Polymer Grafting to Polydopamine Free Radicals for Universal Surface Functionalization.

Modifying surfaces using free radical polymerization (FRP) offers a means to incorporate the diverse physicochemical properties of vinyl polymers onto new materials. Here, we harness the universal surface attachment of polydopamine (PDA) to "prime" a range of different surfaces for free radical polymer attachment, including glass, cotton, paper, sponge, and stainless steel. We show that the intrinsic free radical species present in PDA can serve as an anchor point for subsequent attachment of propagating vinyl polymer macroradicals through radical-radical coupling. Leveraging a straightforward, twofold soak-wash protocol, FRP over the PDA-functionalized surfaces results in covalent polymer attachment on both porous and nonporous substrates, imparting new properties to the functionalized materials, including enhanced hydrophobicity, fluorescence, or temperature responsiveness. Our strategy is then extended to covalently incorporate PDA nanoparticles into organo-/hydrogels via radical cross-linking, yielding tunable PDA-polymer composite networks. The propensity of PDA free radicals to quench FRP is studied using in situ 1H nuclear magnetic resonance and electron paramagnetic resonance spectroscopy, revealing a surface area-dependent macroradical scavenging mechanism that underpins PDA-polymer conjugation. By combining the arbitrary surface attachment of PDA with the broad physicochemical properties of vinyl polymers, our strategy provides a straightforward route for imparting unlimited new functionality to practically any surface.

Controlling the Biological Behaviors of Polymer-Coated Upconverting Nanoparticles by Adjusting the Linker Length of Estrone Ligands.

The estrone ligand is used for modifying nanoparticle surfaces to improve their targeting effect on cancer cell lines. However, to date, there is no common agreement on the ideal linker length to be used for the optimum targeting performance. In this study, we aimed to investigate the impact of poly(poly ethylene glycol methyl ether methacrylate) (PPEGMEMA) linker length on the cellular uptake behavior of polymer-coated upconverting nanoparticles (UCNPs). Different triblock terpolymers, poly(poly (ethylene glycol) methyl ether methacrylate)-block-polymethacrylic acid-block-polyethylene glycol methacrylate phosphate (PPEGMEMAx-b-PMAAy-b-PEGMP3: x = 7, 15, 33, and 80; y = 16, 20, 18, and 18), were synthesized with different polymer linker chain lengths between the surface and the targeting ligand by reversible addition-fragmentation chain transfer polymerization. The estrone ligand was attached to the polymer via specific terminal conjugation. The cellular association of polymer-coated UCNPs with linker chain lengths was evaluated in MCF-7 cells by flow cytometry. Our results showed that the bioactivity of ligand modification is dependent on the length of the polymer linker. The shortest polymer PPEGMEMA7-b-PMAA16-b-PEGMP3 with estrone at the end of the polymer chain was found to have the best cellular association behavior in the estrogen receptor (ER)α-positive expression cell line MCF-7. Additionally, the anticancer drug doxorubicin•HCl was encapsulated in the nanocarrier to evaluate the 2D and 3D cytotoxicity. The results showed that estrone modification could efficiently improve the cellular uptake in ERα-positive expression cell lines and in 3D spheroid models.

A ratiometric fluorescence strategy based on polyethyleneimine surface-modified carbon dots and Eosin Y for the ultrasensitive determination of protamine and trypsin.

In this work, we report a novel and ultrasensitive dual-signal fluorescence emission detection system for protamine and trypsin based on the electrostatic interaction between polyethyleneimine (PEI) surface-modified positively charged carbon quantum dots (CDs-PEI) and the anionic fluorescent dye Eosin Y. The fluorescence system exhibited yellow-green fluorescence from Eosin Y and blue fluorescence from CDs-PEI. As a cationic peptide, protamine quenched the yellow-green fluorescence of Eosin Y at 542 nm through electrostatic interaction. In the presence of trypsin, protamine was specifically hydrolyzed by trypsin, which led to the subsequent recovery of the fluorescence of Eosin Y. Simultaneously, the blue fluorescence emission of CDs-PEI at 452 nm remained constant during the whole process. Hence, a ratiometric fluorescent nanoprobe for protamine and trypsin detection with high sensitivity was successfully constructed based on CDs-PEI and Eosin Y. For protamine detection, the ratiometric fluorescence intensity (I542/I452) exhibited an excellent linear relationship in the range of 0.1-5.2 µg mL-1 with a limit of detection (LOD) of 0.03 µg mL-1. And the linear relationship between I542/I452 and trypsin concentration ranged from 0.4 to 56 ng mL-1 with an LOD of 0.21 ng mL-1. Upon evaluating the performance of this method for the detection of trypsin in actual human urine samples, satisfactory results were finally obtained.

