction of almost no improvement when boosting. Conclusions: The predicted efficacy of moderate boosts depends sensitively on α. Presumably, the larger values of α are

  8. Repopulation of interacting tumor cells during fractionated radiotherapy: stochastic modeling of the tumor control probability.

    Science.gov (United States)

    Fakir, Hatim; Hlatky, Lynn; Li, Huamin; Sachs, Rainer

    2013-12-01

    Optimal treatment planning for fractionated external beam radiation therapy requires inputs from radiobiology based on recent thinking about the "five Rs" (repopulation, radiosensitivity, reoxygenation, redistribution, and repair). The need is especially acute for the newer, often individualized, protocols made feasible by progress in image guided radiation therapy and dose conformity. Current stochastic tumor control probability (TCP) models incorporating tumor repopulation effects consider "stem-like cancer cells" (SLCC) to be independent, but the authors here propose that SLCC-SLCC interactions may be significant. The authors present a new stochastic TCP model for repopulating SLCC interacting within microenvironmental niches. Our approach is meant mainly for comparing similar protocols. It aims at practical generalizations of previous mathematical models. The authors consider protocols with complete sublethal damage repair between fractions. The authors use customized open-source software and recent mathematical approaches from stochastic process theory for calculating the time-dependent SLCC number and thereby estimating SLCC eradication probabilities. As specific numerical examples, the authors consider predicted TCP results for a 2 Gy per fraction, 60 Gy protocol compared to 64 Gy protocols involving early or late boosts in a limited volume to some fractions. In sample calculations with linear quadratic parameters α = 0.3 per Gy, α∕β = 10 Gy, boosting is predicted to raise TCP from a dismal 14.5% observed in some older protocols for advanced NSCLC to above 70%. This prediction is robust as regards: (a) the assumed values of parameters other than α and (b) the choice of models for intraniche SLCC-SLCC interactions. However, α = 0.03 per Gy leads to a prediction of almost no improvement when boosting. The predicted efficacy of moderate boosts depends sensitively on α. Presumably, the larger values of α are the ones appropriate for individualized

  9. Measurement of local interfacial area concentration in boiling loop

    International Nuclear Information System (INIS)

    Kyoung, Ho Kang; Byong, Jo Yun; Goon, Cherl Park

    1995-01-01

    An accurate prediction of two-phase flow is essential to many energy systems, including nuclear reactors. To model the two-phase flow, detailed information on the internal flow structure is required. The void fraction and interfacial area concentration are important fundamental parameters characterizing the internal structure of two-phase flow. The interfacial area concentration is defined as the available interfacial area per unit volume of the two-phase mixture in calculations of the interfacial transport of mass, momentum, and energy. Although a number of studies have been made in this area, the interfacial area concentration in two-phase flow has not been sufficiently investigated either experimentally or analytically. Most existing models for interfacial area concentration are limited to area-averaged interfacial area concentration in a flow channel. And the studies on local interfacial area concentration are limited to the case of air-water two-phase flow. However, the internal flow structure of steam-water two-phase flow having various bubble sizes could be quite different from that of air-water two-phase flow, the reliability of which weak in practical applications. In this study, the local interfacial area concentration steam-water two-phase flow has been investigated experimentally in a circular boiling tube having a heating rod in the center, and for the low flow with liquid superficial velocity <1 m/s

  10. Tumor penetration with intact MAb and fragments demonstrated in vitro on tumor spheroids and in vivo in the nude mouse model

    International Nuclear Information System (INIS)

    Buchegger, F.; Halpern, S.E.; Sutherland, R.M.; Schreyer, M.; Mach, J.P.

    1986-01-01

    Tumor spheroids grown in culture represent a good in vitro model for the study of tumor penetration phenomena of potential radiotherapeutics. Using this system, it was found that Fab-fragments penetrate tumors more quickly and deeply than complete antibodies. These results were confirmed in tumor bearing nephrectomized nude mice

  11. Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell tumors.

    Science.gov (United States)

    Fendrich, V; Lopez, C L; Manoharan, J; Maschuw, K; Wichmann, S; Baier, A; Holler, J P; Ramaswamy, A; Bartsch, D K; Waldmann, J

    2014-10-01

    Accumulating evidence suggests a role for angiotensin-converting enzymes involving the angiotensin II-receptor 1 (AT1-R) and the cyclooxygenase pathway in carcinogenesis. The effects of ASS and enalapril were assessed in vitro and in a transgenic mouse model of pancreatic neuroendocrine neoplasms (pNENs). The effects of enalapril and ASS on proliferation and expression of the AGTR1A and its target gene vascular endothelial growth factor (Vegfa) were assessed in the neuroendocrine cell line BON1. Rip1-Tag2 mice were treated daily with either 0.6 mg/kg bodyweight of enalapril i.p., 20 mg/kg bodyweight of ASS i.p., or a vehicle in a prevention (weeks 5-12) and a survival group (week 5 till death). Tumor surface, weight of pancreatic glands, immunostaining for AT1-R and nuclear factor kappa beta (NFKB), and mice survival were analyzed. In addition, sections from human specimens of 20 insulinomas, ten gastrinomas, and 12 non-functional pNENs were evaluated for AT1-R and NFKB (NFKB1) expression and grouped according to the current WHO classification. Proliferation was significantly inhibited by enalapril and ASS in BON1 cells, with the combination being the most effective. Treatment with enalapril and ASS led to significant downregulation of known target genes Vegf and Rela at RNA level. Tumor growth was significantly inhibited by enalapril and ASS in the prevention group displayed by a reduction of tumor size (84%/67%) and number (30%/45%). Furthermore, daily treatment with enalapril and ASS prolonged the overall median survival compared with vehicle-treated Rip1-Tag2 (107 days) mice by 9 and 17 days (P=0.016 and P=0.013). The AT1-R and the inflammatory transcription factor NFKB were abolished completely upon enalapril and ASS treatment. AT1-R and NFKB expressions were observed in 80% of human pNENs. Enalapril and ASS may provide an approach for chemoprevention and treatment of pNENs. © 2014 Society for Endocrinology.

  12. Modeling tumor-associated edema in gliomas during anti-angiogenic therapy and its impact on imageable tumor

    Directory of Open Access Journals (Sweden)

    Andrea eHawkins-Daarud

    2013-04-01

    Full Text Available Glioblastoma, the most aggressive form of primary brain tumor is predominantly assessed with gadolinium-enhanced T1-weighted (T1Gd and T2-weighted magnetic resonance imaging (MRI. Pixel intensity enhancement on the T1Gd image is understood to correspond to the gadolinium contrast agent leaking from the tumor-induced neovasculature, while hyperintensity on the T2/FLAIR images corresponds with edema and infiltrated tumor cells. None of these modalities directly show tumor cells; rather, they capture abnormalities in the microenvironment caused by the presence of tumor cells. Thus, assessing disease response after treatments impacting the microenvironment remains challenging through the obscuring lens of MR imaging. Anti-angiogenic therapies have been used in the treatment of gliomas with spurious results ranging from no apparent response to significant imaging improvement with the potential for extremely diffuse patterns of tumor recurrence on imaging and autopsy. Anti-angiogenic treatment normalizes the vasculature, effectively decreasing vessel permeability and thus reducing tumor-induced edema, drastically altering T2-weighted MRI. We extend a previously developed mathematical model of glioma growth to explicitly incorporate edema formation allowing us to directly characterize and potentially predict the effects of anti-angiogenics on imageable tumor growth. A comparison of simulated glioma growth and imaging enhancement with and without bevacizumab supports the current understanding that anti-angiogenic treatment can serve as a surrogate for steroids and the clinically-driven hypothesis that anti-angiogenic treatment may not have any significant effect on the growth dynamics of the overall tumor-cell populations. However, the simulations do illustrate a potentially large impact on the level of edematous extracellular fluid, and thus on what would be imageable on T2/FLAIR MR for tumors with lower proliferation rates.

  13. An Implementation of Interfacial Transport Equation into the CUPID code

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ik Kyu; Cho, Heong Kyu; Yoon, Han Young; Jeong, Jae Jun

    2009-11-15

    A component scale thermal hydraulic analysis code, CUPID (Component Unstructured Program for Interfacial Dynamics), is being developed for the analysis of components for a nuclear reactor, such as reactor vessel, steam generator, containment, etc. It adopted a three-dimensional, transient, two phase and three-field model. In order to develop the numerical schemes for the three-field model, various numerical schemes have been examined including the SMAS, semi-implicit ICE, SIMPLE. The governing equations for a 2-phase flow are composed of mass, momentum, and energy conservation equations for each phase. These equation sets are closed by the interfacial transfer rate of mass, momentum, and energy. The interfacial transfer of mass, momentum, and energy occurs through the interfacial area, and this area plays an important role in the transfer rate. The flow regime based correlations are used for calculating the interracial area in the traditional style 2-phase flow model. This is dependent upon the flow regime and is limited to the fully developed 2-phase flow region. Its application to the multi-dimensional 2-phase flow has some limitation because it adopts the measured results of 2-phase flow in the 1-dimensional tube. The interfacial area concentration transport equation had been suggested in order to calculate the interfacial area without the interfacial area correlations. The source terms to close the interfacial area transport equation should be further developed for a wide ranger usage of it. In this study, the one group interfacial area concentration transport equation has been implemented into the CUPID code. This interfacial area concentration transport equation can be used instead of the interfacial area concentration correlations for the bubbly flow region.

  14. An Implementation of Interfacial Transport Equation into the CUPID code

    International Nuclear Information System (INIS)

    Park, Ik Kyu; Cho, Heong Kyu; Yoon, Han Young; Jeong, Jae Jun

    2009-11-01

    A component scale thermal hydraulic analysis code, CUPID (Component Unstructured Program for Interfacial Dynamics), is being developed for the analysis of components for a nuclear reactor, such as reactor vessel, steam generator, containment, etc. It adopted a three-dimensional, transient, two phase and three-field model. In order to develop the numerical schemes for the three-field model, various numerical schemes have been examined including the SMAS, semi-implicit ICE, SIMPLE. The governing equations for a 2-phase flow are composed of mass, momentum, and energy conservation equations for each phase. These equation sets are closed by the interfacial transfer rate of mass, momentum, and energy. The interfacial transfer of mass, momentum, and energy occurs through the interfacial area, and this area plays an important role in the transfer rate. The flow regime based correlations are used for calculating the interracial area in the traditional style 2-phase flow model. This is dependent upon the flow regime and is limited to the fully developed 2-phase flow region. Its application to the multi-dimensional 2-phase flow has some limitation because it adopts the measured results of 2-phase flow in the 1-dimensional tube. The interfacial area concentration transport equation had been suggested in order to calculate the interfacial area without the interfacial area correlations. The source terms to close the interfacial area transport equation should be further developed for a wide ranger usage of it. In this study, the one group interfacial area concentration transport equation has been implemented into the CUPID code. This interfacial area concentration transport equation can be used instead of the interfacial area concentration correlations for the bubbly flow region

  15. Modified model of VX2 tumor overexpressing vascular endothelial growth factor.

    Science.gov (United States)

    Pascale, Florentina; Ghegediban, Saida-Homayra; Bonneau, Michel; Bedouet, Laurent; Namur, Julien; Verret, Valentin; Schwartz-Cornil, Isabelle; Wassef, Michel; Laurent, Alexandre

    2012-06-01

    To determine whether upregulated expression of vascular endothelial growth factor (VEGF) in VX2 cells can increase vessel density (VD) and reduce tumor necrosis. The VX2 cell line was transfected with expression vectors containing cDNA for rabbit VEGF. Stable clones producing rabbit VEGF (VEGF-VX2) were selected. VEGF-VX2 cells (n = 5 rabbits) or nontransfected VX2 cells (controls; n = 5 rabbits) were implanted into leg muscle of 10 rabbits. The animals were sacrificed at day 21. Tumor volume, percentage of necrosis, VD, and VEGF concentration in tumor protein extract were quantified. Overexpression of VEGF by VX2 cells augmented tumor implantation efficiency 100% and favored cyst formation. The tumor volume was significantly larger for VEGF-VX2 transfected tumors versus controls (P = .0143). Overexpression of VEGF in VX2 cells significantly increased the VD of the tumors (P = .0138). The percentage of necrosis was reduced in VEGF-VX2 tumors versus controls (19.5% vs 38.5 %; P = .002). VEGF concentration in VEGF-VX2 tumors was significantly higher than in control tumors (P = .041) and was correlated with tumor volume (ρ = .883, P = .012). The overexpression of VEGF increased tumor growth and vascularization, favored cyst formation, and reduced tumor necrosis. This new phenotype of the VX2 tumor may offer some advantages over classic models of VX2 tumor for evaluating anticancer therapies. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

  16. Treatment of Murine Tumor Models of Breast Adenocarcinoma by Continuous Dual-Frequency Ultrasound

    Directory of Open Access Journals (Sweden)

    Amir Hoshang Barati

    2009-03-01

    Full Text Available Introduction: Acoustic transient cavitation is the primary mechanism of sonochemical reaction and has potential use for tumor treatment. In this study, the in vivo anti-tumor effect of simultaneous dual-frequency ultrasound at low-level intensity (ISATA < 6 W/cm2 was investigated in a spontaneous murine model of breast adenocarcinoma in Balb/c mice. Materials and Methods: Forty tumor bearing mice were divided into four groups (10 in each group. The treated groups received 15 or 30 minutes of combined dual-frequency ultrasound in continuous mode (1 MHzcon + 150 kHzcon respectively. The control and the sham groups contained the untreated mice. The tumor growth delay parameters including tumor volume, relative tumor volume, T5 and T2 (the needed time for each tumor to reach 5 and 2 times the initial tumor volume, respectively, survival period and percent of tumor growth inhibition ratio were measured on different days after treatment. Results: The results showed that the 30 min treatment was effective in tumor growth delay and percent of tumor growth inhibitory ratio compared to the sham and the control groups. The tumor volume growth and relative volume of tumors in the same treated group showed an anti-tumor effect relative to the sham and the control groups. There was a significant difference in tumor volume growth between this 30 min treatment group and the sham group 12 days after treatment (p-value

  17. Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

    Energy Technology Data Exchange (ETDEWEB)

    Malinowski, Kathleen T. [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); McAvoy, Thomas J. [Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); Department of Chemical and Biomolecular Engineering and Institute of Systems Research, University of Maryland, College Park, MD (United States); George, Rohini [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Dieterich, Sonja [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); D' Souza, Warren D., E-mail: wdsou001@umaryland.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States)

    2012-04-01

    Purpose: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

  18. Use of the vasodilator sodium nitroprusside during local hyperthermia: effects on tumor temperature and tumor response in a rat tumor model

    International Nuclear Information System (INIS)

    Krossnes, Baard Kronen; Mella, Olav; Dahl, Olav

    1996-01-01

    .3 and 0.4 deg. C higher during SNP infusion in the MFF and pentobarbital group, respectively. Conclusion: We have developed a small animal model in inbred rats feasible for exploring the influence of a stable blood pressure reduction induced by SNP, on the effect of HT given alone or in combination with other treatment modalities to a transplantable tumor. The greatly increased cytotoxic effect of local waterbath HT in the present tumor response experiments is probably a consequence of increased tumor temperature during SNP infusion

  19. Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging.

    Directory of Open Access Journals (Sweden)

    David Fecher

    Full Text Available Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.

  20. A 3-D model of tumor progression based on complex automata driven by particle dynamics.

    Science.gov (United States)

    Wcisło, Rafał; Dzwinel, Witold; Yuen, David A; Dudek, Arkadiusz Z

    2009-12-01

    The dynamics of a growing tumor involving mechanical remodeling of healthy tissue and vasculature is neglected in most of the existing tumor models. This is due to the lack of efficient computational framework allowing for simulation of mechanical interactions. Meanwhile, just these interactions trigger critical changes in tumor growth dynamics and are responsible for its volumetric and directional progression. We describe here a novel 3-D model of tumor growth, which combines particle dynamics with cellular automata concept. The particles represent both tissue cells and fragments of the vascular network. They interact with their closest neighbors via semi-harmonic central forces simulating mechanical resistance of the cell walls. The particle dynamics is governed by both the Newtonian laws of motion and the cellular automata rules. These rules can represent cell life-cycle and other biological interactions involving smaller spatio-temporal scales. We show that our complex automata, particle based model can reproduce realistic 3-D dynamics of the entire system consisting of the tumor, normal tissue cells, blood vessels and blood flow. It can explain phenomena such as the inward cell motion in avascular tumor, stabilization of tumor growth by the external pressure, tumor vascularization due to the process of angiogenesis, trapping of healthy cells by invading tumor, and influence of external (boundary) conditions on the direction of tumor progression. We conclude that the particle model can serve as a general framework for designing advanced multiscale models of tumor dynamics and it is very competitive to the modeling approaches presented before.

  1. Iridium Interfacial Stack (IRIS)

    Science.gov (United States)

    Spry, David James (Inventor)

    2015-01-01

    An iridium interfacial stack ("IrIS") and a method for producing the same are provided. The IrIS may include ordered layers of TaSi.sub.2, platinum, iridium, and platinum, and may be placed on top of a titanium layer and a silicon carbide layer. The IrIS may prevent, reduce, or mitigate against diffusion of elements such as oxygen, platinum, and gold through at least some of its layers.

  2. Effects of Mechanical Properties on Tumor Invasion: Insights from a Cellular Model

    KAUST Repository

    Li, YZ

    2014-08-01

    Understanding the regulating mechanism of tumor invasion is of crucial importance for both fundamental cancer research and clinical applications. Previous in vivo experiments have shown that invasive cancer cells dissociate from the primary tumor and invade into the stroma, forming an irregular invasive morphology. Although cell movements involved in tumor invasion are ultimately driven by mechanical forces of cell-cell interactions and tumor-host interactions, how these mechanical properties affect tumor invasion is still poorly understood. In this study, we use a recently developed two-dimensional cellular model to study the effects of mechanical properties on tumor invasion. We study the effects of cell-cell adhesions as well as the degree of degradation and stiffness of extracellular matrix (ECM). Our simulation results show that cell-cell adhesion relationship must be satisfied for tumor invasion. Increased adhesion to ECM and decreased adhesion among tumor cells result in invasive tumor behaviors. When this invasive behavior occurs, ECM plays an important role for both tumor morphology and the shape of invasive cancer cells. Increased stiffness and stronger degree of degradation of ECM promote tumor invasion, generating more aggressive tumor invasive morphologies. It can also generate irregular shape of invasive cancer cells, protruding towards ECM. The capability of our model suggests it a useful tool to study tumor invasion and might be used to propose optimal treatment in clinical applications.

  3. Dynamic density functional theory of solid tumor growth: Preliminary models

    Directory of Open Access Journals (Sweden)

    Arnaud Chauviere

    2012-03-01

    Full Text Available Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth.

  4. Investigation of HIFU-induced anti-tumor immunity in a murine tumor model

    Directory of Open Access Journals (Sweden)

    Lyerly H Kim

    2007-07-01

    Full Text Available Abstract Background High intensity focused ultrasound (HIFU is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment. Methods Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. In vivo dendritic cell activity was assessed along with the host's response to challenge tumor growth. Results Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio. Conclusion These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to

  5. Salinomycin nanoparticles interfere with tumor cell growth and the tumor microenvironment in an orthotopic model of pancreatic cancer.

    Science.gov (United States)

    Daman, Zahra; Faghihi, Homa; Montazeri, Hamed

    2018-05-02

    Recently, salinomycin (SAL) has been reported to inhibit proliferation and induce apoptosis in various tumors. The aim of this study was to deliver SAL to orthotopic model of pancreatic cancer by the aid of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The NPs were physico-chemically characterized and evaluated for cytotoxicity on luciferase-transduced AsPC-1 cells in vitro as well as implanted orthotopically into the pancreas of nude mice. SAL (3.5 mg/kg every other day) blocked tumor growth by 52% compared to the control group after 3 weeks of therapy. Western blotting of tumor protein extracts indicated that SAL treatment leads to up-regulation of E-cadherin, β-catenin, and transforming growth factor beta receptor (TGFβR) expressions in AsPC-1 orthotopic tumor. Noteworthy, immunofluorescence staining of adjacent tumor sections showed that treatment with SAL NPs cause significant apoptosis in the tumor cells rather than the stroma. Further investigations also revealed that TGFβR2 over-expression was induced in stroma cells after treatment with SAL NPs. These results highlight SAL-loaded PLGA NPs as a promising system for pancreatic cancer treatment, while the mechanistic questions need to be subsequently tested.

  6. Coupled Hybrid Continuum-Discrete Model of Tumor Angiogenesis and Growth.

    Directory of Open Access Journals (Sweden)

    Jie Lyu

    Full Text Available The processes governing tumor growth and angiogenesis are codependent. To study the relationship between them, we proposed a coupled hybrid continuum-discrete model. In this model, tumor cells, their microenvironment (extracellular matrixes, matrix-degrading enzymes, and tumor angiogenic factors, and their network of blood vessels, described by a series of discrete points, were considered. The results of numerical simulation reveal the process of tumor growth and the change in microenvironment from avascular to vascular stage, indicating that the network of blood vessels develops gradually as the tumor grows. Our findings also reveal that a tumor is divided into three regions: necrotic, semi-necrotic, and well-vascularized. The results agree well with the previous relevant studies and physiological facts, and this model represents a platform for further investigations of tumor therapy.

  7. Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.

    Directory of Open Access Journals (Sweden)

    Tineke W H Meijer

    Full Text Available BACKGROUND AND PURPOSE: Carbonic anhydrase IX (CAIX plays a pivotal role in pH homeostasis, which is essential for tumor cell survival. We examined the effect of the CAIX inhibitor 4-(3'(3",5"-dimethylphenyl-ureidophenyl sulfamate (S4 on the tumor microenvironment in a laryngeal tumor model by analyzing proliferation, apoptosis, necrosis, hypoxia, metabolism and CAIX ectodomain shedding. METHODS: SCCNij202 tumor bearing-mice were treated with S4 for 1, 3 or 5 days. CAIX ectodomain shedding was measured in the serum after therapy. Effects on tumor cell proliferation, apoptosis, necrosis, hypoxia (pimonidazole and CAIX were investigated with quantitative immunohistochemistry. Metabolic transporters and enzymes were quantified with qPCR. RESULTS: CAIX ectodomain shedding decreased after treatment with S4 (p<0.01. S4 therapy did neither influence tumor cell proliferation nor the amount of apoptosis and necrosis. Hypoxia (pimonidazole and CAIX expression were also not affected by S4. CHOP and MMP9 mRNA as a reference of intracellular pH did not change upon treatment with S4. Compensatory mechanisms of pH homeostasis at the mRNA level were not observed. CONCLUSION: As the clinical and biological meaning of the decrease in CAIX ectodomain shedding after S4 therapy is not clear, studies are required to elucidate whether the CAIX ectodomain has a paracrine or autocrine signaling function in cancer biology. S4 did not influence the amount of proliferation, apoptosis, necrosis and hypoxia. Therefore, it is unlikely that S4 can be used as single agent to influence tumor cell kill and proliferation, and to target primary tumor growth.

  8. Modeling tissue contamination to improve molecular identification of the primary tumor site of metastases

    DEFF Research Database (Denmark)

    Vincent, Martin; Perell, Katharina; Nielsen, Finn Cilius

    2014-01-01

    with any predictor model. The usability of the model is illustrated on primary tumor site identification of liver biopsies, specifically, on a human dataset consisting of microRNA expression measurements of primary tumor samples, benign liver samples and liver metastases. For a predictor trained on primary...... tumor and benign liver samples, the contamination model decreased the test error on biopsies from liver metastases from 77 to 45%. A further reduction to 34% was obtained by including biopsies in the training data....

  9. Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments

    Science.gov (United States)

    Kwakwa, Kristin A.; Vanderburgh, Joseph P.; Guelcher, Scott A.

    2018-01-01

    Purpose of Review Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. Recent Findings 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. Summary 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes. PMID:28646444

  10. In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform.

    Science.gov (United States)

    Katt, Moriah E; Placone, Amanda L; Wong, Andrew D; Xu, Zinnia S; Searson, Peter C

    2016-01-01

    In vitro tumor models have provided important tools for cancer research and serve as low-cost screening platforms for drug therapies; however, cancer recurrence remains largely unchecked due to metastasis, which is the cause of the majority of cancer-related deaths. The need for an improved understanding of the progression and treatment of cancer has pushed for increased accuracy and physiological relevance of in vitro tumor models. As a result, in vitro tumor models have concurrently increased in complexity and their output parameters further diversified, since these models have progressed beyond simple proliferation, invasion, and cytotoxicity screens and have begun recapitulating critical steps in the metastatic cascade, such as intravasation, extravasation, angiogenesis, matrix remodeling, and tumor cell dormancy. Advances in tumor cell biology, 3D cell culture, tissue engineering, biomaterials, microfabrication, and microfluidics have enabled rapid development of new in vitro tumor models that often incorporate multiple cell types, extracellular matrix materials, and spatial and temporal introduction of soluble factors. Other innovations include the incorporation of perfusable microvessels to simulate the tumor vasculature and model intravasation and extravasation. The drive toward precision medicine has increased interest in adapting in vitro tumor models for patient-specific therapies, clinical management, and assessment of metastatic potential. Here, we review the wide range of current in vitro tumor models and summarize their advantages, disadvantages, and suitability in modeling specific aspects of the metastatic cascade and drug treatment.

  11. Experimental Characterisation of the Interfacial Structure during Counter-Current Flow Limitation in a Model of the Hot Leg of a PWR

    Directory of Open Access Journals (Sweden)

    Christophe Vallée

    2012-01-01

    Full Text Available In order to investigate the two-phase flow behaviour during counter-current flow limitation in the hot leg of a pressurised water reactor, dedicated experiments were performed in a scaled down model of Kobe University. The experiments were performed with air and water at atmospheric pressure and room temperature. At high flow rates, CCFL occurs and the discharge of water to the reactor pressure vessel simulator is limited by the formation of slugs carrying liquid back to the steam generator. The structure of the interface was observed from the side of the channel test section using a high-speed video camera. An algorithm was developed to recognise the stratified interface in the camera frames after background subtraction. This method allows extracting the water level at any position in the image as well as performing further statistical treatments. The evolution of the interfacial structure along the horizontal part of the hot leg is shown by the visualisation of the probability distribution of the water level and analysed in function of the liquid and gas flow rates. The data achieved are useful for the analysis of the flow conditions as well as for the validation of modelling approaches like computational fluid dynamics.

  12. Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

    Directory of Open Access Journals (Sweden)

    Millard M

    2017-10-01

    Full Text Available Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France; 3Laboratory of Biophysics and Biotechnology, 4International Sakharov Environmental Institute, Belarusian State University, Minsk, Belarus; 5Department of Radiology, Medical Company Sunkar, Almaty, Kazakhstan Abstract: The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a

  13. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors.

    Science.gov (United States)

    Espinoza, I; Peschke, P; Karger, C P

    2015-01-01

    In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the model, tumor shrinkage was

  14. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors

    International Nuclear Information System (INIS)

    Espinoza, I.; Peschke, P.; Karger, C. P.

    2015-01-01

    Purpose: In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. Methods: A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. Results: The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the

  15. Halofuginone Inhibits Angiogenesis and Growth in Implanted Metastatic Rat Brain Tumor Model-an MRI Study

    Directory of Open Access Journals (Sweden)

    Rinat Abramovitch

    2004-09-01

    Full Text Available Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF is a potent inhibitor of collagen type α1(I. In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI, we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001. Treatment with HF significantly prolonged survival of treated animals (142%; P = .001. In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05. Additionally, HF treatment inhibited vessel maturation (P = .03. Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

  16. Effect of Irradiation on Tumor Microenvironment and Bone Marrow Cell Migration in a Preclinical Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Kane, Jonathan L. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Hanna, Alaa [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Raffel, Thomas R. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Wilson, George D. [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Marples, Brian, E-mail: Brian.Marples@beaumont.edu [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States)

    2016-09-01

    Purpose: To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. Methods and Materials: Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy using a 5 days on, 2 days off schedule to mimic clinical delivery. Radiation-induced tumor microenvironment changes were examined after treatment using flow cytometry and antibody-specific histopathology. Normal tissue effects were measured using noninvasive {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography after naïve animals were given whole-lung irradiation to 40 Gy in 4 weeks using the same 2-Gy/d regimens. Results: Over the 2 weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate (0.31 ± 0.02 mm{sup 3}/d and 0.55 ± 0.04 mm{sup 3}/d, respectively; P<.007). Histopathology showed a significant comparative reduction in the levels of Ki-67 (14.5% ± 3%), hypoxia (10% ± 3.5%), vascular endothelial growth factor (2.3% ± 1%), and stromal-derived factor-1α (2.5% ± 1.4%), as well as a concomitant decrease in CD45{sup +} bone marrow–derived cell (BMDC) migration (7.8% ± 2.2%) after PRT. The addition of AMD3100 also decreased CD45{sup +} BMDC migration in treated tumors (0.6% ± 0.1%). Higher vessel density was observed in treated tumors. No differences were observed in normal lung tissue after PRT or SRT. Conclusions: Pulsed RT–treated tumors exhibited slower growth and reduced hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by tumors in low oxygen microenvironments, including angiogenesis and recruitment of BMDCs.

  17. Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

    Science.gov (United States)

    Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

    2018-06-01

    The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Basic equations of interfacial area transport in gas-liquid two-phase flow

    International Nuclear Information System (INIS)

    Kataoka, I.; Yoshida, K.; Naitoh, M.; Okada, H.; Morii, T.

    2011-01-01

    The rigorous and consistent formulations of basic equations of interfacial area transport were derived using correlation functions of characteristic function of each phase and velocities of each phase. Turbulent transport term of interfacial area concentration was consistently derived and related to the difference between interfacial velocity and averaged velocity of each phase. Constitutive equations of turbulent transport terms of interfacial area concentration were proposed for bubbly flow. New transport model and constitutive equations were developed for churn flow. These models and constitutive equations are validated by experimental data of radial distributions of interfacial area concentration in bubbly and churn flow. (author)

  19. Development of interfacial area transport equation

    International Nuclear Information System (INIS)

    Kim, Seung Jin; Ishii, Mamoru; Kelly, Joseph

    2005-01-01

    The interfacial area transport equation dynamically models the changes in interfacial structures along the flow field by mechanistically modeling the creation and destruction of dispersed phase. Hence, when employed in the numerical thermal-hydraulic system analysis codes, it eliminates artificial bifurcations stemming from the use of the static flow regime transition criteria. Accounting for the substantial differences in the transport mechanism for various sizes of bubbles, the transport equation is formulated for two characteristic groups of bubbles. The group 1 equation describes the transport of small-dispersed bubbles, whereas the group 2 equation describes the transport of large cap, slug or churn-turbulent bubbles. To evaluate the feasibility and reliability of interfacial area transport equation available at present, it is benchmarked by an extensive database established in various two-phase flow configurations spanning from bubbly to churn-turbulent flow regimes. The geometrical effect in interfacial area transport is examined by the data acquired in vertical air-water two-phase flow through round pipes of various sizes and a confined flow duct, and by those acquired in vertical co-current downward air-water two-phase flow through round pipes of two different sizes

  20. Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

    International Nuclear Information System (INIS)

    Malinowski, Kathleen T.; McAvoy, Thomas J.; George, Rohini; Dieterich, Sonja; D'Souza, Warren D.

    2012-01-01

    Purpose: To investigate the effect of tumor site, measurement precision, tumor–surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor–surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor–surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3–3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

  1. Interfacial solvation thermodynamics

    International Nuclear Information System (INIS)

    Ben-Amotz, Dor

    2016-01-01

    Previous studies have reached conflicting conclusions regarding the interplay of cavity formation, polarizability, desolvation, and surface capillary waves in driving the interfacial adsorptions of ions and molecules at air–water interfaces. Here we revisit these questions by combining exact potential distribution results with linear response theory and other physically motivated approximations. The results highlight both exact and approximate compensation relations pertaining to direct (solute–solvent) and indirect (solvent–solvent) contributions to adsorption thermodynamics, of relevance to solvation at air–water interfaces, as well as a broader class of processes linked to the mean force potential between ions, molecules, nanoparticles, proteins, and biological assemblies. (paper)

  2. Evaluation of silicon nitride as a substrate for culture of PC12 cells: an interfacial model for functional studies in neurons.

