• Title, Summary, Keyword: glioblastoma (GBM)

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MicroRNA-203 As a Stemness Inhibitor of Glioblastoma Stem Cells

  • Deng, Yifan;Zhu, Gang;Luo, Honghai;Zhao, Shiguang
    • Molecules and Cells
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    • v.39 no.8
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    • pp.619-624
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    • 2016
  • Glioblastoma stem cells (GBM-SCs) are believed to be a subpopulation within all glioblastoma (GBM) cells that are in large part responsible for tumor growth and the high grade of therapeutic resistance that is so characteristic of GBM. MicroRNAs (miR) have been implicated in regulating the expression of oncogenes and tumor suppressor genes in cancer stem cells, including GBM-SCs, and they are a potential target for cancer therapy. In the current study, miR-203 expression was reduced in $CD133^+$ GBM-SCs derived from six human GBM biopsies. MicroRNA-203 transfected GBM-SCs had reduced capacity for self-renewal in the cell sphere assay and increased expression of glial and neuronal differentiation markers. In addition, a reduced proliferation rate and an increased rate of apoptosis were observed. Therefore, miR-203 has the potential to reduce features of stemness, specifically in GBM-SCs, and is a logical target for GBM gene therapy.

Glioblastoma Multiforme with Subcutaneous Metastases, Case Report and Literature Review

  • Guo, Liemei;Qiu, Yongming;Ge, Jianwei;Zhou, Dongxue
    • Journal of Korean Neurosurgical Society
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    • v.52 no.5
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    • pp.484-487
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    • 2012
  • Glioblastoma multiforme (GBM) is the most common primary brain tumor and the most malignant astrocytoma in adults, with rare extra-cranial metastases, especially for subcutaneous metastases. It could be easily misdiagnosed as primary subcutaneous tumor. In this report, we describe a patient with pontine GBM who developed a subcutaneous swelling at the ipsilateral posterior cervical region 8 months after operation, and the pathological and immunocytochemical examination carry the same characteristics as the primary intracranial GBM cells, which defined it as subcutaneous metastasis. GBM with subcutaneous metastasis is extremely rare, and knowledge of a prior intracranial GBM, pathological examinations and immunocytochemical tests with markers typically expressed by GBM are of vital importance for the diagnosis of GBM metastasis. Surgical resection of subcutaneous swelling, followed by chemotherapy and radiotherapy, could be the best strategy of treatment for the patients with GBM subcutaneous metastasis.

The origin-of-cell harboring cancer-driving mutations in human glioblastoma

  • Lee, Joo Ho;Lee, Jeong Ho
    • BMB Reports
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    • v.51 no.10
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    • pp.481-483
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    • 2018
  • Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

Cerebellar Glioblastoma Multiforme in an Adult

  • Hur, Hyuk;Jung, Shin;Jung, Tae-Young;Kim, In-Young
    • Journal of Korean Neurosurgical Society
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    • v.43 no.4
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    • pp.194-197
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    • 2008
  • Primary cerebellar glioblastoma multiforme (GBM) is a rare tumor in adults that accounts for just 1% of all cases of GBM. Due to their rarity, cerebellar GBMs are not yet completely understood about the pathogenesis and the prognosis. Here, we present a case of GBM in a 69-year-old man. Neurologic examination revealed the presence of cerebellar signs. Magnetic resonance imaging (MRI) showed a 4.5${\times}$3.6 cm-sized, ill-defined, heterogeneously enhancing mass in the left cerebellum and two patchy hyperintense lesions in the right cerebellum with minimal enhancement. After operation, glioblastoma was histologically confrimed. Postoperative radiotherapy with concomittent and adjuvant temozolomide chemotherapy was subsequently followed. Here, a case of unusual GBM in the cerebellum is reported with review of literature regarding the pathogenesis, the differential diagnosis and prognosis. There was no evidence of recurrence during postoperative one year. This patient showed a good prognosis in spite of the multiple lesions.

