10 results on '"Park, Saewhan"'
Search Results
2. Intracellular delivery of nuclear localization sequence peptide mitigates COVID-19 by inhibiting nuclear transport of inflammation-associated transcription factors
- Author
-
Lee, Seokwon, Yoon, Sang-Sun, Jo, Minhee, Kang, Mingu, Lee, Seungwoo, Seo, Young-Jin, Park, Saewhan, Paik, Young-Ki, and Jo, Daewoong
- Published
- 2024
- Full Text
- View/download PDF
3. Fam20C Kinase as a Key Regulator of Bevacizumab Resistance in Mesenchymal Glioblastoma.
- Author
-
Kim, Chan Il, Kim, Sooheon, Park, Seong‐Min, Kim, Sung Soo, Kwon, Hyung Joon, Lin, Weiwei, Park, Saewhan, Ha, Seokjun, Ha, Kyung Hee, Park, Sanha, Park, Seung Min, Kim, Tae Hoon, Kim, Kyung‐Hee, Kim, Yun‐Hee, Kim, Jong Heon, and Park, Jong Bae
- Published
- 2024
- Full Text
- View/download PDF
4. Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP downregulates stemness phenotype and mesenchymal trans-differentiation after irradiation in glioblastoma multiforme.
- Author
-
Lee, Shin Heon, Kwon, Hyung Joon, Park, Saewhan, Kim, Chan Il, Ryu, Haseo, Kim, Sung Soo, Park, Jong Bae, and Kwon, Jeong Taik
- Subjects
MACROPHAGE migration inhibitory factor ,CANCER stem cells ,GLIOBLASTOMA multiforme ,PHENOTYPES ,TREATMENT effectiveness - Abstract
Radiation therapy is among the most essential treatment methods for glioblastoma multiforme (GBM). Radio-resistance and cancer stem cell properties can cause therapeutic resistance, cancer heterogeneity, and poor prognoses in association with GBM. Furthermore, the GBM subtype transition from proneural to the most malignant mesenchymal subtype after radiation therapy also accounts for high resistance to conventional treatments. Here, we demonstrate that the inhibition of macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) by 4-iodo-6-phenylpyrimidine (4-IPP), a dual inhibitor targeting MIF and DDT, downregulates stemness phenotype, intracellular signaling cascades, mesenchymal trans-differentiation, and induces apoptosis in proneural glioma stem cells (GSCs). In an analysis of The Cancer Genome Atlas, high MIF and DDT expression were associated with poor prognosis. GSC growth was effectively inhibited by 4-IPP in a time- and dose-dependent manner, and 4-IPP combined with radiation therapy led to significantly reduced proliferation compared with radiation therapy alone. The expression of stemness factors, such as Olig2 and SOX2, and the expression of pAKT, indicating PI3K signaling pathway activation, were decreased in association with both 4-IPP monotherapy and combination treatment. The expression of mesenchymal markers, TGM2 and NF-κB, and expression of pERK (indicating MAPK signaling pathway activation) increased in association with radiation therapy alone but not with 4-IPP monotherapy and combination therapy. In addition, the combination of 4-IPP and radiation therapy significantly induced apoptosis compared to the monotherapy of 4-IPP or radiation. In vivo results demonstrated a significant tumor-suppressing effect of 4-IPP when combined with radiation therapy. Collectively, our results showed that the targeted inhibition of MIF and DDT has the potential to strengthen current clinical strategies by enhancing the anticancer effects of radiation therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. Analysis of electric cigarette liquid effect on mouse brain tumor growth through EGFR and ERK activation.
