Angiogenesis in life, disease and medicine

The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.     

Angiogenesis in cancer and other diseases

Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases. Concentrated efforts in this area of research are leading to the discovery of a growing number of pro- and anti-angiogenic molecules, some of which are already in clinical trials. The complex interactions among these molecules and how they affect vascular structure and function in different environments are now beginning to be elucidated. This integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases. But owing to several unanswered questions, caution is needed.     

Corneal avascularity is due to soluble VEGF receptor-1

Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.     

PPARγ罗格列酮对HT-29的生长抑制作用

PPARγ配体在抗肿瘤中发挥着重要的作用,这些配体具有抗肿瘤、诱导分化和抗血管生成等效果.目的主要是评估PPARγ激动剂罗格列酮对结肠癌细胞株HT-29生长的抑制作用.结果显示,罗格列酮可以有效地抑制体外培养的结肠癌细胞株HT-29的生长及克隆形成,并能抑制HT-29裸鼠移植瘤的生长.与此同时,罗格列酮能够升高PPARγ, p- PPARγ的表达水平.以上结果初步证明罗格列酮在体内外均可抑制结肠癌细胞株HT-29的成长,提示罗格列酮有可能发展成为治疗结肠癌的有效药物.     

傅里叶红外光谱法在肿瘤分析中的应用

综述了傅里叶红外光谱(FTIR)在鉴定癌症中的应用研究进展.目前,对其诊断主要是依靠病理学诊断,但是病理学诊断不仅过程烦琐,而且常受人为因素影响.傅里叶红外光谱及其相关技术的迅速发展,使其越来越广泛用于蛋白质,核酸等生物大分子的结构研究上,同时已开始更深入地应用于研究细胞和组织等更加复杂的体系.研究结果表明,FTIR可以从分子水平上揭示肿瘤组织的特性,极有可能发展成为一种可定量化地鉴定肿瘤的手段.     

Tumour biology: herceptin acts as an anti-angiogenic cocktail

Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments.     

A Hybrid Mathematical Model of Tumor-Induced Angiogenesis with Blood Perfusion

Angiogenesis, the growth of new blood vessel from existing ones, is a pivotal stage in cancer development,and is an important target for cancer therapy. We develop a hybrid mathematical model to understand the mechanisms behind tumor-induced angiogenesis. This model describes uptake of Tumor Angiogenic Factor（TAF）at extracellular level, uses partial differential equation to describe the evolution of endothelial cell density including TAF induced proliferation, chemotaxis to TAF, and haptotaxis to extracellular matrix. In addition we also consider the phenomenon of blood perfusion in the micro-vessels. The model produces sprout formation with realistic morphological and dynamical features, including the so-called brush border effect, the dendritic branching and fusing of the capillary sprouts forming a vessel network. The model also demonstrates the effects of individual mechanisms in tumor angiogenesis： Chemotaxis to TAF is the key driving mechanisms for the extension of sprout cell; endothelial proliferation is not absolutely necessary for sprout extension; haptotaxis to Extra Cellular Matrix（ECM） gradient provides additional guidance to sprout extension, suggesting potential targets for anti-angiogenic therapies.     

Use of DNAzymes for cancer research and therapy

DNAzymes(Dzs) are single-stranded DNA catalysts that specifically cleave the mRNA of targeted genes.Compared with other gene-silencing technologies,such as ribozymes,antisense oligonucleotide and small interference RNA(siRNA),DNAzymes have several advantages,including small molecular weight,diversity,low cost and relative stability in serum.With the evolution of molecular technology,the first DNAzyme was generated in vitro in 1994.From then on,DNAzymes have been studied in order to understand their structures,chemistry and biological applications.Particularly,DNAzymes have been widely applied as a new interference strategy in the treatment of many conditions,including cancer,viral diseases,and cardiovascular diseases.This review mainly summarizes the use of DNAzymes in the areas of cancer research and therapy.     

