Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2

Background: Human melanoma frequently colonizes bone marrow (BM) since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC) microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2) in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown. Methods: Herein we analyzed the effect of cyclooxygenase-2 (COX-2) inhibitor celecoxib in a model of generalized BM dissemination of left cardiac ventricle-injected B16 melanoma (B16M) cells into healthy and bacterial endotoxin lipopolysaccharide (LPS)-pretreated mice to induce inflammation. In addition, B16M and human A375 melanoma (A375M) cells were exposed to conditioned media from basal and LPS-treated primary cultured murine and human BMSCs, and the contribution of COX-2 to the adhesion and proliferation of melanoma cells was also studied. Results: Mice given one single intravenous injection of LPS 6 hour prior to cancer cells significantly increased B16M metastasis in BM compared to untreated mice; however, administration of oral celecoxib reduced BM metastasis incidence and volume in healthy mice, and almost completely abrogated LPS-dependent melanoma metastases. In vitro, untreated and LPS-treated murine and human BMSC-conditioned medium (CM) increased VCAM-1-dependent BMSC adherence and proliferation of B16M and A375M cells, respectively, as compared to basal medium-treated melanoma cells. Addition of celecoxib to both B16M and A375M cells abolished adhesion and proliferation increments induced by BMSC-CM. TNF alpha and VEGF secretion increased in the supernatant of LPS-treated BMSCs; however, anti-VEGF neutralizing antibodies added to B16M and A375M cells prior to LPS-treated BMSC-CM resulted in a complete abrogation of both adhesion-and proliferation-stimulating effect of BMSC on melanoma cells. Conversely, recombinant VEGF increased adherence to BMSC and proliferation of both B16M and A375M cells, compared to basal medium-treated cells, while addition of celecoxib neutralized VEGF effects on melanoma. Recombinant TNFa induced B16M production of VEGF via COX-2-dependent mechanism. Moreover, exogenous PGE2 also increased B16M cell adhesion to immobilized recombinant VCAM-1. Conclusions: We demonstrate the contribution of VEGF-induced tumor COX-2 to the regulation of adhesion-and proliferation-stimulating effects of TNFa, from endotoxin-activated bone marrow stromal cells, on VLA-4-expressing

Variations in year-class strength and estimates of the catchability coefficient of yellowfin tuna, Thunnus albacares, in the Eastern Pacific Ocean

ENGLISH: Year-class composition of catch, virtual population size and yearclass strength were determined from serial samples of size composition of catches and catch records. Murphy's Solution to the catch equation, which is free from the effects caused by changes in fishing pressure, was used to estimate year-class strength, i.e. the total population of fish age 3/4 years. The resultant estimates indicated that the X55, X56, X57, X62 and X63 year classes were above average and the X58, X59, X60, X61 and X64 year classes were below average. The year-class designation refers to the year of actual entry or presumed year of entry into the commercial fishery (at approximately 1 year of age). The strongest and poorest year classes were the X57 and X61 classes, respectively. The ratio of the strongest to the weakest year class was 2.6. This amount of variation is small compared to that found for other species of fish. It was found that the relationship between stock size and yearclass strength is of no value in predicting year-class strength. As a by-product of the analysis, estimates of the catchability coefficients (qN) of the age groups in the fishery were obtained, These estimates were found to vary with age and time. Age-two fish apparently showed the greatest vulnerability to fishing gear, followed by ages three and one, respectively. The average estimate of the catchability coefficient in weight was calculated and found to compare favorably with Schaefer's estimate. The influence of sea-surface water temperature upon year-class strength was investigated to determine whether the latter can be predicted from a knowledge of sea-surface temperatures prevailing during and following spawning. No correlation was evident. SPANISH: La composición de la clase anual en la captura, el tamaño de la población virtual y la fuerza de clase anual, fueron determinados según una serie de muestras de la composición de tamaño de las capturas y de los registros de captura. La Solución de Murphy de la ecuación de captura, que está libre de los efectos causados por los cambios de la presión de pesca, fue usada para estimar la fuerza de la clase anual, i.e. la población total de peces de 3/4 años. Las estimaciones resultantes indican que las clases anuales X55, X56, X57, X62 y X63 fueron superiores al promedio y que las clases anuales X58, X59, X60, X61 y X64 fueron inferiores al promedio. La designación de la clase anual se refiere al año actual de entrada o al año supuesto de entrada en la pesca comercial (aproximadamente a la edad de 1 año). Las clases anuales más fuertes y más pobres fueron la X57 y X61 respectivamente. La razón de la clase anual más fuerte en relación a la más débil fue 2.6. Esta cantidad de variación es pequeña comparada con la encontrada para otras especies de peces. Se encontró que la relación entre en tamaño del stock y la fuerza de la clase anual no tiene valor en predecir la fuerza de la clase anual. Se obtuvieron estimaciones de los coeficientes de capturabilidad (qN) de los grupos de edad en la pesquería como un producto derivado del análisis. Se encontraron que estas estimaciones variaron con la edad y tiempo. Los peces de edad dos aparentemente presentaron la vulnerabilidad más grande en relación al arte pesquero, seguidos por las edades tres y una, respectivamente. La estimación promedio del coeficiente de capturabilidad en peso fue calculada y se encontró que podía compararse favorablemente con la estimación de Schaefer. La influencia de la temperatura del agua superficial del mar sobre la fuerza de la clase anual fue investigada para determinar si se podía predecir esta última según el conocimíento de las temperaturas superficiales del mar prevalecientes durante el desove y después de éste. No hubo correlación evidente. (PDF contains 44 pages.)

