Network pharmacological mechanism of Cinobufotalin against glioma.

OBJECTIVE: Cinobufotalin was extracted from the skin of Chinese giant salamander or black sable with good clinical effect against tumor. This study aims to explore the mechanism of Cinobufotalin components and predict the target of action of Cinobufotalin on glioma. METHODS: The active components of Cinobufotalin were screened by the Chinese medicine pharmacology database and analysis platform (TCMSP), PubChem database, etc. The potential molecular components and targets were identified and enrichment analysis was conducted through the construction of related networks and analysis of their characteristics. Relevant targets of glioma were searched through TTD, DRUGBANK, and other databases, and the intersection was found and the key targets were found too. RESULTS: A total of 21 active components and 184 target genes of Cinobufotalin were found. According to the enrichment analysis results, the pharmacological mechanism of Cinobufotalin mainly includes inhibition of the cell cycle, promotion of cell apoptosis, and regulation of immunity. On this basis, RAC1, FOS, and NOS3 can be preliminarily predicted as potential targets of Cinobufotalin in the treatment of glioma. CONCLUSIONS: The screening of active ingredients and target prediction based on network pharmacology can provide a new research idea for the multi-target treatment of glioma with Cinobufotalin.

Multimodal imaging in the differential diagnosis of glioma recurrence from treatment-related effects: A protocol for systematic review and network meta-analysis.

BACKGROUND: Glioma is the most common malignant primary brain tumor and it will always recur. To date, various multimodal imaging including magnetic resonance imaging (MRI) and positron emission tomography computed tomography (PET/CT) was used to differentiate the diagnosis of true tumor recurrent (TuR) and treatment-related effects (TrE) in glioma patient but with no overall conclusion. In this study, SROC curve and Bayesian network meta-analysis will be used to conduct a comprehensive analysis of the results of different clinical reports, and assess the efficacy of multimodal imaging in difference TuR and TrE. METHODS: To find more comprehensive information about the application of multimodal imaging in glioma patients, we searched the EMBASE, Pubmed, and Cochrane Central Register of Controlled Trials for relevant clinical trials. We also reviewed their reference lists to avoid omissions. QUADAS-2, RevMan software, Stata, and R software will be used. RESULTS: This study will provide reliable evidence for the efficacy of multimodal imaging in the differential diagnosis of TuR and TrE in glioma patients. CONCLUSION: We will evaluate the effectiveness of different and rank each imaging method in glioma patients to provide a decision-making reference on which method to choose for clinicians. Protocol registration number: CRD42020217861.

The therapeutic and neuroprotective effects of an antiepileptic drug valproic acid in glioma patients.

Glioma is the most common primary malignant brain tumor in adults and the patients have poor prognosis despite treatment with surgery, radiotherapy and chemotherapy. The anti-epileptic drug, valproic acid (VPA) as a HDAC inhibitors is often used in glioma patients even if the patients don't have brain tumors associated epilepsy (BAE). Some previous studies have found that VPA not only has anti-epileptic effect, but also has anti-glioma growth effect through enhance radiotherapy sensitivity or other mechanism. Then VPA is reported to improve the survival of glioma patients receiving chemoradiation therapy. In addition, there are limited researches have shown that VPA has a neuroprotective effect in protect normal cells and tissues from the deleterious effects of treatment of glioma, especially radiotherapy. We'll give a brief overview of these effects of VPA in glioma patients.

Inhibitory effect of Siwei Xiaoliuyin on glioma angiogenesis in nude mice.

OBJECTIVE: Application of Siwei Xiaoliuyin in glioma mice. Explore the effect of Siwei Xiaoliuyin on angiogenesis of nude mice glioma and its mechanism. METHODS: Establish human glioma cell line U87 tumor model. Mice were randomized to the saline group, the conventional dose of Siwei Xiaoliuyin, high dose group of Siwei Xiaoliuyin, TMZ group, combination therapy group, record the tumor volume. Using the method of Weidner counted the microvessel density. ELISA enzyme-linked adsorption method to detect the content of nude mice serum VEGF and ES. The difference was statistically significant (P<0.05). RESULTS: The tumor volume and MVD of conventional dose group, large dose group, Siwei Xiaoliuyin combined temozolomide group was smaller than the blank group，the difference was statistically significant (P<0.05). VEGF levels in three groups of nude mice were lower than the blank group and ES content is higher than blank group, the difference was statistically significant (P<0.05). CONCLUSION: Siwei Xiaoliuyin can inhibit glioma angiogenesis. Its mechanism of glioma angiogenesis inhibition may be through regulation VEGF and down-regulation of endostatin expression of vascular endothelial growth factor achieved. Down-regulation of endostatin expression of vascular endothelial growth factor achieved.

