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Search Results: 1 - 10 of 126970 matches for " Xinqun Li "
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1, 9-Pyrazoloanthrones Downregulate HIF-1α and Sensitize Cancer Cells to Cetuximab-Mediated Anti-EGFR Therapy
Yang Lu,Xinqun Li,Haiquan Lu,Zhen Fan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015823
Abstract: Cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR), is currently approved for the treatment of several types of solid tumors. We previously showed that cetuximab can inhibit hypoxia-inducible factor-1 alpha (HIF-1α) protein synthesis by inhibiting the activation of EGFR downstream signaling pathways including Erk, Akt, and mTOR. 1, 9-pyrazoloanthrone (1, 9 PA) is an anthrapyrazolone compound best known as SP600125 that specifically inhibits c-jun N-terminal kinase (JNK). Here, we report 1, 9 PA can downregulate HIF-1α independently of its inhibition of JNK. This downregulatory effect was abolished when the oxygen-dependent domain (ODD) of HIF-1α (HIF-1α-ΔODD, the domain responsible for HIF-1α degradation) was experimentally deleted or when the activity of HIF-1α prolyl hydroxylase (PHD) or the 26S proteasomal complex was inhibited, indicating that the 1, 9 PA downregulates HIF-1α by promoting PHD-dependent HIF-1α degradation. We found that the combination of 1, 9 PA and cetuximab worked synergistically to induce apoptosis in cancer cells in which cetuximab or 1, 9 PA alone had no or only weak apoptotic activity. This synergistic effect was substantially decreased in cancer cells transfected with HIF-1α-ΔODD, indicating that downregulation of HIF-1α was the mechanism of this synergistic effect. More importantly, 1, 9 PA can downregulate HIF-1α in cancer cells that are insensitive to cetuximab-induced inhibition of HIF-1α expression due to overexpression of oncogenic Ras (RasG12V). Our findings suggest that 1, 9 PA is a lead compound of a novel class of drugs that may be used to enhance the response of cancer cells to cetuximab through a complementary effect on the downregulation of HIF-1α.
Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells
Xinqun Li, Yang Lu, Ke Liang, Bolin Liu, Zhen Fan
Breast Cancer Research , 2005, DOI: 10.1186/bcr1259
Abstract: The levels of Akt phosphorylation and activity were measured by Western blot analysis with an anti-Ser473-phosphorylated Akt antibody and by in vitro Akt kinase assay using glycogen synthase kinase-3 as a substrate.Within 24 hours after exposure to doxorubicin, MCF7, MDA468 and T47D cells showed a drug-dose-dependent increase in the levels of phosphorylated Akt; in contrast, SKBR3 and MDA231 cells showed a decrease in the levels of phosphorylated Akt, and minimal or no changes were detected in MDA361, MDA157 and BT474 cells. The doxorubicin-induced Akt phosphorylation was correlated with increased kinase activity and was dependent on phosphoinositide 3-kinase (PI3-K). An increased baseline level of Akt was also found in MCF7 cells treated with ionizing radiation. The cellular responses to doxorubicin-induced Akt phosphorylation were potentiated after the expression of Akt upstream activators including HER2, HER3 and focal adhesion kinase.Taken together with our recent published results showing that constitutive Akt mediates resistance to chemotherapy or radiotherapy, our present data suggest that the doxorubicin-induced phosphorylation and activation of Akt might reflect a cellular defensive mechanism of cancer cells to overcome doxorubicin-induced cytotoxic effects, which further supports the current efforts of targeting PI3-K/Akt for enhancing the therapeutic responses of breast cancer cells to chemotherapy and radiotherapy.Cancer cells with an inherent or acquired capability to resist induction of apoptosis at some point(s) in the signal cascade pathway leading to cell death generally tend to be resistant to chemotherapy or radiotherapy. The serine–threonine protein kinase Akt has received much interest in recent years because it suppresses apoptosis induced by chemotherapy or radiotherapy through interaction with several critical molecules that regulate or execute apoptosis. For instance, after activation, Akt could do the following: it phosphorylates the proapo
Responses of cancer cells with wild-type or tyrosine kinase domain-mutated epidermal growth factor receptor (EGFR) to EGFR-targeted therapy are linked to downregulation of hypoxia-inducible factor-1α
Yang Lu, Ke Liang, Xinqun Li, Zhen Fan
Molecular Cancer , 2007, DOI: 10.1186/1476-4598-6-63
Abstract: We found that, compared with previously studied response markers, including EGFR per se and three EGFR downstream signal molecules (ERK, Akt, and STAT3), which showed variable post-treatment changes in levels of phosphorylation and no consistent link of the changes to therapeutic responses, HIF-1α showed a selective decrease in protein levels only in responsive cell lines. To demonstrate a critical role of HIF-1α downregulation by EGFR-targeted treatment, we introduced a constitutively expressed HIF-1α mutant (HIF-1α/ΔODD) that is resistant to cetuximab-induced downregulation in a cetuximab-responsive cell line (A431); we found that the HIF-1α/ΔODD-transfected cells remained sensitive to cetuximab-induced inhibition of Akt and ERK phosphorylation but were remarkably less responsive to cetuximab-induced growth inhibition compared with corresponding control cells.Our data indicates that downregulation of HIF-1α is associated with positive therapeutic responses of cancer cells to EGFR-targeted therapy and suggest further investigation using HIF-1α as an indicator of tumor response to EGFR-targeted therapy in preclinical studies and in the clinical setting.Epidermal growth factor receptor (EGFR) has been implicated in the development and progression of a diverse type of solid tumors. Over the past two decades, experimental cancer therapies targeting EGFR have been studied extensively [1-4]. Recent clinical studies have found that targeting EGFR with receptor-blocking monoclonal antibodies such as cetuximab and panitumumab, or with small-molecule EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, is effective against several types of solid tumors [5-9]. TKI is particularly effective against a subset of non-small cell lung cancers (NSCLCs) that have several somatic mutations in the EGFR tyrosine kinase domain [10-12]. However, many patients do not experience favorable responses to EGFR-targeted therapy, regardless of positive or even high EGFR express

