92 results on '"Yong-Min, Huh"'
Search Results
2. Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer
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Seo Young Jang, Youngae Jung, Sang Chul Lee, Min Wook Kim, Eun-Woo Lee, Jung-Eun Kim, Jong Woo Kim, Jaewhan Song, Miso Nam, Jin-Ho Seo, Baek Soo Han, Jeong Ki Min, Kyoung Jin Oh, Geum-Sook Hwang, Kwang-Hee Bae, Ji Yoon Lee, Hye Young Son, Won Kon Kim, Seon Jin Yoon, Jihye Kim, Eunji Jang, Yong Min Huh, Jae-Hoon Kim, and Kwangbeom Hyun
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Fatty Acid Desaturases ,Fatty Acid Elongases ,FADS1 ,Linoleic acid ,Lipid peroxidation ,chemistry.chemical_compound ,Delta-5 Fatty Acid Desaturase ,Stomach Neoplasms ,Cell Line, Tumor ,Ferroptosis ,Humans ,Promoter Regions, Genetic ,Fatty Acid Desaturase 1 ,chemistry.chemical_classification ,Arachidonic Acid ,Multidisciplinary ,Fatty acid ,Lipid metabolism ,DNA Methylation ,Biological Sciences ,Lipid Metabolism ,Gene Expression Regulation, Neoplastic ,Enhancer Elements, Genetic ,chemistry ,Biochemistry ,Fatty Acids, Unsaturated ,Arachidonic acid ,Carbolines ,Polyunsaturated fatty acid - Abstract
Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
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- 2020
3. Ambient carbon monoxide exposure and elevated risk of mortality in the glioblastoma patients: A double‐cohort retrospective observational study
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Sahng Wook Park, Yong Min Huh, Seok Gu Kang, Se Hoon Kim, Ju Hyung Moon, Hye Young Son, Juhwan Noh, Jong Hee Chang, Seon Jin Yoon, and Eui Hyun Kim
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Brain tumor ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Epidemiology ,Republic of Korea ,medicine ,Risk of mortality ,Humans ,Radiology, Nuclear Medicine and imaging ,Original Research ,Aged ,Retrospective Studies ,Air Pollutants ,Carbon Monoxide ,Inhalation Exposure ,business.industry ,Brain Neoplasms ,glioblastoma ,Clinical Cancer Research ,Retrospective cohort study ,Perioperative ,Middle Aged ,medicine.disease ,Prognosis ,mortality ,United States ,030104 developmental biology ,Health effect ,030220 oncology & carcinogenesis ,Cohort ,Female ,ambient air pollution ,business ,Glioblastoma ,SEER Program - Abstract
An increasing number of studies indicate air pollutants infiltrate into the brain. We aimed to find the association of cumulative air pollution exposure in the main body of primary brain tumor: glioblastoma (GBM). In this double‐cohort, retrospective analysis study with a protocol, we compared the health effect of air pollution on the GBM patients from the SEER (Surveillance, Epidemiology, and End Results Program) in 27 U.S. counties from 10 states and GBM patients of Severance cohort of Korea. From 2000 to 2015, 10621 GBM patients of the SEER were individually evaluated for the cumulative average exposure for each pollutant, and 9444 (88.9%) mortality events were reported. From 2011 to 2018, 398 GBM patients of the Severance with the same protocol showed 259 (65.1%) mortality events. The multi‐pollutant models show that the association level of risk with CO is increased in the SEER (HR 1.252; 95% CI 1.141‐1.373) with an increasing linear trend of relative death rate in the spline curve. The Severance GBM data showed such a statistically significant result of the health impact of CO on GBM patients. The overall survival gain of the less exposure group against CO was 2 and 3 months in the two cohorts. Perioperative exposure to CO may increase the risk of shorter survival of GBM patients of the SEER and the Severance cohort., This retrospective observational study found that chronic exposure to ambient level of carbon monoxide is associated with a shorter survival of glioblastoma patients (2‐3 months). Such association was validated in the cohorts of the United states (N=10621, HR 1.252, 95% CI 1.141‐1.373) and Korea (N=398, HR 2.874, 95% CI 1.040‐7.944).
