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1.
目的 观察重组人血管内皮抑制素(rhEndo)联合顺铂对人骨肉瘤MG-63细胞VEGF基因表达、增殖及侵袭力的影响.方法 顺铂、rhEndo、rhEndo联合顺铂分别处理MG-63细胞,采用RT-PCR和Western blot检测细胞VEGF mRNA和蛋白表达量,CCK-8实验检测细胞增殖,流式细胞术检测细胞凋亡,Transwell小室体外迁移实验检测细胞侵袭和迁移能力.结果 rhEndo联合顺铂组对VEGF mRNA和蛋白表达量、细胞增殖、侵袭迁移的抑制作用以及对细胞凋亡的促进作用均显著高于rhEndo、顺铂单药组,差异有统计学意义(P<0.05).结论 重组人血管内皮抑制素联合顺铂能够在抑制骨肉瘤MG-63细胞VEGF表达、细胞增殖和侵袭力、促进细胞凋亡方面发挥协同作用.  相似文献   

2.
目的观察柚皮苷与顺铂联用对MG63细胞增殖和迁移的效果。方法将传代的MG63细胞分为顺铂处理组(顺铂组)、柚皮苷处理组(柚皮苷组)和两种药物联合处理组(联合组),分别使用不同浓度的药物在不同时间点用MTT方法检测MG63细胞光密度值(OD 490),观察细胞增殖情况;在药物作用24 h后观察细胞迁移情况。随后通过Western blot实验检测药物对cyclin d1蛋白和MMP2蛋白表达情况的调节作用。结果对细胞处理24 h后,20μg/m L柚皮苷组、5μg/m L顺铂及二者联合处理对MG63细胞的增殖抑制率分别为7.52%±2.31%、26.89%±0.19%、42.51%±2.53%,联合组抑制率高于各单药组(P<0.01)。顺铂与柚皮苷均可以抑制MG63细胞的迁移,二者联合作用后对细胞迁移的抑制作用更为明显。蛋白检测显示,顺铂和柚皮苷作用MG63细胞24 h后,均可以在一定程度上抑制cyclin d1和MMP2的表达,联合作用后抑制作用增强。结论柚皮苷与顺铂联合使用对抑制骨肉瘤细胞增殖和迁移有协同效果,可以降低顺铂的使用浓度,进而减少治疗时化疗药物的毒副作用。  相似文献   

3.
目的 研究长链非编码RNA SNHG18基因在膀胱癌组织膀胱癌细胞系中的表达情况及其对细胞恶性生物学行为的影响。方法 选取2021年8月至2022年10月行手术治疗的膀胱癌患者42例,应用RT-qPCR检测SNHG18基因在42例膀胱癌组织及3株膀胱癌细胞(5637、T24、SW780)中的表达情况;构建过表达载体pcDNA3.1-SNHG18与敲低载体SNHG18分别转染膀胱癌细胞,应用细胞增殖实验、细胞克隆形成实验、划痕实验、Transwell小室侵袭实验来观察膀胱癌细胞增殖、迁移、侵袭能力的变化。结果 SNHG18在膀胱癌组织及细胞中的表达低于正常的膀胱上皮组织和膀胱上皮细胞,差异有统计学意义(P<0.05);SNHG18的表达量与性别、年龄、有无吸烟、有无高血压、有无糖尿病、有无淋巴结和远处转移及临床分期间无相关性(P>0.05);过表达SNHG18可抑制膀胱癌细胞的体外增殖、迁移和侵袭能力(P<0.05);敲低SNHG18可增强膀胱癌细胞的体外增殖、迁移和侵袭能力(P<0.05)。结论 SNHG18在膀胱癌组织中表达量降低,与临床参数无关,与膀胱癌细胞...  相似文献   

