Efficacy of intensity modulated radiotherapy with sequential chemotherapy in the treatment of high-grade glioma and analysis of influential factors / 中国基层医药

Objective:To investigate the efficacy of intensity-modulated radiotherapy with sequential chemotherapy in the treatment of high-grade glioma and analyze the influential factors.Methods:A total of 56 patients with high-grade glioma who received treatment in Yantai Municipal Laiyang Central Hospital from January 2014 to January 2016 were retrospectively analyzed. All patients underwent three-dimensional conformal radiotherapy or enhanced radiotherapy. The use of bevacizumab, pathological grade, and preoperative and postoperative Karnofsky Performance Status scores in all patients were recorded. Cox and other proportional risk regression models were used to analyze the predictors of patient mortality and receiver operating characteristic (ROC) curve analysis was performed.Results:All patients were followed up to April 2022. Follow-up results showed that the median survival time of patients receiving concurrent chemotherapy with temozolomide and adjuvant chemotherapy with temozolomide was 11.6 months. Univariate analysis showed that pathological grade, Karnofsky Performance Status scores, and the degree of tumor resection were correlated with the prognosis of patients ( P = 0.022, 0.049, 0.022). Multivariate analysis showed that the degree of tumor resection and pathological grade were the independent influential factors of prognosis ( P = 0.010, 0.010). Survival curve analysis revealed that the median survival time of patients subjected to total tumor resection was 12.6 months and that of patients subjected to partial tumor resection was 4.8 months. The median survival time of patients subjected to total tumor resection was longer than that of patients subjected to partial tumor resection. The median survival time of patients with WHO grade Ⅲ tumors was 25.2 months, and it was 6.3 months for patients with WHO grade Ⅳ tumors. The median survival time of patients with WHO grade Ⅲ tumors was longer than that of patients with WHO grade Ⅳ tumors. The receiver operating characteristic curve analysis results showed that the area under the receiver operating characteristic curve plotted for using WHO classification of tumors in the neurological system and surgical methods to predict the death of patients with high-grade glioma was 0.783 and 0.814, respectively. WHO tumor grade and surgical methods for prediction of prognosis of high-grade glioma had high accuracy. Conclusion:Low pathological grade and total resection are independent protective factors for the prognosis of patients with high-grade glioma.

A rare case of pediatric medulloblastoma presented with radiographic characteristics of pontine glioma

Medulloblastoma is a common malignant brain tumor of childhood which characterized as an infratentorial mass in the roof of the 4th ventricle, causing mass effect and non-communicating hydrocephalus. A 3 years old boy with history of chronic progressive weakness one-month prior admission, followed by difficulty in walking and ataxia. His MRI examination showed an intraaxial well defined mass, partial irregular border, size 4.2x4.0x4.1 cm at pons, hypointense in T1W1, hyperintense in T2W1, iso-hypointense in flair, and showing inhomogen contras enhancement after gadolinium administration. It pressed the 4th ventricle without dilatation of other ventricles, suggesting a pontine glioma. Patient underwent surgery to remove mass and the pathological examination revealed small round cells, with differential diagnose of medulloblastoma and anaplastic astrocytoma. This case presented as there was a discrepancy in the clinicoradiological diagnosis with the pathological diagnose of medulloblastoma. The mass was located at the pontine without any sign of hydrocephalus suggested a pontine glioma. Both medulloblastoma and pontine glioma are common for infratentorial mass of pediatric population, but difficult to diagnose due to its heterogeneous presentation. Good comprehension of both radiological characteristics is noteworthy.

Diffuse Intrinsic Pontine Gliomas Exhibit Cell Biological and Molecular Signatures of Fetal Hindbrain-Derived Neural Progenitor Cells / 神经科学通报·英文版

Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG. The PPCs not only harbored similar cell biological and molecular signatures as DIPG glioma stem cells, but also had the potential to be immortalized by the DIPG-specific mutation H3K27M in vitro. These findings provide researchers with a candidate normal control and a potential medicine carrier for preclinical research on DIPG.

Bioinformatics analysis of microarray data to reveal the pathogenesis of diffuse intrinsic pontine glioma

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death. This study was designed to identify key genes associated with DIPG. METHODS: The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by limma package. Functional and pathway enrichment analyses were performed by the DAVID tool. Protein-protein interaction (PPI) network, and transcription factor (TF)-microRNA (miRNA)-target gene network were constructed using Cytoscape. Moreover, the expression levels of several genes were validated in human glioma cell line U251 and normal glia HEB cells through real-time polymerase chain reaction (PCR). RESULTS: A total of 378 DEGs were screened (74 up-regulated and 304 down-regulated genes). In the PPI network, GRM1, HTR2A, GRM7 and GRM2 had higher degrees. Besides, GRM1 and HTR2A were significantly enriched in the neuroactive ligand-receptor interaction pathway, and calcium signaling pathway. In addition, TFAP2C was a significant down-regulated functional gene and hsa-miR-26b-5p had a higher degree in the TF-miRNA-target gene network. PCR analysis revealed that GRM7 and HTR2A were significantly downregulated while TFAP2C was upregulated in U251 cells compared with that in HEB cells (p < 0.001). GRM2 was not detected in cells. CONCLUSIONS: GRM1 and HTR2A might function in DIPG through the neuroactive ligand-receptor interaction pathway and the calcium signaling pathway. Furthermore, the TFAP2C and hsa-miR-26b-5p might play important roles in the development and progression mechanisms of DIPG.

Malignant Brain Tumours in Children : Present and Future Perspectives

In contrast to many of the malignant tumors that occur in the central nervous system in adults, the management, responses to therapy, and future perspectives of children with malignant lesions of the brain hold considerable promise. Within the past 5 years, remarkable progress has been made with our understanding of the basic biology of the molecular genetics of several pediatric malignant brain tumors including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumour, and high grade glioma/diffuse intrinsic pontine glioma. The recent literature in pediatric neuro-oncology was reviewed, and a summary of the major findings are presented. Meaningful sub-classifications of these tumors have arisen, placing children into discrete categories of disease with requirements for targeted therapy. While the mainstay of therapy these past 30 years has been a combination of central nervous system irradiation and conventional chemotherapy, now with the advent of high resolution genetic mapping, targeted therapies have emerged, and less emphasis is being placed on craniospinal irradiation. In this article, the present and future perspective of pediatric brain malignancy are reviewed in detail. The progress that has been made offers significant hope for the future for patients with these tumours.

Malignant Brain Tumours in Children : Present and Future Perspectives

In contrast to many of the malignant tumors that occur in the central nervous system in adults, the management, responses to therapy, and future perspectives of children with malignant lesions of the brain hold considerable promise. Within the past 5 years, remarkable progress has been made with our understanding of the basic biology of the molecular genetics of several pediatric malignant brain tumors including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumour, and high grade glioma/diffuse intrinsic pontine glioma. The recent literature in pediatric neuro-oncology was reviewed, and a summary of the major findings are presented. Meaningful sub-classifications of these tumors have arisen, placing children into discrete categories of disease with requirements for targeted therapy. While the mainstay of therapy these past 30 years has been a combination of central nervous system irradiation and conventional chemotherapy, now with the advent of high resolution genetic mapping, targeted therapies have emerged, and less emphasis is being placed on craniospinal irradiation. In this article, the present and future perspective of pediatric brain malignancy are reviewed in detail. The progress that has been made offers significant hope for the future for patients with these tumours.