胚胎着床过程中血管生成相关因子的表达及其调控

血管生成（angiogenesis）主要在雌性生殖器官中发生,在其它器官和组织中则很少见。许多血管生成相关因子参与血管生成。在哺乳动物的胚胎着床过程中,胚胎着床位点处子宫内膜的血管通透性发生变化,随后进行蜕膜化及胎盘形成,以利于胎儿进一步发育,这些过程均与血管生成相关。本文综述了近年来关于血管内皮生长因子等血管生成因子在着床过程中的表达、调节以及作用机制。     

肿瘤血管生成及抗血管生成的分子影像学研究进展

血管生成是肿瘤发生、发展的重要生物学过程,因此针对其的抗肿瘤血管生成治疗成为肿瘤治疗的重要策略.随着分子影像学的出现,以及对血管生成机制研究的不断深入,活体监测肿瘤血管生成及评价靶向介入治疗的疗效成为可能.本文就血管生成与肿瘤血管生成、肿瘤抗血管生成治疗,以及介入导向的抗血管生成治疗在肿瘤分子影像学领域的研究进展做一综述.     

子宫内膜癌血管生成相关因子的研究进展

血管内皮生长因子（VEGF）是近年研究较广泛的参与内皮细胞活化和血管生成的重要因子,它通过与其特异性受体结合发挥生物学作用。缺氧诱导因子-1α（HIF-1α）是缺氧条件下被激活,参与肿瘤发生、发展的一类核转录因子,通过激活下游基因发挥促进肿瘤血管生成的作用。葡萄糖转运蛋白（GULT-1）是新近研究发现的与子宫内膜癌血管生成相关的因子。血小板衍化生长因子（PDGF）一类重要的促有丝分裂多肽生长因子。其在肿瘤血管新生中的作用有待于进一步研究。目前许多研究发现,以上几种因子与子宫内膜癌关系密切,直接或间接参与了子宫内膜癌的病理生理过程。对这几种因子的深入研究将为子宫内膜癌的防治与抗血管生成治疗提供新的理论依据及治疗靶点。     

内皮抑素抗肿瘤血管生成的分子机制

内皮抑素(endostatin)是目前广泛关注的血管生成抑制剂,能特异性地抑制内皮细胞的增殖和迁移,在体内具有良好的抗肿瘤效果。该分子的抗肿瘤作用可能与金属蛋白酶活性、信号通路分子、整合素、原肌球蛋白及黏附受体有关。     

微RNA参与调控肿瘤血管生成

肿瘤血管生成是由多种因子参与调控的复杂过程,对肿瘤的生长、侵袭和转移起着关键作用.微 RNA(microRNA, miRNA)是一段长约22 nt的非编码RNA序列,参与调节细胞增殖、分化、凋亡,肿瘤发生、发展等多种生命活动.认识miRNA与肿瘤血管生成的关系不但能加深对血管生成分子机制的理解,同时对阐明 miRNA的功能具有重要意义.     

血管生成因子研究进展

近年来,随着基因重组技术和蛋白质工程技术的完善和发展,一类可促进新生血管生成的蛋白多肽被相继发现,它们被统称为血管生成因子(ａｎｇｉｏｇｅｎｉｃｆａｃｔｏｒ,ＡＦ)[1]。目前已被分离纯化和克隆的有:成纤维细胞生长因子(ｆｉｂｒｏｂｌａｓｔｇｒｏｗｔｈｆａｃ ｔｏｒ,ＦＧＦ)、血管内皮细胞生长因子(ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｃｅｌｌｇｒｏｗｔｈｆａｃｔｏｒ,ＶＥＧＦ)、血小板衍生生长因子(ｐｌａｔｅｌｅｔｄｅｒｉｖｅｄｇｒｏｗｔｈｆａｃｔｏｒ,ＰＤＧＦ)、转化生长因子(ｔｒａｎｓｆｏｒｍｉｎｇｇｒｏ…     

软骨血管生成抑制因子抑制血管生成的研究

小牛气管软骨经盐酸胍抽提,丙酮分级沉淀,膜超滤,柱层析等步骤得到软骨血管生成抑制因子(cartilage angiogenesis inhibiting factor,CAIF).SDS-聚丙烯酰胺凝胶电泳显示CAIF由单一组分组成,分子量为27700.通过[ ³H]-TdR掺入,活细胞检测等方法测定CAIF对内皮细胞、Hela细胞、QGY7703细胞与小鼠骨髓细胞、人皮肤成纤维细胞等的DNA合成的影响,以及细胞毒作用.采用鸡胚绒毛尿囊膜实验测定CAIF对血管生成的抑制效应.结果显示:CAIF对内皮细胞产生强的抑制作用,对Hela细胞抑制很弱,对QGY7703细胞、小鼠骨髓细胞、人皮肤成纤维细胞均无抑制作用;对鸡胚绒毛尿囊膜的血管生成产生明显的抑制作用.提示CAIF能较特异地抑制血管生成,CAIF达到电泳纯,是专一性较强的血管生成抑制因子.     

