汉防己甲素滴眼液对高眼压模型大鼠的降眼压作用

目的比较观察汉防己甲素滴眼液与0.5%噻吗心安滴眼液对高眼压模型大鼠及正常大鼠降眼压的作用。方法正常SD大鼠共分4组：不同浓度的汉防己甲素滴眼液组（0.1%、0.2%、0.3%）及阳性对照组0.5%噻吗心安,药物滴右眼各一滴,阴性对照组生理盐水滴左眼、测量滴药前24h和滴药后1、3、6、24、48、72h的眼压。应用倍频532激光对SD大鼠右眼上巩膜静脉以及小梁网所在区域实施光凝术建立高眼压大鼠模型。高眼压模型鼠共分5组：不同浓度的汉防己甲素滴眼液0.05%、0.1%、0.2%、0.3%及阳性对照组0.5%噻吗心安,右眼即模型眼滴用药物,左眼作为空白对照。测量术前后的眼压。结果汉防己甲素滴眼液对大鼠正常眼压无降压作用（P〉0.05）。对高眼压大鼠用药后24h、72h、1周后,0.3%汉防己甲素滴眼液组降低眼压的幅度与0.5%噻吗心安滴眼液降低眼压的幅度相似（P〉0.05）;0.05%、0.1%、0.2%汉防己甲素滴眼液组也有明显的降压作用,但与0.5%噻吗心安滴眼液相比,降压幅度低于后者（P〈0.05）。结论0.05%、0.1%、0.2%、0.3%汉防己甲素滴眼液均有降低大鼠高眼压的作用,其中0.3%浓度的汉防己甲素滴眼液降眼压效果与0.5%的噻吗心安类似。汉防已甲素滴眼液作为一种治疗青光眼的药物有着良好应用前景。     

汉防己甲素及其联合氟康唑对白念珠菌细胞周期影响的初步研究

目的 探讨汉防己甲素联合氟康唑对白念珠菌细胞周期的影响.方法 将白念珠菌CA-1菌悬液与汉防己甲素和（或）氟康唑共培养12h,应用流式细胞仪测定空白对照组、汉防己甲素组、氟康唑组及汉防己甲素联合氟康唑组DNA含量.比较细胞周期各期DNA含量变化并计算增殖抑制率PI％,分析汉防己甲素及其联合氟康唑对白念珠菌细胞周期的影响.结果 汉防己甲素、氟康唑组与对照组S期DNA含量相比,分别能增加17.25％ （P =0.018）与6.54％ （P ＞0.05）,其联合运用效果更明显,S期DNA含量可增加31.52％ （P =0.002）.这说明汉防己甲素能将白念珠菌细胞阻滞在S期.结论 汉防己甲素能抑制白念珠菌细胞DNA合成,阻断白念珠菌细胞周期进程,抑制细胞分裂,其与氟康唑联用时阻滞作用更显著.     

汉防己甲素对四氧嘧啶引致大鼠胰岛β细胞损伤的保护作用

本实验采用四氧嘧啶损伤大鼠胰岛β细胞,复制糖尿病动物模型。若预先腹腔注射汉防己甲素（１００ｍｇ／ｋｇ）则可完全预防引发的糖尿病。预防组血糖（７．６３±０．４４ｍｍｏｌ／Ｌ）明显低于对照组（２５．４６±１．２１ｍｍｏｌ／Ｌ,Ｐ＜０．００１）;血清胰岛素水平（１１．３３±１．９７μＵ／ｍｌ）高于对照组（７．１３±０．４５μＵ／ｍｌ,Ｐ＜０．０５）;血浆胰高血糖素（６６．８５±５．０７ｐｇ／ｍｌ）明显低于对照组（９０．３５±３．１５ｐｇ／ｍｌ,Ｐ＜０．０１）．口服葡萄糖耐量实验显示预防组耐糖功能较对照组明显改善,糖耐量曲线下血糖面积预防组（２９．４５±１．６３ｍｌ·ｈ／Ｌ）低于对照组（１１３．２８±５．０２ｍｍｏｌ·ｈ／Ｌ,ｐ＜０．００１）。胰岛β细胞免疫组织化学染色结果显示,预防组胰岛β细胞数目及胰岛素分泌颗粒的含量均与正常大鼠胰岛相同,无形态学改变,而对照组胰岛内β细胞免疫反应阳性产物减少甚至消失。结果表明,汉防己甲素对四氧嘧啶引起的胰岛β细胞急性损伤有保护作用。     

