塞来昔布对肿瘤放射治疗的增敏作用

目的探讨塞来昔布对肿瘤放射治疗的增敏作用。方法选取2014年1月至2015年6月间德阳市第二人民医院收治的60例肿瘤患者,采用随机数法分为观察组和对照组,每组30例。观察组患者采用塞来昔布辅助放射治疗,对照组患者采用单纯放射治疗。比较两组患者临床疗效及不良反应。结果观察组原发灶退缩有效率83.3%,淋巴结退缩有效率78.9%,较对照组的70.0%和66.7%,差异无统计学意义(P>0.05)。所有患者均出现放射性皮炎,观察组胃肠道反应、白细胞减少和肝功能异常发生率分别为10.0%、10.0%和0.0%,较对照组的6.7%、10.0%和3.3%差异均无统计学意义(均P>0.05)。结论塞来昔布辅助放射治疗肿瘤的疗效、不良反应与单纯放疗类似,即塞来昔布对放射增敏作用不明显。     

塞来昔布对人鼻咽癌CNE-2细胞放疗的增敏作用

目的:探讨塞来昔布对人鼻咽癌CNE-2细胞的放射增敏作用及其可能机制。方法:四唑盐比色法（MTT）测定塞来昔布对人鼻咽癌CNE-2细胞株的抑制率。采用克隆形成实验检测塞来昔布处理的CNE-2细胞经不同剂量X 线(0、2、4、6、8 和10Gy)照射后的存活分数(SF),并通过单击多靶模型拟合细胞存活曲线,计算增敏比(SER)。流式细胞仪（FCM）分析细胞周期分布及凋亡率。结果:MTT实验显示塞来昔布在（10～80）μg/ml范围内对CNE-2细胞有抑制作用,抑制率与浓度、时间呈依赖关系;在2～10Gy照射范围内,10、20、40、80μg/ml塞来昔布处理后的SF均低于0μg/ml(P<0.05),且SF随塞来昔布浓度的增加而降低;相对于0μg/ml,10、20、40、80μg/ml塞来昔布处理后的SER分别为1.06、1.79、2.29 和3.34;流式细胞仪测得塞来昔布可呈浓度依赖的方式诱导CNE-2细胞凋亡(P<0.05),S期细胞比例降低,G2/M期细胞比例升高。结论:塞来昔布能抑制人鼻咽癌CNE-2细胞增殖,诱导CNE-2细胞细胞周期阻滞,促进细胞凋亡,具有放疗增敏作用。     

塞来昔布对乳腺癌细胞株的放射增敏作用

背景与目的:塞来昔布(celecoxib)能有效增强放射线对肿瘤的作用,但其作用机制尚不清楚.本研究探讨塞来昔布对人乳腺癌MDA-MB-231细胞放射增敏的作用机制.方法:取对数生长期MDA-MB-231细胞株2×106个,分为对照组、药物组、照射组及实验组(照射线联合塞来昔布),流式细胞分析法(flowcytometry,FCM)检测各组细胞凋亡率;克隆形成实验检测放射增敏作用;Western blot法检测Akt、pAkt蛋白表达.结果:实验组凋亡率[(31.20±1.27)%]显著高于照射组[(17.99±1.01)%](t=14.01,P<0.05);与照射组相比较,实验组反映放射敏感性的指标准域剂量(Dq)、平均致死剂量(D0)、2 Gy照射的存活分数(SF2)值均显著降低(0.437 vs 1.175,1.874 vs 2.394,0.52 vs 0.79),放射增敏比(SERD0)为1.277;各组Akt蛋白表达无明显差异,但塞来昔布能抑制pAkt的表达,而放射线能上调其表达,两者联合使用对pAkt表达有明显抑制作用(P<0.05).结论:塞来昔布对人乳腺癌MDA-MB-231细胞有放射增敏作用,其可能的机制是阻断PI3K/Akt信号通路的活化,从而提高乳腺癌放射敏感性.     

