卡氮芥联合全反式维甲酸诱导脑胶质瘤的凋亡及其分子机制

C6、U251细胞G1期比例分别由(42.18±2.52)%至(63.04±4.05)%、(57.14±2.52)%至(69.50±4.05)%,C6、U251细胞凋亡率2.46±1.02至17.43±2.03、10.36±1.76至21.32±2.03;Cyclin E、CDK2 mRNA表达下调,p27Kip1 mRNA表达上调.结论 BCNU与ATRA协同应用诱导脑胶质瘤细胞的凋亡,其诱导凋亡的分子机制可能是通过改变相关细胞周期蛋白导致细胞周期改变.     

阿霉素控释剂对大鼠C6脑胶质瘤治疗的研究

目的 探讨自制阿霉素控释剂在体内、外释药效果及对大鼠Ｃ６胶质瘤动物模型的治疗作用。方法 应用荧光光谱法检测阿霉素控制剂在人工脑脊液及１８只正常家兔脑内药物释放的情况；检测阿霉素控释剂对１０只脑内荷瘤ＳＤ大鼠生存期的影响以及不同给药方式（避部或腹腔给药）对３０只ＳＤ大鼠皮下接种肿瘤生长的抑制作用。结果 阿霉素控释剂在人工脑脊液和兔脑内可持续释放达１０ｄ以上；局部控释化疗可明显延长脑内荷瘤大鼠的生存期，实验组中位生存时间为３１ｄ。局部阿霉素控释化疗对于皮下肿瘤有明显抑制效应，与腹腔注射等量阿霉素化疗组相比，差异有非常显著性（Ｐ〈０．０１）。结论 控释化疗在避免系统化疗全身毒性的，增加肿瘤局部药物浓度，可有效抑制肿瘤生长。     

脑胶质瘤治疗的现状与进展

脑胶质瘤（神经胶质瘤）是由神经外胚叶衍化而来的胶质细胞即星形胶质细胞、少枝胶质细胞和室管膜胶质细胞等发生的肿瘤,是颅内肿瘤中最常见的一种,国内统计占颅内肿瘤的３５．２６％～６０．９６％（平均４４．６９％）。由于肿瘤细胞分化不一致,可以表现为不同的胶质瘤类型。在基础研究上已进入分子生物学特性与脑胶质瘤发生的关系,以及基因治疗的研究在脑胶质瘤的应用。在临床上呈现不同的生物学特性,脑胶质瘤是一常见的危害人类健康疾病,也是神经外科的难题和医学研究的重要课题之一。近年来,随着高新诊疗技术的发展,如ＣＴ、…     

烟曲霉醇与卡氮芥联合应用抑制U-251细胞异种移植瘤的研究

目的 观察烟曲酶醇(TNP-470)和卡氮芥(BCNU)联合应用对U-251胶质母细胞瘤细胞裸鼠皮下移植瘤生长的影响.方法 将U-251细胞株接种至裸鼠皮下,第7天荷瘤裸鼠随机分为TNP-470治疗组、BCNU治疗组、TNP-470和BCNU联合治疗组、对照组.测体质量、肿瘤体积、抑瘤率、肿瘤微血管密度(MVD).结果 (1)各组裸鼠体质量于治疗前后均无显著变化(P均>0.05).(2)治疗后第21天联合治疗组移植瘤体积[(108.93±17.63)mm~3]明显小于TNP-470治疗组[(576.10±114.29)mm~3]及BCNU治疗组[(473.01±48.04)mm~3](P均<0.01);各治疗组移植瘤体积均小于对照组[(1512.61±70.25)mm~3](P均<0.01);TNP-470治疗组与BCNU治疗组间移植瘤体积差异无统计学意义(P>0.05).(3)治疗后第21天联合治疗组的抑瘤率(92.80±11.37)%显著高于TNP-470治疗组(61.91±6.29)%和BCNU治疗组(68.73±9.65)%(P均<0.01),TNP-470治疗组与BCNU治疗组间抑瘤率差异无统计学意义(P>0.05).(4)联合治疗组移植瘤MVD[(4.23±0.83)个/视野]明显低于TNP-470治疗组[(5.70±0.85)个/视野]和BCNU治疗组[(8.60±0.87)个/视野](P均<0.05);TNP-470治疗组移植瘤MVD显著低于BCNU治疗组(P<0.05);各治疗组移植瘤MVD均较对照组[(11.32±1.50)个/视野]显著降低(P均<0.05).结论 TNP-470和BCNU联用对U-251胶质母细胞瘤细胞裸鼠皮下移植瘤的生长有显著抑制作用而无明显不良反应.     

