Analysis of Clinical Characteristics and Risk Factors of Postoperative Recurrence and Malignant Transformation of Low-Grade Glioma.

This research was developed to explore the clinical characteristics and related risk factors of postoperative recurrence and malignant transformation of low-grade glioma (LGG). The subjects were rolled into observation group (19 cases) and control group (51 cases) according to recurrence and malignant transformation during the follow-up period. The clinical data of the two groups were compared, and the risk factors of recurrence and malignant transformation were analyzed with the time of recurrence and malignant transformation as independent variables. The experimental results showed that the proportion of patients aged over 45 years in the observation group (63.16%) was higher than that in the control group (50.98%). The proportion of preoperative functional status score (KPS) ≥80 in the observation group (68.42%) was lower than that in the control group (78.43%). The proportion of patients with tumor over 5 cm in the control group (27.45%) was lower than that in the observation group (52.63%), and the proportion of total resection of tumor in the control group (47.06%) was higher than that in the observation group (21.05%). Furthermore, the multivariate analysis showed that preoperative KPS score, preoperative duration of disease, resection scope, postoperative treatment, oncotesticular antigen (OY-TES-1) mRNA, P53, mouse double microbody amplification gene (MDM2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) were independent risk factors (all P < 0.05). In summary, patients with postoperative recurrence and malignant transformation had poorer physical condition and higher degree of malignancy before surgery. Preoperative KPS score, duration of disease, surgical resection scope, postoperative treatment, OY-TES-1 mRNA, P53, MDM2, VEGF, and EGFR were the risk factors.

Candidate genes and microRNAs for glioma pathogenesis and prognosis based on gene expression profiles.

Glioma is the most common malignant brain tumor, and the incidence of glioma demonstrates an upward trend. It is vital to elucidate the pathogenesis of glioma and seek effective therapies. The aim of the present study was to identify the potential gene markers associated with glioma based on GSE31262 gene expression profiles, and to explore the underlying mechanism of glioma progression by analyzing the gene markers. The microarray dataset GSE31262 was downloaded and neural stem cell samples (control group) and glioma samples (glioma group) were analyzed to identify the differentially expressed genes (DEGs) between the two groups. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using DAVID software. Subsequently, a protein­protein interaction (PPI) network was constructed and important modules were extracted from this network. Additionally, the miRNA­target regulatory network was established. In total, 1377 DEGs with P<0.01 and |log2 fold change| ≥2 were identified between the control and glioma groups. The DEGs that were upregulated in glioma samples compared with controls were primarily associated with functions such as the M phase and cell cycle pathway, while the downregulated genes were associated with functions such as nerve impulse and the axon guidance pathway. The results also indicated that certain DEGs, including cyclin­dependent kinase 1 (CDK1) and cadherin 1 (CDH1), had important roles in the PPI network. The MCODE tool in Cytoscape software was used to identify upregulated and downregulated modules in the PPI network, and 5 upregulated and 2 downregulated modules were extracted. Furthermore, the WebGestal online tool was used to identify potential interactions of the upregulated and downregulated genes with microRNAs (miRNA/miR), and miR­135A/B and its two targets, discs large MAGUK scaffold protein 2 and forkhead box O1 (FOXO1), had the highest number of connections in the miRNA­target regulatory network. In addition, cell division cycle 20 and FOXO1 were confirmed to be upregulated in U87 glioma cells compared with normal human astrocytes (HA1800) by reverse transcription­quantitative polymerase chain reaction. In conclusion, M phase function and the axon guidance pathway may be vital for glioma progression. In addition, CDK1 and CDH1 may be associated with the process of glioma. Furthermore, miR­135A/B, and the target FOXO1, may be potential therapy targets for glioma treatment.

Long noncoding RNA FTX is upregulated in gliomas and promotes proliferation and invasion of glioma cells by negatively regulating miR-342-3p.

Gliomas remain a major public health challenge, posing a high risk for brain tumor-related morbidity and mortality. However, the mechanisms that drive the development of gliomas remain largely unknown. Emerging evidence has shown that long noncoding RNAs are key factors in glioma pathogenesis. qRT-PCR analysis was used to assess the expression of FTX and miR-342-3p in the different stages of gliomas in tissues. Bioinformatics tool DIANA and TargetSCan were used to predict the targets of FTX and miR-342-3p, respectively. Pearson's correlation analysis was performed to test the correlation between the expression levels of FTX, miR-342-3p, and astrocyte-elevated gene-1 (AEG-1). To examine the role of FTX in regulating proliferation and invasion of glioma cells, specific siRNA was used to knockdown FTX, and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and transwell assays were performed. Furthermore, rescue experiments were performed to further confirm the regulation of miR-342-3p by FTX. We then found that the expression of FTX and miR-342-3p was associated with progression of gliomas. FTX directly inhibited the expression of miR-342-3p, which subsequently regulates the expression of AEG-1. Collectively, FTX is critical for proliferation and invasion of glioma cells by regulating miR-342-3p and AEG-1. Our findings indicate that FTX and miR-342-3p may serve as a biomarker of glioma diagnosis, and offer potential novel therapeutic targets of treatment of gliomas.

NFATc1 activation promotes the invasion of U251 human glioblastoma multiforme cells through COX-2.