Atomistic Simulation On Size-Dependent Yield Strength And Defects Evolution Of Metal Nanowires

A simple derivation based on continuum mechanics is given, which shows the surface stress is critical for yield strength at ultra-small scales. Molecular dynamics (MD) simulations with modified embedded atom method (MEAM) are employed to investigate the mechanical behaviors of single-crystalline metal nanowires under tensile loading. The calculated yield strengths increasing with the decrease of the cross-sectional area of the nanowires are in accordance with the theoretical prediction. Reorientation induced by stacking faults is observed at the nanowire edge. In addition. the mechanism of yielding is discussed in details based on the snapshots of defects evolution. The nanowires in different crystallographic orientations behave differently in stretching deformation. This study on the plastic properties of metal nanowires will be helpful to further understanding of the mechanical properties of nanomaterials. (C) 2009 Elsevier B.V. All rights reserved.

Mechanics of adhesive contact on a power-law graded elastic half-space

We consider adhesive contact between a rigid sphere of radius R and a graded elastic half-space with Young's modulus varying with depth according to a power law E = E-0(z/c(0))(k) (0 < k < 1) while Poisson's ratio v remaining a constant. Closed-form analytical solutions are established for the critical force, the critical radius of contact area and the critical interfacial stress at pull-off. We highlight that the pull-off force has a simple solution of P-cr= -(k+3)pi R Delta gamma/2 where Delta gamma is the work of adhesion and make further discussions with respect to three interesting limits: the classical JKR solution when k = 0, the Gibson solid when k --> 1 and v = 0.5, and the strength limit in which the interfacial stress reaches the theoretical strength of adhesion at pull-off. (C) 2009 Elsevier Ltd. All rights reserved.

High-Strength Composite Fibers: Realizing True Potential of Carbon Nanotubes in Polymer Matrix through Continuous Reticulate Architecture and Molecular Level Couplings

Carbon nanotubes have unprecedented mechanical properties as defect-free nanoscale building blocks, but their potential has not been fully realized in composite materials due to weakness at the interfaces. Here we demonstrate that through load-transfer-favored three-dimensional architecture and molecular level couplings with polymer chains, true potential of CNTs can be realized in composites as Initially envisioned. Composite fibers with reticulate nanotube architectures show order of magnitude improvement in strength compared to randomly dispersed short CNT reinforced composites reported before. The molecular level couplings between nanotubes and polymer chains results in drastic differences in the properties of thermoset and thermoplastic composite fibers, which indicate that conventional macroscopic composite theory falls to explain the overall hybrid behavior at nanoscale.

Stabilizing to disruptive transition of focal adhesion response to mechanical forces

Strong mechanical forces can, obviously, disrupt cell-cell and cell-matrix adhesions, e.g., cyclic uniaxial stretch induces instability of cell adhesion, which then causes the reorientation of cells away from the stretching direction. However, recent experiments also demonstrated the existence of force dependent adhesion growth (rather than dissociation). To provide a quantitative explanation for the two seemingly contradictory phenomena, a microscopic model that includes both integrin-integrin interaction and integrin-ligand interaction is developed at molecular level by treating the focal adhesion as an adhesion cluster. The integrin clustering dynamics and integrin-ligand binding dynamics are then simulated within one unified theoretical frame with Monte Carlo simulation. We find that the focal adhesion will grow when the traction force is higher than a relative small threshold value, and the growth is dominated by the reduction of local chemical potential energy by the traction force. In contrast, the focal adhesion will rupture when the traction force exceeds a second threshold value, and the rupture is dominated by the breaking of integrin-ligand bonds. Consistent with the experiments, these results suggest a force map for various responses of cell adhesion to different scales of mechanical force. PMID: 20542514

EVALUATION OF FILM-SUBSTRATE ADHESION VIA IMPACT USING COATED BULLETS

A method was devised to evaluate the adhesion between a film and a substrate. A front-end coated bullet is accelerated by a gas gun and hits the substrate of the specimen under test. The impact generates a compressive stress pulse that propagates toward the film. After transmission through the interface, part of the pulse is reflected on the free surface of the film, and tensile stress arises at the film-substrate interface, possibly inducing debonding of the film. This dynamic process was demonstrated analytically and simulated numerically by the finite element method. The results validate the initial concept and lay the foundation for further optimization of this method.

On a novel method of impact by a front-end-coated bullet to evaluate the interface adhesion between film and substrate

A preliminary experiment was carried out to validate the feasibility of the method of impact by a front-end-coated bullet to evaluate the interface adhesion between film and substrate. The theoretical description of the initiation, propagation and evolution of the stress pulse during impact was generalized and formulized. The effects of the crucial parameters on the interface stress were further investigated with FEM. The results found the promising prospect of the application of such a method and provided useful guidance for experimental design.