Cytotoxic T lymphocyte epitopes from human heparanase can elicit a potent anti-tumor immune response in mice

Heparanase is expressed in almost all advanced tumors, and therefore it may serve as a potential target for tumor therapy. Our previous study has shown that heparanase can serve as a potential universal tumor-associated antigen (TAA) for the immunotherapy of advanced tumors. Further study demonstrated that the HLA-A*0201-restricted Cytotoxic T lymphocytes (CTL) epitopes Hpa525 (PAFSYSFFV), Hpa277 (KMLKSFLKA) and Hpa405 (WLSLLFKKL) from human heparanase could induce a potent anti-tumor immune response in vitro. The present study was designed to investigate whether the above peptides could induce immune responses in mice. Our results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched. We also found that these peptide-specific CTLs did not lyse autologous lymphocytes that had low heparanase activity. Further study revealed that Hpa525, Hpa277, and Hpa405 peptides increased the frequency of IFN-γ-producing T cells as compared to a negative peptide. These results suggest that Hpa525, Hpa277, and Hpa405 peptides are novel HLA-A*0201-restricted CTL epitopes capable of inducing heparanase-specific CTLs in mice. Because heparanase is expressed in most advanced malignant tumors, Hpa525, Hpa277, and Hpa405 peptide-based vaccines may be useful for the immunotherapy of patients with advanced tumors.     

Resveratrol derivative,trans‐3,5,4′‐trimethoxystilbene,exerts antiangiogenic and vascular‐disrupting effects in zebrafish through the downregulation of VEGFR2 and cell‐cycle modulation

Angiogenesis plays an important role in the development of neoplastic diseases such as cancer. Resveratrol and its derivatives exert antiangiogenic effects, but the mechanisms of their actions remain unclear. The aim of this study was to evaluate the antiangiogenic activity of resveratrol and its derivative trans‐3,5,4′‐trimethoxystilbene in vitro using human umbilical vein endothelial cells (HUVECs) and in vivo using transgenic zebrafish, and to clarify their mechanisms of action in zebrafish by gene expression analysis of the vascular endothelial growth factor (VEGF) receptor (VEGFR2/KDR) and cell‐cycle analysis. trans‐3,5,4′‐Trimethoxystilbene showed significantly more potent antiangiogenic activity than that of resveratrol in both assays. In zebrafish, trans‐3,5,4′‐trimethoxystilbene caused intersegmental vessel regression and downregulated VEGFR2 mRNA expression. Trans‐3,5,4′‐trimethoxystilbene also induced G2/M cell‐cycle arrest, most specifically in endothelial cells of zebrafish embryos. We propose that the antiangiogenic and vascular‐targeting activities of trans‐3,5,4′‐trimethoxystilbene result from the downregulation of VEGFR2 expression and cell‐cycle arrest at G2/M phase. J. Cell. Biochem. 109: 339–346, 2010. © 2009 Wiley‐Liss, Inc.     

Design and synthesis of novel Gefitinib analogues with improved anti-tumor activity

There is an urgent need to design and develop new and more potent EGFR inhibitors with improved anti-tumor activity. Here we describe the design and synthesis of two series of 4-benzothienyl amino quinazolines as new analogues of the EGFR inhibitor Gefitinib. The anti-tumor activity of these novel Gefitinib analogues in 6 human cancer cell lines was examined. Compared with the parental Gefitinib, most of the new compounds show a markedly increased cytotoxicity to cancer cells. Furthermore, several of the series B compounds that side chains at position 7 contain either a methyl or ethyl group are potent pan-RTK inhibitors. Two representative compounds in this class, 15 and 17, have an enhanced capability to inhibit cancer cell growth and induce apoptosis in vitro and inhibit tumor formation in vivo in human cancer cells with high HER-2, as compared with the parental Gefitinib. Thus they may be promising lead compounds to be developed as an alternative for current Gefitinib therapy or for Gefitinb-resistant patients, potentially via simultaneously blocking multiple RTK signaling pathways.     

不同育苗方式对移栽后侧柏和白榆幼苗根系生长的影响

不同类型苗木,具有不同的根系结构特征,其根系结构也将影响林木的生长和恢复生态系统的稳定性。以侧柏和白榆为研究对象,对移栽18个月后的种基盘苗与营养钵苗根系的生长进行了调查。结果表明:侧柏种基盘苗的总根长和平均直径比营养钵苗分别增加了316.20 cm和0.05mm,白榆苗则分别增加了651.54 cm和0.88mm。侧柏和白榆种基盘苗的根系表面积比营养钵苗分别增加了40.05%和73.04%。侧柏种基盘苗的根系总体积与营养钵苗的差异不显著,而白榆种基盘苗的根系总体积则比营养钵苗增加了54.70%。侧柏和白榆营养钵苗的一级侧根数量大于种基盘苗,增幅分别为42.31%和30.65%。对于侧柏来说,营养钵苗的根尖总数比种基盘苗的增加324个,但白榆苗差异不显著。各种处理的幼苗总根长与根系表面积都有显著相关性,但与根体积不具有显著相关性。营养钵苗的根系平均直径和根尖数量具有相对独立性,而种基盘的根系平均直径与总根长以及根体积均表现为显著相关。种基盘苗能提高侧柏、白榆幼苗的根冠比,促进幼苗株高、地径和主根的生长。采用种基盘苗进行植被恢复,由于其具有较大的根表面积和根长度,林木便具有了较大的吸收水分和营养的能力,以及较高的固结表层土壤能力。     