广东省高校人才培养与区域经济协同发展研究

结合广东省高校人才培养的现状,通过对广东省高校人才培养和区域经济增长进行协整分析、误差修正模型和格兰杰因果检验,结果表明,广东高校人才培养与经济增长存在长期、短期均衡关系,经济增长是高校人才培养的Granger原因.     

鳄鱼资源开发和生物活性物质研究进展

鳄鱼是两亿多年前与恐龙同时代的最原始脊椎类两栖爬行动物，有强盛的生长、繁殖、抗病和抗逆境能力，是生物医学与生态环保等研究的重要物种.近年研究表明，鳄鱼血有强的抗菌、抗病毒和抗癌活性，特别是对抗药性病源菌和人类艾滋病毒有较强抗性，鳄鱼血的抗菌作用可能通过血清中的补体蛋白诱导机体自身免疫系统和产生多种直接作用于细菌细胞膜的抗菌肽而起作用；鳄鱼胆汁提取物显著抑制胆管癌细胞和肝癌细胞的生长，可能通过破坏线粒体膜电位和提高活性氧含量来诱导癌细胞凋亡；鳄鱼油有显著的抗菌、抗炎、防皮肤冻伤和促进皮肤烧伤愈合等作用.鳄鱼的工业利用价值和医药与功能食品开发价值，使其成为经济价值高的养殖动物，在广东、海南和江苏等东南沿海地区大量养殖.该文综述了近年来鳄鱼驯养繁殖和生物活性成分等方面研究进展.     

Snail的结构及功能与肿瘤生长侵袭的研究进展

Snail为锌指蛋白超家族的第一个成员,在转录调控、形成抑制性染色质结构、细胞信号和发育过程中发挥积极作用。也可以由于放松管制而导致疾病。有研究表明,Snail可促使上皮-间质转化及E-cadherin和桥粒芯糖蛋白的降解,在胃癌、结肠癌、肝癌、卵巢癌、头颈部鳞状细胞癌等许多肿瘤组织中呈中高表达,被认为是促进肿瘤侵袭转移的因素。对Snail的深入研究不仅能更进一步阐明Snail的作用机制,并且为进一步研究以Snail为靶点的肿瘤治疗策略提供理论依据。本文对Snail的结构、功能以及Snail与肿瘤生长与侵袭进行了综述。     

Endothelial cells and VEGF in vascular development

The intricate patterning processes that establish the complex vascular system during development depend on a combination of intrinsic pre-patterning and extrinsic responses to environmental parameters. Mutational studies in mice and fish have shown that the vascular system is highly sensitive to genetic disruption and have identified potential targets for therapeutic interventions. New insights into non-vascular roles of vascular endothelial growth factor and the requirement for endothelial cells in adult organs and stem-cell niches highlight possible side effects of anti-angiogenic therapy and the need for new targets.     

Role of FGF-2／FGFR signaling pathway in cancer and its signification in breast cancer

Fibroblast growth factor-2 (FGF-2) is a member of a large family of proteins that bind heparin and heparan sulfate and modulate the function of a wide range of cell types. It has been proved that FGF-2 stimulates the growth and development of new blood vessels (angiogenesis) that contribute to the pathogenesis of several diseases (i.e. cancer, atherosclerosis). However, many of the biological activities of FGF-2 have been found to depend on its receptor抯 intrinsic tyrosine kinase activity and second messengers such as the mitogen activated protein kinases. This review will focus on the mechanism of FGF-2/FGFR induced signaling pathway in tumor and human breast cancer.     

HSVECs血管生成模型和HUVECs血管生成模型的比较

 首次利用人隐静脉内皮细胞(HSVECs)在体外建立血管生成模型,并与脐静脉内皮细胞(HUVECs)模型进行比较.在不加入任何生长因子的条件下,在三维胶原系统中经过3 d的培养,HSVECs能形成毛细血管样网状结构.genistein是一种酪氨酸酶抑制剂,它能影响毛细血管网的形成.与HUVECs模型比较两者存在明显的差异性.HSVECs在体外三维模型中能形成一种变异型的毛细血管样网状结构.     