Luo Xinqun Li Aiguo,

现代图书情报技术 , 1994,
Abstract: 本文讨论了小型图书馆, 特别是属于同一行业或系统内的小型图书馆如何建设图书联合馆藏数据库的问题; 简述了建立图书联合馆藏数据库的必要性和可行性以及基本条件; 具体地介绍了联合建库的模式结构、系统设计过程和应注意的问题。
Primary hepatic carcinoid tumor
Jinbo Gao, Zhijian Hu, Junwei Wu, Lishan Bai, Xinqun Chai
World Journal of Surgical Oncology , 2011, DOI: 10.1186/1477-7819-9-151
Abstract: Carcinoid tumors are neoplasms that originate from the cells of neuroendocrine system, and were first characterized by Oberndorfer in 1907. They are usually low-grade malignant tumors that may cause the carcinoid syndrome by secretion of serotonin and other vasoactive hormones. Most of them occur within the gastrointestinal tract, primarily in the appendix and the terminal ileum [1,2]. Primary hepatic carcinoid tumors (PHCT) are very rare. Here, we report a case of PHCT, and describe the clinical features and treatment of this case.A 53-year-old female presented with right upper quadrant abdominal pain and was admitted to our hospital in May 2007. The patient had no history of jaundice, vomiting, flushing or diarrhea. Her past medical history included hypertension and a cholecystectomy due to gallstones 10 years previously. Physical examination showed no abnormality except for the presence of a scar in the right upper quadrant of abdomen. Laboratory investigations, including liver function test, renal function test, blood routine test and tumor markers (AFP, CEA, CA19-9, CA242, CA125 and CA15-3), were within normal limits. Serum hepatitis B surface antigen and hepatitis C antibody were negative.Computer tomography (CT) revealed a low density nodule in segment 4 of liver. Dynamic CT scans showed enhanced of the nodule in the arterial phase and early washout in the portal phase (Figure 1). Liver ultrasound confirmed the presence of the hypervascular mass. No enlarged lymph nodes were found by CT or ultrasonic. Based on the imaging finding, hepatocelluar carcinoma was highly suspected. A fine-needle aspiration biopsy was performed under ultrasonographic guidance for definite diagnosis. The histological examination of the biopsy specimens suggested the tumor was a carcinoid tumor. The neoplastic cells were round or columnar cells with round nuclei and pale eosinophilic cytoplasm. Immunohistochemistry was positive for pancytokeratin AE1/AE3, synaptophysin and chromorgran
Clinical value of ADMA in patients with pulmonary arterial#br# hypertension combination with congenital heart disease

CHEN Pengfei
, HUANG Yiyuan, FANG Zhenfei, HU Xinqun, SHEN Xiangqian, ZHOU Shenghua