    Directory of Open Access Journals (Sweden)

    Johan Jaime Medina Benavente

    Full Text Available Silicon nitride is a biocompatible material that is currently used as an interfacial surface between cells and large-scale integration devices incorporating ion-sensitive field-effect transistor technology. Here, we investigated whether a poly-L-lysine coated silicon nitride surface is suitable for the culture of PC12 cells, which are widely used as a model for neural differentiation, and we characterized their interaction based on cell behavior when seeded on the tested material. The coated surface was first examined in terms of wettability and topography using contact angle measurements and atomic force microscopy and then, conditioned silicon nitride surface was used as the substrate for the study of PC12 cell culture properties. We found that coating silicon nitride with poly-L-lysine increased surface hydrophilicity and that exposing this coated surface to an extracellular aqueous environment gradually decreased its roughness. When PC12 cells were cultured on a coated silicon nitride surface, adhesion and spreading were facilitated, and the cells showed enhanced morphological differentiation compared to those cultured on a plastic culture dish. A bromodeoxyuridine assay demonstrated that, on the coated silicon nitride surface, higher proportions of cells left the cell cycle, remained in a quiescent state and had longer survival times. Therefore, our study of the interaction of the silicon nitride surface with PC12 cells provides important information for the production of devices that need to have optimal cell culture-supporting properties in order to be used in the study of neuronal functions.

  3. A mechanistic model for long-term nuclear waste glass dissolution integrating chemical affinity and interfacial diffusion barrier

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Teqi [Northwest Institute of Nuclear Technology, No.28 Pingyu Road, Baqiao District, Xi' an,Shaanxi, 710024 (China); Mechanics and Physics of Solids Research Group, Modelling and Simulation Centre, The University of Manchester, Oxford Road, Manchester, M13 9PL (United Kingdom); Jivkov, Andrey P., E-mail: andrey.jivkov@manchester.ac.uk [Mechanics and Physics of Solids Research Group, Modelling and Simulation Centre, The University of Manchester, Oxford Road, Manchester, M13 9PL (United Kingdom); Li, Weiping; Liang, Wei; Wang, Yu; Xu, Hui [Northwest Institute of Nuclear Technology, No.28 Pingyu Road, Baqiao District, Xi' an,Shaanxi, 710024 (China); Han, Xiaoyuan, E-mail: xyhan_nint@sina.cn [Northwest Institute of Nuclear Technology, No.28 Pingyu Road, Baqiao District, Xi' an,Shaanxi, 710024 (China)

    2017-04-01

    Understanding the alteration of nuclear waste glass in geological repository conditions is critical element of the analysis of repository retention function. Experimental observations of glass alterations provide a general agreement on the following regimes: inter-diffusion, hydrolysis process, rate drop, residual rate and, under very particular conditions, resumption of alteration. Of these, the mechanisms controlling the rate drop and the residual rate remain a subject of dispute. This paper offers a critical review of the two most competitive models related to these regimes: affinity–limited dissolution and diffusion barrier. The limitations of these models are highlighted by comparison of their predictions with available experimental evidence. Based on the comprehensive discussion of the existing models, a new mechanistic model is proposed as a combination of the chemical affinity and diffusion barrier concepts. It is demonstrated how the model can explain experimental phenomena and data, for which the existing models are shown to be not fully adequate.

  4. Scaling of interfacial jump conditions; Escalamiento de condiciones de salto interfacial

    Energy Technology Data Exchange (ETDEWEB)

    Quezada G, S.; Vazquez R, A.; Espinosa P, G., E-mail: sequga@gmail.com [Universidad Autonoma Metropolitana, Unidad Iztapalapa, Area de Ingenieria en Recursos Energeticos, Apdo. Postal 55-535, 09340 Ciudad de Mexico (Mexico)

    2015-09-15

    To model the behavior of a nuclear reactor accurately is needed to have balance models that take into account the different phenomena occurring in the reactor. These balances have to be coupled together through boundary conditions. The boundary conditions have been studied and different treatments have been given to the interface. In this paper is a brief description of some of the interfacial jump conditions that have been proposed in recent years. Also, the scaling of an interfacial jump condition is proposed, for coupling the different materials that are in contact within a nuclear reactor. (Author)

  5. Microencapsulated tumor assay: Evaluation of the nude mouse model of pancreatic cancer

    Science.gov (United States)

    Ma, Ming-Zhe; Cheng, Dong-Feng; Ye, Jin-Hua; Zhou, Yong; Wang, Jia-Xiang; Shi, Min-Min; Han, Bao-San; Peng, Cheng-Hong

    2012-01-01

    AIM: To establish a more stable and accurate nude mouse model of pancreatic cancer using cancer cell microencapsulation. METHODS: The assay is based on microencapsulation technology, wherein human tumor cells are encapsulated in small microcapsules (approximately 420 μm in diameter) constructed of semipermeable membranes. We implemented two kinds of subcutaneous implantation models in nude mice using the injection of single tumor cells and encapsulated pancreatic tumor cells. The size of subcutaneously implanted tumors was observed on a weekly basis using two methods, and growth curves were generated from these data. The growth and metastasis of orthotopically injected single tumor cells and encapsulated pancreatic tumor cells were evaluated at four and eight weeks postimplantation by positron emission tomography-computed tomography scan and necropsy. The pancreatic tumor samples obtained from each method were then sent for pathological examination. We evaluated differences in the rates of tumor incidence and the presence of metastasis and variations in tumor volume and tumor weight in the cancer microcapsules vs single-cell suspensions. RESULTS: Sequential in vitro observations of the microcapsules showed that the cancer cells in microcapsules proliferated well and formed spheroids at days 4 to 6. Further in vitro culture resulted in bursting of the membrane of the microcapsules and cells deviated outward and continued to grow in flasks. The optimum injection time was found to be 5 d after tumor encapsulation. In the subcutaneous implantation model, there were no significant differences in terms of tumor volume between the encapsulated pancreatic tumor cells and cells alone and rate of tumor incidence. There was a significant difference in the rate of successful implantation between the cancer cell microencapsulation group and the single tumor-cell suspension group (100% vs 71.43%, respectively, P = 0.0489) in the orthotropic implantation model. The former method

  6. PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models

    NARCIS (Netherlands)

    Meehan, Terrence F.; Conte, Nathalie; Goldstein, Theodore; Inghirami, Giorgio; Murakami, Mark A.; Brabetz, Sebastian; Gu, Zhiping; Wiser, Jeffrey A.; Dunn, Patrick; Begley, Dale A.; Krupke, Debra M.; Bertotti, Andrea; Bruna, Alejandra; Brush, Matthew H.; Byrne, Annette T.; Caldas, Carlos; Christie, Amanda L.; Clark, Dominic A.; Dowst, Heidi; Dry, Jonathan R.; Doroshow, James H.; Duchamp, Olivier; Evrard, Yvonne A.; Ferretti, Stephane; Frese, Kristopher K.; Goodwin, Neal C.; Greenawalt, Danielle; Haendel, Melissa A.; Hermans, Els; Houghton, Peter J.; Jonkers, Jos; Kemper, Kristel; Khor, Tin O.; Lewis, Michael T.; Lloyd, K. C. Kent; Mason, Jeremy; Medico, Enzo; Neuhauser, Steven B.; Olson, James M.; Peeper, Daniel S.; Rueda, Oscar M.; Seong, Je Kyung; Trusolino, Livio; Vinolo, Emilie; Wechsler-Reya, Robert J.; Weinstock, David M.; Welm, Alana; Weroha, S. John; Amant, Frédéric; Pfister, Stefan M.; Kool, Marcel; Parkinson, Helen; Butte, Atul J.; Bult, Carol J.

    2017-01-01

    Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models

  7. Noninvasive Multimodality Imaging of the Tumor Microenvironment: Registered Dynamic Magnetic Resonance Imaging and Positron Emission Tomography Studies of a Preclinical Tumor Model of Tumor Hypoxia

    Directory of Open Access Journals (Sweden)

    HyungJoon Cho

    2009-03-01

    Full Text Available In vivo knowledge of the spatial distribution of viable, necrotic, and hypoxic areas can provide prognostic information about the risk of developing metastases and regional radiation sensitivity and may be used potentially for localized dose escalation in radiation treatment. In this study, multimodality in vivo magnetic resonance imaging (MRI and positron emission tomography (PET imaging using stereotactic fiduciary markers in the Dunning R3327AT prostate tumor were performed, focusing on the relationship between dynamic contrast-enhanced (DCE MRI using Magnevist (Gd-DTPA and dynamic 18F-fluoromisonidazole (18F-Fmiso PET. The noninvasive measurements were verified using tumor tissue sections stained for hematoxylin/eosin and pimonidazole. To further validate the relationship between 18F-Fmiso and pimonidazole uptake, 18F digital autoradiography was performed on a selected tumor and compared with the corresponding pimonidazole-stained slices. The comparison of Akep values (kep = rate constant of movement of Gd-DTPA between the interstitial space and plasma and A = amplitude in the two-compartment model (Hoffmann U, Brix G, Knopp MV, Hess T and Lorenz WJ (1995. Magn Reson Med 33, 506– 514 derived from DCE-MRI studies and from early 18F-Fmiso uptake PET studies showed that tumor vasculature is a major determinant of early 18F-Fmiso uptake. A negative correlation between the spatial map of Akep and the slope map of late (last 1 hour of the dynamic PET scan 18F-Fmiso uptake was observed. The relationships between DCE-MRI and hematoxylin/eosin slices and between 18F-Fmiso PET and pimonidazole slices confirm the validity of MRI/PET measurements to image the tumor microenvironment and to identify regions of tumor necrosis, hypoxia, and well-perfused tissue.

  8. Exchange bias mediated by interfacial nanoparticles (invited)

    Energy Technology Data Exchange (ETDEWEB)

    Berkowitz, A. E., E-mail: aberk@ucsd.edu [Department of Physics, University of California, San Diego, La Jolla, California 92093 (United States); Center for Magnetic Recording Research, University of California, California 92093 (United States); Sinha, S. K. [Department of Physics, University of California, San Diego, La Jolla, California 92093 (United States); Fullerton, E. E. [Center for Magnetic Recording Research, University of California, California 92093 (United States); Smith, D. J. [Department of Physics, Arizona State University, Tempe, Arizona 85287 (United States)

    2015-05-07

    The objective of this study on the iconic exchange-bias bilayer Permalloy/CoO has been to identify those elements of the interfacial microstructure and accompanying magnetic properties that are responsible for the exchange-bias and hysteretic properties of this bilayer. Both epitaxial and polycrystalline samples were examined. X-ray and neutron reflectometry established that there existed an interfacial region, of width ∼1 nm, whose magnetic properties differed from those of Py or CoO. A model was developed for the interfacial microstructure that predicts all the relevant properties of this system; namely; the temperature and Permalloy thickness dependence of the exchange-bias, H{sub EX}, and coercivity, H{sub C}; the much smaller measured values of H{sub EX} from what was nominally expected; the different behavior of H{sub EX} and H{sub C} in epitaxial and polycrystalline bilayers. A surprising result is that the exchange-bias does not involve direct exchange-coupling between Permalloy and CoO, but rather is mediated by CoFe{sub 2}O{sub 4} nanoparticles in the interfacial region.

  9. Modeling the effect of water vapor on the interfacial behavior of high-temperature air in contact with Fe20Cr surfaces

    International Nuclear Information System (INIS)

    Chialvo, Ariel A.; Brady, Michael P.; Keiser, James R.; Cole, David R.

    2011-01-01

    Highlights: → Atomistic view of the contrasting interfacial behavior between high-temperature dry- and wet-air in contact with stainless steels. → H 2 O preferentially adsorbs and displaces oxygen at the metal-fluid interface. → Findings are consistent with Ehlers et al.'s proposed competitive adsorption mechanism for the interpretation of the breakaway oxidation. → Significant impact of the inhomogeneous density distribution between the interfacial- and bulk-environments on the fluid transport. -- This work uses molecular dynamics simulation to provide an atomistic view of the contrasting interfacial behavior between high-temperature dry air and wet (10-40 vol.% water) air in contact with stainless steels. A key finding was that H 2 O preferentially adsorbs and displaces oxygen at the metal-fluid interface. We also discuss how these findings are consistent with Ehlers et al. proposed competitive adsorption mechanism for the interpretation of the breakaway oxidation, and highlight their impact on other properties.

  10. Model of avascular tumor growth and response to low dose exposure

    International Nuclear Information System (INIS)

    Rodriguez Aguirre, J M; Custidiano, E R

    2011-01-01

    A single level cellular automata model is described and used to simulate early tumor growth, and the response of the tumor cells under low dose radiation affects. In this model the cell cycle of the population of normal and cancer cells is followed. The invasion mechanism of the tumor is simulated by a local factor that takes into account the microenvironment hardness to cell development, in a picture similar to the AMTIH model. The response of normal and cancer cells to direct effects of radiation is tested for various models and a model of bystander response is implemented.

  11. Molecular dynamics study on interfacial thermal conductance of unirradiated and irradiated SiC/C

    International Nuclear Information System (INIS)

    Wang, Qingyu; Wang, Chenglong; Zhang, Yue; Li, Taosheng

    2014-01-01

    SiC f /SiC composite materials have been considered as candidate structural materials for several types of advanced nuclear reactors. Both experimental and computer simulations studies have revealed the degradation of thermal conductivity for this material after irradiation. The objective of this study is to investigate the effect of SiC/graphite interface structure and irradiation on the interfacial thermal conductance by using molecular dynamics simulation. Five SiC/graphite composite models were created with different interface structures, and irradiation was introduced near the interfaces. Thermal conductance was calculated by means of reverse-NEMD method. Results show that there is a positive correlation between the interfacial energy and interfacial C–Si bond quantity, and irradiated models showed higher interfacial energy compared with their unirradiated counterparts. Except the model with graphite atom plane parallel to the interface, the interfacial thermal conductance of unirradiated and irradiated (1000 eV) models, increases as the increase of interfacial energy, respectively. For all irradiated models, lattice defects are of importance in impacting the interfacial thermal conductance depending on the interface structure. For the model with graphite layer parallel to the interface, the interfacial thermal conductance increased after irradiation, for the other models the interfacial thermal conductance decreased. The vibrational density of states of atoms in the interfacial region was calculated to analyze the phonon mismatch at the interface

  12. Modeling triple-negative breast cancer heterogeneity: effects of stromal macrophages, fibroblasts and tumor vasculature.

    Science.gov (United States)

    Norton, Kerri-Ann; Jin, Kideok; Popel, Aleksander S

    2018-05-08

    A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells. In vivo studies also demonstrated that blocking signaling of selected secreted factors inhibits tumor growth and metastasis in mouse xenograft models. We investigate the influences of increased migration and proliferation rates on tumor growth, the effect of the presence on fibroblasts or macrophages on growth and morphology, and the contributions of macrophage infiltration on tumor growth. We find that while the presence of macrophages increases overall tumor growth, the increase in macrophage infiltration does not substantially increase tumor growth and can even stifle tumor growth at excessive rates. Copyright © 2018. Published by Elsevier Ltd.

  13. Using a 3-d model system to screen for drugs effective on solid tumors

    OpenAIRE

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  14. Interfacial crack arrest in sandwich beams subjected to fatigue loading using a novel crack arresting device – Numerical modelling

    DEFF Research Database (Denmark)

    Martakos, G.; Andreasen, J.H.; Berggreen, Christian

    2017-01-01

    A novel crack arresting device is implemented in foam-cored composite sandwich beams and tested using the Sandwich Tear Test (STT) configuration. A finite element model of the setup is developed, and the predictions are correlated with observations and results from a recently conducted experiment...... concept, as well as a design tool that can be used for the implementation of crack arresting devises in engineering applications of sandwich components and structures....

  15. Sensitivity of Tumor Motion Simulation Accuracy to Lung Biomechanical Modeling Approaches and Parameters

    OpenAIRE

    Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

    2015-01-01

    Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional com...

  16. Referent 3D tumor model at cellular level in radionuclide therapy

    International Nuclear Information System (INIS)

    Spaic, R.; Ilic, R.D.; Petrovic, B.J.

    2002-01-01

    Aim Conventional internal dosimetry has a lot of limitations because of tumor dose nonuniformity. The best approach for absorbed dose at cellular level for different tumors in radionuclide therapy calculation is Monte Carlo method. The purpose of this study is to introduce referent tumor 3D model at cellular level for Monte Carlo simulation study in radionuclide therapy. Material and Methods The moment when tumor is detectable and when same therapy can start is time period in which referent 3D tumor model at cellular level was defined. In accordance with tumor growth rate at that moment he was a sphere with same radius (10 000 μm). In that tumor there are cells or cluster of cells, which are randomly distributed spheres. Distribution of cells/cluster of cells can be calculated from histology data but it was assumed that this distribution is normal with the same mean value and standard deviation (100±50 mm). Second parameter, which was selected to define referent tumor, is volume density of cells (30%). In this referent tumor there are no necroses. Stroma is defined as space between spheres with same concentration of materials as in spheres. Results: Referent tumor defined on this way have about 2,2 10 5 cells or cluster of cells random distributed. Using this referent 3D tumor model and for same concentration of radionuclides (1:100) and energy of beta emitters (1000 keV) which are homogeneously distributed in labeled cells absorbed dose for all cells was calculated. Simulations are done using FOTELP Monte Carlo code, which is modified for this purposes. Results of absorbed dose in cells are given in numerical values (1D distribution) and as the images (2D or 3D distributions). Conclusion Geometrical module for Monte Carlo simulation study can be standardized by introducing referent 3D tumor model at cellular level. This referent 3D tumor model gives most realistic presentation of different tumors at the moment of their detectability. Referent 3D tumor model at

  17. Basic fibroblast growth factor in an animal model of spontaneous mammary tumor progression.

    Science.gov (United States)

    Kao, Steven; Mo, Jeffrey; Baird, Andrew; Eliceiri, Brian P

    2012-06-01

    Although basic fibroblast growth factor (FGF2) was the first pro-angiogenic molecule discovered, it has numerous activities on the growth and differentiation of non-vascular cell types. FGF2 is both stimulatory and inhibitory, depending on the cell type evaluated, the experimental design used and the context in which it is tested. Here, we investigated the effects of manipulating endogenous FGF2 on the development of mammary cancer to determine whether its endogenous contribution in vivo is pro- or anti-tumorigenic. Specifically, we examined the effects of FGF2 gene dosing in a cross between a spontaneous breast tumor model (PyVT+ mice) and FGF2-/- (FGF KO) mice. Using these mice, the onset and progression of mammary tumors was determined. As predicted, female FGF2 WT mice developed mammary tumors starting around 60 days after birth and by 80 days, 100% of FGF2 WT female mice had mammary tumors. In contrast, 80% of FGF2 KO female mice had no palpable tumors until nearly three weeks later (85 days) at times when 100% of the WT cohort was tumor positive. All FGF KO mice were tumor-bearing by 115 days. When we compared the onset of mammary tumor development and the tumor progression curves between FGF het and FGF KO mice, we observed a difference, which suggested a gene dosing effect. Analysis of the tumors demonstrated that there were significant differences in tumor size depending on FGF2 status. The delay in tumor onset supports a functional role for FGF2 in mammary tumor progression, but argues against an essential role for FGF2 in overall mammary tumor progression.

  18. Increased Plasma Colloid Osmotic Pressure Facilitates the Uptake of Therapeutic Macromolecules in a Xenograft Tumor Model

    Directory of Open Access Journals (Sweden)

    Matthias Hofmann

    2009-08-01

    Full Text Available Elevated tumor interstitial fluid pressure (TIFP is a characteristic of most solid tumors. Clinically, TIFP may hamper the uptake of chemotherapeutic drugs into the tumor tissue reducing their therapeutic efficacy. In this study, a means of modulating TIFP to increase the flux of macromolecules into tumor tissue is presented, which is based on the rationale that elevated plasma colloid osmotic pressure (COP pulls water from tumor interstitium lowering the TIFP. Concentrated human serum albumin: (20% HSA, used as an agent to enhance COP, reduced the TIFP time-dependently from 8 to 2 mm Hg in human tumor xenograft models bearing A431 epidermoid vulva carcinomas. To evaluate whether this reduction facilitates the uptake of macromolecules, the intratumoral distribution of fluorescently conjugated dextrans (2.5 mg/ml and cetuximab (2.0 mg/ml was probed using novel time domain nearinfrared fluorescence imaging. This method permitted discrimination and semiquantification of tumor-accumulated conjugate from background and unspecific probe fluorescence. The coadministration of 20% HSA together with either dextrans or cetuximab was found to lower the TIFP significantly and increase the concentration of the substances within the tumor tissue in comparison to control tumors. Furthermore, combined administration of 20%HSA plus cetuximab reduced the tumor growth significantly in comparison to standard cetuximab treatment. These data demonstrate that increased COP lowers the TIFP within hours and increases the uptake of therapeutic macromolecules into the tumor interstitium leading to reduced tumor growth. This model represents a novel approach to facilitate the delivery of therapeutics into tumor tissue, particularly monoclonal antibodies.

  19. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    International Nuclear Information System (INIS)

    Juliachs, Mercè; Viñals, Francesc; Vidal, August; Muro, Xavier Garcia del; Piulats, Josep M; Condom, Enric; Casanovas, Oriol; Graupera, Mariona; Germà, Jose R; Villanueva, Alberto

    2013-01-01

    Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

  20. Tumor affinity of radiolabeled peanut agglutinin compared with that of Ga-67 citrate in animal models

    International Nuclear Information System (INIS)

    Yokoyama, K.; Aburano, T.; Watanabe, N.; Kawabata, S.; Ishida, H.; Mukai, K.; Tonami, N.; Hisada, K.

    1985-01-01

    Peanut agglutinin (PNA) binds avidly to the immunodominant group of the tumor associated T antigen. The purpose of this study was to evaluate oncodiagnostic potential of radiolabeled PNA in animal models. PNA was labeled with I-125 or I-131 by Iodogen and also with In-111 by cyclic DTPA anhydride. The biological activity of PNA was examined by a hemaglutination titer with a photometer before and after labeling. Animal tumor models used were Lewis Lung Cancer(LLC), B-16 Melanotic Melanoma(MM), Yoshida Sarcoma(YS), Ehrlich Ascites Tumor(EAT and Hepatoma AH109A(HAH). Inflammatory tissue induced by turpentine oil was used as an abscess model. Serial scintigraphic images were obtained following IV injections of 100 μCi of I-131 or In-111-DTPA-PNA. The tumor affinity of Ga-67 citrate was studied to compare that of radiolabeled PNA. Tissue biodistribution was studied in EAT bearing mice. All of these tumor models except HAH were clearly visible by radiolabeled PNA without subtraction techniques. In the models of LLC and EAT, PNA showed the better accumulation into the tumor tissue than Ga-67 citrate. In YS and MM, PNA represented almost the same accumulation as Ga-67 citrate. The localization of PNA into abscess tissue wasn't found although Ga-67 citrate markedly accumulated into abscess tissue as well as tumor tissue. The clearance of PNA from tumor was slower than those from any other organs. Tumor to muscle ratio was 5.1 at 48hrs. and tumor to blood ratio increased with time to 2.3 at 96hrs. These results suggested that radiolabeled PNA may have a potential in the detection of tumor

  1. Modeling polymer-induced interactions between two grafted surfaces: comparison between interfacial statistical associating fluid theory and self-consistent field theory.

    Science.gov (United States)

    Jain, Shekhar; Ginzburg, Valeriy V; Jog, Prasanna; Weinhold, Jeffrey; Srivastava, Rakesh; Chapman, Walter G

    2009-07-28

    The interaction between two polymer grafted surfaces is important in many applications, such as nanocomposites, colloid stabilization, and polymer alloys. In our previous work [Jain et al., J. Chem. Phys. 128, 154910 (2008)], we showed that interfacial statistical associating fluid density theory (iSAFT) successfully calculates the structure of grafted polymer chains in the absence/presence of a free polymer. In the current work, we have applied this density functional theory to calculate the force of interaction between two such grafted monolayers in implicit good solvent conditions. In particular, we have considered the case where the segment sizes of the free (sigma(f)) and grafted (sigma(g)) polymers are different. The interactions between the two monolayers in the absence of the free polymer are always repulsive. However, in the presence of the free polymer, the force either can be purely repulsive or can have an attractive minimum depending upon the relative chain lengths of the free (N(f)) and grafted polymers (N(g)). The attractive minimum is observed only when the ratio alpha = N(f)/N(g) is greater than a critical value. We find that these critical values of alpha satisfy the following scaling relation: rho(g) square root(N(g)) beta(3) proportional to alpha(-lambda), where beta = sigma(f)/sigma(g) and lambda is the scaling exponent. For beta = 1 or the same segment sizes of the free and grafted polymers, this scaling relation is in agreement with those from previous theoretical studies using self-consistent field theory (SCFT). Detailed comparisons between iSAFT and SCFT are made for the structures of the monolayers and their forces of interaction. These comparisons lead to interesting implications for the modeling of nanocomposite thermodynamics.

  2. Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Zawaski, Janice A. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Gaber, M. Waleed, E-mail: gaber@bcm.edu [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States); Sabek, Omaima M. [Department of Surgery, Methodist Hospital Research Institute, Houston, TX (United States); Wilson, Christy M. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Duntsch, Christopher D. [Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN (United States); Merchant, Thomas E. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Department of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2012-03-01

    Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results: The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.

  3. EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

    Science.gov (United States)

    Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

    2013-01-01

    Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

  4. Effect of Compatibilization on Interfacial Polarization and Intrinsic Length Scales in Biphasic Polymer Blends of PαMSAN and PMMA : A Combined Experimental and Modeling Dielectric Study

    NARCIS (Netherlands)

    Bharati, A.; Wübbenhorst, M.; Moldenaers, Paula; Cardinaels, Ruth

    2016-01-01

    We describe an approach to tailor the dielectric interfacial properties of polymer blends by the interplay of compatibilizer effects on blend morphology and on blocking of charge carriers. A systematic study of the effect of the concentration of the compatibilizer, a random copolymer of

  5. A deterministic and stochastic model for the system dynamics of tumor-immune responses to chemotherapy

    Science.gov (United States)

    Liu, Xiangdong; Li, Qingze; Pan, Jianxin

    2018-06-01

    Modern medical studies show that chemotherapy can help most cancer patients, especially for those diagnosed early, to stabilize their disease conditions from months to years, which means the population of tumor cells remained nearly unchanged in quite a long time after fighting against immune system and drugs. In order to better understand the dynamics of tumor-immune responses under chemotherapy, deterministic and stochastic differential equation models are constructed to characterize the dynamical change of tumor cells and immune cells in this paper. The basic dynamical properties, such as boundedness, existence and stability of equilibrium points, are investigated in the deterministic model. Extended stochastic models include stochastic differential equations (SDEs) model and continuous-time Markov chain (CTMC) model, which accounts for the variability in cellular reproduction, growth and death, interspecific competitions, and immune response to chemotherapy. The CTMC model is harnessed to estimate the extinction probability of tumor cells. Numerical simulations are performed, which confirms the obtained theoretical results.

  6. Naked DNA Immunization for Prevention of Prostate Cancer in a Dunning Rat Prostate Tumor Model

    National Research Council Canada - National Science Library

    Mincheff, Milcho

    2003-01-01

    ...: H-PSMA-T, R-"PSMA"-T, H-PSA, H-PSA-T, H-PAP-T and R"PSMA"-S. Preliminary studies using the Copenhagen rat tumor prostate model showed uniform tumor development in rats that were injected subcutaneously with 100 000 AT3B-lPSMA,PSA cells...

  7. Accessing key steps of human tumor progression in vivo by using an avian embryo model

    Science.gov (United States)

    Hagedorn, Martin; Javerzat, Sophie; Gilges, Delphine; Meyre, Aurélie; de Lafarge, Benjamin; Eichmann, Anne; Bikfalvi, Andreas

    2005-02-01

    Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, and major ethical concerns. To avoid these shortcomings, we investigated whether tumor growth on the chick chorio-allantoic membrane after human glioblastoma cell grafting would replicate characteristics of the human disease. Avascular tumors consistently formed within 2 days, then progressed through vascular endothelial growth factor receptor 2-dependent angiogenesis, associated with hemorrhage, necrosis, and peritumoral edema. Blocking of vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor signaling pathways by using small-molecule receptor tyrosine kinase inhibitors abrogated tumor development. Gene regulation during the angiogenic switch was analyzed by oligonucleotide microarrays. Defined sample selection for gene profiling permitted identification of regulated genes whose functions are associated mainly with tumor vascularization and growth. Furthermore, expression of known tumor progression genes identified in the screen (IL-6 and cysteine-rich angiogenic inducer 61) as well as potential regulators (lumican and F-box-only 6) follow similar patterns in patient glioma. The model reliably simulates key features of human glioma growth in a few days and thus could considerably increase the speed and efficacy of research on human tumor progression and preclinical drug screening. angiogenesis | animal model alternatives | glioblastoma

  8. Multiple-Tumor Analysis with MS_Combo Model (Use with BMDS Wizard)

    Science.gov (United States)

    Exercises and procedures on setting up and using the MS_Combo Wizard. The MS_Combo model provides BMD and BMDL estimates for the risk of getting one or more tumors for any combination of tumors observed in a single bioassay.

  9. Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

    DEFF Research Database (Denmark)

    Schrama, D.; Voigt, H.; Eggert, A.O.

    2008-01-01

    BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...... response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction...... of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells...

  10. A non-equilibrium thermodynamic model for tumor extracellular matrix with enzymatic degradation

    Science.gov (United States)

    Xue, Shi-Lei; Li, Bo; Feng, Xi-Qiao; Gao, Huajian

    2017-07-01

    The extracellular matrix (ECM) of a solid tumor not only affords scaffolding to support tumor architecture and integrity but also plays an essential role in tumor growth, invasion, metastasis, and therapeutics. In this paper, a non-equilibrium thermodynamic theory is established to study the chemo-mechanical behaviors of tumor ECM, which is modeled as a poroelastic polyelectrolyte consisting of a collagen network and proteoglycans. By using the principle of maximum energy dissipation rate, we deduce a set of governing equations for drug transport and mechanosensitive enzymatic degradation in ECM. The results reveal that osmosis is primarily responsible for the compression resistance of ECM. It is suggested that a well-designed ECM degradation can effectively modify the tumor microenvironment for improved efficiency of cancer therapy. The theoretical predictions show a good agreement with relevant experimental observations. This study aimed to deepen our understanding of tumor ECM may be conducive to novel anticancer strategies.

  11. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    International Nuclear Information System (INIS)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

    2014-01-01

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

  12. The role of neutrophil myeloperoxidase in models of lung tumor development.

    Science.gov (United States)

    Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  13. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Energy Technology Data Exchange (ETDEWEB)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  14. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Directory of Open Access Journals (Sweden)

    Amy L. Rymaszewski

    2014-05-01

    Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  15. Interfacial forces in aqueous media

    CERN Document Server

    van Oss, Carel J

    2006-01-01

    Thoroughly revised and reorganized, the second edition of Interfacial Forces in Aqueous Media examines the role of polar interfacial and noncovalent interactions among biological and nonbiological macromolecules as well as biopolymers, particles, surfaces, cells, and both polar and apolar polymers. The book encompasses Lifshitz-van der Waals and electrical double layer interactions, as well as Lewis acid-base interactions between colloidal entities in polar liquids such as water. New in this Edition: Four previously unpublished chapters comprising a new section on interfacial propertie

  16. Interfacial Instabilities in Evaporating Drops

    Science.gov (United States)

    Moffat, Ross; Sefiane, Khellil; Matar, Omar

    2007-11-01

    We study the effect of substrate thermal properties on the evaporation of sessile drops of various liquids. An infra-red imaging technique was used to record the interfacial temperature. This technique illustrates the non-uniformity in interfacial temperature distribution that characterises the evaporation process. Our results also demonstrate that the evaporation of methanol droplets is accompanied by the formation of wave-trains in the interfacial temperature field; similar patterns, however, were not observed in the case of water droplets. More complex patterns are observed for FC-72 refrigerant drops. The effect of substrate thermal conductivity on the structure of the complex pattern formation is also elucidated.

