铁死亡在胶质瘤治疗领域的作用

爱拉斯汀（Erastin）通过抑制SLC7A11摄取胱氨酸/谷氨酸的能力引起铁死亡（一种非细胞凋亡，坏死性凋亡和自噬形式的细胞死亡方式）.然而，铁死亡调节的分子机制仍然很大程度上未知.研究铁死亡对胶质细胞的影响对胶质瘤的治疗具有重要作用.本文利用MTS法和细胞计数器分别对加药组细胞和辐照后的细胞进行计数.加入不同浓度的Erastin培养野生型胶质瘤细胞U87MG和P53突变型胶质瘤细胞U251MG，本文发现U87MG对Erastin敏感.伽马射线不能进一步促进Erastin引起的铁死亡.具有抗氧化作用的传统中药龙血竭能有效抑制Erastin引起的铁死亡.总之，本文发现Erastin在胶质瘤化疗领域的重要作用，同时龙血竭在抑制铁死亡和保护健康细胞方面具有重要作用.     

颅内胶质瘤术后放疗43例临床分析

目的：回顾总结４３例脑胶质瘤术后放疗的病例，分析影响预后的因素。方法：１９８８年３月至１９９２年１２月，４３例经术后病理证实为脑胶质瘤的病例。其中手术部分切除３７例（８６％），肉眼全切６例（１４％），术后放疗采用＾６０Ｃｏγ线。放射剂量为３０￣６０Ｇｙ，常规分割。结果：４３例总５年生存率２５．６％。高分级组１、３、５年生存率分别为７２％、２０％、１２％，低分级组的１、３、５年生存率分别为７２．２％     

腺病毒载体介导胸苷激酶基因/ACV对大鼠脑胶质瘤的离体和活体杀伤作用

建立缺陷型重组腺病毒载体介导的胸苷激酶基因治疗系统（Adtk／ACV）,进行离休和活体治疗大鼠C6脑胶质瘤研究．将质粒pAdtk与pJM17共转染腺病毒包装细胞──293细胞,同源重组后制备纯化的Adtk并以PCR证实;Adtk对离休C6细胞的杀伤作用随着Adtk滴度和ACV剂量增加而增强,并有旁观者效应,而未转染C6细胞和AdLacZ转染C6细胞均未被杀伤;扫描电镜下见Adtk／ACV处理的细胞呈明显病理改变;ACV可有效杀伤Adtk／C6细胞．在大鼠脑立体定向仪引导下于右额叶接种2×106个C6细胞,分别于第3,6,8和10天原位注射Adtk,同时腹腔注射ACV（100mg／（kg·d-1））,3d组、6d组、8d组大鼠成活期在90d以上,组织学检查未发现肿瘤细胞．10d组成活期（28．5±4．6）d,而C6未治疗组和AdLacZ／ACV治疗组成活期分别为（1．8±3．1）d和（14．0±2．2）d．本文建立的Adtk／ACV在离体和活体水平对大鼠C6脑胶质瘤有强烈的杀伤作用,效果确实,应用方便,ACV价格便宜,有潜在临床应用价值．     

边缘系统低级别胶质瘤的诊断与手术治疗

目的 :探讨边缘系统低级别胶质瘤的诊断、手术治疗及其效果。方法 :对1997年7月至2003年7月应用显微手术广泛性切除的13例边缘系统低级别胶质瘤作回顾性分析。结果 :13例均行肿瘤切除 ,9例全切除 ,4例次全切除 ,术后除2例出现暂时性失语外 ,均恢复良好 ,术后无严重的手术并发症和死亡。结论 :边缘系统低级别胶质瘤源于原始皮质 ,可通过手术广泛性切除肿瘤而不致损伤重要功能结构 ,可很好地控制癫痫。     

运用HSV－tk／ACV系统进行肿瘤基因治疗研究

构建了含ｐｇｋ启动子驱动的ＨＳＶ－ｔｋ基因的反转录病毒载体ｐＬＮＴＫ，将ＨＳＶ－ｔｋ基因转移至人脑胶质瘤ＳＨＧ４４细胞（命名为ＳＨＧＬＮＴＫ）及小鼠黑色素瘤细胞Ｂ１６（命名为Ｂ１６ＬＮＴＫ）．体外实验证实核着类似物ＡＣＶ对ＳＨＧＬＮＴＫ细胞和Ｂ１６ＬＮＴＫ细胞的杀伤敏感性分别高于亲本细胞１０００和４００倍．转ＨＳＶ－ｔｋ基因细胞与亲本细胞按不同比例共培养时，亲本细胞对ＡＣＶ的敏感性明显增高，存在旁观者效应．首次应用人脑胶质瘤细胞株进行裸鼠体内实验，结果表明：ＡＣＶ能完全抑制ＳＨＧＬＮＴＫ细胞在裸小鼠体内肿瘤的形成，对裸小鼠体内已形成的ＳＨＧＬＮＴＫ肿瘤的治疗效果与对照ＳＨＧ４４肿瘤相比，肿瘤体积缩小８０％；用Ｂ１６ＬＮＴＫ细胞接种同系Ｃ５７／ＢＬ小鼠，经ＡＣＶ治疗后，Ｂ１６ＬＮＴＫ组小鼠的肿瘤较对照组Ｂ１６肿瘤小９５％．ＨＳＶ－ＴＫ／ＡＣＶ系统原位基因转移治疗ＳＨＧ荷瘤裸小鼠、Ｂ１６荷瘤小鼠，原位注射病毒悬液／ＡＣＶ治疗组的ＳＨＧ肿瘤、Ｂ１６肿瘤分别较对照组肿瘤小５０％，４３％，原位注射ＰＡ３１７／ＬＮＴＫ细胞，ＡＣＶ治疗的ＳＨＧ肿瘤较对照组肿瘤小９０％，以上实验结果，统计学上差异极显著，Ｐ＜０．０１．实验     

