• Title, Summary, Keyword: gliomas

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Deregulated Expression of Cry1 and Cry2 in Human Gliomas

  • Luo, Yong;Wang, Fan;Chen, Lv-An;Chen, Xiao-Wei;Chen, Zhi-Jun;Liu, Ping-Fei;Li, Fen-Fen;Li, Cai-Yan;Liang, Wu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5725-5728
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    • 2012
  • Growing evidence shows that deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of gene chnages controlling circadian rhythm in glioma cells have not been explored. Using real time polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, cry1 and cry2, in 69 gliomas. In this study, out of 69 gliomas, 38 were cry1-positive, and 51 were cry2-positive. The expression levels of cry1 and cry2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of cry1 and cry 2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was non-significant (P>0.05) but there was a difference in the intensity of immunoactivity for cry 2 between high-grade gliomas and low-grade gliomas (r=-0.384, P=0.021). In this study, we found that the expression of cry1 and cry2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in cry1 and cry2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.

Combination Therapy for Gliomas Using Temozolomide and Interferon-Beta Secreting Human Bone Marrow Derived Mesenchymal Stem Cells

  • Park, Jae-Hyun;Ryu, Chung Heon;Kim, Mi Jin;Jeun, Sin-Soo
    • Journal of Korean Neurosurgical Society
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    • v.57 no.5
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    • pp.323-328
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    • 2015
  • Objective : Malignant gliomas are the most common primary tumors of the central nervous system and the prognosis of patients with gliomas is poor. The combination of interferon-bata (IFN-${\beta}$) and temozolomide (TMZ) has shown significant additive antitumor effects in human glioma xenograft models. Considering that the poor survival of patients with human malignant gliomas relates partly to the inability to deliver therapeutic agents to the tumor, the tropism of human bone marrow-derived mesenchymal stem cells (MSC) for malignant gliomas can be exploited to therapeutic advantages. We investigated the combination effects of TMZ and MSCs that secrete IFN-${\beta}$ on gliomas. Methods : We engineered human MSCs to secret mouse IFN-${\beta}$ (MSC-IFN-${\beta}$) via adenoviral transduction and confirmed their secretory capacity using enzyme-linked immunosorbent assays. In vitro and in vivo experiments were performed to determine the effects of the combined TMZ and MSC-IFN-${\beta}$ treatment. Results : In vitro, the combination of MSC-IFN-${\beta}$ and TMZ showed significantly enhanced antitumor effects in GL26 mouse glioma cells. In vivo, the combined MSC-IFN-${\beta}$ and TMZ therapy significantly reduced the tumor size and improved the survival rates compared to each treatment alone. Conclusion : These results suggest that MSCs can be used as an effective delivery vehicle so that the combination of MSC-IFN-${\beta}$ and TMZ could be considered as a new option for the treatment of malignant gliomas.

Reclassification of Mongolian Diffuse Gliomas According to the Revised 2016 World Health Organization Central Nervous System Tumor Classification

