20 results on '"Yong-Min, Huh"'
Search Results
2. Clinical molecular subtyping reveals intrinsic mesenchymal reprogramming in gastric cancer cells
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Eunji Jang, Min-Kyue Shin, Hyunki Kim, Joo Yeon Lim, Jae Eun Lee, Jungmin Park, Jungeun Kim, Hyeseon Kim, Youngmin Shin, Hye-Young Son, Yoon Young Choi, Woo Jin Hyung, Sung Hoon Noh, Jin-Suck Suh, Ji-Yong Sung, Yong-Min Huh, and Jae-Ho Cheong
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Clinical Biochemistry ,Molecular Medicine ,Molecular Biology ,Biochemistry - Abstract
The mesenchymal cancer phenotype is known to be clinically related to treatment resistance and a poor prognosis. We identified gene signature-based molecular subtypes of gastric cancer (GC, n = 547) based on transcriptome data and validated their prognostic and predictive utility in multiple external cohorts. We subsequently examined their associations with tumor microenvironment (TME) features by employing cellular deconvolution methods and sequencing isolated GC populations. We further performed spatial transcriptomics analysis and immunohistochemistry, demonstrating the presence of GC cells in a partial epithelial-mesenchymal transition state. We performed network and pharmacogenomic database analyses to identify TGF-β signaling as a driver pathway and, thus, a therapeutic target. We further validated its expression in tumor cells in preclinical models and a single-cell dataset. Finally, we demonstrated that inhibition of TGF-β signaling negated mesenchymal/stem-like behavior and therapy resistance in GC cell lines and mouse xenograft models. In summary, we show that the mesenchymal GC phenotype could be driven by epithelial cancer cell-intrinsic TGF-β signaling and propose therapeutic strategies based on targeting the tumor-intrinsic mesenchymal reprogramming of medically intractable GC.
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- 2023
3. Inhibition of PD-L1 and tumor growth in triple-negative breast cancer using a magnetic nanovector with microRNA34a
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Seung-Hyun Yang, Hye Young Son, Mirae Park, Hyun Wook Rho, Hwunjae Lee, and Yong-Min Huh
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Oncology ,Biomedical Engineering ,Pharmaceutical Science ,Physical and Theoretical Chemistry - Abstract
Background Clinical applications of RNA interference for cancer treatment and immune therapy require the development of simultaneous therapy and imaging systems for microRNA. This research was performed to fabricate the miRNA34a-loaded magnetic nanoparticles and investigate its anticancer effects against triple-negative breast cancer (TNBC) in mice model. Results Using two types of polymers to improve their water dispersibility and gene delivery, iron oxide magnetic nanoparticles were prepared for delivery of miRNA34a. The iron oxide magnetic nanoparticles were delivered to TNBC cells, and their efficacy was evaluated in vitro and in vivo. Delivery of miRNA34a reduced TNBC cell migration and decreased the expression of PD-L1 at the mRNA and protein levels. In animal experiments, delivery of miRNA34a reduced tumor growth, and immunostaining and algorithmic analysis confirmed the decrease in PD-L1 expression. Conclusion This study is the first to modulate PD-L1 by delivering miRNA34a with magnetic nanoparticles, and the results suggest that miRNA34a can be delivered effectively using magnetic nanoparticles and has potential as a molecular imaging contrast agent.