Radiotherapy vs sequential pegaspargase, gemcitabine, cisplatin and dexamethasone and radiotherapy in newly diagnosed early natural killer/T-cell lymphoma: A randomized, controlled, open-label, multicenter study.

To compare the efficacy and safety of radiotherapy (RT) and chemotherapy of pegaspargase, gemcitabine, cisplatin and dexamethasone (DDGP) combined with RT in newly diagnosed stage I-II natural killer/T-cell lymphoma (NKTL), we designed a randomized, controlled, open-label, multicenter clinical trial. Data from 65 stage I-II NKTL patients whose diagnoses were confirmed using immunohistochemistry were enrolled from January 2011 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Patients were randomly divided into the RT group (n = 35) and the DDGP combined with RT group (n = 30). There was a difference between the Eastern Cooperative Oncology Group (ECOG) score in the two arms (P = .013). The complete response rate (CRR) and objective response rate (ORR) of DDGP combined with RT group were superior to those in the RT group (CRR: 73.3% vs 48.6%; ORR: 83.3% vs 60.0%, respectively). The 5-year progression-free survival (PFS) rate and overall survival (OS) rate in the DDGP combined with RT group were higher than those in the RT group (82.9% vs 56.5% for PFS, P = .023; 85.7% vs 60.4% for OS, P = .040), and treatment methods and lactate dehydrogenase were independent risk factors. Myelosuppression (P < .001), gastrointestinal reactions (P < .001), abnormal liver function (P = .007), coagulation abnormalities (P < .001) and baldness (P < .001) were more likely to occur in the DDGP combined with RT group. In conclusion, DDGP combined with radiotherapy obviously obtained great efficacy and prolonged the survival time of patients, also the side effects were mild for stage I-II NKTL. This trial was registered at https://register.clinicaltrials.gov as #NCT01501136.

Downregulated miR-524-5p Participates in the Tumor Microenvironment of Ameloblastoma by Targeting the Interleukin-33 (IL-33)/Suppression of Tumorigenicity 2 (ST2) Axis.

BACKGROUND Ameloblastoma (AB) is a common odontogenic epithelial tumor, with locally invasive behavior and high recurrence. In this study, we hypothesized that miR-524-5p could be involved in the tumor microenvironment by targeting interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) in AB. MATERIAL AND METHODS The microRNA (miRNA) expression profile of AB tissues and normal oral mucosa tissues (NOM; 6 paired samples) was analyzed. The miRNAs with fold change ≥2 and P<0.05 were considered to be differentially expressed. Among them, downregulated miR-524-5p was verified by real-time qPCR. Potential targets of miR-524-5p were predicted by bioinformatics analysis. The expression levels of target genes were detected using real-time qPCR and Western blot, respectively. Immunohistochemistry analysis of target genes was performed, and we also assessed the correlation between miR-524-5p and its target. RESULTS Microarray analysis results first indicated miR-524-5p is a downregulated miRNA in AB tissues. Real-time qPCR results confirmed the expression pattern of miR-524-5p in AB tissues. Moreover, IL-33 and its receptor ST2 were significantly overexpressed. As shown in immunohistochemistry results, IL-33 was positively expressed in lymphocytes and plasma cells, suggesting that IL-33/ST2 participates in tumor immune responses in the tumor microenvironment. Correlation analysis suggested that miR-524-5p expression was negatively correlated with IL-33/ST2. CONCLUSIONS Our findings reveal that downregulated miR-524-5p can participate in the tumor microenvironment of AB by targeting the IL-33/ST2 axis.