索拉非尼联合顺铂对胃癌SGC7901细胞的抑制作用

目的:探讨索拉非尼联合顺铂(DDP)对胃癌SGC7901细胞的抑制作用以及可能的分子机制.方法:选取人胃癌细胞株SGC7901,用索拉非尼和DDP单药或联合作用于细胞,观察最佳抑制效果.MTT法检测索拉非尼、DDP及两药联用对胃癌SGC7901细胞的增殖抑制作用并计算半数抑制浓度(IC50);用流式细胞仪检测细胞凋亡;用Western blot观察ERK及pERK蛋白的表达.结果:MTT检测结果显示胃癌SGC7901细胞经索拉非尼、DDP单独处理以及两者联合处理后,在不同浓度均能出现细胞生长抑制作用,并且其抑制作用呈时间-剂量依赖效应.与单药组相比,联合作用组对细胞的抑制率明显增高,表现为协同作用(P＜0.05).流式细胞仪检测凋亡的结果显示,经药物处理后细胞凋亡率均较空白对照组升高,两药联合作用的凋亡率要明显高于单药组.单药组及联合用药组对SGC7901细胞ERK的表达无明显影响,但是pERK在单用索拉非尼及联合用药组的表达则降低,以联合用药组尤甚.结论:索拉非尼联合顺铂对胃癌SGC7901细胞有增殖抑制及促凋亡的作用,两药联合表现为协同作用,其机制可能与细胞增殖通路Raf/MEK/ERK的机制有关.     

汉防己甲素及克矽平时矽肺大鼠I型和Ⅲ型胶原mRNA的影响

汉防己甲素（汉甲）及克矽平是目前较为有效的抑制矽肺纤维化的药物,本文研究了其对胶原ｍＲＮＡ水平的影响。斑点杂交实验表明大鼠接尘６０天和１２０天后α１（Ⅲ）ｍＲＮＡ水平明显上升。经汉甲或克矽平治疗１个月域３个月后,胶原ｍＲＮＡ水平明显下降,原位杂交结果表明胶原ｍＲ－ＮＡ银颗粒与细胞性结节和增厚的肺泡壁的成纤维细胞分重事,汉甲或克矽平治疗后银颗粒数下降。提示汉甲及克矽平对矽肺进程中的胶原基因表达增强有     

褪黑素联合顺铂对A549细胞凋亡相关基因的影响

观察褪黑素以及褪黑素联合顺铂是否可以抑制A549细胞增殖并促进细胞凋亡,探讨ERK1/2MAPK信号通路在这一过程中的作用,为肺腺癌的研究提供实验依据。用不同浓度的褪黑素、不同浓度的顺铂、褪黑素联合顺铂刺激体外培养的肺腺癌细胞系A549细胞,MTT法检测各组细胞的活性,运用Real-time RT-PCR检测凋亡相关基因Bcl-2、Bax、p53的表达水平,Western-blot检测ERK1/2MAPK的活性变化。结果:1)单纯使用褪黑素和顺铂均可抑制A549细胞增殖,褪黑素联合顺铂时,抑制作用更加显著,一定浓度的褪黑素可降低顺铂的使用浓度;2)未经处理的A549细胞Bcl-2/Bax很高,p53基因表达较低,经褪黑素以及褪黑素联合顺铂刺激后A549细胞中Bcl-2/Bax明显下降,p53基因表达明显升高,并有浓度依赖;3)经褪黑素和顺铂刺激后A549细胞中磷酸化ERK1/2MAPK水平明显降低。褪黑素联合顺铂可抑制A549细胞增殖并且诱导凋亡相关基因表达,褪黑素和顺铂对A549细胞的抑制作用可能与ERK1/2MAPK信号通路有关。     