Recent studies have revealed that the nuclear factor of activated T-cells (NFAT) is a transcription factor that is highly expressed in aggressive cancer cells and tissues, and mediates invasion through the transcriptional induction of pro-invasion and pro-migration genes. However, the mechanisms through which nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), in particular, translocates to the nucleus and regulates the invasion of human glioblastoma multiforme (GBM) cells have not yet been fully elucidated. In the present study, to investigate the role of NFATc1 in GBM cells, we established a U251 cell line expressing a constitutively active form of NFATc1 (CA-NFATc1). On the other hand, RNA interference was used to knock down NFATc1 expression in the U251 cell line. Our results demonstrated that the expression of CA-NFATc1 promoted cancer cell invasion, while small interfering RNA (siRNA) against NFATc1 successfully inhibited the invasion ability of the U251 cell line. Moreover, we demonstrated that NFATc1 promoted U251 cell invasion through the induction of cyclooxygenase-2 (COX­2). NFAT transcriptionally regulates the induction of COX-2 induction in U251 cells and binds to the promoter. We also demonstrated that a large proportion of GBM specimens expressed NFATc1. NFATc1 expression increased according to the histopathological grade of the glioma. However, no NFATc1 staining was observed in the non-neoplastic brain tissues. These findings suggest that the inhibition of the activation of the NFATc1 pathway is an effective therapeutic strategy for the clinical management of GBM.

Resveratrol inhibited GH3 cell growth and decreased prolactin level via estrogen receptors.

AIMS: Pituitary prolactinoma is one of the estrogen-related tumors, some anti-estrogen compounds have suppressive effects on prolactinoma. Previous studies have suggested that resveratrol, a phytoestrogen, displays anti-estrogen and anti-tumor characteristics. Therefore, We determined whether resveratrol could inhibit the cell proliferation and decrease prolactin level in prolactinoma cell line, and identify the signaling pathways that mediate the effects of resveratrol. MAIN METHODS: Prolactinoma cell line, GH3 cells were treated with resveratrol. Changes in proliferation, cell cycle, and apoptosis were assessed. The level of prolactin was assayed by Western blot or EIA. Expression of total Rb (retinoblastoma protein), phosphorylated Rb (pRb) and cyclin D3 were measured by Western blot. The changes of estrogen receptors and their roles in the effects of resveratrol were also determined. KEY FINDINGS: We report that resveratrol had a dose-dependent inhibitory effect on GH3 cell proliferation. Inhibitory effects of resveratrol persisted, even on removal of resveratrol. The growth-inhibitory effect of resveratrol was accompanied by decreased expression of cyclin D3 and pRb. In addition, resveratrol induced G0/G1 cell cycle block and apoptosis. Furthermore, resveratrol suppressed intracellular levels and release of prolactin. Finally, we show that two types of estrogen receptor were involved in the different effects of resveratrol. SIGNIFICANCE: Taken together, we demonstrate that resveratrol could inhibit prolactinoma cell proliferation, induce cell cycle block and apoptosis, and decrease prolactin production and release, and estrogen receptors mediate its antitumor effects. And thus, these results lead us to propose developing resveratrol as a novel therapeutic agent for treatment of prolactinoma.

Changes of TXA2 and PGI2 during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage.

In order to explore the changes and the roles of TXA2 and PGI2 during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage, 31 cases subject to craniotomy were divided into three groups: group A, 9 patients with postoperative hypertensive crisis; group B, 13 patients without postoperative hypertensive crisis; and group C, 9 patients without history of hypertension and hypertensive intracerebral hemorrhage. TXA2, TXB2, 6-keto-PGF1 alpha and PGI2 were measured after operation in the three groups respectively. The postoperative blood pressure in group A, including SBP and DBP, was elevated more obviously than that in the other two groups. TXA2 and PGI2 in group A were significantly higher than those in other two groups (P<0.01). Moreover, the ratio of TXB2 to 6-keto-PGF1 alpha in group A was significantly higher than that in other two groups (P<0.05). The increase of TXA2 and the relative inadequacy of prostacyclin, especially 6-keto-PGF1 alpha, may play roles in the postoperative hypertensive crisis. And the increased value of TXB2 to 6-keto-PGF1 alpha could provide the basis for diagnosis of postoperative hypertensive crisis.

Changes of TXA2 and PGI2 during Postoperative Hypertensive Crisis in Patients with Hypertensive Intracerebral Hemorrhage / 华中科技大学学报（医学）（英德文版）

In order to explore the changes and the roles of TXA2 and PGI2 during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage, 31 cases subject to crani- otomy were divided into three groups: group A, 9 patients with postoperative hypertensive crisis; group B, 13 patients without postoperative hypertensive crisis; and group C, 9 patients without his- tory of hypertension and hypertensive intracerebral hemorrhage. TXA2＞, TXB2＞, 6-keto-PGF1α and PGI2＞ were measured after operation in the three groups respectively. The postoperative blood pres- sure in group A, including SBP and DBP, was elevated more obviously than that in the other two groups. TXA2＞ and PGI2＞ in group A were significantly higher than those in other two groups (P＜0.01). Moreover, the ratio of TXB2＞ to 6-keto-PGF1α in group A was significantly higher than that in other two groups (P＜0.05). The increase of TXA2＞ and the relative inadequacy of prostacyclin, especially 6-keto-PGF1α, may play roles in the postoperative hypertensive crisis. And the increased value of TXB2＞ to 6-keto-PGF1α could provide the basis for diagnosis of postoperative hypertensive crisis.