  17. Mathematical modeling of tumor-associated macrophage interactions with the cancer microenvironment.

    Science.gov (United States)

    Mahlbacher, Grace; Curtis, Louis T; Lowengrub, John; Frieboes, Hermann B

    2018-01-30

    Immuno-oncotherapy has emerged as a promising means to target cancer. In particular, therapeutic manipulation of tumor-associated macrophages holds promise due to their various and sometimes opposing roles in tumor progression. It is established that M1-type macrophages suppress tumor progression while M2-types support it. Recently, Tie2-expressing macrophages (TEM) have been identified as a distinct sub-population influencing tumor angiogenesis and vascular remodeling as well as monocyte differentiation. This study develops a modeling framework to evaluate macrophage interactions with the tumor microenvironment, enabling assessment of how these interactions may affect tumor progression. M1, M2, and Tie2 expressing variants are integrated into a model of tumor growth representing a metastatic lesion in a highly vascularized organ, such as the liver. Behaviors simulated include M1 release of nitric oxide (NO), M2 release of growth-promoting factors, and TEM facilitation of angiogenesis via Angiopoietin-2 and promotion of monocyte differentiation into M2 via IL-10. The results show that M2 presence leads to larger tumor growth regardless of TEM effects, implying that immunotherapeutic strategies that lead to TEM ablation may fail to restrain growth when the M2 represents a sizeable population. As TEM pro-tumor effects are less pronounced and on a longer time scale than M1-driven tumor inhibition, a more nuanced approach to influence monocyte differentiation taking into account the tumor state (e.g., under chemotherapy) may be desirable. The results highlight the dynamic interaction of macrophages within a growing tumor, and, further, establish the initial feasibility of a mathematical framework that could longer term help to optimize cancer immunotherapy.

  18. A Time-Delayed Mathematical Model for Tumor Growth with the Effect of a Periodic Therapy.

    Science.gov (United States)

    Xu, Shihe; Wei, Xiangqing; Zhang, Fangwei

    2016-01-01

    A time-delayed mathematical model for tumor growth with the effect of periodic therapy is studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a time delay in cell proliferation process. Sufficient conditions for the global stability of tumor free equilibrium are given. We also prove that if external concentration of nutrients is large the tumor will not disappear and the conditions under which there exist periodic solutions to the model are also determined. Results are illustrated by computer simulations.

  19. A Time-Delayed Mathematical Model for Tumor Growth with the Effect of a Periodic Therapy

    Directory of Open Access Journals (Sweden)

    Shihe Xu

    2016-01-01

    Full Text Available A time-delayed mathematical model for tumor growth with the effect of periodic therapy is studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a time delay in cell proliferation process. Sufficient conditions for the global stability of tumor free equilibrium are given. We also prove that if external concentration of nutrients is large the tumor will not disappear and the conditions under which there exist periodic solutions to the model are also determined. Results are illustrated by computer simulations.

  20. TumorML: Concept and requirements of an in silico cancer modelling markup language.

    Science.gov (United States)

    Johnson, David; Cooper, Jonathan; McKeever, Steve

    2011-01-01

    This paper describes the initial groundwork carried out as part of the European Commission funded Transatlantic Tumor Model Repositories project, to develop a new markup language for computational cancer modelling, TumorML. In this paper we describe the motivations for such a language, arguing that current state-of-the-art biomodelling languages are not suited to the cancer modelling domain. We go on to describe the work that needs to be done to develop TumorML, the conceptual design, and a description of what existing markup languages will be used to compose the language specification.

  1. Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

    Science.gov (United States)

    Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M

    2017-12-09

    Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO₂) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1-e.g., by OTX008-may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.

  2. Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

    Science.gov (United States)

    1984-10-01

    lung tumor system the specific aims are: 1. To conduct studies of the effect of 3-methylchlanthrene (MCA) on DNA synthesis and cell proliferation in...alkylation of nucleic acids of the rat by N-methyl-N- nitrosourea , dimethylnitrosamine, dimethylsulfate, and methylmethanesulfonate. Biochem. J. 110:39-47

  3. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    Science.gov (United States)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  4. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    International Nuclear Information System (INIS)

    Unkelbach, Jan; Dittmann, Florian; Le, Matthieu; Shih, Helen A; Menze, Bjoern H; Ayache, Nicholas; Konukoglu, Ender

    2014-01-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher–Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  5. A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment

    Science.gov (United States)

    Nör, Jacques Eduardo

    2018-01-01

    Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics. By including the molecular details of IL-6 binding, we are able to quantify the temporal changes in fractional occupancies of bound receptors and their influence on tumor volume. There is a strong correlation between the model output and experimental data for primary tumor xenografts. We also used the model to predict tumor response to administration of the humanized IL-6R monoclonal antibody, tocilizumab (TCZ), and we found that as little as 1mg/kg of TCZ administered weekly for 7 weeks is sufficient to result in tumor reduction and a sustained deceleration of tumor growth. PMID:29351275

  6. Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression.

    Directory of Open Access Journals (Sweden)

    Katharina Galmbacher

    Full Text Available A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TDeltaaroA and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TDeltaaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

  7. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... invasion and tumor stemness into account. METHODS: Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice...

  8. Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

    International Nuclear Information System (INIS)

    Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D.; Morris, G.M.

    2000-01-01

    In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED 50 ) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

  9. Ultrasonic characterization of three animal mammary tumors from three-dimensional acoustic tissue models

    Science.gov (United States)

    Mamou, Jonathan M.

    This dissertation investigated how three-dimensional (3D) tissue models can be used to improve ultrasonic tissue characterization (UTC) techniques. Anatomic sites in tissue responsible for ultrasonic scattering are unknown, which limits the potential applications of ultrasound for tumor diagnosis. Accurate 3D models of tumor tissues may help identify the scattering sites. Three mammary tumors were investigated: a rat fibroadenoma, a mouse carcinoma, and a mouse sarcoma. A 3D acoustic tissue model, termed 3D impedance map (3DZM), was carefully constructed from consecutive histologic sections for each tumor. Spectral estimates (scatterer size and acoustic concentration) were obtained from the 3DZMs and compared to the same estimates obtained with ultrasound. Scatterer size estimates for three tumors were found to be similar (within 10%). The 3DZMs were also used to extract tissue-specific scattering models. The scattering models were found to allow clear distinction between the three tumors. This distinction demonstrated that UTC techniques may be helpful for noninvasive clinical tumor diagnosis.

  10. Hyperbolastic modeling of tumor growth with a combined treatment of iodoacetate and dimethylsulphoxide

    International Nuclear Information System (INIS)

    Eby, Wayne M; Tabatabai, Mohammad A; Bursac, Zoran

    2010-01-01

    An understanding of growth dynamics of tumors is important in understanding progression of cancer and designing appropriate treatment strategies. We perform a comparative study of the hyperbolastic growth models with the Weibull and Gompertz models, which are prevalently used in the field of tumor growth. The hyperbolastic growth models H1, H2, and H3 are applied to growth of solid Ehrlich carcinoma under several different treatments. These are compared with results from Gompertz and Weibull models for the combined treatment. The growth dynamics of the solid Ehrlich carcinoma with the combined treatment are studied using models H1, H2, and H3, and the models are highly accurate in representing the growth. The growth dynamics are also compared with the untreated tumor, the tumor treated with only iodoacetate, and the tumor treated with only dimethylsulfoxide, and the combined treatment. The hyperbolastic models prove to be effective in representing and analyzing the growth dynamics of the solid Ehrlich carcinoma. These models are more precise than Gompertz and Weibull and show less error for this data set. The precision of H3 allows for its use in a comparative analysis of tumor growth rates between the various treatments

  11. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model.

    Directory of Open Access Journals (Sweden)

    Debbie Liao

    2009-11-01

    Full Text Available Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer.We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+ T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression.Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer.

  12. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model.

    Science.gov (United States)

    Liao, Debbie; Luo, Yunping; Markowitz, Dorothy; Xiang, Rong; Reisfeld, Ralph A

    2009-11-23

    Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer. We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+) T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression. Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer.

  13. Efficacy of continuous treatment with radiation in a rat brain-tumor model

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Kaufman, K.

    1981-01-01

    Rats bearing intracerebral 9L/Ro tumors were treated with 10 daily fractions of cesium-137 gamma-rays, BCNU, or combinations of these to agents beginning on either Day 10 or Day 12 after implantation. The treatments were administered either 5 days/week for 2 weeks, with the weekend off, or 10 consecutive days. The median day of death for untreated tumor-bearing rats was Day 15, so Day 12 tumors can be considered late tumors and Day 10 tumors can be considered moderately early. Although all single- and multiple-agent treatments significantly (p less than 0.05) increased the lifespan of tumor-bearing rats over that of the untreated controls, and all multiple-agent schedules significantly (p less than 0.05) increased the lifespan over that of the single-agent therapies, none of the 10 consecutive day schedules increased the lifespan of tumor-bearing rats significantly (p less than 0.2) over that obtained with the 5-day/week schedules. Thus, the evidence from this tumor model suggests that no significant improvement in lifespan would be expected if malignant brain tumors were treated with radiation 7 days a week, either alone or in combination with chemotherapeutic agents such as BCNU

  14. Mesoscale Interfacial Dynamics in Magnetoelectric Nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Shashank, Priya [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States)

    2009-12-14

    Biphasic composites are the key towards achieving enhanced magnetoelectric response. In order understand the control behavior of the composites and resultant symmetry of the multifunctional product tensors, we need to synthesized model material systems with the following features (i) interface formation through either deposition control or natural decomposition; (ii) a very high interphase-interfacial area, to maximize the ME coupling; and (iii) an equilibrium phase distribution and morphology, resulting in preferred crystallographic orientation relations between phases across the interphase-interfacial boundaries. This thought process guided the experimental evolution in this program. We initiated the research with the co-fired composites approach and then moved on to the thin film laminates deposited through the rf-magnetron sputtering and pulsed laser deposition process

  15. Evaluating interfacial shear stresses in composite hollo

    Directory of Open Access Journals (Sweden)

    Aiham Adawi

    2016-09-01

    Full Text Available Analytical evaluation of the interfacial shear stresses for composite hollowcore slabs with concrete topping is rare in the literature. Adawi et al. (2014 estimated the interfacial shear stiffness coefficient (ks that governs the behavior of the interface between hollowcore slabs and the concrete topping using push-off tests. This parameter is utilized in this paper to provide closed form solutions for the differential equations governing the behavior of simply supported composite hollowcore slabs. An analytical solution based on the deformation compatibility of the composite section and elastic beam theory, is developed to evaluate the shear stresses along the interface. Linear finite element modeling of the full-scale tests presented in Adawi et al. (2015 is also conducted to validate the developed analytical solution. The proposed analytical solution was found to be adequate in estimating the magnitude of horizontal shear stress in the studied composite hollowcore slabs.

  16. Delay equations modeling the effects of phase-specific drugs and immunotherapy on proliferating tumor cells.

    Science.gov (United States)

    Barbarossa, Maria Vittoria; Kuttler, Christina; Zinsl, Jonathan

    2012-04-01

    In this work we present a mathematical model for tumor growth based on the biology of the cell cycle. For an appropriate description of the effects of phase-specific drugs, it is necessary to look at the cell cycle and its phases. Our model reproduces the dynamics of three different tumor cell populations: quiescent cells, cells during the interphase and mitotic cells. Starting from a partial differential equations (PDEs) setting, a delay differential equations (DDE) model is derived for an easier and more realistic approach. Our equations also include interactions of tumor cells with immune system effectors. We investigate the model both from the analytical and the numerical point of view, give conditions for positivity of solutions and focus on the stability of the cancer-free equilibrium. Different immunotherapeutic strategies and their effects on the tumor growth are considered, as well.

  17. Cystatin C deficiency suppresses tumor growth in a breast cancer model through decreased proliferation of tumor cells.

    Science.gov (United States)

    Završnik, Janja; Butinar, Miha; Prebanda, Mojca Trstenjak; Krajnc, Aleksander; Vidmar, Robert; Fonović, Marko; Grubb, Anders; Turk, Vito; Turk, Boris; Vasiljeva, Olga

    2017-09-26

    Cysteine cathepsins are proteases that, in addition to their important physiological functions, have been associated with multiple pathologies, including cancer. Cystatin C (CstC) is a major endogenous inhibitor that regulates the extracellular activity of cysteine cathepsins. We investigated the role of cystatin C in mammary cancer using CstC knockout mice and a mouse model of breast cancer induced by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium. We showed that the ablation of CstC reduced the rate of mammary tumor growth. Notably, a decrease in the proliferation of CstC knockout PyMT tumor cells was demonstrated ex vivo and in vitro , indicating a role for this protease inhibitor in signaling pathways that control cell proliferation. An increase in phosphorylated p-38 was observed in CstC knockout tumors, suggesting a novel function for cystatin C in cancer development, independent of the TGF-β pathway. Moreover, proteomic analysis of the CstC wild-type and knockout PyMT primary cell secretomes revealed a decrease in the levels of 14-3-3 proteins in the secretome of knock-out cells, suggesting a novel link between cysteine cathepsins, cystatin C and 14-3-3 proteins in tumorigenesis, calling for further investigations.

  18. Interfacial structures in downward two-phase bubbly flow

    International Nuclear Information System (INIS)

    Paranjape, S.S.; Kim, S.; Ishii, M.; Kelly, J.

    2003-01-01

    Downward two-phase flow was studied considering its significance in view of Light Water Reactor Accidents (LWR) such as Loss of Heat Sink (LOHS) by feed water loss or secondary pipe break. The flow studied, was an adiabatic, air-water, co-current, vertically downward two-phase flow. The experimental test sections had internal hydraulic diameters of 25.4 mm and 50.8 mm. Flow regime map was obtained using the characteristic signals obtained from an impedance void meter, employing neural network based identification methodology to minimize the subjective judgment in determining the flow regimes. A four sensor conductivity probe was used to measure the local two phase flow parameters, which characterize the interfacial structures. The local time averaged two-phase flow parameters measured were: void fraction (α), interfacial area concentration (a i ), bubble velocity (v g ), and Sauter mean diameter (D Sm ). The flow conditions were from the bubbly flow regime. The local profiles of these parameters as well as their axial development revealed the nature of the interfacial structures and the bubble interaction mechanisms occurring in the flow. Furthermore, this study provided a good database for the development of the interfacial area transport equation, which dynamically models the changes in the interfacial area along the flow field. An interfacial area transport equation was developed for downward flow based on that developed for the upward flow, with certain modifications in the bubble interaction terms. The area averaged values of the interfacial area concentration were compared with those predicted by the interfacial area transport model. (author)

  19. Application of Benchtop-magnetic resonance imaging in a nude mouse tumor model

    Directory of Open Access Journals (Sweden)

    Mäder Karsten

    2011-07-01

    Full Text Available Abstract Background MRI plays a key role in the preclinical development of new drugs, diagnostics and their delivery systems. However, very high installation and running costs of existing superconducting MRI machines limit the spread of MRI. The new method of Benchtop-MRI (BT-MRI has the potential to overcome this limitation due to much lower installation and almost no running costs. However, due to the low field strength and decreased magnet homogeneity it is questionable, whether BT-MRI can achieve sufficient image quality to provide useful information for preclinical in vivo studies. It was the aim of the current study to explore the potential of BT-MRI on tumor models in mice. Methods We used a prototype of an in vivo BT-MRI apparatus to visualise organs and tumors and to analyse tumor progression in nude mouse xenograft models of human testicular germ cell tumor and colon carcinoma. Results Subcutaneous xenografts were easily identified as relative hypointense areas in transaxial slices of NMR images. Monitoring of tumor progression evaluated by pixel extension analyses based on NMR images correlated with increasing tumor volume calculated by calliper measurement. Gd-BOPTA contrast agent injection resulted in a better differentiation between parts of the urinary tissues and organs due to fast elimination of the agent via kidneys. In addition, interior structuring of tumors could be observed. A strong contrast enhancement within a tumor was associated with a central necrotic/fibrotic area. Conclusions BT-MRI provides satisfactory image quality to visualize organs and tumors and to monitor tumor progression and structure in mouse models.

  20. [Study of the immunological mechanism of anti-tumor effects of 5-FU by establishing EL4 tumor-bearing mouse models].

    Science.gov (United States)

    Li, Mo-Lin; Li, Chuan-Gang; Shu, Xiao-Hong; Li, Ming-Xia; Jia, Yu-Jie; Qin, Zhi-Hai

    2007-11-01

    To investigate the immunological mechanism of anti-tumor effect of 5-FU by establishing lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice, respectively. The mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, 5-FU of different doses was administered intraperitoneally to treat these wild type C57BL/6 tumor-bearing mice. The size of tumors in the wild type C57BL/6 mice was observed and recorded to explore the minimal dose of 5-FU that could cure the tumor-bearing mice. Then the same amount of EL4 tumor cells was inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, 5-FU of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tumor-bearing mice. The size of tumors in the two different types of mice was observed and recorded. A single dose of 5-FU (75 mg/kg) cured both the EL4 tumor-bearing wild type C57BL/6 mice and the EL4 tumor-bearing nude C57BL/6 mice in the first week. Two weeks after 5-FU treatment, all of the nude mice died of tumor relapse while most of the wild type C57BL/6 mice were fully recovered. A single dose of 5-FU has marked anti-tumor effects on lymphoma EL4 tumor-bearing C57BL/6 mice with or without T lymphocytes. The relapse of tumors after 5-FU treatment might be related to the function of T lymphocytes.

  1. Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma.

    Science.gov (United States)

    Markowitz, Geoffrey J; Michelotti, Gregory A; Diehl, Anna Mae; Wang, Xiao-Fan

    2015-04-01

    Initiation and progression of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue. This diseased liver tissue background is a drastically different microenvironment from the healthy liver, especially with regard to immune cell prevalence and presence of mediators of immune function. To better understand the consequences of liver disease on tumor growth and the interplay with its microenvironment, we utilized two standard methods of fibrosis induction and orthotopic implantation of tumors into the inflamed and fibrotic liver to mimic the liver condition in human HCC patients. Compared to non-diseased controls, tumor growth was significantly enhanced under fibrotic conditions. The immune cells that infiltrated the tumors were also drastically different, with decreased numbers of natural killer cells but greatly increased numbers of immune-suppressive CD11b + Gr1 hi myeloid cells in both models of fibrosis. In addition, there were model-specific differences: Increased numbers of CD11b + myeloid cells and CD4 + CD25 + T cells were found in tumors in the bile duct ligation model but not in the carbon tetrachloride model. Induction of fibrosis altered the cytokine production of implanted tumor cells, which could have farreaching consequences on the immune infiltrate and its functionality. Taken together, this work demonstrates that the combination of fibrosis induction with orthotopic tumor implantation results in a markedly different tumor microenvironment and tumor growth kinetics, emphasizing the necessity for more accurate modeling of HCC progression in mice, which takes into account the drastic changes in the tissue caused by chronic liver disease.

  2. Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors.

    Science.gov (United States)

    Sweeney, Carol; Boucher, Kenneth M; Samowitz, Wade S; Wolff, Roger K; Albertsen, Hans; Curtin, Karen; Caan, Bette J; Slattery, Martha L

    2009-01-01

    Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and TP16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population-based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and TP16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis.

  3. Interfacial structures and area transport in upward and downward two-phase flow

    International Nuclear Information System (INIS)

    Paranjape, S. S.; Kim, S.; Ishii, M.; Kelly, J.

    2003-01-01

    An experimental study has been carried out for upward and downward two-phase flow to study local interfacial structures and interfacial area transport. The flow studied, is an adiabatic, air-water, co-current, two-phase flow, in 25.4 mm and 50.8 mm ID test sections. Flow regime map is obtained using the characteristic signals obtained from an impedance void meter, employing neural network based identification methodology. A four sensor conductivity probe is used to measure the local two phase flow parameters, in bubbly flow regime. The local profiles of these parameters as well as their axial development reveal the nature of the interfacial structures and the bubble interaction mechanisms occurring in the flow. Furthermore, this study provides a good database for the development of the interfacial area transport equation, which dynamically models the changes in the interfacial area along a flow field. An interfacial area transport equation is used for downward flow based on that developed for the upward flow, with certain modifications in the bubble interaction terms. The area averaged values of the interfacial area concentration are compared with those predicted by the interfacial area transport model. The differences in the interfacial structures and interfacial area transport in co-current downward and upward two-phase flows are studied

  4. Failure of the cultivated mushroom (Agaricus bisporus) to induce tumors in the A/J mouse lung tumor model

    DEFF Research Database (Denmark)

    Pilegaard, Kirsten; Kristiansen, E.; Meyer, Otto A.

    1997-01-01

    We studied whether the cultivated mushroom (Agaricus bisporus) or 4-(carboxy)phenylhydrazine (CP) induce lung adenomas in the A/J mouse lung tumor model. For 26 weeks female mice were fed a semisynthetic diet where 11 or 22% of the diet was replaced by freeze-dried mushrooms. The intake...... of the mushroom diets was equivalent to an intake of agaritine, the major phenylhydrazine derivative occurring in the mushroom, of 92 or 166 mg/kg body weight per day. The intake of CP was 106 mg/kg body weight per day. Neither the;freeze-dried mushroom nor CP induced statistically significant increased numbers...

  5. A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion.

    Science.gov (United States)

    Shelton, Laura M; Mukherjee, Purna; Huysentruyt, Leanne C; Urits, Ivan; Rosenberg, Joshua A; Seyfried, Thomas N

    2010-09-01

    Glioblastoma multiforme (GBM) is a rapidly progressive disease of morbidity and mortality and is the most common form of primary brain cancer in adults. Lack of appropriate in vivo models has been a major roadblock to developing effective therapies for GBM. A new highly invasive in vivo GBM model is described that was derived from a spontaneous brain tumor (VM-M3) in the VM mouse strain. Highly invasive tumor cells could be identified histologically on the hemisphere contralateral to the hemisphere implanted with tumor cells or tissue. Tumor cells were highly expressive for the chemokine receptor CXCR4 and the proliferation marker Ki-67 and could be identified invading through the pia mater, the vascular system, the ventricular system, around neurons, and over white matter tracts including the corpus callosum. In addition, the brain tumor cells were labeled with the firefly luciferase gene, allowing for non-invasive detection and quantitation through bioluminescent imaging. The VM-M3 tumor has a short incubation time with mortality occurring in 100% of the animals within approximately 15 days. The VM-M3 brain tumor model therefore can be used in a pre-clinical setting for the rapid evaluation of novel anti-invasive therapies.

  6. Stochastic fluctuation induced the competition between extinction and recurrence in a model of tumor growth

    International Nuclear Information System (INIS)

    Li, Dongxi; Xu, Wei; Sun, Chunyan; Wang, Liang

    2012-01-01

    We investigate the phenomenon that stochastic fluctuation induced the competition between tumor extinction and recurrence in the model of tumor growth derived from the catalytic Michaelis–Menten reaction. We analyze the probability transitions between the extinction state and the state of the stable tumor by the Mean First Extinction Time (MFET) and Mean First Return Time (MFRT). It is found that the positional fluctuations hinder the transition, but the environmental fluctuations, to a certain level, facilitate the tumor extinction. The observed behavior could be used as prior information for the treatment of cancer. -- Highlights: ► Stochastic fluctuation induced the competition between extinction and recurrence. ► The probability transitions are investigated. ► The positional fluctuations hinder the transition. ► The environmental fluctuations, to a certain level, facilitate the tumor extinction. ► The observed behavior can be used as prior information for the treatment of cancer.

  7. Microarray profiling shows distinct differences between primary tumors and commonly used preclinical models in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Weining; Iyer, N. Gopalakrishna; Tay, Hsien Ts’ung; Wu, Yonghui; Lim, Tony K. H.; Zheng, Lin; Song, In Chin; Kwoh, Chee Keong; Huynh, Hung; Tan, Patrick O. B.; Chow, Pierce K. H.

    2015-01-01

    Despite advances in therapeutics, outcomes for hepatocellular carcinoma (HCC) remain poor and there is an urgent need for efficacious systemic therapy. Unfortunately, drugs that are successful in preclinical studies often fail in the clinical setting, and we hypothesize that this is due to functional differences between primary tumors and commonly used preclinical models. In this study, we attempt to answer this question by comparing tumor morphology and gene expression profiles between primary tumors, xenografts and HCC cell lines. Hep G2 cell lines and tumor cells from patient tumor explants were subcutaneously (ectopically) injected into the flank and orthotopically into liver parenchyma of Mus Musculus SCID mice. The mice were euthanized after two weeks. RNA was extracted from the tumors, and gene expression profiling was performed using the Gene Chip Human Genome U133 Plus 2.0. Principal component analyses (PCA) and construction of dendrograms were conducted using Partek genomics suite. PCA showed that the commonly used HepG2 cell line model and its xenograft counterparts were vastly different from all fresh primary tumors. Expression profiles of primary tumors were also significantly divergent from their counterpart patient-derived xenograft (PDX) models, regardless of the site of implantation. Xenografts from the same primary tumors were more likely to cluster together regardless of site of implantation, although heat maps showed distinct differences in gene expression profiles between orthotopic and ectopic models. The data presented here challenges the utility of routinely used preclinical models. Models using HepG2 were vastly different from primary tumors and PDXs, suggesting that this is not clinically representative. Surprisingly, site of implantation (orthotopic versus ectopic) resulted in limited impact on gene expression profiles, and in both scenarios xenografts differed significantly from the original primary tumors, challenging the long

  8. Towards an integrative computational model for simulating tumor growth and response to radiation therapy

    Science.gov (United States)

    Marrero, Carlos Sosa; Aubert, Vivien; Ciferri, Nicolas; Hernández, Alfredo; de Crevoisier, Renaud; Acosta, Oscar

    2017-11-01

    Understanding the response to irradiation in cancer radiotherapy (RT) may help devising new strategies with improved tumor local control. Computational models may allow to unravel the underlying radiosensitive mechanisms intervening in the dose-response relationship. By using extensive simulations a wide range of parameters may be evaluated providing insights on tumor response thus generating useful data to plan modified treatments. We propose in this paper a computational model of tumor growth and radiation response which allows to simulate a whole RT protocol. Proliferation of tumor cells, cell life-cycle, oxygen diffusion, radiosensitivity, RT response and resorption of killed cells were implemented in a multiscale framework. The model was developed in C++, using the Multi-formalism Modeling and Simulation Library (M2SL). Radiosensitivity parameters extracted from literature enabled us to simulate in a regular grid (voxel-wise) a prostate cell tissue. Histopathological specimens with different aggressiveness levels extracted from patients after prostatectomy were used to initialize in silico simulations. Results on tumor growth exhibit a good agreement with data from in vitro studies. Moreover, standard fractionation of 2 Gy/fraction, with a total dose of 80 Gy as a real RT treatment was applied with varying radiosensitivity and oxygen diffusion parameters. As expected, the high influence of these parameters was observed by measuring the percentage of survival tumor cell after RT. This work paves the way to further models allowing to simulate increased doses in modified hypofractionated schemes and to develop new patient-specific combined therapies.

  9. A nonlinear competitive model of the prostate tumor growth under intermittent androgen suppression.

    Science.gov (United States)

    Yang, Jing; Zhao, Tong-Jun; Yuan, Chang-Qing; Xie, Jing-Hui; Hao, Fang-Fang

    2016-09-07

    Hormone suppression has been the primary modality of treatment for prostate cancer. However long-term androgen deprivation may induce androgen-independent (AI) recurrence. Intermittent androgen suppression (IAS) is a potential way to delay or avoid the AI relapse. Mathematical models of tumor growth and treatment are simple while they are capable of capturing the essence of complicated interactions. Game theory models have analyzed that tumor cells can enhance their fitness by adopting genetically determined survival strategies. In this paper, we consider the survival strategies as the competitive advantage of tumor cells and propose a new model to mimic the prostate tumor growth in IAS therapy. Then we investigate the competition effect in tumor development by numerical simulations. The results indicate that successfully IAS-controlled states can be achieved even though the net growth rate of AI cells is positive for any androgen level. There is crucial difference between the previous models and the new one in the phase diagram of successful and unsuccessful tumor control by IAS administration, which means that the suggestions from the models for medication can be different. Furthermore we introduce quadratic logistic terms to the competition model to simulate the tumor growth in the environment with a finite carrying capacity considering the nutrients or inhibitors. The simulations show that the tumor growth can reach an equilibrium state or an oscillatory state with the net growth rate of AI cells being androgen independent. Our results suggest that the competition and the restraint of a limited environment can enhance the possibility of relapse prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Modeling and Analysis of a Nonlinear Age-Structured Model for Tumor Cell Populations with Quiescence

    Science.gov (United States)

    Liu, Zijian; Chen, Jing; Pang, Jianhua; Bi, Ping; Ruan, Shigui

    2018-05-01

    We present a nonlinear first-order hyperbolic partial differential equation model to describe age-structured tumor cell populations with proliferating and quiescent phases at the avascular stage in vitro. The division rate of the proliferating cells is assumed to be nonlinear due to the limitation of the nutrient and space. The model includes a proportion of newborn cells that enter directly the quiescent phase with age zero. This proportion can reflect the effect of treatment by drugs such as erlotinib. The existence and uniqueness of solutions are established. The local and global stabilities of the trivial steady state are investigated. The existence and local stability of the positive steady state are also analyzed. Numerical simulations are performed to verify the results and to examine the impacts of parameters on the nonlinear dynamics of the model.

  11. Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique

    Directory of Open Access Journals (Sweden)

    Jie Ni

    2016-02-01

    Full Text Available Prostate cancer (CaP is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D ultrasound system equipped with photoacoustic (PA imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8. Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r2 = 0.948, 0.955, and 0.953, respectively and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P < .001. The application of 3D ultrasound imaging proved to be a useful imaging modality in monitoring tumor growth in an orthotopic mouse model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research.

  12. A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation

    International Nuclear Information System (INIS)

    Kavanagh, Brian D.; Secomb, Timothy W.; Hsu, Richard; Lin, P.-S.; Venitz, Jurgen; Dewhirst, Mark W.

    2002-01-01

    Purpose: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. Methods and Materials: Hemoglobin affinity is expressed in terms of P 50 , the partial pressure of oxygen (Po 2 ) at half saturation. Effects of changing P 50 on arterial Po 2 are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. Results: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P 50 , but increases with further increases of P 50 , in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P 50 is predicted to improve tumor oxygenation. Conclusions: The results support the administration of synthetic agents to increase P 50 during radiation treatment of tumors

  13. Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea.

    Science.gov (United States)

    Vilaseca, Antoni; Campillo, Noelia; Torres, Marta; Musquera, Mireia; Gozal, David; Montserrat, Josep M; Alcaraz, Antonio; Touijer, Karim A; Farré, Ramon; Almendros, Isaac

    2017-01-01

    We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.

  14. Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea.

    Directory of Open Access Journals (Sweden)

    Antoni Vilaseca

    Full Text Available We investigate the effects of intermittent hypoxia (IH, a characteristic feature of obstructive sleep apnea (OSA, on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50 of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001 and circulating VEGF (p<0.001 in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.

  15. Concurrent Longitudinal EPR Monitoring of Tissue Oxygenation, Acidosis, and Reducing Capacity in Mouse Xenograft Tumor Models.

    Science.gov (United States)

    Bobko, Andrey A; Evans, Jason; Denko, Nicholas C; Khramtsov, Valery V

    2017-06-01

    Tissue oxygenation, extracellular acidity, and tissue reducing capacity are among crucial parameters of tumor microenvironment (TME) of significant importance for tumor pathophysiology. In this paper, we demonstrate the complementary application of particulate lithium octa-n-butoxy-naphthalocyanine and soluble nitroxide paramagnetic probes for monitoring of these TME parameters using electron paramagnetic resonance (EPR) technique. Two different types of therapeutic interventions were studied: hypothermia and systemic administration of metabolically active drug. In summary, the results demonstrate the utility of EPR technique for non-invasive concurrent longitudinal monitoring of physiologically relevant chemical parameters of TME in mouse xenograft tumor models, including that under therapeutic intervention.

  16. Biological models in vivo for boron neutronic capture studies as tumors therapy

    International Nuclear Information System (INIS)

    Kreimann, Erica L.; Dagrosa, Maria A.; Schwint, Amanda E.; Itoiz, Maria E.; Pisarev, Mario A.; Farias, Silvia S.; Garavaglia, Ricardo N.; Batistoni, Daniel A.

    1999-01-01

    The use of experimental models for Boron Neutronic Capture studies as Tumors Therapy have as two main objectives: 1) To contribute to the basic knowledge of the biological mechanisms involved to increase the method therapeutical advantage, and 2) To explore the possible application of this therapeutic method to other pathologies. In this frame it was studied the carcinogenesis model of hamster cheek pouch, a type of human buccal cancer. Biodistribution studies of boron compound were performed in tumor, blood and in different precancerous and normal tissues as well as BNCT studies. Results validated this method for BNCT studies and show the capacity of the oral mucosa tumors of selectively concentrate the boron compound, showing a deleterious clear effect on the tumor after 24 hours with BNCT treatment. (author)

  17. Adsorption induced losses in interfacial cohesion

    International Nuclear Information System (INIS)

    Asaro, R.J.

