The molecular subsets of glioma behave in biologically distinct ways. The present study detected isocitrate dehydrogenase (IDH) 1 and IDH2 mutations in glioma to analyze whether IDH-mutated gliomas are situated in certain preferential areas and to investigate their correlation with magnetic resonance imaging (MRI) characteristics. A series of 193 patients with astrocytic neoplasms (111 diffuse and 82 anaplastic astrocytomas), grouped according to prelabeled anatomical structures and the risk of surgery, were retrospectively reviewed for IDH1 and IDH2 mutations to compare the tumor location and MRI features. A total of 111 IDH1 mutations at codon 132 (57.5%) and six IDH2 mutations at codon 172 (3.1%) were detected. The IDH1/2 mutations were found to predict longer survival, independent of the histological type in this series of patients. The IDH-mutated gliomas were predominantly located in a single lobe, such as the frontal lobe, temporal lobe or cerebellum and rarely in the diencephalon or brain stem. Furthermore, according to the risk of surgery, the IDH-mutated tumors were rarely located in the high-risk regions of the brain, where surgery exhibits a high mortality rate intraoperatively and postoperatively. In addition, gliomas with IDH mutations were significantly more likely to exhibit a unilateral pattern of growth, sharp tumor margins, homogeneous signal intensity and less contrast enhancement on MRI. The results of the current study suggested that the prolonged survival of patients with IDH-mutated gliomas is primarily due to a less aggressive biological behavior according to tumor site and MRI features.
The current method for making dental ceramic prostheses in a subtractive manner causes a severe waste of materials while requires excessive manual works that bring in the uncertainty for control of quality. The rapid development and commercialisation of additive manufacturing (AM) has aroused interest and wonders both in material and dental communities about their potentials and challenges in fabricating of ceramic prostheses in a materials-saving manner. In this work, AM approach was applied to fabricate the dental bridges and implants made of zirconia. The achieved geometries and dimensional accuracy are used to demonstrate the potential of this technique in fabricating of dental ceramic prostheses, whereas the observed macro and micro defects formed during the treatment process is used to reveal the challenges facing in order to adapt this technology into real dental practice. Suggestions are provided for future development of the technology, particularly on minimising the processing defects.
In this work, we prepared Al2O3 ceramic green parts with complex geometry and architecture using an additive manufacturing process based on stereolithography. The rheological and thermal behavior of Al2O3 slurry was firstly examined and used to establish the conditions for molding and debinding. As opposed to previous researches that only focused on manufacture techniques, the sintering behavior and densification process were systematically investigated. In addition, special attentions were paid to the evolution of microstructure between green bodies and sintered parts. The results showed that debound parts were equipped with uniform particle packing and narrow pore size distribution. The dimensions of the Al2O3 parts changed anisotropically with the different processing steps. The densification process was greatly accelerated by the decrease in pore size and annihilating of interconnected pores in which significant grain growth was observed above 1450°C. The sintered part also had a homogeneous microstructure and no interface between adjacent layers. High densification (relative density of 99.1%) and much desirable Vickers hardness (17.9 GPa) of Al2O3 parts were achieved at the sintering temperature of 1650°C.
Summary Aims In this study, we examined the expression of GINS2 in glioma and determined its role in glioma development. Methods The protein expression of GINS2 was assessed in 120 human glioma samples via immunohistochemistry. Then, we suppressed the expression of GINS2 in glioma cell strains U87 and U251 using a short hairpin RNA lentiviral vector. In addition, RNA sequencing and bioinformatics analysis were performed on glioma cells before and after GINS2 knockdown. Subsequent co‐immunoprecipitation and western blot experiments indicated possible downstream regulatory molecules. Results The present results showed that GINS2 can accelerate the growth of glioma cells, whereas the suppression of GINS2 expression decreased the proliferation and tumorigenicity of glioma cells. Mechanism research experiments proved that GINS2 can block the cell cycle by regulating certain downstream molecules, such as MCM2, ATM, and CHEK2. Conclusion GINS2 is closely related to the occurrence and development of glioma, and is likely to become a prognostic marker for glioma patients, as well as a potential therapeutic target in the treatment of glioma.
Differentially expressed proteins between the U251 and U87 cell lines are associated with regulation of nicotinamide nucleotide metabolism, RNA splicing, glycolysis, and purine metabolism pathways. Further studies on these pathways may identify whether these various pathways account for the observed phenotype differences between the U87 and U251 GBM cell lines.
Temozolomide (TMZ) is the main chemotherapeutic drug utilized for the treatment of glioblastoma multiforme (GMB), however, drug resistance often leads to tumor recurrence and poor outcomes. GMB cell lines were treated with TMZ for up to two weeks and then subjected to proteomics analysis to identify the underlying molecular pathology that is associated with TMZ resistance. Proteomics data showed that TMZ altered expression of proteins that related to cytoskeleton structure and function, such as DHC2 and KIF2B. qRT-PCR and immunofluorescence were used to verify expression of DHC2 and KIF2B in these cells. Immunohistochemistry was used to verify expression of these two proteins in xenografts of a nude mouse model, and ex vivo GBM tissue samples. Their expression was knocked down using siRNA to confirm their role in the regulation of GBM cell sensitivity to TMZ. Knockdown of DHC2 expression enhanced sensitivity of U87 cells to TMZ treatment. Ex vivo data showed that DHC2 expression in GBM tissue samples was associated with tumor recurrence after TMZ chemotherapy. These results indicated cytoskeleton related protein DHC2 reduced sensitivity of GBM cells to TMZ treatment. Further studies should assess DHC2 as a novel target in GBM for TMZ combination treatment.
With the recent rapid development of the additive manufacturing family of technologies, the interest in application potential of stereolithography on producing ceramic dental prostheses has aroused and been widely discussed. While someone claimed the birth of 'stereolithography-fabricated ceramic dental prostheses', an overall evaluation based on the clinical requirements is lacking, making the optimism a kind of unrealistic. In this article, the prototypes of ceramic dental prostheses and standard specimens produced by the ceramic stereolithography approach are compared with those made by the classic subtractive manufacturing method by following the critical clinical requirements. Concerns on the upcoming challenges and future improvement towards clinical applications are presented that include productivity, delivery time, dimensional tolerance, mechanical and aesthetic properties. It is concluded that it is far too early to call 'stereolithography-fabricated ceramic dental prostheses' as a success as usable and competitive products for clinical applications.
In this study, we developed a unique defect healing method for 3D printed ceramic compact via cold isostatic pressing (CIP) after debinding, and typical features of interlayer interface defects of 3D-printed zirconia compact were characterized and found to be reduced significantly. The characteristic sintering kinetics window and microstructure evolution of the healed sintered bodies were systematically investigated, which was found to be quite different from conventional shaping methods. The three sintering stages are probed by their feature microstructure details such as the mechanically flattening surface at the early sintering stage, the heterogeneous microstructure and high porosity in the interlayer interface region at the middle stage, and the slightly ripple-like structural features combined with the healed interlayer defects at the final stage. The evolution of the pore structure of the healed 3D printed bodies were traced and the mechanical properties such as the Young's modulus, hardness, and fracture toughness were measured to understand the significance of the heal effect. K E Y W O R D S3D printing, defects, kinetics, sintering Di An and Wei Liu contributed equally to this work.
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