4.
目的研究人类白细胞介素(hIL)-24基因联合顺铂对人宫颈癌Siha细胞的生长抑制作用以及hIL-24基因对Siha宫颈癌细胞侵袭、迁移能力的影响。方法构建重组质粒pDC316-hIL-24,使用脂质体携带pDC316-hIL-24质粒转染Siha细胞;聚合酶链反应(PCR)法检测hIL-24基因在宫颈癌细胞中的表达情况。Siha细胞在转染hIL-24基因后,添加不同剂量的顺铂,用CCK-8试剂检测hIL-24基因联合顺铂对Siha细胞增殖抑制效果;Transwell实验检测hIL-24基因对Siha细胞迁移侵袭能力的影响。结果重组质粒pDC316-hIL-24成功转染Siha宫颈癌细胞;hIL-24联合顺铂对Siha细胞的增殖抑制作用大于单独使用顺铂或hIL-24基因组(P<0.05);Transwell实验中,hIL-24干预组肿瘤细胞的穿膜细胞数最少(P<0.05)。结论 hIL-24基因的表达可增加Siha宫颈癌细胞对顺铂的敏感性;hIL-24基因可以明显抑制Siha宫颈癌细胞的迁移侵袭能力。  相似文献   

5.
目的:初步探讨培美曲塞联合顺铂通过TRAIL诱导非小细胞肺癌A549细胞凋亡发挥的抗癌效果。方法:将肺癌细胞株A549做4种处理并分为4组:空白组(Blank组)、顺铂处理组(CDPP组)、培美曲塞处理组(MTA组)、培美曲塞联合顺铂处理组(MTA+CDPP组),应用CCK-8和流式细胞术检测4种处理细胞的细胞活性和细胞凋亡变化;qPCR检测顺铂单药治疗组和培美曲塞联合顺铂治疗组的细胞肿瘤坏死因子相关凋亡诱导配体(TRAIL)表达差异;干扰TRAIL后再次检测各处理组细胞的细胞活性和细胞凋亡变化;qPCR和WB检测干扰TRAIL后BCL-2转录水平和蛋白表达。结果:培美曲塞联合顺铂(CDDP)在非小细胞肺癌细胞中起到降低细胞活性和诱导细胞凋亡的作用,二者协同发挥抗肿瘤效果;培美曲塞联合顺铂治疗组TRAIL转录表达显著高于顺铂处理组;干扰TRAIL后,顺铂与培美曲塞联合诱导的细胞活力的降低作用被抑制,并逆转了顺铂与培美曲塞联合对细胞凋亡的促进作用;培美曲塞联合顺铂通过TRAIL降低Bcl-2的转录水平和蛋白表达来发挥促进肿瘤细胞凋亡的作用。结论:培美曲塞可联合顺铂(CDDP)在非小细胞肺癌细胞中发挥抗肿瘤效果,其通过TRAIL降低Bcl-2的表达来诱导肿瘤细胞凋亡,从而发挥抗肿瘤作用。  相似文献   

6.
贺武斌  苏荣健 《天津医药》2016,44(3):302-305
[摘要]目的 探讨白头翁皂苷D联合索拉非尼对人肝癌细胞株侵袭与转移的影响。 方法 将人肝癌细胞BEL-7402分为白头翁皂苷D单药处理组、索拉非尼单药处理组及两药联合处理组,观察比较三种处理方式对肝癌细胞侵袭和转移的影响。结果 检测分析各组黏附抑制率,作用3h,索拉非尼组显著高于白头翁皂苷D组(P<0.05或<0.01),联合用药组显著高于索拉非尼组和白头翁皂苷D组(P<0.01);作用5h,白头翁皂苷D组黏附抑制率显著高于索拉非尼组(P<0.01),并且高于白头翁皂苷D组作用3h(P<0.01),说明两药联合对肝癌细胞的黏附抑制率具有协同作用(Q=2.33>1.15);检测分析各组迁移抑制率,索拉非尼单药组和两药联合组对肝癌细胞的迁移抑制率均显著高于白头翁皂苷D单药组(P<0.01),并且两药联合组的抑制率显著高于索拉非尼单药组(P<0.01),说明两药联合对肝癌细胞的迁移抑制作用具有协同作用(Q=1.39>1.15);检测分析侵袭抑制率,索拉非尼单药组和两药联合组均显著高于白头翁皂苷D组(P<0.01),说明两药联合对肝癌细胞的侵袭抑制作用具有拮抗作用(Q=0.68<0.85)。各组的VEGF-C、MMP-9表达情况:白头翁皂苷D单药组的MMP-9表达水平显著下降,索拉非尼组和两药联合组的VEGF-C、MMP-9及表达水平均显著下降(P<0.05);与白头翁皂苷D单药组比较,两药联合组的VEGF-C表达水平显著下降;两药联合组较白头翁皂苷D单药组VEGF-C水平显著下降(P<0.05)。结论 白头翁皂苷D、索拉非尼单药以及两药联合对肝癌细胞BEL-7402细胞株的黏附、迁移、侵袭具有一定的抑制作用,且二者对肝癌细胞的黏附、迁移的抑制具有协同作用。  相似文献   