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- 2020
4. Loss of desmoglein-2 promotes gallbladder carcinoma progression and resistance to EGFR-targeted therapy through Src kinase activation
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Dong Gwang Lee, Young-Lai Cho, Young-Jun Park, Nayoung Kim, Jin-Man Kim, Jeong-Ki Min, Kwang-Hee Bae, Seon-Jin Lee, Hyun-Soo Cho, Jangwook Lee, Tae-Su Han, Hyo Jin Lee, Heung Jin Jeon, Sang-Hyun Lee, Jang-Seong Kim, Mina Joo, Moo-Seung Lee, Deog Yeon Jo, Hwan Jung Yun, Yong Min Huh, and Jong-Gil Park
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0301 basic medicine ,Lymphovascular invasion ,medicine.medical_treatment ,Mice, Nude ,Article ,Targeted therapy ,Metastasis ,Tumour biomarkers ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,Cell Movement ,Cell Line, Tumor ,medicine ,Carcinoma ,Animals ,Humans ,Neoplasm Invasiveness ,Tumour-suppressor proteins ,Molecular Biology ,Protein Kinase Inhibitors ,Cell Proliferation ,Mice, Inbred BALB C ,Desmoglein 2 ,business.industry ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,In vitro ,Dasatinib ,ErbB Receptors ,030104 developmental biology ,src-Family Kinases ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,Disease Progression ,Gallbladder Neoplasms ,business ,Proto-oncogene tyrosine-protein kinase Src ,medicine.drug ,Signal Transduction - Abstract
Gallbladder carcinoma (GBC) exhibits poor prognosis due to local recurrence, metastasis, and resistance to targeted therapies. Using clinicopathological analyses of GBC patients along with molecular in vitro and tumor in vivo analysis of GBC cells, we showed that reduction of Dsg2 expression was highly associated with higher T stage, more perineural, and lymphatic invasion. Dsg2-depleted GBC cells exhibited significantly enhanced proliferation, migration, and invasiveness in vitro and tumor growth and metastasis in vivo through Src-mediated signaling activation. Interestingly, Dsg2 binding inhibited Src activation, whereas its loss activated cSrc-mediated EGFR plasma membrane clearance and cytoplasmic localization, which was associated with acquired EGFR-targeted therapy resistance and decreased overall survival. Inhibition of Src activity by dasatinib enhanced therapeutic response to anti-EGFR therapy. Dsg2 status can help stratify predicted patient response to anti-EGFR therapy and Src inhibition could be a promising strategy to improve the clinical efficacy of EGFR-targeted therapy.
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- 2020
5. Simultaneous dual-targeted monitoring of breast cancer circulating miRNA via surface-enhanced Raman spectroscopy
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Jinyoung Kim, Joowon Park, Jisun Ki, Hyun Wook Rho, Yong-Min Huh, Eunjung Kim, Hye Young Son, and Seungjoo Haam
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Silver ,Biomedical Engineering ,Biophysics ,Metal Nanoparticles ,Breast Neoplasms ,General Medicine ,Biosensing Techniques ,Spectrum Analysis, Raman ,MicroRNAs ,Electrochemistry ,Humans ,Female ,Circulating MicroRNA ,Gold ,Biotechnology - Abstract
Breast cancer is one of the most common cancers globally. Because the 5-year survival rate of breast cancer greatly increases when treated in its initial stage, the importance of early detection has been increasing. Herein, one-spot multiple breast cancer circulating microRNA (miRNA) detection via surface-enhanced Raman spectroscopy (SERS) with seed-mediated grown Ag nanopillars (SMGAPs) is described. The electrochemical reduction on the pre-distributed 40 nm gold nanoparticle seeds (sGNP) acted as scaffolds for silver ion growth, and a nanopillar-shaped silver structure was successfully grown on the gold substrate surface. The synthesized structure showed uniform and remarkably increased signal enhancement for malachite green isothiocyanate. Based on this consistency, two circulating miRNA markers for breast cancer (miR-21 and miR-155) were used as the SERS diagnostic target. The limit of detection (LOD) of each labeled target was 451 zmol and 1.65 amol respectively. Moreover, miRNAs in four types of cancer cell extracts (HCC1143, HCC1954, MDA-MB-231, MCF-7) were sorted by miR-21 and miR-155 copies. Finally, quantitative analysis of miRNA in urine was successful compared to that in the healthy group.