血管生成拟态和肿瘤的关系

血管生成拟态指由恶性肿瘤细胞而非血管内皮细胞连接形成的、能为肿瘤提供血供的管网状结构．存在于恶性黑素瘤、卵巢癌、前列腺癌、炎性乳腺癌和某些软组织肉瘤。其发生和肿瘤细胞呈现出多潜能的胚胎样表型有关。进一步研究血管生成拟态的分子机制,探索有效的拮抗其过程的方案,有可能提供一种能有效治疗肿瘤、并且对正常生理过程的影响较小的策略     

血管内皮生长因子与血管生成

本综述了血管内皮生长因子结构特点、体内分布,正常及病理条件下的表达水平变化及其生物学功能,并对血管通透性与血管生成之间的关系进行了评述。     

子宫自然杀伤细胞在人类早孕蜕膜血管 生成中的作用研究

子宫内膜蜕膜化过程伴随着活跃的血管生成是妊娠时新血管形成的关键步骤. 本研究旨在明确子宫自然杀伤细胞(uNK, CD56⁺细胞)在人类早期妊娠蜕膜组织中的分布, 并观察这类细胞是否表达血管内皮生长因子(VEGF-A)和促血管生成素2(Ang2). 免疫组化研究发现, uNK细胞(CD56⁺)大量存在于子宫蜕膜间质中, 主要集中在血管和腺体周围的间质组织, 蛋白水平的VEGF-A和Ang2表达于蜕膜间质细胞、微血管内皮细胞和腺上皮细胞中, uNK细胞在子宫蜕膜间质中的阳性率与平均微血管密度(MVD)、uNK细胞的阳性率与VEGF-A蛋白阳性表达率呈正相关关系, 而与Ang2无相关性. 另外, 在激光微切获得的单个uNK细胞进行巢式PCR的研究结果显示, 人类蜕膜的uNK细胞能够表达VEGF mRNA, 未测得Ang2 mRNA在单个uNK细胞表达. 表明人类早孕子宫蜕膜中的uNK细胞通过表达VEGF-A, 在蜕膜化过程和胎盘早期形成时的血管生成中发挥重要作用.     

Angiogenesis in the female reproductive system.

In adult tissues, capillary growth (angiogenesis) occurs normally during tissue repair, such as in healing of wounds and fractures. Rampant capillary growth is associated with various pathological conditions, including tumor growth, retinopathies, hemangiomas, fibroses and rheumatoid arthritis. The female reproductive organs (i.e., ovary, uterus, and placenta) exhibit dynamic, periodic growth and regression accompanied by equally dramatic changes in rates of blood flow. It is not surprising, therefore, that they are some of the few adult tissues in which angiogenesis occurs as a normal process. Thus, the female reproductive system provides a unique model for studying regulation of angiogenesis during growth and differentiation of normal adult tissues. Ovarian, uterine, and placental tissues recently have been shown to contain and produce angiogenic and anti-angiogenic factors. This review discusses the current state of knowledge regarding angiogenic processes and their regulation in female reproductive tissues. In addition, implications of this research for regulation of fertility as well as for control of angiogenesis in other normal and pathological processes are discussed.     

Wnts and the female reproductive system.

Wnts are intercellular growth and differentiation factors that regulate several key developmental steps, such as gastrulation, neurulation, and organogenesis, including the development of the midbrain, central nervous system, kidney, and limbs. Wnts are also needed for a normal development of the reproductive system. Deficiency of Wnt-4, -5a, and -7a, for example, results in sex reversal, infertility, and/or malformation of the internal and external genitals. Here we focus on the importance of Wnts in the female reproductive system.     

Proteasome activity in tumors of the female reproductive system

Although proteasomes (multiproteinase protein complexes) are known to play an important role in cancer pathogenesis, there is little information about their activity in human tumor tissues. The chymotrypsin-like activity of proteasomes in breast cancer (BC) and endometrial cancer (EC) tissues was studied. It was shown that the chymotrypsin-like total proteasome activity and the 20S and 26S proteasome pool activities were significantly higher in malignant than in normal tissues. An increase in the size of either BC or EC tumors did not affect the proteasome activity, whereas the propagation of a malignant process did. If compared with BC non-metastatic tumors, a reliable decrease in the total activity and the 26S proteasome activity was observed in BC tumors with regional lymph node metastases. In EC tissues, the total proteasome activity and the 20S and 26S proteasome pool activities increased when the depth of tumor myometrial invasion grew. These data demonstrated that the proteasome activity significantly varied in the process of carcinogenesis. Further proteasome studies could serve as the basis for the development of new criteria for prognosis of female reproductive system cancer and the search for effective antitumor agents in targeted therapy.     

