Rare earth (RE) doped SrS phosphor has attracted a lot of attention on a wide range of photo-, cathodo-, thermo-, and electroluminescent applications. Upon doping with different RE elements (e.g., ...Ce, Pr, Eu, Yb), the luminescence from SrS can be varied over the entire visible region by appropriately choosing the composition of the strontium sulfide host. The main applications include flat panel displays and SrS-based powder electroluminescence (EL) for back lights. Sulfide materials known for providing Eu
2+
based red emission band and preferred as a color conversion material in white light emitting diodes are discussed. Especially, the applications of RE doped SrS are described in light of their utility as conversion and storage phosphors. The effect of energy level splitting, EL efficiency, post-annealing, milling time, and impurity on luminescence properties for SrS are also discussed.
Abstract Introduction The purpose of this study was to investigate the relationships between the location of the mental foramen (MF) and the mandibular canal (MC) and the surgical access line (SAL) ...of the mandibular posterior teeth using cone-beam computed tomographic (CBCT) scans. Methods CBCT scans of 204 subjects ranging in age from 18–76 years old were evaluated. The vertical and horizontal distances from the MF to the SAL of the mandibular premolars and first molars and the vertical distance from the MC to the SAL of the second premolars and first molars were measured via CBCT scans. Results The average vertical distance between the MF and the SALs showed significant increases sequentially from the first premolars to the distal roots of the first molars, and the shortest average distance of 2.74 mm was obtained for the first premolars. The SALs of the second premolars were the closest to the MF in the horizontal direction with an average distance of 1.5 mm. In 19.9% of the cases, the vertical and horizontal distances between the MF and the SALs of the second premolars were less than 2 mm. In addition, the MF was located superior to the root apices in 6.62% of the cases. The majority of the SALs were located at a vertical distance from the MC that was more than 2 mm. Men and women exhibited significant differences in both the horizontal distance from the MF to the SALs of the first premolars and the vertical distance from the MC to the SALs of the second premolars. Conclusions To improve the success of endodontic microsurgery, adequate knowledge of the anatomic relationships between the location of the MF and MC and the SAL of the mandibular posterior teeth is indispensable to surgeons.
Purpose
Bone metastasis in breast cancer has been linked to activity of c-Src kinase, one of the extensively explored tyrosine kinases in cell biology. The impact of TNF-related apoptosis inducing ...ligand (TRAIL) and TRAIL receptors has just recently been integrated into this conception.
Methods
An osteotropic clone of MDA-MB-231 cells simulated a model for bone metastasis of triple-negative breast cancer (TNBC). The effects of Dasatinib, a clinically established inhibitor of Src kinases family and Abl were evaluated in vitro and in vivo. In vivo effects of Dasatinib treatment on the occurrence of skeletal metastases were tested in a xenograft mouse model after intra-cardiac injection of osteotropic MDA-MB-231-cells. Ex vivo analyses of the bone sections confirmed intraosseous growth of metastases and allowed determination of osteoclastic activity.
Results
Treatment of osteotropic MDA-MB-231 cells with Dasatinib inhibited proliferation rates in vitro. A shift in TRAIL-receptor expression towards an induction of oncogenic TRAIL-R2 was observed. In vivo, 15 of 30 mice received an intra-peritoneal treatment with Dasatinib. These mice showed significantly less skeletal metastases in bioluminescence scans. Moreover, a pronounced increase in bone volume was observed in the treatment group, as detected by µ-Computed Tomography. Dasatinib treatment also led to a greater increase in bone density in tibiae without metastatic affection, which was accompanied by reduced recruitment of osteoclasts.
Conclusion
Our observations support the concept of utilizing Dasatinib in targeting early-stage bone metastatic TNBC and sustaining bone health.
