环氧合酶-2在胃癌中的研究进展

我国胃癌发病人数居全球首位,其发生机制及安全有效的治疗是研究重点。大量研究结果表明,环氧化酶-2(Cyclooxygenase-2,COX-2)过度表达促进肿瘤细胞增殖和抑制细胞凋亡,并与胃癌的发生发展、淋巴转移、分化程度、病理分期及预后密切相关。随着COX-2与胃癌关系的研究的深入,COX-2已逐渐成为胃癌治疗的新的靶点。近年来,针对细胞受体、信号传导、细胞周期和血管生成等靶点的抗肿瘤治疗已成为肿瘤治疗研究的新方向。因此,以COX-2为特异靶点的治疗策略有望为胃癌治疗提供新的思路。     

腰痹通胶囊联合塞来昔布胶囊治疗椎间盘源性腰痛的疗效及对血清炎性因子和疼痛介质的影响

摘要 目的：探讨腰痹通胶囊联合塞来昔布胶囊治疗椎间盘源性腰痛（DLBP）的疗效及对血清炎性因子和疼痛介质的影响。方法：选择2017年5月~2022年5月期间我院接收的75例DLBP患者。依据信封抽签法将患者分为对照组（n=37）和研究组（n=38）,对照组接受塞来昔布胶囊治疗,研究组接受腰痹通胶囊联合塞来昔布胶囊治疗。对比两组疗效、临床症状评分、血清炎性因子和疼痛介质的变化情况,同时观察两组用药安全性。结果：研究组痊愈8例,显效10例,有效18例,临床总有效率94.74%,高于对照组的痊愈4例,显效8例,有效17例,临床总有效率78.38%（P<0.05）。治疗1个月后,研究组的视觉疼痛模拟（VAS）评分、Oswestry功能障碍指数（ODI）较对照组更低（P<0.05）,改良日本骨科协会（JOA）评分较对照组更高（P<0.05）。治疗1个月后,研究组的血清白细胞介素-6（IL-6）、C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）水平较对照组更低（P<0.05）。治疗1个月后,研究组的血清 P物质（SP）、多巴胺（DA）、前列腺素E₂（PGE₂）水平较对照组更低（P<0.05）。两组不良反应发生率组间对比差异不显著（P>0.05）。结论：腰痹通胶囊联合塞来昔布胶囊治疗DLBP,可有效减轻疼痛,恢复腰椎功能,降低血清炎性因子和疼痛介质水平。     

Determination of celecoxib in human plasma by normal-phase high-performance liquid chromatography with column switching and ultraviolet absorbance detection

A method is described for the determination of celecoxib in human plasma. Samples were extracted using 3M Empore membrane extraction cartridges and separated under normal-phase HPLC conditions using a Nucleosil-NO₂ (150×4.6 mm, 5 μm) column. Detection was accomplished using UV absorbance at 260 nm. The HPLC method included a column switching procedure, in which late eluting compounds were diverted to waste, to reduce run-time to 12 min. The assay was linear in the concentration range of 25–2000 ng/ml when 1-ml aliquots of plasma were extracted. Recoveries of celecoxib were greater than 91% over the calibration curve range. Intraday precision and accuracy for this assay were 5.7% C.V. or better and within 2.3% of nominal, respectively. The assay was used to analyze samples collected during human clinical studies.     

正清风痛宁片联合塞来昔布对类风湿关节炎患者疾病活动指标、炎症因子及红细胞免疫功能的影响

目的:探讨正清风痛宁片联合塞来昔布对类风湿关节炎(RA)患者疾病活动指标、炎症因子及红细胞免疫功能的影响。方法:选取2016年8月～2019年10月我院接收的117例RA患者。根据随机数字表法分为研究组(n=59)、对照组(n=58)。对照组予以塞来昔布治疗,研究组在对照组的基础上联合正清风痛宁片治疗,两组均治疗1个月。统计两组治疗1个月后的临床疗效。比较两组治疗前、治疗1个月后的疾病活动指标[类风湿因子(RF)、C反应蛋白(CRP)、血沉(ESR)],红细胞免疫功能指标CR1、CD59以及炎症因子指标[肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)以及白介素-6(IL-6)],记录两组治疗期间不良反应情况。结果:研究组治疗1个月后的总有效率为89.83%(53/59),高于对照组的72.41%(42/58)(P0.05)。两组不良反应发生率对比无差异(P0.05)。两组治疗1个月后RF、CRP、ESR、TNF-α、IL-1β以及IL-6水平均较治疗前下降,且研究组低于对照组(P0.05)。两组治疗1个月后CR1、CD59均较治疗前升高,且研究组高于对照组(P0.05)。结论:正清风痛宁片联合塞来昔布治疗RA患者,疗效显著,可有效降低患者疾病活动指标、炎症因子水平,提高红细胞免疫功能,且不增加不良反应发生率。     