Progress in human tumour immunology and immunotherapy

Studies of the administration of interleukin-2 to patients with metastatic melanoma or kidney cancer have shown that immunological manipulations can mediate the durable regression of metastatic cancer. The molecular identification of cancer antigens has opened new possibilities for the development of effective immunotherapies for patients with cancer. Clinical studies using immunization with peptides derived from cancer antigens have shown that high levels of lymphocytes with anti-tumour activity can be raised in cancer-bearing patients. Highly avid anti-tumour lymphocytes can be isolated from immunized patients and grown in vitro for use in cell-transfer therapies. Current studies are aimed at understanding the mechanisms that enable the cancer to escape from immune attack.     

NF-kappaB functions as a tumour promoter in inflammation-associated cancer

The causes of sporadic human cancer are seldom recognized, but it is estimated that carcinogen exposure and chronic inflammation are two important underlying conditions for tumour development, the latter accounting for approximately 20% of human cancer. Whereas the causal relationship between carcinogen exposure and cancer has been intensely investigated, the molecular and cellular mechanisms linking chronic inflammation to tumorigenesis remain largely unresolved. We proposed that activation of the nuclear factor kappaB (NF-kappaB), a hallmark of inflammatory responses that is frequently detected in tumours, may constitute a missing link between inflammation and cancer. To test this hypothesis, we studied the Mdr2-knockout mouse strain, which spontaneously develops cholestatic hepatitis followed by hepatocellular carcinoma, a prototype of inflammation-associated cancer. We monitored hepatitis and cancer progression in Mdr2-knockout mice, and here we show that the inflammatory process triggers hepatocyte NF-kappaB through upregulation of tumour-necrosis factor-alpha (TNFalpha) in adjacent endothelial and inflammatory cells. Switching off NF-kappaB in mice from birth to seven months of age, using a hepatocyte-specific inducible IkappaB-super-repressor transgene, had no effect on the course of hepatitis, nor did it affect early phases of hepatocyte transformation. By contrast, suppressing NF-kappaB inhibition through anti-TNFalpha treatment or induction of IkappaB-super-repressor in later stages of tumour development resulted in apoptosis of transformed hepatocytes and failure to progress to hepatocellular carcinoma. Our studies thus indicate that NF-kappaB is essential for promoting inflammation-associated cancer, and is therefore a potential target for cancer prevention in chronic inflammatory diseases.     

Xenogeneic homologous genes, molecular evolution and cancer therapy

Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.     

远红外在生物医学临床上的应用及其作用机制

 远红外是一种具有强热作用的放射线.作为物理治疗的一种,远红外用于辅助治疗心血管疾病、糖尿病、慢性肾病等多种疾病,表现出良好的临床效果,但是其作用的分子机制尚不清楚.本文从分子信号通路视角,分析远红外与细胞周期、细胞自身保护、第二信使和后转录调控因子等的关系,提出远红外治疗诸多疾病的可能的分子机制,并总结了近年来远红外在生物医学临床中的应用.     

A Toll-like receptor recognizes bacterial DNA

DNA from bacteria has stimulatory effects on mammalian immune cells, which depend on the presence of unmethylated CpG dinucleotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response. Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies for cancer, allergy and infectious diseases. Despite its promising clinical use, the molecular mechanism by which CpG DNA activates immune cells remains unclear. Here we show that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9. TLR9-deficient (TLR9-/-) mice did not show any response to CpG DNA, including proliferation of splenocytes, inflammatory cytokine production from macrophages and maturation of dendritic cells. TLR9-/- mice showed resistance to the lethal effect of CpG DNA without any elevation of serum pro-inflammatory cytokine levels. The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.     

Genome maintenance mechanisms for preventing cancer

The early notion that cancer is caused by mutations in genes critical for the control of cell growth implied that genome stability is important for preventing oncogenesis. During the past decade, knowledge about the mechanisms by which genes erode and the molecular machinery designed to counteract this time-dependent genetic degeneration has increased markedly. At the same time, it has become apparent that inherited or acquired deficiencies in genome maintenance systems contribute significantly to the onset of cancer. This review summarizes the main DNA caretaking systems and their impact on genome stability and carcinogenesis.