血管新生与疾病

很多疾病均伴有血管的变化。血管 ,特别是微血管 ,常与组织、器官的生长、发育和功能密切相关。疾病时它们发生相应的改变。有些疾病的发生发展和治疗与微血管新生有密切的联系 ,治疗时要抑制血管新生 ,如肿瘤等 ;有些疾病的发生发展有微血管的闭塞和退化 ,治疗时要促进微血管新生 ,如血栓性疾病等。因此近年来血管新生与疾病的关系在整体、细胞和分子水平上开展了广泛的研究 ,下面作一简要介绍。１肿瘤的血管新生与抗血管新生治疗１．１肿瘤血管新生肿瘤是人体细胞异常分化增殖的恶性疾病。肿瘤在表现其生长、转移等生物学行为时与其中的微…     

外泌体在肿瘤血管新生中的作用

肿瘤的生长与转移依赖于充足的血管生成以及血液供养,越来越多的研究证实肿瘤来源的外泌体参与促进肿瘤血管新生。本文通过综述外泌体如何驱动血管新生,为改进现有的抗血管生成疗法增加新的选择。     

DLL4与血管生成的关系

血管生成是胚胎发育和肿瘤生长的重要因素.多项研究发现,参与Notch信号的Delta配体4(Delta-like ligand 4,DLL4)能抑制新生血管分支生成,促进新生血管的成熟.阻断DLL4可增加无功能性新生血管的数量,从而抑制肿瘤生长,这为肿瘤抗血管生成疗法提供了新的策略,使DLL4有可能成为肿瘤治疗的新靶点.     

抗视网膜脉络膜新生血管性疾病治疗药物靶点的研究进展

新生血管性年龄相关性黄斑变性(nAMD)、糖尿病视网膜病变(DR)等眼底病继发形成新生血管,是致盲的重要原因之一。抗血管内皮生长因子(VEGF)治疗是当前主流疗法。但仍存在部分患者对其疗效欠佳等局限,临床仍需要开发新的药物靶点。     

血管生成及靶向治疗

血管是胚胎发育第一器官并形成人体最大网络系统。正常血管生成受到各种细胞因子的严格控制。异常的血管生成导致各种疾病,例如肿瘤、糖尿病、免疫病、先兆子痫、肢体缺血等。因此,血管生成已成为治疗这些疾病的药物靶点。2004年,第一个抗血管生成药物用于结肠癌的治疗,标志着抗血管生成疗法的成功。然而,随着血管生成药物的临床应用,新的问题也逐渐显露出来。这不仅给我们提出了新的挑战,而且展现出新的希望。     

靶向性抗癌蛋白色素上皮衍生因子在肿瘤中的研究进展

在肿瘤靶向治疗研究中,抗血管生成治疗是近十年来的一个研究热点.目前已有许多血管生成抑制剂应用于临床试验中.色素上皮衍生因子(PEDF)是一个能有效抑制新生血管形成的蛋白,与血管内皮生长因子(VEGF)等共同调控新生血管的发生过程.PEDF表达和抑制肿瘤生长、减少转移、良好的预后相关,对PEDF的深入研究有助于发挥其在肿瘤治疗中的作用.     

周细胞在抗肿瘤血管生成中的研究进展

众所周知,肿瘤的生长和转移依赖于新生血管,没有新生血管,肿瘤将停止生长。肿瘤新生血管由内皮细胞、周细胞／平滑肌细胞、基底膜组成。目前抗肿瘤血管生成的研究主要在内皮细胞和内皮祖细胞,对周细胞的研究很少。而周细胞在肿瘤血管的发展、稳定、成熟及重塑过程中发挥着关键作用,成为抗血管生成治疗的热点和新靶点。本文就近年来关于周细胞在抗肿瘤血管生成中的研究作一综述。     

抗血管生成抑制剂疗法研究进展

1　抗血管生成抑制剂的研究　　肿瘤血管形成的主要过程目前认为是:诱发因素→肿瘤细胞被活化分泌可能性血管生成刺激因子,如VEGF(血管内皮生长因子)、FGF(成纤维细胞生长因子)→激活内皮细胞和金属蛋白酶→基底膜被破坏,内皮细胞收缩,趋化,迁移,增殖,形成血管芽→血管芽吻合成血管。因为肿瘤血管及其生长过程的某些特殊性使得其更有利于肿瘤生长和转移,而抗血管生成的所有方法都是靶定内皮细胞而不是肿瘤细胞,这样使得抗血管疗法具有不产生耐药性,而广泛性、毒副作用小等优点。目前抗血管生成抑制剂疗法主要有三种:1.1　“血管生成抑制…     