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- 2023
4. C5α secreted by tumor mesenchymal stem-like cells mediates resistance to 5-aminolevulinic acid-based photodynamic therapy against glioblastoma tumorspheres
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Junseong, Park, Seung Jae, Oh, Jin-Kyoung, Shim, Young Bin, Ji, Ju Hyung, Moon, Eui Hyun, Kim, Yong-Min, Huh, Jin-Suck, Suh, Jong Hee, Chang, Su-Jae, Lee, and Seok-Gu, Kang
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Cancer Research ,Oncology ,General Medicine - Abstract
Advancements in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) as a standard care in cancer therapy have been limited. This study is aimed to investigate the clinical availability of 5-aminolevulinic acid (5-ALA)-based PDD and PDT in glioblastoma (GBM) patient-derived tumorspheres (TSs) and mouse orthotopic xenograft model.PDT was performed using a 635 nm light-emitting diode (LED). Transcriptome profiles were obtained from microarray data. For knockdown of C5α, siRNA was transfected into tumor mesenchymal stem-like cells (tMSLCs). The invasiveness of TSs was quantified using collagen-based 3D invasion assays.Treatment with 1 mM 5 ALA induced distinct protoporphyrin IX (PpIX) fluorescence in GBM TSs, but not in non-tumor cells or tissues, including tMSLCs. These observations were negatively correlated with the expression levels of FECH, which catalyzes the conversion of accumulated PpIX to heme. Furthermore, the 5-ALA-treated GBM TSs were sensitive to PDT, thereby significantly decreasing cell viability and invasiveness. Notably, the effects of PDT were abolished by culturing TSs with tMSLC-conditioned media. Transcriptome analysis revealed diverse tMSLC-secreted chemokines, including C5α, and their correlations with the expression of stemness- or mesenchymal transition-associated genes. By adding or inhibiting C5α, we confirmed that acquired resistance to PDT was induced via tMSLC-secreted C5α.Our results show substantial therapeutic effects of 5-ALA-based PDT on GBM TSs, suggesting C5α as a key molecule responsible for PDT resistance. These findings could trigger PDT as a standard clinical modality for the treatment of GBM.
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- 2022
5. Investigation of Keratinizing Squamous Cell Carcinoma of the Tongue Using Terahertz Reflection Imaging
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Yong Min Huh, Young Han Lee, Young Bin Ji, Yoon Woo Koh, Jung Min Kim, Da Hee Kim, Yuna Choi, Jin Suck Suh, and Seung Jae Oh
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010302 applied physics ,Pathology ,medicine.medical_specialty ,Radiation ,integumentary system ,Chemistry ,Terahertz radiation ,High water content ,Condensed Matter Physics ,01 natural sciences ,Tumor tissue ,Terahertz spectroscopy and technology ,010309 optics ,stomatognathic diseases ,medicine.anatomical_structure ,Keratinizing Squamous Cell Carcinoma ,Tongue ,0103 physical sciences ,Reflection (physics) ,medicine ,Electrical and Electronic Engineering ,Instrumentation ,Keratin pearl - Abstract
We investigated the feasibility of using terahertz (THz) reflection imaging to detect keratinizing squamous cell carcinoma (SCC) of the tongue. Four fresh keratinizing SCC tissues were studied, which had been surgically resected. All of the keratinizing SCCs were well distinguished from normal healthy tissues. We showed that the tumor regions exhibited low THz reflection despite having higher water content than normal regions. The refractive indices and absorption coefficients were low in the tumor tissues despite the relatively high water content. Our results showed that there were dominant factors such as keratin pearls, other than the water content affecting the THz reflection signal.
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- 2019
6. Deconvolution of diffuse gastric cancer and the suppression of CD34 on the BALB/c nude mice model
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Young Min Shin, Seok Gu Kang, Yong Min Huh, Jungmin Park, Yuna Choi, Sahng Wook Park, Seon Jin Yoon, and Hye Young Son
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Adult ,Male ,Cancer Research ,Histology ,BALB/c nude mouse ,CD34 ,Mice, Nude ,Antigens, CD34 ,lcsh:RC254-282 ,BALB/c ,Extracellular matrix ,Transcriptome ,Small hairpin RNA ,Mice ,Magnetic resonance imaging ,Stomach Neoplasms ,Surgical oncology ,Cell Line, Tumor ,Human Umbilical Vein Endothelial Cells ,Genetics ,Animals ,Humans ,Aged ,Oligonucleotide Array Sequence Analysis ,Aged, 80 and over ,Diffuse gastric cancer ,Mice, Inbred BALB C ,Gene knockdown ,biology ,Sequence Analysis, RNA ,Gene Expression Profiling ,High-Throughput Nucleotide Sequencing ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,biology.organism_classification ,Gene Expression Regulation, Neoplastic ,Phenotype ,Oncology ,Cancer cell ,Cancer research ,Female ,Knockdown ,Neoplasm Transplantation ,Research Article - Abstract