汉防己甲素及克矽平对矽肺大鼠Ⅰ型和Ⅲ型胶原mRNA的影响

汉防己甲素（汉甲）及克矽平（Ｐｏｌｙｖｉｎｙｌｐｙｒｉｄｉｎｅ－Ｎ－Ｏｘｉｄｅ,ＰＶＮＯ）是目前较为有效的抑制矽肺纤维化的药物。本文研究了其对胶原ｍＲＮＡ水平的影响．斑点杂交实验表明大鼠接尘６０天和１２０天后α１（Ⅰ）及α１（Ⅲ）ｍＲＮＡ水平明显上升,经汉甲或克矽平治疗１个月或３个月后,胶原ｍＲＮＡ水平明显下降。原位杂交结果表明胶原ｍＲ－ＮＡ银颗粒与细胞性结节和增厚的肺泡壁的成纤维细胞分布重合。汉甲或克矽平治疗后银颗粒数下降。提示汉甲及克矽平对矽肺进程中的胶原基因表达增强有抑制作用。     

Experimental Characterization of MCF-10A Normal Cells Using AFM: Comparison with MCF-7 Cancer Cells

The mechanical properties of single cells have been recently identified as the basis of an emerging approach in medical applications since they are closely related to the biological processes of cells and human health conditions. The problem in hand is how to measure mechanical properties in order to obtain them more accurately and applicably. Some of the cell’s properties such as elasticity module and adhesion have been measured before using various methods; nevertheless, comprehensive tests for two healthy and cancerous cells have not been performed simultaneously. As a Nanoscale device, AFM has been used for some biological cells, however for breast cells, it has been utilized just to measure elasticity module. To provide a more accurate comparison for the healthy and the malignant cancer cells of breast, mechanical properties of MCF-10A cells such as topography, elasticity module, adhesion force, viscoelastic characteristics, bending and axial rigidity were determined and compared to the MCF-7 cells results obtained in previous works. Results revealed that the healthy breast cells are stiffer and less adhesive in comparison with the cancerous ones. Topography images revealed that cancerous cells have bigger radii. These results can help with the diagnosis of malignant cancer cells and even the level of the disease.     

吉西他滨与长春瑞滨联合顺铂治疗晚期乳腺癌的临床效果分析

目的:探讨吉西他滨与长春瑞滨联合顺铂治疗晚期乳腺癌的近期疗效。方法:选取2012年5月-2013年12月在我院接受治疗的晚期乳腺癌患者80例,随机分为观察组和对照组,每组40例。对照组给予吉西他滨+顺铂治疗,观察组给予长春瑞滨+顺铂治疗。比较两组患者的近期总有效率和不良反应的发生情况。结果:观察组治疗总有效率为70%,对照组为62.5%,两组临床疗效无显著差异(P0.05);两组患者治疗后均出现不同程度的不良反应。其中,观察组患者血小板减少、白细胞减少、静脉炎、恶心呕吐及脱发等毒副反应的发生率为50%,而对照组患者毒副反应的发生率为72.5%。观察组显著低于对照组,差异具有统计学意义(P0.05)。结论:吉西他滨与长春瑞滨联合顺铂治疗晚期乳腺癌具有显著的临床疗效,且安全性较高,值得临床应用。     