分析塞来昔布与不同剂量艾瑞昔布治疗axSpA的效果及对骨代谢的影响

目的:探究塞来昔布和2种剂量艾瑞昔布治疗中轴脊柱关节炎(axSpA)的效果及对患者骨代谢的影响。方法:选取我院96例axSpA患者为研究对象,采用随机数字表法分为A组、B组、C组各32例。A组给予0.2 g/d艾瑞昔布治疗,B组给予0.4 g/d艾瑞昔布治疗C组给予0.4 g/d塞来昔布治疗。比较3组治疗前及治疗12周后疾病活动性[C反应蛋白(CRP)、红细胞沉降率(ESR)、Bath强直性脊柱炎疾病活动指数(BASDAI)]、躯体活动度(踝间距、腰椎侧弯度)、功能状态[Bath强直性脊柱炎功能指数(BASFI)、加拿大脊柱骨关节研究协会评分系统(SPARCC)]、骨代谢[血清骨形成发生蛋白-2(BMP-2)、血管内皮生长因子(VEGF)、Dickkopf相关蛋白1(DKK-1)]差异,并记录3组治疗期间不良反应发生情况。结果:治疗12周后,3组疾病活动性(CRP、ESR、BASDAI)、功能状态(BASFI、SPARCC)、骨代谢(BMP-2、VEGF、DKK-1)均较治疗前降低(P<0.05),躯体活动度(踝间距及左右侧腰椎侧弯度)则较治疗前升高(P<0.05);但B组及C组组间比较,差异无统计学意义(P>0.05),而A组上述指标变化幅度低于B组及C组(P<0.05)。3组治疗期间不良反应发生情况比较,差异均无统计学意义(P>0.05)。结论:较高剂量(0.4 g/d)艾瑞昔布疗效明显优于较低剂量(0.2 g/d),不良反应也未增加,且0.4 g/d艾瑞昔布及同剂量塞来昔布治疗axSpA具有相似的疗效及安全性,适用于临床治疗。     

Design,synthesis of celecoxib-tolmetin drug hybrids as selective and potent COX-2 inhibitors

Three novel series of diarylpyrazole 10b-d and triarylpyrazole derivatives 11a-d &12a-d were synthesized through Vilsmier-Haack condition. The structures of prepared compounds were determined through IR, ¹H NMR, ¹³C NMR, Mass spectral and elemental analysis. Docking of the synthesized compounds over COX-2 active site ensure their selectivity. Moreover, the target compounds were evaluated for both in vitro and in vivo inhibitory activity. All compounds were more selective for COX-2 isozyme than COX-1 isozyme and with excellent anti-inflammatory activity. Compounds 11b, 11d and 12b showed the highest anti-inflammatory activity (67.4%, 62.7%, 61.4% respectively), lower ulcerogenic liability (UI = 2.00, 2.75, 3.25 respectively) than indomethacin (UI = 14) and comparable to celecoxib (UI = 1.75) which were confirmed from the histopatholgical study.     

塞来昔布对直肠癌HCA-7 细胞放射敏感性的实验研究

目的:观察环氧合酶-2(COX-2)抑制剂塞来昔布对直肠癌HCA-7细胞株的放射敏感性及探讨其机制。方法:采用MTT法检测塞来昔布作用不同时间对直肠癌HCA-7细胞株增殖的影响,计算出塞来昔布的半数抑制浓度IC50;HCA-7细胞克隆形成实验用于检测塞来昔布对HCA-7细胞的放射敏感性,并绘制存活曲线;流式细胞仪(FCM)测定塞来昔布对HCA-7的细胞周期的影响。结果:塞来昔布对HCA-7细胞株的抑制率随时间的延长而升高,48h的IC50是40.19μmol/L;照射组+药物组的SF2、D0、Dq、SER较单纯照射组均有所下降。塞来昔布使HCA-7细胞发生G2和M期阻滞,并抑制S期的比例。结论:塞来昔布能增加直肠癌HCA-7细胞的放射敏感性。     

Celecoxib 联合X 线对胆管癌细胞株QBC939 凋亡的影响

目的:研究塞来昔布联合X线在体外环境下对人胆管癌细胞株QBC939凋亡的影响并对其机制进行初步探讨。方法:CCK-8检测出不同浓度的塞来昔布及不同剂量的X线对QBC939细胞株的增值抑制率,确定塞来昔布组的IC50及X线组的IC50。将QBC939细胞株分为5组:对照组(control)、X线组(R)、塞来昔布组(C)、塞来昔布再加X线组(C+R),X线再加塞来昔布组(R+C)。用流式细胞仪检测各组的凋亡率,western blot检测凋亡相关基因survivin蛋白的表达。结果:联合使用塞来昔布和放疗组的凋亡率有明显的增加,从8.268%,11.233%到15.733%,22.133%(P<0.05)。western结果显示联合组survivin蛋白的表达也明显低于对照组(P<0.05)。先用塞来昔布再加放疗的效果要优于先用放疗后用塞来昔布的效果。结论:塞来昔布联合X线对QBC939细胞株有凋亡增敏作用,作用可能机制之一是通过降低或下调凋亡相关基因survivin蛋白的表达。     

Inhibitory effects of norcantharidin against human lung cancer cell growth and migration

The effects of norcantharidin (NCTD), an anticancer drug in China, on the growth and migration in human lung cancer cells were investigated by in vitro and ex vivo assays. NCTD significantly inhibited the in vitro and ex vivo growth of human non-small cell lung cancer A549 cells in dose- and time-dependent manners. Western blot analysis indicated that NCTD dose-dependently down-regulated the expression of anti-apoptotic protein Bcl-2 and up-regulated the level of pro-apoptotic protein Bax, eventually leading the reduction of ratio of Bcl-2/Bax proteins in A549 cells. Moreover, NCTD significantly suppressed the A549 cell migration in the case of without reducing the cell viability. More importantly, NCTD significantly enhanced the anticancer activity of anticancer agents such as trichostatin A (the histone deacetylase inhibitor), celecoxib (the inhibitor of cyclooxygenase-2) and lovastatin (the inhibitor of HMG-CoA reductase) by strongly reducing the viability and/or the ratio of Bcl-2/Bax protein in A549 cells. Our findings suggest that NCTD may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human lung cancer.