MRI表现在脑胶质瘤恶性度诊断中的作用

本文比较了１０７例脑胶质瘤的病理分级与磁共振影像表现,结果显示两者之间有密切的关系（Ｐ＜０００５）。高度恶性胶质瘤中,ＭＲＩ诊断正确率为８８１０％,而低度恶性胶质瘤中为６４６２％（Ｐ＜０００５）。各单项ＭＲＩ表现,如病灶强化程度、瘤周水肿程度、囊变、坏死等在高或低度恶性胶质瘤中出现率无明显差异（Ｐ值均大于００５）。表明ＭＲＩ表现可在很大程度上反映脑胶质瘤的恶性程度,但在低度恶性胶质瘤中,易出现“过诊断现象”。     

Chemotherapy and immunotherapy of malignant glioma: molecular mechanisms and clinical perspectives

Despite the considerable progress in modern tumor therapy, the prognosis for patients with glioblastoma, the most frequent malignant brain tumor, has not been substantially improved. Although cytoreductive surgery and radiotherapy are the mainstays of treatment for malignant glioma at present, novel cytotoxic drugs and immunotherapeutic approaches hold great promise as effective weapons against these malignancies. Thus, great efforts are being made to enhance antitumoral efficacy by combining various cytotoxic agents, by novel routes of drug administration, or by combining anticancer drugs and immune modulators. Immunotherapeutic approaches include cytotoxic cytokines, targeted antibodies, and vaccination strategies. However, the success of most of these experimental therapies is prevented by the marked molecular resistance of glioma cells to diverse cytotoxic agents or by glioma-associated immunosuppression. One promising experimental strategy to target glioma is the employment of death ligands such as CD95 (Fas/Apo1) ligand or Apo2 ligand (TRAIL). Specific proapoptotic approaches may overcome many of the obvious obstacles to a satisfactory management of malignant brain tumors. Received 8 March 1999; received after revision 27 May 1999; accepted 14 June 1999     

羟基磷灰石纳米粒子运载Stat3 shRNA对鼠胶质瘤C6细胞的促凋亡效应

目的探讨羟基磷灰石纳米粒子运载Stat3 shRNA对鼠胶质瘤C6细胞的促凋亡作用,并探讨相关机制.方法羟基磷灰石纳米粒子包被的Stat3 shRNA转染到C6胶质瘤细胞内,MTT法检测细胞增殖情况,应用流式细胞术及吖啶橙染色观察细胞周期分布及凋亡情况,TUNEL染色观察细胞的凋亡及增殖情况.结果羟基磷灰石纳米粒子运载Stat3 shRNA转染C6细胞后,呈时间依赖性抑制C6细胞生长和增殖.通过流式细胞术检测证实:该质粒可使细胞阻滞在细胞周期的G0/G1期,细胞凋亡率明显增加(P<0.05),与对照组比较差异有统计学意义;吖啶橙及TUNEL染色发现其明显促进细胞凋亡(P<0.05),与对照组比较差异有统计学意义;结论羟基磷灰石纳米粒子运载Stat3 shRNA体外可明显抑制胶质瘤C6细胞增殖,并促进其凋亡,是治疗胶质瘤较理想的方法.     

化疗作用对C6胶质瘤细胞药物敏感性的实验研究

通过几种化疗药物对C6胶质瘤细胞的药敏实验，观察化疗药物加增敏剂（NMD）后，单独化疗和联合化疗药物的敏感性，为临床提从有效的治疗依据，利用体外细胞培养，采用MTT和^3H-TDR方法，分别测定几种休疗药物单独使用和联合使用对肿瘤的抑制率，BCNU，Vm-26两种化疗药物联合使用加增敏剂，使药物浓度降低了100倍，其对细胞的抑制率可达97．04％，高于BCNU＋NMD的抑制效果，也明显高于Vm-26 NMD的抑制效果，联合用药优于单独用药，具有低浓度，低毒，高效的作用，同时也增加了药物对瘤组织的抑制作用，说明联合用药，具有协同和相加作用。     

TRAIL induces proliferation of human glioma cells by c-FLIPL-mediated activation of ERK1/2

TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in TRAIL-sensitive human malignant glioma cells. We show for the first time that TRAIL stimulates cell growth in TRAIL-resistant glioma cells. TRAIL-induced cell growth in resistant cells occurred through increased cell cycle progression as determined by flow cytometry and Western blot analysis of retinoblastoma protein phosphorylation. Western blot analysis of TRAIL-treated resistant cells revealed phosphorylation of ERK1/2 proteins and in vitro kinase analysis confirmed the activation of the ERK1/2 kinases. Inhibition of MEK1 eliminated both TRAIL-induced ERK1/2 activation and cell proliferation. In addition, siRNA inhibition of c-FLIP expression eliminates TRAIL-induced ERK1/2 activation and proliferation. Furthermore, overexpression of c-FLIP_L potentiates TRAIL-induced ERK1/2 activation and proliferation of resistant glioma cells. Our results have shown for the first time that TRAIL-induced ERK1/2 activation and proliferation of TRAIL-resistant human glioma cells is dependent upon the expression of the long form of the caspase-8 inhibitor c-FLIP_L. Received 2 November 2007; received after revision 14 December 2007; accepted 21 December 2007