• 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.

• Journal of Korean Neurosurgical Society
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• v.55 no.4
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• pp.205-207
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• 2014

Meningioma is a common primary tumor of central nervous system. However, extracranial extension of the intracranial meningioma is unusual, and mostly accompanied the osteolytic change of the skull. We herein describe an atypical meningioma having extracranial extension with hyperostotic change of the skull. The patient was a 72-year-old woman who presented a large mass in the right frontal scalp and left hemiparesis. Brain magnetic resonance imaging and computed tomography scans revealed an intracranial mass, diffuse meningeal thickening, hyperostotic change of the skull with focal extension into the right frontal scalp. She underwent total removal of extracranial tumor, bifrontal craniectomy, and partial removal of intracranial tumor followed by cranioplasty. Tumor pathology was confirmed as atypical meningioma, and she received adjuvant radiotherapy. In this report, we present and discuss a meningioma en plaque of atypical histopathology having an extracranial extension with diffuse intracranial growth and hyperostotic change of the skull.

• BMB Reports
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• v.53 no.12
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• pp.664-669
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• 2020

Breast cancer is one of the most frequently diagnosed cancers. Although biomarkers are continuously being discovered, few specific markers, rather than classification markers, representing the aggressiveness and invasiveness of breast cancer are known. In this study, we used samples from canine mammary tumors in a comparative approach. We subjected 36 fractions of both canine normal and mammary tumor plasmas to high-performance quantitative proteomics analysis. Among the identified proteins, LCAT was selectively expressed in mixed tumor samples. With further MRM and Western blot validation, we discovered that the LCAT protein is an indicator of aggressive mammary tumors, an advanced stage of cancer, possibly highly metastatic. Interestingly, we also found that LCAT is overexpressed in high-grade and lymph-node-positive breast cancer in silico data. We also demonstrated that LCAT is highly expressed in the sera of advanced-stage human breast cancers within the same classification. In conclusion, we identified a possible common plasma protein biomarker, LCAT, that is highly expressed in aggressive human breast cancer and canine mammary tumor.

• The Korean Journal of Nuclear Medicine
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• v.34 no.6
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• pp.465-477
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• 2000

Purpose: Thallim-201 ($^{201}Tl$) brain SPECT and proton ($^1H$) magnetic resonance spectroscopy (MRS) have been used to evaluate tumor grade and viability of glioma. We assessed the correlations between $^{201}Tl$ brain index or spectrum of metabolites of $^1H$ MRS and grade of glioma or histopathologic findings. Materials and Methods: We studied 17 patients (4 astrocytoma, 7 anaplastic astrocytoma and 6 glioblastoma). On $^{201}Tl$ Brain SPECT, $^{201}Tl$ index was measured as the ratio of average counts for region of interest to those for the contralateral normal brain. On $^1H$ MRS, we calculated choline (Cho) /creatine (Cr) ratio and N-acetylaspartate (NAA)/Cr ratio in ROI defined as tumor center. Histopathologic findings were graded by Ki-67 index, cellularity, mitosis, pleomorphism, necrosis and endothelial proliferation. An unpaired t test and statistical correlations were performed to evaluate these data. Results: Tl-index showed the best correlation with Ki-67 index (p<0.01), less correlations with cellularity, mitosis, and endothelial proliferation, but no correlation with results of MRS, pleomorphism, or necrosis. The findings of MRS did not correlate with all of the above. The cases of glioblastoma demonstrated a higher Tl-index, Cho/cr ratio, Ki-67 index and lower NAA/Cr ratio, albeit without statistical significance. Conclusion: Even though $^{201}Tl$ brain SPECT did not correlate directly with grade of malignancy, it may still be useful in determining biological aggressiveness of tumor and prognosis of patients because it correlated well with Ki-67 index, a growth fraction of glioma, cellularity, mitosis and endothelial proliferation.

