抗人脑胶质瘤单克隆抗体─—阿霉素免疫交联物在荷瘤鼠体内药代动力学研究

 采用DextranT-40桥联法将抗人脑胶质瘤单克隆抗体SZ-39与肿瘤化疗药物氚标记阿霉素交联，制各成免疫交职物³H-Adr(阿霉素)-PAD(多醛葡聚糖)-MAb(单克隆抗体)SZ-39在荷瘤鼠体内研究免疫交联物药代动力学特征。结果显示Adr-MAbSZ-39在相关肿瘤内浓聚，发挥了单抗高选择性作用，为胶质瘤的治疗提供了高效低毒的新一代良药。但在肝内摄入较多，为其可能的副作用。血药浓度-时间曲线符合三室线性模型，T_1/2长于游离Adr，有效分布体积大于游离Adr，以2周问隔多疗程治疗为佳。     

Investigation of germline PTEN,p53, p16INK4A/p14ARF,and CDK4 alterations in familial glioma

Epidemiological studies suggest that some familial aggregations of glioma may be due to inherited predisposition. Many genes involved in familial cancers are frequently altered in the corresponding sporadic forms. We have investigated several genes known to be altered in sporadic gliomas for their potential contribution to familial glioma. Fifteen glioma patients with a family history of brain tumors were identified through the Mayo Clinic Department of Neurology (nine diffuse astrocytomas, two oligodendrogliomas, two mixed oligoastrocytomas, one pilocytic astrocytoma, and one pineal glioma). Eleven of the propositi had one or more first degree relative with a glioma. Lymphocyte DNA was derived from each of the patients and analyzed by polymerase chain reaction (PCR) and direct sequencing of the PTEN, p53, p16^INK4A/p14^ARF, and CDK4 genes. In addition, fluorescence in situ hybridization (FISH) was performed on EBV‐transformed lymphocytes from each affected individual to detect germline copy number of the p16^INK4A/p14^ARF tumor suppressor region. A p53 germline point mutation was identified in one family with some findings of Li‐Fraumeni syndrome, and a hemizygous germline deletion of the p16^INK4A/p14^ARF tumor suppressor region was demonstrated by FISH in a family with history of both astrocytoma and melanoma. Thus, whereas germ‐line mutations of PTEN, p53, p16^INK4A/p14^ARF, and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16^INK4A/p14^ARF tumor suppressor region may account for a subset of familial glioma cases. Collectively, these data lend genetic support to the heritable nature of some cases of glioma. Am. J. Med. Genet. 92:136–141, 2000. © 2000 Wiley‐Liss, Inc.     

不同强度有氧运动对脑胶质瘤术后化疗患者癌因性疲乏及HPA轴功能的影响

目的 探讨不同强度有氧运动对脑胶质瘤术后化疗患者癌因性疲乏(CRF)及下丘脑-垂体-肾上腺皮质(HPA)轴功能的影响.方法 选取脑胶质瘤术后化疗并发CRF患者76例,随机分为2组,各38例.A组予以25％VO2max的强度进行有氧运动,B组予以50％VO2max的强度进行有氧运动,2组均连用8周.统计分析2组治疗前后H...     

白藜芦醇联合顺铂对神经胶质瘤细胞的作用

目的： 探讨白藜芦醇联合顺铂对神经胶质瘤细胞C6 的作用。方法：不同浓度的白藜芦醇与顺铂单独联合 作用于神经胶质瘤细胞C6,24、48 h 和72 h 后,CCK8法检测增殖,并选出合适浓度进行后续试验;不同浓度的 药物作用于细胞24 h 后,吖啶橙法观察细胞形态变化、流式细胞仪检测细胞凋亡、细胞周期和免疫印迹检测蛋白 Bax、Bcl-2 和p-Erk1/2 变化。结果：白藜芦醇与顺铂能协同抑制神经胶质瘤细胞C6 的增殖。联合用药后细胞周 期抑制在S 期。免疫印迹结果显示凋亡蛋白Bax 的表达量增加,而凋亡抑制蛋白Bcl-2 的表达量减少,细胞外调 节蛋白激酶p-Erk1/2 的表达量减少。结论：白藜芦醇与顺铂联合对神经胶质瘤细胞具有相互增敏作用,能够协同 抑制细胞增殖,并通过Ras-Raf-MEK-Erk 信号通路促进其凋亡。     

双配体修饰的阿霉素脂质体靶向于脑胶质瘤的体外研究

目的筛选和优化转铁蛋白、叶酸共同修饰的阿霉素脂质体的处方及制备工艺,以期得到具有良好的脑胶质瘤靶向治疗作用的给药系统。方法采用薄膜分散和硫酸铵梯度法制备阿霉素脂质体。将叶酸连接至二硬脂酸磷脂酰乙醇胺-聚乙二醇2000(DSPE-PEG2000-NH2)得到DSPE-PEG2000-Folic,考察不同磷脂种类、药脂比、水化介质和载药时间,对脂质体粒径、包封率和稳定性的影响,确定脂质体的处方工艺。以大鼠的脑毛细血管内皮细胞(bEnd3)和星形胶质细胞组成体外血脑屏障(blood-brain barrier,BBB),并结合大鼠胶质瘤C6细胞,构建体外模拟胶质瘤靶向治疗的复合BBB模型。考察阿霉素脂质体在bEnd3细胞中的摄取机制和透过BBB的转运速率及对C6细胞的毒性。结果确定了DSPC作为主要磷脂组分,并以120 mmol.L 1的硫酸铵作为水化介质,药脂比为1∶1 5,载药时间选择60 min,成功制备了高包封率和稳定性的双配体脂质体。其在bEnd3细胞中摄取远大于普通脂质体(P<0.05),摄取过程受网格蛋白和小窝内陷介导的细胞内吞作用,并受转铁蛋白和叶酸的影响;同时其在BBB模型中的药物透过速率、及其进一步透过BBB后对下层C6细胞的毒性,均显著高于其他脂质体组。结论转铁蛋白和叶酸共同修饰的阿霉素脂质体具有较好的体外脑胶质瘤靶向治疗作用。     

立体定向放射治疗联合替莫唑胺治疗复发性脑胶质瘤的疗效

目的：探讨立体定向放射治疗联合替莫唑胺治疗复发性脑胶质瘤的临床疗效。方法：回顾性总结36例复 发性脑胶质瘤患者的临床资料,其中24例患者予以立体定向放射治疗联合替莫唑胺治疗(SRT-TMZ组),12例患者予 以立体定向放射治疗(SRT组),比较2组的临床疗效及不良反应。结果：复发性脑胶质瘤治疗后总有效率为66.67%, 总局控率为93.94%,无晚期不良反应。其中SRT-TMZ组的总有效率为77.27%,局控率为95.45%;优于SRT组,但差异 无统计学意义(P>0.05)。33例患者0.5,1,2,3年生存率分别为90.91%,63.64%,42.42%,15.15%,其中SRT-TMZ组 0.5,1,2,3年生存率分别为95.45%,72.72%,54.54%,22.73%;SRT组0.5,1,2,3年生存率分别为81.82%,45.45%, 18.18%,0%。生存分析显示SRT-TMZ组生存时间长于SRT组(30.00个月 vs 14.00个月,P=0.010)。结论：立体定向放射 治疗联合替莫唑胺是姑息性治疗复发性脑胶质瘤的有效手段,对于提高患者近期疗效和生存率有积极作用。