显微手术后间质化疗联合增敏放疗治疗恶性脑胶质瘤

目的探讨显微外科手术后间质化疗联合增敏放疗治疗脑胶质瘤的临床疗效。方法对45例恶性脑胶质瘤患者行开颅显微手术全切除，术中于瘤腔内安置化疗囊，并行化疗药物体外敏感性及放疗增敏作用检测，术后第2．4、8、12周和6个月分别行经皮穿刺注入敏感化疗药物联合增敏放疗。随访6～36个月，并与以前随访的40例接受肉眼下全切后常规放化疗的脑胶质瘤患者相比较。结果45例患者均获随访，生存期明显延长，半年内复发4例(8．9％)，死亡3例(6．7％)；1年内复发9例(20．0％)，死亡7例(15．6％)；2年内复发19例(42．2％)，死亡15例(33．3％)；3年内复发25例(55．6％)，死亡22例(48．9％)。未发现明显的毒副反应，生存质量得到明显改善。结论显微外科手术力争全切除，术后敏感药物间质化疗联合增敏放疗，是一种可供选择的治疗人脑恶性胶质瘤的安全有效方法。     

五例脑胶质瘤综合治疗的体会

我院1994年7月至12月对5例脑胶质瘤术中及术后进行局部热化疗，其中2例加作放疗，取得良好疗效。现报告如下。临床资料一、一般资料：我科收住经CT与手术证实的脑胶质瘤患者。男3例，女2例，年龄32～51岁。肿瘤均单发，位于额叶3例，颞叶1例，顶叶1例。肿瘤直径3.5～6.5cm，最大1例同时侵犯额颞顶叶。术前除头痛、呕吐外，2例合并轻度偏瘫，均存在不同程度眼底水肿。行肿瘤全切除3例，次全切除2例。术后病检示Ⅱ～Ⅲ级星形细胞瘤。二、热化放方法：全麻下行胶质瘤切除或显微切除后，肿瘤残腔或瘤床充分电凝止血，用平阳霉素15mg溶解后填充…     

脑胶质瘤的显微手术治疗

目的 探讨如何提高脑胶质瘤的手术效果。方法 对79例脑胶质瘤病例进行显微手术和传统手术切除肿瘤的术式比较和效果进行回顾性分析。结果 43例应用显微外科作肿瘤切除术，其中全切除25例，大部分切除12例，有效率86．1％。术后32例随访半年～3年，结果复发11例，复发率34．4％，死亡3例。36例传统开颅肿瘤切除术，其中全切除14例，大部分切除10例，有效率66．6％。术后28例随访半年～3年，复发13例，复发率46．4％，死亡6例。结论 应用显微外科对胶质瘤进行切除手术，可以提高肿瘤全切除率，减少复发和死亡。     

骨桥蛋白在脑胶质瘤中的表达及与其预后的关系

骨桥蛋白（OPN）首先是在骨基质中发现的一种分泌型钙结合糖磷酸化蛋白，有促进细胞的趋化、黏附、迁移和增殖等作用。近年发现OPN在肿瘤组织及其转移灶中高表达。我们通过检测脑胶质瘤中OPN的表达。探讨OPN与脑胶质瘤临床、病理及预后之间的关系，进一步了解OPN在脑胶质瘤发生、发展中的作用。     

Intracarotid infusion of ACNU and BCNU as adjuvant therapy of malignant gliomas

Summary Thirty patients with malignant gliomas were treated by operation, radiotherapy and additional intracarotid infusions of ACNU and BCNU.Positive results were obtained in the treatement of oligodendrogliomas and astrocytomas grade III and IV. On the contrary, the results in cases of glioblastoma multiforme were disappointing: neither survival time nor quality of life had been significantly improved. The protective effect of phenobarbitone against systemic toxicity by ACNU was not always confirmed in this study.Based on literature reports and our own experience the indications, technical aspects, unexpected complications and results of this therapeutic approach are discussed.Dedicated to Prof. Dr. Jean Brihaye at the occasion of his 65th anniversary.     