7.
目的探讨羟喜树碱(HCPT)联合顺铂热化疗对人肝癌细胞的毒性增效作用,观察其腹腔热灌注治疗肝癌癌腹腔积液的疗效。方法流式细胞术检测温热条件下HCPT联合顺铂处理后肝癌细胞的凋亡。观察48例晚期肝癌腹腔积液患者热灌注化疗的疗效及不良反应。检测治疗前后血清AFP水平变化。结果HCFF联合顺铂化疗显著增加对肝癌细胞的细胞凋亡率。热灌注HCPT联合顺铂治疗肝癌腹腔积液的有效率为60%(18/30),显著高于顺铂单药灌注组38.9%,不良反应轻微。血清AFP治疗后显著下降,且与疗效相关。结论HCPT联合顺铂热化疗能显著诱导肝癌细胞凋亡,热灌注HCPT联合顺铂是晚期肝癌腹腔积液安全有效的治疗方法。  相似文献   

8.
摘要:目的 探讨T-钙黏蛋白联合顺铂对黑色素瘤顺铂耐药株的作用。方法 采用大剂量冲击和逐步增加剂 量相结合的方法诱导建立小鼠黑色素瘤B16F10顺铂耐药细胞株(CDDP-R B16F10)。MTT法检测CDDP-R B16F10 的增殖能力。将T-钙黏蛋白转染肿瘤细胞。分别采用反转录聚合酶链式反应(RT-PCR)和免疫组化SP法检测转染 后T-钙黏蛋白mRNA和蛋白的表达。实验将CDDP-R B16F10细胞分为空白对照组、pEGFP-N1组、pEGFP-N1-T cadherin组、顺铂组、pEGFP-N1联合顺铂组、pEGFP-N1-T-cadherin 联合顺铂组。采用Wound-healing 划痕实验和 transwell侵袭实验检测T-钙黏蛋白联合顺铂对CDDP-R B16F10细胞迁移和侵袭力的影响。结果 成功建立黑色素 瘤顺铂耐药细胞株。MTT法结果显示,CDDP-R B16F10细胞增殖能力与B16F10细胞相比差异无统计学意义(P> 0.05)。RT-PCR和免疫组化SP法检测表明,转染后细胞可稳定转录和表达T-钙黏蛋白。pEGFP-N1-T-cadherin联 合顺铂组细胞迁移率和穿膜细胞数低于pEGFP-N1-T-cadherin组(P<0.05),而pEGFP-N1-T-cadherin组低于空白 对照组、pEGFP-N1 组、顺铂组和 pEGFP-N1 联合顺铂组(P<0.05)。析因分析显示,T-钙黏蛋白与顺铂联合对 CDDP-R B16F10细胞迁移率及侵袭力的抑制有交互作用(P<0.05)。结论 T-钙黏蛋白可恢复顺铂对黑色素瘤顺 铂耐药细胞株迁移及侵袭力的抑制作用。  相似文献   

