Although gene therapy was regarded as a promising approach for glioma treatment,its therapeutic efficacy was often disappointing because of the lack of efficient drug delivery systems.Mesenchymal stem cells(MSCs) have been reported to have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy.Therefore,in this study,we attempted to treat glioma by using MSCs as a vehicle for delivering replication-competent adenovirus.We firstly compared the infectivity of type 3,type 5,and type 35 fiber-modified adenoviruses in MSCs.We also determined suitable adenovirus titer in vitro and then used this titer to analyze the ability of MSCs to deliver replication-competent adenovirus into glioma in vivo.Our results indicated that type 35 fiber-modified adenovirus showed higher infectivity than did naked type 3 or type 5 fiber-modified adenovirus.MSCs carrying replication-competent adenovirus significantly inhibited tumor growth in vivo compared with other control gr

Although gene therapy was regarded as a promising approach for glioma treatment,its therapeutic efficacy was often disappointing because of the lack of efficient drug delivery systems.Mesenchymal stem cells (MSCs) have been reported to have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy.Therefore,in this study,we attempted to treat glioma by using MSCs as a vehicle for delivering replication-competent adenovirus.We firstly compared the infectivity of type 3,type 5,and type 35 fiber-modified adenoviruses in MSCs.We also determined suitable adenovirus titer in vitro and then used this titer to analyze the ability of MSCs to deliver replication-competent adenovirus into glioma in vivo.Our results indicated that type 35 fiber-modified adenovirus showed higher infectivity than did naked type 3 or type 5 fiber-modified adenovirus.MSCs carrying replication-competent adenovirus significantly inhibited tumor growth in vivo compared with other control g

Radioiodine i s a routine therapy for differentiated thyroid cancers.Non-thyroid cancers can intake radioiodine after transfection of the human sodium iodide symporter (hNIS) gene.The human telomerase reverse transcriptase (hTERT) promoter,an excellent tumor-specific promoter,has potential value for targeted gene therapy of glioma.We used the hTERT promoter to drive the expression of the hNIS and human thyroid peroxidase (hTPO) gene as a primary step for testing the effects of radioiodine therapy on malignant glioma.The U87 and U251 cells were co-transfected with two adenoviral vectors,in which the hNIS gene had been coupled to the hTERT promoter and the hTPO gene had been coupled to the CMV promoter,respectively.Then,we performed Western blot,125I intake and efflux assays,and clonogenic assay with cancer cells.We also did 99mTc tumor imaging of nude mice models.After co-transfection with Ad-hTERT-hNIS and Ad-CMV-hTPO,glioma cells showed the 125I intake almost 1.5 times higher than cel

Radioiodine is a routine therapy for differentiated thyroid cancers. Non-thyroid cancers can intake radioiodine after transfection of the human sodium iodide symporter (hNIS) gene. The human telomerase reverse transcriptase (hTERT) promoter, an excellent tumor-specific promoter, has potential value for targeted gene therapy of glioma. We used the hTERT promoter to drive the expression of the hNIS and human thyroid peroxidase (hTPO) gene as a primary step for testing the effects of radioiodine therapy on malignant glioma. The U87 and U251 cells were co-transfected with two adenoviral vectors, in which the hNIS gene had been coupled to the hTERT promoter and the hTPO gene had been coupled to the CMV promoter, respectively. Then, we performed Western blot, 135l intake and efflux assays, and clonogenic assay with cancer cells. We also did 99mTc tumor imaging of nude mice models. After co-transfection with Ad-hTERT-hNIS and Ad-CMV-hTPO, glioma cells showed the 125l intake almost 1.5 times h

Glioma stem/progenitor cells(GSPCs) are considered to be responsible for the initiation,propagation,and recurrence of gliomas.The factors determining their differentiation remain poorly defined.Accumulating evidences indicate that alterations in autophagy may influence cell fate during mammalian development and differentiation.Here,we investigated the role of autophagy in GSPC differentiation.SU-2 cells were treated with rapamycin,3-methyladenine(3-MA) plus rapamycin,E64d plus rapamycin,or untreated as control.SU-2 cell xenografts in nude mice were treated with rapamycin or 3-MA plus rapamycin,or untreated as control.Western blotting and immunocytochemistry showed up-regulation of microtubule-associated protein light chain-3(LC3)-II in rapamycin-treated cells.The neurosphere formation rate and the number of cells in each neurosphere were significantly lower in the rapamycin treatment group than in other groups.Real-time PCR and immunocytochemistry showed down-regulation of stem/progeni

Glioma stem/progenitor cells(GSPCs) are considered to be responsible for the initiation,propagation,and recurrence of gliomas.The factors determining their differentiation remain poorly defined.Accumulating evidences indicate that alterations in autophagy may influence cell fate during mammalian development and differentiation.Here,we investigated the role of autophagy in GSPC differentiation.SU-2 cells were treated with rapamycin,3-methyladenine (3-MA) plus rapamycin,E64d plus rapamycin,or untreated as control.SU-2 cell xenografts in nude mice were treated with rapamycin or 3-MA plus rapamycin,or untreated as control.Western blotting and immunocytochemistry showed up-regulation of microtubule-associated protein light chain-3(LC3)-II in rapamycin-treated cells.The neurosphere formation rate and the number of cells in each neurosphere were significantly lower in the rapamycin treatment group than in other groups.Real-time PCR and immunocytochemistry showed down-regulation of stem/progen

目的研究神经胶质瘤及瘤旁组织中的沉默信息调节因子1(Sirt1)基因的表达差异。方法应用基因芯片技术检测30例Sirt1基因在神经胶质瘤及瘤旁组织的表达差异,随后应用RT-PCR及免疫组织化学实验验证并分析Sirt1基因的表达差异。结果基因芯片筛选出存在差异表达的基因,其中Sirt1基因在神经胶质瘤中的表达较瘤旁组织中的表达明显下降,RT-PCR实验证实与基因芯片结果一致,免疫组织化学实验结果与基因芯片、RT-PCR结果一致。结论Sirt1在神经胶质瘤及瘤旁组织中的表达存在明显差异,Sirt1基因的表达可能与神经胶质瘤的发生发展密切相关。

Objective To explore the changes in gene Sirt1 expressions in tissues of human glioma and para - glioma. Methods A 44 000 gene cDNA microarray(Affymetrix)was used to examine gene expressions in the tissues of human glioma and para - glioma. The Sirt1 genes were identified and subjected to real - time PCR analysis. Results The expression of Sirt1 in tissues of glioma was extremely lower than that in tissues of para - glioma. The results of real - time PCR were consistent with those of genechip analysis. Conclusion The expressions of Sirt1 were obviously different between tissues of glioma and para - glioma. Sirt1 may be associated with carcinogenesis of glioma.

钙离子通道在神经胶质瘤中异常表达，并且在胶质瘤的发生、增殖、转移、肿瘤血管生成等方面起关键性作用。研究发现，不同类型钙通道表达升高或下降能够影响胶质瘤的生长发展及其细胞周期的再分布，提示其可能成为胶质瘤治疗的新靶点，为控制胶质瘤的进展提供新的思路。

Calcium channels express abnormally in glioma,and play a key role in the physiological functions of glioma such as tumorigenesis,proliferation,metastasis and angiogenesis. Researches show that low or high expressions of different types of calcium channels have influence on the development of glioma and cell-cycle redistribution. Such calcium channels may represent new targets in treating glioma,which provide new ideas for controlling glioma.