雄激素受体在肿瘤中的作用及机制研究进展

雄激素受体(androgen receptor, AR)是类固醇核受体超家族的成员之一。AR在正常生理和代谢过程以及在肿瘤等多种疾病的发生与发展中起着重要作用。AR在不同肿瘤中作用不同,如在前列腺癌、黑色素瘤及胃癌等肿瘤中发挥促进作用,而在雌激素受体阳性乳腺癌中发挥肿瘤抑制作用。AR通过调节免疫(抑制肿瘤浸润性CD8^(+)T细胞的活性和干性)间接发挥促进肿瘤发生发展。该文回顾并总结AR在肿瘤中的主要作用、分子机制与最新研究进展,阐明AR的研究前景,为AR的进一步研究提供思路。

结肠癌白细胞介素-8表达与肿瘤促血管生长因子关系的初步探讨

目的探讨结肠癌白细胞介素-8(IL-8)表达与肿瘤促血管生长因子的关系。方法选择2012年12月至2013年5月该院治疗的60例不同时期的结肠癌患者为实验组,并以同期在该院健康体检者60例作为健康对照组。比较结肠癌患者手术前后与健康者血清中IL-8和血管内皮生长因子(VEGF)的含量。结果结肠癌手术后患者IL-8和VEGF的含量均低于手术前,差异有统计学意义(P<0.05)。与健康对照组比较,差异有统计学意义(P<0.05)。结论实验组患者治疗过程中IL-8与肿瘤促血管生长因子的含量显著相关。IL-8和VEGF较为敏感,对及时准确检测患者病情提供数据诊断,具有临床意义。

分子伴侣对可溶性肿瘤坏死因子相关促凋亡配体在巴斯德毕赤酵母中表达的影响

目的:提高外源蛋白可溶性肿瘤坏死因子相关促凋亡配体(sTRAIL)在巴斯德毕赤酵母中的分泌表达。方法:根据GenBank公共数据库中公布的模式生物酿酒酵母的分子伴侣(Ssa1p、YDJ1、Kar2p和PDI)基因序列设计引物,利用PCR方法从酿酒酵母基因组中得到各基因片段,并将单独Ssa1p或Kar2p、组合YDJ1+PDI、Kar2p+PDI或YDJ1+PDI+PDI分别构建到pPIB2Z表达载体中,并整合到外源蛋白sTRAIL工程菌(毕赤酵母GS115)中进行筛选和诱导表达。结果:SDS-PAGE分析表明,sTRAIL的表达量明显提高,特别是整合了分子伴侣组合YDJ1+PDI的工程菌。Western印迹分析整合的分子伴侣基因后,分子伴侣蛋白在工程菌中的表达量得到了提高。结论:提高细胞内分子伴侣的表达,可以增加外源蛋白的分泌表达,为进一步研究巴斯德毕赤酵母奠定了基础。

Ⅰ型分裂蛋白转导素样增强子在肿瘤中的作用研究进展

Ⅰ型分裂蛋白转导素样增强子(TLE1)是转录共抑制因子Groucho(Gro)/TLE基因家族成员。TLE1蛋白通过介导细胞的分化和发育,在胚胎发育、造血细胞发育分化、神经发生以及多种恶性肿瘤发生与发展过程中起着重要作用。TLE1作为重要转录因子,在不同肿瘤中作用不同,可能是促肿瘤因子(如在肺癌、乳腺癌、胃癌),也可能是肿瘤抑制因子(如在肝癌、白血病),参与调节细胞增殖、凋亡、转移等过程。TLE1可作为潜在的诊断标志物(尤其是滑膜肉瘤)和治疗靶点。现就TLE1在肿瘤中的主要作用与最新研究进展作简要综述。

肿瘤血管生成的二维数值模拟

血管生成(angiogenesis),指从已存在的血管网络中成长出新的血管网络。肿瘤毛细血管生成在肿瘤的生长、转移等阶段发挥着重要的作用。在此过程中内皮细胞积极参与其中的各个阶段:首先是各种各样的肿瘤促血管生成因子的释放(tumorangiogenesisfactors,TAF),激活内皮细胞;新生的内皮细胞在一系列的内部和外部因素的调节下向着肿瘤迁移,最终新生成的毛细血管到达肿瘤并穿越它。目前对肿瘤内及其周围的毛细血管网络了解很少,这给临床上对肿瘤的研究和治疗带来一定困难。本文考虑内皮细胞与胞外间质的相互作用、对TAF的响应,根据肿瘤内外的生理和病理条件描述肿瘤促血管生成的特点,并根据肿瘤内的复杂特性建立二维离散数学模型,研究肿瘤内部的毛细血管网络的生成。数值模拟的结果显示该模型在一定程度上可以产生符合真实的肿瘤内外的毛细血管分层特点的网络,同时也给后续的研究提供了一定的依据。