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- 2021
6. Active colorimetric lipid-coated polyaniline nanoparticles for redox state sensing in cancer cells
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Hyun Ouk Kim, Hyun-Soo Kim, Yoochan Hong, Hyun Wook Rho, Hwunjae Lee, Ohwon Kwon, and Yong Min Huh
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Materials science ,Biomedical Engineering ,Nanoparticle ,Redox ,Absorbance ,chemistry.chemical_compound ,Cell Line, Tumor ,Polyaniline ,Humans ,General Materials Science ,Viability assay ,Aniline Compounds ,Scattering ,Optical Imaging ,General Chemistry ,General Medicine ,Dark field microscopy ,Lipids ,chemistry ,Chemical engineering ,Cancer cell ,Colonic Neoplasms ,Nanoparticles ,Colorimetry ,sense organs ,Oxidation-Reduction - Abstract
Herein, lipid-coated polyaniline (LiPAni) nanoparticles were fabricated to monitor the redox state of cancer cells. To confirm the characteristics of LiPAni, we firstly analyzed the size and chemical structures of the LiPAni nanoparticles. The absorbance properties of the LiPAni nanoparticles were observed to vary with the pH conditions. Furthermore, cell viability tests conducted with breast cancer cell lines showed that the cell viability of the cells with LiPAni nanoparticles was dramatically increased compared to those with the Tween80-coated polyaniline nanoparticles (TPAni) as a control. Subsequently, the colors of the LiPAni nanoparticles were observed and analyzed using spectroscopic methods. Finally, in order to investigate the more accurate sensing of the redox state using the color changes of the LiPAni nanoparticles with cancer cell lines, dark field microscopic images and scattering spectra were recorded at the single nanoparticle scale. For the TPAni nanoparticles, there was only a change in brightness and no change in color, but for the LiPAni nanoparticles, there was a change of color from yellow to pink in the dark field images.
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- 2021
7. Co-expression of cancer driver genes: IDH-wildtype glioblastoma-derived tumorspheres
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Hye Young Son, Sahng Wook Park, Yong Min Huh, Se Hoon Kim, Jin Kyoung Shim, Seok Gu Kang, Jong Hee Chang, Seon Jin Yoon, Ju Hyung Moon, Eui Hyun Kim, and Wan-Yee Teo
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0301 basic medicine ,IDH1 ,Tumorsphere ,lcsh:Medicine ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Single cell RNAseq ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Isocitrate dehydrogenase-wildtype glioblastoma ,Gene expression ,medicine ,PTEN ,Humans ,Gene ,Retrospective Studies ,Temozolomide ,Brain Neoplasms ,Receptor-Like Protein Tyrosine Phosphatases, Class 5 ,Research ,lcsh:R ,General Medicine ,Prognosis ,Isocitrate Dehydrogenase ,030104 developmental biology ,Isocitrate dehydrogenase ,030220 oncology & carcinogenesis ,PTPRZ1 ,Mutation ,biology.protein ,Cancer research ,Neoplasm Recurrence, Local ,Glioblastoma ,medicine.drug - Abstract
Background Driver genes of GBM may be crucial for the onset of isocitrate dehydrogenase (IDH)-wildtype (WT) glioblastoma (GBM). However, it is still unknown whether the genes are expressed in the identical cluster of cells. Here, we have examined the gene expression patterns of GBM tissues and patient-derived tumorspheres (TSs) and aimed to find a progression-related gene. Methods We retrospectively collected primary IDH-WT GBM tissue samples (n = 58) and tumor-free cortical tissue samples (control, n = 20). TSs are isolated from the IDH-WT GBM tissue with B27 neurobasal medium. Associations among the driver genes were explored in the bulk tissue, bulk cell, and a single cell RNAsequencing techniques (scRNAseq) considering the alteration status of TP53, PTEN, EGFR, and TERT promoter as well as MGMT promoter methylation. Transcriptomic perturbation by temozolomide (TMZ) was examined in the two TSs. Results We comprehensively compared the gene expression of the known driver genes as well as MGMT, PTPRZ1, or IDH1. Bulk RNAseq databases of the primary GBM tissue revealed a significant association between TERT and TP53 (p TERT and TP53 expressing cells are in a same single cell cluster. The driver-enriched cluster dominantly expressed the glioma-associated long noncoding RNAs. Most of the driver-associated genes were downregulated after TMZ except IGFBP5. Conclusions GBM tissue level expression patterns of EGFR, TERT, PTEN, IDH1, PTPRZ1, and MGMT are observed in the GBM TSs. The driver gene-associated cluster of the GBM single cells were enriched with the glioma-associated long noncoding RNAs.
