• Journal of Life Science
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• v.29 no.5
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• pp.530-536
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• 2019

Glioblastoma (GBM) is the most incurable brain cancer derived from the transformed glial cells. Standard anti-GBM treatment, including surgery and chemoradiotherapy, does not ensure good prognosis for the patients with GBM, because successful therapy is often impeded by presence of glioma stem cells (GSCs). GSCs, which is generally divided into proneural (PN) and mesenchymal (MES) subtype, are understood as subpopulation of cancer cells responsible for GBM initiation, progression and recurrence after standard treatments. In the present study, we demonstrate that PN subtype GSCs differentially transit to MES subtype GSCs by specific cytokines. The expression of CD44, a marker of MES subtype GSCs, was observed when GSC11 PN subtype GSCs were exposed to tumor necrosis factor alpha ($TNF-{\alpha}$) cytokine and GSC23 PN subtype GSCs were treated to transforming growth factor beta 1 ($TGF-{\beta}1$) cytokine. Ivy glioblastoma atlas project (Ivy GAP) bioinformatics database showed that $TNF-{\alpha}$ and $TGF-{\beta}1$ were highly expressed in necrotic region and perivascular region, respectively. In addition, $TNF-{\alpha}$ signaling was relatively upregulated in necrotic region, while $TGF-{\beta}$ signaling was increased in perivascular region. Taken together, our observations suggest that MES subtype GSCs can be derived from various PN subtype GSCs by multimodal cytokine stimuli provided by neighboring tumor microenvironment.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.45-57
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• 2020

In the neurovascular unit, the neuronal and vascular systems communicate with each other. O₂ and nutrients, reaching endothelial cells (ECs) through the blood stream, spread into neighboring cells, such as neural stem cells, and neurons. The proper function of neural circuits in adults requires sufficient O₂ and glucose for their metabolic demands through angiogenesis. In a central nervous system (CNS) injury, such as glioma, Parkinson's disease, and Alzheimer's disease, damaged ECs can contribute to tissue hypoxia and to the consequent disruption of neuronal functions and accelerated neurodegeneration. This review discusses the current evidence regarding the contribution of oxygen deprivation to CNS injury, with an emphasis on hypoxia-inducible factor (HIF)-mediated pathways and Notch signaling. Additionally, it focuses on adult neurological functions and angiogenesis, as well as pathological conditions in the CNS. Furthermore, the functional interplay between HIFs and Notch is demonstrated in pathophysiological conditions.

• 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.

• The Korea Journal of Herbology
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• v.27 no.3
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• pp.39-55
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• 2012

Objectives : Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of herbal medicine. This paper was aimed to review herbal medicine playing its anticancer role in terms of apoptosis, inflammation control, differentiation and telomerase. Methods : New studies for tang, medicinal herb itself or effective ingradients of medicinal herb showing anti-cancer effectiveness were reviewed and summarized in terms of pharmacological action. Results : Ethanol extracts of $Spatholobus$ $suberectus$ greatly inhibited cancer cell growth inducing cell apoptosis and cytotoxic effects. $Scutellaria$ $baicalensis$ may be responsible for its anticancer activity showing inhibition of $PGE_2$ synthesis via suppression of COX-2 expression. Saikosaponins isolated from $Bupleurum$ induced the differentiation of C6 glioma cells, cancer cells, into astrocytes, normal cells. Acetone extract of $Bupleurum$ $scorzonerifolium$ inhibited proliferation of human lung cancer cells via inducing apoptosis and suppressing telomerase activity. Conclusions : Herbal medicine inhibited cancer cell growth inducing cell apoptosis and cytotoxic effects. Inflammation persisting for a decade eventually elevates the risk of cancer sufficiently that it is discernible in case control epidemiological studies. Differentiation therapy is defined as a therapy to treat cancers by inducing differentiation of the stem cells. Telomerase expression is a hallmark of cancer. Nearly the complete spectrum of human tumors has been shown to be telomerase positive.