塞来昔布对宫颈癌细胞的化疗增敏作用

目的探讨特异性环氧化酶-2（COX-2）抑制剂塞来昔布对顺铂诱导宫颈癌Hela细胞增殖与凋亡的作用及机制。方法采用四甲基偶氮唑蓝比色法（MTT）,测定塞来昔布对顺铂诱导Hela细胞增殖活性的作用;应用流式细胞仪检测细胞凋亡率;Western blot检测Hela细胞中Bcl-2、Bax蛋白的表达情况。结果 5、10μmol/L的塞来昔布分别与顺铂联合应用,可增强顺铂对Hela细胞增殖抑制作用。塞来昔布（5μmol/L）能促进顺铂诱导Hela细胞的凋亡。塞来昔布作用于Hela细胞后,Bcl-2蛋白表达水平下调、Bax蛋白表达水平上调呈浓度依赖关系。结论塞来昔布能促进顺铂对Hela细胞增殖抑制和诱导凋亡作用,起化疗增敏作用,可能与其下调Bcl-2蛋白表达水平、上调Bax蛋白表达水平有关。     

塞来昔布对胃癌BGC823细胞的放射增敏作用

目的：探讨环氧化酶2（COX-2）抑制剂塞来昔布对人胃癌BGC823细胞株的放射增敏作用及其机制。方法：MTT实验测定塞来昔布对胃癌BGC823细胞株的抑制率,计算半数抑制浓度（IC50）。克隆形成实验检测塞来昔布联合不同剂量X线照射后细胞的存活率,计算放射敏感性相关参数,评价增敏效果。流式细胞仪（FCM）分析细胞周期分布情况。结果：MTT实验显示塞来昔布对BGC823细胞作用24h、48h、72h的IC50分别是162.6μmol/L、95.4μmol/L、62.1μmol/L;克隆形成实验测得联合组的D0、Dq及SF2均明显低于单纯照射组（1.705VS 2.185,1.032VS 2.327,0.495 VS 0.745）,SER为1.3。流式细胞仪检测联合组G0/G1期细胞增多,S期细胞减少。结论：塞来昔布能增强胃癌BGC823细胞的放射敏感性,其机制可能与减少肿瘤细胞亚致死性损伤修复和细胞周期再分布有关。     

塞来昔布对人肝癌细胞增殖抑制及放疗增敏作用

目的探讨塞来昔布对肝癌细胞huh-7增殖抑制及放疗增敏作用。方法以人肝癌细胞株huh-7为研究对象,以塞来昔布和高能射线作为干预手段,采用四唑氮蓝还原法(MTT),检测不同浓度塞来昔布和作用不同时间对huh-7细胞的增殖抑制作用,采用流式细胞技术,检测塞来昔布联合放疗对huh-7细胞凋亡和周期的影响。结果 MTT显示塞来昔布对人肝癌细胞huh-7生长有显著抑制作用,且呈时间和剂量依赖性;塞来昔布对肝癌放疗具有明显增敏作用。与对照组比较,药物组G0/G1期细胞比例增加,S期细胞比例减少,G2/M变化无明显意义;照射组G2/M期细胞比例升高,联合组G0/G1期细胞比例增加,S期细胞比例减少。结论塞来昔布能提高人肝癌细胞株huh-7放疗敏感性作用,其作用可能是通过诱导细胞凋亡、改变细胞周期时相分布来实现的。     