Spinal Metastases from Supratentorial Glioblastoma

  • Han, Seong-Rok;Yee, Gi-Taek;Lee, Dong-Jun;Whang, Choong-Jin
    • Journal of Korean Neurosurgical Society
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    • v.38 no.6
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    • pp.475-477
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    • 2005
  • The tendency of glioblastoma multiforme[GBM] to metastasize to the cerebrospinal fluidis well documented. However, symptomatic intradural extramedullary metastasis of GBM in the spinal cord are rarely reported. A 31-year-old female with a previously treated supratentorial GBM presented with back pain and lower extremities weakness. Magnetic resonance imaging of the thoracic spine demonstrated an intradural extramedullary mass at levels of T2-T4 and arachnoid membrane enhancement. The patient underwent an operation. Pathologic diagnosis was confirmed as spinal metastases of GBM. We present a case of spinal metastases from supratentorial GBM presented with paraparesis.

Primary Glioblastoma of the Cerebellopontine Angle : Case Report and Review of the Literature

  • Lee, Ji-Hye;Kim, Jong Hyun;Kwon, Taek-Hyun
    • Journal of Korean Neurosurgical Society
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    • v.60 no.3
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    • pp.380-384
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    • 2017
  • Glioblastoma multiforme (GBM) is located most frequently in the cerebral hemispheres. Glioblastoma presenting as an extraaxial mass of cerebellopontine angle (CPA) is very rare in adults. We report a rare case of GBM arising in the CPA. The patient was a 71-year-old female, who complained of progressive gait disturbance and poor memory. Initial magnetic resonance imaging (MRI) revealed a $1.4{\times}1.3cm$ mass in the left CPA, with broad base to the petrous bone, showing homogenous enhancement. Follow-up MRI showed a rapid increase in size of mass ($2.7{\times}2.2cm$) with a necrotic portion. A stereotactic biopsy was done under the guidance of navigation system, and the histopathologic diagnosis was GBM, World Heath Organization grade IV. Further surgical resection was not performed considering her general condition, and the patient underwent concurrent chemotherapy with radiation therapy. Although rare, the possibility of glioblastoma should be included in the differential diagnosis of atypical CPA tumor.

Lack of Sunlight Exposure Influence on Primary Glioblastoma Survival

  • Mutlu, Hasan;Akca, Zeki;Erden, Abdulsamet;Aslan, Tuncay;Ucar, Kadir;Kaplan, Bunyamin;Buyukcelik, Abdullah
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4165-4168
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    • 2014
  • Background: The prognosis of primary glioblastoma (GBM) is poor. Approximately 2/3 of primary brain tumor diagnoses are GBM, of which 95% are primary lesions. In this study, we aimed to evaluate whether more sunlight exposure has an effect on survival of patients with primary GBM. Materials and Methods: A total of 111 patients with primary GBM were enrolled from Kayseri in inner Anatolia which has a cold climate (n: 40) and Mersin in Mediterranean region with a warm climate and more sunlight exposure (n: 71). The patients with primary GBM were divided into two groups as Kayseri and Mersin and compared for progression free survival (PFS) and overall survival (OS).Results: The PFS values were 7.0 and 4.7 months for Kayseri and Mersin groups, respectively (p=0.10) and the repsective OS values were 13.3 and 9.4 months (p=0.13). We did not found any significant difference regarding age, sex, comorbidity, smoking, surgery, resurgery, adjuvant chemoradiotherapy and palliative chemotherapy between the groups. Conclusions: We found that more sunlight exposure had no impact on prognosis of patients with primary GBM, adding inconsistency to the literature about the relationship between sunlight and GBM.