  • Ochirjav, Enkhee;Enkhbat, Bayarmaa;Baldandorj, Tuul;Choe, Gheeyoung
    • Journal of Pathology and Translational Medicine
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    • v.53 no.5
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    • pp.298-307
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    • 2019
  • Background: The 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors has been modified to incorporate the IDH mutation and 1p/19q co-deletion in the diagnosis of diffuse gliomas. In this study, we aimed to evaluate the feasibility and prognostic significance of the revised 2016 WHO classification of CNS tumors in Mongolian patients with diffuse gliomas. Methods: A total of 124 cases of diffuse gliomas were collected, and tissue microarray blocks were made. IDH1 mutation was tested using immunohistochemistry, and 1p/19q co-deletion status was examined using fluorescence in situ hybridization analysis. Results: According to the 2016 WHO classification, 124 cases of diffuse brain glioma were reclassified as follows: 10 oligodendroglioma, IDHmut and 1p/19q co-deleted; three anaplastic oligodendroglioma, IDHmut and 1p/19q co-deleted; 35 diffuse astrocytoma, IDHmut, 11 diffuse astrocytoma, IDHwt, not otherwise specified (NOS); 22 anaplastic astrocytoma, IDHmut, eight anaplastic astrocytoma, IDHwt, NOS; and 35 glioblastoma, IDHwt, NOS, respectively. The 2016 WHO classification presented better prognostic value for overall survival in patients with grade II tumors than traditional histological classification. Among patients with grade II tumors, those with oligodendroglioma IDHmut and 1p/19q co-deleted and diffuse astrocytoma IDHmut showed significantly higher survival than those with diffuse astrocytoma IDHwt, NOS (p<.01). Conclusions: Mongolian diffuse gliomas could be reclassified according to the new 2016 WHO classification. Reclassification revealed substantial changes in diagnosis of both oligodendroglial and astrocytic entities. We have confirmed that the revised 2016 WHO CNS tumor classification has prognostic significance in Mongolian patients with diffuse gliomas, especially those with grade II tumors.

Molecular Investigation of Isocitrate Dehydrogenase Gene (IDH) Mutations in Gliomas: First Report of IDH2 Mutations in Indian Patients

  • Ranjan Das, Bibhu;Tangri, Rajiv;Ahmad, Firoz;Roy, Arnab;Patole, Kamlakar
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7261-7264
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    • 2013
  • Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome. These mutations have become molecular markers of significant diagnostic and prognostic relevance in the assessment of human gliomas. In the current study we evaluated IDH1 (R132) and IDH2 (R172) in 32 gliomas of various grades and tumor subtypes. Sequencing analysis revealed R132H mutations in 18.7% tumors, while none of the cases showed IDH2 (R172) mutations. The frequency of IDH1 mutations was higher in females (21.4%) than males (11.1%), and it was significantly higher in younger patients. Histological analyses demonstrated presence of necrosis and micro vascular proliferation in 69% and 75% respectively. Interestingly, IDH1 mutations were predominantly present in non-necrotic tumors as well as in cases showing microvascular proliferation. Of the six IDH1 positive cases, three were glioblastomas (IV), and one each were anaplastic oligoastrocytoma (III), anaplastic oligodendroglioma III (n=1) and diffuse astrocytoma. In conclusion, IDH1 mutations are quite frequent in Indian glioma patients while IDH2 mutations are not observed. Since IDH mutations are associated with good prognosis, their use in routine clinical practice will enable better risk stratification and management of glioma patients.

Expression of Telomerase Activity and Apoptosis in Human Brain Tumors (인체 뇌종양조직에서 텔로머레이즈의 발현과 세포사멸)

  • Kim, Choong Hyun;Cheong, Jin Hwan;Bak, Koang Hum;Kim, Jae Min;Ko, Yong;Oh, Suck Jun
    • Journal of Korean Neurosurgical Society
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    • v.30 no.2
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    • pp.137-143
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    • 2001
  • Objective : Telomerase, a ribonucleoprotein adds telomere repeats to the ends of telomeres to compensate for the progressive loss. A favorable prognosis associated with low or no telomerase activity in some tumors, and cells transfected with antisense human telomerase lost telomeric repeats and die. We studied about the relationship between telomerase activity and apoptosis in the human brain tumors. Material and Methods : Between July 1998 and December 1999, 62 patients with brain tumors underwent surgery and their surgical specimens were obtained. Telomerase activity was investigated by telomeric repeats amplification protocol(TRAP) assay. Apoptosis was also evaluated by DNA fragmentation analysis. Differences and correlation in data were analyzed using Mann-Whitney test and Wilcoxon-signed rank test. Results : Expression rate of telomerase activity and apoptosis were 80% and 30% in malignant gliomas, 33% and 0% in low grade gliomas, 63% and 38% in meningiomas, 67% and 33% in pituitary adenomas, 33% and 33% in metastatic tumors, 67% and 17% in acoustic neurinomas, 100% and 100% in pineoblastomas, 100% and 0% in the hemangioblastoma, respectively. There was no significant difference of telomerase activity and apoptosis between histological types. But a significant difference was noted in the expression of telomerase activity between malignant gliomas and low grade gliomas(p = 0.022). Brain tumors with telomerase activity expressed the lower rate of apoptosis. A significant correlation was also found between telomerase activity and absence of apoptosis in the human brain tumors(p = 0.005). Conclusions : Our data suggests that telomerase may protect from apoptosis of the human brain tumors and also may play an important role in the biological malignancy of the gliomas.