Development of bio-based PLA/cellulose antibacterial packaging and its application for the storage of shiitake mushroom.

This study presents the extraction of cellulose from water bamboo byproducts to prepare polylactic acid (PLA)/cellulose antibacterial packaging material. The cellulose was modified using a silane coupling agent, which improved the interfacial compatibility between cellulose and PLA. Upon coating the PLA onto the modified cellulose sheet, the water contact angle of the composite material increased from 11.42° to 132.12° and the water absorption rate decreased from 182.52% to 55.71%, which improved the water resistance performance of the material. The addition of cinnamaldehyde in the PLA layer imparted antibacterial activity to the PLA/cellulose packaging material. This packaging material effectively inhibited the mycelial growth and spore germination of Aspergillus niger and Trichoderma harzianum isolated from shiitake mushroom. Additionally, the study investigated the effects of the composite on the postharvest quality of shiitake mushroom. Overall, the packaging material contributed to shiitake mushroom storage and can be applied to other perishable food products.

Determination of catecholamine in human serum by a fluorescent quenching method based on a water-soluble fluorescent conjugated polymer-enzyme hybrid system.

In this paper, a sensitive water-soluble fluorescent conjugated polymer biosensor for catecholamine (dopamine DA, adrenaline AD and norepinephrine NE) was developed. In the presence of horse radish peroxidase (HRP) and H(2)O(2), catecholamine could be oxidized and the oxidation product of catecholamine could quench the photoluminescence (PL) intensity of poly(2,5-bis(3-sulfonatopropoxy)-1,4-phenylethynylenealt-1,4-poly(phenylene ethynylene)) (PPESO(3)). The quenching PL intensity of PPESO(3) (I(0)/I) was proportional to the concentration of DA, AD and NE in the concentration ranges of 5.0 × 10(-7) to 1.4 × 10(-4), 5.0 × 10(-6) to 5.0 × 10(-4), and 5.0 × 10(-6) to 5.0 × 10(-4) mol L(-1), respectively. The detection limit for DA, AD and NE was 1.4 × 10(-7) mol L(-1), 1.0 × 10(-6) and 1.0 × 10(-6) mol L(-1), respectively. The PPESO(3)-enzyme hybrid system based on the fluorescence quenching method was successfully applied for the determination of catecholamine in human serum samples with good accuracy and satisfactory recovery. The results were in good agreement with those provided by the HPLC-MS method.

The multi-scale meso-mechanics model of viscoelastic dentin.

Human dentin is a hierarchical material with multi-level micro-/nano-structures, consisting of tubule, perti-tubular dentin (PTD) and intertubular dentin (ITD) as the major constituents at microscale; and the PTD and ITD are further composed of collagen and hydroxyapatite (HAp) crystals with different volume fractions at nanoscale. In most cases, the HAp is considered as elastic while the collagen as viscoelastic material. It is of great significance to study the hierarchical structure and viscoelasticity of human dentin to understand the mechanical properties of dentin for further development of restorative materials. Based on this, this paper focuses on multiscale modeling of the elastic properties and dynamic viscoelastic response of dentin and establishes a bottom-up micromechanics model from nano-to macro-scale. In order to study the nanostructural effect on the viscoelastic behavior of hierarchical structures, the homogenization theories of random platelets composites (HTRPC) and the locally-exact homogenization theory (LEHT) are introduced for the homogenization of heterogeneous materials of microstructures at different levels. The HTRPC, based on Eshelby Inclusion theory, is used to predict the effective modulus of PTD and ITD. The LEHT is a method for homogenizing multiphase dentin characterized by repeated unit cells (RUCs). The resulting predictions are in very good agreement with several experimental data from the literature. In addition, the results of nanostructrual effect on dentin show that the viscoelasticity of dentin is majorly contributed by collagen and the HAp greatly provide the strength and hardness of dentin. Furthermore, the ageing effect on dentin's viscoelasticity is considered from the proposed multiscale micromechanics model. It is demonstrated that the ageing effect is much more influential in affecting the loss moduli of dentin than the storage.

