A recent trend in Magnetic Resonance Imaging (MRI) research is to combine MRI scanners with other medical modalities to provide multiple image information or image-guided therapy. Splitting an MRI system into two halves, including splitting the main magnet and the gradient coils, is one of the approaches used to design such hybrid MRI systems. However, it is very difficult to design split-gradient coil sets that have a high performance, particularly if the gap between the two halves is large. The consequences of reduced performance may include, reduced switching times, increased eddy current induction or reduced linearity resulting in an MR image distortion. Therefore, this thesis studies the impact of incorporating a central gap into an MRI system in terms of the gradient system performance, eddy current effects and gradient-induced electric fields and current densities in the patientrs body. It also improves the system performance by designing a novel splittransverse gradient coil. This study will enable split MRI scanners by providing high quality gradient set designs. To understand the potential problems involved in split-gradient coil design, this thesis first introduces the principles of the MRI systems and the nature of example MRI hybrid systems, followed by descriptions of all the simulation methods used in this thesis. Second, the gradient performance and the gradient-induced eddy current effects in a split MRI system were analysed and studied as a function of the central gap size. It was found that when the gap size increased, the gradient performance tended to decrease, while the eddy current effects intensified. An optimal central gap size was found in this work. A split MRI system with this gap size could provide a system performance similar to a conventional non-split system. Third, to improve the deteriorated performance of the split-MRI system, a novel split-transverse gradient coil geometry was proposed, specifically designed for split systems with a large central gap. When compared with other existing coil designs, this design was shown to provide a similar coil performance, but with a more linear gradient field in the region of interest (ROI). By analysing the currentinduced Ohmic power dissipated in the surrounding conductive materials, it was found that this novel coil induced a moderate amount of eddy currents. When an MRI scanner is split with a large central gap to enable the perpendicular use of Linear accelerators (LINAC), the gap could be made large enough for a patient to be placed in the radial direction. It is suspected that the electric field and currents induced by the switching gradient field ii in the conductive human tissues would be influenced by the change in the patientrs location. Fourth, an investigation of the gradient-induced electric field and current densities in the patient models was undertaken. The simulation results showed that the amplitudes and distributions of the fields and current densities induced by different split x-gradient coils were similar in the ROI of the body model, but varied outside of the target region. The results also indicated that the distributions of the peak current densities varied when the body position, orientation or gender changed, while the peak electric fields occurred mainly in the skin and fat tissue.n
The results arising out of authors participating an inter-national collaborative study organized by 2nd AOHW in 1982 were reported, when HLA frequencies in 50 newly diagnosed NPC patients were compared with those in 40 normal controls, there is an increased risk of NPC associated with B17(RR=2.54) and a decreased with A11 (RR=0.28). On the other hand, there is an excess of DR double blanks among NPC patients, which are probably associated with increased risk of NPC (RR=2.82). Association between antigen BW46 and NPC has not been confirmed in this study. This may be attributable to the smaller size of the sample.
Epstein-Barr virus (EBV) is widely found in nasopharyngeal carcinoma (NPC) tissue and associated with poor prognosis of patients. EBV nuclear antigen 1 (EBNA1) is expressed in all NPC tumors and plays multiple biological roles in both virus and host cells. Triptolide is a natural product extracted from Tripterygium and shows anti-cancer activities. The goal of this work was to illustrate the anti-cancer effect of triptolide and elucidate a novel anti-apoptotic mechanism of EBNA1 in NPC cells encountered with triptolide. In the present study, a CCK-8 assay was used to analyze the proliferation of NPC cells treated with triptolide in a dose- and time-dependent ways. Effects of triptolide on NPC cell cycle and apoptosis were investigated by flow cytometric analysis. EBNA1 expression in mRNA and protein levels was determined by quantitative real-time PCR and Western blot, respectively. Our results showed that triptolide effectively inhibited proliferation of NPC cells. Triptolide arrested NPC cell cycles in S phase and induced apoptosis through a caspase-9-dependent apoptosis pathway. Low-dose of triptolide reduced the half-life of EBNA1 and significantly decreased EBNA1 expression by promoting the process of proteasome-ubiquitin pathway. Over-expression of EBNA1, which was independent from EBV genome, effectively attenuated the apoptosis induced by triptolide. In addition, triptolide significantly inhibited proliferations of tumors induced by EBV-positive cells in vivo. Furthermore, EBNA1 were expressed in all NPC biopsies of Chinese patients. In summary, our study provides the evidence that triptolide induces EBNA1 degradation and stimulates NPC apoptosis through mitochondria apoptotic pathway. In addition, EBNA1 assists NPC cells to resist triptolide-induced apoptosis through inhibiting caspase-9-dependent apoptotic pathway.
Hepatocellular carcinoma (HCC) is one of the most common and malignant cancers. The HCC incidence gets a strong sexual dimorphism as men are the major sufferers in this disaster. Although several studies have uncovered the presentative correlation between the axis of androgen/androgen receptor (AR) and HCC incidence, the mechanism is still largely unknown. Cancer stem cells (CSCs) are a small subgroup of cancer cells contributing to multiple tumors malignant behaviors, which play an important role in oncogenesis of various cancers including HCC. However, whether androgen/AR axis involves in regulation of HCC cells stemness remains unclear. Our previous study had identified that the pluripotency factor Nanog is not only a stemness biomarker, but also a potent regulator of CSCs in HCC. In this study, we revealed androgen/AR axis can promote HCC cells stemness by transcriptional activation of Nanog expression through directly binding to its promoter. In HCC tissues, we found that AR expression was abnormal high and got correlation with Nanog. Then, by labeling cellular endogenous Nanog with green fluorescent protein (GFP) through CRISPR/Cas9 system, it verified the co-localization of AR and Nanog in HCC cells. With in vitro experiments, we demonstrated the axis can promote HCC cells stemness, which effect is in a Nanog-dependent manner and through activating its transcription. And the xenografted tumor experiments confirmed the axis effect on tumorigenesis facilitation in vivo. Above all, we revealed a new sight of androgen/AR axis roles in HCC and provided a potential way for suppressing the axis in HCC therapy.
Cervical cancer is a major cause of cancer death in women worldwide. Targeting human papillomavirus (HPV) viral oncoproteins E6 and E7 is a new strategy for cervical cancer immunotherapy and has been associated with resolution of HPV-induced lesions. How to efficiently induce T cell target killing of HPV infected cervical cancer is of great potential benefit for cervical cancer treatment. Fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for Toll-like receptor 4 (TLR4), and HPVE7 (EDA-E7) has been shown to efficiently induce dendritic cells maturation and trigger specific antitumor CD8+ T cells response in mice. In this study, we constructed EDA-E7 fusion protein of human origin and tested its function in dendritic cell maturation as well as antitumor T cell response. We found that EDA-E7 could be efficiently captured by human PBMC derived dendritic cells (DCs) in vitro and induce DCs maturation. Importantly, this effect could work in synergy with the TLR ligand anti-CD40 agonist, polyinosinic-polycytidylic acid [poly (I:C)], R848, and CpG2216. EDA-E7 matured DCs could activate T cells and trigger an anti-tumor response in vitro. Single cell RNA sequencing and T cell targeted killing assay confirmed the activation of T cells by EDA-E7 matured DCs. Therefore, therapeutic vaccination with EDA-E7 fusion protein maybe effective for human cervical carcinoma treatment.
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