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.     

Radio- and chemotherapy of malignant gliomas. Pathological changes in the normal nervous tissue

Summary The pathological effects of radio- and chemotherapy on the normal nervous tissue have been studied in 42 brains with malignant gliomas. The brains have been examined by means of the complete study technique. In seven cases the picture of delayed radionecrosis has been found. Apart from this, many histological features have been related to post-operative survival, radiation dose, interval between radiation and death, chemotherapy, steroids, size and activity of the tumour. Some alterations, such as peritumoural necroses, macrophage areas, vessel wall degenerations etc. result from radiotherapy. The relations and pathogenesis are discussed.     

以生物蛋白胶为载体配合丝裂霉素缓释化疗腹腔恶性肿瘤的临床研究

目的　探讨以生物蛋白胶为载体配合丝裂霉素缓释化疗辅助治疗腹腔恶性肿瘤的有效性和安全性。方法　将 5 3例腹腔恶性肿瘤患者随机分为实验组 (n =2 7) ,对照组 (n =2 6) ,术后实验组将生物蛋白胶溶解丝裂霉素喷洒在腹腔及瘤床周围 ,对照组未使用 ,比较实验组与对照组的疗效差异。结果　术后实验组和对照组患者化疗不良反应的发生率分别为 5 4.2 % ,61.5 % ,两组无显著差异 (P >0 .0 5 )。术后 1年 ,对照组生存率为 5 0 % ,实验组生存率为 77.8% ,两组有统计学差异 (P <0 .0 5 )。结论　以生物蛋白胶为载体配合丝裂霉素术后腹腔缓释化疗能够延长病人的生存期 ,安全有效。     

Pathology of human malignant gliomas after radiation and chemotherapy

Summary The pathological effects of radio- and chemotherapy have been studied in 31 malignant gliomas. The brains have been examined by means of the complete study technique. Many histological features have been related to surgery, localization, preoperative duration, postoperative survival, irradiation, and chemotherapy. No specific alterations have been found, but some positive correlations have been established: decrease of mitoses, occurrence of macrophages and vessel degeneration after radiation, increase of monstrous cells after chemotherapy.This paper was presented in part at the Fall Meeting of BTSG (Brain Tumor Study Group) at the National Institutes of Health, Bethesda, Maryland, 7 December 1979.Supported in part by NIH Grant No. 1 CM 67056.We are greatly indebted to Mrs. Margherita Bessone Valsasna for skilful technical assistance.     

Intravenous administration of high doses of carboplatin in multimodal treatment of high grade gliomas: a phase II study

Summary The object of this study is to evaluate the efficacy of a high dose of carboplatin in 20 patients operated on for high grade glioma (Group A) compared with a matched control (Group B) treated with BCNU administered after radiotherapy. The toxicity profile has been evaluated during the therapy. The survival of patients entering this study was measured in terms of months: the mean survival time was 10.45 months and the median 11.0 months in the — group treated with carboplatin (8 patients are still alive); the 18-month survival rate was 10%. The mean survival time of the control group was 9.85 months and the median 10.5 months; no patients are still alive and the 18-month survival rate was 0%. On the basis of our phase II clinical study, we could conclude that i.v. administration of high-doses of carboplatin in high grade gliomas is generally well tolerated and the results are better than those of a matched control treated with 1–2 courses of BCNU (low-dose). The adjuvant treatment and the role of carboplatin in the therapy of high grade gliomas is discussed.     

