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51.
目的:评价预防性应用选择性环氧化酶-2(COX-2)抑制剂塞莱昔布对化学诱导大鼠乳腺肿瘤及正常乳腺组织病理分级的影响。方法:雌性SD大鼠予二甲基苯并蒽(DMBA)1次性灌胃诱发乳腺肿瘤过程中,给予不同剂量塞莱昔布,观察肿瘤发生率、数量和体积,并与正常对照组进行病理学分析。结果:与对照组相比,塞莱昔布100和150 mg/kg两剂量组大鼠乳腺肿瘤发生率和肿瘤数量均显著低于模型对照组,但各组间肿瘤平均体积差异无统计学意义,P>0.05。塞莱昔布显著降低大鼠乳腺肿瘤的组织病理分级(100 mg/kg,P=0.021;150 mg/kg,P=0.036),显著降低DMBA导致的乳腺小叶和腺泡的病变程度(100 mg/kg,P=0.004)。结论:预防性应用塞莱昔布具有降低乳腺肿瘤的病理分级,保护正常乳腺组织的作用,其临床应用价值值得进一步探索。 相似文献
52.
塞来昔布诱导人肝癌细胞株QGY-7701凋亡的研究 总被引:1,自引:1,他引:0
目的探讨塞来昔布体外诱导人肝癌细胞株QGY-7701凋亡的作用。方法设立空白对照组(培养液中不加任何药物)及塞来昔布5、25、50、100、150μmol.L-1 5个剂量组,作用时间分为24、48、72 h,应用四甲基偶氮唑盐(MTT)法观察塞来昔布不同浓度和作用时间对QGY-7701细胞生存率的影响,选择合适的作用时间和3个剂量再做其他凋亡方法的检测;采用Hoechst 33258染色荧光显微镜观察凋亡细胞的形态学变化;采用双荧光染色(AnnexinV-EGFP/PI)流式细胞检测、末端脱氧核苷酰基转移酶介导性dUTP切口末端标记(TUNEL)检测、DNA含量分析(检测细胞周期)等方法多指标检测细胞凋亡率。结果通过Hoechst 33258染色可以从细胞形态上看出塞来昔布诱导QGY-7701细胞凋亡,而Annexin V-EGFP/PI流式细胞检测、TUNEL检测、细胞周期及MTT检测结果显示随着塞来昔布浓度升高和作用时间延长,凋亡率升高(P<0.05,P<0.01)。结论塞来昔布有诱导肝癌细胞QGY-7701凋亡,抑制其生长的作用,具有治疗肝癌的潜在功能。 相似文献
53.
This study aimed to investigate the effects of celecoxib, synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylicacid
(CD437) and the combination of the two on cell proliferation, apoptosis, and cycle arrest of human malignant melanoma A375
cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay (MTT assay) was applied to determine the anti-proliferative
effects of the drugs on human malignant melanoma A375 cells. Flow cytometry was performed to investigate the influence of
the drugs on cell cycle and cell apoptosis. Both celecoxib and CD437 could inhibit the growth of human malignant melanoma
A375 cells in a dose-dependent manner. Celecoxib at 80 μmol/L inhibited proliferation, induced apoptosis and G2/M cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (50.2
± 2.51)%, apoptosis rate: (35.91 ± 1.80)%]. CD437 at 10 μmol/L inhibited proliferation, induced apoptosis and G0/G1 cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (58.6 ±
2.38)%, apoptosis rate: (28.03 ± 0.77)%]. Celecoxib in combination with CD437 could significantly enhance the effects of inhibiting
proliferation and inducing apoptosis of human malignant melanoma A375 cells 24 h after treatment compared with the drug alone
[proliferation inhibiting rate: (68.92 ± 1.72)%, apoptosis rate: (42.09 ± 1.05)%, both P<0.05] and decrease the proportion of the S phase in the cell cycle. Celecoxib could inhibit the growth of human malignant
melanoma A375 cells by inducing apoptosis and G2/M cycle arrest. CD437 could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G0/G1 cycle arrest. Celecoxib exhibited additive effects with CD437 on retarding the growth and inducing apoptosis of human malignant
melanoma A375 cells. Celecoxib in combination with CD437 may become an effective method for prevention and treatment of human
melanoma. 相似文献
54.