• Clinical and Experimental Pediatrics
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• v.50 no.11
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• pp.1110-1115
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• 2007

Purpose : Idiopathic central diabetes insipidus (CDI) is defined in CDI patients without definite etiology. Some patients initially diagnosed as idiopathic CDI progressed to organic causes. We reviewed clinical, endocrinological, and radiological courses of 20 patients who was initially diagnosed as idiopathic CDI, to assess the predicting factors for progression to brain tumors. Methods : We reviewed the medical data and followed up their clinical courses in 20 CDI patients who had no definite organic etiology, such as malformation, tumor, at the time of diagnosis. Results : Our study included 15 males and 5 females. Mean age of CDI diagnosis was $7.8{\pm}3.6$ (2.1-14.7) years. Mean follow-up duration was $8.6{\pm}5.1$ (1.5-18) years. Six (30%) patients were diagnosed as brain tumor during follow-up. Ten (50%) of 20 patients had growth hormone deficiency. Multiple pituitary hormone deficiencies were found more frequently in brain tumor patients than idiopathic patients (60% vs 7%, P=0.037). Pituitary stalk thickening (PST) and loss of posterior pituitary signal were observed in 9 patients (47%), respectively. The newly development of PST was observed in patients diagnosed as brain tumor. Conclusion : About 30% of idiopathic CDI patients progress to organic disease such as germ cell tumor or histiocytosis. If there are multiple anterior pituitary hormone deficiency or newly development of PST, more close and careful follow-up is needed.

• Journal of Korean Neurosurgical Society
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• v.58 no.3
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• pp.205-210
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• 2015

Objective : This study was aimed at optimizing the treatment of non-small-cell lung cancer (NSCLC) patients who are candidates for stereotactic radiosurgery (SRS) for brain metastases and harbor activating epithelial growth factor receptor (EGFR) mutations. Methods : We retrospectively reviewed the medical records from 2005 to 2010 of NSCLC patients with brain metastases harboring an activating EGFR mutation. Patients who received a combination therapy of SRS and EGFR-tyrosine kinase inhibitor (TKI) for brain metastases and those who received SRS without EGFR-TKI were compared. The primary endpoint was progression-free survival (PFS) of the brain metastases. Results : Thirty-one patients were eligible for enrolment in this study (SRS with TKI, 18; SRS without TKI, 13). Twenty-two patients (71.0%) were women and the median overall age was 56.0 years. PFS of brain lesions was not significantly prolonged in SRS with TKI treatment group than in SRS without TKI group (17.0 months vs. 9.0 months, p=0.45). Local tumor control rate was 83.3% in the combination therapy group, and 61.5% in the SRS monotherapy group (p=0.23). There were no severe adverse events related with treatment in both groups. Conclusions : Therapeutic outcome of concurrent SRS and TKI treatment was not superior to SRS monotherapy, however, there was no additive adverse events related with combined treatment.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.593-602
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• 2020

Background: Heat stress orchestrates neurodegenerative disorders and results in the formation of reactive oxygen species that leads to cell death. Although the immunomodulatory effects of ginseng are well studied, the mechanism by which ginseng alleviates heat stress in the brain remains elusive. Methods: Rats were exposed to intermittent heat stress for 6 months, and brain samples were examined to elucidate survival and antiinflammatory effect after Korean Red Ginseng (KRG) treatment. Results: Intermittent long-term heat stress (ILTHS) upregulated the expression of cyclooxygenase 2 and inducible nitric oxide synthase, increasing infiltration of inflammatory cells (hematoxylin and eosin staining) and the level of proinflammatory cytokines [tumor necrosis factor α, interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6], leading to cell death (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) and elevated markers of oxidative stress damage (myeloperoxidase and malondialdehyde), resulting in the downregulation of antiapoptotic markers (Bcl-2 and Bcl-x_L) and expression of estrogen receptor beta and brain-derived neurotrophic factor, key factors in regulating neuronal cell survival. In contrast, KRG mitigated ILTHS-induced release of proinflammatory mediators, upregulated the mRNA level of the antiinflammatory cytokine IL-10, and increased myeloperoxidase and malondialdehyde levels. In addition, KRG significantly decreased the expression of the proapoptotic marker (Bax), did not affect caspase-3 expression, but increased the expression of antiapoptotic markers (Bcl-2 and Bcl-x_L). Furthermore, KRG significantly activated the expression of both estrogen receptor beta and brain-derived neurotrophic factor. Conclusion: ILTHS induced oxidative stress responses and inflammatory molecules, which can lead to impaired neurogenesis and ultimately neuronal death, whereas, KRG, being the antioxidant, inhibited neuronal damage and increased cell viability.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.423-430
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• 2020

Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α. Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

• Journal of the Korean Magnetic Resonance Society
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• v.13 no.2
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• pp.64-83
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• 2009

The purpose of this study was to evaluate the usefulness of in vivo 3T $^1H$ MRS with short TE for prescreening various brain diseases. Together with ten normal volunteers, 12 brain tumor patients(2 lymphomas, 5 malignant gliomas) and 5(benign meningiomas) and 10 brain ischemic disease patients(6 acute and 4 subacute infarctions) participated. Lymphomas showed increased intensities of Cho and Lac. Likewise, gliomas showed increased Cho and Lac, but with decreased NAA and ${\beta}\;{\gamma}$-Glx; in higher grade of gliomas, Lac, Cho, mI and Lip predominantly increased with decrease of NAA. Benign meningiomas showed increased Cho, Lac and ${\beta}\;{\gamma}$-Glx; with decreased of NAA. The alanine peak at 1.47 ppm is a neuronal marker for meningiomas. Infarctions showed increased Lac and Lip and decreased NAA, ${\alpha}$-Glx and ${\beta}\;{\gamma}$-Glx where Lac increased with decreased of ${\alpha}$-Glx in acute, and Cho, Lac and Lip increased with decrease of NAA in subacute. Elevated Lac and decreased NAA levels were more aggravated in subacute. Clinical application of the $^1H$ MRS with short TE at 3T is able to povide valuable spectral information for prescreening various brain diseases by monitoring the changes of disease-specific cerebral metabolite concentrations in vivo, and consequently, it can be applicable to assessment of differential diagnosis and malignancy as well.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.145-153
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• 2013

Objectives : Neuroinflammation is characterized by microglial activation and the expression of major inflammatory mediators. The present study investigated the inhibitory effect of ginsenoside Rg1 ($GRg_1$), a principle active ingredient in Panax ginseng, on pro-inflammatory cytokines and microglial activation induced by systemic lipopolysaccharide (LPS) treatment in the mouse brain tissue. Methods : Varying doses of $GRg_1$ was orally administered (10, 20, and 30 mg/kg) 1 h before the LPS injection (3 mg/kg, intraperitoneally). The mRNA expression of pro-inflammatory cytokines in the brain tissue was measured using the quantitative real-time PCR method at 4 h after the LPS injection, Microglial activation was evaluated using western blotting and immunohistochemistry against ionized calcium binding adaptor molecule 1 (Iba1) in the brain tissue. Cyclooxigenase-2 (COX-2) expressions also observed using western blotting and immunohistochemistry at 4 h after the LPS injection, In addition, double-immunofluorescent labeling of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and COX-2 with microglia and neurons was processed in the brain tissue. Results : $GRg_1$ (30 mg/kg) significantly attenuated the upregulation of TNF-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 mRNA in the brain tissue at 4 h after LPS injection. Morphological activation and Iba1 protein expression of microglia induced by systemic LPS injection were reduced by the $GRg_1$ (30 mg/kg) treatment. Upregulation of COX-2 protein expression in the brain tissue was also attenuated by the $GRg_1$ (30 mg/kg) treatment. Conclusion : The results suggest that $GRg_1$ is effective in the early stage of neuroinflammation which causes neurodegenerative diseases.