Background Gastric cancer is a considerable burden for worldwide patients. And diffuse gastric cancer is the most insidious subgroup with poor survival. The phenotypic characterization of the diffuse gastric cancer cell line can be useful for gastric cancer researchers. In this article, we aimed to characterize the diffuse gastric cancer cells with MRI and transcriptomic data. We hypothesized that gene expression pattern is associated with the phenotype of the cells and that the heterogeneous enhancement pattern and the high tumorigenicity of SNU484 can be modulated by the perturbation of the highly expressed gene. Methods We evaluated the 9.4 T magnetic resonance imaging and transcriptomic data of the orthotopic mice models from diffuse gastric cancer cells such as SNU484, Hs746T, SNU668, and KATO III. We included MKN74 as an intestinal cancer control cell. After comprehensive analysis integrating MRI and transcriptomic data, we selected CD34 and validated the effect by shRNA in the BALB/c nude mice models. Results SNU484, SNU668, Hs746T, and MKN74 formed orthotopic tumors by the 5 weeks after cell injection. The diffuse phenotype was found in the SNU484 and Hs746T. SNU484 was the only tumor showing the heterogeneous enhancement pattern on T2 images with a high level of CD34 expression. Knockdown of CD34 decreased the round-void shape in the H&E staining (P = 0.028), the heterogeneous T2 enhancement, and orthotopic tumorigenicity (100% vs 66.7%). The RNAseq showed that the suppressed CD34 is associated with the downregulated gene-sets of the extracellular matrix remodeling. Conclusion Suppression of CD34 in the human-originated gastric cancer cell suggests that it is important for the round-void histologic shape, heterogeneous enhancement pattern on MRI, and the growth of gastric cancer cell line.
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- 2020
7. Potential use of glioblastoma tumorsphere: clinical credentialing
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Jong Hee Chang, Yong Min Huh, Sun Ho Kim, Jae Ho Cheong, Seok Gu Kang, and Eui Hyun Kim
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Oncology ,medicine.medical_specialty ,Biomedical Research ,business.industry ,Organic Chemistry ,Pharmacology toxicology ,Pharmacy ,medicine.disease ,Credentialing ,Cancer treatment ,Cancer stem cell ,Internal medicine ,Drug Discovery ,Neoplastic Stem Cells ,Animals ,Humans ,Molecular Medicine ,Medicine ,Medical physics ,Molecular Targeted Therapy ,Glioblastoma ,business - Abstract
A decade ago, cancer stem cells (CSCs) were introduced as target cells for an innovative cancer treatment. Particularly, there have been a lot of biological researches on glioblastoma (GBM) CSCs. However, as there is a comprehensive change in the concept of CSCs, it is required to review how the different CSCs for patients can be clinically used, or clinical credentialing, and summarize the possibilities of clinical credentialing. In this regard, this review aims to introduce the tumorsphere obtained from GBM specimen and summarize the clinical dilemma and clinically applicable areas.
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- 2015
8. Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging
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Na Young Choi, Yong Min Huh, Jinse Park, Hojin Choi, Hyun Jeung Yu, Young Joo Lee, Kyu Yong Lee, Seong-Ho Koh, and Seok-Ho Lee
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0301 basic medicine ,MAPK/ERK pathway ,medicine.medical_specialty ,Free Radicals ,Cell Survival ,MAP Kinase Signaling System ,Atorvastatin ,Neuroscience (miscellaneous) ,Oxidative phosphorylation ,medicine.disease_cause ,Neuroprotection ,Antioxidants ,Cell Line ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,LY294002 ,PI3K/AKT/mTOR pathway ,Motor Neurons ,Dose-Response Relationship, Drug ,Kinase ,Free Radical Scavengers ,Enzyme Activation ,Oxidative Stress ,Neuroprotective Agents ,030104 developmental biology ,Endocrinology ,Neurology ,chemistry ,lipids (amino acids, peptides, and proteins) ,030217 neurology & neurosurgery ,Oxidative stress ,medicine.drug - Abstract
Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase inhibitors, are generally used to decrease levels of circulating cholesterol, they have also been reported to have neuroprotective effects through various mechanisms. However, recent results have indicated that they may be harmful in patients with amyotrophic lateral sclerosis (ALS). In this study, we investigate whether atorvastatin protects motor neuron-like cells (NSC-34D) from oxidative stress. To evaluate the effects of atorvastatin or hydrogen peroxide or both on NSC-34D cells, the cells were treated with various combinations of these agents. To evaluate the viability of the cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue staining were performed. Levels of free radicals and intracellular signaling proteins were evaluated using the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western blotting, respectively. Atorvastatin protected NSC-34D cells against oxidative stress in a concentration-dependent manner. This neuroprotective effect of atorvastatin was blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor and by FR180204, a selective extracellular signal-related kinase (ERK) inhibitor. Atorvastatin treatment increased the expression levels of p85αPI3K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3β, phosphorylated ERK, and Bcl-2, which are proteins related to survival. Furthermore, atorvastatin decreased the levels of cytosolic cytochrome C, Bax, cleaved caspase-9, and cleaved caspase-3, which are associated with death in oxidative stress-injured NSC-34D cells. We conclude that atorvastatin has a protective effect against oxidative stress in motor neurons by activating the PI3K and ERK pathways as well as by scavenging free radicals. These findings indicate that statins could help protect motor neurons from oxidative stress.