The purpose of this study was to evaluate the effectiveness of application of muscle relaxants and celecoxib in early recovery after total knee arthroplasty (TKA). One hundred and fifty patients were randomized 1:1:1 to receive either both of muscle relaxants and celecoxib or muscle relaxants alone or placebo for 2 weeks (50 patients in each group). VAS pain scores as primary efficacy, active range of motion, morphine consumption, blood loss, and postoperative complications including postoperative nausea and vomiting (PONV), extremities myasthenia and deep vein thrombosis (DVT) were determined postoperatively. Group A improved better with reduced VAS pain scores compared with another two groups. These results demonstrated that application of muscle relaxants and celecoxib into patients undergoing TKA for 2 weeks postoperative consequently improved their convalescence. 相似文献
55.
56.
目的:观察环氧合酶-2(cyclooxygenase-2, COX-2)在肝癌细胞中表达,探讨COX-2抑制剂celecoxib对肝癌细胞增殖和凋亡的作用.方法:免疫细胞化学、逆转录聚合酶链反应(RT-PCR)方法研究COX-2在肝癌细胞株中表达;MTT法观察COX-2抑制剂对肝癌细胞增殖的影响;透射电镜及流式细胞仪观察 celecoxib诱导肝癌细胞凋亡的作用、对细胞周期的影响及MDR1/P-gp表达的变化;用RTPCR 方法检测Survivin mRNA药物处理后表达的变化.结果:celecoxib对肝癌细胞抑制增殖、诱导凋亡呈时间和剂量依赖性.celecoxib作用HepG2 48 h抑制率为70.98%±0.67%(200 μmol/L)、 47.93%±1.08%(100 μmol/L);Bel-7402为 57.29%±0.67%(200 μmol/L)、43.84%± 0.86%(100 μmol/L);同样浓度但作用20 h, HepG2为45.51%±1.35%(200 μmol/L), 14.35%±1.55%(100 μmol/L);Bel-7402则为34.35%±0.63%(200 μmol/L),15.35%± 0.88%(100 μmol/L),不同浓度以及不同作用时间相比均有显著差异(P<0.01);100 μmol/L celecoxib作用24,48,72,96 h的肝癌细胞凋亡率分别为12.2%±2.44%,4.0%±1.67%,20.4%±4.38%,57.9%±5.74%(HepG2)和3.0%± 1.05%,18.5%±3.51%,29.3%±3.25%,48.4%±4.77%(Bel-7402),与对照组相比有显著差异(P<0.01);细胞周期分布改变,G0/G1期细胞比例增加,24,48,72 h分别为:44.17%±1.01%,59.60%±0.61%,62.7%±1.22% (HepG2)和47.80%±0.41%,58.60%±0.46%, 78.40%±1.95%(Bel-7402),与对照组比较有显著差异(P<0.01);对照组PCNA蛋白表达呈强阳性( ),经药物处理后表达减弱,并随时间延长而显著;HepG2中COX-2蛋白表达明显弱于Bel-7402,药物处理后表达也不同.Survivin在肝癌细胞株中呈高表达状态, celecoxib作用48 h mRNA表达降至零,而72 h 后表达水平又有上升;两株肝癌细胞中经 celecoxib处理后,MDR1/P-gp表达有降低的趋势(Bel-7402),或是基本上不受影响(HepG2).结论:COX-2抑制剂celecoxib体外对肝癌细胞有较强的细胞毒作用且以剂量、时间依赖方式抑制细胞增殖,并诱导凋亡,使细胞周期阻滞于G1/S期.COX-2与P-gp,Survivin表达密切相关. 相似文献
57.