急性脑梗死患者血清炎症因子与血瘀的多重线性回归分析

目的:探讨急性脑梗死(acute cerebral infarction,ACI)患者血清炎症因子与血瘀的相关性,从炎症方面认识血瘀本质,从炎症因子新角度探讨血瘀物质基础。方法:采用ELISA等方法检测ACI血瘀患者血清促炎、抑炎因子含量,评估患者血瘀积分,Multiple linear regression法分析炎症因子与血瘀相关性。结果:血瘀积分与血清C-反应蛋白(C-reactive protein,CRP)、促炎因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin 6,IL-6)、白细胞介素-1β(interleukin 1 beta,IL-1β)、白细胞介素-10(interleukin-10,IL-10)含量存在多重线性相关,回归系数分别为0. 460、0. 825、1. 867、0. 116、-1. 190。结论:ACI患者血瘀程度与其血清CRP、TNF-α、IL-6、IL-1β、IL-10含量呈多重线性相关,即在其他变量保持不变的情况下,CRP、TNF-α、IL-6、IL-1β含量越高,IL-10含量越低,则其血瘀程度越重,以上诸因子或为血瘀相关炎症因子物质基础。

Synergistic effect of bromocriptine and tumor necrosis factor-a on reversing hepatoceiiuiar carcinoma multidrug resistance in nude mouse MDRl model of liver neoplasm

AIM： To investigate the effect of bromocripUne （BCT） and tumor necrosis factor-α ClNF-α） on hepatocellular carcinoma （HCC） multidrug resistance （MDR） in nude mouse HDR model of liver neoplasm. METHODS： Human hepatocarcinoma cell line HepG2t drug resistant hepatocarcinoma cell line HepG2/adriamycin （ADM） and hepatocarcinoma cell line transfected with TNF-α gene HepG2JADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established （HepG2t ADM, TNF, BCT groups）. Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor his^logical character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins （MRP, LRP） of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. RESULTS： The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group （67%） compared to ADM and TNF groups, and similar to HepG2group （54%）. MDRI and LRPmRNA could be detected in all groups, but TNF-α was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG2 group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay. CONCLUSION： BCT and TNF-a can reverse HCC MDR in nude mouse MDR1 model of liver neoplasm. 2005 The WJG Press and Elsevier Inc. All rights reserved

Effect of electroacupuncture on egg quality and tumor necrosis factor-a of patients with polycystic ovarian syndrome

Objective To observe the effect of electroacupuncture （EA） on egg quality of polycystic ovarian syndrome （PCOS） patients, and to explore its mechanism. Methods Two hundred patients who received in vitro fertilization-embryo transfer （IVF-ET） were divided into an EA group （102 cases） and a control group （98 cases） according to random number table. All the patients in the two groups were given Diane-35 and gonadotropin-releasing hormone agonist （GnRH-α） for ovarian hyperstimulation. Besides, EA intervention was applied to Shenshu （肾俞 BL 23）, Qihai （气海 GV 6）, Zusanli （足三里ST 36）, Sanyinjiao （三阴交 SP 6）, Neiguan （内关 PC 6） and Zigong （子宫 EX-CA1）, etc. in the EA group. Then egg quality, final outcome of pregnancy and levels of tumor necrosis factor-α （TNF-α） were compared between the two groups. Results （1） EA intervention significantly improved high quality embryo rate of PCOS patients （P〈0.05）, and clinical pregnancy rate was increased by 8.36%; （2） EA intervention significantly reduced the TNF-α levels of follicular fluid （13.61±15.46 vs 34.09±93.53, P〈0.05）; （3） TNF-α levels of serum and follicular fluid in the pregnancy group were lower than those of non-pregnancy group [pregnancy group： （53.91±63.32） pg/mL, （14.93±25.37） pg/mL, nonpregnancy group： （76.82 ± 82.96） pg/mL, （25.04 ± 35.79） pg/mL], and the differences were significant （both P〈0.05）. Conclusion EA improves egg quality of PCOS patients and increases the clinical pregnancy rate of IVF-ET, the mechanism may be related to TNF-α levels.