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- 2015
9. Colourimetric redox-polyaniline nanoindicator for in situ vesicular trafficking of intracellular transport
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Byunghoon Kang, Myeong Hoon Kim, Kwangyeol Lee, Eunji Jang, Eun Bi Choi, Jin Suck Suh, Seo Ryung Bae, Byeongyoon Kim, Hyun Ouk Kim, Seungjoo Haam, Jihye Choi, and Yong Min Huh
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Conductive polymer ,Quenching (fluorescence) ,Condensed Matter Physics ,Redox ,Atomic and Molecular Physics, and Optics ,Vesicular transport protein ,chemistry.chemical_compound ,Förster resonance energy transfer ,chemistry ,Biochemistry ,Polyaniline ,Biophysics ,General Materials Science ,Electrical and Electronic Engineering ,Cyanine ,Intracellular - Abstract
Vesicular pH modulates the function of many organelles and plays a pivotal role in cell metabolism processes such as proliferation and apoptosis. Here, we introduce a simple colorimetric redox-polyaniline nanoindicator, which can detect and quantify a broader biogenic pH range with superior sensitivity compared to pre-established trafficking agents employing one-dimensional turn-on of the fluorescence resonance-energy-transfer (FRET) signal. We fabricated polyaniline-based nanoprobes, which exhibited convertible transition states according to the proton levels, as an in situ indicator of vesicular transport pH. Silica-coated Fe3O4-MnO heterometal nanoparticles were synthesised and utilised as a metal oxidant to polymerise the aniline monomer. Finally, silica-coated polyaniline nanoparticles with adsorbed cyanine dye fluorophores Cy3 and Cy7 (FPSNICy3 and FPSNICy7) were fabricated as proton-sensitive nanoindicators. Owing to the selective quenching induced by the local pH variations of vesicular transport, FPSNICy3 and FPSNICy7 demonstrated excellent intracellular trafficking and provided sensitive optical indication of minute proton levels.
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- 2014
10. Isolation of tumor spheres and mesenchymal stem-like cells from a single primitive neuroectodermal tumor specimen
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Seok Gu Kang, Hye Jin Shin, Jiyong Kwak, Eun Kyung Park, Jong Hee Chang, Dong Seok Kim, Eui Hyun Kim, Se Hoon Kim, Ji Hyun Lee, Su Jae Lee, Jin Kyoung Shim, Sun Ho Kim, Yong Kil Hong, and Yong Min Huh
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Pathology ,medicine.medical_specialty ,Cell Separation ,Flow cytometry ,Cancer stem cell ,Glioma ,medicine ,Cell separation ,Humans ,Neuroectodermal Tumors, Primitive ,Child ,Cells, Cultured ,medicine.diagnostic_test ,Brain Neoplasms ,business.industry ,fungi ,Mesenchymal stem cell ,Infant ,food and beverages ,Mesenchymal Stem Cells ,General Medicine ,Flow Cytometry ,medicine.disease ,Immunohistochemistry ,Mesenchymal stem like ,Primitive neuroectodermal tumor ,Pediatrics, Perinatology and Child Health ,Neoplastic Stem Cells ,Female ,Neurology (clinical) ,business - Abstract
It has been reported that cancer stem cells (CSCs) can be isolated from primitive neuroectodermal tumor (PNET) specimens. Moreover, mesenchymal stem-like cells (MSLCs) have been isolated from Korean glioma specimens. Here, we tested whether tumor spheres and MSLCs can be simultaneously isolated from a single PNET specimen, a question that has not been addressed.We isolated single-cell suspensions from PNET specimens, then cultured these cells using methods for MSLCs or CSCs. Cultured cells were analyzed for surface markers of CSCs using immunocytochemistry and for surface markers of bone marrow-derived mesenchymal stem cells (BM-MSCs) using fluorescence-activated cell sorting (FACS). Tumor spheres were exposed to neural differentiation conditions, and MSLCs were exposed to mesenchymal differentiation conditions. Possible locations of MSLCs within PNET specimens were determined by immunofluorescence analysis of tumor sections.Cells similar to tumor spheres and MSLCs were independently