中国土地利用多功能性动态的区域分析

当前,国际学术界针对土地利用的研究正由土地利用格局变化向土地空间多功能变化及其可持续性的方向发展,其宗旨是确定和度量土地多元化利用所提供的产品、服务和功能,及其带来的环境和社会经济效应,实现对土地利用的科学管理。基于可持续发展三维度的理念及其指标体系,界定并定量评价了我国区域土地利用的10项功能,深入研究了在经济快速发展、生态环境保护紧密相随的过去20a间,各项功能的时空变化特征。研究表明,我国土地多功能性的10项功能中,就业支持功能表现出区域增减不一的特点,生态过程维持功能具有高度的稳定性。健康保障、交通功能、居住家园、生物性土地生产、人工化土地生产、资源供给与维持、污染接收器、景观与文化支持功能在各个区域得到了不断改善与提高,但各个功能变化的强势区和弱势区在时空分布上表现出了很强的区域性特点。区域自然条件禀赋、社会经济条件以及土地利用政策在功能变化中起着关键作用。研究结果揭出中国区域土地多功能性尚存在巨大的提升空间;土地政策应具有系统性、功能针对性和时空针对性,并应关注土地利用功能变化的链发效应。     

重组Hepcidin融合蛋白的氧化复性及活性鉴定

将诱导表达的His-hepcidin融合蛋白包涵体通过固定化金属离子配体亲和层析(IMAC)柱分离纯化后,在cys-teine/cystine氧化还原体系中氧化形成二硫键,稀释复性后用肠激酶将融合蛋白的his-tag切除。酶切后所得的Hepcidin经抑菌圈试验检验,对枯草芽孢杆菌等革兰氏阳性菌和部分革兰氏阴性菌具有抗菌活性。     

2009年中国植物科学若干领域重要研究进展

2009年中国植物科学在水稻和拟南芥研究等方面取得＂爆发性＂的快速发展。中国科学家在植物科学各领域中取得了大量的原创性研究成果,尤其是在基于新一代测序技术和计算生物学理论的基因组学、水稻功能基因挖掘、激素受体和信号转导以及转基因作物产业化和生态安全性研究等方面取得一系列重大进展,受到了国内外广泛关注。该文对2009年中国本土植物生命科学若干领域取得的重要研究进展进行概括性评述,旨在全面追踪当前中国植物科学领域发展的最新前沿和热点事件,并展现我国科学家们所取得的杰出成就。     

基于CSSL的水稻抽穗期QTL定位及遗传分析

抽穗期是水稻（Oryza sativa）品种的重要农艺性状之一,适宜的抽穗期是获得理想产量的前提。鉴定和定位水稻抽穗期基因/QTL,分析其遗传效应对改良水稻抽穗期至关重要。以籼稻品种9311（Oryzasativa ssp.indica‘Yangdao 6’）为受体,粳稻品种日本晴（Oryza sativa ssp.japonica‘Nipponbare’）为供体构建的94个染色体片段置换系群体为材料,以P≤0.01为阈值,对置换片段上的抽穗期QTL进行了鉴定。采用代换作图法共定位了4个控制水稻抽穗期的QTL,分别位于第3、第4、第5和第8染色体;QTL的加性效应值变化范围为–6.4––2.7,加性效应百分率变化范围为–6.4%––2.7%;qHD-3和qHD-8加性效应值较大,表现主效基因特征。为了进一步定位qHD-3和qHD-8,在目标区域加密16对SSR引物,qHD-3和qHD-8分别被界定在第3染色体RM3166–RM16206之间及第8染色体RM4085–RM8271之间,其遗传距离分别为13.9cM和6.4cM。研究结果为利用分子标记辅助选择改良水稻抽穗期奠定了基础。     

生长素调控植物重力反应的分子机理研究

重力反应是植物对环境的一种适应现象。生长素参与植物环境适应与发育调控的过程,重力反应过程的核心之一是在重力反应器官形成生长素的浓度梯度,诱导下游基因的差异表达。生长素的合成、代谢、极性运输及信号转导在此过程中发挥了关键作用。该文以拟南芥和水稻的研究为基础,综述了近几年对生长素调控植株重力反应的分子机理的研究进展,并对该领域未来的研究进行展望。     

分类多样性在大型底栖动物生态学方面的应用:以黄海底栖动物为例

根据文献资料,系统整理了黄海大型底栖动物物种名录,并得到了其平均分类差异指数和分类差异变异指数的理论平均值及95%置信区间漏斗图。结果表明,黄海共有大型底栖动物1,360种,分属于17门35纲91目368科842属。其平均分类差异指数的理论平均值为93.7,分类差异变异指数为213.6。将已知受到中度扰动的胶州湾部分站位真实值叠加到平均分类差异指数的95%置信区间漏斗图中,发现全部站位均显著低于95%置信区间,显示了平均分类差异指数在海洋污染监测方面的良好应用前景。