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Usefulness of $^{11}C-Methyl-L-and$ D-Methionine PET in Gliomas : with Special Attention to Recurrence

  • Cho, Won-Sang;Kim, Chi-Heon;Kim, Jeong-Eun;Chung, June-Key;Paek, Sun-Ha;Jung, Hee-Won
    • Journal of Korean Neurosurgical Society
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    • v.39 no.3
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    • pp.176-182
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    • 2006
  • Objective : This study concernes the usefulness of $^{11}C-methyl-L-and$ D-methionine[Met]-positron emission tomography[PET] for glioma grading and detection of recurrence in gliomas, compared with fluorine-18, 2-fluoro-deoxyglucose[FDG]-PET. Methods : Eighty patients underwent Met-PET study for evaluation of glioma : 37 astrocytomas [WHO grade II, 3; III, 8; IV, 26]. 27 oligodendrogliomas [WHO grade II, 16; III, 11]. and 12 suspicious recurrent gliomas. All images were taken within 2 weeks before operation. For suspicious recurrent cases on magnetic resonance images, both FDG-PET and Met-PET were performed. Results : In astrocytoma, Mean maximum standard uptake value[SUV] of region of interest[ROI] was not different between WHO grades [p=0.108]. but ROI/normal contralateral tissue SUV [T/N] ratio was statistically different between WHO grades [p=0.002]. T/N ratio was more closely related to visual scale than maximum SUV of ROI [p<0.001 and p=0.107 respectively]. In oligodendroglioma, there was no statistical difference between WHO grades in view of maximum SUV and T/N ratio. For recurrent gliomas, sensitivity of FDG-PET and Met-PET was 25% and 100%, while specificity of FDG-PET and Met-PET were 100% and 80%, respectively. Conclusion : Met-PET might be an appropriate tool for tumor grading in astrocytoma and be more sensitive for detection of recurrence in gliomas than FDG-PET.

An Updated Pooled Analysis of Glutathione S-transferase Genotype Polymorphisms and Risk of Adult Gliomas

  • Yao, Lei;Ji, Guixiang;Gu, Aihua;Zhao, Peng;Liu, Ning
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.157-163
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    • 2012
  • Objective: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in the detoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studies investigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors have reported conflicting results. The rationale of this pooled analysis was to determine whether the presence of a GST variant increases adult glioma susceptibility by combining data from multiple studies. Methods: In our meta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT and EMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1 Ile105Val. Between-study heterogeneity was assessed using ${\chi}^2$-based Q statistic and the $I^2$ statistic. Crude odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. Results: The quantitative synthesis showed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 or GSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively; 95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Conclusions: Overall, this study did not suggest any strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adult gliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history on glioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potential confounding factors are needed to confirm these results.

Association of XRCC3 Thr241Met Polymorphisms and Gliomas Risk: Evidence from a Meta-analysis

  • Liang, Hong-Jie;Yan, Yu-Lan;Liu, Zhi-Ming;Chen, Xu;Peng, Qi-Liu;Wang, Jian;Mo, Cui-Ju;Sui, Jing-Zhe;Wu, Jun-Rong;Zhai, Li-Min;Yang, Shi;Li, Tai-Jie;Li, Ruo-Lin;Li, Shan;Qin, Xue
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4243-4247
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    • 2013
  • The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36-2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results.