    1977-07-01

    A model for interfacial cohesion is developed which describes the loss in the strength of an interface due to the segregation and adsorption of impurities on it. Distinctions are made between interface separations that occur too rapidly for any significant redistribution of adsorbing matter to take place and separations that are slow enough to allow full adsorption equilibrium. Expressions for the total work of complete decohesion are presented for both cases. The results are applied to well-known model adsorption isotherms and some experimental data for grain boundary adsorption of phosphorus in iron is analyzed with respect to the losses in intergranular cohesion

  18. Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy

    International Nuclear Information System (INIS)

    Goodman, J.H.; McGregor, J.M.; Clendenon, N.R.; Gahbauer, R.A.; Barth, R.F.; Soloway, A.H.; Fairchild, R.G.

    1990-01-01

    This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity

  19. Impact of MR-guided boiling histotripsy in distinct murine tumor models.

    Science.gov (United States)

    Hoogenboom, Martijn; Eikelenboom, Dylan C; van den Bijgaart, Renske J E; Heerschap, Arend; Wesseling, Pieter; den Brok, Martijn H; Fütterer, Jurgen J; Adema, Gosse J

    2017-09-01

    Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft tissue into submicron fragments with limited temperature increase using the shock wave and cavitation effects of HIFU. Research on BH has been largely limited to ex vivo experiments. As a consequence, the in vivo pathology after BH treatment and the relation to preexistent tissue characteristics are not well understood. This study reports on in vivo MR guided BH treatment, either with 100 or 200 pulses per focal spot, in three different subcutaneous mouse tumor models: a soft-tissue melanoma (B16OVA), a compact growing thymoma (EL4), and a highly vascularized neuroblastoma (9464D). Extensive treatment evaluation was performed using MR imaging followed by histopathology 2h after treatment. T2 weighted MRI allowed direct in vivo visualization of the BH lesions in all tumor models. The 100-pulse treated area in the B16OVA tumors was larger than the predicted treatment volume (500±10%). For the more compact growing EL4 and 9464D tumors this was 95±13% and 55±33%, respectively. Histopathology after the 100-pulse treatment revealed completely disintegrated lesions in the treated area with sharp borders in the compact EL4 and 9464D tumors, while for B16OVA tumors the lesion contained a mixture of discohesive (partly viable) clusters of cells, micro-vessel remainings, and tumor cell debris. The treatment of B16OVA with 200 pulses increased the fragmentation of tumor tissue. In all tumor types only micro-hemorrhages were detected after ablation (slightly higher after 200-pulse treatment for the highly vascularized 9464D tumors). Collagen staining revealed that the collagen fibers were to a greater or lesser extent still intact and partly clotted together near the lesion border in all tumor models. In conclusion, this study reveals effective mechanical fragmentation of different tumor types using BH without

  20. Detection of high GS risk group prostate tumors by diffusion tensor imaging and logistic regression modelling.

    Science.gov (United States)

    Ertas, Gokhan

    2018-07-01

    To assess the value of joint evaluation of diffusion tensor imaging (DTI) measures by using logistic regression modelling to detect high GS risk group prostate tumors. Fifty tumors imaged using DTI on a 3 T MRI device were analyzed. Regions of interests focusing on the center of tumor foci and noncancerous tissue on the maps of mean diffusivity (MD) and fractional anisotropy (FA) were used to extract the minimum, the maximum and the mean measures. Measure ratio was computed by dividing tumor measure by noncancerous tissue measure. Logistic regression models were fitted for all possible pair combinations of the measures using 5-fold cross validation. Systematic differences are present for all MD measures and also for all FA measures in distinguishing the high risk tumors [GS ≥ 7(4 + 3)] from the low risk tumors [GS ≤ 7(3 + 4)] (P Logistic regression modelling provides a favorable solution for the joint evaluations easily adoptable in clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

    Directory of Open Access Journals (Sweden)

    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  2. Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters.

    Science.gov (United States)

    Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

    2015-11-21

    Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney-Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney-Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney-Rivlin material model along left-right, anterior-posterior, and superior-inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation.

  3. Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters

    International Nuclear Information System (INIS)

    Tehrani, Joubin Nasehi; Wang, Jing; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu

    2015-01-01

    Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney–Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney–Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney–Rivlin material model along left-right, anterior–posterior, and superior–inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation. (paper)

  4. Integration of Oncogenes via Sleeping Beauty as a Mouse Model of HPV16+ Oral Tumors and Immunologic Control.

    Science.gov (United States)

    Lin, Yi-Hsin; Yang, Ming-Chieh; Tseng, Ssu-Hsueh; Jiang, Rosie; Yang, Andrew; Farmer, Emily; Peng, Shiwen; Henkle, Talia; Chang, Yung-Nien; Hung, Chien-Fu; Wu, T-C

    2018-01-23

    Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors. However, the rate of tumor formation is inconsistent, and the host often develops immune tolerance to the viral oncoproteins. We developed a preclinical, spontaneous, HPV16 + buccal tumor model using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRas G12V , luciferase, and sleeping beauty (SB) transposase, followed by electroporation in the buccal mucosa. We evaluated responses to immunization with a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRas G12V , luciferase, and SB transposase developed tumors within 3 weeks. We also found transient anti-CD3 administration is required to generate tumors in immunocompetent mice. Bioluminescence signals from luciferase correlated strongly with tumor growth, and tumors expressed HPV16-associated markers. We showed that pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor-bearing mice. Lastly, we demonstrated that the generated tumor could migrate to tumor-draining lymph nodes. Our model provides an efficient method to induce spontaneous HPV + tumor formation, which can be used to identify effective therapeutic interventions, analyze tumor migration, and conduct tumor biology research. Cancer Immunol Res; 6(3); 1-15. ©2018 AACR. ©2018 American Association for Cancer Research.

  5. Perfusion of tumor-bearing kidneys as a model for scintigraphic screening of monoclonal antibodies

    International Nuclear Information System (INIS)

    van Dijk, J.; Oosterwijk, E.; van Kroonenburgh, M.J.; Jonas, U.; Fleuren, G.J.; Pauwels, E.K.; Warnaar, S.O.

    1988-01-01

    Tumor-bearing human kidneys were used in an ex vivo perfusion model to screen monoclonal antibodies, recognizing renal cell carcinoma-associated antigens for diagnostic potential in vivo. Perfusion of tumor-bearing kidneys with /sup 99m/Tc-labeled G250 and RC38 antibody resulted in visualization of the tumor, whereas perfusion with two other monoclonal antibodies, RC2 and RC4, did not lead to tumor visualization. Uptake of radiolabel in normal kidney tissue was low for G250 and RC38 antibody. Tumor-to-kidney tissue ratios after perfusion with G250 and RC38 antibody were 2.7 and 2.2, respectively. After rinsing for 3 hr with unlabeled perfusion fluid the tumor-to-kidney tissue ratios increased to 8.6 for G250 antibody and to 2.7 for RC38 antibody. We conclude that perfusion of tumor-bearing human kidneys with radiolabeled monoclonal antibodies is a relatively simple way to evaluate renal cell carcinoma associated monoclonal antibodies as diagnostic agents in vivo

  6. White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

    Science.gov (United States)

    Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

    2010-01-01

    The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

  7. Uncertainty analysis of an interfacial area reconstruction algorithm and its application to two group interfacial area transport equation validation

    International Nuclear Information System (INIS)

    Dave, A.J.; Manera, A.; Beyer, M.; Lucas, D.; Prasser, H.-M.

    2016-01-01

    Wire mesh sensors (WMS) are state of the art devices that allow high resolution (in space and time) measurement of 2D void fraction distribution over a wide range of two-phase flow regimes, from bubbly to annular. Data using WMS have been recorded at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Lucas et al., 2010; Beyer et al., 2008; Prasser et al., 2003) for a wide combination of superficial gas and liquid velocities, providing an excellent database for advances in two-phase flow modeling. In two-phase flow, the interfacial area plays an integral role in coupling the mass, momentum and energy transport equations of the liquid and gas phase. While current models used in best-estimate thermal-hydraulic codes (e.g. RELAP5, TRACE, TRACG, etc.) are still based on algebraic correlations for the estimation of the interfacial area in different flow regimes, interfacial area transport equations (IATE) have been proposed to predict the dynamic propagation in space and time of interfacial area (Ishii and Hibiki, 2010). IATE models are still under development and the HZDR WMS experimental data provide an excellent basis for the validation and further advance of these models. The current paper is focused on the uncertainty analysis of algorithms used to reconstruct interfacial area densities from the void-fraction voxel data measured using WMS and their application towards validation efforts of two-group IATE models. In previous research efforts, a surface triangularization algorithm has been developed in order to estimate the surface area of individual bubbles recorded with the WMS, and estimate the interfacial area in the given flow condition. In the present paper, synthetically generated bubbles are used to assess the algorithm’s accuracy. As the interfacial area of the synthetic bubbles are defined by user inputs, the error introduced by the algorithm can be quantitatively obtained. The accuracy of interfacial area measurements is characterized for different bubbles

  8. Uncertainty analysis of an interfacial area reconstruction algorithm and its application to two group interfacial area transport equation validation

    Energy Technology Data Exchange (ETDEWEB)

    Dave, A.J., E-mail: akshayjd@umich.edu [Department of Nuclear Engineering and Rad. Sciences, University of Michigan, Ann Arbor, MI 48105 (United States); Manera, A. [Department of Nuclear Engineering and Rad. Sciences, University of Michigan, Ann Arbor, MI 48105 (United States); Beyer, M.; Lucas, D. [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Fluid Dynamics, 01314 Dresden (Germany); Prasser, H.-M. [Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich (Switzerland)

    2016-12-15

    Wire mesh sensors (WMS) are state of the art devices that allow high resolution (in space and time) measurement of 2D void fraction distribution over a wide range of two-phase flow regimes, from bubbly to annular. Data using WMS have been recorded at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Lucas et al., 2010; Beyer et al., 2008; Prasser et al., 2003) for a wide combination of superficial gas and liquid velocities, providing an excellent database for advances in two-phase flow modeling. In two-phase flow, the interfacial area plays an integral role in coupling the mass, momentum and energy transport equations of the liquid and gas phase. While current models used in best-estimate thermal-hydraulic codes (e.g. RELAP5, TRACE, TRACG, etc.) are still based on algebraic correlations for the estimation of the interfacial area in different flow regimes, interfacial area transport equations (IATE) have been proposed to predict the dynamic propagation in space and time of interfacial area (Ishii and Hibiki, 2010). IATE models are still under development and the HZDR WMS experimental data provide an excellent basis for the validation and further advance of these models. The current paper is focused on the uncertainty analysis of algorithms used to reconstruct interfacial area densities from the void-fraction voxel data measured using WMS and their application towards validation efforts of two-group IATE models. In previous research efforts, a surface triangularization algorithm has been developed in order to estimate the surface area of individual bubbles recorded with the WMS, and estimate the interfacial area in the given flow condition. In the present paper, synthetically generated bubbles are used to assess the algorithm’s accuracy. As the interfacial area of the synthetic bubbles are defined by user inputs, the error introduced by the algorithm can be quantitatively obtained. The accuracy of interfacial area measurements is characterized for different bubbles

  9. State-Dependent Impulsive Control Strategies for a Tumor-Immune Model

    Directory of Open Access Journals (Sweden)

    Kwang Su Kim

    2016-01-01

    Full Text Available Controlling the number of tumor cells leads us to expect more efficient strategies for treatment of tumor. Towards this goal, a tumor-immune model with state-dependent impulsive treatments is established. This model may give an efficient treatment schedule to control tumor’s abnormal growth. By using the Poincaré map and analogue of Poincaré criterion, some conditions for the existence and stability of a positive order-1 periodic solution of this model are obtained. Moreover, we carry out numerical simulations to illustrate the feasibility of our main results and compare fixed-time impulsive treatment effects with state-dependent impulsive treatment effects. The results of our simulations say that, in determining optimal treatment timing, the model with state-dependent impulsive control is more efficient than that with fixed-time impulsive control.

  10. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior

    Directory of Open Access Journals (Sweden)

    Milcah C. Scott

    2016-12-01

    Full Text Available Osteosarcoma (OS is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2 for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of

  11. Novel mouse model for simulating microsurgical tumor excision with facial nerve preservation.

    Science.gov (United States)

    Lim, Jae H; Boyle, Glen M; Panizza, Benedict

    2016-01-01

    To determine the feasibility of using a mouse tumor model as a microsurgical training tool for otolaryngology-head and neck surgery (OHNS) trainees. Animal study. We injected athymic nude mice with human cutaneous squamous cell carcinoma (A431 cell line) deep to the parotid region overlying the masseter muscle. We sacrificed the animals 1 to 3 weeks postinjection, once a visible tumor growth was confirmed. We then asked 10 OHNS trainees to excise the tumor with preservation of the facial nerves under a high-magnification dissecting microscope. The trainees graded the tasks in several areas of specific measures using a visual analogue scale (VAS) including 1) tumor texture, 2) surgical realism, 3) usefulness, and 4) difficulty of the task. Noticeable tumor growth occurred within 5 days following A431 cell injection and reached measureable size (0.5-1.5 cm) within 1 to 3 weeks. The tumor displaced the facial nerve laterally and medially, with few demonstrating infiltration of the nerve. VAS scores (± standard deviation) were 8.1 (± 1.7), 7.7 (± 2.5), 9.0 (± 0.9) and 6.6 (± 1.9) for tumor texture, surgical realism, usefulness, and the difficulty of the task, respectively. We demonstrate a novel, reliable and cost-effective mouse model for simulating tumor extirpation microsurgery with preservation of important neural structures. OHNS trainees have found this simulation model to be realistic, useful, and appropriately challenging. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior.

    Science.gov (United States)

    Scott, Milcah C; Tomiyasu, Hirotaka; Garbe, John R; Cornax, Ingrid; Amaya, Clarissa; O'Sullivan, M Gerard; Subramanian, Subbaya; Bryan, Brad A; Modiano, Jaime F

    2016-12-01

    Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2) for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of OS. © 2016

  13. WE-E-17A-01: Characterization of An Imaging-Based Model of Tumor Angiogenesis

    International Nuclear Information System (INIS)

    Adhikarla, V; Jeraj, R

    2014-01-01

    Purpose: Understanding the transient dynamics of tumor oxygenation is important when evaluating tumor-vasculature response to anti-angiogenic therapies. An imaging-based tumor-vasculature model was used to elucidate factors that affect these dynamics. Methods: Tumor growth depends on its doubling time (Td). Hypoxia increases pro-angiogenic factor (VEGF) concentration which is modeled to reduce vessel perfusion, attributing to its effect of increasing vascular permeability. Perfused vessel recruitment depends on the existing perfused vasculature, VEGF concentration and maximum VEGF concentration (VEGFmax) for vessel dysfunction. A convolution-based algorithm couples the tumor to the normal tissue vessel density (VD-nt). The parameters are benchmarked to published pre-clinical data and a sensitivity study evaluating the changes in the peak and time to peak tumor oxygenation characterizes them. The model is used to simulate changes in hypoxia and proliferation PET imaging data obtained using [Cu- 61]Cu-ATSM and [F-18]FLT respectively. Results: Td and VD-nt were found to be the most influential on peak tumor pO2 while VEGFmax was marginally influential. A +20 % change in Td, VD-nt and VEGFmax resulted in +50%, +25% and +5% increase in peak pO2. In contrast, Td was the most influential on the time to peak oxygenation with VD-nt and VEGFmax playing marginal roles. A +20% change in Td, VD-nt and VEGFmax increased the time to peak pO2 by +50%, +5% and +0%. A −20% change in the above parameters resulted in comparable decreases in the peak and time to peak pO2. Model application to the PET data was able to demonstrate the voxel-specific changes in hypoxia of the imaged tumor. Conclusion: Tumor-specific doubling time and vessel density are important parameters to be considered when evaluating hypoxia transients. While the current model simulates the oxygen dynamics of an untreated tumor, incorporation of therapeutic effects can make the model a potent tool for analyzing

  14. Visualization of Tumor Angiogenesis Using MR Imaging Contrast Agent Gd-DTPA-anti-VEGF Receptor 2 Antibody Conjugate in a Mouse Tumor Model

    International Nuclear Information System (INIS)

    Jun, Hong Young; Yin, Hong Hua; Kim, Sun Hee; Park, Seong Hoon; Kim, Hun Soo; Yoon Kwon Ha Yoon

    2010-01-01

    To visualize tumor angiogenesis using the MRI contrast agent, Gd- DTPA-anti-VEGF receptor 2 antibody conjugate, with a 4.7-Tesla MRI instrument in a mouse model. We designed a tumor angiogenesis-targeting T1 contrast agent that was prepared by the bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and an anti-vascular endothelial growth factor receptor-2 (VEGFR2) antibody. The specific binding of the agent complex to cells that express VEGFR2 was examined in cultured murine endothelial cells (MS-1 cells) with a 4.7-Tesla magnetic resonance imaging scanner. Angiogenesis-specific T1 enhancement was imaged with the Gd-DTPA-anti-VEGFR2 antibody conjugate using a CT-26 adenocarcinoma tumor model in eight mice. As a control, the use of the Gd-DTPA-anti-rat immunoglobulin G (Gd-DTPA-anti-rat IgG) was imaged with a tumor model in eight mice. Statistical significance was assessed using the Mann-Whitney test. Tumor tissue was examined by immunohistochemical analysis. The Gd-DTPA-anti-VEGFR2 antibody conjugate showed predominant binding to cultured endothelial cells that expressed a high level of VEGFR2. Signal enhancement was approximately three-fold for in vivo T1-weighted MR imaging with the use of the Gd-DTPA-anti-VEGFR2 antibody conjugate as compared with the Gd-DTPA-rat IgG in the mouse tumor model (p < 0.05). VEGFR2 expression in CT-26 tumor vessels was demonstrated using immunohistochemical staining. MR imaging using the Gd-DTPA-anti-VEGFR2 antibody conjugate as a contrast agent is useful in visualizing noninvasively tumor angiogenesis in a murine tumor model

  15. Visualization of Tumor Angiogenesis Using MR Imaging Contrast Agent Gd-DTPA-anti-VEGF Receptor 2 Antibody Conjugate in a Mouse Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Hong Young; Yin, Hong Hua; Kim, Sun Hee; Park, Seong Hoon; Kim, Hun Soo; Yoon Kwon Ha Yoon [Wonkwang University School of Medicine, Iksan (Korea, Republic of)

    2010-08-15

    To visualize tumor angiogenesis using the MRI contrast agent, Gd- DTPA-anti-VEGF receptor 2 antibody conjugate, with a 4.7-Tesla MRI instrument in a mouse model. We designed a tumor angiogenesis-targeting T1 contrast agent that was prepared by the bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and an anti-vascular endothelial growth factor receptor-2 (VEGFR2) antibody. The specific binding of the agent complex to cells that express VEGFR2 was examined in cultured murine endothelial cells (MS-1 cells) with a 4.7-Tesla magnetic resonance imaging scanner. Angiogenesis-specific T1 enhancement was imaged with the Gd-DTPA-anti-VEGFR2 antibody conjugate using a CT-26 adenocarcinoma tumor model in eight mice. As a control, the use of the Gd-DTPA-anti-rat immunoglobulin G (Gd-DTPA-anti-rat IgG) was imaged with a tumor model in eight mice. Statistical significance was assessed using the Mann-Whitney test. Tumor tissue was examined by immunohistochemical analysis. The Gd-DTPA-anti-VEGFR2 antibody conjugate showed predominant binding to cultured endothelial cells that expressed a high level of VEGFR2. Signal enhancement was approximately three-fold for in vivo T1-weighted MR imaging with the use of the Gd-DTPA-anti-VEGFR2 antibody conjugate as compared with the Gd-DTPA-rat IgG in the mouse tumor model (p < 0.05). VEGFR2 expression in CT-26 tumor vessels was demonstrated using immunohistochemical staining. MR imaging using the Gd-DTPA-anti-VEGFR2 antibody conjugate as a contrast agent is useful in visualizing noninvasively tumor angiogenesis in a murine tumor model

  16. Continuous Release of Tumor-Derived Factors Improves the Modeling of Cachexia in Muscle Cell Culture

    Directory of Open Access Journals (Sweden)

    Robert W. Jackman

    2017-09-01

    Full Text Available Cachexia is strongly associated with a poor prognosis in cancer patients but the biological trigger is unknown and therefore no therapeutics exist. The loss of skeletal muscle is the most deleterious aspect of cachexia and it appears to depend on secretions from tumor cells. Models for studying wasting in cell culture consist of experiments where skeletal muscle cells are incubated with medium conditioned by tumor cells. This has led to candidates for cachectic factors but some of the features of cachexia in vivo are not yet well-modeled in cell culture experiments. Mouse myotube atrophy measured by myotube diameter in response to medium conditioned by mouse colon carcinoma cells (C26 is consistently less than what is seen in muscles of mice bearing C26 tumors with moderate to severe cachexia. One possible reason for this discrepancy is that in vivo the C26 tumor and skeletal muscle share a circulatory system exposing the muscle to tumor factors in a constant and increasing way. We have applied Transwell®-adapted cell culture conditions to more closely simulate conditions found in vivo where muscle is exposed to the ongoing kinetics of constant tumor secretion of active factors. C26 cells were incubated on a microporous membrane (a Transwell® insert that constitutes the upper compartment of wells containing plated myotubes. In this model, myotubes are exposed to a constant supply of cancer cell secretions in the medium but without direct contact with the cancer cells, analogous to a shared circulation of muscle and cancer cells in tumor-bearing animals. The results for myotube diameter support the idea that the use of Transwell® inserts serves as a more physiological model of the muscle wasting associated with cancer cachexia than the bolus addition of cancer cell conditioned medium. The Transwell® model supports the notion that the dose and kinetics of cachectic factor delivery to muscle play a significant role in the extent of pathology.

  17. Interfacial characteristics of hybrid nanocomposite under thermomechanical loading

    Science.gov (United States)

    Choyal, Vijay; Kundalwal, Shailesh I.

    2017-12-01

    In this work, an improved shear lag model was developed to investigate the interfacial characteristics of three-phase hybrid nanocomposite which is reinforced with microscale fibers augmented with carbon nanotubes on their circumferential surfaces. The shear lag model accounts for (i) radial and axial deformations of different transversely isotropic constituents, (ii) thermomechanical loads on the representative volume element (RVE), and (iii) staggering effect of adjacent RVEs. The results from the current newly developed shear lag model are validated with the finite element simulations and found to be in good agreement. This study reveals that the reduction in the maximum value of the axial stress in the fiber and the interfacial shear stress along its length become more pronounced in the presence of applied thermomechanical loads on the staggered RVEs. The existence of shear tractions along the RVE length plays a significant role in the interfacial characteristics and cannot be ignored.

  18. Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.

    Science.gov (United States)

    Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang

    2016-12-01

    Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

  19. ¹H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors.

    Science.gov (United States)

    Hulsey, Keith M; Mashimo, Tomoyuki; Banerjee, Abhishek; Soesbe, Todd C; Spence, Jeffrey S; Vemireddy, Vamsidhara; Maher, Elizabeth A; Bachoo, Robert M; Choi, Changho

    2015-01-01

    Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used (1) H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N-acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models

    International Nuclear Information System (INIS)

    Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

    2010-01-01

    Purpose: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Methods and Materials: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. Results: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. Conclusions: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

  1. A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

    Directory of Open Access Journals (Sweden)

    Chantal Scheepbouwer

    Full Text Available Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics.

  2. The Pig as a Large Animal Model for Studying Anti-Tumor Immune Responses

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr

    but also generates a selective pressure, which may lead to selection of tumor cell variants with reduced immunogenicity; thereby, increasing the risk of tumor escape. Cancer immunotherapy includes treatment strategies aimed at activating anti-tumor immune responses or inhibiting suppressive and tumor......-favorable immune mechanisms. One of the promising arms of cancer immunotherapy is peptide-based therapeutic vaccines; yet, no such vaccine has been approved for use in human oncology. For many years, mouse models have provided invaluable understanding of complex immunological pathways; however, the majority...... tolerance towards IDO and the establishment of an antigen-specific cell-mediated immune (CMI) response. When comparing the different CAF09-formulated antigen doses, we demonstrate the induction of a CMI-dominant response upon exposure to a low endogenous peptide dose. In contrast, a mixed CMI and humoral...

  3. Fluctuations induced extinction and stochastic resonance effect in a model of tumor growth with periodic treatment

    Energy Technology Data Exchange (ETDEWEB)

    Li Dongxi, E-mail: lidongxi@mail.nwpu.edu.c [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an 710072 (China); Xu Wei; Guo, Yongfeng; Xu Yong [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an 710072 (China)

    2011-01-31

    We investigate a stochastic model of tumor growth derived from the catalytic Michaelis-Menten reaction with positional and environmental fluctuations under subthreshold periodic treatment. Firstly, the influences of environmental fluctuations on the treatable stage are analyzed numerically. Applying the standard theory of stochastic resonance derived from the two-state approach, we derive the signal-to-noise ratio (SNR) analytically, which is used to measure the stochastic resonance phenomenon. It is found that the weak environmental fluctuations could induce the extinction of tumor cells in the subthreshold periodic treatment. The positional stability is better in favor of the treatment of the tumor cells. Besides, the appropriate and feasible treatment intensity and the treatment cycle should be highlighted considered in the treatment of tumor cells.

  4. Fluctuations induced extinction and stochastic resonance effect in a model of tumor growth with periodic treatment

    International Nuclear Information System (INIS)

    Li Dongxi; Xu Wei; Guo, Yongfeng; Xu Yong

    2011-01-01

    We investigate a stochastic model of tumor growth derived from the catalytic Michaelis-Menten reaction with positional and environmental fluctuations under subthreshold periodic treatment. Firstly, the influences of environmental fluctuations on the treatable stage are analyzed numerically. Applying the standard theory of stochastic resonance derived from the two-state approach, we derive the signal-to-noise ratio (SNR) analytically, which is used to measure the stochastic resonance phenomenon. It is found that the weak environmental fluctuations could induce the extinction of tumor cells in the subthreshold periodic treatment. The positional stability is better in favor of the treatment of the tumor cells. Besides, the appropriate and feasible treatment intensity and the treatment cycle should be highlighted considered in the treatment of tumor cells.

  5. Perfusion kinetics in human brain tumor with DCE-MRI derived model and CFD analysis.

    Science.gov (United States)

    Bhandari, A; Bansal, A; Singh, A; Sinha, N

    2017-07-05

    Cancer is one of the leading causes of death all over the world. Among the strategies that are used for cancer treatment, the effectiveness of chemotherapy is often hindered by factors such as irregular and non-uniform uptake of drugs inside tumor. Thus, accurate prediction of drug transport and deposition inside tumor is crucial for increasing the effectiveness of chemotherapeutic treatment. In this study, a computational model of human brain tumor is developed that incorporates dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data into a voxelized porous media model. The model takes into account realistic transport and perfusion kinetics parameters together with realistic heterogeneous tumor vasculature and accurate arterial input function (AIF), which makes it patient specific. The computational results for interstitial fluid pressure (IFP), interstitial fluid velocity (IFV) and tracer concentration show good agreement with the experimental results. The computational model can be extended further for predicting the deposition of chemotherapeutic drugs in tumor environment as well as selection of the best chemotherapeutic drug for a specific patient. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Image-based modeling of tumor shrinkage in head and neck radiation therapy1

    Science.gov (United States)

    Chao, Ming; Xie, Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing, Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the “ground truth” with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy. PMID:20527569

  7. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    International Nuclear Information System (INIS)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  8. In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

    Science.gov (United States)

    Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

    2017-09-01

    Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  9. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei [Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 and Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States); Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States)

    2010-05-15

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  10. MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

    Directory of Open Access Journals (Sweden)

    Ali H Zaidi

    Full Text Available To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC.The incidence of esophageal adenocarcinoma (EAC has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies.The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5 and metastasis negative (n=28 primary tumors.The epithelial origin of distant metastasis was established by IF using villin (VIL1 and mucin 5AC (MUC5AC antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001, miR-141-3p (p=0.0022, miR-451-1a (p=0.0181 and miR133a-3p (p=0.0304. Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2.In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.

  11. Ultimate dynamics of the Kirschner-Panetta model: Tumor eradication and related problems

    Science.gov (United States)

    Starkov, Konstantin E.; Krishchenko, Alexander P.

    2017-10-01

    In this paper we consider the ultimate dynamics of the Kirschner-Panetta model which was created for studying the immune response to tumors under special types of immunotherapy. New ultimate upper bounds for compact invariant sets of this model are given, as well as sufficient conditions for the existence of a positively invariant polytope. We establish three types of conditions for the nonexistence of compact invariant sets in the domain of the tumor-cell population. Our main results are two types of conditions for global tumor elimination depending on the ratio between the proliferation rate of the immune cells and their mortality rate. These conditions are described in terms of simple algebraic inequalities imposed on model parameters and treatment parameters. Our theoretical studies of ultimate dynamics are complemented by numerical simulation results.

  12. Solid tumor models for the assessment of different treatment modalities. XIV. The evaluation of host and tumor response to cyclophosphamide and radiation

    International Nuclear Information System (INIS)

    Looney, W.B.; Hopkins, H.A.; MacLeod, M.S.; Ritenour, E.R.

    1979-01-01

    The effect of increasing doses of cyclophosphamide (50 to 250 mg/kg) on the time of occurrence of maximal and minimal tumor growth rates, tumor volume reduction, and linear doubling times (LDT) on the solid tumor model H-4-II-E has been determined. Tumor response to cyclophosphamide was classified as class I, tumor regression; class II, pseudo-regression; and class III, slow-down. The overall treatment efficiency (OTE) has been used to assess the magnitude of tumor volume changes after treatment. The maximum OTE occurred after 150 mg/kg of cyclophosphamide. Increasing the dose to 200 and 250 mg/kg of cyclophosphamide resulted in a decrease in OTE. Similar parameters were utilized to measure the effectiveness of increasing doses of local tumor radiation (750, 1500, 2000, 2500, 3000 and 3500R). The major increase in OTE occurs when the radiation dose is increased from 750R to 2000R. Increasing the dose further to 3500R results in smaller incremental increases in the OTE. Results of the study indicate that increasing the cyclophosphamide dose beyond a certain level (i.e., 150 mg/kg) increases mortality and morbidity without concomitant therapeutic benefit. The effects of increasing the dose of local tumor radiation on life span have given results which suggest that increasing the total radiation dose beyond a certain limit is less effective in increasing life span

  13. Interfacial and Surface Science | Materials Science | NREL

    Science.gov (United States)

    Science group within the Material Science Center. He oversees research studies of surfaces and interfaces Interfacial and Surface Science Interfacial and Surface Science Image of irregular-outlined, light address a broad range of fundamental and applied issues in surface and interfacial science that are

  14. Dentin-cement Interfacial Interaction

    Science.gov (United States)

    Atmeh, A.R.; Chong, E.Z.; Richard, G.; Festy, F.; Watson, T.F.

    2012-01-01

    The interfacial properties of a new calcium-silicate-based coronal restorative material (Biodentine™) and a glass-ionomer cement (GIC) with dentin have been studied by confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), micro-Raman spectroscopy, and two-photon auto-fluorescence and second-harmonic-generation (SHG) imaging. Results indicate the formation of tag-like structures alongside an interfacial layer called the “mineral infiltration zone”, where the alkaline caustic effect of the calcium silicate cement’s hydration products degrades the collagenous component of the interfacial dentin. This degradation leads to the formation of a porous structure which facilitates the permeation of high concentrations of Ca2+, OH-, and CO32- ions, leading to increased mineralization in this region. Comparison of the dentin-restorative interfaces shows that there is a dentin-mineral infiltration with the Biodentine, whereas polyacrylic and tartaric acids and their salts characterize the penetration of the GIC. A new type of interfacial interaction, “the mineral infiltration zone”, is suggested for these calcium-silicate-based cements. PMID:22436906

  15. Interfacial behaviour of biopolymer multilayers

    NARCIS (Netherlands)

    Corstens, Meinou N.; Osorio Caltenco, Lilia A.; Vries, de Renko; Schroën, Karin; Berton-Carabin, Claire C.

