The inhibition of tamoxifen on sodium channel in SHG-44 glioma cell-line / 中国应用生理学杂志

<p><b>AIM</b>To explore the effect of tamoxifen on voltage-dependent sodium channels in SHG-44 glioma cell line.</p><p><b>METHODS</b>Whole-cell patch clamp technique was used to record the Na currents in SHG-44 cell line and to investigate the effect of tamoxifen of different concentration on this channel currents.</p><p><b>RESULTS</b>This channel activated and inactivated quickly. Tamoxifen could significantly decrease the amplitude of Na currents of SHG-44 cell line. This block effect was dose dependent and voltage dependent. When the holding potential was 0 mV, 8 micromol/L tamoxifen could block this currents 69%. The half inhibition concentration (IC50) was 5.54 micromol/L.</p><p><b>CONCLUSION</b>Tamoxifen could significantly block the voltage dependent sodium channel in malignant glioma cell line SHG-44. It might be one of the mechanisms that tamoxifen inhibit glioma proliferation. clamp technique was used to record the Na currents in SHG-44 cell line and to investigate the effect of tamoxifen of different concentration on this channel currents.</p><p><b>RESULTS</b>This channel activated and inactivated quickly. Tamoxifen could significantly decrease the amplitude of Na currents of SHG-44 cell line. This block effect was dose dependent and voltage dependent. When the holding potential was 0 mV, 8 micromol/L tamoxifen could block this currents 69%. The half inhibition concentration (IC50) was 5.54 micromol/L.</p><p><b>CONCLUSION</b>Tamoxifen could signifi-cantly block the voltage dependent sodium channel in malignant glioma cell line SHG-44. It might be one of the mechanisms that tamoxifen inhibit glioma proliferation.</p>

Tropism of bone marrow stromal cells to glioma and their neural differentiation potential / 肿瘤

Objective: To observe the tropism of bone marrow stromal cells (BMSCs) to intracranial glioma and their differentiation in the brain of rats bearing glioma, and to investigate the corresponding mechanism. Methods: The in vitro tropism of cultured BMSCs to glioma cells, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor(FGF), platelet derived growth factor (PDGF) were observed under microscope and detected by performing Transwell experiment. The in vivo tropism of BMSCs to intracranial glioma was observed by immunofluorescence method. The differentiation of BMSCs was induced in vitro and observed. After BMSCs were transplanted in the brain of glioma-bearing rats for 15 days, their in vivo differentiation was observed by immunofluorescence staining. Results: BMSCs displayed obvious in vitro tropism to glioma, PDGF, and EGF and in vivo tropism to intracranial glioma. They could migrate to satellite lesions of glioma in vivo. BMSCs were induced to differentiate into neural progenitor cells (8.4% ± 3.5%), neurons (53.7% ± 7.4%), and astrocytes (22.3% ± 5.2%) in vitro. After being transplanted into the brain of glioma-bearing rats, they also differentiated into neural progenitor cells (8.3% ± 3.6%), neurons (15.7% ± 4.3%) and astrocytes (32.5% ± 7.2%). There was significant difference in the differentiation ratio to neurons between in vitro and in vivo experiments (P0.05). Conclusion: BMSCs display extensive tropism to glioma. The direction of the differentiation of BMSCs may be related with local microenvironment.

Anti-glioma activity of treatment by bone marrow stromal cells transfected with HSV-tk in the rat / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the anti-glioma activity of treatment by bone marrow stromal cells (BMSCs) transfected with AdCMV-tk containing HSV-tk gene in rats.</p><p><b>METHODS</b>Primary cultured BMSCs were obtained and transfected with HSV-tk (BMSCs/tk) and were injected into contralateral brain of glioma-bearing rats to observe their tropism for glioma cells. RT-PCR was performed to examine the transduct of tk gene after it was transduced into BMSCs. C6 glioma cells were co-cultured with BMSCs transfected with HSV-tk. MTT test was performed to examine its antitumor activity. BMSCs, after being transfected with HSV-tk, were injected into contralateral brain tissue of glioma-bearing rats to show their in vivo antitumor activity. Dynamic MRI was performed to monitor the development of intracranial glioma.</p><p><b>RESULTS</b>Purified BMSCs were obtained by primary cultured bone marrow cells. After being transfected with HSV-TK, the cells still stably displayed extensive tropism for intracranial glioma and transcripted tk gene. RT-PCR showed that BMSCs/tk were transduced tk gene obviously at 21 days after AdCMV-tk transfection. BMSCs/tk showed a clear bystander effect after being co-cultured with C6 glioma cells in vitro. TUNEL assay showed that BMSCs/tk could obviously show bystander effect and induce apoptosis of glioma cells in vivo with an apoptosis positive ratio of 20.38% +/- 2.57%, showing a statistically significant difference in comparison with BMSCs group (2.56% +/- 0.52%, P = 0.023) and control group (2.74% +/- 0.38%, P = 0.025). Compared with the control group (21.40 +/- 1.63 days), BMSCs/tk transplantation significantly prolonged the survival time of glioma-bearing rats (52.60 +/- 13.11 days, P = 0.000). MRI detection showed that the least volume of intracranial glioma in BMSCs/tk group (8.28 +/- 2.64 mm3), significantly smaller than that in BMSCs group (134.51 +/- 16.37 mm3, P = 0.001) and control group (147.22 +/- 31.05 mm3, P = 0.001). Some of the intracranial gliomaa disappeared after transplantation of BMSCs/tk.</p><p><b>CONCLUSION</b>BMSCs transfected with AdCMV-tk may become an effective therapy method in the treatment for glioma.</p>

Preliminary analysis on the gene expression profiles of medulloblastomas by use of cDNA array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the molecular genesis of medulloblastomas with cDNA array.</p><p><b>METHODS</b>Four samples of medulloblastomas and 1 sample of normal brain tissue were collected freshly. After total RNA extraction, the (32)P targeted cDNA probes were converted and then hybridized with Atlas Human Cancer Array 1.2. The gene expression profiles were acquired through autoradiography. The discrepancy between the tumor and the normal brain tissue was analyzed with Atlas Image 1.01a.</p><p><b>RESULTS</b>In comparison with the genes in the normal brain tissue, 6 down-regulated and 35 up-regulated genes in the medulloblastomas were revealed by means of the microarrays and autoradiography, and were verified by reverse transcriptase-PCR. The regulatory trends of most differential expression genes were in compliance with the biological features of this tumor.</p><p><b>CONCLUSION</b>Medulloblastomas are diseases involving multiple genes with some molecular pathological mechanisms different from the astrocytic gliomas. There are complex interrelationships between these genes, which need to be further researched.</p>

Preliminary study on the gene expression profiles of ependymomas with cDNA array / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the differential gene expression of ependymomas.</p><p><b>METHODS</b>Four fresh samples of ependymomas and 1 of normal brain tissue were collected during operation. The extracted total RNAs were converted as (32)P tagged cDNA probes, which were then hybridized with the Atlas Human Cancer Array, producing the array based hybridization maps following the protocol provided with the kit. A set of special software was applied to the analysis and RT-PCR was performed to test the result.</p><p><b>RESULT</b>In comparison with the normal brain tissue, there were 31 upregulated gene and 1 downregulated gene in ependymomas, most of which were firstly found to be differentially expressed in this kind of tumor.</p><p><b>CONCLUSION</b>The discrepancy of gene expression profiles between ependymomas and normal brain tissues is highly put through and effectively detected with cDNA array, which provides new information for the further research on the molecular mechanisms of this lesion.</p>