Intensive chemotherapy with autologous bone marrow rescue for recurrent malignant gliomas

Summary Eight patients, four male and four female, were treated with high dose chemotherapy followed by bone marrow transplantation. In the first two patients, high dose ACNU was used for the treatment without combination with other drugs. This showed severe side effects such as intratumorous bleeding on the 18th day of treatment in the first case and pulmonary fibrosis on the 35th day of treatment in the second case. Considering these results, we considered another treatment schedule which consisted of high dose ADM (100 mg/m²), VCR (1.5 mg/m²), CDDP (80 mg/m² × 4) and Ex (800 mg/m²) within seven days.Six patients were treated with this schedule and the results indicated that two patients had a partial response (more than 50% reduction of tumour size measured by CT scan), one had a complete remission (no tumour detected by CT scan), two showed no change and one, progression of the lesion.The patients recovered from the suppression of bone marrow function after the bone marrow transplantation as indicated. Granulocytes and platelets in blood began to increase from 10 to 14 days after the transplantation and became normal within three weeks after this.Serial measurements of S-GOT and alkaline phosphatase revealed reversible elevation, if any, within four weeks of the treatment.The number of our cases is still small, but results showed that autologous bone marrow transplantation made high dose chemotherapy possible.The necessity for consideration of the blood-brain barrier for this treatment is also discussed.     

Effect of perfluorochemicals on BCNU chemotherapy: Preliminary study in a rat brain tumor model

This preliminary study was undertaken to identify the combined efficacy of perfluorochemicals (Fluosol-43) and a chemotherapeutic agent (BCNU) in a rat brain tumor model. The brain tumor model was produced by the intracerebral transplantation of C₆ rat glioma cells. Fluosol-43 plus BCNU in an oxygen environment produced a significant prolongation of mean survival time compared to that of BCNU treatment alone. Per-fluorochemicals (Fluosol-43) seem to have some synergistic effect on BCNU chemotherapy for this brain tumor model.     

恶性脑胶质瘤单放和放化疗临床疗效5年随诊分析

目的 分析恶性脑胶质瘤术后单纯放射治疗、同步放射治疗加化学治疗的临床疗效。方法 本次研究我们回顾性分析了南开大学附属环湖医院神经外科自2015年10月至2016年9月共99例恶性脑胶质瘤患者资料,单纯放射治疗（单放）组48例,同步放射治疗加化疗（放化）组51例。两组患者均在术后20 d左右开始常规放射治疗,进行2 Gy/天,分30次,共计60 Gy的放疗,持续42天（周六、周日不放疗）。同步放射治疗加化疗（放化）组在持续42 d的放疗中同时加用化疗,方案为口服替莫唑胺胶囊75 mg/m²·d,共计42天;随后同步放射治疗加化疗期结束后4周,接受共计6个周期的替莫唑胺的辅助治疗,每个周期为28天,每个周期的方案为200 mg/m²·d,每日1次,共5 d,然后停药23 d,治疗可一直持续到肿瘤病变出现进展,最长治疗时间为2年。统计所有病例的1、3、5年生存率,分析恶性脑胶质瘤术后单纯放射治疗、同步放射治疗加化学治疗的临床疗效。结果 1、3、5年生存率单放组分别为54.2%、29.2%、10.4%,放化组分别为74.5%、51.0%、31.4%,放化组高于单放组（P<0.05）。放化组恶心、呕吐等急性反应明显加重,骨髓抑制和听力水平下降、记忆力减退等远期损伤两组病例无显著差异性。结论 恶性脑胶质瘤术后采用同步放射治疗加化学治疗可提高疗效。     

Chemotherapy for malignant gliomas of the brain: a review of ten-years experience

Summary In recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours.In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.Abbreviations AA anaplastic astrocytoma - ACNU (l-4-amino-2methil-5pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea - AraC cytosine arabinoside - AZQ aziridinylbenzoquinone - BCNU 1,3-bis(2-chloroetyl)-1-nitrosourea - BTSG Brain Tumor Study Group (USA) - BTCG Brain Tumor Cooperative Group (USA) - BUdR 5-bromodeoxyuridine - CCNU 1-(2-chloroethyl)-3cyclohexyl-1 -nitrosourea - CDDP cisplatin - DAG dianhydrogalacticol - DBD dibromodulcitol - DTIC imidazolcarboxamide - EORTC European Organization for Research on Treatment of Cancer - 5-FU fluorouracil - GBM glioblastoma - HU hydroxyurea - MeCCNU methyl-CCNU - Miso misonidazole - MP 6-mercaptopurine - MST median survival time - MTTP median time to tumor progression - PCNU 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea - PCZ procarbazine - RT radiotherapy - VCR vincristine - VM26 teniposide - VP16 etoposide