A novel signal amplification strategy electrochemical immunosensor for ultra-sensitive determination of p53 protein.

In this work, we fabricated a novel sandwich-type electrochemical immunosensor for quantitative and ultra-sensitive determination of tumor suppressor protein p53 by signal amplification strategy. Conductive polymers poly (3, 4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS) has significantly effect on enhancing charge transfer and markedly increases the sensitivity of electrochemical immunosensing. Gold nanoparticles (AuNPs) as high conductivity nanocarriers were also used to capture monoclonal antibodies (Ab1) due to their large specific surface areas. In addition, pH responsive zeolitic imidazolate framework (ZIF-8) was used to load the redox probe 2, 3-diaminophenazine (DAP) and the secondary antibodies (Ab2) to form a sensitive-type ZIF-8-DAP-Ab2 immunoprobe. After the sandwich-type immunoassay with the free p53 protein, with the release of probe DAP after the electrochemical signal amplificated by PEDOT:PSS and AuNPs, the ultra-sensitive and quantitative determination of p53 protein was realized with working range of 1-120 ng mL-1 and low detection limit of 0.09 ng mL-1. Besides, the fabricated electrochemical immunosensor exhibited good recovery, high sensitivity, reliability, and selectivity.

Suppressive effects of gecko cathelicidin on biofilm formation and cariogenic virulence factors of Streptococcus mutans.

OBJECTIVE: The aims of this study were to investigate the effectivity of gecko cathelicidin Gj-CATH2 on biofilm formation and cariogenic virulence factors of S. mutans, and preliminary explore its function mechanisms. DESIGN: Minimum inhibitory concentration and bacterial killing kinetics assays were performed to assess the antimicrobial effect of Gj-CATH2.The influence of Gj-CATH2 on S. mutans biofilm formation was determined by crystal violet staining method and observed by SEM. The effects of Gj-CATH2 on exopolysaccharides (EPS) synthesis, bacterial aggregation, acidogenicity and aciduricity of S. mutans were also investigated. Quantitative real-time PCR was conducted to acquire the expression profile of related genes. RESULTS: Gj-CATH2 showed strong bactericidal and anti-biofilm effects on S. mutans. SEM confirmed the reduction of the dense structure in S. mutans biofilm in Gj-CATH2-treated groups. Gj-CATH2 significantly inhibited EPS synthesis, cell aggregation, acid production of S. mutans, but showed no influence on its acid proof. Furthermore, the expression of genes related to biofilm formation (gtfB/C/D, gbpB/D), quorum sensing system (luxS and comD/E) and acidogenicity (ldh) was significantly suppressed by Gj-CATH2. Gj-CATH2 also displayed advantageous resistance in human saliva and exhibited negligible toxicity against mammalian cells. CONCLUSIONS: Gj-CATH2 inhibited S. mutans biofilm formation by targeting the bacterial adhesion and the biofilm maturation stages. Gj-CATH2 significantly suppressed virulence factors production of S. mutans, resulting in decreased EPS synthesis and reduced acidogenicity of bacteria. These findings suggest Gj-CATH2 might be a promising agent for clinical application in prevention of dental caries.

Hollow cellulose-carbon nanotubes composite beads with aligned porous structure for fast methylene blue adsorption.

Polysaccharide based beads with unique porous structure have gained considerable interests due to their specific adsorption behaviors and biodegradability. The purpose of this paper was to develop hollow cellulose/carbon nanotubes composite beads with aligned porous structure which have potential applications in fast adsorption field. The composite beads were fabricated by ice template and freeze-drying technology. Different characterizations have proved that the carbon nanotubes and magnetic nanoparticles have been incorporated into the cellulose beads. Higher concentration of carbon nanotubes and cellulose would result in a larger diameter of the composite beads. The composite beads can effectively adsorb the methylene blue (MB). The pseudo-second-order model and Langmuir isotherm were best fitted to the adsorption. The composite beads showed a fast adsorption behavior towards MB with a t1/2 of 1.07 min obtained from pseudo-second-order model. The maximum adsorption capacity was 285.71 mg g-1 at pH 7.0. The composite beads also showed good reusability and biodegradability. We anticipate that different polysaccharides based composite beads with aligned porous structure can be obtained through the similar methods and applied in adsorption fields.