Effect of electroacupuncture at conception vessel and governor vessel on correlative signals of stress-injury-repair in cerebral ischemia reperfusion rats

Objective To explore the effect of electroacupuncture at conception vessel and governor vessel on correlative signals of inflammatory response stressinjury-repair in cerebral ischemia reperfusion rats. Methods A total of 216 rats were included in the experiment, of which 192 rats were randomly divided into four groups, including sham operation group（group A）, model group（group B）, governor vessel group（group C）, and conception vessel and governor vessel group（group D）, 48 rats in each group. The rats in each group were further divided into six sub-groups, including 12 h group, 24 h group, 48 h group, 72 h group, 96 h group and 144 h group. MCAO operation course was simulated in group A, and the common carotid artery, internal carotid artery and external carotid artery on the right side were exposed, without insertion of suture or treatment. After completion of modeling in group B, treatment was not conducted. After completion of modeling in group C, ＂Shuǐgōu（水沟 GV 26）＂, ＂Bǎihuì（百会 GV 20）＂ and ＂Dàzhuī（大椎 GV 14）＂ of governor vessel were selected, and electroacupuncture device was connected with ＂GV 14＂ and ＂GV 20＂. After completion of modeling in group D, ＂GV 26＂, ＂GV 20＂ and ＂GV 14＂ of governor vessel, and ＂Qìhǎi（气海 CV 6）＂, ＂Guānyuán（关元 CV 4）＂ and ＂Chéngjiāng（承浆 CV 24）＂ of conception vessel were selected; electroacupuncture device was connected with ＂GV 14＂ and ＂GV 20＂, ＂CV 4＂ and ＂CV 6＂. Neurological severity score was conducted.Enzyme linked immunosorbent assay（ELISA） was applied to determine the concentration of peripheral serum adrenocorticotropic hormone（ACTH） of rats, and immunohistochemical method was adopted to detect the expression levels of tumor necrosis factor α（TNF-α） and transforming growth factor β1（TGF-β1） in brain tissue of rats. The other 24 rats were also randomly divided into four groups mentioned above, 6 rats in each group, to detect cerebral ischemie volume. Results Compared with group B, the ischemia volume in brain tissue at 144 h after cerebral ischemia reperfusion decreased significantly in group C and group D（P〈0.05）, and the ischemia volume in group D was less than that in group C（P〈0.05）. The neurological impairment scores of group C and group D at all time points were lower than those of group B, and the differences were statistically significant（all P〈0.05）. The scores of group D at all time points were lower than those of group C, and the differences since 24 h were statistically significant（all P〈0.05）. Compared with group B, the excessive expression of ACTH was suppressed dynamically and generally in group C and group D（P〈0.05）; the expression level of TNF-α was down-regulated and TGF-β1 was up-regulated as well in group C and group D（P〈0.05）. The effect in group D was superior to that in group C. Conclusion Electroacupuncture at conception vessel and governor vessel can protect brain through the intervention of the expression of correlative signals of inflammatory response stress-injury-repair of cerebral ischemia reperfusion.

CRP, but not TNF-α or IL-6, decreases after weight loss in patients with morbid obesity exposed to intensive weight reduction and balneological treatment

Objective：The aim of this study was to evaluate the concentrations of C-reactive protein （CRP）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6）, and the degree of homeostasis model assessment-insulin resistance （HOMA-IR） in patients with morbid obesity exposed to a three-week low-calorie diet and balneotherapy. Methods：The study included 33 patients （25 females and 8 males; mean age 46 years） with body mass index （BMI） values of〉40 kg/m2. Evaluations of CRP, IL-6, TNF-α, lipid profile, HOMA-IR, and fasting glucose were carried out before （baseline data） and three weeks after the treatment. The control group consisted of 20 healthy volunteers （15 females and 5 males） with a mean age of 39 years and BMI values of≤24.9 kg/m2. Results：In the blood of patients with morbid obesity we found significantly elevated levels of CRP, TNF-α, triglycerides, HOMA-IR and fasting glucose, but a de-creased level of high density lipoprotein （HDL）-cholesterol, compared with the healthy individuals. The treatment resulted in about a 9.4%reduction in body weight from 122.5 to 111.0 kg and a significant decrease in the concen-tration of CRP, but no change in TNF-αor IL-6. HOMA-IR was significantly reduced. Conclusions：The decrease in CRP level without changes in TNF-α or IL-6 concentrations after the low-calorie diet and balneological treatment, suggests that an essential amount of adipose tissue must be removed before proper adipocyte function is restored. The decrease in HOMA-IR indicates an improvement in insulin sensitivity, which is beneficial in obese patients.