塞来昔布对人鼻咽癌CNE-2细胞生长抑制及放射增敏研究

Objective To investigate the growth inhibition and radiosensitization of Celecoxib in hu-man nasopharyngeal carcinoma cell line CNE-2. Methods CNE-2 growth inhibition by Celecoxib was eval-uated by MTT method. Apoptosis-related changes in morphology were observed by transmission electron mi-croscopy (TEM). Cell cycle distribution and apoptosis rate were measured by flowcytometry (FCM). The ex-pression of COX-2 protein was observed by SP method after the treatment of Celecoxib. Cells were randomly planted into four groups: irradiation control(Ci), drug group(Cd), irradiation group(R), and Celecoxib plus irradiation group(D+R). Single irradiation of 2,4,6,8,and 10 Gy were administered for colonogenic assay. Cell cycle distribution and apoptosis rate were analyzed at 6 Gy irradiation. Results The growth of CNE-2 cell was inhibited by celecoxib in a dose-and time-dependent manner, the IC50 was 80 μmol/L After the treatment, cell ratio of GO and G, phases was increased (47.03±2.76 vs 56.17±1.95, t=4.68, P= 0.010), whereas the ratio of S and G2/M phases was decreased (33.07±1.86 vs 24.87±1.76, t=5.54, P = 0.010; 19.30±0.53: 17.73±0.83, t=2.75, P=0.050), and the apoptosis rate was increased (1.57±0.47:10.47±0.31, t = 27.39, P = 0.000) in a dose-dependent manner. Apoptosis with nuclear chromatin condensation, fragmentation and cell shrinkage was found by TEM. SP method showed that Celeib decreased COX-2 expression (17.48±0.34 vs 12.82±0.51,t=13.20,P =0.00). The sensitivity ratio(D0) was 1.15. FCM showed that the percentage of cells in G2/M phase was significanty more in R and D+R groups than in Ci and Cd groups (68.00±1.65,54.27±5.74,17.60±0.80,14.86±1.23, t=47.70,P=0.000; t=11.63, P=0.000), and also significantly different between R group and D + R group (t=3.99, P= 0.020). The apoptosis rate was higher in R and D + R groups than Ci and Cd groups(4.83±0.97,9.50± 1.35,1.33±0.86 and 2.28±0.42,t=4.67,P=0.010;t=8.81, P=0.000), D + R group than R group(t =4.85,P=0.010). Conclusions Celecoxib can markedly inhibit the growth and induce apoptosis in CNE-2 cells,which may depend on COX-2 pathway. Celeeoxib potently enhances the radiosensitivity of CNE-2 cells,which may due to the repair inhibit of radiation-induced DNA damage, inhibit of cell proliferation,and enhancement of cell apoptosis after irradiation.     

塞来昔布对人鼻咽癌CNE-2细胞生长抑制及放射增敏研究

目的 研究塞来昔布对人鼻咽癌细胞系CNE-2细胞生长影响及有无放射增敏作用.方法 (1)细胞生长抑制研究:用MTT法检测细胞生长抑制,流式细胞术检测细胞周期分布及凋亡,透射电子显微镜观察细胞凋亡形态,SP法检测细胞COX-2表达.(2)放射增敏研究:随机设置照射对照、药物对照、单纯照射、药物+照射组,其中成克隆实验单次照射2、4、6、8、10 Gy,细胞周期分布和凋亡实验单次照射6 Gy.结果 塞来昔布显著抑制CNE-2细胞生长并呈浓度和时间依赖性,IC50为80 μmol/L.细胞周期分布显示G0+G1期细胞显著升高(47.03±2.76:56.17±1.95,t=4.68,P=0.010),而S、G2+M期细胞明显下降(33.07±1.86:24.87±1.76,t=5.54,P=0.010;19.30±0.53:17.73±0.83.t=2.75,P=0.050)并呈浓度依赖性.凋亡率显著增高(1.57±0.47:10.47±0.31,t=27.39,P=0.000)并呈浓度依赖性.电镜观察到细胞皱缩、核质浓缩、核碎裂等凋亡形态学改变.SP法检测塞来昔布显著下调CNE-2中COX-2表达[17.48±0.34、12.82±0.51(t=13.20,P=0.00)].塞来昔布的放射增敏比(D0值比为1.74:1.52)为1.15.4个组别细胞周期分布结果 显示单纯照射、药物+照射组的G2+M期细胞明显高于照射对照、药物对照组(68.00±1.65、54.27±5.74、17.60±0.80、14.86±1.23,t=47.70,P=0.000;t=11.63,P=0.000),且单纯照射与药物+照射组间也不同(t=3.99,P=0.020);单纯照射、药物+照射组的细胞凋亡率也明显高于照射对照、药物对照组(4.83±0.97、9.50±1.35、1.33±0.36、2.28±0.42,t=4.67,P=0.01;t=8.81,P=0.000),且单纯照射与药物+照射组也不同(t=4.85,P=0.010).结论 塞来昔布能抑制人鼻咽癌CNE-2细胞生长和诱导凋亡,其机制可能涉及COX-2依赖途径.塞来昔布还能增强CNE-2细胞放射敏感性,可能机制与抑制放射后亚致死损伤修复、直接抑制细胞增殖和增强细胞对放射诱导凋亡率有关.     

