Color-gradient lattice Boltzmann model with nonorthogonal central moments: Hydrodynamic melt-jet breakup simulations

We develop a lattice Boltzmann (LB) model for immiscible two-phase flow simulations with central moments (CMs). This successfully combines a three-dimensional nonorthogonal CM-based LB scheme [De Rosis, Phys. Rev. E 95, 013310 (2017)] with our previous color-gradient LB model [Saito, Abe, and Koyama, Phys. Rev. E 96, 013317 (2017)]. Hydrodynamic melt-jet breakup simulations show that the proposed model is significantly more stable, even for flow with extremely high Reynolds numbers, up to O(106). This enables us to investigate the phenomena expected under actual reactor conditions

UniPR1331, a small molecule targeting Eph/ephrin interaction, prolongs survival in glioblastoma and potentiates the effect of antiangiogenic therapy in mice

Glioblastoma multiforme (GBM) is the most malignant brain tumor, showing high resistance to standard therapeutic approaches that combine surgery, radiotherapy, and chemotherapy. As opposed to healthy tissues, EphA2 has been found highly expressed in specimens of glioblastoma, and increased expression of EphA2 has been shown to correlate with poor survival rates. Accordingly, agents blocking Eph receptor activity could represent a new therapeutic approach. Herein, we demonstrate that UniPR1331, a pan Eph receptor antagonist, possesses significant in vivo anti-angiogenic and anti-vasculogenic properties which lead to a significant anti-tumor activity in xenograft and orthotopic models of GBM. UniPR1331 halved the final volume of tumors when tested in xenografts (p<0.01) and enhanced the disease-free survival of treated animals in the orthotopic models of GBM both by using U87MG cells (40 vs 24 days of control, p<0.05) or TPC8 cells (52 vs 16 days, p<0.01). Further, the association of UniPR1331 with the anti-VEGF antibody Bevacizumab significantly increased the efficacy of both monotherapies in all tested models. Overall, our data promote UniPR1331 as a novel tool for tackling GBM

Color-gradient lattice Boltzmann model with nonorthogonal central moments:Hydrodynamic melt-jet breakup simulations

We develop a lattice Boltzmann (LB) model for immiscible two-phase flow simulations with central moments (CMs). This successfully combines a three-dimensional nonorthogonal CM-based LB scheme [De Rosis, (2017)] with our previous color-gradient LB model [Saito, Abe, and Koyama, (2017)]. Hydrodynamic melt-jet breakup simulations show that the proposed model is significantly more stable, even for flow with extremely high Reynolds numbers, up to O(106). This enables us to investigate the phenomena expected under actual reactor conditions.</p

A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence

The Eph kinases are the largest receptor tyrosine kinases (RTKs) family in humans. PC3 human prostate adenocarcinoma cells are a well-established model for studying Eph-ephrin pharmacology as they naturally express a high level of EphA2, a promising target for new cancer therapies. A pharmacological approach with agonists did not show significant efficacy on tumor growth in prostate orthotopic murine models, but reduced distal metastasis formation. In order to improve the comprehension of the pharmacological targeting of Eph receptors in prostate cancer, in the present work, we investigated the efficacy of Eph antagonism both in vitro and in vivo, using UniPR1331, a small orally bioavailable Eph-ephrin interaction inhibitor. UniPR1331 was able to inhibit PC3 cells' growth in vitro in a dose-dependent manner, affecting the cell cycle and inducing apoptosis. Moreover, UniPR1331 promoted the PC3 epithelial phenotype, downregulating epithelial mesenchymal transition (EMT) markers. As a consequence, UniPR1331 reduced in vitro PC3 migration, invasion, and vasculomimicry capabilities. The antitumor activity of UniPR1331 was confirmed in vivo when administered alone or in combination with cytotoxic drugs in PC3-xenograft mice. Our results demonstrated that Eph antagonism is a promising strategy for inhibiting prostate cancer growth, especially in combination with cytotoxic drugs