Ongoing evolution of response assessment in glioma: Where do we stand?

The investigation and development of recently introduced agents or radiological measurements caused emergent misunderstandings to the response assessment of glioma. To date, the classical Macdonald criteria and the response assessment of neuro-oncology (RANO) criteria have been used successively for the evaluation of glioma outcome. However, ongoing efforts on complementary assessments are necessary to combat this malignancy. In this review, we highlight the shortcomings of the current criteria and introduce the initiative effort of RANO guideline and its offspring. We also discuss some future barriers for accurate assessment of treatment response in glioma

Extraction and purification of tumorigenic Schwann cells in vitro from neurofibromatosis type 2 tissues

Objective To establish a simple method to extract and purify tumorigenic Schwann cells (TSCs) from neurofibromatosis type 2 (NF2) tumor tissues in vitro, in order to improve the successful rate of primary culture and obtain a large number of TSCs from NF2 patients for further study. Methods Six fresh tumor tissues from patients with NF2 were obtained from 2009 to 2010 in our hospital. TSCs were extracted after collagenase digestion, followed by cell purification through rapid digestion with low trypsin concentration, differential detachment and clone screening. Morphological changes of TSCs were observed under inverted microscope and cultured TSCs were identified immunocytochemically by S ⁃ 100 protein staining. Results TSCs were successfully cultured from 3 NF2 specimens. A large number of bipolar spindle or triangular⁃shaped cells could be seen on the third day of primary culture and 4 to 5 clones were formed after the third passage in each successfully cultured specimen. Purified TSCs expressed S ⁃ 100 protein detected by immunocytochemistry with the rate of positive cells of above 95%, and their cell activity was fine and were able to be passaged stably in the subculture. Conclusion It is a successful culture method to extract and purify TSCs, combining primary culture with rapid trypsin digestion with low concentration and differential detachment. After clone screening, the purified and energetic TSCs can be obtained and applied to clinical study for NF2 pathogenesis and treatment. Fibroblasts (FBs) can be removed effectively as well. DOI：10.3969/j.issn.1672-6731.2011.01.01

Effect of temozolomide and methylprednisolone on the radiosensitivity in radiotherapy of human brain glioma cells

Objective To investigate the effect of temozolomide (TMZ) and methylprednisolone (MP) on the radiosensitivity of human glioma cells (U251 cells), and to provide experimental evidence for optimal chemotherapy in malignant glioma. Methods Human U251 cells were used for this experiment, and treated respectively by 5 schemes: group C (control, not irradiated and no TMZ and MP), R (irradiated alone), R + TMZ (irradiated and TMZ), R + MP (irradiated and MP) and R + TMZ + MP (irradiated, TMZ and MP). Sulforhodamine B (SRB) assay was used to calculate the cell viability percentage. The apoptosis rate of U251 cells was determined by flow cytometry. The expression of Bax and Bcl⁃2 protein in the treated cells was detected by Western blotting. Results After treatment, the survival rate in group R + MP was significantly higher than group R, R + TMZ and R + TMZ + MP (P = 0.000, for all). The proliferation rate of group R + TMZ + MP at 24 and 48 h was higher than group R + TMZ (P = 0.000). The detection of apoptosis showed that the apoptosis rate in experimental groups increased obviously (P = 0.000, for all), but not in group C. In cell apoptosis elevated groups, the apoptosis rate of group R + MP increased less than group R, R + TMZ and R + TMZ + MP (P = 0.000, for all). The Bax expression in group R + TMZ and R + TMZ + MP was clearly higher than group C, R and R + MP (P = 0.000, for all). The Bcl⁃2 protein in group R + MP and R + TMZ + MP was expressed significantly higher than group C, R and R + TMZ (P = 0.000, for all). The highest Bax/Bcl⁃2 ratio was in group R + TMZ (P = 0.000), and the lowest Bax/Bcl⁃ 2 ratio was in group R + MP (P = 0.000). Conclusion MP could induce human glioma cells to resist radiation. TMZ could improve the radioresistant induced by MP. During the radiotherapy in malignant glioma, the radiation resistant effect induced by using MP to reduce radiotherapeutic adverse reaction could be offset by TMZ. DOI：10.3969/j.issn.1672-6731.2011.03.01

Jagged1 is Clinically Prognostic and Promotes Invasion of Glioma-Initiating Cells by Activating NF-κB(p65) Signaling

Background/Aims: Jagged1 is the ligands of the Notch signaling and has been shown to promote glioma-initiating cells (GICs) in glioblastoma. The role of Jagged1 in GICs invasion and underlying molecular mechanisms remain unclear. Methods: Survival data from R2 genomics analysis, the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and visualization platform database were used to evaluate the effects of Jagged1 on overall patient survival. we investigated Jagged1 induced the GICs cells’ invasion by matrix degradation assays and Transwell cell invasion assays in vitro, then we further explored the underlying molecular mechanisms using Co-immunoprecipitation (co-IP) analysis. Results: High expression of Jagged1 in human glioma was associated with poor survival. Clinical data analysis showed that the Jagged1 was positively correlated with NF-κB(p65). Jagged1-induced invasion of GICs cells through activation of NF-κB(p65) pathway. In vivo, knockdown of Jagged1 could suppress the tumorigenicity of GICs cells through NF-κB(p65) signaling. Conclusion: Insights gained from these findings suggest that Jagged1 plays an important oncogenic role in GICs malignancy by activation of NF-κB(p65) signaling, and Jagged1 could be employed as an effective therapeutic target for GICs