塞来昔布对人鼻咽癌CNE-2细胞生长抑制及放射增敏研究

Objective To investigate the growth inhibition and radiosensitization of Celecoxib in hu-man nasopharyngeal carcinoma cell line CNE-2. Methods CNE-2 growth inhibition by Celecoxib was eval-uated by MTT method. Apoptosis-related changes in morphology were observed by transmission electron mi-croscopy (TEM). Cell cycle distribution and apoptosis rate were measured by flowcytometry (FCM). The ex-pression of COX-2 protein was observed by SP method after the treatment of Celecoxib. Cells were randomly planted into four groups: irradiation control(Ci), drug group(Cd), irradiation group(R), and Celecoxib plus irradiation group(D+R). Single irradiation of 2,4,6,8,and 10 Gy were administered for colonogenic assay. Cell cycle distribution and apoptosis rate were analyzed at 6 Gy irradiation. Results The growth of CNE-2 cell was inhibited by celecoxib in a dose-and time-dependent manner, the IC50 was 80 μmol/L After the treatment, cell ratio of GO and G, phases was increased (47.03±2.76 vs 56.17±1.95, t=4.68, P= 0.010), whereas the ratio of S and G2/M phases was decreased (33.07±1.86 vs 24.87±1.76, t=5.54, P = 0.010; 19.30±0.53: 17.73±0.83, t=2.75, P=0.050), and the apoptosis rate was increased (1.57±0.47:10.47±0.31, t = 27.39, P = 0.000) in a dose-dependent manner. Apoptosis with nuclear chromatin condensation, fragmentation and cell shrinkage was found by TEM. SP method showed that Celeib decreased COX-2 expression (17.48±0.34 vs 12.82±0.51,t=13.20,P =0.00). The sensitivity ratio(D0) was 1.15. FCM showed that the percentage of cells in G2/M phase was significanty more in R and D+R groups than in Ci and Cd groups (68.00±1.65,54.27±5.74,17.60±0.80,14.86±1.23, t=47.70,P=0.000; t=11.63, P=0.000), and also significantly different between R group and D + R group (t=3.99, P= 0.020). The apoptosis rate was higher in R and D + R groups than Ci and Cd groups(4.83±0.97,9.50± 1.35,1.33±0.86 and 2.28±0.42,t=4.67,P=0.010;t=8.81, P=0.000), D + R group than R group(t =4.85,P=0.010). Conclusions Celecoxib can markedly inhibit the growth and induce apoptosis in CNE-2 cells,which may depend on COX-2 pathway. Celeeoxib potently enhances the radiosensitivity of CNE-2 cells,which may due to the repair inhibit of radiation-induced DNA damage, inhibit of cell proliferation,and enhancement of cell apoptosis after irradiation.     