9.
目的 研究洛伐他汀单用或与化疗药物顺铂联用时对人肝癌HepG2细胞生物学特性的影响,初步探索其抗肿瘤作用机制。方法 不同浓度洛伐他汀、洛伐他汀联合顺铂处理细胞 48 h后,CCK-8法检测HepG2细胞的增殖抑制作用,金氏公式计算联合应用效果;平板克隆形成实验评价药物作用于肝癌细胞的远期效应;划痕实验检测药物对细胞迁移能力的影响;Transwell小室法检测药物对细胞侵袭能力的影响;流式细胞术检测药物处理后细胞周期和凋亡情况;蛋白印迹技术(Western-blot)检测凋亡相关蛋白Bcl-2、Bax、Caspase-3的表达水平变化。结果 洛伐他汀呈浓度依赖性抑制HepG2细胞的增殖,金氏公式计算结果显示洛伐他汀可协同增强顺铂的抗肿瘤作用;平板克隆形成实验结果表明洛伐他汀能显著抑制HepG2细胞克隆形成率;划痕实验提示洛伐他汀能显著降低肝癌细胞的迁移率;Transwell小室侵袭实验结果发现洛伐他汀能明显减少穿膜细胞数量;流式细胞检测发现洛伐他汀可引起G0/G1期细胞增加,S期细胞减少,细胞凋亡率增加;Western-blot检测结果显示洛伐他汀可下调Bcl-2蛋白表达,同时上调Bax和Caspase-3蛋白表达。结论 洛伐他汀可明显抑制HepG2细胞增殖、迁移和侵袭能力,与顺铂联用可增强顺铂体外抗肿瘤效果,通过线粒体途径诱导肿瘤细胞凋亡是其可能的抗肿瘤作用机制之一。  相似文献   

10.
目的:研究凋亡促进因子Omi/HtrA2基因过表达对食管癌细胞EC9706凋亡及对耐药性的影响。方法用脂质体包裹转染人食管癌EC9706细胞,实验分为对照组、空载体组、Omi载体组、顺铂组、Omi+顺铂联合组,采用RT-PCR检测不同干预组Omi/HtrA2基因mRNA表达的变化,MTT法检测不同干预组细胞生长抑制率,流式细胞术检测不同干预组细胞的凋亡率,分析Omi/HtrA2基因蛋白表达对细胞耐药性的影响。结果①Omi/HtrA2基因mRNA在EC9706细胞中的表达:对照组为(0.113±0.009),空载体组为(0.106±0.006),Omi载体组为(0.436±0.021),顺铂组为(0.196±0.013),Omi+顺铂联合组为(0.639±0.032),顺铂组、Omi+顺铂联合组较对照组、空载体组明显增强,差异有统计学意义(P<0.01,P=0.011,P=0.000),对照组与空载体组比较无显著性差异(P>0.05,P=0.725)。②MTT法检测Omi/HtrA2的表达对细胞生长的抑制率:对照组为0,空载体组为2.89%,Omi载体组为27.61%,顺铂组为30.02%,Omi+顺铂联合组为48.47%,与对照组相比,Omi载体组、顺铂组、Omi+顺铂联合组均显著抑制EC9706细胞的生长,差异具有显著性(P=0.000)。③流式细胞术检测Omi/HtrA2的表达对凋亡的影响:对照组细胞凋亡率为10.76%,空载体组为13.26%,Omi载体组为38.14%,顺铂组为45.86%,Omi载体+顺铂联合组为56.64%,与对照组、空载体组比较,Omi载体组、顺铂组、Omi载体+顺铂联合干预组细胞凋亡率明显提高,差异具有显著性意义(P=0.000)。结论 Omi/HtrA2基因过表达可以明显抑制癌细胞的生长,提高癌细胞的凋亡率及癌细胞对化疗药物的敏感性,且Omi/HtrA2基因的表达与化疗药物具有协同抗癌作用。  相似文献   

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12.
Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.  相似文献   

13.
Nestorov I 《Toxicology letters》2001,120(1-3):411-420
Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.  相似文献   

14.
The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.  相似文献   

15.
Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.  相似文献   

16.
骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制(内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等)及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。  相似文献   

17.
The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.  相似文献   

18.
益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.  相似文献   

19.
[6,7-3H] Estrone (E) and [6,7-3H]estradiol-17 (E2) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E2 were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E2, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E2, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 103–104 have been found for potent, 102 for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983  相似文献   

20.
Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH4HCO3, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.  相似文献   

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