- Author
-
Kwon, Hyung Joon, Oh, Young Taek, Park, Saewhan, Kim, Sung Soo, Park, Jinju, Yin, Jinlong, Hong, Jun Hee, Kim, Chan Il, Ryu, Haseo, Park, Jong Bae, and Lim, Min Kyung
- Subjects
TUMOR growth ,NEURAL development ,BRAIN tumors ,MAGNETIC resonance imaging ,EPIDERMAL growth factor receptors ,CARCINOGENICITY - Abstract
Introduction: Recently, electric cigarettes with liquid (e-liquid) were introduced as an alternative to tobacco smoking. They were promoted as possible cessation aids and were considered to be potentially less harmful than traditional tobacco-based cigarettes. However, there is little information on the toxicants present in e-liquids and their possible carcinogenic effects. Methods: Western blot analysis was performed to identify the protein levels of cancer progression related signal transducers. Patient-derived brain tumor cells (CSC2) were injected into mouse brains and tumor growth was then observed by performing magnetic resonance imaging (MRI) and hematoxylin and eosin (H&E) staining of the whole brain. Immunohistochemistry (IHC) staining and Immunofluorescence staining were performed to study the expression of pEGFR and pERK. Results: Western blotting revealed that e-liquids increased pEGFR and pERK expression in a dose dependent manner. Animal experiments revealed that the e-liquid treated group had accelerated tumor growth and poor prognosis compared to the vehicle group. Histological staining showed activation of pEGFR and pERK in the e-liquid treated group. Conclusion: Our study revealed that e-liquid activates pEGFR and pERK, leading to accelerated brain tumor growth and poor prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
6. Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.
- Author
-
Hong, Jun-Hee, Kang, Sangjo, Sa, Jason K, Park, Gunwoo, Oh, Young Taek, Kim, Tae Hoon, Yin, Jinlong, Kim, Sung Soo, D'Angelo, Fulvio, Koo, Harim, You, Yeonhee, Park, Saewhan, Kwon, Hyung Joon, Kim, Chan Il, Ryu, Haseo, Lin, Weiwei, Park, Eun Jung, Kim, Youn-Jae, Park, Myung-Jin, and Kim, Hyunggee
- Subjects
GLIOBLASTOMA multiforme ,METHYLGUANINE ,MYELIN oligodendrocyte glycoprotein ,TREATMENT effectiveness ,GENES ,GENE ontology ,STEM cells ,CANCER cell differentiation ,PROTEIN metabolism ,ANIMAL experimentation ,GLIOMAS ,PROTEOLYTIC enzymes ,BRAIN tumors ,NERVE tissue ,CELL lines ,MICE - Abstract
As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
7. Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition.
- Author
-
Park S, Kim KH, Bae YH, Oh YT, Shin H, Kwon HJ, Kim CI, Kim SS, Choi HG, Park JB, and Lee BD
- Abstract
Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.
- Published
- 2024
- Full Text
- View/download PDF
8. Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.
- Author
-
Hong JH, Kang S, Sa JK, Park G, Oh YT, Kim TH, Yin J, Kim SS, D'Angelo F, Koo H, You Y, Park S, Kwon HJ, Kim CI, Ryu H, Lin W, Park EJ, Kim YJ, Park MJ, Kim H, Kim MS, Chung S, Park CK, Park SH, Kang YH, Kim JH, Saya H, Nakano I, Gwak HS, Yoo H, Lee J, Hur EM, Shi B, Nam DH, Iavarone A, Lee SH, and Park JB
- Subjects
- Animals, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, Inhibitor of Differentiation Protein 1 metabolism, Inhibitor of Differentiation Proteins metabolism, Mice, Inbred BALB C, Myelin Sheath pathology, Ubiquitin-Specific Proteases metabolism, Mice, Brain Neoplasms metabolism, Brain Neoplasms pathology, Glioblastoma metabolism, Glioblastoma pathology, Myelin Sheath metabolism, Nogo Receptor 1 metabolism
- Abstract
As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
9. Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C/EBPβ Signaling.