塞来昔布对人鼻咽癌CNE-2细胞生长抑制及放射增敏研究

Objective To investigate the growth inhibition and radiosensitization of Celecoxib in hu-man nasopharyngeal carcinoma cell line CNE-2. Methods CNE-2 growth inhibition by Celecoxib was eval-uated by MTT method. Apoptosis-related changes in morphology were observed by transmission electron mi-croscopy (TEM). Cell cycle distribution and apoptosis rate were measured by flowcytometry (FCM). The ex-pression of COX-2 protein was observed by SP method after the treatment of Celecoxib. Cells were randomly planted into four groups: irradiation control(Ci), drug group(Cd), irradiation group(R), and Celecoxib plus irradiation group(D+R). Single irradiation of 2,4,6,8,and 10 Gy were administered for colonogenic assay. Cell cycle distribution and apoptosis rate were analyzed at 6 Gy irradiation. Results The growth of CNE-2 cell was inhibited by celecoxib in a dose-and time-dependent manner, the IC50 was 80 μmol/L After the treatment, cell ratio of GO and G, phases was increased (47.03±2.76 vs 56.17±1.95, t=4.68, P= 0.010), whereas the ratio of S and G2/M phases was decreased (33.07±1.86 vs 24.87±1.76, t=5.54, P = 0.010; 19.30±0.53: 17.73±0.83, t=2.75, P=0.050), and the apoptosis rate was increased (1.57±0.47:10.47±0.31, t = 27.39, P = 0.000) in a dose-dependent manner. Apoptosis with nuclear chromatin condensation, fragmentation and cell shrinkage was found by TEM. SP method showed that Celeib decreased COX-2 expression (17.48±0.34 vs 12.82±0.51,t=13.20,P =0.00). The sensitivity ratio(D0) was 1.15. FCM showed that the percentage of cells in G2/M phase was significanty more in R and D+R groups than in Ci and Cd groups (68.00±1.65,54.27±5.74,17.60±0.80,14.86±1.23, t=47.70,P=0.000; t=11.63, P=0.000), and also significantly different between R group and D + R group (t=3.99, P= 0.020). The apoptosis rate was higher in R and D + R groups than Ci and Cd groups(4.83±0.97,9.50± 1.35,1.33±0.86 and 2.28±0.42,t=4.67,P=0.010;t=8.81, P=0.000), D + R group than R group(t =4.85,P=0.010). Conclusions Celecoxib can markedly inhibit the growth and induce apoptosis in CNE-2 cells,which may depend on COX-2 pathway. Celeeoxib potently enhances the radiosensitivity of CNE-2 cells,which may due to the repair inhibit of radiation-induced DNA damage, inhibit of cell proliferation,and enhancement of cell apoptosis after irradiation.     

尼妥珠单抗联合放化疗治疗局部晚期鼻咽癌的临床观察

目的 评价尼妥珠单抗联合放化疗治疗局部晚期鼻咽癌的近期疗效和患者不良反应.方法 回顾性分析尼妥珠单抗联合放化疗治疗42例局部晚期鼻咽癌的近期疗效和患者不良反应.所有患者采用调强放疗（IMRT）技术,鼻咽原发灶处方剂量70 ～ 78.2 Gy,32 ～ 37次,41 ～49 d,颈部淋巴结65 ～ 76 Gy,32～37次,41 ～ 49 d;放疗同时每周应用尼妥珠单抗;全身化疗方案以（多西）紫杉醇＋奈达铂（TP）、复方氟尿嘧啶＋奈达铂（FP）及（多西）紫杉醇＋复方氟尿嘧啶＋奈达铂（TFP）为主.结果 主要不良反应为口腔黏膜炎、骨髓抑制、放射性皮炎和口腔干燥.其中1～2级、3级口腔黏膜炎分别有29例（69.0％）、2例（4.8％）,未出现4级黏膜炎;白细胞下降1～2级、3～4级分别为25例（59.5％）、16例（38.1％）,未发生白细胞减少性发热.全组无痤疮型皮疹、过敏反应及治疗相关的死亡.治疗结束后1个月疗效评价,完全缓解（CR）率90.5％（38/42）,部分缓解（PR）率9.5 ％（4/42）,总有效率100％;其中鼻咽原发灶CR率92.9％（39/42）、PR率7.1％（3/42）,颈部阳性淋巴结CR率97.6％（41/42）,PR率2.4％（1/42）.中位随访22.5个月,1年局部区域控制率100％,1年无远处转移生存率92.7％,1年总生存率95.2％.结论 尼妥珠单抗联合放化疗治疗局部晚期鼻咽癌近期疗效良好,不良反应轻微可耐受.     

Chk1 inhibitor Gö6976 enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy in vitro and in vivo

Nasopharyngeal carcinoma (NPC) is a malignant tumor. This type of carcinoma has a low 5-year patient survival rate. Thus, there is a need for improved therapeutics. We determined that the Chk1 inhibitor Gö6976 enhanced the sensitivity of CNE1 and CNE2 cells to ionizing radiation (IR) or cisplatin by abrogating S and G₂/M arrest and subsequently promoting apoptosis. Furthermore, Gö6976 appeared to sensitize NPC xenografts in nude mice to IR or cisplatin treatment. This is the first report to show that the Chk1 inhibitor Gö6976 sensitizes NPC cells to treatment using in vitro and in vivo models.     

