• Title, Summary, Keyword: Glioblastoma

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Kaposi's Sarcoma-Associated Herpesvirus Infection Modulates the Proliferation of Glioma Stem-Like Cells

  • Jeon, Hyungtaek;Kang, Yun Hee;Yoo, Seung-Min;Park, Myung-Jin;Park, Jong Bae;Lee, Seung-Hoon;Lee, Myung-Shin
    • Journal of Microbiology and Biotechnology
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    • v.28 no.1
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    • pp.165-174
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    • 2018
  • Glioblastoma multiforme is the most lethal malignant brain tumor. Despite many intensive studies, the prognosis of glioblastoma multiforme is currently very poor, with a median overall survival duration of 14 months and 2-year survival rates of less than 10%. Although viral infections have been emphasized as potential cofactors, their influences on pathways that support glioblastoma progression are not known. Some previous studies indicated that human Kaposi's sarcoma-associated herpesvirus (KSHV) was detected in healthy brains, and its microRNA was also detected in glioblastoma patients' plasma. However, a direct link between KSHV infection and glioblastoma is currently not known. In this study, we infected glioblastoma cells and glioma stem-like cells (GSCs) with KSHV to establish an in vitro cell model for KSHV-infected glioblastoma cells and glioma stem-like cells in order to identify virologic outcomes that overlap with markers of aggressive disease. Latently KSHV-infected glioblastoma cells and GSCs were successfully established. Additionally, using these cell models, we found that KSHV infection modulates the proliferation of glioma stem-like cells.

Farnesyl diphosphate synthase is important for the maintenance of glioblastoma stemness

  • Kim, Hee Yeon;Kim, Dong Keon;Bae, Seung-Hyun;Gwak, HyeRan;Jeon, Ji Hoon;Kim, Jong Kwang;Lee, Byung Il;You, Hye Jin;Shin, Dong Hoon;Kim, Young-Ho;Kim, Soo Youl;Han, Sung-Sik;Shim, Jin-Kyoung;Lee, Ji-Hyun;Kang, Seok-Gu;Jang, Hyonchol
    • Experimental and Molecular Medicine
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    • v.50 no.10
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    • pp.7.1-7.12
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    • 2018
  • Glioblastoma is a highly malignant tumor that easily acquires resistance to treatment. The stem-cell-like character (stemness) has been thought to be closely associated with the treatment resistance of glioblastoma cells. In this study, we determined that farnesyl diphosphate synthase (FDPS), a key enzyme in isoprenoid biosynthesis, plays an important role in maintaining glioblastoma stemness. A comparison of the mRNA expression in patient-derived glioblastoma sphere cells, which maintain stemness, and their differentiated counterparts, which lose stemness, via RNA sequencing showed that most of the altered genes were networked in the cholesterol biosynthesis pathway. We screened Federal Drug Administration (FDA)-approved drugs targeting specific enzymes in the cholesterol biosynthesis pathway for their ability to inhibit glioblastoma sphere formation. Inhibitors of FDPS, such as alendronate and zoledronate, significantly reduced the formation of glioblastoma spheres, and alendronate was effective at a lower molar concentration than zoledronate. Knockdown of FDPS using short hairpin RNA also completely inhibited the formation of secondary spheres. FDPS mRNA in patients with glioblastoma was associated with malignancy in three independent microarray data sets. RNA sequencing showed that alendronate treatment reduced the embryonic stem cell signature and activated development- and necrosis-related pathways in glioblastoma spheres. These results suggest that FDPS is important for the maintenance of glioblastoma stemness and that alendronate, a drug widely used to treat osteoporosis, can be repositioned to treat glioblastoma.

AntagomiR-27a Targets FOXO3a in Glioblastoma and Suppresses U87 Cell Growth in Vitro and in Vivo

  • Ge, Yun-Fei;Sun, Jun;Jin, Chun-Jie;Cao, Bo-Qiang;Jiang, Zhi-Feng;Shao, Jun-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.963-968
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    • 2013
  • Objective: To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. Methods: The miR-27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. Results: qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. Conclusion: MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.

