High-grade serous ovarian cancer (HGS-OvCA) is an aggressive form of epithelial ovarian cancer (EOC), and accounts for the majority of deaths due to EOC. The critical cellular processes and underlying molecular mechanisms that define this malignancy remain poorly understood. Using a syngeneic murine model, we investigated the changes that accompanied the progression to increased aggressiveness induced by in vivo passage of mouse EOC cells. We found that enhanced anoikis resistance was a key cellular process associated with greater aggressiveness and tumorigenicity in vivo. Biochemical studies revealed that the enhanced anoikis resistance was associated with the activation of the Src/Akt/Erk signaling pathway. A higher rate of metabolism and autophagy were also associated with increased anoikis resistance. Blocking these pathways with specific inhibitors and/or genetic modifications significantly increased anoikis in vitro and inhibited tumor development in vivo. In addition, we demonstrated that similar signaling pathways were also involved in a human EOC cell line model. Collectively, our data suggest that anoikis resistance represents a critical and a distinguishing feature underlying the aggressiveness of ovarian cancer cells.

The momentum exchange method has been widely used in lattice Boltzmann simulations for particle-fluid interactions. Although proved accurate for still walls, it will result in inaccurate particle dynamics without corrections. In this work, we reveal the physical cause of this problem and find that the initial momentum of the net mass transfer through boundaries in the moving-boundary treatment is not counted in the conventional momentum exchange method. A corrected momentum exchange method is then proposed by taking into account the initial momentum of the net mass transfer at each time step. The method is easy to implement with negligible extra computation cost. Direct numerical simulations of a single elliptical particle sedimentation are carried out to evaluate the accuracy for our method as well as other lattice Boltzmann-based methods by comparisons with the results of the finite element method. A shear flow test shows that our method is Galilean invariant.

No abstract

Purpose Our goals are to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. Experimental Design We combined bacteria- and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were invested in ex vivo, in vitro, and in vivo studies. Results Both bacteria- and LPS-induced acute lung injury/inflammation significantly enhanced lung metastasis of four tail vein-injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells orthotopically injected. The broncheoalveolar lavage fluid (BALF) from LPS- or bacteria- injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a CXCR4 inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin (Ub), but not SDF-1, in BALF were significantly increased by LPS. Ub was able to induce AMD3100-sensitive migration of tumor cells. Finally, the anti-bacterial amoxicillin and AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis. Conclusions Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic “niche”. This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis.

Fluid dynamic equations are valid in their respective modeling scales, such as the particle mean free path scale of the Boltzmann equation and the hydrodynamic scale of the Navier-Stokes (NS) equations. With a variation of the modeling scales, theoretically there should have a continuous spectrum of fluid dynamic equations. Even though the Boltzmann equation is claimed to be valid in all scales, many Boltzmann solvers, including direct simulation Monte Carlo method, require the cell resolution to the particle mean free path scale. Therefore, they are still single scale methods. In order to study multiscale flow evolution efficiently, the dynamics in the computational fluid has to be changed with the scales. A direct modeling of flow physics with a changeable scale may become an appropriate approach. The unified gaskinetic scheme (UGKS) is a direct modeling method in the mesh size scale, and its underlying flow physics depends on the resolution of the cell size relative to the particle mean free path. The cell size of UGKS is not limited by the particle mean free path. With the variation of the ratio between the numerical cell size and local particle mean free path, the UGKS recovers the flow dynamics from the particle transport and collision in the kinetic scale to the wave propagation in the hydrodynamic scale. The previous UGKS is * Corresponding author mostly constructed from the evolution solution of kinetic model equations. Even though the UGKS is very accurate and effective in the low transition and continuum flow regimes with the time step being much larger than the particle mean free time, it is still necessary to develop more accurate flow solver in the rarefied regime, where the time step is comparable with the local particle mean free time. In such a scale, there is dynamic difference from the full Boltzmann collision term and the model equations. This work is about the further development of the UGKS with the implementation of the full Boltzmann collision term in the region where it is needed. The central ingredient of the UGKS is the coupled treatment of particle transport and collision in the flux evaluation across a cell interface, where a continuous flow dynamics from kinetic to hydrodynamic scales is modeled. The newly developed UGKS has the asymptotic preserving (AP) property of recovering the NS solutions in the continuum flow regime, and the full Boltzmann solution in the rarefied regime. In the mostly unexplored transition regime, the UGKS itself provides a valuable tool for the flow study in this regime. The mathematical properties of the scheme, such as stability, accuracy, and the asymptotic preserving, will be analyzed in this paper as well.