鼻咽癌推量放疗研究进展

鼻咽癌的治疗仍以外照射为主,常规放疗鼻咽癌的5年生存率为36%～58%。既往常规外照射方式限制了照射剂量的个体化,局部残存是放射治疗失败的一个主要原因。对持续存在的鼻咽癌进行推量的方法颇多,目前多采用近距离放疗、立体定向放射外科(SRS)、调强放疗(IMRT)等方法,但哪一种方法较优,仍没有一个系统的分析。     

鼻咽癌调强放射治疗进展

鼻咽癌的主要治疗方式是放射治疗.调强放疗技术具有很大优势,计划设计个体化,靶区剂鼍分布安全合理.与常规放疗相比,调强放疗提高了疗效,减少了并发症.因此调强放疗将成为鼻咽癌治疗的更重要的方式.     

鼻咽癌推量放疗研究进展

鼻咽癌的治疗仍以外照射为主，常规放疗鼻咽癌的5年生存率为36％～58％。既往常规外照射方式限制了照射剂量的个体化，局部残存是放射治疗失败的一个主要原因。对持续存在的鼻咽癌进行推量的方法颇多，目前多采用近距离放疗、立体定向放射外科（SRS）、调强放疗（IMRT）等方法，但哪一种方法较优，仍没有一个系统的分析。     

同步放化疗对局部晚期鼻咽癌患者营养状况的影响

目的研究调查分析同步三维适形放疗联合化疗对局部晚期鼻咽癌患者营养状况的影响。方法回顾性调查分析我院89例接受同步三维适形放疗联合化疗的局部晚期鼻咽癌患者治疗前后的营养相关生化指标及体重和身体质量指数(BMI)的变化。结果所有患者均有体重下降,83.1%的患者体重下降明显。同步放化疗前后患者血浆白蛋白浓度和血浆甘油三酯浓度比较,差异有显著性(P<0.05)。而患者血浆总蛋白,钙、镁离子浓度在治疗前后无显著变化。结论同步放化疗对局部晚期鼻咽癌患者的营养相关指标有显著影响,尤其是血浆白蛋白和甘油三酯浓度。     

鼻咽癌化疗研究进展

局部晚期鼻咽癌治疗失败的主要原因为远处转移和局部复发。鼻咽癌对化疗比较敏感．化疗联合放疗可提高治疗获益。目前同步放化疗已成为局部晚期鼻咽癌的标准治疗。新辅助化疗也开始显示出良好疗效。     

鼻咽癌化疗研究进展

局部晚期鼻咽癌治疗失败的主要原因为远处转移和局部复发。鼻咽癌对化疗比较敏感,化疗联合放疗可提高治疗获益。目前同步放化疗已成为局部晚期鼻咽癌的标准治疗。新辅助化疗也开始显示出良好疗效。     

塞来昔布联合放射对人鼻咽癌细胞生物效应的研究

目的 探讨COX-2选择性抑制剂塞来昔布联合放射对CNE-1细胞存活和凋亡的影响，并初步探讨其与药物浓度之间的相关性。方法 选择鼻咽癌CNE-1细胞系作为实验对象，以药物浓度0、1．25、2．50、5．00μmol／L设A、B、C、D实验组。4个组分别予6MVX线照射0、2、4、6Gy后分别行成克隆实验、流式细胞仪检测细胞存活分数（SF）及细胞早、晚期凋亡率。结果B、C、D组与A组之间SF值及晚期凋亡率差异有统计学意义（P〈0．05）；B组与C、D组之间差异有统计学意义（P〈0．05）；C组与D组间SF值、晚期凋亡率差异无统计学意义（P〉0．05）；各组间早期凋亡率差异无统计学意义（P〉0．05）。结论塞来昔布联合放射对CNE-1细胞存活下降和晚期凋亡增加有影响，并随药物浓度增加而增加，且在2．50μmol／L达最高值，但对早期凋亡无影响。     

鼻咽癌调强放疗存在的问题

调强放射治疗因其卓越的剂量学优势使得放射治疗进入了一个崭新的时代,在靶区形状特殊的鼻咽癌治疗中应用尤其广泛.但是,鼻咽癌调强放疗中靶区确定、剂量限定、危及器官保护等方面尚存在一些待解决的问题.