Stratis V. Sotirchos

Bio: Stratis V. Sotirchos is an academic researcher from University of Rochester. The author has contributed to research in topics: Deposition (phase transition) & Methyltrichlorosilane. The author has an hindex of 25, co-authored 87 publications receiving 2697 citations. Previous affiliations of Stratis V. Sotirchos include Foundation for Research & Technology – Hellas.

Variations in tumor cell growth rates and metabolism with oxygen concentration, glucose concentration, and extracellular pH.

Abstract: Tumors and multicellular tumor spheroids can develop gradients in oxygen concentration, glucose concentration, and extracellular pH as they grow. In order to calculate these gradients and assess their impact on tumor growth, it is necessary to quantify the effect of these variables on tumor cell metabolism and growth. In this work, the oxygen consumption rates, glucose consumption rates, and growth rates of EMT6/Ro mouse mammary tumor cells were measured at a variety of oxygen concentrations, glucose concentrations, and extracellular pH levels. At an extracellular pH of 7.25, the oxygen consumption rate of EMT6/Ro cells increased by nearly a factor of 2 as the glucose concentration was decreased from 5.5 mM to 0.4 mM. This effect of glucose concentration on oxygen consumption rate, however, was slight at an extracellular pH of 6.95 and disappeared completely at an extracellular pH of 6.60. The glucose consumption rate of EMT6/Ro cells increased by roughly 40% when the oxygen concentration was reduced from 0.21 mM to 0.023 mM and decreased by roughly 60% when the extracellular pH was decreased from 7.25 to 6.95. The growth rate of EMT6/Ro cells decreased with decreasing oxygen concentration and extracellular pH; however, severe conditions were required to stop cell growth (0.0082 mM oxygen and an extracellular pH of 6.60). Empirical correlations were developed from these data to express EMT6/Ro cell growth rates, oxygen consumption rates, and glucose consumption rates, as functions of oxygen concentration, glucose concentration, and extracellular pH. These empirical correlations make it possible to mathematically model the gradients in oxygen concentration, glucose concentration, and extracellular pH in EMT6/Ro multicellular spheroids by solution of the diffusion/reaction equations. Computations such as these, along with oxygen and pH microelectrode measurements in EMT6/Ro multicellular spheroids, indicated that nutrient concentration and pH levels in the inner regions of spheroids were low enough to cause significant changes in nutrient consumption rates and cell growth rates. However, pH and oxygen concentrations measured or calculated in EMT6/Ro spheroids where quiescent cells have been observed were not low enough to cause the cessation of cell growth, indicating that the observed quiescence must have been due to factors other than acidic pH, oxygen depletion, or glucose depletion.

Ordinary and transition regime diffusion in random fiber structures

Abstract: The problem of bulk, transition and Knudsen regime diffusion in structures of freely overlapping fibers of various orientation distributions was numerically investigated, and the interrelation of the resulting effective diffusivities was examined. Fibers were randomly positioned and oriented in d = 1, 2, or 3 directions. A Monte Carlo simulation scheme was employed to determine the effective diffusivities from the mean-square displacement of random walkers traveling in the interior of the porous structure. The effective diffusivity was found to depend strongly on the orientational distribution of the fibers, porosity of the fibrous structures, and Knudsen number. The tortuosity factor decreased in general with increasing porosity, approaching at the limit of dilute beds the lower bound derived for each direction of diffusion from variational principles. The simulation results agreed well with experimental values of the bulk tortuosity of fibrous beds from the literature. It was also found that the reciprocal additivity or harmonic average effective diffusivity expression (Bosanquet formula), commonly used to estimate transition regime diffusivities from the values at the ordinary and Knudsen diffusion limits, provides an excellent approximation for the effective diffusivity of fibrous beds, except for that parallel to the fibers of a unidirectional structure.

Mathematical modelling of microenvironment and growth in EMT6/Ro multicellular tumour spheroids.

Abstract: In order to determine the role of micromilieu in tumour spheroid growth, a mathematical model was developed to predict EMT6/Ro spheroid growth and microenvironment based upon numerical solution of the diffusion/reaction equation for oxygen, glucose, lactate ion, carbon dioxide, bicarbonate ion, chlorine ion and hydrogen ion along with the equation of electroneutrality. This model takes into account the effects of oxygen concentration, glucose concentration and extracellular pH on cell growth and metabolism. Since independent measurements of EMT6/Ro single cell growth and metabolic rates, spheroid diffusion constants, and spinner flask mass transfer coefficients are available, model predictions using these parameters were compared with published data on EMT6/Ro spheroid growth and micro-environment. The model predictions of reduced spheroid growth due to reduced cell growth rates and cell shedding fit experimental spheroid growth data below 700 microns, but overestimated the spheroid growth rate at larger diameters. Predicted viable rim thicknesses based on predicted near zero glucose concentrations fit published viable rim thickness data for 1000 microns spheroids grown at medium glucose concentrations of 5.5 mM or less. However, the model did not accurately predict the onset of necrosis. Moreover, the model could not predict the observed decreases in oxygen and glucose metabolism seen in spheroids with time, nor could it predict the observed growth plateau. This suggests that other unknown factors, such as inhibitors or cell-cell contact effects, must also be important in affecting spheroid growth and cellular metabolism.