Ursolic Acid Targets Glucosyltransferase and Inhibits Its Activity to Prevent Streptococcus mutans Biofilm Formation.

Streptococcus mutans (S. mutans), the prime pathogen of dental caries, can secrete glucosyltransferases (GTFs) to synthesize extracellular polysaccharides (EPSs), which are the virulence determinants of cariogenic biofilms. Ursolic acid, a type of pentacyclic triterpene natural compound, has shown potential antibiofilm effects on S. mutans. To investigate the mechanisms of ursolic acid-mediated inhibition of S. mutans biofilm formation, we first demonstrated that ursolic acid could decrease the viability and structural integrity of biofilms, as evidenced by XTT, crystal violet, and live/dead staining assays. Then, we further revealed that ursolic acid could compete with the inherent substrate to occupy the catalytic center of GTFs to inhibit EPS formation, and this was confirmed by GTF activity assays, computer simulations, site-directed mutagenesis, and capillary electrophoresis (CE). In conclusion, ursolic acid can decrease bacterial viability and prevent S. mutans biofilm formation by binding and inhibiting the activity of GTFs.

Multicolor quantum dot-encoded microspheres for the fluoroimmunoassays of chicken newcastle disease and goat pox virus.

Semiconductor nanocrystals (or quantum dots, QDs) have the potential to overcome some of the limitations encountered by traditional fluorophores in fluorescence labeling applications. The unique spectroscopic properties of QDs make them hold immense promise as versatile labels for biological applications. In this work, we employ the layer-by-layer (LbL) method for the construction of bio-functional multicolor QD-encoded microspheres. Polystyrene microspheres with diameter of 3 microm were used as templates for the deposition of different sized CdTe QDs/polyelectrolyte multilayers. Two different antigens, Chicken newcastle disease (CND) antigen and goat pox virus (GPV) antigen, were conjugated to two kinds of biofunctional multicolor microspheres with different optical encoding. The multicolor microspheres can capture corresponding antibodies labeled with QDs, QDs-CND antibody and QDs-GPV antibody in the fluoroimmunoassays. The microspheres can be distinguished from each other based on their optical encoding.

Highly Biocompatible Nanoparticles of Au@Fluorescent Polymers as Novel Contrast Agent for In Vivo Bimodality NIR Fluorescence/CT Imaging.

In this work, one kind of biocompatible and all-in-one dual-modal nanoprobe, based on Au nanoparticles and NIR emissive semiconducting fluorescence polymers, was developed by the one-step solvent-mediated self-assembly method for in vivo X-ray computed tomography (CT) and fluorescence bioimaging for the first time. After preparation, a series of comprehensive evaluations were performed, and the nanoprobe exhibited smart size and modification, good compatibility, inducement of autophagy, long blood circulation, unconspicuous in vivo toxicity, and excellent fluorescence/CT imaging effects. Overall, the studies in this work assuredly indicate that the synthesized Au@FP nanoparticles as a noninvasive contrast agent is suitable for in vivo fluorescence/X-ray CT bimodality biomedical imaging and diagnosis.

Influence of Surface Treatment on the Interfacial and Mechanical Properties of Short S-Glass Fiber-Reinforced Dental Composites.