    2017-01-01

    Although multilayered emulsions have been related to reduced lipolysis, the involved interfacial phenomena have never been studied directly. In this work, we systematically built multilayers of whey protein and pectin, which we further subjected to digestive conditions, using two different

  16. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

    2017-01-01

    Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

  17. Oxygen distribution in tumors: A qualitative analysis and modeling study providing a novel Monte Carlo approach

    International Nuclear Information System (INIS)

    Lagerlöf, Jakob H.; Kindblom, Jon; Bernhardt, Peter

    2014-01-01

    Purpose: To construct a Monte Carlo (MC)-based simulation model for analyzing the dependence of tumor oxygen distribution on different variables related to tumor vasculature [blood velocity, vessel-to-vessel proximity (vessel proximity), and inflowing oxygen partial pressure (pO 2 )]. Methods: A voxel-based tissue model containing parallel capillaries with square cross-sections (sides of 10 μm) was constructed. Green's function was used for diffusion calculations and Michaelis-Menten's kinetics to manage oxygen consumption. The model was tuned to approximately reproduce the oxygenational status of a renal carcinoma; the depth oxygenation curves (DOC) were fitted with an analytical expression to facilitate rapid MC simulations of tumor oxygen distribution. DOCs were simulated with three variables at three settings each (blood velocity, vessel proximity, and inflowing pO 2 ), which resulted in 27 combinations of conditions. To create a model that simulated variable oxygen distributions, the oxygen tension at a specific point was randomly sampled with trilinear interpolation in the dataset from the first simulation. Six correlations between blood velocity, vessel proximity, and inflowing pO 2 were hypothesized. Variable models with correlated parameters were compared to each other and to a nonvariable, DOC-based model to evaluate the differences in simulated oxygen distributions and tumor radiosensitivities for different tumor sizes. Results: For tumors with radii ranging from 5 to 30 mm, the nonvariable DOC model tended to generate normal or log-normal oxygen distributions, with a cut-off at zero. The pO 2 distributions simulated with the six-variable DOC models were quite different from the distributions generated with the nonvariable DOC model; in the former case the variable models simulated oxygen distributions that were more similar to in vivo results found in the literature. For larger tumors, the oxygen distributions became truncated in the lower

  18. Predicting oropharyngeal tumor volume throughout the course of radiation therapy from pretreatment computed tomography data using general linear models.

    Science.gov (United States)

    Yock, Adam D; Rao, Arvind; Dong, Lei; Beadle, Beth M; Garden, Adam S; Kudchadker, Rajat J; Court, Laurence E

    2014-05-01

    The purpose of this work was to develop and evaluate the accuracy of several predictive models of variation in tumor volume throughout the course of radiation therapy. Nineteen patients with oropharyngeal cancers were imaged daily with CT-on-rails for image-guided alignment per an institutional protocol. The daily volumes of 35 tumors in these 19 patients were determined and used to generate (1) a linear model in which tumor volume changed at a constant rate, (2) a general linear model that utilized the power fit relationship between the daily and initial tumor volumes, and (3) a functional general linear model that identified and exploited the primary modes of variation between time series describing the changing tumor volumes. Primary and nodal tumor volumes were examined separately. The accuracy of these models in predicting daily tumor volumes were compared with those of static and linear reference models using leave-one-out cross-validation. In predicting the daily volume of primary tumors, the general linear model and the functional general linear model were more accurate than the static reference model by 9.9% (range: -11.6%-23.8%) and 14.6% (range: -7.3%-27.5%), respectively, and were more accurate than the linear reference model by 14.2% (range: -6.8%-40.3%) and 13.1% (range: -1.5%-52.5%), respectively. In predicting the daily volume of nodal tumors, only the 14.4% (range: -11.1%-20.5%) improvement in accuracy of the functional general linear model compared to the static reference model was statistically significant. A general linear model and a functional general linear model trained on data from a small population of patients can predict the primary tumor volume throughout the course of radiation therapy with greater accuracy than standard reference models. These more accurate models may increase the prognostic value of information about the tumor garnered from pretreatment computed tomography images and facilitate improved treatment management.

  19. Percutaneous radiofrequency ablation of lung tumors in a large animal model.

    Science.gov (United States)

    Ahrar, Kamran; Price, Roger E; Wallace, Michael J; Madoff, David C; Gupta, Sanjay; Morello, Frank A; Wright, Kenneth C

    2003-08-01

    Percutaneous radiofrequency ablation (RFA) is accepted therapy for liver tumors in the appropriate clinical setting, but its use in lung neoplasms remains investigational. We undertook this study to evaluate the feasibility and immediate effectiveness of RFA for treatment of both solitary pulmonary nodules and clusters of lung tumors in a large animal model. Percutaneous RFA of 14 lung tumors in five dogs was performed under CT guidance. Animals were euthanatized 8-48 hours after the procedure. The lungs and adjacent structures were harvested for gross and histopathologic evaluation. Five solitary pulmonary nodules (range, 17-26 mm) and three clusters of three nodules each (range, 7-17 mm per nodule) were treated with RFA. All ablations were technically successful. Perilesional ground-glass opacity and small asymptomatic pneumothoraces (n = 4) were visualized during the RFA sessions. One dog developed a large pneumothorax treated with tube thoracostomy but was euthanatized 8 hours post-RFA for persistent pneumothorax and continued breathing difficulty. Follow-up CT 48 hours post-RFA revealed opacification of the whole lung segment. Gross and histopathologic evaluation showed complete thermal coagulation necrosis of all treated lesions without evidence of any viable tumor. The region of thermal coagulation necrosis typically extended to the lung surface. Small regions of pulmonary hemorrhage and congestion often surrounded the areas of coagulation necrosis. RFA can be used to treat both solitary pulmonary nodules and clusters of tumor nodules in the canine lung tumor model. This model may be useful for development of specific RFA protocols for human lung tumors.

  20. Numerical Simulation of a Tumor Growth Dynamics Model Using Particle Swarm Optimization.

    Science.gov (United States)

    Wang, Zhijun; Wang, Qing

    Tumor cell growth models involve high-dimensional parameter spaces that require computationally tractable methods to solve. To address a proposed tumor growth dynamics mathematical model, an instance of the particle swarm optimization method was implemented to speed up the search process in the multi-dimensional parameter space to find optimal parameter values that fit experimental data from mice cancel cells. The fitness function, which measures the difference between calculated results and experimental data, was minimized in the numerical simulation process. The results and search efficiency of the particle swarm optimization method were compared to those from other evolutional methods such as genetic algorithms.

  1. Solid/liquid interfacial free energies in binary systems

    Science.gov (United States)

    Nason, D.; Tiller, W. A.

    1973-01-01

    Description of a semiquantitative technique for predicting the segregation characteristics of smooth interfaces between binary solid and liquid solutions in terms of readily available thermodynamic parameters of the bulk solutions. A lattice-liquid interfacial model and a pair-bonded regular solution model are employed in the treatment with an accommodation for liquid interfacial entropy. The method is used to calculate the interfacial segregation and the free energy of segregation for solid-liquid interfaces between binary solutions for the (111) boundary of fcc crystals. The zone of compositional transition across the interface is shown to be on the order of a few atomic layers in width, being moderately narrower for ideal solutions. The free energy of the segregated interface depends primarily upon the solid composition and the heats of fusion of the component atoms, the composition difference of the solutions, and the difference of the heats of mixing of the solutions.

  2. First-principles prediction of liquid/liquid interfacial tension

    DEFF Research Database (Denmark)

    Andersson, Martin Peter; Bennetzen, M.V.; Klamt, A.

    2014-01-01

    of groundwater aquifers contaminated by chlorinated solvents to drug delivery and a host of industrial processes. Here, we present a model for predicting interfacial tension from first principles using density functional theory calculations. Our model requires no experimental input and is applicable to liquid...

  3. Anti-tumor effects of 125I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice

    International Nuclear Information System (INIS)

    Xiao Zhongdi; Liang Chunlin; Zhang Guoli; Jing Yue; Zhang Yucheng; Gai Baodong

    2011-01-01

    Objective: To study the anti-tumor effects of 125 I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice and clarify their anti-tumor mechanisms. Methods 120 nude mice transplantated with human breast cancer cells MCF-7 were randomly divided into 3 groups (n=40): 125 I radioactive particles implanted group, non-radioactive particles implanted group and non-particles implanted group. The articles were implanted into mice according to Pairs system principle. The expressions of Fas mRNA and protein and the activaties of caspase-3 and caspase-8 enzyme were detected by RT-PCR and Western blotting. The changes of cell cycle were detected by flow cytometry. Results: Compared with non-radioactive particles implanted group and non-particles implanted group, the size of cancer tissues in 125 I radioactive particles implanted group was reduced significantly (P 0 /G 1 phase was significantly increased (P 125 I radioactive particles into transplantated tumor model of human breast cancer cells can kill tumor cells, inhibit the growth cycle of tumor cells and induce the apoptosis of tumor cells in nude mice. (authors)

  4. Stereoscopic virtual reality models for planning tumor resection in the sellar region

    Directory of Open Access Journals (Sweden)

    Wang Shou-sen

    2012-11-01

    Full Text Available Abstract Background It is difficult for neurosurgeons to perceive the complex three-dimensional anatomical relationships in the sellar region. Methods To investigate the value of using a virtual reality system for planning resection of sellar region tumors. The study included 60 patients with sellar tumors. All patients underwent computed tomography angiography, MRI-T1W1, and contrast enhanced MRI-T1W1 image sequence scanning. The CT and MRI scanning data were collected and then imported into a Dextroscope imaging workstation, a virtual reality system that allows structures to be viewed stereoscopically. During preoperative assessment, typical images for each patient were chosen and printed out for use by the surgeons as references during surgery. Results All sellar tumor models clearly displayed bone, the internal carotid artery, circle of Willis and its branches, the optic nerve and chiasm, ventricular system, tumor, brain, soft tissue and adjacent structures. Depending on the location of the tumors, we simulated the transmononasal sphenoid sinus approach, transpterional approach, and other approaches. Eleven surgeons who used virtual reality models completed a survey questionnaire. Nine of the participants said that the virtual reality images were superior to other images but that other images needed to be used in combination with the virtual reality images. Conclusions The three-dimensional virtual reality models were helpful for individualized planning of surgery in the sellar region. Virtual reality appears to be promising as a valuable tool for sellar region surgery in the future.

  5. Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model.

    Science.gov (United States)

    Pishali Bejestani, Elham; Cartellieri, Marc; Bergmann, Ralf; Ehninger, Armin; Loff, Simon; Kramer, Michael; Spehr, Johannes; Dietrich, Antje; Feldmann, Anja; Albert, Susann; Wermke, Martin; Baumann, Michael; Krause, Mechthild; Bornhäuser, Martin; Ehninger, Gerhard; Bachmann, Michael; von Bonin, Malte

    2017-01-01

    The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model. In addition, we analyzed phenotypic and functional changes of cancer cells and UniCAR-T cells in association with the administration of the targeting module to reveal potential immunoevasive mechanisms. Most notably, UniCAR-T cell activation induced upregulation of immune-inhibitory molecules such as programmed death ligands. In conclusion, this work illustrates that the UniCAR platform mediates potent anti-tumor activity in a relevant in vitro and in vivo solid tumor model.

  6. A preoperative mathematic model for computed tomographic guided microwave ablation treatment of hepatic dome tumors.

    Science.gov (United States)

    Gao, Fei; Wang, Guo-Bao; Xiang, Zhan-Wang; Yang, Bin; Xue, Jing-Bing; Mo, Zhi-Qiang; Zhong, Zhi-Hui; Zhang, Tao; Zhang, Fu-Jun; Fan, Wei-Jun

    2016-05-03

    This study sought to prospectively evaluate the feasibility and safety of a preoperative mathematic model for computed tomographic(CT) guided microwave(MW) ablation treatment of hepatic dome tumors. This mathematic model was a regular cylinder quantifying appropriate puncture routes from the bottom up. A total of 103 patients with hepatic dome tumors were enrolled and randomly divided into 2 groups based on whether this model was used or not: Group A (using the model; n = 43) versus Group B (not using the model; n = 60). All tumors were treated by CT-guided MW ablation and follow-up contrast CT were reviewed. The average number of times for successful puncture, average ablation time, and incidence of right shoulder pain were less in Group A than Group B (1.4 vs. 2.5, P = 0.001; 8.8 vs. 11.1 minutes, P = 0.003; and 4.7% vs. 20%, P = 0.039). The technical success rate was higher in Group A than Group B (97.7% vs. 85.0%, P = 0.032). There were no significant differences between the two groups in primary and secondary technique efficacy rates (97.7% vs. 88.3%, P = 0.081; 90.0% vs. 72.7%, P = 0.314). No major complications occurred in both groups. The mathematic model of regular cylinder is feasible and safe for CT-guided MW ablation in treating hepatic dome tumors.

  7. A tissue-engineered gastric cancer model for mechanistic study of anti-tumor drugs

    International Nuclear Information System (INIS)

    Gao, Ming; Cai, Yiting; Wu, Wei; Shi, Yazhou; Fei, Zhewei

    2013-01-01

    The use of the traditional xenograft subcutaneous tumor model has been contested because of its limitations, such as a slow tumorigenesis, inconsistent chemotherapeutic results, etc. In light of these challenges, we aim to revamp the traditional model by employing an electrospun scaffold composed of polydioxanone, gelatin and elastin to boost the tumorigenesis. The scaffold featured a highly porous microstructure and successfully supported the growth of tumor cells in vitro without provoking apoptosis. In vivo studies showed that in the scaffold model the tumor volume increased by 43.27% and the weight by 75.58%, respectively, within a 12-week period. In addition, the scaffold model saw an increase of CD24 + and CD44 + cells in the tumor mass by 42% and 313%, respectively. The scaffolding materials did not lead to phenotypic changes during the tumorigenesis. Thereafter, in the scaffold model, we found that the chemotherapeutic regimen of docetaxel, cisplatin and fluorouracil unleashed a stronger capability than the regimen comprising cisplatin and fluorouracil to deplete the CD44 + subpopulation. This discovery sheds mechanistic lights on the role of docetaxel for its future chemotherapeutic applications. This revamped model affords cancer scientists a convenient and reliable platform to mechanistically investigate the chemotherapeutic drugs on gastric cancer stem cells. (paper)

  8. Innovative Disease Model: Zebrafish as an In Vivo Platform for Intestinal Disorder and Tumors

    Directory of Open Access Journals (Sweden)

    Jeng-Wei Lu

    2017-09-01

    Full Text Available Colorectal cancer (CRC is one of the world’s most common cancers and is the second leading cause of cancer deaths, causing more than 50,000 estimated deaths each year. Several risk factors are highly associated with CRC, including being overweight, eating a diet high in red meat and over-processed meat, having a history of inflammatory bowel disease, and smoking. Previous zebrafish studies have demonstrated that multiple oncogenes and tumor suppressor genes can be regulated through genetic or epigenetic alterations. Zebrafish research has also revealed that the activation of carcinogenesis-associated signal pathways plays an important role in CRC. The biology of cancer, intestinal disorders caused by carcinogens, and the morphological patterns of tumors have been found to be highly similar between zebrafish and humans. Therefore, the zebrafish has become an important animal model for translational medical research. Several zebrafish models have been developed to elucidate the characteristics of gastrointestinal diseases. This review article focuses on zebrafish models that have been used to study human intestinal disorders and tumors, including models involving mutant and transgenic fish. We also report on xenograft models and chemically-induced enterocolitis. This review demonstrates that excellent zebrafish models can provide novel insights into the pathogenesis of gastrointestinal diseases and help facilitate the evaluation of novel anti-tumor drugs.

  9. Comparison between model-predicted tumor oxygenation dynamics and vascular-/flow-related Doppler indices.

    Science.gov (United States)

    Belfatto, Antonella; Vidal Urbinati, Ailyn M; Ciardo, Delia; Franchi, Dorella; Cattani, Federica; Lazzari, Roberta; Jereczek-Fossa, Barbara A; Orecchia, Roberto; Baroni, Guido; Cerveri, Pietro

    2017-05-01

    Mathematical modeling is a powerful and flexible method to investigate complex phenomena. It discloses the possibility of reproducing expensive as well as invasive experiments in a safe environment with limited costs. This makes it suitable to mimic tumor evolution and response to radiotherapy although the reliability of the results remains an issue. Complexity reduction is therefore a critical aspect in order to be able to compare model outcomes to clinical data. Among the factors affecting treatment efficacy, tumor oxygenation is known to play a key role in radiotherapy response. In this work, we aim at relating the oxygenation dynamics, predicted by a macroscale model trained on tumor volumetric data of uterine cervical cancer patients, to vascularization and blood flux indices assessed on Ultrasound Doppler images. We propose a macroscale model of tumor evolution based on three dynamics, namely active portion, necrotic portion, and oxygenation. The model parameters were assessed on the volume size of seven cervical cancer patients administered with 28 fractions of intensity modulated radiation therapy (IMRT) (1.8 Gy/fraction). For each patient, five Doppler ultrasound tests were acquired before, during, and after the treatment. The lesion was manually contoured by an expert physician using 4D View ® (General Electric Company - Fairfield, Connecticut, United States), which automatically provided the overall tumor volume size along with three vascularization and/or blood flow indices. Volume data only were fed to the model for training purpose, while the predicted oxygenation was compared a posteriori to the measured Doppler indices. The model was able to fit the tumor volume evolution within 8% error (range: 3-8%). A strong correlation between the intrapatient longitudinal indices from Doppler measurements and oxygen predicted by the model (about 90% or above) was found in three cases. Two patients showed an average correlation value (50-70%) and the remaining

  10. Ecto-5'-Nucleotidase Overexpression Reduces Tumor Growth in a Xenograph Medulloblastoma Model.

    Directory of Open Access Journals (Sweden)

    Angélica R Cappellari

    Full Text Available Ecto-5'-nucleotidase/CD73 (ecto-5'-NT participates in extracellular ATP catabolism by converting adenosine monophosphate (AMP into adenosine. This enzyme affects the progression and invasiveness of different tumors. Furthermore, the expression of ecto-5'-NT has also been suggested as a favorable prognostic marker, attributing to this enzyme contradictory functions in cancer. Medulloblastoma (MB is the most common brain tumor of the cerebellum and affects mainly children.The effects of ecto-5'-NT overexpression on human MB tumor growth were studied in an in vivo model. Balb/c immunodeficient (nude 6 to 14-week-old mice were used for dorsal subcutaneous xenograph tumor implant. Tumor development was evaluated by pathophysiological analysis. In addition, the expression patterns of adenosine receptors were verified.The human MB cell line D283, transfected with ecto-5'-NT (D283hCD73, revealed reduced tumor growth compared to the original cell line transfected with an empty vector. D283hCD73 generated tumors with a reduced proliferative index, lower vascularization, the presence of differentiated cells and increased active caspase-3 expression. Prominent A1 adenosine receptor expression rates were detected in MB cells overexpressing ecto-5'-NT.This work suggests that ecto-5'-NT promotes reduced tumor growth to reduce cell proliferation and vascularization, promote higher differentiation rates and initiate apoptosis, supposedly by accumulating adenosine, which then acts through A1 adenosine receptors. Therefore, ecto-5'-NT might be considered an important prognostic marker, being associated with good prognosis and used as a potential target for therapy.

  11. Sensitivity of MRI tumor biomarkers to VEGFR inhibitor therapy in an orthotopic mouse glioma model.

    Directory of Open Access Journals (Sweden)

    Christian T Farrar

    Full Text Available MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI and a slight decrease in the water apparent diffusion coefficient (ADC were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV, relative microvascular blood volume (rMBV, transverse relaxation time (T2, blood vessel permeability (K(trans, and extravascular-extracellular space (ν(e. The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.

  12. Simplified realistic human head model for simulating Tumor Treating Fields (TTFields).

    Science.gov (United States)

    Wenger, Cornelia; Bomzon, Ze'ev; Salvador, Ricardo; Basser, Peter J; Miranda, Pedro C

    2016-08-01

    Tumor Treating Fields (TTFields) are alternating electric fields in the intermediate frequency range (100-300 kHz) of low-intensity (1-3 V/cm). TTFields are an anti-mitotic treatment against solid tumors, which are approved for Glioblastoma Multiforme (GBM) patients. These electric fields are induced non-invasively by transducer arrays placed directly on the patient's scalp. Cell culture experiments showed that treatment efficacy is dependent on the induced field intensity. In clinical practice, a software called NovoTalTM uses head measurements to estimate the optimal array placement to maximize the electric field delivery to the tumor. Computational studies predict an increase in the tumor's electric field strength when adapting transducer arrays to its location. Ideally, a personalized head model could be created for each patient, to calculate the electric field distribution for the specific situation. Thus, the optimal transducer layout could be inferred from field calculation rather than distance measurements. Nonetheless, creating realistic head models of patients is time-consuming and often needs user interaction, because automated image segmentation is prone to failure. This study presents a first approach to creating simplified head models consisting of convex hulls of the tissue layers. The model is able to account for anisotropic conductivity in the cortical tissues by using a tensor representation estimated from Diffusion Tensor Imaging. The induced electric field distribution is compared in the simplified and realistic head models. The average field intensities in the brain and tumor are generally slightly higher in the realistic head model, with a maximal ratio of 114% for a simplified model with reasonable layer thicknesses. Thus, the present pipeline is a fast and efficient means towards personalized head models with less complexity involved in characterizing tissue interfaces, while enabling accurate predictions of electric field distribution.

  13. [Establishment of EL4 tumor-bearing mouse models and investigation on immunological mechanisms of anti-tumor effect of melphalan].

    Science.gov (United States)

    Li, Mo-lin; Li, Chuan-gang; Shu, Xiao-hong; Jia, Yu-jie; Qin, Zhi-hai

    2006-03-01

    To establish mouse lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice respectively, and to further investigate the immunological mechanisms of anti-tumor effect of melphalan. Mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, melphalan of different doses were administered intraperitoneally to treat these wild type C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of melphalan that could cure the tuomr-bearing mice. Then the same amount of EL4 tumor cells were inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, melphalan of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded in these two different types of mice subsequently. A single dose of melphalan (7.5 mg/kg) could cure EL4 tumor-bearing wild type C57BL/6 mice, but could not induce tumor regression in EL4 tumor-bearing nude C57BL/6 mice. A single dose of melphalan has obvious anti-tumor effect on mouse lymphoma EL4 tumor-bearing wild type C57BL/6mice, which requires the involvement of T lymphocytes in the host probably related to their killing functions.

  14. In vivo targeting of dead tumor cells in a murine tumor model using a monoclonal antibody specific for the La autoantigen.

    Science.gov (United States)

    Al-Ejeh, Fares; Darby, Jocelyn M; Pensa, Katherine; Diener, Kerrilyn R; Hayball, John D; Brown, Michael P

    2007-09-15

    To investigate the potential of the La-specific monoclonal antibody (mAb) 3B9 as an in vivo tumor-targeting agent. The murine EL4 lymphoma cell line was used for in vitro studies and the EL4 model in which apoptosis was induced with cyclophosphamide and etoposide was used for in vivo studies. In vitro studies compared 3B9 binding in the EL4 cell with that in its counterpart primary cell type of the thymocyte. For in vivo studies, 3B9 was intrinsically or extrinsically labeled with carbon-14 or 1,4,7,10-tetra-azacylododecane-N,N',N'',N''''-tetraacetic acid-indium-111, respectively, and biodistribution of the radiotracers was investigated in EL4 tumor-bearing mice, which were treated or not with chemotherapy. La-specific 3B9 mAb bound EL4 cells rather than thymocytes, and binding was detergent resistant. 3B9 binding to dead EL4 cells in vitro was specific, rapid, and saturable. Significantly, more 3B9 bound dead EL4 tumor explant cells after host mice were treated with chemotherapy, which suggested that DNA damage induced 3B9 binding. Tumor binding of 3B9 in vivo was antigen specific and increased significantly after chemotherapy. Tumor accumulation of 3B9 peaked at approximately 50% of the injected dose per gram of tumor 72 h after chemotherapy and correlated with increased tumor cell death. Tumor/organ ratios of 3B9 biodistribution, which included the tumor/blood ratio, exceeded unity 48 or more hours after chemotherapy. La-specific mAb selectively targeted dead tumor cells in vivo, and targeting was augmented by cytotoxic chemotherapy. This novel cell death radioligand may be useful both for radioimmunoscintigraphy and radioimmunotherapy.

  15. Interfacial area transport of bubbly flow in a small diameter pipe

    International Nuclear Information System (INIS)

    Hibiki, Takashi; Takamasa, Tomoji; Ishii, Mamoru

    2001-01-01

    In relation to the development of the interfacial area transport equation, this study focused on modeling of the interfacial area transport mechanism of vertical adiabatic air-water bubbly flows in a relatively small diameter pipe where the bubble size-to-pipe diameter ratio was relatively high and the radial motion of bubbles was restricted by the presence of the pipe wall. The sink term of the interfacial area concentration was modeled by considering wake entrainment as a possible bubble coalescence mechanism, whereas the source term was neglected by assuming negligibly small bubble breakup for low liquid velocity conditions based on visual observation. One-dimensional interfacial area transport equation with the derived sink term was evaluated by using five datasets of vertical adiabatic air-water bubbly flows measured in a 9.0 mm-diameter pipe (superficial gas velocity: 0.013-0.052 m/s, superficial liquid velocity: 0.58-1.0 m/s). The modeled interfacial area transport equation could reproduce the proper trend of the axial interfacial area transport and predict the measured interfacial area concentrations within an average relative deviation of ±11.1%. It was recognized that the present model would be promising for predicting the interfacial area transport of the examined bubbly flows. (author)

  16. Interfacial morphologies and growth modes of F.C.C. metallic crystals from liquid alloys

    International Nuclear Information System (INIS)

    Camel, Denis

    1980-01-01

    Equilibrium and growth morphologies of f.c.c. metallic crystals in contact with liquid alloys have been observed in-situ using transmission electron microscopy. These morphologies have been discussed in terms of atomic interfacial structure and growth mechanisms with the help of a statistical thermodynamic model which takes into account the effects of chemical interactions and interfacial adsorption. (author) [fr

  17. Cell of Origin and Cancer Stem Cells in Tumor Suppressor Mouse Models of Glioblastoma.

    Science.gov (United States)

    Alcantara Llaguno, Sheila R; Xie, Xuanhua; Parada, Luis F

    2016-01-01

    The cellular origins and the mechanisms of progression, maintenance of tumorigenicity, and therapeutic resistance are central questions in the glioblastoma multiforme (GBM) field. Using tumor suppressor mouse models, our group recently reported two independent populations of adult GBM-initiating central nervous system progenitors. We found different functional and molecular subtypes depending on the tumor-initiating cell lineage, indicating that the cell of origin is a driver of GBM subtype diversity. Using an in vivo model, we also showed that GBM cancer stem cells (CSCs) or glioma stem cells (GSCs) contribute to resistance to chemotherapeutic agents and that genetic ablation of GSCs leads to a delay in tumor progression. These studies are consistent with the cell of origin and CSCs as critical regulators of the pathogenesis of GBM. © 2016 Alcantara Llaguno et al; Published by Cold Spring Harbor Laboratory Press.

  18. Periodic and chaotic oscillations in a tumor and immune system interaction model with three delays

    International Nuclear Information System (INIS)

    Bi, Ping; Ruan, Shigui; Zhang, Xinan

    2014-01-01

    In this paper, a tumor and immune system interaction model consisted of two differential equations with three time delays is considered in which the delays describe the proliferation of tumor cells, the process of effector cells growth stimulated by tumor cells, and the differentiation of immune effector cells, respectively. Conditions for the asymptotic stability of equilibria and existence of Hopf bifurcations are obtained by analyzing the roots of a second degree exponential polynomial characteristic equation with delay dependent coefficients. It is shown that the positive equilibrium is asymptotically stable if all three delays are less than their corresponding critical values and Hopf bifurcations occur if any one of these delays passes through its critical value. Numerical simulations are carried out to illustrate the rich dynamical behavior of the model with different delay values including the existence of regular and irregular long periodic oscillations

  19. Temperature and compositional dependence of solid-liquid interfacial energy: application of the Cahn-Hilliard theory

    International Nuclear Information System (INIS)

    Shimizu, I.; Takei, Y.

    2005-01-01

    A simple thermodynamic method to estimate the solid-liquid interfacial energy (or interfacial tension) is proposed, based on the Cahn-Hilliard theory. In the model, the liquid is treated as a regular solution, and the interfacial layers are assumed to have liquid-like thermodynamic properties. In eutectic systems, interfacial adsorption occurs within a few atomic layers, and interfacial energy monotonously increases with decreasing concentration of the solid species in the liquid phase. If non-ideal atomic interaction is strong and the liquid immiscibility region appears in the phase diagrams (this is the case of monotectic systems), the interfacial thickness drastically increases and the interfacial energy is reduced around the immiscibility gap

  20. Personalized 3D printed model of kidney and tumor anatomy: a useful tool for patient education.

    Science.gov (United States)

    Bernhard, Jean-Christophe; Isotani, Shuji; Matsugasumi, Toru; Duddalwar, Vinay; Hung, Andrew J; Suer, Evren; Baco, Eduard; Satkunasivam, Raj; Djaladat, Hooman; Metcalfe, Charles; Hu, Brian; Wong, Kelvin; Park, Daniel; Nguyen, Mike; Hwang, Darryl; Bazargani, Soroush T; de Castro Abreu, Andre Luis; Aron, Monish; Ukimura, Osamu; Gill, Inderbir S

    2016-03-01

    To assess the impact of 3D printed models of renal tumor on patient's understanding of their conditions. Patient understanding of their medical condition and treatment satisfaction has gained increasing attention in medicine. Novel technologies such as additive manufacturing [also termed three-dimensional (3D) printing] may play a role in patient education. A prospective pilot study was conducted, and seven patients with a primary diagnosis of kidney tumor who were being considered for partial nephrectomy were included after informed consent. All patients underwent four-phase multi-detector computerized tomography (MDCT) scanning from which renal volume data were extracted to create life-size patient-specific 3D printed models. Patient knowledge and understanding were evaluated before and after 3D model presentation. Patients' satisfaction with their specific 3D printed model was also assessed through a visual scale. After viewing their personal 3D kidney model, patients demonstrated an improvement in understanding of basic kidney physiology by 16.7 % (p = 0.018), kidney anatomy by 50 % (p = 0.026), tumor characteristics by 39.3 % (p = 0.068) and the planned surgical procedure by 44.6 % (p = 0.026). Presented herein is the initial clinical experience with 3D printing to facilitate patient's pre-surgical understanding of their kidney tumor and surgery.

  1. 3D bioprinting: improving in vitro models of metastasis with heterogeneous tumor microenvironments

    Directory of Open Access Journals (Sweden)

    Jacob L. Albritton

    2017-01-01

    Full Text Available Even with many advances in treatment over the past decades, cancer still remains a leading cause of death worldwide. Despite the recognized relationship between metastasis and increased mortality rate, surprisingly little is known about the exact mechanism of metastatic progression. Currently available in vitro models cannot replicate the three-dimensionality and heterogeneity of the tumor microenvironment sufficiently to recapitulate many of the known characteristics of tumors in vivo. Our understanding of metastatic progression would thus be boosted by the development of in vitro models that could more completely capture the salient features of cancer biology. Bioengineering groups have been working for over two decades to create in vitro microenvironments for application in regenerative medicine and tissue engineering. Over this time, advances in 3D printing technology and biomaterials research have jointly led to the creation of 3D bioprinting, which has improved our ability to develop in vitro models with complexity approaching that of the in vivo tumor microenvironment. In this Review, we give an overview of 3D bioprinting methods developed for tissue engineering, which can be directly applied to constructing in vitro models of heterogeneous tumor microenvironments. We discuss considerations and limitations associated with 3D printing and highlight how these advances could be harnessed to better model metastasis and potentially guide the development of anti-cancer strategies.

  2. 3D bioprinting: improving in vitro models of metastasis with heterogeneous tumor microenvironments.

    Science.gov (United States)

    Albritton, Jacob L; Miller, Jordan S

    2017-01-01

    Even with many advances in treatment over the past decades, cancer still remains a leading cause of death worldwide. Despite the recognized relationship between metastasis and increased mortality rate, surprisingly little is known about the exact mechanism of metastatic progression. Currently available in vitro models cannot replicate the three-dimensionality and heterogeneity of the tumor microenvironment sufficiently to recapitulate many of the known characteristics of tumors in vivo Our understanding of metastatic progression would thus be boosted by the development of in vitro models that could more completely capture the salient features of cancer biology. Bioengineering groups have been working for over two decades to create in vitro microenvironments for application in regenerative medicine and tissue engineering. Over this time, advances in 3D printing technology and biomaterials research have jointly led to the creation of 3D bioprinting, which has improved our ability to develop in vitro models with complexity approaching that of the in vivo tumor microenvironment. In this Review, we give an overview of 3D bioprinting methods developed for tissue engineering, which can be directly applied to constructing in vitro models of heterogeneous tumor microenvironments. We discuss considerations and limitations associated with 3D printing and highlight how these advances could be harnessed to better model metastasis and potentially guide the development of anti-cancer strategies. © 2017. Published by The Company of Biologists Ltd.