This study reports targetable micelles developed after covalent functionalization of α-tocopheryl polyethylene glycol succinate (TPGS) with amino phenylboronic acid (APBA). Nuclear magnetic resonance ...(NMR) and infrared (IR) spectroscopic results showed successful attachment of APBA to the hydrophilic segment of TPGS. Dynamic light scattering and small-angle neutron scattering studies revealed that the conjugate self-assembled in water to produce spherical core-shell micelles (14–20 nm) which remained stable against temperature (ca. 25–45 °C) and pH changes. The micelles could solubilize a high payload of paclitaxel (PLX) without exhibiting changes in the average size. However, at the saturation solubility, drug molecules migrated from the core to the shell region and engaged with APBA groups via π–π stacking interaction. Confocal microscopy and cell sorting analyses verified the effective translocation ability of TPGS-APBA micelles in sialic acid (SA) expressing MDA-MB-453 cells. At equivalent PLX dose, TPGS-APBA micelles showed about a twofold improvement in apoptotic death among the cells exposed for 2 h. Our findings indicate that the attachment of APBA can be a potential strategy for improving the intra-cellular localization of carriers among cancer cells expressing SA residues.
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed when liver metastases already emerged. This study elucidated the impact of hepatic stromal cells on growth behavior of premalignant and ...malignant pancreatic ductal epithelial cells (PDECs). Liver sections of tumor-bearing KPC mice comprised micrometastases displaying low proliferation located in an unobtrusive hepatic microenvironment whereas macrometastases containing more proliferating cells were surrounded by hepatic myofibroblasts (HMFs). In an age-related syngeneic PDAC mouse model livers with signs of age-related inflammation exhibited significantly more proliferating disseminated tumor cells (DTCs) and micrometastases despite comparable primary tumor growth and DTC numbers. Hepatic stellate cells (HSC), representing a physiologic liver stroma, promoted an IL-8 mediated quiescence-associated phenotype (QAP) of PDECs in coculture. QAP included flattened cell morphology, Ki67-negativity and reduced proliferation, elevated senescence-associated β galactosidase activity and diminished p-Erk/p-p38-ratio. In contrast, proliferation of PDECs was enhanced by VEGF in the presence of HMF. Switching the micromilieu from HSC to HMF or blocking VEGF reversed QAP in PDECs. This study demonstrates how HSCs induce and maintain a reversible QAP in disseminated PDAC cells, while inflammatory HMFs foster QAP reversal and metastatic outgrowth. Overall, the importance of the hepatic microenvironment in induction and reversal of dormancy during PDAC metastasis is emphasized.
Multiple myeloma is one of the most common hematological diseases and is characterized by an aberrant proliferation of plasma cells within the bone marrow. As a result of crosstalk between cancer ...cells and the bone microenvironment, bone homeostasis is disrupted leading to osteolytic lesions and poor prognosis. Current diagnostic strategies for myeloma typically rely on detection of excess monoclonal immunoglobulins or light chains in the urine or serum. However, these strategies fail to localize the sites of malignancies. In this study we sought to identify novel biomarkers of myeloma bone disease which could target the malignant cells and/or the surrounding cells of the tumor microenvironment. From these studies, the KISS1 receptor (KISS1R), a G-protein-coupled receptor known to play a role in the regulation of endocrine functions, was identified as a target gene that was upregulated on mesenchymal stem cells (MSCs) and osteoprogenitor cells (OPCs) when co-cultured with myeloma cells. To determine the potential of this receptor as a biomarker, in vitro and in vivo studies were performed with the KISS1R ligand, kisspeptin, conjugated with a fluorescent dye. In vitro microscopy showed binding of fluorescently-labeled kisspeptin to both myeloma cells as well as MSCs under direct co-culture conditions. Next, conjugated kisspeptin was injected into immune-competent mice containing myeloma bone lesions. Tumor-burdened limbs showed increased peak fluorescence compared to contralateral controls. These data suggest the utility of the KISS1R as a novel biomarker for multiple myeloma, capable of targeting both tumor cells and host cells of the tumor microenvironment.
