模拟调强技术照射鼻咽低分化鳞癌细胞的生物效应机制研究

Objective To study the altered radiobiological effect of simulative intensity-modulated radiotherapy (SIMR) in cultured human nasopharyngeal carcinoma (NPC) cells and the related mechanism. Methods Single cell suspension of exponentially growing CNE-2 cells, a poor differentiated NPC cell line, was seeded and cultured for 12 hours, then the cells were irradiated in two different models by 6 MV X-ray beams at 3 Gy/min. In single fraction irradiation (SFR) model, cells were irradiated a single fraction of 0, 2, 4, 6 or 8 Gy within 0 to 3 minutes. In S1MR model, cells were irradiated 0, 2, 4, 6 or 8 Gy in 5 frac-tions with interval of 8.0-8.5 minutes between. Clonogenic assay was performed to determine the radiosen-sitivity. Cellular apoptosis was measured by flow cytometry. RT-PCR was used to detect mRNA expressions of Bax and Bcl-2, Respectively. Results Compared with SFR group, the survival fraction in SIMR group was higher at all the dose levels. The values of α, β, D0 and Dq were higher in SIMR group than in SFR group. At dose levels of 2 Gy, 4 Gy and 6 Gy, The early and late apoptotic cells in SIMR group were lower than in SFR group (21.20%: 15.89%, F=18.51, P=0.020;13.00%: 10.20, F=15.67, P=0.040).The mRNA expression of Bax was upregulated in a dose-dependent manner in the both groups. Compared with SFR group, the mRNA expression of Bax in SIMR group was lower at all the dose levels (Mean value of 76.75% : 62.50%, F =36.57, P =0.000). Bcl-2 mRNA expression at every dose level had no significant difference between the two groups (Mean value of 29.25% : 29.75%, F=0.74, P=0.800). Conclusions Prolonged delivery time in SIMR model can decrease the radiobiological effects.     

西妥昔单抗联合放化疗治疗中晚期恶性肿瘤

背景与目的：西妥昔单抗是一种特异性阻断EGFR的单克隆抗体.本研究观察西妥昔单抗联合放化疗治疗晚期头颈部和结直肠癌的有效性和安全性.方法：全组6例患者,均经病理证实,西妥昔单抗联合伊立替康、卡培他滨方案治疗晚期结直肠癌;联合多西他赛、放疗治疗晚期头颈鳞癌.西妥昔单抗首剂400 mg/m2,然后250 mg/m2每周1次维持.结果：6例患者治疗后取得PR 2例,SD 3例,PD 1例,中位TTP 18.5周.其中3例晚期头颈鳞癌患者,PR 1例,SD 2例;3例晚期中分化结直肠癌患者,PR 1例,SD 1例,PD 1例.主要的毒性反应是痤疮样皮疹和腹泻.结论：西妥昔单抗联合多西他赛＋放疗治疗晚期头颈鳞癌,西妥昔单抗联合伊立替康、卡培他滨治疗晚期结直肠癌患者有效.除皮疹之外,毒副反应较单用化疗、放疗无明显增加.     

模拟调强技术照射鼻咽低分化鳞癌细胞的生物效应机制研究

Objective To study the altered radiobiological effect of simulative intensity-modulated radiotherapy (SIMR) in cultured human nasopharyngeal carcinoma (NPC) cells and the related mechanism. Methods Single cell suspension of exponentially growing CNE-2 cells, a poor differentiated NPC cell line, was seeded and cultured for 12 hours, then the cells were irradiated in two different models by 6 MV X-ray beams at 3 Gy/min. In single fraction irradiation (SFR) model, cells were irradiated a single fraction of 0, 2, 4, 6 or 8 Gy within 0 to 3 minutes. In S1MR model, cells were irradiated 0, 2, 4, 6 or 8 Gy in 5 frac-tions with interval of 8.0-8.5 minutes between. Clonogenic assay was performed to determine the radiosen-sitivity. Cellular apoptosis was measured by flow cytometry. RT-PCR was used to detect mRNA expressions of Bax and Bcl-2, Respectively. Results Compared with SFR group, the survival fraction in SIMR group was higher at all the dose levels. The values of α, β, D0 and Dq were higher in SIMR group than in SFR group. At dose levels of 2 Gy, 4 Gy and 6 Gy, The early and late apoptotic cells in SIMR group were lower than in SFR group (21.20%: 15.89%, F=18.51, P=0.020;13.00%: 10.20, F=15.67, P=0.040).The mRNA expression of Bax was upregulated in a dose-dependent manner in the both groups. Compared with SFR group, the mRNA expression of Bax in SIMR group was lower at all the dose levels (Mean value of 76.75% : 62.50%, F =36.57, P =0.000). Bcl-2 mRNA expression at every dose level had no significant difference between the two groups (Mean value of 29.25% : 29.75%, F=0.74, P=0.800). Conclusions Prolonged delivery time in SIMR model can decrease the radiobiological effects.     