The influence of interfacial shear strength (IFSS) between processed short S-glass fibers (250 and 350 µm in length, 5 µm in diameter) and the dental resin (a mixture of urethane dimethacrylate and triethylene glycol dimethacrylate monomers) on the mechanical properties has been studied experimentally. The surface profile of short S-glass fibers was modified using a selective atomic level metal etching process and simple silanization process to enhance the interfacial properties. The S-glass fibers were etched in acid solutions to increase the surface roughness and selectively remove Al3+ and Mg2+ ions, which promoted the mechanical and chemical interfacial bonding reactions. The single glass fiber tensile and microdroplet pull-out tests were performed to investigate the effects of interfacial properties on the flexural strength of the resultant composites. The surface modified S-glass fibers showed an increase of 11-40% in IFSS compared to untreated glass fibers. Composites reinforced with 350 µm length glass fibers (AR-70), which were treated in piranha solution for 4 h, showed the highest improvement in overall mechanical properties, flexural strength (34.2%), modulus (9.7%), and breaking energy (51.9%), compared to the untreated fiber-reinforced composites. The modified Lewis-Nielsen equation was developed using the effective fiber length factor to accurately predict the modulus of the short fiber-reinforced composites and validated with experimental results.

Selective Atomic-Level Etching on Short S-Glass Fibres to Control Interfacial Properties for Restorative Dental Composites.

Interfacial bonding between fibre and matrix is most critical to obtain enhanced mechanical properties of the resulting composites. Here we present a new surface tailoring method of selective wet etching and organosilicon monomers (3-(Trimethoxysilyl) propyl methacrylate, TMSPMA) deposition process on the short S-Glass fibre as a reinforcing material, resulting in increased mechanical retention and strong chemical bonding between glass fibres and polymer resin (a mixture of triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) monomers). The effect of surface modification on fibre matrix interfacial strength was investigated through microdroplet tests. An S-Glass fibre treated with piranha solution (a mixture of H2O2 and H2SO4) for 24 hours followed by TMSPMA surface silanization shows highest increase up to 39.6% in interfacial shear strength (IFSS), and critical fibre length could be reduced from 916.0 µm to 432.5 µm. We find the optimal surface treatment condition in that the flexural strength of dental composites reinforced by the S-Glass fibres enhanced up to 22.3% compared to the composites without fibre surface treatments. The significant elevation in strength is attributed to changes in the surface roughness of glass fibres at atomic scale, specifically by providing the multiplied spots of the chemical bridge and nano-mechanical interlocking. The findings offer a new strategy for advanced tailoring of short S-Glass fibres to maximise the mechanical properties of biomedical and dental composites.

A biologic scaffold-associated type 2 immune microenvironment inhibits tumor formation and synergizes with checkpoint immunotherapy.

Biomaterials in regenerative medicine are designed to mimic and modulate tissue environments to promote repair. Biologic scaffolds (derived from decellularized tissue extracellular matrix) promote a wound-healing (proregenerative) immune phenotype and are used clinically to treat tissue loss, including in the context of tumor resection. It is unknown whether a biomaterial microenvironment that encourages tissue formation may also promote tumor development. We implanted a urinary bladder matrix (UBM) scaffold, which is used clinically for wound management, with syngeneic cancer cell lines in mice to study how wound-healing immune responses affect tumor formation and sensitivity to immune checkpoint blockade. The UBM scaffold created an immune microenvironment that inhibited B16-F10 melanoma tumor formation in a CD4+ T cell-dependent and macrophage-dependent manner. In-depth immune characterization revealed an activated type 2-like immune response that was distinct from the classical tumor microenvironment, including activated type 2 T helper T cells, a unique macrophage phenotype, eosinophil infiltration, angiogenic factors, and complement. Tumor growth inhibition by PD-1 and PD-L1 checkpoint blockade was potentiated in the UBM scaffold immune microenvironment. Engineering the local tumor microenvironment to promote a type 2 wound-healing immune signature may serve as a therapeutic target to improve immunotherapy efficacy.

A theranostic nanoplatform: magneto-gold@fluorescence polymer nanoparticles for tumor targeting T1&T2-MRI/CT/NIR fluorescence imaging and induction of genuine autophagy mediated chemotherapy.