Advanced multimodal imaging in differentiating glioma recurrence from post-radiotherapy changes.

Gliomas are the most common malignant primary brain tumor, and their prognosis is extremely poor. Radiotherapy is an important treatment for glioma patients, but the changes caused by radiotherapy have brought difficulties in clinical image evaluation because differentiating glioma recurrence from post-radiotherapy changes including pseudo-progression (PD) and radiation necrosis (RN) remains a challenge. Therefore, accurate and reliable imaging evaluation is very important for making clinical decisions. In recent years, advanced multimodal imaging techniques have been applied to achieve the goal of better differentiating glioma recurrence from post-radiotherapy changes for minimizing errors associated with interpretation of treatment effects. In this review, we discuss the recent applications of advanced multimodal imaging such as diffusion MRI sequences, amide proton transfer MRI sequences, perfusion MRI sequences, MR spectroscopy and multinuclides PET/CT in the evaluation of post-radiotherapy treatment response in glioma patients and highlight their potential role in differentiating post-radiotherapy changes from glioma recurrence.

New advances on the inhibition of Siwei Xiaoliuyin combined with Temozolomide in glioma based on the regulatory mechanism of miRNA21/221.

OBJECTIVE: To provide evidence for the mechanism of Chinese medicine to treat glioma. We observe the effects of Si wei xiao xiu yin combined with chemotherapy on the growth of subcutaneous xenografts in nude mice and the expression of miRNA-21 and miRNA-221 in tumor tissues. METHODS: The subcutaneous transplantation model of nude mice was established by subcutaneous inoculation of glioma U87 cell suspension. They were randomly divided into saline group, traditional Chinese medicine group, temozolomide group and traditional Chinese medicine combined with temozolomide group to observe the changes in body weight, and the tumor weight, length, short diameter, volume of mice. The relative expression levels of miRNA-21 and miRNA-221 in tumor tissues were detected by qRT-PCR, and the differences between groups were compared. RESULTS: After 28 days of gavage, the tumor growth of the other three groups was slower than that of saline group, and the difference was most significant in the combination group (P=0.008<0.05), besides, the relative expression of the three groups of miRNA-21 and miRNA-221 was significantly inhibited compared with saline group, and the difference was significant in the combination group (F=8.918, P=0.010<0.05). CONCLUSION: To some extent, Si wei xiao xiu yin combined with temozolomide can inhibit the growth of subcutaneous xenografts in glioma nude mice. The mechanism may be related to the inhibition of miRNA-21 and miRNA-221 expression.

Curcumin Suppresses Tumor Growth and Angiogenesis in Human Glioma Cells Through Modulation of Vascular Endothelial Growth Factor/ Angiopoietin-2/Thrombospondin-1 Signaling.

PURPOSE: To investigate the effect of curcumin on tumor growth and angiogenesis of human gliomas and identify the underlying molecular mechanisms. METHODS: A mouse xenograft glioma model was established by subcutaneously inoculating tumor cell aggregates derived from the U87 cell line. Mice were treated with 0.01ml/g body weight of curcumin or saline. Tumor volume was measured. Microvessel density was assessed by CD34 immunostaining, and angiogenesis by immunohistochemical staining of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and thrombospondin 1 (TSP-1). RESULTS: At 28 days after treatment, tumor weights in the curcumin-treated group were much smaller than in the control group (0.23±0.11g vs 0.44±0.15g，p＜0.05), resulting in a 45.8% inhibition of tumor growth. Curcumin also markedly inhibited microvessel density. Expression of VEGF and Ang-2 was inhibited by curcumin, whereas TSP-1 expression was up-regulated. CONCLUSION: This study shows that curcumin inhibits tumor growth by inhibiting VEGF/Ang-2/TSP-1- mediated angiogenesis in a xenograft glioma mouse model.

Silencing of histone deacetylase 2 suppresses malignancy for proliferation, migration, and invasion of glioblastoma cells and enhances temozolomide sensitivity.

Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells. Furthermore, silencing of HDAC2 can increase the sensitivity of GBM cells to temozolomide (TMZ), a standard-of-care during clinical GBM treatment. This might be due to that si-HDAC can significantly down-regulate the mRNA and protein expression of MRP1, while has no effect on ABCB1 and ABCG2. Schisandrin B (Sch B), a specific inhibitor of MRP1, can further increase the TMZ sensitivity in HDAC2-knocked down GBM cells. Collectively, our data revealed that targeted HDAC2 can suppress the malignancy of GBM cells and increase their sensitivity of TMZ via down-regulation of MRP1. It suggested that HDAC2 might be a potential target for GBM therapy and improvement in TMZ therapy efficiency.