AFM对人乳腺癌细胞外纤连蛋白原纤维的形态学观察

探讨原子力显微镜在研究细胞和细胞外基质间的相互作用及细胞外基质的功能等方面的应用前景。应用原子力显微镜观察培养的人乳腺癌MCF 7 R细胞分泌的纤连蛋白原纤维的分布和排列规律 ,并与其他常规观察技术进行比较。应用原子力显微镜获得了多个乳腺癌细胞和细胞外纤连蛋白原纤维的整体和局部形貌图像 ,发现这些原纤维的分布和排列方式非常有规律 ,而且这些规律与其功能相适应。由于样品制备简单和分辨率较高等优点 ,原子力显微镜较适合于细胞外基质的原位观察     

乳腺癌患者循环肿瘤细胞检测的研究进展

血行播散是乳腺癌转移的重要途径,检测腋窝淋巴结已经不能完全准确判断乳腺癌患者是否存在转移。肿瘤细胞进入外周血是肿瘤远处转移的前提,对乳腺癌患者循环肿瘤细胞的检测将有助于判断预后,指导治疗,监测治疗效果。简要综述了乳腺癌循环肿瘤细胞及其检测方法的研究进展。     

Effects of Osthole on Migration and Invasion in Breast Cancer Cells

Osthole, a natural coumarin derivative, is extracted from the fruit of Cnidium monnieri Cusson. Breast cancer is one of the most commonly diagnosed cancers and the leading cause of death in women. Recent studies have shown that Osthole has anti-tumor activity. However, the effects of Osthole on the migration and invasion of cancer cells have not yet been reported. Here, we found that Osthole is effective in inhibiting the migration and invasion of breast cancer cells by wound healing and transwell assays. Luciferase and zymography assays revealed that Osthole effectively inhibits matrix metalloproteinase-2 promoter and enzyme activity, which might be one of the causes that lead to the inhibition of migration and invasion by Osthole. This is the first report on the inhibitory function of Osthole in migration and invasion in breast cancer cells. Our findings indicate a need for further evaluation of Osthole in breast cancer chemotherapy and chemoprevention.     

Cold Atmospheric Plasma-Activated Media Improve Paclitaxel Efficacy on Breast Cancer Cells in a Combined Treatment Model

Simple SummaryBreast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality in females, with chemotherapy currently the only adjunctive therapy. However, the disadvantages of chemotherapy are represented by toxicity/side effects, and for many women the benefit is uncertain. Cold atmospheric plasma in in vitro and in vivo experiments proved that it is able to selectively inhibit the growth of cancer cells in various cancer types, with less deleterious side effects. Current guidelines include paclitaxel as a chemotherapy of choice for various types of breast cancers. The aim of the study was to evaluate in vitro, on human breast cancer cell lines, a plasma-activated media as a cytotoxic agent and as an associative agent in a combined treatment for breast cancer with paclitaxel. The collected data indicated that the plasma-activated media amplified the cytotoxic effect of paclitaxel.AbstractThe use of plasma-activated media (PAM), an alternative to direct delivery of cold atmospheric plasma to cancer cells, has recently gained interest in the plasma medicine field. Paclitaxel (PTX) is used as a chemotherapy of choice for various types of breast cancers, which is the leading cause of mortality in females due to cancer. In this study, we evaluated an alternative way to improve anti-cancerous efficiency of PTX by association with PAM, the ultimate achievement being a better outcome in killing tumoral cells at smaller doses of PTX. MCF-7 and MDA-MB-231 cell lines were used, and the outcome was measured by cell viability (MTT assay), the survival rate (clonogenic assay), apoptosis occurrence, and genotoxicity (COMET assay). Treatment consisted of the use of PAM in combination with under IC50 doses of PTX in short- and long-term models. The experimental data showed that PAM had the capacity to improve PTX’s cytotoxicity, as viability of the breast cancer cells dropped, an effect maintained in long-term experiments. A higher frequency of apoptotic, dead cells, and DNA fragmentation was registered in cells treated with the combined treatment as compared with those treated only with PT. Overall, PAM had the capacity to amplify the anti-cancerous effect of PTX.     