模拟调强技术照射鼻咽低分化鳞癌细胞的生物效应机制研究

Objective To study the altered radiobiological effect of simulative intensity-modulated radiotherapy (SIMR) in cultured human nasopharyngeal carcinoma (NPC) cells and the related mechanism. Methods Single cell suspension of exponentially growing CNE-2 cells, a poor differentiated NPC cell line, was seeded and cultured for 12 hours, then the cells were irradiated in two different models by 6 MV X-ray beams at 3 Gy/min. In single fraction irradiation (SFR) model, cells were irradiated a single fraction of 0, 2, 4, 6 or 8 Gy within 0 to 3 minutes. In S1MR model, cells were irradiated 0, 2, 4, 6 or 8 Gy in 5 frac-tions with interval of 8.0-8.5 minutes between. Clonogenic assay was performed to determine the radiosen-sitivity. Cellular apoptosis was measured by flow cytometry. RT-PCR was used to detect mRNA expressions of Bax and Bcl-2, Respectively. Results Compared with SFR group, the survival fraction in SIMR group was higher at all the dose levels. The values of α, β, D0 and Dq were higher in SIMR group than in SFR group. At dose levels of 2 Gy, 4 Gy and 6 Gy, The early and late apoptotic cells in SIMR group were lower than in SFR group (21.20%: 15.89%, F=18.51, P=0.020;13.00%: 10.20, F=15.67, P=0.040).The mRNA expression of Bax was upregulated in a dose-dependent manner in the both groups. Compared with SFR group, the mRNA expression of Bax in SIMR group was lower at all the dose levels (Mean value of 76.75% : 62.50%, F =36.57, P =0.000). Bcl-2 mRNA expression at every dose level had no significant difference between the two groups (Mean value of 29.25% : 29.75%, F=0.74, P=0.800). Conclusions Prolonged delivery time in SIMR model can decrease the radiobiological effects.     

X线立体定向放射治疗脑转移瘤48例疗效观察

目的：评价X线立体定向放射治疗脑转移瘤的临床疗效。方法：对22例脑转移瘤患者采用单纯立体定向放射治疗（SRT），26例脑转移瘤患者行立体定向放射治疗加全脑放射治疗（WBRT）。立体定向放射治疗采用6MV-X线处方量，5～80y／次．每周3次．共3～5次，总计量20～32Gy。全脑照射30～40Gy／3～4周。结果：单纯SRT局部控制率为89．4％．SRT＋WBRT局部控制率为92．3％。2组近期局控率差异无统计学意义（P〉0．05），脑水肿减轻或消失分别为95．5％和92．3％。姑论：立体定向放射治疗对脑转移瘤是安全、有效、痛苦小、疗效明显的治疗方法，可使患者的生存质量有明显改善。     

模拟IMRT对CNE-2细胞周期及Cyclin D1/Cyclin B1表达的影响

目的 探讨模拟调强放射治疗(IMRT)对人鼻咽低分化鳞癌细胞株(CNE-2)细胞周期及细胞周期素Cyclin D1、Cyclin B1转录水平的影响.方法 CNE-2分为急速照射(ART)组和模拟IMRT组,两组分别给予6MV X线2、4、6和8 Gy 四个剂量点的照射;ART组的照射时间为1～3 min,模拟IMRT组的完成时间为35 min.另设空白对照组,不接受照射,其余条件相同.照射后12 h,流式细胞术分析细胞周期分布,RT-PCR检测细胞周期素Cyclin D1和Cyclin B1的转录水平.结果 在相同剂量点,模拟IMRT组G2期细胞比例均低于ART组,两组G2期细胞比例随照射剂量的增加而逐渐增加.模拟IMRT组与ART组在相同剂量点之间比较,Cyclin D1转录水平的差异均无统计学意义(P均＞0.05);Cyclin B1转录水平的差异均有统计学意义(P均<0.05),且随照射剂量的增加而下降,模拟IMRT组Cyclin B1的表达高于ART组.结论 模拟IMRT照射时间延长对G2期阻滞作用下降,细胞周期素Cyclin B1的表达相对升高.     

模拟IMRT模式下相对剂量率变化对CNE-2细胞周期及Cyclin D1、Cyclin B1蛋白表达的影响

目的探讨模拟调强放射治疗（intensity-modulated radiation therapy IMRT）对人鼻咽低分化鳞癌细胞株（CNE-2）细胞周期及Cyclin D1、Cyclin B1蛋白水平的影响。方法选取CNE-2为实验对象,分为空白对照组、急速照射组（acute radiation AR）及模拟IMRT（simulational intensity-modulated radiation SIMR）组,后2组分别给予6MV-X线2、4、6、8 Gy 4个剂量点的照射。急速照射组完成时间1-3分钟;模拟IMRT组：各个剂量点分别等分分割5次,每次间隔8-8.5分钟,总时间35分钟照射完成。应用流式细胞术（FCM）分析细胞周期再分布的差异;应用Western blotting检测细胞周期相关因子Cyclin B1、Cyclin D1的蛋白水平。结果在相同剂量点,模拟IMRT组G2期细胞比例低于急速照射组,G2期细胞比例随照射剂量的增加而逐渐增加。急速照射与模拟IMRT组不同剂量点之间以及在相同剂量点比较,Cyclin D1的蛋白表达差异均无统计学意义（P值均〉0.05）;Cyclin B1的蛋白表达差异均有统计学意义（P值均〈0.05）,且随照射剂量的增加而下降,模拟IMRT组Cyclin B1的表达高于急速照射组。结论模拟IMRT照射时间延长,对G2期阻滞作用下降,细胞周期素Cyclin B1的表达相对升高。     