  3. Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

    Directory of Open Access Journals (Sweden)

    Michael Welter

    Full Text Available Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law and sources (vessels and sinks (lymphatics for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss

  4. Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

    Science.gov (United States)

    Welter, Michael; Rieger, Heiko

    2013-01-01

    Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various

  5. Effective treatment of diverse medulloblastoma models with mebendazole and its impact on tumor angiogenesis.

    Science.gov (United States)

    Bai, Ren-Yuan; Staedtke, Verena; Rudin, Charles M; Bunz, Fred; Riggins, Gregory J

    2015-04-01

    Medulloblastoma is the most common malignant brain tumor in children. Current standard treatments cure 40%-60% of patients, while the majority of survivors suffer long-term neurological sequelae. The identification of 4 molecular groups of medulloblastoma improved the clinical management with the development of targeted therapies; however, the tumor acquires resistance quickly. Mebendazole (MBZ) has a long safety record as antiparasitic in children and has been recently implicated in inhibition of various tyrosine kinases in vitro. Here, we investigated the efficacy of MBZ in various medulloblastoma subtypes and MBZ's impact on vascular endothelial growth factor receptor 2 (VEGFR2) and tumor angiogenesis. The inhibition of MBZ on VEGFR2 kinase was investigated in an autophosphorylation assay and a cell-free kinase assay. Mice bearing orthotopic PTCH1-mutant medulloblastoma allografts, a group 3 medulloblastoma xenograft, and a PTCH1-mutant medulloblastoma with acquired resistance to the smoothened inhibitor vismodegib were treated with MBZ. The survival benefit and the impact on tumor angiogenesis and VEGFR2 kinase function were analyzed. We determined that MBZ interferes with VEGFR2 kinase by competing with ATP. MBZ selectively inhibited tumor angiogenesis but not the normal brain vasculatures in orthotopic medulloblastoma models and suppressed VEGFR2 kinase in vivo. MBZ significantly extended the survival of medulloblastoma models derived from different molecular backgrounds. Our findings support testing of MBZ as a possible low-toxicity therapy for medulloblastomas of various molecular subtypes, including tumors with acquired vismodegib resistance. Its antitumor mechanism may be partially explained by inhibition of tumor angiogenesis. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. MRI monitoring of tumor response following angiogenesis inhibition in an experimental human breast cancer model

    International Nuclear Information System (INIS)

    Turetschek, Karl; Preda, Anda; Shames, David M.; Novikov, Viktor; Roberts, Timothy P.L.; Fu, Yanjun; Brasch, Robert C.; Floyd, Eugenia; Carter, Wayne O.; Wood, Jeanette M.

    2003-01-01

    The aim of this study was to evaluate the potential of dynamic magnetic resonance imaging (MRI) enhanced by macromolecular contrast agents to monitor noninvasively the therapeutic effect of an anti-angiogenesis VEGF receptor kinase inhibitor in an experimental cancer model. MDA-MB-435, a poorly differentiated human breast cancer cell line, was implanted into the mammary fat pad in 20 female homozygous athymic rats. Animals were assigned randomly to a control (n=10) or drug treatment group (n=10). Baseline dynamic MRI was performed on sequential days using albumin-(GdDTPA) 30 (6.0 nm diameter) and ultrasmall superparamagnetic iron oxide (USPIO) particles (30 nm diameter). Subjects were treated either with PTK787/ZK 222584, a VEGF receptor tyrosine kinase inhibitor, or saline given orally twice daily for 1 week followed by repeat MRI examinations serially using each contrast agent. Employing a unidirectional kinetic model comprising the plasma and interstitial water compartments, tumor microvessel characteristics including fractional plasma volume and transendothelial permeability (K PS ) were estimated for each contrast medium. Tumor growth and the microvascular density, a histologic surrogate of angiogenesis, were also measured. Control tumors significantly increased (P PS ) based on MRI assays using both macromolecular contrast media. In contrast, tumor growth was significantly reduced (P PS values declined slightly. Estimated values for the fractional plasma volume did not differ significantly between treatment groups or contrast agents. Microvascular density counts correlated fairly with the tumor growth rate (r=0.64) and were statistically significant higher (P PS ), using either of two macromolecular contrast media, were able to detect effects of treatment with a VEGF receptor tyrosine kinase inhibitor on tumor vascular permeability. In a clinical setting such quantitative MRI measurements could be used to monitor tumor anti-angiogenesis therapy. (orig.)

  7. Advanced age negatively impacts survival in an experimental brain tumor model.

    Science.gov (United States)

    Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

    2016-09-06

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Automatic lung tumor segmentation on PET/CT images using fuzzy Markov random field model.

    Science.gov (United States)

    Guo, Yu; Feng, Yuanming; Sun, Jian; Zhang, Ning; Lin, Wang; Sa, Yu; Wang, Ping

    2014-01-01

    The combination of positron emission tomography (PET) and CT images provides complementary functional and anatomical information of human tissues and it has been used for better tumor volume definition of lung cancer. This paper proposed a robust method for automatic lung tumor segmentation on PET/CT images. The new method is based on fuzzy Markov random field (MRF) model. The combination of PET and CT image information is achieved by using a proper joint posterior probability distribution of observed features in the fuzzy MRF model which performs better than the commonly used Gaussian joint distribution. In this study, the PET and CT simulation images of 7 non-small cell lung cancer (NSCLC) patients were used to evaluate the proposed method. Tumor segmentations with the proposed method and manual method by an experienced radiation oncologist on the fused images were performed, respectively. Segmentation results obtained with the two methods were similar and Dice's similarity coefficient (DSC) was 0.85 ± 0.013. It has been shown that effective and automatic segmentations can be achieved with this method for lung tumors which locate near other organs with similar intensities in PET and CT images, such as when the tumors extend into chest wall or mediastinum.

  9. Automatic Lung Tumor Segmentation on PET/CT Images Using Fuzzy Markov Random Field Model

    Directory of Open Access Journals (Sweden)

    Yu Guo

    2014-01-01

    Full Text Available The combination of positron emission tomography (PET and CT images provides complementary functional and anatomical information of human tissues and it has been used for better tumor volume definition of lung cancer. This paper proposed a robust method for automatic lung tumor segmentation on PET/CT images. The new method is based on fuzzy Markov random field (MRF model. The combination of PET and CT image information is achieved by using a proper joint posterior probability distribution of observed features in the fuzzy MRF model which performs better than the commonly used Gaussian joint distribution. In this study, the PET and CT simulation images of 7 non-small cell lung cancer (NSCLC patients were used to evaluate the proposed method. Tumor segmentations with the proposed method and manual method by an experienced radiation oncologist on the fused images were performed, respectively. Segmentation results obtained with the two methods were similar and Dice’s similarity coefficient (DSC was 0.85 ± 0.013. It has been shown that effective and automatic segmentations can be achieved with this method for lung tumors which locate near other organs with similar intensities in PET and CT images, such as when the tumors extend into chest wall or mediastinum.

  10. Investigation in clinical potential of polarization sensitive optical coherence tomography in laryngeal tumor model study

    Science.gov (United States)

    Zhou, Xin; Oak, Chulho; Ahn, Yeh-Chan; Kim, Sung Won; Tang, Shuo

    2018-02-01

    Polarization-sensitive optical coherence tomography (PS-OCT) is capable of measuring tissue birefringence. It has been widely applied to access the birefringence in tissues such as skin and cartilage. The vocal cord tissue consists of three anatomical layers from the surface to deep inside, the epithelium that contains almost no collagen, the lamina propria that is composed with abundant collagen, and the vocalis muscle layer. Due to the variation in the organization of collagen fibers, the different tissue layers show different tissue birefringence, which can be evaluated by PS-OCT phase retardation measurement. Furthermore, collagen fibers in healthy connective tissues are usually well organized, which provides relatively high birefringence. When the collagen organization is destroyed by diseases such as tumor, the birefringence of the tissue will decrease. In this study, a rabbit laryngeal tumor model with different stages of tumor progression is investigated ex-vivo by PS-OCT. The PS-OCT images show a gradual decrease in birefringence from normal tissue to severe tumor tissue. A phase retardation slope-based analysis is conducted to distinguish the epithelium, lamina propria, and muscle layers, respectively. The phase retardation slope quantifies the birefringence in different layers. The quantitative study provides a more detailed comparison among different stages of the rabbit laryngeal tumor model. The PS-OCT result is validated by the corresponding histology images of the same samples.

  11. Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor

    Directory of Open Access Journals (Sweden)

    Zhao Junfeng

    2012-03-01

    Full Text Available Abstract The testicular yolk sac tumor (TYST is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST.

  12. Analysis of a diffuse interface model of multispecies tumor growth

    Czech Academy of Sciences Publication Activity Database

    Dai, M.; Feireisl, Eduard; Rocca, E.; Schimperna, G.; Schonbek, M.E.

    2017-01-01

    Roč. 30, č. 4 (2017), s. 1639-1658 ISSN 0951-7715 EU Projects: European Commission(XE) 320078 - MATHEF Institutional support: RVO:67985840 Keywords : Cahn-Hilliard equation * Darcy law * diffuse interface model Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 1.767, year: 2016 http://iopscience.iop.org/article/10.1088/1361-6544/aa6063/meta

  13. Measurement of Interfacial Area Production and Permeability within Porous Media

    International Nuclear Information System (INIS)

    Crandall, Dustin; Ahmadi, Goodarz; Smith, Duane H.

    2010-01-01

    An understanding of the pore-level interactions that affect multi-phase flow in porous media is important in many subsurface engineering applications, including enhanced oil recovery, remediation of dense non-aqueous liquid contaminated sites, and geologic CO 2 sequestration. Standard models of two-phase flow in porous media have been shown to have several shortcomings, which might partially be overcome using a recently developed model based on thermodynamic principles that includes interfacial area as an additional parameter. A few static experimental studies have been previously performed, which allowed the determination of static parameters of the model, but no information exists concerning the interfacial area dynamic parameters. A new experimental porous flow cell that was constructed using stereolithography for two-phase gas-liquid flow studies was used in conjunction with an in-house analysis code to provide information on dynamic evolution of both fluid phases and gas-liquid interfaces. In this paper, we give a brief introduction to the new generalized model of two-phase flow model and describe how the stereolithography flow cell experimental setup was used to obtain the dynamic parameters for the interfacial area numerical model. In particular, the methods used to determine the interfacial area permeability and production terms are shown.

  14. Classification of brain tumors using texture based analysis of T1-post contrast MR scans in a preclinical model

    Science.gov (United States)

    Tang, Tien T.; Zawaski, Janice A.; Francis, Kathleen N.; Qutub, Amina A.; Gaber, M. Waleed

    2018-02-01

    Accurate diagnosis of tumor type is vital for effective treatment planning. Diagnosis relies heavily on tumor biopsies and other clinical factors. However, biopsies do not fully capture the tumor's heterogeneity due to sampling bias and are only performed if the tumor is accessible. An alternative approach is to use features derived from routine diagnostic imaging such as magnetic resonance (MR) imaging. In this study we aim to establish the use of quantitative image features to classify brain tumors and extend the use of MR images beyond tumor detection and localization. To control for interscanner, acquisition and reconstruction protocol variations, the established workflow was performed in a preclinical model. Using glioma (U87 and GL261) and medulloblastoma (Daoy) models, T1-weighted post contrast scans were acquired at different time points post-implant. The tumor regions at the center, middle, and peripheral were analyzed using in-house software to extract 32 different image features consisting of first and second order features. The extracted features were used to construct a decision tree, which could predict tumor type with 10-fold cross-validation. Results from the final classification model demonstrated that middle tumor region had the highest overall accuracy at 79%, while the AUC accuracy was over 90% for GL261 and U87 tumors. Our analysis further identified image features that were unique to certain tumor region, although GL261 tumors were more homogenous with no significant differences between the central and peripheral tumor regions. In conclusion our study shows that texture features derived from MR scans can be used to classify tumor type with high success rates. Furthermore, the algorithm we have developed can be implemented with any imaging datasets and may be applicable to multiple tumor types to determine diagnosis.

  15. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  16. A Gaussian mixture model for definition of lung tumor volumes in positron emission tomography

    International Nuclear Information System (INIS)

    Aristophanous, Michalis; Penney, Bill C.; Martel, Mary K.; Pelizzari, Charles A.

    2007-01-01

    The increased interest in 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in radiation treatment planning in the past five years necessitated the independent and accurate segmentation of gross tumor volume (GTV) from FDG-PET scans. In some studies the radiation oncologist contours the GTV based on a computed tomography scan, while incorporating pertinent data from the PET images. Alternatively, a simple threshold, typically 40% of the maximum intensity, has been employed to differentiate tumor from normal tissue, while other researchers have developed algorithms to aid the PET based GTV definition. None of these methods, however, results in reliable PET tumor segmentation that can be used for more sophisticated treatment plans. For this reason, we developed a Gaussian mixture model (GMM) based segmentation technique on selected PET tumor regions from non-small cell lung cancer patients. The purpose of this study was to investigate the feasibility of using a GMM-based tumor volume definition in a robust, reliable and reproducible way. A GMM relies on the idea that any distribution, in our case a distribution of image intensities, can be expressed as a mixture of Gaussian densities representing different classes. According to our implementation, each class belongs to one of three regions in the image; the background (B), the uncertain (U) and the target (T), and from these regions we can obtain the tumor volume. User interaction in the implementation is required, but is limited to the initialization of the model parameters and the selection of an ''analysis region'' to which the modeling is restricted. The segmentation was developed on three and tested on another four clinical cases to ensure robustness against differences observed in the clinic. It also compared favorably with thresholding at 40% of the maximum intensity and a threshold determination function based on tumor to background image intensities proposed in a recent paper. The parts of the

  17. Immunological considerations of modern animal models of malignant primary brain tumors

    Directory of Open Access Journals (Sweden)

    James C David

    2009-10-01

    Full Text Available Abstract Recent advances in animal models of glioma have facilitated a better understanding of biological mechanisms underlying gliomagenesis and glioma progression. The limitations of existing therapy, including surgery, chemotherapy, and radiotherapy, have prompted numerous investigators to search for new therapeutic approaches to improve quantity and quality of survival from these aggressive lesions. One of these approaches involves triggering a tumor specific immune response. However, a difficulty in this approach is the the scarcity of animal models of primary CNS neoplasms which faithfully recapitulate these tumors and their interaction with the host's immune system. In this article, we review the existing methods utilized to date for modeling gliomas in rodents, with a focus on the known as well as potential immunological aspects of these models. As this review demonstrates, many of these models have inherent immune system limitations, and the impact of these limitations on studies on the influence of pre-clinical therapeutics testing warrants further attention.

  18. On the interfacial energy of coherent interfaces

    International Nuclear Information System (INIS)

    Kaptay, G.

    2012-01-01

    A thermodynamic model has been developed for interfacial energies of coherent interfaces using only the molar Gibbs energy and the molar volume of the two phases surrounding the interface as the initial data. The analysis is started from the simplest case of the interface formed by two solutions on the two sides of a miscibility gap, when both phases are described by the same Gibbs energy and molar volume functions. This method is applied to the fcc Au–Ni, liquid Ga–Pb and liquid Al–Bi systems. Reasonable agreement was found with the measured values in liquid Ga–Pb and Al–Bi systems. It was shown that the calculated results are sensitive to the choice of the Calphad-estimated thermodynamic data. The method is extended to the case where the two phases are described by different Gibbs energy and molar volume functions. The extended model is applied to the interface present in an Ni-based superalloy between the AlNi 3 face-centered cubic (fcc) compound and the Ni–Al fcc disordered solid solution. The calculated results are found to be similar to other values recently obtained from the combination of kinetic and thermodynamic data. The method is extended to ternary and higher order systems. It is predicted that the interfacial energy will gradually decrease with the increase in number of components in the system.

  19. Experimental model of ultrasound thermotherapy in rats inoculated with Walker-236 tumor Modelo experimental de termoterapia ultrassônica em ratos inoculados com tumor de Walker-236

    Directory of Open Access Journals (Sweden)

    José Antonio Carlos Otaviano David Morano

    2011-01-01

    Full Text Available PURPOSE: To develop a model to evaluate the effects of focal pulsed ultrasound (US waves as a source of heat for treatment of murine subcutaneous implanted Walker tumor. METHODS: An experimental, controlled, comparative study was conducted. Twenty male Wistar rats (160-300 g randomized in 2 equal groups (G-1: Control and G-2: Hyperthermia were inoculated with Walker-256 carcinosarcoma tumor. After 5 days G-2 rats were submitted to 45ºC hyperthermia. Heat was delivered directly to the tumor by an ultrasound (US equipment (3 MHz frequency, 1,5W/cm³. Tumor temperature reached 45º C in 3 minutes and was maintained at this level for 5 minutes. Tumor volume was measured on days 5, 8, 11, 14 e 17 post inoculation in both groups. Unpaired t-test was used for comparison. POBJETIVO: Desenvolver um modelo para avaliar os efeitos do ultra-som focal pulsado como fonte de calor para o tratamento de tumores de Walker subcutâneos implantados em ratos. MÉTODOS: Um estudo experimental, controlado, comparativo foi realizado. Vinte ratos Wistar machos (160-300 g divididos em dois grupos (G-1: Controle e G-2: hipertermia foram inoculados com tumor de Walker carcinossarcoma-256. Após cinco dias os ratos do grupo G-2 ratos foram submetidos a hipertermia (45ºC. O calor foi aplicado diretamente no tumor por um equipamento de ultrassonografia (3 MHz, 1,5 W/cm³. A temperatura no tumor atingiu 45ºC em 3 minutos e foi mantida nesse nível por 5 minutos. O volume do tumor foi medido nos dias 5, 8, 11, 14 e 17 após a inoculação, em ambos os grupos. Teste t não pareado foi utilizado para comparação. P <0,05 foi considerado significante. RESULTADOS: O volume do tumor foi significativamente maior no 5º dia e diminuiu nos dias 11, 14 e 17 nos ratos tratados. Animais submetidos à hipertermia sobreviveram mais tempo que os animais do grupo controle. No 29º dia após a inoculação do tumor, 40% dos ratos do grupo controle e 77,78% dos ratos tratados com

  20. The bivariate probit model of uncomplicated control of tumor: a heuristic exposition of the methodology

    International Nuclear Information System (INIS)

    Herbert, Donald

    1997-01-01

    Purpose: To describe the concept, models, and methods for the construction of estimates of joint probability of uncomplicated control of tumors in radiation oncology. Interpolations using this model can lead to the identification of more efficient treatment regimens for an individual patient. The requirement to find the treatment regimen that will maximize the joint probability of uncomplicated control of tumors suggests a new class of evolutionary experimental designs--Response Surface Methods--for clinical trials in radiation oncology. Methods and Materials: The software developed by Lesaffre and Molenberghs is used to construct bivariate probit models of the joint probability of uncomplicated control of cancer of the oropharynx from a set of 45 patients for each of whom the presence/absence of recurrent tumor (the binary event E-bar 1 /E 1 ) and the presence/absence of necrosis (the binary event E 2 /E-bar 2 ) of the normal tissues of the target volume is recorded, together with the treatment variables dose, time, and fractionation. Results: The bivariate probit model can be used to select a treatment regime that will give a specified probability, say P(S) = 0.60, of uncomplicated control of tumor by interpolation within a set of treatment regimes with known outcomes of recurrence and necrosis. The bivariate probit model can be used to guide a sequence of clinical trials to find the maximum probability of uncomplicated control of tumor for patients in a given prognostic stratum using Response Surface methods by extrapolation from an initial set of treatment regimens. Conclusions: The design of treatments for individual patients and the design of clinical trials might be improved by use of a bivariate probit model and Response Surface Methods

  1. Tumor Growth Model with PK Input for Neuroblastoma Drug Development

    Science.gov (United States)

    2015-09-01

    Your credit card order has been processed on  Tuesday  2 December 2014 at 3:05 PM. Status: Complete 12/3/2014 Oasis, The Online Abstract Submission System...pharmacokinetic models. Toxicol Ind Health, 1997. 13(4): p. 407-84. PMID: 9249929 4. Davies, B. and T. Morris , Physiological parameters in laboratory animals and humans. Pharm Res, 1993. 10(7): p. 1093-5. PMID: 8378254

  2. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

    Science.gov (United States)

    Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A

    2013-11-18

    Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  3. Chaotic attractors in tumor growth and decay: a differential equation model.

    Science.gov (United States)

    Harney, Michael; Yim, Wen-sau

    2015-01-01

    Tumorigenesis can be modeled as a system of chaotic nonlinear differential equations. A simulation of the system is realized by converting the differential equations to difference equations. The results of the simulation show that an increase in glucose in the presence of low oxygen levels decreases tumor growth.

  4. Modeling tumor control probability for spatially inhomogeneous risk of failure based on clinical outcome data

    DEFF Research Database (Denmark)

    Lühr, Armin; Löck, Steffen; Jakobi, Annika

    2017-01-01

    PURPOSE: Objectives of this work are (1) to derive a general clinically relevant approach to model tumor control probability (TCP) for spatially variable risk of failure and (2) to demonstrate its applicability by estimating TCP for patients planned for photon and proton irradiation. METHODS AND ...

  5. Selenium prevents tumor development in a rat model for chemical carcinogenesis

    DEFF Research Database (Denmark)

    Bjorkhem-Bergman, L.; Torndal, U. B.; Eken, S.

    2005-01-01

    Previous studies in animals and humans have shown that selenium compounds can prevent cancer development. In this work we studied the tumor preventive effect of selenium supplementation, administrated as selenite, in the initiation, promotion and progression phases in a synchronized rat model for...

  6. Hopf bifurcation of a free boundary problem modeling tumor growth with two time delays

    International Nuclear Information System (INIS)

    Xu Shihe

    2009-01-01

    In this paper, a free boundary problem modeling tumor growth with two discrete delays is studied. The delays respectively represents the time taken for cells to undergo mitosis and the time taken for the cell to modify the rate of cell loss due to apoptosis. We show the influence of time delays on the Hopf bifurcation when one of delays as a bifurcation parameter.

  7. Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

    International Nuclear Information System (INIS)

    Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

    2013-01-01

    Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

  8. Ovarian tumor attachment, invasion and vascularization reflect unique microenvironments in the peritoneum:Insights from xenograft and mathematical models

    Directory of Open Access Journals (Sweden)

    Mara P. Steinkamp

    2013-05-01

    Full Text Available Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian tumor cells with the peritoneal tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection of fluorescent SKOV3.ip1 ovarian cancer cells. Intra-vital microscopy of mixed GFP-RFP cell populations injected into the peritoneum demonstrated that tumor cells aggregate and attach as mixed spheroids, emphasizing the importance of homotypic adhesion in tumor formation. Electron microscopy provided high resolution structural information about local attachment sites. Experimental measurements from the mouse model were used to build a three-dimensional cellular Potts ovarian tumor model (OvTM that examines ovarian tumor cell attachment, chemotaxis, growth and vascularization. OvTM simulations provide insight into the relative influence of tumor cell-cell adhesion, oxygen availability, and local architecture on tumor growth and morphology. Notably, tumors on the mesentery, omentum or spleen readily invade the open architecture, while tumors attached to the gut encounter barriers that restrict invasion and instead rapidly expand into the peritoneal space. Simulations suggest that rapid neovascularization of SKOV3.ip1 tumors is triggered by constitutive release of angiogenic factors in the absence of hypoxia. This research highlights the importance of cellular adhesion and tumor microenvironment in the seeding of secondary ovarian tumors on diverse organs within the peritoneal cavity. Results of the OvTM simulations indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors. The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer relapse.

  9. Liquid flow along a solid surface reversibly alters interfacial chemistry.

    Science.gov (United States)

    Lis, Dan; Backus, Ellen H G; Hunger, Johannes; Parekh, Sapun H; Bonn, Mischa

    2014-06-06

    In nature, aqueous solutions often move collectively along solid surfaces (for example, raindrops falling on the ground and rivers flowing through riverbeds). However, the influence of such motion on water-surface interfacial chemistry is unclear. In this work, we combine surface-specific sum frequency generation spectroscopy and microfluidics to show that at immersed calcium fluoride and fused silica surfaces, flow leads to a reversible modification of the surface charge and subsequent realignment of the interfacial water molecules. Obtaining equivalent effects under static conditions requires a substantial change in bulk solution pH (up to 2 pH units), demonstrating the coupling between flow and chemistry. These marked flow-induced variations in interfacial chemistry should substantially affect our understanding and modeling of chemical processes at immersed surfaces. Copyright © 2014, American Association for the Advancement of Science.

  10. Interfacial trap states in junctions of molecular semiconductors

    International Nuclear Information System (INIS)

    Schlettwein, D.; Oekermann, T.; Jaeger, N.; Armstrong, N.R.; Woehrle, D.

    2002-01-01

    Interfacial states that were established in contacts of molecular semiconductors with aqueous electrolytes or in contacts with another organic semiconductor as a solid film were analyzed by photoelectrochemical experiments and by photoelectron spectroscopy. A crucial role of such states was indicated in the interfacial charge transfer and recombination kinetics of light-induced charge carriers and also in the energetic alignment in the solid contacts. Unsubstituted zinc-phthalocyanine (PcZn) served as model compound. The role of chemical interactions in the establishment of these interfacial states was investigated by use of different reaction partners, i.e., different redox couples in the electrolyte contacts and molecular semiconductors of different ionization potential in the solid contacts. Implications of these results for the use of organic semiconductor thin films in devices of molecular electronics and of dye molecules in dye-sensitized solar cells were also discussed

  11. Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology.

    Science.gov (United States)

    Gill, Bartley J; West, Jennifer L

    2014-06-27

    Cancer progression is mediated by complex epigenetic, protein and structural influences. Critical among them are the biochemical, mechanical and architectural properties of the extracellular matrix (ECM). In recognition of the ECM's important role, cancer biologists have repurposed matrix mimetic culture systems first widely used by tissue engineers as new tools for in vitro study of tumor models. In this review we discuss the pathological changes in tumor ECM, the limitations of 2D culture on both traditional and polyacrylamide hydrogel surfaces in modeling these characteristics and advances in both naturally derived and synthetic scaffolds to facilitate more complex and controllable 3D cancer cell culture. Studies using naturally derived matrix materials like Matrigel and collagen have produced significant findings related to tumor morphogenesis and matrix invasion in a 3D environment and the mechanotransductive signaling that mediates key tumor-matrix interaction. However, lack of precise experimental control over important matrix factors in these matrices have increasingly led investigators to synthetic and semi-synthetic scaffolds that offer the engineering of specific ECM cues and the potential for more advanced experimental manipulations. Synthetic scaffolds composed of poly(ethylene glycol) (PEG), for example, facilitate highly biocompatible 3D culture, modular bioactive features like cell-mediated matrix degradation and complete independent control over matrix bioactivity and mechanics. Future work in PEG or similar reductionist synthetic matrix systems should enable the study of increasingly complex and dynamic tumor-ECM relationships in the hopes that accurate modeling of these relationships may reveal new cancer therapeutics targeting tumor progression and metastasis. © 2013 Published by Elsevier Ltd.

  12. Targeted hyperthermia after selective embolization with ferromagnetic nanoparticles in a VX2 rabbit liver tumor model

    Directory of Open Access Journals (Sweden)

    Sun HL

    2013-10-01

    Full Text Available Hongliang Sun,1 Linfeng Xu,1 Tianyuan Fan,2 Hongzhi Zhan,3 Xiaodong Wang,3 Yanfei Zhou,2 Ren-jie Yang3 1Department of Interventional Therapy, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 2Pharmacy School of Beijing University, Beijing, 3Department of Interventional Therapy, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China Background: The purpose of this study was to observe the effect and feasibility of hyperthermia and the influence of heat on surrounding organs in a VX2 rabbit liver model exposed to an alternating magnetic field after embolization with ferromagnetic nanoparticles. Methods: Forty rabbits containing implanted hepatic VX2 carcinomas were divided into four groups, each containing ten rabbits. Fourteen days after tumor transplantation, we opened the abdomen to observe the size and shape of the tumor. A transfemoral retrograde approach was then used for hepatic arterial catheterization in groups B, C, and D to perform angiography and embolization. The next day, three rabbits in group B and all rabbits in group D were exposed to an alternating magnetic field, and the temperature was recorded simultaneously in the center of the tumor, at the edge of the tumor, and in the normal liver parenchyma. On day 28, all animals was euthanized to observe changes in the implanted liver tumor and the condition of the abdomen. A pathologic examination was also done. Results: Before surgery, there was no significant difference in tumor volume between the four groups. Three different temperature points (center of the tumor, edge of the tumor, and in the normal liver parenchyma of group B under an alternating magnetic field were 37.2°C ± 1.1°C, 36.8°C ± 1.2°C, and 36.9°C ± 2.1°C, none of which were significantly different from pretreatment values. Three points basal temperature in group D showed no significant difference (F = 1.038, P = 0.413. Seven to 26

  13. Interfacial area transport in a confined Bubbly flow

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S.; Sun, X.; Ishii, M. [Purdue Univ., Lafayette, IN (United States). School of Nuclear Engineering; Lincoln, F. [Bettis Atomic Power Lab., West Mifflin, Bechtel Bettis, Inc., PA (United States)

    2001-07-01

    The interfacial area transport equation applicable to the bubbly flow is presented. The model is evaluated against the data acquired in an adiabatic air-water upward two-phase flow loop with a test section of 20 cm in width and 1 cm in gap. In general, a good agreement, within the measurement error of {+-}10%, is observed for a wide range in the bubbly flow regime. The sensitivity analysis on the individual particle interaction mechanisms demonstrates the active interactions between the bubbles and highlights the mechanisms playing the dominant role in interfacial area transport. (author)

  14. Interfacial phenomena as related to oil recovery mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Melrose, J C

    1970-12-01

    Thermodynamic and hydrostatic principles are applied to commingled immiscible fluid phases occupying the interstices fo a porous solid. Particular attention is given to the conditions of hydrostatic equilibrium for systems which include both fluid-fluid interfacial and 3-phase contact line regions. The configurational stability of fluid interfaces also is examined. Some model pore systems are considered, and estimates obtained for the magnitude of the hysteresis in capillary pressure in such cases. These considerations define the role of interfacial phenomena in determining the extent to which a nonwetting fluid can be displaced from a porous solid. (31 refs.)

  15. An Investigation of Interfacial Fatigue in Fiber Reinforced Composites

    Science.gov (United States)

    Yanhua, Chen; Zhifei, Shi

    2005-09-01

    Based on the shear-lag model and the modified degradation formula for coefficient of friction, the interfacial fatigue and debonding for fiber reinforced composites under cyclic loading are studied. The loading condition is chosen as the kind that is the most frequently used in fiber-pull-out experiments. The stress components in the debonded and bonded regions are obtained according to the maximum and minimum applied loading. By the aid of theory of fracture mechanics and Paris formula, the governing equation is solved numerically and the interfacial debonding is simulated. The relationships between the parameters (such as the debond rate, debond length, debond force) and the number of cycles are obtained.

  16. The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models

    Energy Technology Data Exchange (ETDEWEB)

    Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany)

    2014-08-19

    The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.

  17. Raloxifene inhibits tumor growth and lymph node metastasis in a xenograft model of metastatic mammary cancer

    Directory of Open Access Journals (Sweden)

    Li Zhong-Lian

    2010-10-01

    Full Text Available Abstract Background The effects of raloxifene, a novel selective estrogen receptor modulator, were studied in a mouse metastatic mammary cancer model expressing cytoplasmic ERα. Methods Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879luc2 cells, were subsequently treated with raloxifene at 0, 18 and 27 mg/kg/day using mini-osmotic pumps. Results In vitro study demonstrated that the ERα in BJMC3879luc2 cells was smaller (between 50 and 64 kDa than the normal-sized ERα (66 kDa and showed cytoplasmic localization. A statistically significant but weak estradiol response was observed in this cell line. When BJMC3879luc2 tumors were implanted into mice, the ERα mRNA levels were significantly higher in females than in males. In vitro studies showed that raloxifene induced mitochondria-mediated apoptosis and cell-cycle arrest in the G1-phase and a decrease in the cell population in the S-phase. In animal experiments, tumor volumes were significantly suppressed in the raloxifene-treated groups. The multiplicity of lymph node metastasis was significantly decreased in the 27 mg/kg group. Levels of apoptosis were significantly increased in the raloxifene-treated groups, whereas the levels of DNA synthesis were significantly decreased in these groups. No differences in microvessel density in tumors were observed between the control and raloxifene-treated groups. The numbers of dilated lymphatic vessels containing intraluminal tumor cells were significantly reduced in mammary tumors in the raloxifene-treated groups. The levels of ERα mRNA in mammary tumors tended to be decreased in the raloxifene-treated groups. Conclusion These results suggest that the antimetastatic activity of raloxifene in mammary cancer expressing cytoplasmic ERα may be a crucial finding with clinical applications and that raloxifene may be useful as an adjuvant therapy and for the chemoprevention of breast cancer development.