Glucose Diffusivity in Multicellular Tumor Spheroids

Abstract: In order to understand the role of glucose limitations in controlling multicellular tumor spheroid growth, knowledge of the glucose diffusion coefficient is essential. The effective diffusivity of glucose in spheroids of rodent and human tumor cell lines has been determined by measuring the efflux of tritium labeled L-glucose from spheroids with time. When the rapid and irreversible binding of L-glucose in spheroids is properly taken into account, measurements of the efflux of this diffusion tracer from spheroids into label-free medium can be correlated to the diffusion equation in order to obtain the effective glucose diffusivity in spheroids. Such measurements have been made in EMT6/Ro mouse mammary tumor spheroids as well as in spheroids derived from human colon carcinoma cells (HT29, CO112, and WiDr) and from human squamous carcinoma cells (CaSki and A431). EMT6/Ro spheroids have a glucose diffusivity of 1.1 x 10(-6) cm2/s, while glucose diffusion coefficients in the human cell spheroids studied vary from 5.5 x 10(-7) cm2/s to 2.3 x 10(-7) cm2/s. These values are low enough to suggest that significant gradients in glucose concentration may exist in spheroids and tumors. It is thus believed that these glucose diffusivities, as well as their variation with cell line, may have important implications for the role played by glucose in the growth and cellular heterogeneity of spheroids and tumors.

Transport properties of random arrays of freely overlapping cylinders with various orientation distributions

Abstract: We present dimensionless effective transport coefficients (formation factors) for arrays of cylinders of various orientation distributions, namely, cylinders randomly positioned and oriented with their axes parallel to a line, parallel to a plane, or in the three‐dimensional space with no preferred orientation. Both cases of conducting cylinders dispersed in a nonconducting matrix and nonconducting cylinders dispersed in a conducting matrix are considered. The transport coefficients are computed by means of a random walk simulation scheme. A comprehensive survey of past studies on transport properties of random arrays of cylinders is also presented, and our results are compared with the predictions of various analytical approximations or bounds and with experimental data of the literature.

Electrospinning: A Fascinating Method for the Preparation of Ultrathin Fibers

Abstract: Electrospinning is a highly versatile method to process solutions or melts, mainly of polymers, into continuous fibers with diameters ranging from a few micrometers to a few nanometers. This technique is applicable to virtually every soluble or fusible polymer. The polymers can be chemically modified and can also be tailored with additives ranging from simple carbon-black particles to complex species such as enzymes, viruses, and bacteria. Electrospinning appears to be straightforward, but is a rather intricate process that depends on a multitude of molecular, process, and technical parameters. The method provides access to entirely new materials, which may have complex chemical structures. Electrospinning is not only a focus of intense academic investigation; the technique is already being applied in many technological areas.

Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation.

Abstract: The partial pressure of oxygen (pO2) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (≤10 μm) measurements of interstitial pH and pO2 profiles between adjacent vessels in a human tumor xenograft, using fluorescence ratio imaging and phosphorescence quenching microscopy. We found (1) heterogeneity in shapes of pH and pO2 profiles; (2) a discordant relation between local pH profiles and corresponding pO2 profiles, yet a strong correlation between mean pH and pO2 profiles; (3) no correlation between perivascular pH/pO2 and nearest vessel blood flow; and (4) well-perfused tumor vessels that were hypoxic and, consequently, large hypoxic areas in the surrounding interstitium. Such multiparameter measurements of the in vivo microenvironment provide unique insights into biological processes in tumors and their response to treatment.

Inhibition of t cell proliferation by macrophage tryptophan catabolism

Abstract: We have recently shown that expression of the enzyme indoleamine 2,3-dioxygenase (IDO) during murine pregnancy is required to prevent rejection of the allogeneic fetus by maternal T cells. In addition to their role in pregnancy, IDO-expressing cells are widely distributed in primary and secondary lymphoid organs. Here we show that monocytes that have differentiated under the influence of macrophage colony-stimulating factor acquire the ability to suppress T cell proliferation in vitro via rapid and selective degradation of tryptophan by IDO. IDO was induced in macrophages by a synergistic combination of the T cell–derived signals IFN-γ and CD40-ligand. Inhibition of IDO with the 1-methyl analogue of tryptophan prevented macrophage-mediated suppression. Purified T cells activated under tryptophan-deficient conditions were able to synthesize protein, enter the cell cycle, and progress normally through the initial stages of G1, including upregulation of IL-2 receptor and synthesis of IL-2. However, in the absence of tryptophan, cell cycle progression halted at a mid-G1 arrest point. Restoration of tryptophan to arrested cells was not sufficient to allow further cell cycle progression nor was costimulation via CD28. T cells could exit the arrested state only if a second round of T cell receptor signaling was provided in the presence of tryptophan. These data reveal a novel mechanism by which antigen-presenting cells can regulate T cell activation via tryptophan catabolism. We speculate that expression of IDO by certain antigen presenting cells in vivo allows them to suppress unwanted T cell responses.

The Maxwell-Stefan approach to mass transfer

Abstract: The limitations of the Fick's law for describing diffusion are discussed. It is argued that the Maxwell-Stefan formulation provides the most general, and convenient, approach for describing mass transport which takes proper account of thermodynamic non-idealities and influence of external force fields. Furthermore, the Maxwell-Stefan approach can be extended to handle diffusion in macro- and microporous catalysts, adsorbents and membranes.

Effective diffusivity and water-saturation distribution in single- and two-layer PEMFC diffusion medium

Abstract: The formation–distribution of condensed water in diffusion medium of proton exchange membrane fuel cells, and its tendency to reduce the local effective mass diffusivity and to influence cell performance, are studied. First the local effective mass diffusivity of a fibrous diffusion medium is determined as a function of the local porosity and local water saturation, using the network model for species diffusion. Then using this along with the hydrodynamics of capillary, two-phase flow in hydrophobic porous media, the water formation rate (hydrogen–oxygen reaction), and condensation kinetics, the one-dimensional distribution of water saturation is determined and roles of fiber diameter, porosity, and capillary pressure on cell performance are explored. The results point to a two-layer medium (similar to the added conventional microlayer) which is then analyzed for optimum performance.