胸腺肽α1在鼻咽癌治疗中的应用研究

目的：评价胸腺肽α1（Tα1）在鼻咽癌放化疗中的作用.方法：选择新疆医科大学附属肿瘤医院2007-03/2008-12病理确诊的初治鼻咽癌患者42例,随机分成调强放化疗联合胸腺肽α1组（简称Tα1组）与调强放化疗组（简称对照组）,用ELISPOT方法检测放化疗前和放化疗后3个月患者外周血中分泌IFN-γ的特异性细胞毒性T细胞（CTL）的频数变化,比较Tα1组与对照组近期疗效、急性皮肤粘膜反应及骨髓抑制的差异,分析联合应用免疫增强剂后免疫功能的变化.结果：Tα1组和对照组治疗前后外周血中分泌IFN-γ的CTL细胞频数的差异均有统计学意义（P〈0.05）;两组之间CTL细胞频数差异在治疗前后均无统计学意义,但Tα1组患者的CTL细胞增加数目明显高于对照组.两组皮肤、粘膜反应差异有统计学意义,骨髓抑制差异无统计学意义.结论：鼻咽癌患者调强放化疗联合Tα1可能有助于提高患者的特异性细胞免疫能力,减轻放疗引起的急性皮肤、粘膜反应.     

模拟调强放疗照射离体细胞的质量保证

目的：在模拟调强放疗方式照射细胞的过程中，保证细胞按调强方式被照射，照射剂量准确。方法：在细胞培养瓶中装满细胞培养液，水平固定在标准水箱（30cm×30cm×30cm）电离室横梁上，在水箱中加水到电离室上方5cm，用CT机（philips brilliance bigbor CT）扫描获取图像，传到计划系统（ECLIPSE 7．0）中；再用一个空的培养瓶替换装满培养液的培养瓶，重新用CT机扫描，获取图像，传到计划系统中。采用先设野中野后合并野中野的设计方法，设计模拟调强照射计划，设定电离室处的吸收剂量400cGy。再把此水箱放到加速器（Varian 600-C／D）下，按设计的模拟调强照射计划进行照射，同时用电离室（NE 0．6cc）剂量仪（NE FARMER 2570）测量得到实际吸收剂量。结果：在细胞培养瓶中装满细胞培养液时模拟调强照射实测得到397cGy，与理论值相差-0．8％；在细胞培养瓶中不装细胞培养液时模拟调强照射实测得到395cGy，与理论值相差-1.3％。结论：用CT模拟定位，用计划系统通过设野中野的方法设计模拟调强照射计划是可行的，可以实现模拟调强照射离体细胞，理论剂量与实测剂量相差小于2％。     

模拟调强技术照射鼻咽低分化鳞癌细胞的生物效应机制研究

Objective To study the altered radiobiological effect of simulative intensity-modulated radiotherapy (SIMR) in cultured human nasopharyngeal carcinoma (NPC) cells and the related mechanism. Methods Single cell suspension of exponentially growing CNE-2 cells, a poor differentiated NPC cell line, was seeded and cultured for 12 hours, then the cells were irradiated in two different models by 6 MV X-ray beams at 3 Gy/min. In single fraction irradiation (SFR) model, cells were irradiated a single fraction of 0, 2, 4, 6 or 8 Gy within 0 to 3 minutes. In S1MR model, cells were irradiated 0, 2, 4, 6 or 8 Gy in 5 frac-tions with interval of 8.0-8.5 minutes between. Clonogenic assay was performed to determine the radiosen-sitivity. Cellular apoptosis was measured by flow cytometry. RT-PCR was used to detect mRNA expressions of Bax and Bcl-2, Respectively. Results Compared with SFR group, the survival fraction in SIMR group was higher at all the dose levels. The values of α, β, D0 and Dq were higher in SIMR group than in SFR group. At dose levels of 2 Gy, 4 Gy and 6 Gy, The early and late apoptotic cells in SIMR group were lower than in SFR group (21.20%: 15.89%, F=18.51, P=0.020;13.00%: 10.20, F=15.67, P=0.040).The mRNA expression of Bax was upregulated in a dose-dependent manner in the both groups. Compared with SFR group, the mRNA expression of Bax in SIMR group was lower at all the dose levels (Mean value of 76.75% : 62.50%, F =36.57, P =0.000). Bcl-2 mRNA expression at every dose level had no significant difference between the two groups (Mean value of 29.25% : 29.75%, F=0.74, P=0.800). Conclusions Prolonged delivery time in SIMR model can decrease the radiobiological effects.