  18. CT perfusion for determination of pharmacologically mediated blood flow changes in an animal tumor model.

    Science.gov (United States)

    Hakimé, Antoine; Peddi, Himaja; Hines-Peralta, Andrew U; Wilcox, Carol J; Kruskal, Jonathan; Lin, Shezhang; de Baere, Thierry; Raptopoulos, Vassilios D; Goldberg, S Nahum

    2007-06-01

    To prospectively compare single- and multisection computed tomographic (CT) perfusion for tumor blood flow determination in an animal model. All animal protocols and experiments were approved by the institutional animal care and use committee before the study was initiated. R3230 mammary adenocarcinoma was implanted in 11 rats. Tumors (18-20 mm) were scanned with dynamic 16-section CT at baseline and after administration of arsenic trioxide, which is known to cause acute reduction in blood flow. The concentration of arsenic was titrated (0-6 mg of arsenic per kilogram of body weight) to achieve a defined blood flow reduction (0%-75%) from baseline levels at 60 minutes, as determined with correlative laser Doppler flowmetry. The mean blood flow was calculated for each of four 5-mm sections that covered the entire tumor, as well as for the entire tumor after multiple sections were processed. Measurements obtained with both methods were correlated with laser Doppler flowmetry measurements. Interobserver agreement was determined for two blinded radiologists, who calculated the percentage of blood flow reduction for the "most representative" single sections at baseline and after arsenic administration. These results were compared with the interobserver variability of the same radiologists obtained by summing blood flow changes for the entire tumor volume. Overall correlations for acute blood flow reduction were demonstrated between laser Doppler flowmetry and the two CT perfusion approaches (single-section CT, r=0.85 and r(2)=0.73; multisection CT, r=0.93 and r(2)=0.87; pooled data, P=.01). CT perfusion disclosed marked heterogeneity of blood flow, with variations of 36% +/- 13 between adjacent 5-mm sections. Given these marked differences, interobserver agreement was much lower for single-section CT (standard deviation, 0.22) than for multisection CT (standard deviation, 0.10; P=.01). Multisection CT perfusion techniques may provide an accurate and more reproducible

  19. Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade.

    Science.gov (United States)

    Gu, Yi-Feng; Cohn, Shannon; Christie, Alana; McKenzie, Tiffani; Wolff, Nicholas; Do, Quyen N; Madhuranthakam, Ananth J; Pedrosa, Ivan; Wang, Tao; Dey, Anwesha; Busslinger, Meinrad; Xie, Xian-Jin; Hammer, Robert E; McKay, Renée M; Kapur, Payal; Brugarolas, James

    2017-08-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutations, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl ) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with PAX8, a transcription factor frequently overexpressed in ccRCC, led to ccRCC of different grades. Bap1 -deficient tumors were of high grade and showed greater mTORC1 activation than Pbrm1 -deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1 , in Pbrm1 -deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histologic grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCCs arise from Bowman capsule cells. Significance: Determinants of tumor grade and aggressiveness across cancer types are poorly understood. Using ccRCC as a model, we show that Bap1 and Pbrm1 loss drives tumor grade. Furthermore, we show that the conversion from low grade to high grade can be promoted by activation of mTORC1. Cancer Discov; 7(8); 900-17. ©2017 AACR. See related commentary by Leung and Kim, p. 802 This article is highlighted in the In This Issue feature, p. 783 . ©2017 American Association for Cancer Research.

  20. Experimental study on interfacial area transport in downward two-phase flow

    Science.gov (United States)

    Wang, Guanyi

    In view of the importance of two group interfacial area transport equations and lack of corresponding accurate downward flow database that can reveal two group interfacial area transport, a systematic database for adiabatic, air-water, vertically downward two-phase flow in a round pipe with inner diameter of 25.4 mm was collected to gain an insight of interfacial structure and provide benchmarking data for two-group interfacial area transport models. A four-sensor conductivity probe was used to measure the local two phase flow parameters and data was collected with data sampling frequency much higher than conventional data sampling frequency to ensure the accuracy. Axial development of local flow parameter profiles including void fraction, interfacial area concentration, and Sauter mean diameter were presented. Drastic inter-group transfer of void fraction and interfacial area was observed at bubbly to slug transition flow. And the wall peaked interfacial area concentration profiles were observed in churn-turbulent flow. The importance of local data about these phenomenon on flow structure prediction and interfacial area transport equation benchmark was analyzed. Bedsides, in order to investigate the effect of inlet conditions, all experiments were repeated after installing the flow straightening facility, and the results were briefly analyzed. In order to check the accuracy of current data, the experiment results were cross-checked with rotameter measurement as well as drift-flux model prediction, the averaged error is less than 15%. Current models for two-group interfacial area transport equation were evaluated using these data. The results show that two-group interfacial area transport equations with current models can predict most flow conditions with error less than 20%, except some bubbly to slug transition flow conditions and some churn-turbulent flow conditions. The disagreement between models and experiments could result from underestimate of inter

  1. Interfacial transport processes and rheology

    CERN Document Server

    Brenner, Howard

    1991-01-01

    This textbook is designed to provide the theory, methods of measurement, and principal applications of the expanding field of interfacial hydrodynamics. It is intended to serve the research needs of both academic and industrial scientists, including chemical or mechanical engineers, material and surface scientists, physical chemists, chemical and biophysicists, rheologists, physiochemical hydrodynamicists, and applied mathematicians (especially those with interests in viscous fluid mechanics and continuum mechanics).As a textbook it provides materials for a one- or two-semester graduate-level

  2. Interfacial friction in low flowrate vertical annular flow

    International Nuclear Information System (INIS)

    Kelly, J.M.; Freitas, R.L.

    1993-01-01

    During boil-off and reflood transients in nuclear reactors, the core liquid inventory and inlet flowrate are largely determined by the interfacial friction in the reactor core. For these transients, annular flow occurs at relatively modest liquid flowrates and at the low heat fluxes typical of decay heat conditions. The resulting low vapor Reynolds numbers, are out of the data range used to develop the generally accepted interfacial friction relations for annular flow. In addition, most existing annular flow data comes from air/liquid adiabatic experiments with fully developed flows. By contrast, in a reactor core, the flow is continuously developing along the heated length as the vapor flowrate increases and the flow regimes evolve from bubbly to annular flow. Indeed, the entire annular flow regime may exist only over tens of L/D's. Despite these limitations, many of the advanced reactor safety analysis codes employ the Wallis model for interfacial friction in annular flow. Our analyses of the conditions existing at the end-of-reflood in the PERICLES tests have indicated that the Wallis model seriously underestimates the interfacial shear for low vapor velocity cocurrent upflow. To extend the annular flow data base to diabatic low flowrate conditions, the DADINE tests were re-analyzed. In these tests, both pressure drop and local cross-section averaged void fractions were measured. Thus, both the wall and interfacial shear can be deduced. Based on the results of this analysis, a new correlation is proposed for interfacial friction in annular flow. (authors). 5 figs., 12 refs

  3. The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

    Science.gov (United States)

    Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J

    2017-11-01

    Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Micro-MRI at 11.7 T of a Murine Brain Tumor Model Using Delayed Contrast Enhancement

    Directory of Open Access Journals (Sweden)

    Rex A. Moats

    2003-07-01

    Full Text Available In vivo imaging methodologies allow for serial measurement of tumor size, circumventing the need for sacrificing mice at given time points. In orthotopically transplanted murine models of brain tumors, cross-section micro-MRI allows for visualization and measurement of the physically inaccessible tumors. To allow for long resident times of a contrast agent in the tumor, intraperitoneal administration was used as a route of injection for contrast-enhanced micro-MRI, and a simple method for relative tumor volume measurements was examined. A strategy for visualizing the variability of the delayed tumor enhancement was developed. These strategies were applied to monitor the growth of brain tumors xenotransplanted into nude mice and either treated with the antiangiogenic peptide EMD 121974 or an inactive control peptide. Each mouse was used as its own control. Serial imaging was done weekly, beginning at Day 7 after tumor cell implantation and continued for 7 weeks. Images obtained were reconstructed on the MRI instrument. The image files were transferred off line to be postprocessed to assess tumor growth (volume and variability in enhancement (three-dimensional [3-D] intensity models. In a small study, tumor growth and response to treatment were followed using this methodology and the high-resolution images displayed in 3-D allowed for straightforward qualitative assessment of variable enhancement related to vascular factors and tumor age.

  5. Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

    Directory of Open Access Journals (Sweden)

    Maciej H Swat

    Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

  6. Small Animal [18F]FDG PET Imaging for Tumor Model Study

    International Nuclear Information System (INIS)

    Woo, Sang Keun; Kim, Kyeong Min; Cheon, Gi Jeong

    2008-01-01

    PET allows non-invasive, quantitative and repetitive imaging of biological function in living animals. Small animal PET imaging with [ 18 F]FDG has been successfully applied to investigation of metabolism, receptor, ligand interactions, gene expression, adoptive cell therapy and somatic gene therapy. Experimental condition of animal handling impacts on the biodistribution of [ 18 F]FDG in small animal study. The small animal PET and CT images were registered using the hardware fiducial markers and small animal contour point. Tumor imaging in small animal with small animal [ 18 F]FDG PET should be considered fasting, warming, and isoflurane anesthesia level. Registered imaging with small animal PET and CT image could be useful for the detection of tumor. Small animal experimental condition of animal handling and registration method will be of most importance for small lesion detection of metastases tumor model

  7. Integrated intravital microscopy and mathematical modeling to optimize nanotherapeutics delivery to tumors

    Directory of Open Access Journals (Sweden)

    Anne L. van de Ven

    2012-03-01

    Full Text Available Inefficient vascularization hinders the optimal transport of cell nutrients, oxygen, and drugs to cancer cells in solid tumors. Gradients of these substances maintain a heterogeneous cell-scale microenvironment through which drugs and their carriers must travel, significantly limiting optimal drug exposure. In this study, we integrate intravital microscopy with a mathematical model of cancer to evaluate the behavior of nanoparticle-based drug delivery systems designed to circumvent biophysical barriers. We simulate the effect of doxorubicin delivered via porous 1000 x 400 nm plateloid silicon particles to a solid tumor characterized by a realistic vasculature, and vary the parameters to determine how much drug per particle and how many particles need to be released within the vasculature in order to achieve remission of the tumor. We envision that this work will contribute to the development of quantitative measures of nanoparticle design and drug loading in order to optimize cancer treatment via nanotherapeutics.

  8. Mathematical Modelling and Analysis of the Tumor Treatment Regimens with Pulsed Immunotherapy and Chemotherapy.

    Science.gov (United States)

    Pang, Liuyong; Shen, Lin; Zhao, Zhong

    2016-01-01

    To begin with, in this paper, single immunotherapy, single chemotherapy, and mixed treatment are discussed, and sufficient conditions under which tumor cells will be eliminated ultimately are obtained. We analyze the impacts of the least effective concentration and the half-life of the drug on therapeutic results and then find that increasing the least effective concentration or extending the half-life of the drug can achieve better therapeutic effects. In addition, since most types of tumors are resistant to common chemotherapy drugs, we consider the impact of drug resistance on therapeutic results and propose a new mathematical model to explain the cause of the chemotherapeutic failure using single drug. Based on this, in the end, we explore the therapeutic effects of two-drug combination chemotherapy, as well as mixed immunotherapy with combination chemotherapy. Numerical simulations indicate that combination chemotherapy is very effective in controlling tumor growth. In comparison, mixed immunotherapy with combination chemotherapy can achieve a better treatment effect.

  9. A note on modeling of tumor regression for estimation of radiobiological parameters

    International Nuclear Information System (INIS)

    Zhong, Hualiang; Chetty, Indrin

    2014-01-01

    Purpose: Accurate calculation of radiobiological parameters is crucial to predicting radiation treatment response. Modeling differences may have a significant impact on derived parameters. In this study, the authors have integrated two existing models with kinetic differential equations to formulate a new tumor regression model for estimation of radiobiological parameters for individual patients. Methods: A system of differential equations that characterizes the birth-and-death process of tumor cells in radiation treatment was analytically solved. The solution of this system was used to construct an iterative model (Z-model). The model consists of three parameters: tumor doubling time T d , half-life of dead cells T r , and cell survival fraction SF D under dose D. The Jacobian determinant of this model was proposed as a constraint to optimize the three parameters for six head and neck cancer patients. The derived parameters were compared with those generated from the two existing models: Chvetsov's model (C-model) and Lim's model (L-model). The C-model and L-model were optimized with the parameter T d fixed. Results: With the Jacobian-constrained Z-model, the mean of the optimized cell survival fractions is 0.43 ± 0.08, and the half-life of dead cells averaged over the six patients is 17.5 ± 3.2 days. The parameters T r and SF D optimized with the Z-model differ by 1.2% and 20.3% from those optimized with the T d -fixed C-model, and by 32.1% and 112.3% from those optimized with the T d -fixed L-model, respectively. Conclusions: The Z-model was analytically constructed from the differential equations of cell populations that describe changes in the number of different tumor cells during the course of radiation treatment. The Jacobian constraints were proposed to optimize the three radiobiological parameters. The generated model and its optimization method may help develop high-quality treatment regimens for individual patients

  10. A novel Tc-99m and fluorescence-labeled arginine-arginine-leucine-containing peptide as a multimodal tumor imaging agent in a murine tumor model.

    Science.gov (United States)

    Kim, Myoung Hyoun; Kim, Seul-Gi; Kim, Dae-Weung

    2018-06-15

    We developed a Tc-99m and TAMRA-labeled peptide, Tc-99m arginine-arginine-leucine (RRL) peptide (TAMRA-GHEG-ECG-RRL), to target tumor cells and evaluated the diagnostic performance of Tc-99m TAMRA-GHEG-ECG-RRL as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-RRL was synthesized using Fmoc solid-phase peptide synthesis. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with PC-3 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-RRL complexes were prepared in high yield (>96%). The K d of Tc-99m TAMRA-GHEG-ECG-RRL determined by saturation binding was 41.7 ± 7.8 nM. Confocal microscopy images of PC-3 cells incubated with TAMRA-GHEG-ECG-RRL showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of RRL. Specific uptake of Tc-99m TAMRA-GHEG-ECG-RRL was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In conclusion, in vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tc-99m TAMRA-GHEG-ECG-RRL has potential as a dual-modality tumor imaging agent. Copyright © 2018 John Wiley & Sons, Ltd.

  11. Synthesis and evaluation of Tc-99m and fluorescence-labeled elastin-derived peptide, VAPG for multimodal tumor imaging in murine tumor model.

    Science.gov (United States)

    Kim, Myoung Hyoun; Kim, Chang Guhn; Kim, Seul-Gi; Kim, Dae-Weung

    2017-12-01

    We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-VAPG to target tumor cells and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-VAPG was synthesized by using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-VAPG with Tc-99m was done by using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with SW620 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry by using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-VAPG complexes were prepared in high yield (>96%). The K d of Tc-99m TAMRA-GHEG-ECG-VAPG determined by saturation binding was 16.8 ± 3.6 nM. Confocal microscopy images of SW620 cells incubated with TAMRA-GHEG-ECG-VAPG showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of VAPG. Specific uptake of Tc-99m TAMRA-GHEG-ECG-VAPG was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumor cells. Tc-99m TAMRA-GHEG-ECG-VAPG has potential as a dual-modality tumor imaging agent. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology.

    Science.gov (United States)

    Apps, John Richard; Martinez-Barbera, Juan Pedro

    2017-05-01

    Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ-specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

  13. Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model.

    Science.gov (United States)

    Urrutia-Ortega, Ismael M; Garduño-Balderas, Luis G; Delgado-Buenrostro, Norma L; Freyre-Fonseca, Verónica; Flores-Flores, José O; González-Robles, Arturo; Pedraza-Chaverri, José; Hernández-Pando, Rogelio; Rodríguez-Sosa, Miriam; León-Cabrera, Sonia; Terrazas, Luis I; van Loveren, Henk; Chirino, Yolanda I

    2016-07-01

    Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Applications of Magnetic Resonance in Model Systems: Tumor Biology and Physiology

    Directory of Open Access Journals (Sweden)

    Robert J. Gillies

    2000-01-01

    Full Text Available A solid tumor presents a unique challenge as a system in which the dynamics of the relationship between vascularization, the physiological environment and metabolism are continually changing with growth and following treatment. Magnetic resonance imaging (MRI and magnetic resonance spectroscopy (MRS studies have demonstrated quantifiable linkages between the physiological environment, angiogenesis, vascularization and metabolism of tumors. The dynamics between these parameters continually change with tumor aggressiveness, tumor growth and during therapy and each of these can be monitored longitudinally, quantitatively and non-invasively with MRI and MRS. An important aspect of MRI and MRS studies is that techniques and findings are easily translated between systems. Hence, pre-clinical studies using cultured cells or experimental animals have a high connectivity to potential clinical utility. In the following review, leaders in the field of MR studies of basic tumor physiology using pre-clinical models have contributed individual sections according to their expertise and outlook. The following review is a cogent and timely overview of the current capabilities and state-of-the-art of MRI and MRS as applied to experimental cancers. A companion review deals with the application of MR methods to anticancer therapy.

  15. On the Inclusion of Short-distance Bystander Effects into a Logistic Tumor Control Probability Model.

    Science.gov (United States)

    Tempel, David G; Brodin, N Patrik; Tomé, Wolfgang A

    2018-01-01

    Currently, interactions between voxels are neglected in the tumor control probability (TCP) models used in biologically-driven intensity-modulated radiotherapy treatment planning. However, experimental data suggests that this may not always be justified when bystander effects are important. We propose a model inspired by the Ising model, a short-range interaction model, to investigate if and when it is important to include voxel to voxel interactions in biologically-driven treatment planning. This Ising-like model for TCP is derived by first showing that the logistic model of tumor control is mathematically equivalent to a non-interacting Ising model. Using this correspondence, the parameters of the logistic model are mapped to the parameters of an Ising-like model and bystander interactions are introduced as a short-range interaction as is the case for the Ising model. As an example, we apply the model to study the effect of bystander interactions in the case of radiation therapy for prostate cancer. The model shows that it is adequate to neglect bystander interactions for dose distributions that completely cover the treatment target and yield TCP estimates that lie in the shoulder of the dose response curve. However, for dose distributions that yield TCP estimates that lie on the steep part of the dose response curve or for inhomogeneous dose distributions having significant hot and/or cold regions, bystander effects may be important. Furthermore, the proposed model highlights a previously unexplored and potentially fruitful connection between the fields of statistical mechanics and tumor control probability/normal tissue complication probability modeling.

  16. Analysis of mice tumor models using dynamic MRI data and a dedicated software platform

    Energy Technology Data Exchange (ETDEWEB)

    Alfke, H.; Maurer, E.; Klose, K.J. [Philipps Univ. Marburg (Germany). Dept. of Radiology; Kohle, S.; Rascher-Friesenhausen, R.; Behrens, S.; Peitgen, H.O. [MeVis - Center for Medical Diagnostic Systems and Visualization, Bremen (Germany); Celik, I. [Philipps Univ. Marburg (Germany). Inst. for Theoretical Surgery; Heverhagen, J.T. [Philipps Univ. Marburg (Germany). Dept. of Radiology; Ohio State Univ., Columbus (United States). Dept. of Radiology

    2004-09-01

    Purpose: To implement a software platform (DynaVision) dedicated to analyze data from functional imaging of tumors with different mathematical approaches, and to test the software platform in pancreatic carcinoma xenografts in mice with severe combined immunodeficiency disease (SCID). Materials and Methods: A software program was developed for extraction and visualization of tissue perfusion parameters from dynamic contrast-enhanced images. This includes regional parameter calculation from enhancement curves, parametric images (e.g., blood flow), animation, 3D visualization, two-compartment modeling a mode for comparing different datasets (e.g., therapy monitoring), and motion correction. We analyzed xenograft tumors from two pancreatic carcinoma cell lines (B x PC3 and ASPC1) implanted in 14 SCID mice after injection of Gd-DTPA into the tail vein. These data were correlated with histopathological findings. Results: Image analysis was completed in approximately 15 minutes per data set. The possibility of drawing and editing ROIs within the whole data set makes it easy to obtain quantitative data from the intensity-time curves. In one animal, motion artifacts reduced the image quality to a greater extent but data analysis was still possible after motion correction. Dynamic MRI of mice tumor models revealed a highly heterogeneous distribution of the contrast-enhancement curves and derived parameters, which correlated with differences in histopathology. ASPc1 tumors showed a more hypervascular type of curves with faster and higher signal enhancement rate (wash-in) and a faster signal decrease (wash-out). BXPC3 tumors showed a more hypovascular type with slower wash-in and wash-out. This correlated with the biological properties of the tumors. (orig.)

  17. Analysis of mice tumor models using dynamic MRI data and a dedicated software platform

    International Nuclear Information System (INIS)

    Alfke, H.; Maurer, E.; Klose, K.J.; Celik, I.; Heverhagen, J.T.; Ohio State Univ., Columbus

    2004-01-01

    Purpose: To implement a software platform (DynaVision) dedicated to analyze data from functional imaging of tumors with different mathematical approaches, and to test the software platform in pancreatic carcinoma xenografts in mice with severe combined immunodeficiency disease (SCID). Materials and Methods: A software program was developed for extraction and visualization of tissue perfusion parameters from dynamic contrast-enhanced images. This includes regional parameter calculation from enhancement curves, parametric images (e.g., blood flow), animation, 3D visualization, two-compartment modeling a mode for comparing different datasets (e.g., therapy monitoring), and motion correction. We analyzed xenograft tumors from two pancreatic carcinoma cell lines (B x PC3 and ASPC1) implanted in 14 SCID mice after injection of Gd-DTPA into the tail vein. These data were correlated with histopathological findings. Results: Image analysis was completed in approximately 15 minutes per data set. The possibility of drawing and editing ROIs within the whole data set makes it easy to obtain quantitative data from the intensity-time curves. In one animal, motion artifacts reduced the image quality to a greater extent but data analysis was still possible after motion correction. Dynamic MRI of mice tumor models revealed a highly heterogeneous distribution of the contrast-enhancement curves and derived parameters, which correlated with differences in histopathology. ASPc1 tumors showed a more hypervascular type of curves with faster and higher signal enhancement rate (wash-in) and a faster signal decrease (wash-out). BXPC3 tumors showed a more hypovascular type with slower wash-in and wash-out. This correlated with the biological properties of the tumors. (orig.)

  18. Development of model plans in three dimensional conformal radiotherapy for brain tumors

    International Nuclear Information System (INIS)

    Pyo, Hongryull; Kim, Gwieon; Keum, Kichang; Chang, Sekyung; Suh, Changok; Lee, Sanghoon

    2002-01-01

    Three dimensional conformal radiotherapy planning is being used widely for the treatment of patients with brain tumor. However, it takes much time to develop an optimal treatment plan, therefore, it is difficult to apply this technique to all patients. To increase the efficiency of this technique, we need to develop standard radiotherapy plans for each site of the brain. Therefore we developed several 3 dimensional conformal radiotherapy plans (3D plans) for tumors at each site of brain, compared them with each other, and with 2 dimensional radiotherapy plans. Finally model plans for each site of the brain were decided. Imaginary tumors, with sizes commonly observed in the clinic, were designed for each site of the brain and drawn on CT images. The planning target volumes (PTVs) were as follows; temporal tumor-5.7 x 8.2 x 7.6 cm, suprasellar tumor-3 x 4 x 4.1 cm, thalamic tumor-3.1 x 5.9 x 3.7 cm, frontoparietal tumor-5.5 x 7 x 5.5 cm, and occipitoparietal tumor-5 x 5.5 x 5 cm. Plans using parallel opposed 2-portals and/or 3 portals including fronto-vertex and 2 lateral fields were developed manually as the conventional 2D plans, and 3D noncoplanar conformal plans were developed using beam's eye view and the automatic block drawing tool. Total tumor dose was 54 Gy for a suprasellar tumor, 59.4 Gy and 72 Gy for the other tumors. All dose plans (including 2D plans) were calculated using 3D plan software. Developed plans were compared with each other using dose-volume histograms (DVH), normal tissue complication probabilities (NTCP) and variable dose statistic values (minimum, maximum and mean dose, D5, V83, V85 and V95). Finally a best radiotherapy plan for each site of brain was selected. 1) Temporal tumor; NTCPs and DVHs of the normal tissue of all 3D plans were superior to 2D plans and this trend was more definite when total dose was escalated to 72 Gy (NTCPs of normal brain 2D plans: 27%, 8% → 3D plans: 1%, 1%). Various dose statistic values did not show any

  19. Three-dimensional printing of Hela cells for cervical tumor model in vitro

    International Nuclear Information System (INIS)

    Zhao, Yu; Yao, Rui; Ouyang, Liliang; Ding, Hongxu; Zhang, Ting; Sun, Wei; Zhang, Kaitai; Cheng, Shujun

    2014-01-01

    Advances in three-dimensional (3D) printing have enabled the direct assembly of cells and extracellular matrix materials to form in vitro cellular models for 3D biology, the study of disease pathogenesis and new drug discovery. In this study, we report a method of 3D printing for Hela cells and gelatin/alginate/fibrinogen hydrogels to construct in vitro cervical tumor models. Cell proliferation, matrix metalloproteinase (MMP) protein expression and chemoresistance were measured in the printed 3D cervical tumor models and compared with conventional 2D planar culture models. Over 90% cell viability was observed using the defined printing process. Comparisons of 3D and 2D results revealed that Hela cells showed a higher proliferation rate in the printed 3D environment and tended to form cellular spheroids, but formed monolayer cell sheets in 2D culture. Hela cells in 3D printed models also showed higher MMP protein expression and higher chemoresistance than those in 2D culture. These new biological characteristics from the printed 3D tumor models in vitro as well as the novel 3D cell printing technology may help the evolution of 3D cancer study. (paper)

  20. Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity

    Directory of Open Access Journals (Sweden)

    Vanessa Almendro

    2014-02-01

    Full Text Available Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.

  1. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    International Nuclear Information System (INIS)

    Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; Van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution

  2. Modeling freedom from progression for standard-risk medulloblastoma: a mathematical tumor control model with multiple modes of failure

    DEFF Research Database (Denmark)

    Brodin, Nils Patrik; Vogelius, Ivan R.; Bjørk-Eriksson, Thomas

    2013-01-01

    As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published...

  3. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  4. Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

    Science.gov (United States)

    da Rocha, E L; Porto, L M; Rambo, C R

    2014-01-01

    Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

  5. Interleukin-12 Inhibits Tumor Growth in a Novel Angiogenesis Canine Hemangiosarcoma Xenograft Model

    Directory of Open Access Journals (Sweden)

    Nasim Akhtar

    2004-03-01

    Full Text Available We established a canine hemangiosarcoma cell line derived from malignant endothelial cells comprising a spontaneous tumor in a dog to provide a renewable source of endothelial cells for studies of angiogenesis in malignancy. Pieces of the hemangiosarcoma biopsy were engrafted subcutaneously in a bg/nu/XID mouse allowing the tumor cells to expand in vivo. A cell line, SB-HSA, was derived from the xenograft. SB-HSA cells expressed vascular endothelial growth factor (VEGF receptors 1 and 2, CD31, CD146, and αvβ3 integrin, and produced several growth factors and cytokines, including VEGF, basic fibroblast growth factor, and interleukin (IL-8 that are stimulatory to endothelial cell growth. These results indicated that the cells recapitulated features of mitotically activated endothelia. In vivo, SB-HSA cells stimulated robust angiogenic responses in mice and formed tumor masses composed of aberrant vascular channels in immunocompromised mice providing novel opportunities for investigating the effectiveness of antiangiogenic agents. Using this model, we determined that IL-12, a cytokine with both immunostimulatory and antiangiogenic effects, suppressed angiogenesis induced by, and tumor growth of, SB-HSA cells. The endothelial cell model we have described offers unique opportunities to pursue further investigations with IL-12, as well as other antiangiogenic approaches in cancer therapy.

  6. [Computer aided diagnosis model for lung tumor based on ensemble convolutional neural network].

    Science.gov (United States)

    Wang, Yuanyuan; Zhou, Tao; Lu, Huiling; Wu, Cuiying; Yang, Pengfei

    2017-08-01

    The convolutional neural network (CNN) could be used on computer-aided diagnosis of lung tumor with positron emission tomography (PET)/computed tomography (CT), which can provide accurate quantitative analysis to compensate for visual inertia and defects in gray-scale sensitivity, and help doctors diagnose accurately. Firstly, parameter migration method is used to build three CNNs (CT-CNN, PET-CNN, and PET/CT-CNN) for lung tumor recognition in CT, PET, and PET/CT image, respectively. Then, we aimed at CT-CNN to obtain the appropriate model parameters for CNN training through analysis the influence of model parameters such as epochs, batchsize and image scale on recognition rate and training time. Finally, three single CNNs are used to construct ensemble CNN, and then lung tumor PET/CT recognition was completed through relative majority vote method and the performance between ensemble CNN and single CNN was compared. The experiment results show that the ensemble CNN is better than single CNN on computer-aided diagnosis of lung tumor.

  7. Implementation of plaid model biclustering method on microarray of carcinoma and adenoma tumor gene expression data

    Science.gov (United States)

    Ardaneswari, Gianinna; Bustamam, Alhadi; Sarwinda, Devvi

    2017-10-01

    A Tumor is an abnormal growth of cells that serves no purpose. Carcinoma is a tumor that grows from the top of the cell membrane and the organ adenoma is a benign tumor of the gland-like cells or epithelial tissue. In the field of molecular biology, the development of microarray technology is used in the data store of disease genetic expression. For each of microarray gene, an amount of information is stored for each trait or condition. In gene expression data clustering can be done with a bicluster algorithm, thats clustering method which not only the objects to be clustered, but also the properties or condition of the object. This research proposed Plaid Model Biclustering as one of biclustering method. In this study, we discuss the implementation of Plaid Model Biclustering Method on microarray of Carcinoma and Adenoma tumor gene expression data. From the experimental results, we found three biclusters are formed by Carcinoma gene expression data and four biclusters are formed by Adenoma gene expression data.

  8. Interfacial thermodynamics of water and six other liquid solvents.

    Science.gov (United States)

    Pascal, Tod A; Goddard, William A

    2014-06-05

    We examine the thermodynamics of the liquid-vapor interface by direct calculation of the surface entropy, enthalpy, and free energy from extensive molecular dynamics simulations using the two-phase thermodynamics (2PT) method. Results for water, acetonitrile, cyclohexane, dimethyl sulfoxide, hexanol, N-methyl acetamide, and toluene are presented. We validate our approach by predicting the interfacial surface tensions (IFT--excess surface free energy per unit area) in excellent agreement with the mechanical calculations using Kirkwood-Buff theory. Additionally, we evaluate the temperature dependence of the IFT of water as described by the TIP4P/2005, SPC/Ew, TIP3P, and mW classical water models. We find that the TIP4P/2005 and SPC/Ew water models do a reasonable job of describing the interfacial thermodynamics; however, the TIP3P and mW are quite poor. We find that the underprediction of the experimental IFT at 298 K by these water models results from understructured surface molecules whose binding energies are too weak. Finally, we performed depth profiles of the interfacial thermodynamics which revealed long tails that extend far into what would be considered bulk from standard Gibbs theory. In fact, we find a nonmonotonic interfacial free energy profile for water, a unique feature that could have important consequences for the absorption of ions and other small molecules.

  9. A realistic closed-form radiobiological model of clinical tumor-control data incorporating intertumor heterogeneity

    International Nuclear Information System (INIS)

    Roberts, Stephen A.; Hendry, Jolyon H.