isolated from one of two PNET specimens. Spheroid cells, termed PNET spheres, were positive for CD133 and nestin, and negative for musashi and podoplanin. PNET spheres were capable of differentiation into immature neural cells and astrocytes, but not oligodendrocytes or mature neural cells. FACS analysis revealed that adherent cells isolated from the same PNET specimen, termed PNET-MSLCs, had surface markers similar to BM-MSCs. These cells were capable of mesenchymal differentiation. Immunofluorescence labeling indicated that some CD105(+) cells might be closely related to endothelial cells and pericytes.We showed that both tumor spheres and MSLCs can be isolated from the same PNET specimen. PNET-MSLCs occupied a niche in the vicinity of the vasculature and could be a source of stroma for PNETs.
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- 2013
11. Redox-sensitive colorimetric polyaniline nanoprobes synthesized by a solvent-shift process
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Jaemoon Yang, Seungjoo Haam, Yong Min Huh, Jihye Choi, Yoochan Hong, Eugene Lee, Dae Sung Yoon, Myeong Hoon Kim, and Jin Suck Suh
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Materials science ,Dopant ,Doping ,Nanoparticle ,Nanoprobe ,Polyethylene glycol ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Solvent ,chemistry.chemical_compound ,Colloid ,chemistry ,Chemical engineering ,Polyaniline ,Organic chemistry ,General Materials Science ,Electrical and Electronic Engineering - Abstract
We have synthesized water-stable polyaniline nanoparticles coated with triarmed polyethylene glycol chains using a solvent-shift method and confirmed their colloidal size and aqueous solubility. Furthermore, we have demonstrated that the polyaniline nanoparticles can be doped with biological dopants to produce distinct color changes allowing the detection of live cancer cells.
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- 2013
12. Success of tumorsphere isolation from WHO grade IV gliomas does not correlate with the weight of fresh tumor specimens: an immunohistochemical characterization of tumorsphere differentiation
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Jong Hee Chang, Se Hoon Kim, Jin Kyoung Shim, Su Jae Lee, Sohee Park, Eui Hyun Kim, Sun Ho Kim, Yong Min Huh, Tae Hoon Roh, Seok Gu Kang, Ju Hyung Moon, Ji Hyun Lee, and Kyoung Su Sung
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0301 basic medicine ,WHO Grade IV Glioma ,Pathology ,medicine.medical_specialty ,Cancer Research ,Fresh Specimen ,Tumorsphere ,Fresh specimen ,World health ,Isolation ,03 medical and health sciences ,0302 clinical medicine ,Glioma ,Genetics ,Medicine ,business.industry ,Significant difference ,Who grade ,Weight ,medicine.disease ,030104 developmental biology ,Oncology ,WHO grade IV glioma ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Primary Research ,business ,Optimal weight - Abstract
Background: A trend of stage-by-stage increase in tumorsphere (TS) formation from glioma samples has been reported. Despite this trend, not all surgical specimens give rise to TSs, even World Health Organization (WHO) grade IV gliomas. Furthermore, it has been reported that differences in overall survival of primary glioblastoma patients depends on the propensity of their tumors to form TSs. However, the weights of fresh specimens vary from one surgical isolate to the next. Methods: Accordingly, we evaluated the relationship between the weights of surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs. Thirty-five fresh WHO grade IV glioma specimens were separated into two groups, based on whether they were positive or negative for TS isolation, and the relationship between TS isolation and weight of surgical specimens was assessed. Results: We observed no significant difference in the weights of surgical samples in the two groups, and found that the optimal weight of specimens for TSs isolation was 500 mg. Conclusion: Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens.
