Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials
Edward K. AvilaMarc C. ChamberlainDavid SchiffJaap C. ReijneveldTerri S. ArmstrongRoberta RudàPatrick Y. WenMichael WellerJohan A F KoekkoekSandeep MittalYoshiki ArakawaAli ChoucairJorge González-MartínezDavid MacdonaldRyo NishikawaAashit ShahCharles J. VechtPaula WarrenMartin J. van den BentLisa M. DeAngelis
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Abstract:
Patients with low-grade glioma frequently have brain tumor–related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy. A review of the current literature regarding seizure assessment for low-grade glioma patients reveals a heterogeneous manner in which seizure response has been reported. There is a need for a systematic approach to seizure assessment and its influence on health-related quality-of-life outcomes in patients enrolled in low-grade glioma therapeutic trials. In view of the need to have an adjunctive metric of tumor response in these patients, a method of seizure assessment as a metric in brain tumor treatment trials is proposed.Keywords:
Brain tumor
Malignant glioma is the most common and aggressive primary brain tumor and the overall prognosis for glioma patients remains poor. Clarification of the molecular mechanism responsible for glioma progression is critical for the effective treatment of glioma. Melanoma antigen gene (MAGE)-A2 (MAGEA2) is a member of the MAGE-A family proteins widely studied for cancer vaccine development and identification of tumor markers. However, MAGEA2 clinical significance and biological function in glioma remain unclear, especially for the prognosis of glioma patients. This study investigates MAGEA2 expression in glioma tissue samples and its significance in predicting glioma patient prognosis. MAGEA2 protein expression in tissue samples was measured by immunohistochemistry and western blotting, and MAGEA2 mRNA expression was determined by real-time polymerase chain reaction. Our results confirmed that MAGEA2 mRNA and protein expression levels were upregulated in glioma tissues, compared with normal brain tissue. The high expression of MAGEA2 in glioma tissues significantly correlated with World Health Organization advanced grade. Univariate and multivariate analyses revealed that high MAGEA2 expression is an independent prognostic factor for glioma patient poor overall survival. The P53 mRNA expression levels were downregulated in glioma tissues compared to noncancerous brain tissue and MAGEA2 expression negatively correlated with P53 expression. Taken together, our results suggest that MAGEA2 plays an oncogenic role in glioma progression, and they provide insight into MAGEA2 application as a novel predictor of clinical outcomes and a potential glioma biomarker.
Clinical Significance
Tumor progression
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Epilepsy is one of the most common glioma complications, and the two may be connected in more ways than we understand. We aimed to investigate the clinical features of glioma-associated epilepsy and explore the risk factors associated with it.We collected clinical information from 485 glioma patients in the Nanjing Brain Hospital and conducted 4 periodic follow-up visits. Based on the collected data, we analyzed the clinical characteristics of glioma patients with or without epilepsy and their relationship with survival.Among glioma patients, younger people were more likely to have epilepsy. However, epilepsy incidence was independent of gender. Patients with grade II gliomas were most likely to develop epilepsy, while those with grade IV gliomas were least likely. There was no difference in Karnofsky Performance Status scores between patients with glioma-associated epilepsy and those without epilepsy. Additionally, epilepsy was independently associated with longer survival in the World Health Organization grade IV glioma patients. For grades II, III, and IV tumors, the 1-year survival rate of the epilepsy group was higher than that of the non-epilepsy group.Epilepsy did not lead to worse admission performance and correlated with a better prognosis for patients with grade IV glioma.