Malignant Transformation of Hemispheric Low-Grade Gliomas : Clinical Analysis and Prognostic Factors (뇌반구에 위치한 양성신경교종의 악성전환에 대한 임상적 연구)

  • Cho, Keun-Tae;Gwak, Ho-Shin;Jung, Hee-Won;Paek, Sun-Ha;Chung, Young Seob;Kim, Dong Gyu;Cho, Byung Kyu
    • Journal of Korean Neurosurgical Society
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    • v.30 no.7
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    • pp.855-860
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    • 2001
  • Introduction : It has been reported that the survival of low-grade glioma patients depends upon the time of malignant transformation. The authors presents the clinical analysis of histologically proven trasformed gliomas. Materials and Method : A total 92 patients who were consecutively treated and histologically confirmed hemispheric low-grade gliomas between 1980 and 1998 were analyzed and followed. All cases meet the criteria of WHO glioma classification of grade II. Results : The mean follow-up period was 73 months. Twenty two among 92 cases(24%) were histologically proven to be transformed into malignant ones. The mean time to transformation was 56 months. The 5-year and 10-year survival rates of the transformed group were 66% and 30% respectively and significantly different from the survival rates of the non-transformed group(p=0.0018). Among clinical factors at presentation, the initial tumor volume had a tendency to be larger in the transformed group than that of the non-transformed group and became significant when it was divided into more than $30cm^3$ or not(p=0.02). Among therapeutic factors, the extent of removal had no influence on the rate of malignant transformation. But postoperative radiation therapy were more frequently given to the pre-transformed group than the non-transformed group and the frequency was significantly different(p=0.02). Conclusions : The authors had found that the initial tumor volume and radiation therapy could be clinical prognostic factors for the malignant transformation of low-grade gliomas.

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GRIM-19 Expression and Function in Human Gliomas

  • Jin, Yong-Hao;Jung, Shin;Jin, Shu-Guang;Jung, Tae-Young;Moon, Kyung-Sub;Kim, In-Young
    • Journal of Korean Neurosurgical Society
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    • v.48 no.1
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    • pp.20-30
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    • 2010
  • Objective : We determined whether the expression of GRIM-19 is correlated with pathologic types and malignant grades in gliomas, and determined the function of GRIM-19 in human gliomas. Methods : Tumor tissues were isolated and frozen at $-80^{\circ}C$ just after surgery. The tissues consisted of normal brain tissue (4), astrocytomas (2), anaplastic astrocytomas (2), oligodendrogliomas (13), anaplastic oligodendrogliomas (11), and glioblastomas (16). To profile tumor-related genes, we applied RNA differential display using a $Genefishing^{TM}$ DEG kit, and validated the tumor-related genes by reverse transcription polymerase chain reaction (RT-PCR). A human glioblastoma cell line (U343MG-A) was used for the GRIM-19 functional studies. The morphologic and cytoskeletal changes were examined via light and confocal microscopy. The migratory and invasive abilities were investigated by the simple scratch technique and Matrigel assay. The antiproliferative activity was determined by thiazolyl blue Tetrazolium bromide (MTT) assay and FACS analysis. Results : Based on RT-PCR analysis, the expression of GRIM-19 was higher in astrocytic tumors than oligodendroglial tumors. The expression of GRIM-19 was higher in high-grade tumors than low-grade tumors or normal brain tissue; glioblastomas showed the highest expression. After transfection of GRIM-19 into U343MG-A, the morphology of the sense-transfection cells became larger and more spindly. The antisensetransfection cells became smaller and rounder compared with wild type U343MG-A. The MTT assay showed that the sense-transfection cells were more sensitive to the combination of interferon-$\beta$ and retinoic acid than U343MG-A cells or antisense-transfection cells; the antiproliferative activity was related to apoptosis. Conclusion : GRIM-19 may be one of the gene profiles which regulate cell death via apoptosis in human gliomas.