Microarray Analysis of Gene Expression in Glioblastoma Cells Treated with Gwakhyangjeonggisan Herbal Acupuncture Solution (곽향정기산 약침액이 유해산소로 손상된 Glioblastoma 세포주의 유전자발현에 미치는 영향)

  • Lee, Hong-Seok;Yin, Chang-Shik;Koh, Hyeong-Gyun
    • Journal of Acupuncture Research
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    • v.22 no.6
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    • pp.111-123
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    • 2005
  • Objectives : Neurological disorders have been one of main therapeutic targets of acupuncture. The present study investigated the protective effects of Gwakhyangjeonggisan herbal acupuncture solution (GHAS). Methods : We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in glioblastoma cells, and did microarray analysis with cells exposed to reactive oxigen species (ROS) of hydrogen peroxide by 8.0 k Human cDNA, with cut-off level of 2-fold changes in gene expression. Results : MTT assay showed protective effect of GHAS on the glioblastoma cells exposed to hydrogen peroxide. When glioblastoma cells were exposed to hydrogen peroxide, 16 genes were upregulated. When the cells were pretreated with GHAS before exposure to hydrogen peroxide, 22 genes were upregulated. Most of the genes upregulated by hydrogen peroxide stimulation were reversed to downregulation by GHAS. Conclusion : The gene expression changes observed in the present study are supposed to be related to the protective molecular mechanism of GHAS in the glioblastoma cells exposed to ROS stress.

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Protective Effect of Gwakhyangjeonggisan Herbal Acupuncture Solution in Glioblastoma Cells: Microarray Analysis of Gene Expression (Glioblastoma 세포주의 유해산소 손상을 억제하는 곽향정기산 약침액의 효과에 대한 마이크로어레이 연구)

  • Lee, Hong-Seok;Yin, Chang-Shik;Koh, Hyeong-Gyun
    • Journal of Pharmacopuncture
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    • v.8 no.3
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    • pp.57-69
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    • 2005
  • Objectives : Neurological disorders have been one of main therapeutic targets of acupuncture. The present study investigated the protective effects of Gwakhyangjeonggisan herbal acupuncture solution (GHAS). Methods : We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in glioblastoma cells, and did microarray analysis with cells exposed to reactive oxigen species (ROS) of hydrogen peroxide by 8.0 k Human cDNA, with cut-off level of 2-fold changes in gene expression. Results : MTT assay showed protective effect of GHAS on the glioblastoma cells exposed to hydrogen peroxide. When glioblastoma cells were exposed to hydrogen peroxide, 24 genes were downregulated. When the cells were pretreated with GHAS before exposure to hydrogen peroxide, 46 genes were downregulated. Many of the genes downregulated by hydrogen peroxide stimulation were decreased in the amount of downregulation or reversed to upregulation. Conclusions : The gene expression changes observed in the present study are supposed to be related to the protective molecular mechanism of GHAS in the glioblastoma cells exposed to ROS stress.

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.

Glioblastoma Mimicking Herpes Simplex Encephalitis

  • Nam, Tai-Seung;Choi, Kang-Ho;Kim, Myeong-Kyu;Cho, Ki-Hyun
    • Journal of Korean Neurosurgical Society
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    • v.50 no.2
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    • pp.119-122
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    • 2011
  • We report a case of 70-year-old man with glioblastoma presenting as acute encephalitic illness. The patient exhibited sudden onset of cognitive impairment and headache for 2 days. Initial brain MRI showed left temporal lobe hyperintensity, and cerebrospinal fluid cytology revealed a mild pleocytosis. The patient had initially improved after medical treatment with a presumptive diagnosis of herpes simplex encephalitis (HSE). After 8 months, the patient complained of recurrent seizures. A follow-up brain MRI revealed marked increases in size and surrounding perilesional edema in the left temporal lesion on T2-weighted images and a new contrast-enhancing lesion on gadolinium-enhanced T1-weighted images. Stereotactic brain biopsy revealed a glioblastoma. The atypical encephalitic presentation of glioblastoma should be considered if definitive evidence for the diagnosis of HSE cannot be obtained.