Cisplatin Induces Pyroptosis via Activation of MEG3/NLRP3/caspase-1/GSDMD Pathway in Triple-Negative Breast Cancer

Cisplatin (DDP) was reported to improve pathological complete response (pCR) rates in triple-negative breast cancer (TNBC) patients, however, the molecular mechanism still remains largely unknown. Emerging evidence suggested that some chemotherapeutic drugs played anti-tumor effects by inducing cell pyroptosis. Nevertheless, whether pyroptosis contributes to the DDP-induced anti-tumor effect in TNBC remains unexploited. In the present study, NLRP3/caspase-1/GSDMD pyroptosis pathway was involved in the DDP-induced anti-tumor effect of TNBC in vitro and in vivo, providing evidence that DDP might induce pyroptosis in TNBC. Moreover, DDP activated NLRP3/caspase-1/GSDMD pyroptosis pathway by up-regulating the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3). Furthermore, knockdown of MEG3 not only partly abolished the activation effect of DDP on NLRP3/caspase-1/GSDMD pathway-mediated pyroptosis, but also reversed the suppression of DDP on tumor growth and metastasis ability in vitro and in vivo, further confirming that MEG3 may partially mediate the pyroptotic signaling upon DDP treatment. Thus, our data uncovered a novel mechanism that DDP induced pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in TNBC to exert anti-tumor effects, which may help to develop new strategies for the therapeutic interventions in TNBC.     

鞘氨醇激酶1参与依托泊苷抑制人乳腺癌MDA-MB-231细胞增殖、迁移的研究

目的利用抑制乳腺癌MDA-MB-231细胞中SK-1基因表达,结合依托泊苷对细胞增殖的影响,研究乳腺癌的治疗新方法。方法将依托泊苷分别处理野生型及SK-1敲除型MDA-MB-231细胞,^3H-TdR掺入法分析细胞增殖,Transwell法分析细胞迁移,Western印迹检测SK-1蛋白表达及细胞周期检验点相关信号因子的蛋白表达,RT-PCR检测细胞内SK-1的mRNA表达量。结果依托泊苷在较高剂量时,MDA-MB-231细胞存活率明显下降,但依托泊苷却呈浓度依赖性促进乳腺癌细胞SK-1 mRNA及蛋白水平表达,将SK-1敲除,细胞迁移率下降,而且可以增强G1期各抑癌基因的激活或高表达,使细胞周期阻滞。结论SK-1基因敲除有效增强肿瘤细胞对化疗药物的敏感性。     

小剂量顺铂动脉化疗联合放疗对中晚期宫颈癌的临床疗效

目的:探讨小剂量顺铂用于子宫动脉化疗联合放疗治疗中晚期宫颈癌的临床疗效。方法:选择2010年8月~2012年8月我院收治的中晚期宫颈癌患者75例,根据不同治疗方案将其分为单纯放疗组25例(单纯采用放疗治疗)、小剂量动脉化疗组25例(同时放化疗,顺铂周疗的剂量控制在20 mg·m-2)及标准剂量静脉化疗组25例(同时放化疗,顺铂周疗的剂量控制在40 mg·m-2)。观察并比较三组患者的临床疗效、两年生存率及毒性反应发生情况等。结果:小剂量动脉化疗组与标准剂量静脉化疗组的总有效率及两年生存率显著高于单纯放疗组(P0.05),小剂量动脉化疗组的总有效率和两年生存率高于标准剂量静脉组,差异具有统计学意义(P0.05)。单纯放疗组及小剂量动脉化疗组的毒性反应发生率显著低于标准剂量静脉组(P0.05);单纯放疗组与小剂量动脉化疗组患者的毒性反应发生率对比无统计学差异(P0.05)。结论:小剂量顺铂动脉化疗可以有效降低中晚期宫颈癌患者的急性毒性反应,值得临床进一步推广应用。