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- 2016
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13. Cancer Diagnosis by Terahertz Molecular Imaging Technique
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Jihye Choi, Jin Suck Suh, Seungjoo Haam, Seung Jae Oh, Yong Min Huh, and Joo-Hiuk Son
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Radiation ,Materials science ,business.industry ,Terahertz radiation ,Nanoprobe ,Condensed Matter Physics ,Differential measurement ,Optics ,Electrical and Electronic Engineering ,Molecular imaging ,Surface plasmon resonance ,business ,Preclinical stage ,Instrumentation ,Biomedical engineering - Abstract
We obtained the diagnostic images of cancerous tumors by employing the THz molecular imaging (TMI) technique which measured the THz response change by surface plasmon resonance induced on the surface of nanoparticles with a irradiation of near-infrared (NIR) beam. To demonstrate the principle of the TMI technique, THz images of tissues with nanoprobes were observed and compared with THz only images. The sensitivity of TMI was further enhanced by adopting a THz differential measurement technique, which was realized by modulating the NIR beams. By employing this differential TMI technique, the diagnostic images of cancerous tumors were obtained ex vivo and in vivo in the preclinical stage. These images indicated the feasibility of applying the differential TMI technique in the clinical stage.
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- 2011
14. Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model
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Hyun Su Mok, Frederick F. Lang, Seok Gu Kang, Chun Kun Park, Sang Mok Kim, Su Jae Lee, Sin Soo Jeun, Yong Kil Hong, Na Ri Park, and Yong Min Huh
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Male ,Mice, Nude ,Mice ,Cancer stem cell ,Neurosphere ,Tumor Cells, Cultured ,Animals ,Humans ,Medicine ,CD90 ,neoplasms ,Stem cell transplantation for articular cartilage repair ,Brain Neoplasms ,business.industry ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Amniotic stem cells ,Glioma ,General Medicine ,Xenograft Model Antitumor Assays ,nervous system diseases ,Disease Models, Animal ,Pediatrics, Perinatology and Child Health ,Immunology ,Cancer research ,Neurology (clinical) ,Stromal Cells ,Stem cell ,business ,Adult stem cell - Abstract
High-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expressing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens.We created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling.GS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1](+), CD9(+), CD45(-), CD11b(-), CD31(-), and nerve/glial antigen 2 [NG2](-)). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes.Our results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.
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- 2011
15. Magnetoplex based on MnFe2O4 nanocrystals for magnetic labeling and MR imaging of human mesenchymal stem cells
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Jin Suck Suh, Eun Kyung Lim, Seungjoo Haam, Eun Sook Lee, Jaemoon Yang, and Yong Min Huh
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Materials science ,medicine.diagnostic_test ,Biocompatibility ,Mesenchymal stem cell ,Bioengineering ,Magnetic resonance imaging ,General Chemistry ,equipment and supplies ,Condensed Matter Physics ,Mr imaging ,Atomic and Molecular Physics, and Optics ,chemistry.chemical_compound ,Nuclear magnetic resonance ,chemistry ,Nanocrystal ,Modeling and Simulation ,medicine ,Nanomedicine ,General Materials Science ,human activities ,Iron oxide nanoparticles ,Amphiphilic copolymer - Abstract
For efficient labeling and tracking via magnetic resonance (MR) imaging of human mesenchymal stem cells (h-MSCs), magnetic labeling agents must be responsive to an external magnetic field. Thus, we developed ultrasensitive magnetoplex as a magnetic labeling agent composed of PEGylated MnFe2O4 nanocrystals (PMNCs) and polycationics (poly-l-lysine, PLL) for efficient labeling of the h-MSCs and monitoring of the transplanted h-MSCs for a long term. PMNCs were prepared by nanoemulsion methods composed of MnFe2O4 nanocrystals (MNCs) and amphiphilic polymers (mPEG–dodecanoic acid). The prepared PMNCs exhibited excellent biocompatibility and their polycationic complexes (PMNCs/PLL) demonstrated remarkable sensitivity compared with magnetic iron oxide nanoparticles (MION)/PLL or Ferumoxides/PLL. Furthermore, PMNCs demonstrated the potentials for novel diagnostic and therapeutic strategies with potential applications in various biomedical fields.