Multifunctional nanoparticles, bearing low toxicity and tumor-targeting properties, coupled with multifunctional diagnostic imaging and enhanced treatment efficacy, have drawn tremendous attention due to their enormous potential for medical applications. Herein, we report a new kind of biocompatible and tumor-targeting magneto-gold@fluorescent polymer nanoparticle (MGFs-LyP-1), which is based on ultra-small magneto-gold (Fe3O4-Au) nanoparticles and NIR emissive fluorescent polymers by a solvent-mediated method. This kind of nanoparticle could be taken up efficiently and simultaneously serve for in vivo tumor targeting T1&T2-MRI/CT/near infrared (NIR) fluorescence bioimaging. Furthermore, the nanoparticles exhibit small size, higher tumor targeting accumulation, excellent cytocompatibility for long-term tracking, and no disturbing cell proliferation and differentiation. Moreover, clear and convincing evidence proves that as-synthesized MGFs-LyP-1 could elicit genuine autophagy via inducing autophagosome formation, which offers a definite synergistic effect to enhance cancer therapy with doxorubicin (DOX) at a nontoxic concentration through enhancement of the autophagy flux. Meanwhile, the as-prepared nanoparticles could be rapidly cleared from mice without any obvious organ impairment. The results indeed reveal a promising prospect of an MGFs-LyP-1 contrast agent with low toxicity and high efficiency for promising application in biomedicine.

Expression of WNT1 in ameloblastoma and its significance.

The present study aimed to measure the expression of WNT1 in ameloblastoma (AB). Immunohistochemistry was used to observe changes in WNT1 expression in 80 AB samples, 10 keratocystic odontogenic tumor (KCOT) samples and 10 normal oral mucosa (NOM) samples. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to measure WNT1 protein and mRNA expression, respectively, in 30 AB samples, 5 KCOT samples, 5 NOM samples and 3 tooth germ samples. Ectopic cytoplasmic expression of WNT1 was detected in AB; 88.8% (71/80) of the samples were WNT1-positive. The western blotting results demonstrated that compared with NOM (0.57±0.05), WNT1 expression was significantly higher in AB tissue (1.74±0.36, P<0.05), whereas it was not significantly different between AB and KCOT samples (0.80±0.06, P>0.05). RT-qPCR revealed that the level of WNT1 gene expression in AB was increased 2.43-fold compared with normal mucosa, and 1.77-fold compared with tooth germ tissue. In conclusion, WNT1 protein and mRNA expression were increased in AB, and there was ectopic cytoplasmic expression. This indicates that WNT1 may serve an important role in AB occurrence and development.

Efficacy and safety of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) regimen in newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma: interim analysis of a phase 4 study NCT01501149.

To explore a more effective treatment for newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), we conducted a phase 4 study of the cisplatin, dexamethasone, gemcitabine, pegaspargase (DDGP) regimen. The primary end point was the 2-year progression-free survival (PFS) after the protocol treatment. Secondary endpoints included response rate (RR), overall survival (OS) and median survival time (MST). The interim analysis included data only from March 2011 to September 2013, who received six cycles of DDGP chemotherapy. A total of 25 eligible patients were enrolled. Seventeen patients (17/24, 70.83%) achieved complete response (CR) and four (4/24, 16.67%) achieved partial response (PR), three (3/24, 12.50%) had progressive disease (PD). The RR after treatment was 87.50%. After a median follow-up duration of 24.67 months (range 4-48 months). The 2-year PFS and OS rate were 61.80% (95% CI, 42.00% to 81.60%) and 68.50 % (95% CI, 48.70% to 88.30%), respectively. The MST was 36.55 months (95% CI, 29.41 months to 43.70 months). Grade 3/4 leukopenia occurred in fourteen patients (58.33%) and grade 3/4 thrombocytopenia occurred in eleven patients (45.83%). Twelve patients (50.00%) experienced Activated Partial Phromboplastin Ptime (APTT) elongation and fourteen patients (58.33%) experienced hypofibrinogenemia. In conclusion, DDGP regimen is an effective and tolerated treatment for newly diagnosed, advanced-stage ENKTL. This trial was registered at www.ClinicalTrials.gov as #NCT01501149.