肿瘤的抗血管生成基因治疗策略

以实体瘤没有新血管形成不能生长为基础 ,利用抗血管生成物来抑制肿瘤的生长 ,本文总结了在器官内通过基因转导提供高浓度的抗血管生成蛋白来治疗人类肿瘤的方法。尽管这一方法还存在许多问题 ,然而基因转导策略具有特异靶向肿瘤所在器官 ,提供持久、高浓度抗血管生成介质 ,减少系统毒性的优势 ,具有抑制微小转移灶中内皮细胞生长的作用 ,这一策略可能在低肿瘤负荷状态最为有效。     

肿瘤治疗的新途径-抗肿瘤血管生成的生化和基因治疗

新生血管对于肿瘤的生长、浸润和转移有重要意义.体积超过1mm3～2mm3的肿瘤不仅需要新生血管维持营养供给和排泄代谢产物,还需要提供有利于转移的通道.新生血管形成包括内皮细胞的激活、增殖、迁移、血管基底膜的破坏、血管和血管网的形成,以及先前存在的血管网的连接等过程.抑制新生血管的生成可使肿瘤细胞进入休眠状态并诱导其凋亡.目前用抗血管生成来达到对肿瘤的治疗目的已不再是理论上的可能,而是一个渐趋成熟、实用的治疗方法.我们仅就此作一简要介绍.     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.     

Age-related changes in polyamines in memory-associated brain structures in rats

Polyamines putrescine, spermidine and spermine are positively charged aliphatic amines and have important roles in maintaining normal cellular function, regulating neurotransmitter receptors and modulating learning and memory. Recent evidence suggests a role of putrescine in hippocampal neurogenesis, that is significantly impaired during aging. The present study measured the polyamine levels in memory-related brain structures in 24- (aged), 12- (middle-aged) and 4- (young) month-old rats using liquid chromatography/mass spectrometry and high performance liquid chromatography. In the hippocampus, the putrescine levels were significantly decreased in the CA1 and dentate gyrus, and increased in the CA2/3 with age. Significant age-related increases in the spermidine levels were found in the CA1 and CA2/3. There was no difference between groups in spermine in any sub-regions examined. In the parahippocampal region, increased putrescine level with age was observed in the entorhinal cortex, and age did not alter the spermidine levels. The spermine level was significantly decreased in the perirhinal cortex and increased in the postrhinal cortex with age. In the prefrontal cortex, there was age-related decrease in putrescine, and the spermidine and spermine levels were significantly increased with age. This study, for the first time, demonstrates age-related region-specific changes in polyamines in memory-associated structures, suggesting that polyamine system dysfunction may potentially contribute to aged-related impairments in hippocampal neurogenesis and learning and memory.     

休克过程中肾上腺髓质素变化的研究进展

Adrenomedullin (AM) is a new peptidergic regulator of vascular function. AM serves as a hormone, which has many biological properties, plays an important role in the many pathophysiological processes, especially shock. This review will highlight the structure, biological properties of AM and the relationship between AM and shock.     

Seasonal variations in acute toxoplasmosis in pregnant women in Slovenia

Between December 1999 and December 2004, 40 081 pregnant women were examined for toxoplasmosis with Toxo-IgG, Toxo-IgM enzyme immunoassay. Women with positive results were then retested with the Toxo-IgG avidity assay for recent toxoplasmosis. Recent acute toxoplasmosis in pregnant women was found to be significantly more frequent (p < 0.01) during winter than summer. The incidence of acute toxoplasmosis during winter-spring was also significantly more frequent (p < 0.025) than summer-autumn. This phenomenon should be taken into account when formulating preventive measures for toxoplasmosis, especially for pregnant women.     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Uteroglobin in the developing rabbit conceptus in vivo and in vitro

Summary Uteroglobin (UGL) was measured in day- 4 to day-10 rabbit conceptuses by a competitive ELISA. Levels in blastocyst fluid, tissues, coverings and in the early fetus were determined separately. The total amount of UGL increased from 18.4 ng to 6.8 g per conceptus. The UGL content of individual day-6 blastocysts was studied in vitro. Culturing was carried out up to 60 h in Ham's F10 medium with polyvinylpyrrolidone as macromolecular component, with and without progesterone, and with progesterone plus estradiol. UGL was determined in the blastocyst fluids, tissues with coverings and in the culture media. After labelling with [³⁵S]-methionine, protein patterns of total blastocysts and of culture media were analysed by two-dimensional gel electrophoresis and fluorography. The morphology of cultured blastocysts was examined by electron microscopy. During 60 h of culture, the blastocysts expanded in diameter by 84%, and released 19% of their initial UGL content into the medium, independent of the hormonal substitution. Neither de novo synthesis, nor degradation of UGL was found: the protein remained unlabelled in fluorography, and its total quantity was not significantly different from that of non-cultured controls. Trophoblast, endoderm and embryoblast cells showed well preserved cell organelles and intercellular junctions, while the morphological differentiation of the germ layer was inhibited.