抑制VEGF表达的锤头状核酶系统

目的:建立和评估抑制血管内皮生长因子(VEGF)表达的锤头状核酶(hammerhead ribozyme)技术系统.方法:对VEGF121基因RNA序列进行二级结构分析,选择靶点;设计并构建针对VEGF的分泌肽RNA的可表达锤头状核酶(14)载体系统和VEGF-荧光色素酶融合基因报告质粒;通过试管内切割实验等方法评估核酶对于试管内转录得到的VEGF RNA切割特异性和效率;通过瞬时共转染实验和稳定转染实验评估核酶在细胞内对于VEGF RNA的切割效率.结果:设计和构建了对VEGF RNA二级结构水平上的暴露区( 8, 36和 71位点:核酶1,3和4)和非暴露区( 17位点:核酶2)4个锤头状核酶(14)的两套质粒;试管内切割检测表明,针对 8, 36和 71位点的核酶(1,3和4)可以有效地在试管内对VEGFRNA进行特异性切割,使其水平分别降至对照的61.7%,27.6%和44.8%(荧光色素酶活性)或66.3%,27.0%和30.0%(蛋白质水平);将核酶表达质粒与VEGF-LUC模板质粒瞬时共转染人SMMC-7721肝癌细胞,核酶1,3和4 VEGF-LUC水平分别降低到对照的81.4%,56.6%和69.1%;稳定表达针对VEGF的核酶1,3或4的SMMC-7721细胞株中,内源性VEGF RNA的水平降至对照水平的5%以下.对照未转染的、转染空载体的和转染了核酶2( 17)的SMMC-7721细胞.结论:分别针对VEGF 8, 36和 71位点锤头状核酶可有效地抑制VEGF的RNA水平.     

乐伐替尼治疗恶性肿瘤的研究进展

乐伐替尼是一种口服的多靶点酪氨酸激酶受体抑制剂,用于放射性碘难治性分化型甲状腺癌的单药治疗以及与依维莫司联合治疗晚期肾细胞癌。近年越来越多的临床数据展示出了该药在未来抗肿瘤治疗中的巨大潜力。本文将对其作用机制、研究历程、临床试验以及最新研究进展进行综述,以求使读者能够更全面地了解和认识乐伐替尼并且为我国的临床实践提供建议。     

Kinetics of tumor size and peritumoral brain edema before,during, and after systemic therapy in recurrent WHO grade II or III meningioma

Background

The efficacy of systemic antineoplastic therapy on recurrent World Health Organization (WHO) grades II and III meningiomas is unclear.

Methods

We performed a retrospective multicenter analysis of serial cranial MRI in patients with recurrent WHO II and III meningiomas treated with antineoplastic systemic therapies. Growth rates for tumor volume and diameter, as well as change rates for edema size, were calculated for all lesions.

Results

We identified a total of 34 patients (23 atypical, 11 anaplastic meningiomas) with a total of 57 meningioma lesions who had been treated at 6 European institutions. Systemic therapies included bevacizumab, cytotoxic chemotherapy, somatostatin analogues, and tyrosine kinase inhibitors. Overall, tumor growth rates decreased during systemic therapy by 51% for tumor diameter and 14% for tumor volume growth rates compared with the period before initiation of systemic therapy. The most pronounced decrease in meningioma growth rates during systemic therapy was evident in patients treated with bevacizumab, with a reduction of 80% in diameter and 59% in volume growth. Furthermore, a decrease in size of peritumoral edema after initiation of systemic therapy was exclusively observed in patients treated with bevacizumab (−107%).

Conclusions

Our data indicate that systemic therapy may inhibit growth of recurrent WHO grades II and III meningiomas to some extent. In our small cohort, bevacizumab had the most pronounced inhibitory effect on tumor growth, as well as some anti-edematous activity. Prospective studies are needed to better define the role of medical therapies in this tumor type.     

蟾毒灵抑制血管生成作用的初步观察

目的明确抗肿瘤中药提取物蟾毒灵有无抗血管生成的活性,并检测其量效关系。方法采用MTT法测定蟾毒灵对人脐静脉内皮细胞ECV304生长的抑制作用,计算IC50,观察其量效、时效关系;并以鸡胚绒毛尿囊膜为模型观察蟾毒灵在体内组织器官水平对血管生成的影响。结果蟾毒灵对ECV304细胞的生长有抑制作用,且呈浓度和时间的依赖性。24、48、72hIC50分别为1.104、0.355、0.0905μg/mL。鸡胚绒毛尿囊膜实验表明蟾毒灵可显著抑制血管生成的作用,并呈浓度依赖性。结论蟾毒灵具有明确的抑制血管内皮细胞增殖、抗血管生成的作用。     

软骨细胞培养液对鸡胚绒毛尿囊膜血管抑制效应的研究

目的检测软骨细胞培养液中是否存在抑制血管生长的因子。方法用酶消化、分离鸡胚关节软骨细胞,体外单层培养,收集细胞培养液。采用鸡胚绒毛尿囊膜实验检测该培养液对血管的抑制效应。结果加软骨细胞培养液的实验组血管数为2.75±0.99且血管较细、分支少;不加样的对照组血管数为4.5±1.08且血管较粗、分支多。两组有显著差异(P＜0.05)结论软骨细胞培养液具有抑制血管生长的作用。     

桑黄多糖抗肿瘤机制研究进展

综述桑黄多糖的抗肿瘤机制及研究进展。桑黄多糖的抗肿瘤机制主要表现在免疫调节、抗血管生成、抗氧化三方面；桑黄多糖与环磷酰胺联合用药能够增强疗效,降低副作用。     

参一胶囊与鼻咽癌放疗敏感性的作用研究

目的:探讨参一胶囊对鼻咽癌(nasopharyngeal carcinoma,NPC)患者的放疗敏感性作用。方法:81例接受治疗的患者,随机分入治疗组接受参一胶囊联合放疗或对照组仅放疗。检测两组患者鼻咽活检组织的微血管密度(MVD)情况,分析两组患者放疗疗效及血管内皮生长因子(VEGF)、可溶性细胞黏附因子-1(sICAM-1)、可溶性血管细胞间黏附分子-1(sVCAM-1)表达的差异。结果:治疗组放疗疗效优于对照组(P0.05)。治疗组MVD、VEGF、sICAM-1、sVCAM-1表达水平均低于对照组(P0.05)。结论:参一胶囊对于鼻咽癌患者具有放疗增敏作用,其机理可能与抗血管生成作用相关。     

Immunomodulatory drugs in chronic lymphocytic leukemia: a new treatment paradigm

Immunomodulating drugs belong to a new class of therapeutic agents that have immunomodulatory, antiangiogenic and antiproliferative effects. Although the basis of anti-tumour activity of immunomodulating agents are not clear, results of clinical trials have demonstrated impressive activity in certain hemalogical disorders such as multiple myeloma (MM) and myelodysplastic syndromes (MDS). The peculiar properties of immunomodulating agents prompted investigators to test their role in patients with chronic lymphocytic leukemia (CLL). The efficacy of single-agent thalidomide in refractory CLL is disappointing, although its combination with fludarabine seems promising. Lenalidomide, a thalidomide analogue, is showing anti-tumour activity with durable response in refractory CLL. These preliminary results represent the basis for investigating the potential of lenalidomide in association with established chemotherapy regimens or as maintenance therapy.