In this issue of the Chinese Journal of Cancer, European experts review current standards, trends, and future prospects in the difficult domain of high-grade glioma. In all fields covered by the different authors, the progress has been impressive. For example, discoveries at the molecular level have already impacted imaging, surgery, radiotherapy, and systemic therapies, and they are expected to play an increasing role in the management of these cancers. The European Organization for Research and Treatment of Cancer (EORTC) has pioneered new treatment strategies and contributed to new standards. The articles in this issue will cover basic molecular biological principles applicable today, novel surgical approaches, innovations in radiotherapy planning and delivery, evidence-based standards for radiotherapy alone or combined with chemotherapy, current standards and novel approaches for systemic treatments, and the important but often neglected field of health-related quality of life. Despite the advances described in these articles, the overall prognosis of high-grade glioma, especially glioblastoma, remains poor, and more research is needed to address this problem.
Brain Neoplasms ; pathology ; therapy ; Combined Modality Therapy ; Glioblastoma ; pathology ; therapy ; Glioma ; pathology ; therapy ; Humans ; Neoplasm Grading ; Quality of Life

Cerebral Cortex ; physiology ; Electric Stimulation Therapy ; Electroencephalography ; Epilepsy ; pathology ; physiopathology ; surgery ; Female ; Glioma ; pathology ; physiopathology ; surgery ; Humans ; Middle Aged

Subependymoma is a rare, slow-growing, benign noninvasive tumor of the central nervous system that may be located in the fourth ventricle, the septum pellucidum, the third and the lateral ventricles, the aqueduct, and the proximal spinal cord. Symptoms, if any, usually result either from direct compression of the brain stem or from acute hydrocephalus due to occlusion of the foramen of Monro or aqueduct of Sylvius. In this report, we describe a case of subependymoma of the lateral ventricle with headache in a young female patient. This is the first reported case subependymoma in Korea that was documented along with Magnetic resonance image.
Adult ; Cerebral Ventricle Neoplasms/*diagnosis/pathology ; Female ; Glioma/*drug therapy/pathology ; Headache/complications ; Humans ; Magnetic Resonance Imaging

OBJECTIVETo explore the possibility of tranfecting hNIS and hTPO genes into gliomas cells by recombinant adenovirus for radioactive iodide treatment.

METHODSTo tranfect hNIS gene into human glioma cell line U251 by recombinant adenovirus. The biological functions of the cells stably expressing hNIS and hTPO genes were assessed by (125)I uptake assay, (125)I influx-course and (125)I-efflux-course. A glioma model was established with inoculation of the U251 cells in nude mice, and the inhibiting effect of (131)I on the tumor growth was tested in the mouse models.

RESULTSThe hNIS and hTPO genes were successfully transfected into human gliomas cell line U251 cells by recombinant adenovirus. The radioactive iodide could be intaken by the tumor cells mediated by hNIS gene. The uptake of (125)I was higher in cell lines hNIS-U251 and hNIS-hTPO-U251 cells than in cell line U251 cells. The tumor volume of the mice after (131)I treatment was significantly decreased in comparison with that before treatment.

CONCLUSIONRadioactive (131)I treatment after HNIS-based gene transfer can be enhanced and effectively inhibit the tumor growth in nude mice.

Adenoviridae ; genetics ; Animals ; Brain Neoplasms ; pathology ; therapy ; Genetic Therapy ; Glioma ; pathology ; therapy ; Humans ; In Vitro Techniques ; Iodides ; Iodine Radioisotopes ; metabolism ; therapeutic use ; Mice, Nude ; Symporters ; genetics ; Transfection

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited familial tumor syndrome. Benign tumors such as pilocytic astrocytoma, optic glioma make up the majority of intracranial neoplasms in patients with NF1. There have only been a handful of cases in which adult glioblastoma presented with NF1. A 32-year-old male presented with headache and radiological studies showing a high grade intra-axial tumor. The patient underwent gross total surgical excision and the pathology revealed glioblastoma. After the surgery, he received concomitant chemo-radiotherapy with temozolomide and adjuvant temozolomide chemotherapy. We report a NF1 patient who developed glioblastoma and reviewed related articles.
Adult ; Astrocytoma ; Brain Neoplasms ; Drug Therapy ; Glioblastoma* ; Hand ; Headache ; Humans ; Male ; Neurofibromatosis 1* ; Optic Nerve Glioma ; Pathology

OBJECTIVE: This study aims to determine whether gamma knife radiosurgery (GKR) improves survival in patients with recurrent highgrade gliomas.METHODS: Twenty nine patients with recurrent high-grade glioma underwent 38 GKR. The male-to-female ratio was 10 : 19, and the median age was 53.8 years (range, 20–75). GKR was performed in 11 cases of recurrent anaplastic oligodendrogliomas, five anaplastic astrocytomas, and 22 glioblastomas. The median prescription dose was 16 Gy (range, 10–24), and the median target volume was 7.0 mL (range, 1.1–15.7). Of the 29 patients, 13 (44.8%) received concurrent chemotherapy. We retrospectively analyzed the progression-free survival (PFS) and overall survival (OS) after GKR depending on the Eastern Cooperative Oncology Group (ECOG) performance status (PS), pathology, concurrent chemotherapy, radiation dose, and target tumor volume.RESULTS: Starting from when the patients underwent GKR, the median PFS and OS were 5.0 months (range, 1.1–28.1) and 13.0 months (range, 1.1–75.1), respectively. On univariate analysis, the median PFS was significantly long in patients with anaplastic oligodendroglioma, ECOG PS 1, and target tumor volume less than 10 mL (p < 0.05). Meanwhile, on multivariate analysis, patients with ECOG PS 1 and target tumor volume less than 10 mL showed improved PFS (p=0.043 and p=0.007, respectively). The median OS was significantly increased in patients with ECOG PS 1 and tumor volume less than 10 mL on univariate and multivariate analyses (p < 0.05).CONCLUSION: GKR could be an additional treatment option in recurrent high-grade glioma, particularly in patients with good PS and limited tumor volume.
Astrocytoma ; Disease-Free Survival ; Drug Therapy ; Glioblastoma ; Glioma ; Humans ; Multivariate Analysis ; Oligodendroglioma ; Pathology ; Prescriptions ; Radiosurgery ; Recurrence ; Retrospective Studies ; Tumor Burden

Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas, making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells. However, little is known about the mechanisms underlying the glioma-induced tropism of stem cells. Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas. Here we review the possible mechanisms of stem cells tropism for malignant gliomas.
Brain Neoplasms ; pathology ; therapy ; Cell Movement ; physiology ; Glioma ; pathology ; therapy ; Humans ; Neoplasm Invasiveness ; Neurons ; cytology ; Stem Cells ; classification ; cytology ; physiology ; Tropism ; physiology

Gliomas are malignant primary brain tumors and yet incurable. Palliation and the maintenance or improvement of the patient's quality of life is therefore of main importance. For that reason, health-related quality of life (HRQoL) has become an important outcome measure in clinical trials, next to traditional outcome measures such as overall and progression-free survivals, and radiological response to treatment. HRQoL is a multidimensional concept covering physical, psychological, and social domains, as well as symptoms induced by the disease and its treatment. HRQoL is assessed by using self-reported, validated questionnaires. Various generic HRQoL questionnaires, which can be supplemented with a brain tumor- specific module, are available. Both the tumor and its treatment can have a negative effect on HRQoL. However, treatment with surgery, radiotherapy, chemotherapy, and supportive treatment may also improve patients' HRQoL, in addition to extending survival. It is expected that the impact of HRQoL measurements in both clinical trials and clinical practice will increase. Hence, it is important that HRQoL data are collected, analyzed, and interpreted correctly. Methodological issues such as selection bias and missing data may hamper the interpretation of HRQoL data and should therefore be accounted. In clinical trials, HRQoL can be used to assess the benefits of a new treatment strategy, which should be weighed carefully against the adverse effects of that treatment. In daily clinical practice, HRQoL assessments of an individual patient can be used to inform physicians about the impact of a specific treatment strategy, and it may facilitate the communication between the physicians and the patients.
Brain Neoplasms ; pathology ; psychology ; therapy ; Glioma ; pathology ; psychology ; therapy ; Health Status ; Humans ; Neoplasm Grading ; Outcome Assessment (Health Care) ; Quality of Life ; Surveys and Questionnaires

Anti-angiogenic therapy has shown promising but insufficient efficacy on gliomas. Recent studies suggest that vasculogenic mimicry (VM), or the formation of non-endothelial, tumor-cell-lined microvascular channels, occurs in aggressive tumors, including gliomas. There is also evidence of a physiological connection between the endothelial-lined vasculature and VM channels. Tumor cells, by virtue of their high plasticity, can form vessel-like structures themselves, which may function as blood supply networks. Our previous study on gliomas showed that microvessel density was comparably less in VM-positive tumors than in VM-negative tumors. Thus, VM may act as a complement to ensure tumor blood supply, especially in regions with less microvessel density. Patients with VM-positive gliomas survived a shorter period of time than did patients with VM-negative gliomas. Although the detailed molecular mechanisms for VM are not fully understood, glioma stem cells might play a key role, since they are involved in tumor tissue remodeling and contribute to neovascularization via transdifferentiation. In the future, successful treatment of gliomas should involve targeting both VM and angiogenesis. In this review, we summarize the progress and challenges of VM in gliomas.
Antigens, CD34 ; metabolism ; Brain Neoplasms ; blood supply ; pathology ; therapy ; Glioma ; blood supply ; pathology ; therapy ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Microcirculation ; Neoplasms ; blood supply ; pathology ; therapy ; Neoplastic Stem Cells ; pathology ; Neovascularization, Pathologic ; Prognosis

Glioma-related edema (GRE) is a significant contributor to morbidity and mortality from glioma. GRE is a complicated process involving not only peritumoral edema but also the water content of the tumor body. In terms of etiology, this condition derives from both GRE in the untreated state and GRE secondary to clinical intervention, and different cell types contribute to distinct components of GRE. Peritumoral edema was previously believed to loosen glioma tissue, facilitating tumor-cell invasion; however, the nutrition hypothesis of the tumor microecosystem suggests that tumor cells invade for the sake of nutrition. Edema is the pathologic consequence of the reconstructed trophic linkage within the tumor microecosystem. Glioma cells induce peritumoral brain edema via an active process that supplies a suitable niche for peritumoral invasive cells, suggesting that glioma-related peritumoral brain edema is determined by the invasive property of tumor cells. There are differences between pivotal molecular events and reactive molecular events in the development of GRE. Molecular therapy should target the former, as targeting reactive molecular events will produce undesired or even adverse results. At present, brain glioma angiogenesis models have not been translated into a new understanding of the features of brain images. The effect of these models on peritumoral brain edema is unclear. Clinical approaches should be transformed on the basis of new knowledge of the molecular mechanism underlying GRE. Exploring clinical assessment methods, optimizing the existing control strategy of GRE, and simultaneously developing new treatments are essential.
Brain Edema ; diagnosis ; drug therapy ; metabolism ; pathology ; Brain Neoplasms ; diagnosis ; drug therapy ; metabolism ; pathology ; Glioma ; diagnosis ; drug therapy ; metabolism ; pathology ; Humans ; Magnetic Resonance Imaging ; Molecular Targeted Therapy ; Vascular Endothelial Growth Factor A ; metabolism