- Author
-
Yin J, Oh YT, Kim JY, Kim SS, Choi E, Kim TH, Hong JH, Chang N, Cho HJ, Sa JK, Kim JC, Kwon HJ, Park S, Lin W, Nakano I, Gwak HS, Yoo H, Lee SH, Lee J, Kim JH, Kim SY, Nam DH, Park MJ, and Park JB
- Subjects
- Animals, Apoptosis, Biomarkers, Tumor metabolism, Brain Neoplasms genetics, Brain Neoplasms metabolism, Cell Proliferation, Cell Transdifferentiation, Female, GTP-Binding Proteins metabolism, Glioma genetics, Glioma metabolism, Humans, Mesenchymal Stem Cells metabolism, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Recurrence, Local metabolism, Neoplastic Stem Cells metabolism, Protein Glutamine gamma Glutamyltransferase 2, Transglutaminases metabolism, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Brain Neoplasms pathology, CCAAT-Enhancer-Binding Protein-beta metabolism, GTP-Binding Proteins antagonists & inhibitors, Glioma pathology, Mesenchymal Stem Cells pathology, Neoplasm Recurrence, Local pathology, Neoplastic Stem Cells pathology, Transglutaminases antagonists & inhibitors
- Abstract
Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-κB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973-84. ©2017 AACR ., (©2017 American Association for Cancer Research.)
- Published
- 2017
- Full Text
- View/download PDF
10. Increased 18F-FDG Uptake on PET/CT is Associated With Poor Arterial and Portal Perfusion on Multiphase CT.
- Author
-
Hwang SH, Lee M, Lee N, Park S, Kim CK, Park MA, and Yun M
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Multimodal Imaging, Tomography, X-Ray Computed, Carcinoma, Hepatocellular diagnostic imaging, Fluorodeoxyglucose F18, Liver Neoplasms diagnostic imaging, Perfusion Imaging, Portal System diagnostic imaging, Positron-Emission Tomography, Radiopharmaceuticals
- Abstract
Purpose: To correlate 18F-FDG uptake on PET/CT with patterns of arterial and portal perfusion on multi-detector CT (MDCT) in patients with hepatocellular carcinoma (HCC) and to assess the value of variables from PET/CT and MDCT in predicting histological grades and overall survival., Methods: We retrospectively analyzed MDCT and PET/CT of 66 patients with HCC who underwent surgical treatment. Tumor peak standard uptake value (SUV) was divided by the mean liver SUV (T/LSUV). The mean tumor Hounsfield unit (HU) to mean liver HU was calculated for arterial (T/LHU-A) and portal phases (T/LHU-P). All patients were divided into three groups: I, T/LHU-A ≤l and T/LHU-P <1; II, T/LHU-A >1 and T/LHU-P <1; and III, T/LHU-A >1 and T/LHU-P ≥1. The relationships between the CT perfusion groups and T/LSUV were assessed. Multivariate logistic regression analyses were performed using clinical and imaging parameters for predicting histological grade. Overall survival curves stratified by T/LSUV and CT perfusion groups were estimated using the Kaplan-Meier method., Results: Statistically significant differences in T/LSUV were noted between groups I and II (2.29 [range 1.74-3.60] vs. 1.20 [range 1.07-1.58], P < 0.001) and groups I and III (2.29 [range 1.74-3.60] vs. 1.30 [range 1.07-1.43], P < 0.001). In multivariate analysis, a T/LSUV cutoff of >1.46 was the only independent predictor of tumor grade, with an odds ratio of 8.462 (95% confidence interval 1.799-39.803). Kaplan-Meier curves showed significant differences in OS according to T/LSUV >1.62, group I perfusion pattern, and T/LSUV >1.62 plus group I perfusion pattern (P = 0.04, P = 0.021, and P = 0.002, respectively)., Conclusion: 18F-FDG PET/CT is not commonly used for detecting HCC due to its limited sensitivity. We found that increased 18F-FDG uptake is associated with decreased arterial and portal perfusion on MDCT. This can be used to preselect patients who would benefit the most from PET/CT. Meanwhile, 18F-FDG uptake remained as the only independent predictor of histological grade, and higher 18F-FDG uptake and lower perfusion pattern on MDCT were significantly related to shorter OS.
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.