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- 2010
16. Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging
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Ho-Geun Yoon, Young-wook Jun, Jin Suck Suh, Jung Wook Seo, Jae Hyun Lee, Ho Taek Song, Sungjun Kim, Yong Min Huh, Eun Jin Cho, Jinwoo Cheon, and Jung Tak Jang
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Pathology ,medicine.medical_specialty ,Materials science ,Receptor, ErbB-2 ,Biological objects ,Mice, Nude ,Nanotechnology ,Antibodies, Monoclonal, Humanized ,Ferric Compounds ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Magnetics ,Mice ,Cell Line, Tumor ,Neoplasms ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Small tumors ,Ultra sensitive ,Mice, Inbred BALB C ,medicine.diagnostic_test ,Antibodies, Monoclonal ,Reproducibility of Results ,Magnetic resonance imaging ,Neoplasms, Experimental ,General Medicine ,Trastuzumab ,equipment and supplies ,Magnetic Resonance Imaging ,Transplantation ,Nanoparticles ,Magnetic nanoparticles ,Female ,Molecular imaging ,Molecular probe ,human activities ,HeLa Cells - Abstract
Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task. Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal. Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available. Also, we successfully visualized small tumors implanted in a mouse. Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics.
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- 2006
17. In vivo MR Imaging of Tissue-engineered Human Mesenchymal Stem Cells Transplanted to Mouse: a Preliminary Study
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Eun Sook Lee, Ho Taek Song, Jin Suck Suh, Yong Min Huh, In Kap Ko, and Eun Jin Cho
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Pathology ,medicine.medical_specialty ,Biodistribution ,Iron ,Cell ,Biomedical Engineering ,Contrast Media ,Mice, Nude ,Pilot Projects ,Mesenchymal Stem Cell Transplantation ,Mice ,Tissue engineering ,In vivo ,medicine ,Animals ,Humans ,Viability assay ,Magnetite Nanoparticles ,Cells, Cultured ,Tissue Engineering ,Chemistry ,Cell growth ,Mesenchymal stem cell ,Dextrans ,Mesenchymal Stem Cells ,Oxides ,Image Enhancement ,Magnetic Resonance Imaging ,Ferrosoferric Oxide ,Transplantation ,medicine.anatomical_structure ,Biomedical engineering - Abstract
Current progress integrating stem cell biology and tissue engineering techniques has been invaluable to clinical applications. Prior to the application of cellular transplantation technique to patients, we need to establish techniques that can monitor their tissue biodistribution non-invasively. In this study, we proposed an imaging modality using MRI to not only monitor implanted scaffold in vivo, but also to track transplanted cells and behavior around the implant. For this purpose, human bone marrow-derived mesenchymal stem cells (hMSCs) were labeled with superparamagnetic iron oxide (Feridex) and then labeled hMSCs were cultured in a gelatin sponge used as a scaffold to support cell growth and proliferation. Histological assessment and MTT assay showed that cell labeling with MR contrast agent did not harm cell viability. Also, Feridex-labeled hMSCs showed a significant decrease in T2 signal intensity, even within the gelatin sponge in vitro. After implanting the sponge/cell complex in vivo, we could visualize cellular behavior around the implant over time using a noninvasive MRI modality and this finding was correlated with histological study, which illustrates the potential of a new approach proposed here for in vivo monitoring of implanted cell-based tissue-engineered product.