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- 2020
8. Multimodal cellular redox nanosensors based on self-doped polyaniline nanocomposites
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Yoochan Hong, Hyun Wook Rho, Hwunjae Lee, Yong Min Huh, and Hyun-Soo Kim
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Materials science ,Cell Survival ,Biomedical Engineering ,Polysorbates ,Nanocomposites ,Absorbance ,chemistry.chemical_compound ,symbols.namesake ,Nanosensor ,Cell Line, Tumor ,Polyaniline ,Humans ,General Materials Science ,Nanocomposite ,Aniline Compounds ,General Chemistry ,General Medicine ,Fluorescence ,Solvent ,chemistry ,Chemical engineering ,symbols ,Pyrene ,Butyric Acid ,Nanoparticles ,Raman spectroscopy ,Oxidation-Reduction - Abstract
We have successfully fabricated a nanocomposite, which is composed of polyaniline (PAni) and pyrene butyric acid (Pyba) via a solvent shift method, which was self-doped at a neutral pH value. This PAni nanocomposite can act as a fine nanoagent expressing absorbance, fluorescence, and Raman properties according to the surrounding pH values.
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- 2020
9. In vivo monitoring platform of transplanted human stem cells using magnetic resonance imaging
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Byunghoon Kang, Hye Young Son, Yuna Choi, Eun Kyung Lim, Moo Kwang Shin, Daewon Park, Jeong Ki Min, Yong Min Huh, Seungmin Han, Jongjin Park, and Seungjoo Haam
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Integrin β1 ,medicine.medical_treatment ,Induced Pluripotent Stem Cells ,Biomedical Engineering ,Biophysics ,02 engineering and technology ,Biosensing Techniques ,Biology ,01 natural sciences ,Regenerative medicine ,In vivo ,Electrochemistry ,medicine ,Humans ,medicine.diagnostic_test ,010401 analytical chemistry ,Magnetic resonance imaging ,Cell Differentiation ,General Medicine ,Stem-cell therapy ,021001 nanoscience & nanotechnology ,Magnetic Resonance Imaging ,0104 chemical sciences ,Cell biology ,Transplantation ,biology.protein ,Stem cell ,Antibody ,0210 nano-technology ,Biotechnology ,Stem Cell Transplantation - Abstract
As stem cells show great promise in regenerative therapy, stem cell-mediated therapeutic efficacy must be demonstrated through the migration and transplantation of stem cells into target disease areas at the pre-clinical level. In this study, we developed manganese-based magnetic nanoparticles with hollow structures (MnOHo) and modified them with the anti-human integrin β1 antibody (MnOHo-Ab) to enable the minimal-invasive monitoring of transplanted human stem cells at the pre-clinical level. Compared to common magnetic resonance imaging (MRI)-based stem cell monitoring systems that use pre-labeled stem cells with magnetic particles before stem cell injection, the MnOHo-Ab is a new technology that does not require stem cell modification to monitor the therapeutic capability of stem cells. Additionally, MnOHo-Ab provides improved T1 MRI owing to the hollow structure of the MnOHo. Particularly, the anti-integrin β1 antibody (Ab) introduced in the MnOHo targets integrin β1 expressed in the entire stem cell lineage, enabling targeted monitoring regardless of the differentiation stage of the stem cells. Furthermore, we verified that intravenously injected MnOHo-Ab specifically targeted human induced pluripotent stem cells (hiPSCs) that were transferred to mice testes and differentiated into various lineages. The new stem cell monitoring method using MnOHo-Ab demonstrates whether the injected human stem cells have migrated and transplanted themselves in the target area during long-term stem cell regenerative therapy.