Proteasome activity in tumors of female reproductive system

Proteasomes (multiproteinase protein complexes) are known to play an important role in cancer pathogenesis, however, few information about their activity in human tumor tissues is available so far. We studied chymotrypsin-like activity of proteasomes in tissues of breast cancer (BC) and endometrial cancer (EC). The chymotrypsin-like total proteasome activity and the 20S and 26S proteasome activity in malignant tissues were shown to be significantly higher in malignant tumors than in normal tissues. No increase in proteasome activity was registered with larger tumor size in both BC and EC, whereas proteasome activity was changed with respect to the extent of tumor involvement. In breast cancer tissues, significant reductions in the total and the 26S proteaome activities were observed in tumors with regional lymph node metastases as compared to tumors without metastases. In endometrial cancer tissues, the total proteasome activity and the 20S and 26S proteasome activities were increased as the depth of myometrial invasion. The data obtained indicate that the proteasome acyivity is significantly changed in the process of cancerogenesis and further study is needed to develop new additional prognostic criteria and effective anti-tumor agents in molecular-directed therapy.     

迁粉蝶雌性生殖系统结构研究

解剖和描述了迁粉蝶Catopsilia pomona(Fabricius)的雌性生殖系统结构。结果表明:迁粉蝶外生殖器包括交配囊及其附属结构、导精管、后表皮突和肛突;内生殖器包括1对卵巢、2根侧输卵管、1根中输卵管、受精囊、附腺、外生殖腔及产卵孔。卵巢左右对称,每个卵巢由4根多滋式卵巢管组成。同时提出卵巢发育分级指标,为害虫预测和防治提供指导性意见。     

The female reproductive system of the eastern Australian scorpion

The reproductive system of the female Urodacus manicatus (Scorpionidae) is described. Situated on the ventral side of the ovariuterus tubes are buds and diverticulae belonging to three developmental phases: (1) Bud-like, rudimentary diverticulae that will form future generations. (2) Embryonic diverticulae that will house the present generation. (3) Degenerating (= 'post-partum') diverticulae that contained the previous generation of juveniles just born. The smallest buds could be identified only by scanning electron microscopy of the ovariuterus tube. The various diverticulae were counted and their dimensions were measured. Based on the average number of the embryonic diverticulae, it appears that the average number of young that can be produced by a female during a single parturition is 16.8. This number does not appear to increase significantly with the growth of the female.     

Reflex control of cutaneous vasoconstrictor system is reset by exogenous female reproductive hormones.

To determine whether cardiovascular influences of exogenous female steroid hormones include effects on reflex thermoregulatory control of the adrenergic cutaneous vasoconstrictor system, we conducted ramp decreases in skin temperature (T(sk)) in eight women in both high- and low (placebo)-progesterone/estrogen phases of oral contraceptive use. With the use of water-perfused suits, T(sk) was held at 36 degrees C for 10 min (to minimize initial vasoconstrictor activity) and was then decreased in a ramp, approximately 0.2 degrees C/min for 12-15 min. Subjects rested supine for 30-40 min before each experiment, and the protocol was terminated before the onset of shivering. Skin blood flow was monitored by laser-Doppler flowmetry and arterial pressure by finger photoplethysmography. In all experiments, cutaneous vasoconstriction began immediately with the onset of cooling, and cutaneous vascular conductance (CVC) decreased progressively with decreasing T(sk). Regression analysis of the relationship of CVC to T(sk) showed no difference in slope between phases (low-hormone phase: 17.67 +/- 5.57; high-hormone phase: 17.40 +/- 8.00 %baseline/ degrees C; P > 0.05). Additional studies involving local blockade confirmed this response as being solely due to the adrenergic vasoconstrictor system. Waking oral temperature (T(or)) was significantly higher on high-hormone vs. low-hormone days (36.60 +/- 0.11 vs. 36.37 +/- 0.09 degrees C, respectively; P < 0.02). Integrative analysis of CVC in terms of simultaneous values for T(sk) and T(or) showed that the cutaneous vasoconstrictor response was shifted in the high-hormone phase such that a higher T(or) was maintained throughout cooling (P < 0.05). Thus reflex thermoregulatory control of the cutaneous vasoconstrictor system is shifted to higher internal temperatures by exogenous female reproductive hormones.