- Published
- 2006
18. Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy
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Hwunjae Lee, Warayuth Sajomsang, Eunjung Kim, Byunghoon Kang, Yong Min Huh, Jin Suck Suh, Eun Kyung Lim, Eunji Jang, Yuna Choi, Sang J. Chung, and Seungjoo Haam
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Materials science ,Cancer therapy ,Nanotechnology ,Theragnosis ,Drug delivery ,pH-sensitive ,Magneticresonance imaging ,Nanocomposites ,Chitosan ,chemistry.chemical_compound ,Magnetic resonance imaging ,Materials Science(all) ,medicine ,General Materials Science ,Doxorubicin ,Nanocomposite ,Nano Express ,Cancer ,Condensed Matter Physics ,medicine.disease ,chemistry ,Targeted drug delivery ,Magnetic nanoparticles ,medicine.drug - Abstract
Smart drug delivery systems that are triggered by environmental conditions have been developed to enhance cancer therapeutic efficacy while limiting unwanted effects. Because cancer exhibits abnormally high local acidities compared to normal tissues (pH 7.4) due to Warburg effects, pH-sensitive systems have been researched for effective cancer therapy. Chitosan-based intelligent theragnosis nanocomposites, N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles (N Chitosan-DMNPs), were developed in this study. N Chitosan-DMNPs are capable of pH-sensitive drug release with MR-guided images because doxorubicin (DOX) and magnetic nanocrystals (MNCs) are encapsulated into the designed N-naphthyl-O-dimethymaleoyl chitosan (N-nap-O-MalCS). This system exhibits rapid DOX release as acidity increases, high stability under high pH conditions, and sufficient capacity for diagnosing and monitoring therapeutic responses. These results demonstrate that N Chitosan-DMNPs have potential as theragnosis nanocomposites for effective cancer therapy.
- Published
- 2013
19. Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals
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Jihye Choi, Yong Min Huh, Seungjoo Haam, Jaemin Lee, Taeksu Lee, Eun Kyung Lim, Byunghoon Kang, Jin Suck Suh, and Hyo Seon Park
- Subjects
Materials science ,Biocompatibility ,Hyaluronic acid ,Nanotechnology ,Metastasis ,chemistry.chemical_compound ,Magnetic resonance imaging ,Materials Science(all) ,medicine ,General Materials Science ,Nano Express ,biology ,CD44 ,Cancer ,Condensed Matter Physics ,medicine.disease ,Colloidal nanoparticles ,In vitro ,Nanomedicine ,chemistry ,biology.protein ,Biophysics ,Molecular imaging ,Nanobioimaging - Abstract
Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis.
- Published
- 2013
20. Metabolic stress induces a Wnt-dependent cancer stem cell-like state transition
- Author
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Gordon B. Mills, Eun Lee, Y.-J. Park, Jaemoon Yang, Jin Suck Suh, Yong Min Huh, C. B. Park, Minhee Ku, Jong In Yook, Jae Ho Cheong, Nam Hee Kim, and E. S. Park
- Subjects
Transcriptional Activation ,Cancer Research ,Transcription, Genetic ,Cell Survival ,Immunology ,Mice, Nude ,Breast Neoplasms ,Biology ,Metastasis ,Transcriptome ,Mice ,Cellular and Molecular Neuroscience ,Stress, Physiological ,Cancer stem cell ,Spheroids, Cellular ,Wnt3A Protein ,Tumor Cells, Cultured ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Wnt Signaling Pathway ,Cell Proliferation ,Mice, Inbred BALB C ,Tumor microenvironment ,CD44 ,Wnt signaling pathway ,Cancer ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,Cell biology ,Cancer cell ,Neoplastic Stem Cells ,biology.protein ,Female ,Original Article - Abstract
Reciprocal interactions between cancer cells and the tumor microenvironment drive multiple clinically significant behaviors including dormancy, invasion, and metastasis as well as therapy resistance. These microenvironment-dependent phenotypes share typical characteristics with cancer stem cells (CSC). However, it is poorly understood how metabolic stress in the confined tumor microenvironment contributes to the emergence and maintenance of CSC-like phenotypes. Here, we demonstrate that chronic metabolic stress (CMS) in a long-term nutrient deprivation induces a Wnt-dependent phenoconversion of non-stem cancer cells toward stem-like state and this is reflected in the transcriptome analysis. Addition of Wnt3a as well as transfection of dominant-negative Tcf4 establishes an obligatory role for the Wnt pathway in the acquisition of CSC-like characteristics in response to metabolic stress. Furthermore, systematic characterization for multiple single cell-derived clones and negative enrichment of CD44+/ESA+ stem-like cancer cells, all of which recapitulate stem-like cancer characteristics, suggest stochastic adaptation rather than selection of pre-existing subclones. Finally, CMS in the tumor microenvironment can drive a CSC-like phenoconversion of non-stem cancer cells through stochastic state transition dependent on the Wnt pathway. These findings contribute to an understanding of the metabolic stress-driven dynamic transition of non-stem cancer cells to a stem-like state in the tumor metabolic microenvironment.
- Published
- 2015
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