Effect of celecoxib on experimental liver fibrosis in rat. 总被引:1,自引:0,他引:1
Alex Yui Hui Wai Keung Leung Henry Lik Yuen Chan Francis Ka Leung Chan Minnie Yin Yin Go Ka Kui Chan Bao Dong Tang Eagle Siu Hong Chu Joseph Jao Yiu Sung 《Liver international》2006,26(1):125-136
BACKGROUND/AIM: Cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes prostaglandin synthesis, has been implicated in a number of hepatic stellate cell (HSC) functions. In the current study, we assessed the in vivo effect of celecoxib, a COX-2-selective inhibitor, in experimental liver fibrosis in rats. METHODS: Male Sprague-Dawley rats received experimental treatments for 5 weeks. Serum alanine transminase at the time of sacrifice was measured. Quantitative assessment of liver fibrosis was performed by computerized morphometry. Expression of COX-2, alpha smooth muscle actin and connective tissue growth factor (CTGF) was evaluated by immunohistochemistry. Real-time quantitative PCR was used to determine the expression of genes associated with fibrogenesis and extracellular matrix degradation. RESULTS: Liver fibrosis was significantly worse in rats that received both carbon tetrachloride (CCl4) and celecoxib, compared with rats that received CCl4 and gavage of water (P = 0.037). There was also more HSC activation, and upregulation of collagen alpha1(I), heat-shock protein 47, alphaB crystallin, matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of MMP (TIMP)-2. The expression of TIMP-1 and CTGF was not significantly different between the two groups. The pro-fibrogenic effect of celecoxib in toxin-induced liver fibrosis in rats was further confirmed in thioacetamide model of liver injury. CONCLUSIONS: Celecoxib potentiates experimental liver fibrosis; further studies are warranted to investigate the potential pro-fibrogenic effect of celecoxib in other animal models of liver fibrosis and in patients with chronic hepatitis. 相似文献
58.
59.
Purpose The purpose of the article was to study melt sonocrystallization (MSC) for a drug forming a viscous melt when processed below
its glass transition temperature.
Methods A molten mass of drug was poured in a vessel containing deionized water, maintained at 40°C using cryostatic bath, and sonicated
for 1 min using probe ultrasonicator at an amplitude of 80% and a cycle of 0.8 per second. The product obtained after solidification
of dispersed droplets was separated by filtration and dried at room temperature. MSC celecoxib was characterized by solubility
determination, scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and stability study.
Results The MSC technique was designed for celecoxib, which undergoes fast solidification. The particles obtained by MSC were porous,
irregular in shape, and amorphous in nature. An increase in the apparent solubility was observed for the MSC particles. These
amorphous particles also exhibited a higher stability in the amorphous state as compared with particles obtained by melt quenching.
Conclusions The reported MSC technique for celecoxib demonstrates advantages over other approaches and can be exploited in area of particle
design for the amorphization of drugs. 相似文献
60.
Levin VA Giglio P Puduvalli VK Jochec J Groves MD Yung WK Hess K 《Journal of neuro-oncology》2006,78(1):85-90
Summary In a phase II clinical trial, we sought to determine if combining celecoxib with 13-cis-retinoic acid (13-cRA, Accutane™) was efficacious in the treatment of recurrent (progressive) glioblastoma multiforme (GBM).
In parallel, we also sought to determine to what extent the outcomes from this clinical trial correlated with the findings
from studies utilizing two murine intracerebral GBM models, U87MG and U251HF, to determine the predictive value of these murine
models. In the clinical trial, 25 patients were studied at recurrence. Stable disease, which occurred in 44% of the patients,
was the best response. The median progression-free survival (PFS) was 8 weeks, with a PFS at 6 months of only 19%. For the
patients with stable disease, the median PFS was 24 weeks. The toxicity profile was unremarkable. The modest effect on PFS
seen in this study agreed with the recent findings of another study, which showed a 19% PFS at 6 months in patients treated
with 13-cRA alone. Thus, the combination of 13-cRA with celecoxib is not more effective than 13-cRA in the treatment of progressive
GBM. In the murine model study, we found that long-term dosing with 13-cRA or celecoxib alone or in combination did not increase
survival in animals with U87MG tumors but modestly increased survival in animals with U251HF tumors. There was no evidence
of synergism between the two drugs. From this, we concluded that the animal studies generally predicted that the two agents
would have only a modest effect alone and no additive effect when given in combination to patients. 相似文献