Role of FBXW7 in the quiescence of gefitinib-resistant lung cancer stem cells in EGFR-mutant non-small cell lung cancer

Several recent studies suggest that cancer stem cells (CSCs) are involved in intrinsic resistance to cancer treatment. Maintenance of quiescence is crucial for establishing resistance of CSCs to cancer therapeutics. F-box/WD repeat-containing protein 7 (FBXW7) is a ubiquitin ligase that regulates quiescence by targeting the c-MYC protein for ubiquitination. We previously reported that gefitinib-resistant persisters (GRPs) in EGFR-mutant non-small cell lung cancer (NSCLC) cells highly expressed octamer-binding transcription factor 4 (Oct-4) as well as the lung CSC marker CD133, and they exhibited distinctive features of the CSC phenotype. However, the role of FBXW7 in lung CSCs and their resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in NSCLC is not fully understood. In this study, we developed GRPs from the two NSCLC cell lines PC9 and HCC827, which express an EGFR exon 19 deletion mutation, by treatment with a high concentration of gefitinib. The GRPs from both PC9 and HCC827 cells expressed high levels of CD133 and FBXW7, but low levels of c-MYC. Cell cycle analysis demonstrated that the majority of GRPs existed in the G0/G1 phase. Knockdown of the FBXW7 gene significantly reduced the cell number of CD133-positive GRPs and reversed the cell population in the G0/G1-phase. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in gefitinib-resistant tumors of PC9 cells in mice and in 9 out of 14 tumor specimens from EGFR-mutant NSCLC patients with acquired resistance to gefitinib. These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in EGFR mutation-positive NSCLC

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Discovery of Biomarkers for Osteosarcoma by Proteomics Approaches

Osteosarcomas are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. Global protein expression studies, namely, proteomic studies, can offer important clues to understanding the tumor biology that cannot be obtained by other approaches. These studies, such as two-dimensional gel electrophoresis and mass spectrometry, have provided protein expression profiles of osteosarcoma that can be used to develop novel diagnostic and therapeutic biomarkers, as well as to understand biology of tumor progression and malignancy. In this paper, a brief description of the methodology will be provided followed by a few examples of the recent proteomic studies that have generated new information regarding osteosarcomas

Abstract LB-172: Role of post-translational modification of the RUNX2 transcription factor in osteosarcoma

Abstract Background-Several transcription factors or co-factors have recently been reported to be methylated at certain arginine residues, a post-translational modification mediated by two classes of protein arginine methyltransferases (PRMT). Moreover, some PRMTs have been shown to be key regulators of mesenchymal differentiation, and one of the PRMTs is involved in the epigenetic programming of early embryo development. RUNX2 is major transcription factor in osteoblast differentiation but little is known about its activity or function in osteosarcoma (OS). RUNX1, another member of RUNT family, is known to methylated at R206/R210, within the Runt domain, a region that has considerable homology with RUNX2. Here, we examined the possible role of PRMTs in OS in relation to the post-translational modification of RUNX2 and its possible impact on cell proliferation and differentiation. Method-We generated arginine methylation-specific antibodies to RUNX2. The specificity of this antibody was confirmed by detecting immunoprecipitated RUNX2 from Saos2 cells by Western blot. We also confirmed the expression of RUNX2 and arginine methylated RUNX2 in Saos2 cell by immunofluorescence. We also examined the frequency of arginine methylation of RUNX2 in OS patient samples, compared to total RUNX2, by Western blot. Finally, we examined the influence of arginine methylation on the transcriptional activity of RUNX2 by luciferase assay using osteocalcin promoter plasmid. Results-We found that PRMTs can methylate the arginine residue in the Runt domain of RUNX2. This arginine methylation of RUNX2 alters its transcriptional activity at the osteocalcin promoter. Immunofluorescence with arginine methylation-specific antibody showed weak nuclear positivity in the SAOS-2 cell line. Patient tumor samples also show the expression of arginine methylated RUNX2, as well as total RUNX2. Conclusion- Our results confirm that arginine methylation of RUNX2 affects its function as a transcription factor. Further study of the possible role of arginine methylation of RUNX2 in regulating its effect on osteosarcoma proliferation and differentiation could be of translational interest, given the therapeutic potential of PRMT inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-172. doi:10.1158/1538-7445.AM2011-LB-17

Pfetin as a Risk Factor of Recurrence in Gastrointestinal Stromal Tumors

Background. Despite complete resection of gastrointestinal stromal tumors (GIST), recurrent and/or metastatic disease occurs, often depending on the grade of malignancy. As such, markers are needed that accurately predict patients at high risk for recurrence. Previously our group reported Pfetin as a prognostic biomarker for GIST. In order to create an approach for predicting risk of recurrence, we incorporated Pfetin expression with clinicopathological data to produce a predictive model. Object. Forty-five patients with localized primary GIST were treated with complete gross surgical resection surgically at our institution between 1995 and 2010 were included. The majority of tumors originated in the stomach (38 cases), as well as small intestine (6 cases) and rectum (1 case). Method. (1) We performed retrospective analysis of the connection between Pfetin expression, clinicopathological data, and incidences of recurrence, using bivariate and multivariate analyses. (2) The reactivity of the monoclonal antibody against Pfetin was examined by immunohistochemistry. Pfetin. We have reported Pfetin, identified microarray technology, and compared between statistically different GISTs for good and poor prognoses and for prognostic marker. Results. There were 7 cases of recurrences. (1) By univariate analysis, tumor size, mitoses, exposure to abdominal cavity, and complete tumor removal predicted risk of recurrence. (2) Pfetin-negative cases were significantly related to recurrence (P = 0.002). Conclusions. This analysis demonstrates that lack of Pfetin expression is an additional predictor of recurrence in resected GIST. Further study may determine the role of this variable added to the current predictive model for selection of adjuvant therapy

A case of low-grade fibromyxoid sarcoma with unusual central necrosis in a 77-year-old man confirmed by FUS-CREB3L2 gene fusion

AbstractINTRODUCTIONLow-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor typically affecting young to middle-aged adults. Despite its otherwise benign histologic appearance and indolent nature, it can display fully malignant behavior, and recurrence and metastasis can occur even decades after diagnosis.PRESENTATION OF CASEHerein, we report a case of LGFMS in the buttock of a 77-year-old man. Magnetic resonance imaging uncovered a well-demarcated tumor measuring 27×20mm with a slightly high intensity on T1-weighted images (WIs) and heterogeneously high intensity on T2-WIs. Histologically, the tumor was composed of bland spindle-shaped cells in a whorled growth pattern with alternating fibrous and myxoid stroma. The tumor stroma was variably hyalinized with arcades of curvilinear capillaries and arterioles with associated perivascular fibrosis. Unusual histology, such as central necrosis and cystic formation, was also noted. Reverse transcription polymerase chain reaction from a formalin-fixed, paraffin-embedded biopsy specimen revealed a FUS-CREB3L2 gene fusion (exon6/int/exon5), leading to the diagnosis of LGFMS.DISCUSSIONTo the best of our knowledge, this is the second oldest patient to be diagnosed with LGFMS.CONCLUSIONAt the time of this report, the patient was alive with no evidence of the disease 4 months after diagnosis without any adjuvant therapy