- , 2017, DOI: 10.11817/j.issn.1672-7347.2017.01.006
Abstract: 目的:研究血浆不对称二甲基精氨酸(asymmetrical dimethyl-L-arginine,ADMA)作为先天性心脏病(congenital heart disease,CHD)相关肺动脉高压(pulmonary arterial hypertension,PAH)患者诊断、分层与随访指标的应用价值。 方法:收集湘雅二医院心血管内科2013年10月至2014年10月经超声心动图证实的CHD患者(n=100),将其分为3组: 无PAH组、轻中度PAH组、重度PAH组;重度PAH组又分为动力型亚组、艾森曼格综合征前期亚组、艾森曼格综合征 亚组;同时收集健康成人作为对照组(n=25);对20例阻力型患者使用西地那非治疗后随访6个月。采集入选病例所有 临床一般情况、心脏彩色超声检查和心导管检查结果,检测血浆ADMA浓度。结果:轻中度PAH组血浆ADMA水平 显著高于无PAH组及对照组(均P<0.001);重度PAH组血浆ADMA水平显著高于无PAH组及对照组(均P<0.001);无PAH 组血浆ADMA水平与对照组无统计学差异(P=0.209);在重度PAH组中,艾森曼格综合征亚组患者血浆ADMA水平显著 高于动力型亚组(P<0.001);ADMA水平与平均肺动脉压(mPAP),全肺阻力(PVR)呈显著正相关(r分别为0.61,0.417, P<0.001);血浆ADMA浓度0.485 μmol/L时诊断CHD合并重度PAH敏感度为92.0%,特异性为82.7%(P<0.001);20例阻力 型PAH患者使用西地那非治疗6个月后,肺动脉压力得到改善(P=0.001),血浆ADMA水平显著降低(P<0.01)。结论: 血浆ADMA水平可作为早期识别CHD-PAH的无创性筛查指标,在一定程度上反映西地那非治疗效果,有望成为CHDPAH 患者重要的随访指标
Beneficial Experience from Teaching and Education to Research and Development  [PDF]
Li Li
Creative Education (CE) , 2012, DOI: 10.4236/ce.2012.37B039

Teaching and Education (T&E) constitute the most important activity in knowledge transfer from generation to generation. This can explain why government organizations consider the training of highly qualified personnel as one of the most important criteria in the selection of research and development (R&D) grant applications. A university professor should thus not only play the role of researcher, but also that of teacher. T&E and R&D combine to form an inseparable relationship for university professors. By shooting for excellence in T&E, we could get a new perception of a familiar field or initiate a brand new field altogether, which would in turn enhance our research. The quest for excellence in R&D leads to deeper and better understanding of materials taught, and progress in R&D enriches our T&E endeavors. Here, the author shares a beneficial experience from T&E to R&D.

A Causality Analysis of Coal Consumption and Economic Growth for China and India  [PDF]
Jinke Li, Zhongxue Li
Natural Resources (NR) , 2011, DOI: 10.4236/nr.2011.21007
Abstract: China and India are the two countries with the strongest economic growth in the world. Meanwhile they consume much of the global coal to fuel their economic development. With coal burning as a major factor contributing to global greenhouse gas emissions, China and India are confronted with a dilemma of economic growth and environment protection. Will coal consumption reduction cause economic shocks? Is there a causal relationship between coal consumption and economic growth in China and India? In this paper Granger causality tests were used to examine the relationship between coal consumption and GDP in China and India, using data for the period from 1965 to 2006. It was found that a unidirectional causality from GDP to coal consumption existed in China while a unidirectional causality from coal consumption to GDP did in India. Therefore, developing cleaner and more efficient technologies is essential to reduce their CO2 emissions to reach sustainable development.
An Investigation and Analysis of Information Overload in Manager's Work  [PDF]
Tao Li, Min Li
iBusiness (IB) , 2011, DOI: 10.4236/ib.2011.31008
Abstract: The problem of information overload in management field has been receiving increasing attention, while there are less empirical researches now. This paper proposes a conceptual model and some operational variables, in which information overload is as an intervening variable between the factors of causes and impacts. An investigation and analysis has been conducted from a selected sample of managers. This research suggests that work efficiency and work quality are both not strongly connected with information overload. We also find that the main causes of information overload are the work interruption and work time pressure but the amount of information.
Selection Advantage Pattern of International Sci-Tech Cooperation and Empirical Analysis  [PDF]
Li Li, Bin Yu
Journal of Service Science and Management (JSSM) , 2011, DOI: 10.4236/jssm.2011.41006
Abstract: Traditional international sci-tech cooperation theories mainly focus on the ability and advantage owned by cooperative parties, and according to which to guide the direction of international science and technology cooperation. Based on the integration of traditional theories of international science and technology cooperation and concrete practice, this paper proposes the selection advantage pattern and matching mechanism, which comprehensively take cooperator advantages, specification of project and change in circumstance into account and will play a guiding role in terms of determining the key country or region with which to prior carry out international science and technology cooperation. This paper also gives an analysis of the current status of industry development in Guangdong province and the research upon competitiveness evaluation of the world's related leading technology, puts forward corresponding countermeasures and suggestions on the science and technology cooperation patterns and approaches in terms of technological level and resources of Guangdong province.
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