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Pluronics are triblock (PEOa-b-PPOb-b-PEOa) copolymers, commercially available in a range of amphiphilicity. Usually, pluronics self-assemble in aqueous solution to form core–shell ...micelles, but their aggregation behavior is remarkably influenced by the molecular characteristics, solution temperature, and presence of additives. Accompanying transitions result into formation of rigid structures, such as liquid crystals and viscoelastic gels. Certain pluronics have been approved by United States Food and Drug Administration (US-FDA) and European Medicines Agency (EMA) for usage as injectable pharmaceutical excipients. While these carriers have been explored in drug delivery since long, advancements in polymer synthesis have now shifted the focus toward pluronic-based targeted and stimulti-responsive nanomedicines. Majority of these attempts lean over chemical modification of the hydrophilic block in order to enable distinctive identification and elimination of cancerous cells. This review presents the physicochemical and design aspects of pluronic micelles relevant from the standpoint of targeted drug delivery to cancer cells. Using up-to-date literature reports, we have discussed how therapeutic outcomes can be amplified by facilitating the translocation of carriers from tumor interstitium to specific cytosolic targets.
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•TPGS is a PEG/vitamin E based nonionic amphiphile with GRAS status.•Its core–shell micelles remarkably solubilize the hydrophobic drugs.•It improves dispersion stability and ...circulation half-life of multi-particulate formulations.•It downregulates efflux transporters and re-sensitizes drug resistant tumor cells.•Chemical modification of TPGS have been explored to improve its targetability.
α-Tocopheryl polyethylene glycol succinate (vitamin E-TPGS or TPGS) is a nonionic amphiphile synthesized by the esterification of vitamin E succinate. It has been categorized as a safe excipient by US-FDA and EMA. Like other polyethylene glycol (PEG) condensates, TPGS spontaneously forms kinetically stable core–shell micelles (diameter 12–15 nm) and exhibits interesting properties as solubilizing agent, emulsifier, dispersant and gelling agent. Its aggregation behavior can be tuned in association with other amphiphiles and organic additives. These properties have been exploited for developing a variety of vesicular, semisolid and multi-particulate drug formulations. It improves the bioavailability of drugs through permeation enhancement and down-regulation of P-glycoproteins. Multimodal therapeutic platforms have been explored following its chemical modification with recognizable and stimuli-responsive groups. Research in the past two decades has revealed its specific role in mediating the re-sensitization of multi-drug resistant cancer cells. This review describes the physicochemical and biological properties of TPGS relevant to drug delivery applications. We have emphasized on the role of TPGS in improving the bioavailability and targetability of anticancer drugs.
Active targeting of drug molecules can be achieved by effective attachment of suitable ligands to the surface of carriers. The present work was attempted to prepare mannosylated gelatin microspheres ...(m-GMs) so as to achieve targeted delivery of isoniazid (INH) to alveolar macrophages (AMs) and maintain its therapeutic concentration for prolonged period of time. Microspheres were prepared by emulsification solvent extraction method and evaluated for physicochemical characteristics, drug release,
ex vivo
drug uptake by AMs and pharmacokinetic characteristics. Fourier transform infrared spectroscopy and nuclear magnetic resonance spectral analysis confirmed that mannosylation took place through Schiff base formation between aldehyde and amino groups of mannose and gelatin, respectively. Prepared microspheres offered suitable physicochemical characteristics for their delivery to AMs. Their average size was about 4 μm and drug entrapment efficiency of 56% was achieved with them.
Ex vivo
uptake results indicated that in comparison to plain microspheres, m-GMs were selectively uptaken and were found to be associated with phago-lysosomal vesicles of AMs. Pharmacokinetic studies showed the formulation could maintain the therapeutic concentration of INH for prolonged period of time even with a reduced clinical dose. m-GMs were found to be stable in broncheo-alveolar lavage fluid. The study concluded that ligand decorated carriers could be a potential strategy to improve the therapeutic properties of INH.
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