Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells

Proteomic Validation of Multifunctional Molecules in Mesenchymal Stem Cells Derived from Human Bone Marrow, Umbilical Cord Blood and Peripheral Blood

Mesenchymal stem cells (MSCs) are one of the most attractive therapeutic resources in clinical application owing to their multipotent capability, which means that cells can differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle and marrow stroma. Depending on the cellular source, MSCs exhibit different application potentials according to their different in vivo functions, despite similar phenotypic and cytological characteristics. To understand the different molecular conditions that govern the different application or differentiation potential of each MSC according to cellular source, we generated a proteome reference map of MSCs obtained from bone marrow (BM), umbilical cord blood (CB) and peripheral blood (PB). We identified approximately 30 differentially regulated (or expressed) proteins. Most up-regulated proteins show a cytoskeletal and antioxidant or detoxification role according to their functional involvement. Additionally, these proteins are involved in the increase of cell viability, engraftment and migration in pathological conditions in vivo. In summary, we examined differentially expressed key regulatory factors of MSCs obtained from several cellular sources, demonstrated their differentially expressed proteome profiles and discussed their functional role in specific pathological conditions. With respect to the field of cell therapy, it may be particularly crucial to determine the most suitable cell sources according to target disease

System Coverage and Capacity Analysis on Millimeter-Wave Band for 5G Mobile Communication Systems with Massive Antenna Structure

The use of a millimeter-wave band defined as a 30–300 GHz range is significant element for improving performance of 5th generation (5G) mobile communication systems. However, since the millimeter-wave signal has peculiar propagation characteristics especially toward non-line-of-sight regions, the system architecture and antenna structure for 5G mobile communications should be designed to overcome these propagation limitations. For realization of the 5G mobile communications, electronics and telecommunications research institute (ETRI) is developing central network applying various massive antenna structures with beamforming. In this paper, we have introduced the central network and evaluated the system coverage and capacity through C++ language-based simulations with real geospatial information

The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma

AbstractTo test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity

The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

BACKGROUND: Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7–8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured. Bioluminescence imagings (BLIs) were performed before treatment and at 3, 7, and 14 days after treatment to measure the tumoral activities. The relative signal intensity (RSI) of each tumor was calculated by dividing the BLI signal at each time point by the value measured before treatment. At day 14 post-treatment, all tumor tissues were harvested to assess the apoptosis rates by pathological examination. RESULTS: The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively. CONCLUSIONS: The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model

Vertical ridge augmentation feasibility using unfixed collagen membranes and particulate bone substitutes: A 1- to 7-year retrospective single-cohort observational study

AIM To determine whether vertical ridge augmentation (VRA) can be obtained through guided bone regeneration (GBR) using exclusively resorbable collagen membranes and particulate bone substitutes without additional stabilization. MATERIALS AND METHODS This study retrospectively examined 22 participants who underwent VRA with staged or simultaneous implant placement. The vertical defects of all participants were filled with particulate bone substitutes and covered with resorbable collagen membranes. The augmented sites were stabilized with unfixed collagen membranes and the flap without any additional fixation. The augmented tissue height was assessed using cone-beam computed tomography at baseline, immediately after surgery, and at annual follow-ups. RESULTS The vertical bone gain of the 22 augmented sites amounted to 6.48 ± 2.19 mm (mean ± SD) immediately after surgery and 5.78 ± 1.72 mm at 1- to 7-year follow-up. Of the 22 augmented sites, 18 exhibited changes of less than 1 mm, while the other 4 showed changes of greater than 1 mm. Histological observation of three representative cases revealed new bone apposition on the remaining material. CONCLUSION The present findings indicate that GBR procedures using exclusively collagen membranes and particulate biomaterials without any additional fixation are feasible options for VRA

An Annular Array MPT for Enhanced Generation of Omnidirectional SH Waves in a Plate

If guided wave transducers are fabricated in an annular array type, the excitation and measurement of target guided wave modes could be considerably enhanced (see, e.g., [1]). Accordingly, various annular array transducers have been developed, including those generating omnidirectional Lamb waves in a plate. Here, we newly consider an annular array type MPT (magnetostrictive patch transducer) to generate enhanced SH (shear-horizontal) waves in a plate. This annular array MPT is based on our earlier development of an omnidirectional SH wave MPT [2]. For wave field analysis by the annular array SH wave MPT, the strain response in a plate due to wave excitation by the MPT is calculated by using the Green’s function approach [3]. Using the analysis, an optimal configuration of the annular array MPT which can maximize the transducer output at the given frequency is determined. For the validation of numerical predictions, a series of experiments with varying frequencies were carried out and the numerical results were found to be in good agreement with the experimental results