    1998-01-01

    Purpose: To investigate the role of intertumor heterogeneity in clinical tumor control datasets and the relationship to in vitro measurements of tumor biopsy samples. Specifically, to develop a modified linear-quadratic (LQ) model incorporating such heterogeneity that it is practical to fit to clinical tumor-control datasets. Methods and Materials: We developed a modified version of the linear-quadratic (LQ) model for tumor control, incorporating a (lagged) time factor to allow for tumor cell repopulation. We explicitly took into account the interpatient heterogeneity in clonogen number, radiosensitivity, and repopulation rate. Using this model, we could generate realistic TCP curves using parameter estimates consistent with those reported from in vitro studies, subject to the inclusion of a radiosensitivity (or dose)-modifying factor. We then demonstrated that the model was dominated by the heterogeneity in α (tumor radiosensitivity) and derived an approximate simplified model incorporating this heterogeneity. This simplified model is expressible in a compact closed form, which it is practical to fit to clinical datasets. Using two previously analysed datasets, we fit the model using direct maximum-likelihood techniques and obtained parameter estimates that were, again, consistent with the experimental data on the radiosensitivity of primary human tumor cells. This heterogeneity model includes the same number of adjustable parameters as the standard LQ model. Results: The modified model provides parameter estimates that can easily be reconciled with the in vitro measurements. The simplified (approximate) form of the heterogeneity model is a compact, closed-form probit function that can readily be fitted to clinical series by conventional maximum-likelihood methodology. This heterogeneity model provides a slightly better fit to the datasets than the conventional LQ model, with the same numbers of fitted parameters. The parameter estimates of the clinically

  10. Bioprinting of three dimensional tumor models: a preliminary study using a low cost 3D printer

    Directory of Open Access Journals (Sweden)

    Polley Christian

    2017-09-01

    Full Text Available The deep understanding of cancer and tumor genesis, as well as the development of new therapy strategies still remains one of the emerging challenges in modern medicine. To meet these challenges it seems to be absolutely necessary to overcome the drawbacks of the established 2D in vitro models. Especially the missing microenvironment of the tumor, which means the absence of stroma and immune cells, results in a missing cell-cell and cell-stroma interaction as well as disrupted functional communication pathways. Modern 3D culture systems and 3D printing or rather bioprinting technologies attempt to solve this issue and aim to closely mimic natural tumor microenvironment. In this preliminary work we are going to present the first steps of establishing an artificial 3D tumor model utilising a low cost 3D printer. Therefore the printer had been modified with an open-source syringe pump to become a functional bioprinter using viscosity modulated alginate hydrogel. In the first attempts L929 mouse fibroblasts, which are an integral component of natural stroma, had been incorporated into the hydrogel matrix and printed into scaffolds. Subsequent to the printing process the scaffolds got ionically crosslinked with a 5% w/v aqueous solution of CaCl2 to become mechanically stable. After three days of cultivation viability testing had been performed by utilising FDG staining and PET CT to obtain a volumetric viability measurement. The viability imaging showed vital cells homogeneously distributed in the scaffold and therefore stands as an evidence for a working low cost bioprinting process and a successful first step for the development of an artificial 3D tumor model.

  11. Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models

    Directory of Open Access Journals (Sweden)

    Fabrice Le Boeuf

    2017-09-01

    Full Text Available The reovirus fusion-associated small transmembrane (FAST proteins are the smallest known viral fusogens (∼100–150 amino acids and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant encoding the p14 FAST protein (VSV-p14 was compared with a similar construct encoding GFP (VSV-GFP in cell culture and syngeneic BALB/c tumor models. Compared with VSV-GFP, VSV-p14 exhibited increased oncolytic activity against MCF-7 and 4T1 breast cancer spheroids in culture and reduced primary 4T1 breast tumor growth in vivo. VSV-p14 prolonged survival in both primary and metastatic 4T1 breast cancer models, and in a CT26 metastatic colon cancer model. As with VSV-GFP, VSV-p14 preferentially replicated in vivo in tumors and was cleared rapidly from other sites. Furthermore, VSV-p14 increased the numbers of activated splenic CD4, CD8, natural killer (NK, and natural killer T (NKT cells, and increased the number of activated CD4 and CD8 cells in tumors. FAST proteins may therefore provide a multi-pronged approach to improving oncolytic virotherapy via syncytium formation and enhanced immune stimulation.

  12. Predictive model of thrombospondin-1 and vascular endothelial growth factor in breast tumor tissue.

    Science.gov (United States)

    Rohrs, Jennifer A; Sulistio, Christopher D; Finley, Stacey D

    2016-01-01

    Angiogenesis, the formation of new blood capillaries from pre-existing vessels, is a hallmark of cancer. Thus far, strategies for reducing tumor angiogenesis have focused on inhibiting pro-angiogenic factors, while less is known about the therapeutic effects of mimicking the actions of angiogenesis inhibitors. Thrombospondin-1 (TSP1) is an important endogenous inhibitor of angiogenesis that has been investigated as an anti-angiogenic agent. TSP1 impedes the growth of new blood vessels in many ways, including crosstalk with pro-angiogenic factors. Due to the complexity of TSP1 signaling, a predictive systems biology model would provide quantitative understanding of the angiogenic balance in tumor tissue. Therefore, we have developed a molecular-detailed, mechanistic model of TSP1 and vascular endothelial growth factor (VEGF), a promoter of angiogenesis, in breast tumor tissue. The model predicts the distribution of the angiogenic factors in tumor tissue, revealing that TSP1 is primarily in an inactive, cleaved form due to the action of proteases, rather than bound to its cellular receptors or to VEGF. The model also predicts the effects of enhancing TSP1's interactions with its receptors and with VEGF. To provide additional predictions that can guide the development of new anti-angiogenic drugs, we simulate administration of exogenous TSP1 mimetics that bind specific targets. The model predicts that the CD47-binding TSP1 mimetic dramatically decreases the ratio of receptor-bound VEGF to receptor-bound TSP1, in favor of anti-angiogenesis. Thus, we have established a model that provides a quantitative framework to study the response to TSP1 mimetics.

  13. Visualizing Early-Stage Breast Cancer Tumors in a Mammographic Environment Through a 3-Dimensional Mathematical Model

    National Research Council Canada - National Science Library

    Bassham, Christopher

    1999-01-01

    ... of improving early breast cancer detection. By using modeling and simulation to construct an accurate breast cancer tumor model, we hope to solve the problems associated with mammogram misdiagnosis and, perhaps as a by-product, lend insight...

  14. SU-G-IeP4-11: Monitoring Tumor Growth in Subcutaneous Murine Tumor Model in Vivo: A Comparison Between MRI and Small Animal CT

    Energy Technology Data Exchange (ETDEWEB)

    Wang, B; He, W; Cvetkovic, D; Chen, L; Fan, J; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2016-06-15

    Purpose: The purpose of the study is to compare the volume measurement of subcutaneous tumors in mice with different imaging platforms, namely a GE MRI and a Sofie-Biosciences small animal CT scanner. Methods: A549 human lung carcinoma cells and FaDu human head and neck squamous cell carcinoma cells were implanted subcutaneously into flanks of nude mice. Three FaDu tumors and three A549 tumors were included in this study. The MRI scans were done with a GE Signa 1.5 Tesla MR scanner using a fast T2-weighted sequence (70mm FOV and 1.2mm slice thickness), while the CT scans were done with the CT scanner on a Sofie-Biosciences G8 PET/CT platform dedicated for small animal studies (48mm FOV and 0.2mm slice thickness). Imaging contrast agent was not used in this study. Based on the DICOM images from MRI and CT scans, the tumors were contoured with Philips DICOM Viewer and the tumor volumes were obtained by summing up the contoured area and multiplied by the slice thickness. Results: The volume measurements based on the CT scans agree reasonably with that obtained with MR images for the subcutaneous tumors. The mean difference in the absolute tumor volumes between MRI- and CT-based measurements was found to be −6.2% ± 1.0%, with the difference defined as (VMR – VCT)*100%/VMR. Furthermore, we evaluated the normalized tumor volumes, which were defined for each tumor as V/V{sub 0} where V{sub 0} stands for the volume from the first MR or CT scan. The mean difference in the normalized tumor volumes was found to be 0.10% ± 0.96%. Conclusion: Despite the fact that the difference between normal and abnormal tissues is often less clear on small animal CT images than on MR images, one can still obtain reasonable tumor volume information with the small animal CT scans for subcutaneous murine xenograft models.

  15. Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling.

    Science.gov (United States)

    Rommelfanger, D M; Offord, C P; Dev, J; Bajzer, Z; Vile, R G; Dingli, D

    2012-05-01

    Tumor selective, replication competent viruses are being tested for cancer gene therapy. This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system.

  16. Spectral imaging based in vivo model system for characterization of tumor microvessel response to vascular targeting agents

    Science.gov (United States)

    Wankhede, Mamta

    Functional vasculature is vital for tumor growth, proliferation, and metastasis. Many tumor-specific vascular targeting agents (VTAs) aim to destroy this essential tumor vasculature to induce indirect tumor cell death via oxygen and nutrition deprivation. The tumor angiogenesis-inhibiting anti-angiogenics (AIs) and the established tumor vessel targeting vascular disrupting agents (VDAs) are the two major players in the vascular targeting field. Combination of VTAs with conventional therapies or with each other, have been shown to have additive or supra-additive effects on tumor control and treatment. Pathophysiological changes post-VTA treatment in terms of structural and vessel function changes are important parameters to characterize the treatment efficacy. Despite the abundance of information regarding these parameters acquired using various techniques, there remains a need for a quantitative, real-time, and direct observation of these phenomenon in live animals. Through this research we aspired to develop a spectral imaging based mouse tumor system for real-time in vivo microvessel structure and functional measurements for VTA characterization. A model tumor system for window chamber studies was identified, and then combinatorial effects of VDA and AI were characterized in model tumor system. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

  17. Constructing TC-1-GLUC-LMP2 Model Tumor Cells to Evaluate the Anti-Tumor Effects of LMP2-Related Vaccines

    Science.gov (United States)

    Sun, Liying; Hao, Yanzhe; Wang, Zhan; Zeng, Yi

    2018-01-01

    Epstein-Barr virus (EBV) is related to a variety of malignant tumors, and its encoded protein, latent membrane protein 2 (LMP2), is an effective target antigen that is widely used to construct vector vaccines. However, the model cells carrying LMP2 have still not been established to assess the oncolytic effect of LMP2-related vaccines at present. In this study, TC-1-GLUC-LMP2 tumor cells were constructed as target cells to evaluate the anti-tumor effects of LMP2-assosiated vaccines. The results showed that both LMP2 and Gaussia luciferase (GLuc) genes could be detected by polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) in TC-1-GLUC-LMP2 cells. Western blot results showed that the LMP2 and Gaussia luciferase proteins were stably expressed in tumor cells for at least 30 generations. We mixed 5 × 104 LMP2-specific mouse splenic lymphocytes with 5 × 103 TC-1-GLUC-LMP2 target cells and found that the target cells were killed as the specific killing effect was obviously enhanced by the increased quantities of LMP2-peptide stimulated spleens. Furthermore, the tumor cells could not be observed in the mice inoculated TC-1-GLUC-LMP2 cells after being immunized with vaccine-LMP2, while the vaccine-NULL immunized mice showed that tumor volume gradually grew with increased inoculation time. These results indicated that the TC-1-GLUC-LMP2 cells stably expressing LMP2 and GLuc produced tumors in mice, and that the LMP2-specific cytotoxic T lymphocyte (CTL) effectively killed the cells in vitro and in vivo, suggesting that TC-1-GLUC-LMP2 cells can be used as model cells to assess the immune and antitumor effects of LMP2-related vaccines. PMID:29570629

  18. Interfacial reactions between titanium and borate glass

    Energy Technology Data Exchange (ETDEWEB)

    Brow, R.K. [Sandia National Labs., Albuquerque, NM (United States); Saha, S.K.; Goldstein, J.I. [Lehigh Univ., Bethlehem, PA (United States). Dept. of Materials Science

    1992-12-31

    Interfacial reactions between melts of several borate glasses and titanium have been investigated by analytical scanning electron microscopy (SEM) and x-ray photoelectron spectroscopy (XPS). A thin titanium boride interfacial layer is detected by XPS after short (30 minutes) thermal treatments. ASEM analyses after longer thermal treatments (8--120 hours) reveal boron-rich interfacial layers and boride precipitates in the Ti side of the interface.

  19. Immuno-therapy with anti-CTLA4 antibodies in tolerized and non-tolerized mouse tumor models.

    Directory of Open Access Journals (Sweden)

    Jonas Persson

    Full Text Available Monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4 are a novel form of cancer immunotherapy. While preclinical studies in mouse tumor models have shown anti-tumor efficacy of anti-CTLA4 injection or expression, anti-CTLA4 treatment in patients with advanced cancers had disappointing therapeutic benefit. These discrepancies have to be addressed in more adequate pre-clinical models. We employed two tumor models. The first model is based on C57Bl/6 mice and syngeneic TC-1 tumors expressing HPV16 E6/E7. In this model, the HPV antigens are neo-antigens, against which no central tolerance exists. The second model involves mice transgenic for the proto-oncogen neu and syngeneic mouse mammary carcinoma (MMC cells. In this model tolerance to Neu involves both central and peripheral mechanisms. Anti-CTLA4 delivery as a protein or expression from gene-modified tumor cells were therapeutically efficacious in the non-tolerized TC-1 tumor model, but had no effect in the MMC-model. We also used the two tumor models to test an immuno-gene therapy approach for anti-CTLA4. Recently, we used an approach based on hematopoietic stem cells (HSC to deliver the relaxin gene to tumors and showed that this approach facilitates pre-existing anti-tumor T-cells to control tumor growth in the MMC tumor model. However, unexpectedly, when used for anti-CTLA4 gene delivery in this study, the HSC-based approach was therapeutically detrimental in both the TC-1 and MMC models. Anti-CTLA4 expression in these models resulted in an increase in the number of intratumoral CD1d+ NKT cells and in the expression of TGF-β1. At the same time, levels of pro-inflammatory cytokines and chemokines, which potentially can support anti-tumor T-cell responses, were lower in tumors of mice that received anti-CTLA4-HSC therapy. The differences in outcomes between the tolerized and non-tolerized models also provide a potential explanation for the low efficacy

  20. Development and Validity of a Silicone Renal Tumor Model for Robotic Partial Nephrectomy Training.

    Science.gov (United States)

    Monda, Steven M; Weese, Jonathan R; Anderson, Barrett G; Vetter, Joel M; Venkatesh, Ramakrishna; Du, Kefu; Andriole, Gerald L; Figenshau, Robert S

    2018-04-01

    To provide a training tool to address the technical challenges of robot-assisted laparoscopic partial nephrectomy, we created silicone renal tumor models using 3-dimensional printed molds of a patient's kidney with a mass. In this study, we assessed the face, content, and construct validity of these models. Surgeons of different training levels completed 4 simulations on silicone renal tumor models. Participants were surveyed on the usefulness and realism of the model as a training tool. Performance was measured using operation-specific metrics, self-reported operative demands (NASA Task Load Index [NASA TLX]), and blinded expert assessment (Global Evaluative Assessment of Robotic Surgeons [GEARS]). Twenty-four participants included attending urologists, endourology fellows, urology residents, and medical students. Post-training surveys of expert participants yielded mean results of 79.2 on the realism of the model's overall feel and 90.2 on the model's overall usefulness for training. Renal artery clamp times and GEARS scores were significantly better in surgeons further in training (P ≤.005 and P ≤.025). Renal artery clamp times, preserved renal parenchyma, positive margins, NASA TLX, and GEARS scores were all found to improve across trials (P <.001, P = .025, P = .024, P ≤.020, and P ≤.006, respectively). Face, content, and construct validity were demonstrated in the use of a silicone renal tumor model in a cohort of surgeons of different training levels. Expert participants deemed the model useful and realistic. Surgeons of higher training levels performed better than less experienced surgeons in various study metrics, and improvements within individuals were observed over sequential trials. Future studies should aim to assess model predictive validity, namely, the association between model performance improvements and improvements in live surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. The intraportal injection model: A practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer

    International Nuclear Information System (INIS)

    Thalheimer, Andreas; Waaga-Gasser, Ana M; Otto, Christoph; Bueter, Marco; Illert, Bertram; Gattenlohner, Stefan; Gasser, Martin; Meyer, Detlef; Fein, Martin; Germer, Christoph T

    2009-01-01

    The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. We injected immunoincompetent nude mice intraportally with different numbers (1 × 10 5 , 1 × 10 6 and 5 × 10 6 cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow. Only the injection of 1 × 10 6 cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 × 10 6 cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases. The present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD

  2. Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

    Directory of Open Access Journals (Sweden)

    Thorsten Frenzel

    Full Text Available Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior.Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

  3. Fibroblast spheroids as a model to study sustained fibroblast quiescence and their crosstalk with tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Salmenperä, Pertteli, E-mail: pertteli.salmenpera@helsinki.fi [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Karhemo, Piia-Riitta [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Räsänen, Kati [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Laakkonen, Pirjo [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Vaheri, Antti [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland)

    2016-07-01

    Stromal fibroblasts have an important role in regulating tumor progression. Normal and quiescent fibroblasts have been shown to restrict and control cancer cell growth, while cancer-associated, i. e. activated fibroblasts have been shown to enhance proliferation and metastasis of cancer cells. In this study we describe generation of quiescent fibroblasts in multicellular spheroids and their effects on squamous cell carcinoma (SCC) growth in soft-agarose and xenograft models. Quiescent phenotype of fibroblasts was determined by global down-regulation of expression of genes related to cell cycle and increased expression of p27. Interestingly, microarray analysis showed that fibroblast quiescence was associated with similar secretory phenotype as seen in senescence and they expressed senescence-associated-β-galactosidase. Quiescent fibroblasts spheroids also restricted the growth of RT3 SCC cells both in soft-agarose and xenograft models unlike proliferating fibroblasts. Restricted tumor growth was associated with marginally increased tumor cell senescence and cellular differentiation, showed with senescence-associated-β-galactosidase and cytokeratin 7 staining. Our results show that the fibroblasts spheroids can be used as a model to study cellular quiescence and their effects on cancer cell progression. - Highlights: • Fibroblasts acquire a sustained quiescence when grown as multicellular spheroids. • This quiescence is associated with drastic change in gene expression. • Fibroblasts spheroids secrete various inflammation-linked cytokines and chemokines. • Fibroblasts spheroids reduced growth of RT3 SCC cells in xenograft model.

  4. On Statistical Modeling of Sequencing Noise in High Depth Data to Assess Tumor Evolution

    Science.gov (United States)

    Rabadan, Raul; Bhanot, Gyan; Marsilio, Sonia; Chiorazzi, Nicholas; Pasqualucci, Laura; Khiabanian, Hossein

    2017-12-01

    One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate our model with simulated exponentially expanded populations as well as data from cell line and patient sample dilution experiments, demonstrating its utility in prognosticating tumor progression. Our results may have the potential to identify significant mutations that can cause recurrence. These results are relevant in the pretreatment clinical setting to determine appropriate therapy and prepare for potential recurrence pretreatment.

  5. Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.

    Science.gov (United States)

    Shariatpanahi, Seyed Peyman; Shariatpanahi, Seyed Pooya; Madjidzadeh, Keivan; Hassan, Moustapha; Abedi-Valugerdi, Manuchehr

    2018-04-07

    Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Antibody deposition in tumor in relation to blood clearance using a nephrectomized mouse model

    International Nuclear Information System (INIS)

    Nelp, W.B.; Eary, J.F.; Beaumier, P.; Krohn, K.A.; Hellstrom, K.E.; Hellstrom, I.

    1985-01-01

    The purpose of this experiment was to study tumor deposition of monoclonal anti-p97 melanoma antibody (Fab) as a function of its blood concentration over time. I-131-anti-p97 Fab and I-125 non-specific Fab were injected I.V. into 28 control athymic (nude) mice (CM) bearing human xenografted malignant melanoma containing p-97 antigen. Fab (M.W. 50,000) is rapidly excreted by kidney and >90% excretion occurred in 24 hr. To create maximum sustained high blood concentrations of Fab 10 similar mice were likewise injected 1 hr after acute nephrectomy (NM). In this case 24 hr. body excretion was <1%. Blood clearance in CM was biexponential with initial T-1/2 0.4 hr. (80%) a second T-1/2 of 4.4 hr. In NM clearance was monoexponential with a T-1/2 of 29.6 hr. Blood concentrations at 4 hrs. were 2 vs. 19% dose/gm (CM vs NM) and 0.15 vs 12 at 24 hrs. This tumor binding resembled a 2nd order phenomenon. Such information may be useful in predicting the effect of dosage manipulations (multiple bolus or sustained infusions) designed to increase Fab blood levels and enhance tumor labeling with Fab. The NM model should be useful to study the kinetics of antibody tumor deposition with various antibodies

  7. Advanced Imaging Approaches to Characterize Stromal and Metabolic Changes in In Vivo Mammary Tumor Models

    Science.gov (United States)

    2015-02-01

    Bird , L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, N. Ramanujam, Metabolic mapping of MCF10A human breast cells...1   Award Number: W81XWH-12-1-0025 TITLE: Advanced Imaging Approaches to Characterize Stromal and Metabolic Changes in In Vivo Mammary... Metabolic Changes in In Vivo Mammary Tumor Models 5b. GRANT NUMBER BC112240 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT NUMBER

  8. SU-E-T-751: Three-Component Kinetic Model of Tumor Growth and Radiation Response for Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Y; Dahlman, E; Leder, K; Hui, S [University of Minnesota, Minneapolis, MN (United States)

    2015-06-15

    Purpose: To develop and study a kinetic model of tumor growth and its response to stereotactic radiosurgery (SRS) by assuming that the cells in irradiated tumor volume were made of three types. Methods: A set of ordinary differential equations (ODEs) were derived for three types of cells and a tumor growth rate. It is assumed that the cells were composed of actively proliferating cells, lethally damaged-dividing cells, and non-dividing cells. We modeled the tumor volume growth with a time-dependent growth rate to simulate the saturation of growth. After SRS, the proliferating cells were permanently damaged and converted to the lethally damaged cells. The amount of damaged cells were estimated by the LQ-model. The damaged cells gradually stopped dividing/proliferating and died with a constant rate. The dead cells were cleared from their original location with a constant rate. The total tumor volume was the sum of the three components. The ODEs were numerically solved with appropriate initial conditions for a given dosage. The proposed model was used to model an animal experiment, for which the temporal change of a rhabdomyosarcoma tumor volume grown in a rat was measured with time resolution sufficient to test the model. Results: To fit the model to the experimental data, the following characteristics were needed with the model parameters. The α-value in the LQ-model was smaller than the commonly used value; furthermore, it decreased with increasing dose. At the same time, the tumor growth rate after SRS had to increase. Conclusions: The new 3-component model of tumor could simulate the experimental data very well. The current study suggested that the radiation sensitivity and the growth rate of the proliferating tumor cells may change after irradiation and it depended on the dosage used for SRS. These preliminary observations must be confirmed by future animal experiments.

  9. Tumor-Volume Simulation During Radiotherapy for Head-and-Neck Cancer Using a Four-Level Cell Population Model

    International Nuclear Information System (INIS)

    Chvetsov, Alexei V.; Dong Lei; Palta, Jantinder R.; Amdur, Robert J.

    2009-01-01

    Purpose: To develop a fast computational radiobiologic model for quantitative analysis of tumor volume during fractionated radiotherapy. The tumor-volume model can be useful for optimizing image-guidance protocols and four-dimensional treatment simulations in proton therapy that is highly sensitive to physiologic changes. Methods: The analysis is performed using two approximations: (1) tumor volume is a linear function of total cell number and (2) tumor-cell population is separated into four subpopulations: oxygenated viable cells, oxygenated lethally damaged cells, hypoxic viable cells, and hypoxic lethally damaged cells. An exponential decay model is used for disintegration and removal of oxygenated lethally damaged cells from the tumor. Results: We tested our model on daily volumetric imaging data available for 14 head-and-neck cancer patients treated with an integrated computed tomography/linear accelerator system. A simulation based on the averaged values of radiobiologic parameters was able to describe eight cases during the entire treatment and four cases partially (50% of treatment time) with a maximum 20% error. The largest discrepancies between the model and clinical data were obtained for small tumors, which may be explained by larger errors in the manual tumor volume delineation procedure. Conclusions: Our results indicate that the change in gross tumor volume for head-and-neck cancer can be adequately described by a relatively simple radiobiologic model. In future research, we propose to study the variation of model parameters by fitting to clinical data for a cohort of patients with head-and-neck cancer and other tumors. The potential impact of other processes, like concurrent chemotherapy, on tumor volume should be evaluated.

  10. Ultrasonic Guided Waves in Piezoelectric Layered Composite with Different Interfacial Properties

    Directory of Open Access Journals (Sweden)

    Xiao Chen

    2011-01-01

    Full Text Available Combining the propagation model of guided waves in a multilayered piezoelectric composite with the interfacial model of rigid, slip, and weak interfaces, the generalized dispersion characteristic equations of guided waves propagating in a piezoelectric layered composite with different interfacial properties are derived. The effects of the slip, weak, and delamination interfaces in different depths on the dispersion properties of the lowest-order mode ultrasonic guided wave are analyzed. The theory would be used to characterize the interfacial properties of piezoelectric layered composite nondestructively.

  11. Myeloid leukemias and virally induced lymphomas in miniature inbred swine; development of a large animal tumor model

    Directory of Open Access Journals (Sweden)

    RAIMON eDURAN-STRUUCK

    2015-11-01

    Full Text Available The lack of a large animal transplantable tumor model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable tumor model a close reality. Here, we discuss our experience with myeloid and lymphoid tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable tumor model.

  12. A medaka model of cancer allowing direct observation of transplanted tumor cells in vivo at a cellular-level resolution.

    Science.gov (United States)

    Hasegawa, Sumitaka; Maruyama, Kouichi; Takenaka, Hikaru; Furukawa, Takako; Saga, Tsuneo

    2009-08-18

    The recent success with small fish as an animal model of cancer with the aid of fluorescence technique has attracted cancer modelers' attention because it would be possible to directly visualize tumor cells in vivo in real time. Here, we report a medaka model capable of allowing the observation of various cell behaviors of transplanted tumor cells, such as cell proliferation and metastasis, which were visualized easily in vivo. We established medaka melanoma (MM) cells stably expressing GFP and transplanted them into nonirradiated and irradiated medaka. The tumor cells were grown at the injection sites in medaka, and the spatiotemporal changes were visualized under a fluorescence stereoscopic microscope at a cellular-level resolution, and even at a single-cell level. Tumor dormancy and metastasis were also observed. Interestingly, in irradiated medaka, accelerated tumor growth and metastasis of the transplanted tumor cells were directly visualized. Our medaka model provides an opportunity to visualize in vivo tumor cells "as seen in a culture dish" and would be useful for in vivo tumor cell biology.

  13. A generative model for segmentation of tumor and organs-at-risk for radiation therapy planning of glioblastoma patients

    DEFF Research Database (Denmark)

    Agn, Mikael; Law, Ian; Munck Af Rosenschöld, Per

    2016-01-01

    to model tumor shape. The method is not tuned to any specific imaging protocol and can simultaneously segment the gross tumor volume, peritumoral edema and healthy tissue structures relevant for radiotherapy planning. We validate the method on a manually delineated clinical data set of glioblastoma...

  14. Gleditsia Saponin C Induces A549 Cell Apoptosis via Caspase-Dependent Cascade and Suppresses Tumor Growth on Xenografts Tumor Animal Model

    Directory of Open Access Journals (Sweden)

    Ye Cheng

    2018-01-01

    Full Text Available Saponins are natural compounds and possess the most promising anti-cancer function. Here, a saponin gleditsia saponin C (GSC, extracted from gleditsiae fructus abnormalis, could induce apoptosis of lung tumor cell line A549 via caspase dependent cascade and this effect could be prevented by the caspase inhibitors. In addition, GSC induced cell death companied with an increase ratio of Bax:Bcl-2 and inhibition of ERK and Akt signaling pathways. Meanwhile, GSC suppressed TNFα inducing NF-κB activation and increased the susceptibility of lung cancer cell to TNFα induced apoptosis. Furthermore, on mouse xenograft model, GSC significantly suppressed tumor growth and induced cancer cell apoptosis, which validated the anti-tumor effect of GSC. Based on these results, GSC might be a promising drug candidate of anti-lung cancer for its potential clinical applications.

  15. SU-F-R-44: Modeling Lung SBRT Tumor Response Using Bayesian Network Averaging

    International Nuclear Information System (INIS)

    Diamant, A; Ybarra, N; Seuntjens, J; El Naqa, I

    2016-01-01

    Purpose: The prediction of tumor control after a patient receives lung SBRT (stereotactic body radiation therapy) has proven to be challenging, due to the complex interactions between an individual’s biology and dose-volume metrics. Many of these variables have predictive power when combined, a feature that we exploit using a graph modeling approach based on Bayesian networks. This provides a probabilistic framework that allows for accurate and visually intuitive predictive modeling. The aim of this study is to uncover possible interactions between an individual patient’s characteristics and generate a robust model capable of predicting said patient’s treatment outcome. Methods: We investigated a cohort of 32 prospective patients from multiple institutions whom had received curative SBRT to the lung. The number of patients exhibiting tumor failure was observed to be 7 (event rate of 22%). The serum concentration of 5 biomarkers previously associated with NSCLC (non-small cell lung cancer) was measured pre-treatment. A total of 21 variables were analyzed including: dose-volume metrics with BED (biologically effective dose) correction and clinical variables. A Markov Chain Monte Carlo technique estimated the posterior probability distribution of the potential graphical structures. The probability of tumor failure was then estimated by averaging the top 100 graphs and applying Baye’s rule. Results: The optimal Bayesian model generated throughout this study incorporated the PTV volume, the serum concentration of the biomarker EGFR (epidermal growth factor receptor) and prescription BED. This predictive model recorded an area under the receiver operating characteristic curve of 0.94(1), providing better performance compared to competing methods in other literature. Conclusion: The use of biomarkers in conjunction with dose-volume metrics allows for the generation of a robust predictive model. The preliminary results of this report demonstrate that it is possible

  16. SU-F-R-44: Modeling Lung SBRT Tumor Response Using Bayesian Network Averaging

    Energy Technology Data Exchange (ETDEWEB)

    Diamant, A; Ybarra, N; Seuntjens, J [McGill University, Montreal, Quebec (Canada); El Naqa, I [University of Michigan, Ann Arbor, MI (United States)

    2016-06-15

    Purpose: The prediction of tumor control after a patient receives lung SBRT (stereotactic body radiation therapy) has proven to be challenging, due to the complex interactions between an individual’s biology and dose-volume metrics. Many of these variables have predictive power when combined, a feature that we exploit using a graph modeling approach based on Bayesian networks. This provides a probabilistic framework that allows for accurate and visually intuitive predictive modeling. The aim of this study is to uncover possible interactions between an individual patient’s characteristics and generate a robust model capable of predicting said patient’s treatment outcome. Methods: We investigated a cohort of 32 prospective patients from multiple institutions whom had received curative SBRT to the lung. The number of patients exhibiting tumor failure was observed to be 7 (event rate of 22%). The serum concentration of 5 biomarkers previously associated with NSCLC (non-small cell lung cancer) was measured pre-treatment. A total of 21 variables were analyzed including: dose-volume metrics with BED (biologically effective dose) correction and clinical variables. A Markov Chain Monte Carlo technique estimated the posterior probability distribution of the potential graphical structures. The probability of tumor failure was then estimated by averaging the top 100 graphs and applying Baye’s rule. Results: The optimal Bayesian model generated throughout this study incorporated the PTV volume, the serum concentration of the biomarker EGFR (epidermal growth factor receptor) and prescription BED. This predictive model recorded an area under the receiver operating characteristic curve of 0.94(1), providing better performance compared to competing methods in other literature. Conclusion: The use of biomarkers in conjunction with dose-volume metrics allows for the generation of a robust predictive model. The preliminary results of this report demonstrate that it is possible

  17. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    International Nuclear Information System (INIS)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H; Neelakkantan, Harini; Meeks, Sanford L; Kupelian, Patrick A

    2010-01-01

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  18. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    Energy Technology Data Exchange (ETDEWEB)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  19. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion.

    Science.gov (United States)

    Min, Yugang; Santhanam, Anand; Neelakkantan, Harini; Ruddy, Bari H; Meeks, Sanford L; Kupelian, Patrick A

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.