Bilateral Triple-Negative Invasive Breast Cancer with a BRCA2 Mutation, and Glioblastoma: A Case Report and Literature Review

  • Raufi, Ali;Alsharedi, Mohamed;Khelfa, Yousef;Tirona, Maria
    • Journal of Breast Cancer
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    • v.20 no.1
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    • pp.108-111
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    • 2017
  • Breast cancer is the second leading cause of death among women in North America. Glioblastoma is the most common primary malignant central nervous system tumor in adults. The majority of hereditary breast cancers are associated with deleterious mutations in the BRCA1 and BRCA2 genes. Although few case reports have described the incidence of glioblastoma in patients previously diagnosed with breast cancer, any association between BRCA2 mutations and glioblastoma has not been demonstrated to date. Herein, we report a woman who is a carrier of a familial BRCA2 mutation, and was previously diagnosed with triple-negative breast cancer (TNBC) and subsequently with a second primary TNBC and glioblastoma. Further investigation is required to define the possible relationship between these two aggressive malignances and the BRCA2 mutation, which might be critical for the proper management and treatment of this disease.

Peptide Micelles for Anti-cancer Drug Delivery in an Intracranial Glioblastoma Animal Model

  • Yi, Na;Lee, Minhyung
    • Bulletin of the Korean Chemical Society
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    • v.35 no.10
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    • pp.3030-3034
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    • 2014
  • Bis-chloroethylnitrosourea (BCNU) is currently used as an anti-cancer drug for glioblastoma therapy. In this study, BCNU was loaded into the hydrophobic cores of R3V6 amphiphilic peptide micelles for efficient delivery into brain tumors. The scanning electron microscope (SEM) study showed that the BCNU-loaded R3V6 peptide micelles (R3V6-BCNU) formed spherical micelles. MTT assay showed that R3V6-BCNU more efficiently induced cell death in C6 glioblastoma cells than did BCNU. In the Annexin V assay, R3V6-BCNU more efficiently induced apoptosis than did BCNU alone. Furthermore, the results showed that R3V6 was not toxic to cells. The positive charges of the R3V6 peptide micelles may facilitate the interaction between R3V6-BCNU and the cellular membrane, resulting in an increase in cellular uptake of BCNU. In vivo evaluation with an intracranial glioblastoma rat model showed that R3V6-BCNU more effectively reduced tumor size than BCNU alone. The results suggest that R3V6 peptide micelles may be an efficient carrier of BCNU for glioblastoma therapy.

4G/5G and A-844G Polymorphisms of Plasminogen Activator Inhibitor-1 Associated with Glioblastoma in Iran - a Case-Control Study

  • Pooyan, Honari;Ahmad, Ebrahimi;Azadeh, Rakhshan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6327-6330
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    • 2015
  • Background: Glioblastoma is a highly aggressive and malignant brain tumor. Risk factors are largely unknown however, although several biomarkers have been identified which may support development, angiogenesis and invasion of tumor cells. One of these biomarkers is PAI-1.4G/5G and A-844G are two common polymorphisms in the gene promotor of PAI 1 that may be related to high transcription and expression of this gene. Studies have shown that the prevalence of the 4G and 844G allele is significantly higher in patients with some cancers and genetic disorders. Materials and Methods: We here assessed the association of 4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a case-control study. All 71 patients with clinically confirmed and 140 volunteers with no history and symptoms of glioblastoma as control group were screened for 4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele frequencies of case and control groups were analyzed using the DeFinetti program. Results: Our results showed significant associations between 4G/5G (p=0.01824) and A-844G (p = 0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer risk in our Iranian population. Conclusions: The results of this study supporting an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p = 0.02012) polymorphisms with increasing glioblastoma cancer risk in Iranian patients.