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Abstract Background: Glioma is a type of malignant cancer in the central nervous system. New predictive biomarkers have been investigated in recent years, but the clinical prognosis in glioma remains poor. The function of CPLX2 in glioma and the probable molecular mechanism of tumor suppression was the focus of this investigation. Methods: The glioma transcriptome profile is downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were performed to analyze the expression of CPLX2 in glioma. RT-qPCR was performed to detect the expression of CPLX2 in 68 glioma subjects, these patients who have been followed up. Kaplan-Meier survival analyses were done to evaluate the effect of CPLX2 on the prognosis of glioma patients. The CPLX2 knockdown and overexpressed cell lines were constructed to investigate the effect of CPLX2 on glioma. The cell growth, colony formation, and tumor formation in xenograft were performed. Results: The expression of CPLX2 was downregulated in glioma and negatively correlated to the grade of glioma. The higher expression of CPLX2 predicted a longer survival through the analysis of Kaplan-Meier survival curves. Overexpressed CPLX2 impaired tumorigenesis in glioma progression both in vivo and in vitro . Knocking down of CPLX2 promoted the proliferation of the glioma cells. The analysis of GSEA and co-expression analysis revealed that CPLX2 may affect the malignancy of glioma by regulating hypoxia and inflammation pathway. Conclusions: Our data indicated that CPLX2 functioned as a tumor suppressor and could be used as a potential prognostic marker in glioma.
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People with epilepsy suffer from a considerable lack of physical activity. In addition, an important problem of epilepsy management is the lack of qualified professionals. In this study we present data from a survey which aimed to assess physical educators' general knowledge about epilepsy. One hundred and thirty four physical educators of both sexes answered a questionnaire. Sixty percent of the professionals believe that a seizure is an abnormal electrical discharge of the brain, 13% that epilepsy is a cerebral chronic disease that can not be cured or controlled, 84% that people having convulsions will not necessarily present epilepsy and 5% that people with epilepsy have difficulties of learning. Questions concerned previous professional experience with epilepsy showed that 61% have seen a seizure and 53% have access to some information about epilepsy. Thus, 28% of professionals have a friend or relative with epilepsy, 14% have a student with epilepsy, and 29% helped someone during seizures. Our findings reveal a lack of physical educators' appropriate knowledge about epilepsy. Improvement of this might contribute to the improvement of epilepsy care/management.
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On the basis of the prospective study, concerning 100 children of mothers with epilepsy, observed in the first decade, it was established that epilepsy appeared more often in this period than it was reported in the retrospective studies. The frequency of epilepsy amounted 7%. The pregnant-perinatal negative factors in mothers whose children suffered from epilepsy, weren't essentially larger than in other mothers with epilepsy. The occurrence of epilepsy in mothers till 10 year's of age increases the risk of early appearance of epilepsy in offspring essentially (p < 0.05). The epilepsy with absence seizures in mothers is related to the increased number of children with epilepsy in the first decade significantly more often than the epilepsy only with generalized tonic-clonic seizures (p < 0.012). Among the children with epilepsy, there were cases with the same type as in mothers epilepsy (absence), and with other generalized idiopathic epileptic syndromes (West syndrome, Dose syndrome, epilepsy with tonic-clinic seizures). The course of epilepsy in offspring of mothers with epilepsy was typical for the relevant epileptic syndroms appearing in childhood.
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Glioma is a tumor of the brain. Although the clinical regimens and surgical techniques for glioma have improved, therapies of advanced glioma remain challenging, carrying dismal overall survival and therapeutic success rates. Evidence has shown that miRNAs played important roles in glioma development. The current study aimed at investigating the function of a novel cancerogenic miRNA, miR-93, in glioma progression by investigating the expression and mechanism of it.qRT-PCR was conducted to assess the miR-93 expression and the mRNA expression of target gene in glioma tissues and cells. The invasion and migration abilities of the glioma cells were determined by transwell assays. Luciferase reporter assay was performed to confirm the target of miR-93.The results indicated that miR-93 expression in glioma tissues and cells was increased significantly than that in normal brain tissues and cells. Furthermore, miR-93 promoted glioma cell migration and invasion. RBL2 was recognized as a direct target of miR-93 in glioma cells, and overexpression of RBL2 could reverse the stimulative effect of miR-93 in glioma cell.The above findings suggested that miR-93 together with RBL2 could be diagnostic targets and novel prognostic markers for glioma.
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