• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5137-5142
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• 2012

UHRF2 is a member of the ubiquitin plant homeo domain RING finger family, which has been proven to be frequently up-regulated in colorectal cancer cells and play a role as an oncogene in breast cancer cells. However, the role of UHRF2 in glioma cells remains unclear. In this study, we performed real-time quantitative PCR on 32 pathologically confirmed glioma samples (grade I, 4 cases; grade II, 11 cases; grade III, 10 cases; and grade IV, 7 cases; according to the 2007 WHO classification system) and four glioma cell lines (A172, U251, U373, and U87). The expression of UHRF2 mRNA was significantly lower in the grade III and grade IV groups compared with the noncancerous brain tissue group, whereas its expression was high in A172, U251, and U373 glioma cell lines. An in vitro assay was performed to investigate the functions of UHRF2. Using a lentivirus-based RNA interference (RNAi) approach, we down-regulated UHRF2 expression in the U251 glioma cell line. This down-regulation led to the inhibition of cell proliferation, an increase in cell apoptosis, and a change of cell cycle distribution, in which S stage cells decreased and G2/M stage cells increased. Our results suggest that UHRF2 may be closely related to tumorigenesis and the development of gliomas.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5857-5863
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• 2012

Introduction: Mobile phones are in extensive use worldwide and concerns regarding their role in tumor formation were raised. Over the years multiple studies were published in order to investigate this issue using several approaches. The current study looks at secular trends of brain gliomas (low and high grade) incidence and changes in tumor's laterality over 30 years in a population extensively using this technology with a possible correlation to the spread of use of mobile phones. Materials and Methods: All brain gliomas that were diagnosed from 1980-2009 were included and subdivided into two groups - low and high grade. Secular and periodic time trend analyses of incidence rates and changes in laterality were performed. Preferred side of head using mobile phones was assessed with a questionnaire in a sample of adult individuals. Results: A decrease in incidence of low grade giomas (LGG) that correlated with introduction of mobile technology was found from 2.57, 2.34 and 2.79 for every 100,000 in the period 1980 to the end of 1994 to 1.72, 1.82 and 1.57, respectively, over the last three 5-years periods (1995-2009). High-grade glioma incidences increased significantly from 1980-2009 but in the period after mobile phones were introduced (1994-2009) a lower, non significant, rate of increase was observed in males and a lower one (significant) in females. A shift towards left sided tumor location for all adult gliomas combined and separately for LGG and HGG was noted from 1995 onward. The shift was more marked for those who were diagnosed in ages 20-49 (p=0.03). Conclusions: We found a statistically significant decrease in LGG's over 30-years period that correlates with introducing of mobile phones technology and a shift in laterality towards left-sided tumors, the latter occurred in both low and high-grade gliomas.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8753-8757
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• 2014

Background: Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. Materials and Methods: We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. Results: Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. Conclusions: This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.

• Journal of Korean Neurosurgical Society
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• v.67 no.3
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• pp.364-375
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• 2024

Objective : Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. Methods : Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. Results : The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. Conclusion : Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.

• Journal of Korean Neurosurgical Society
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• v.61 no.4
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• pp.516-524
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• 2018

Objective : This study aims to determine whether gamma knife radiosurgery (GKR) improves survival in patients with recurrent high-grade 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.

• Journal of Korean Neurosurgical Society
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• v.56 no.3
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• pp.261-264
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• 2014

We report perfusion weighted imaging (PWI) findings of nonenhanced anaplastic astrocytoma in a 30-year-old woman. Brain magnetic resonance imaging showed a nonenhanced brain tumor with mild peritumoral edema on the right medial frontal lobe and right genu of corpus callosum, suggesting a low-grade glioma. However, PWI showed increased relative cerebral blood volume, relative cerebral blood flow, and permeability of nonenhanced brain tumor compared with contralateral normal brain parenchyma, suggesting a high-grade glioma. After surgery, final histopathological analysis revealed World Health Organization grade III anaplastic astrocytoma. This case demonstrates the importance of PWI for preoperative evaluation of nonenhanced brain tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5225-5230
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• 2013

Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera ($0.29{\pm}0.54$, $0.03{\pm}0.15$ and $0.16{\pm}0.68$ vs. $0.00{\pm}0.00pg/ml$; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls ($2.34{\pm}4.35$ vs. $4.67{\pm}4.32pg/ml$; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

• Journal of Korean Neurosurgical Society
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• v.61 no.3
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• pp.402-406
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• 2018

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.

• Journal of Korean Neurosurgical Society
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• v.55 no.1
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• pp.5-11
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• 2014

Objective : We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. Methods : Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. Results : Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). Conclusion : Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

• Molecules and Cells
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• v.37 no.1
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• pp.17-23
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• 2014

We already had reported that Bcl-w promotes invasion or migration in gastric cancer cells and glioblastoma multiforme (GBM) by activating matrix metalloproteinase-2 (MMP-2) via specificity protein 1 (Sp1) or ${\beta}$-cateinin, respectively. High expression of Bcl-w also has been reported in GBM which is the most common malignant brain tumor and exhibits aggressive and invasive behavior. These reports propose that Bcl-w-induced signaling is strongly associated with aggressive characteristic of GBM. We demonstrated that Sp1 protein or mRNA expression is induced by Bcl-w using Western blotting or RT-PCR, respectively, and markedly elevated in high-grade glioma specimens compared with low-grade glioma tissues using tissue array. However, relationship between Bcl-w-related signaling and aggressive characteristic of GBM is poorly characterized. This study suggested that Bcl-w-induced Sp1 activation promoted expression of glioma stem-like cell markers, such as Musashi, Nanog, Oct4 and sox-2, as well as neurosphere formation and invasiveness, using western blotting, neurosphere formation assay, or invasion assay, culminating in their aggressive behavior. Therefore, Bcl-w-induced Sp1 activation is proposed as a putative marker for aggressiveness of GBM.