BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a distinct entity of lymphoid tissue. ENKTL is sensitive to radiotherapy (RT), but the prognosis is poorer than for other types of early lymphoma. The treatment schedule is controversial. METHODS: A phase 2 study was conducted of ''sandwich'' protocols, with earlier RT after an initial 2 to 3 cycles of LVP (L-asparaginase, vincristine, and prednisone), followed by further ''consolidation'' cycles. Patients aged 18 years and older who had previously untreated ENKTL and localized lesions in the upper aerodigestive tract were enrolled. The primary endpoints were objective response rate and complete remission rate. The secondary endpoints were 2-year overall survival, 2-year progression-free survival, and toxicity. This study is registered with www.Chictr.org, number ChicTR-TNC-00000394, and is ongoing for long-term follow-up. RESULTS: Twenty-six patients completed total therapy, which resulted in 88.5% response that included 21 patients (80.8%) with complete response (CR) and 2 patients (7.7%) with partial response. Three (11.5%) of 26 patients progressed during therapy. With a median follow-up of 27 months (range, 4-35 months), the 2-year overall survival was 88.5%, and the 2-year progression-free survival was 80.6%. Patients with CR had better prognosis than patients without CR. Only 2 patients (7.7%) experienced grade 3 leukocytopenia. No grade 4 toxicity or treatment-related deaths were observed. CONCLUSIONS: The research showed that the ''sandwich'' protocol of LVP combined with RT was a safe and effective treatment for localized nasal natural killer/T-cell lymphoma, and the results warrant further investigation into this protocol. Cancer 2012;118:3294-
Endothelialization of vascular grafts prior to implantation has been investigated widely to enhance biocompatibility and antithrombogenicity. Thrombosis of artificial vessels is typically caused by platelet adhesion and agglomeration following endothelial cells detachment when exposed to the shear stress of blood circulation. The present study thus aimed at preventing platelet adhesion and aggregation onto biomaterials before the endothelial confluence is fully achieved. We report this modification of poly(lactic-co-glycolic acid) (PLGA) scaffolds, both to impart hemocompatibility to prevent platelet adhesion and aggregation before the endothelial confluence is fully achieved and to support EC growth to accelerate endothelialization. The modification was achieved by covalent immobilization of sulfated silk fibroin on PLGA scaffolds using γ irradiation. Using phosphate-buffered saline (PBS) as an aging medium, it was demonstrated that the scaffolds prepared by γ irradiation had a good retention of sulfated silk fibroin. The systematic in vitro hemocompatibility evaluation revealed that sulfated silk fibroin covalently immobilized PLGA (S-PLGA) scaffolds-reduced platelet adhesion and activation, prolonged whole blood clotting time, activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). To evaluate further in vitro cytocompatibility of the scaffolds, we seeded vascular ECs on the scaffolds and cultured them for 2 weeks. The ECs were seen to attach and proliferate well on S-PLGA scaffolds, forming cell aggregates that gradually increased in size and fused with adjacent cell aggregates to form a monolayer covering the scaffold surface. Moreover, it was demonstrated through the gene transcript levels and the protein expressions of EC-specific markers that the cell functions of ECs on S-PLGA scaffolds were better preserved than those on PLGA scaffolds. Therefore, this study has described the generation of a vascular graft that possesses the unique ability to display excellent hemocompatibility while simultaneously supporting extensive endothelialization.
The topical literature lacks any comparison between stereolithography (SLA) and direct light processing (DLP) printing methods with regard to the accuracy of complete denture base fabrication, thereby utilizing materials certified for this purpose. In order to investigate this aspect, 15 denture bases were printed with SLA and DLP methods using three build angles: 0°, 45° and 90°. The dentures were digitalized using a laboratory scanner (D2000, 3Shape) and analyzed in analyzing software (Geomagic Control X, 3D systems). Differences between 3D datasets were measured using the root mean square (RMS) value for trueness and precision and mean and maximum deviations were obtained for each denture base. The data were statistically analyzed using two-way ANOVA and Tukey’s multiple comparison test. A heat map was generated to display the locations of the deviations within the intaglio surface. The overall tendency indicated that SLA denture bases had significantly higher trueness for most build angles compared to DLP (p < 0.001). The 90° build angle may provide the best trueness for both SLA and DLP. With regard to precision, statistically significant differences were found in the build angles only. Higher precision was revealed in the DLP angle of 0° in comparison to the 45° and 90° angles.
Zn-based biodegradable metallic materials have been regarded as new potential biomaterials for use as biodegradable implants, mainly because of the ideal degradation rate compared with those of Mg-based alloys and Fe-based alloys. In this study, we developed and investigated a novel Zn-4 wt % Ag alloy as a potential biodegradable metal. A thermomechanical treatment was applied to refine the microstructure and, consequently, to improve the mechanical properties, compared to pure Zn. The yield strength (YS), ultimate tensile strength (UTS) and elongation of the Zn-4Ag alloy are 157 MPa, 261 MPa, and 37%, respectively. The corrosion rate of Zn-4Ag calculated from released Zn ions in DMEM extracts is approximately 0.75 ± 0.16 μg cm–2 day–1, which is higher than that of pure Zn. In vitro cytotoxicity tests showed that the Zn-4Ag alloy exhibits acceptable toxicity to L929 and Saos-2 cells, and could effectively inhibit initial bacteria adhesion. This study shows that the Zn-4Ag exhibits excellent mechanical properties, predictable degradation behavior, acceptable biocompatibility, and effective antibacterial properties, which make it a candidate biodegradable material.
MicroRNAs (miRNAs) have been demonstrated to modulate cellular processes in the liver. However, the role of miRNAs in liver fibrosis is poorly understood. Because the activation of hepatic stellate cells (HSCs) is a pivotal event in the initiation and progression of hepatic fibrosis, we investigate the differential expression of miRNAs in activated and quiescent rat HSCs by microarray analysis and find that miR-214 (miR-214-3p) is significantly upregulated during HSC activation. Moreover, the robust induction of miR-214 is correlated with liver fibrogenesis in carbon tetrachloride (CCl4)-treated rats and mice, high-fat diet-induced non-alcoholic steatohepatitis in mice, and cirrhosis in humans. We identify that miR-214 expression is driven by the helix–loop–helix transcription factor Twist1 via the E-box element. The increased miR-214 inhibits the expression of suppressor-of-fused homolog (Sufu), a negative regulator of the Hedgehog signaling pathway, thereby contributing to HSC activation to promote the accumulation of fibrous extracellular matrix and the expression of profibrotic genes in HSCs and LX2 cells. Furthermore, miR-214 expression is inversely correlated with the expression of Sufu in clinical cirrhosis samples. To explore the clinical potential of miR-214, we inject antagomiR-214 oligos into mice to induce hepatic fibrosis. The knockdown of miR-214 in vivo enhances Sufu expression and reduces fibrosis marker expression, which ameliorates liver fibrosis in mice. In conclusions, the Twist1-regulated miR-214 promotes the activation of HSC cells through targeting Sufu involved in the Hedgehog pathway and participates in the development of hepatic fibrosis. Hence, the knockdown of miR-214 expression may be a promising therapeutic strategy for liver fibrosis.
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