Therapeutic effects of dihydroartemisinin and transferrin against glioblastoma

  • Kim, Suk Hee;Kang, Seong Hee;Kang, Bo Sun
    • Nutrition Research and Practice
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    • v.10 no.4
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    • pp.393-397
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    • 2016
  • BACKGROUND/OBJECFTIVES: Artemisinin, a natural product isolated from Gaeddongssuk (artemisia annua L.) and its main active derivative, dihydroartemisinin (DHA), have long been used as antimalarial drugs. Recent studies reported that artemisinin is efficacious for curing diseases, including cancers, and for improving the immune system. Many researchers have shown the therapeutic effects of artemisinin on tumors such as breast cancer, liver cancer and kidney cancer, but there is still insufficient data regarding glioblastoma (GBM). Glioblastoma accounts for 12-15% of brain cancer, and the median survival is less than a year, despite medical treatments such as surgery, radiation therapy, and chemotherapy. In this study, we investigated the anti-cancer effects of DHA and transferrin against glioblastoma (glioblastoma multiforme, GBM). MATERIALS/METHODS: This study was performed through in vitro experiments using C6 cells. The toxicity dependence of DHA and transferrin (TF) on time and concentration was analyzed by MTT assay and cell cycle assay. Observations of cellular morphology were recorded with an optical microscope and color digital camera. The anti-cancer mechanism of DHA and TF against GBM were studied by flow cytometry with Annexin V and caspase 3/7. RESULTS: MTT assay revealed that TF enhanced the cytotoxicity of DHA against C6 cells. An Annexin V immune-precipitation assay showed that the percentages of apoptosis of cells treated with TF, DHA alone, DHA in combination with TF, and the control group were $7.15{\pm}4.15%$, $34.3{\pm}5.15%$, $66.42{\pm}5.98%$, and $1.2{\pm}0.15%$, respectively. The results of the Annexin V assay were consistent with those of the MTT assay. DHA induced apoptosis in C6 cells through DNA damage, and TF enhanced the effects of DHA. CONCLUSION: The results of this study demonstrated that DHA, the derivative of the active ingredient in Gaeddongssuk, is effective against GBM, apparently via inhibition of cancer cell proliferation by a pharmacological effect. The role of transferrin as an allosteric activator in the GBM therapeutic efficacy of DHA was also confirmed.

CXCR4-STAT3 Axis Plays a Role in Tumor Cell Infiltration in an Orthotopic Mouse Glioblastoma Model

  • Han, Ji-hun;Yoon, Jeong Seon;Chang, Da-Young;Cho, Kyung Gi;Lim, Jaejoon;Kim, Sung-Soo;Suh-Kim, Haeyoung
    • Molecules and Cells
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    • v.43 no.6
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    • pp.539-550
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    • 2020
  • Glioblastoma multiforme (GBM) is a fatal malignant tumor that is characterized by diffusive growth of tumor cells into the surrounding brain parenchyma. However, the diffusive nature of GBM and its relationship with the tumor microenvironment (TME) is still unknown. Here, we investigated the interactions of GBM with the surrounding microenvironment in orthotopic xenograft animal models using two human glioma cell lines, U87 and LN229. The GBM cells in our model showed different features on the aspects of cell growth rate during their development, dispersive nature of glioma tumor cells along blood vessels, and invasion into the brain parenchyma. Our results indicated that these differences in the two models are in part due to differences in the expression of CXCR4 and STAT3, both of which play an important role in tumor progression. In addition, the GBM shows considerable accumulation of resident microglia and peripheral macrophages, but polarizes differently into tumor-supporting cells. These results suggest that the intrinsic factors of GBM and their interaction with the TME determine the diffusive nature and probably the responsiveness to non-cancer cells in the TME.

Force-mediated proinvasive matrix remodeling driven by tumor-associated mesenchymal stem-like cells in glioblastoma

  • Lim, Eun-Jung;Suh, Yongjoon;Kim, Seungmo;Kang, Seok-Gu;Lee, Su-Jae
    • BMB Reports
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    • v.51 no.4
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    • pp.182-187
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    • 2018
  • In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling actively occurs in glioblastoma (GBM) and the consequent microenvironmental stiffness is strongly linked to migration behavior of GBM cells. However, in GBM the stromal cells responsible for force-mediated ECM remodeling remain unidentified. We show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide a proinvasive matrix condition in GBM by force-mediated ECM remodeling. Importantly, CCL2-mediated Janus kinase 1 (JAK1) activation increased phosphorylation of myosin light chain 2 in tMSLCs and led to collagen assembly and actomyosin contractility. Collectively, our findings implicate tMSLCs as stromal cells providing force-mediated proinvasive ECM remodeling in the GBM microenvironment, and reminiscent of fibroblasts in carcinoma.