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- 2020
10. Contrast-enhanced ultrasound liver imaging reporting and data system for diagnosing hepatocellular carcinoma: A meta-analysis
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Mi-Suk Park, Heejin Bae, Yong Min Huh, Jin-Young Choi, Yong Eun Chung, Sunyoung Lee, and Jaeseung Shin
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Hepatology ,business.industry ,Quality assessment ,Ultrasound ,Liver Neoplasms ,Contrast Media ,Diagnostic accuracy ,medicine.disease ,Magnetic Resonance Imaging ,Confidence interval ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Meta-analysis ,Hepatocellular carcinoma ,medicine ,Humans ,030211 gastroenterology & hepatology ,Radiology ,business ,Contrast-enhanced ultrasound ,Liver imaging ,Retrospective Studies - Abstract
Background & aims Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing CEUS at high risk for hepatocellular carcinoma (HCC). We performed a meta-analysis to determine the diagnostic performance of the CEUS LR-5 for HCC and the pooled proportions of HCCs in each CEUS LI-RADS category. Methods We searched multiple databases for studies reporting the diagnostic accuracy of the CEUS LI-RADS. Random-effects model was used to determine summary estimates of the diagnostic performance of CEUS LR-5 and the pooled proportions of HCCs in each CEUS LI-RADS category. Risk of bias and concerns regarding applicability were evaluated with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results Eleven studies were included in the final analysis, which consisted of 5535 observations with 3983 HCCs. The pooled per-observation sensitivity and specificity of the CEUS LR-5 for diagnosing HCC were 69% (95% confidence interval [CI], 64%-73%) and 92% (95% CI, 83%-96%) respectively. The pooled proportions of HCCs were 0% (95% CI, 0-0%) for LR-1, 1% (95% CI, 0%-4%) for CEUS LR-2, 26% (95% CI, 14%-39%) for CEUS LR-3, 77% (95% CI, 68%-86%) for CEUS LR-4, 97% (95% CI, 95%-98%) for CEUS LR-5, 57% (95% CI, 44%-69%) for CEUS LR-M and 100% (95% CI, 93%-100%) for CEUS LR-5V or TIV. Conclusions The CEUS LR-5 category showed moderate sensitivity and high specificity for diagnosing HCC. The proportion of HCCs was higher in the higher CEUS LI-RADS categories.
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- 2020
11. 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
12. A radiomics-based model for predicting prognosis of locally advanced gastric cancer in the preoperative setting
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Jie Hyun Kim, Kyunghwa Han, Sung-Won Kim, Joon Seok Lim, Woo Jin Hyung, Jaeseung Shin, Yong Min Huh, and Jae-Joon Chung
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Male ,medicine.medical_specialty ,Science ,Locally advanced ,Kaplan-Meier Estimate ,Models, Biological ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Gastrointestinal cancer ,Prognostic markers ,0302 clinical medicine ,Radiomics ,Stomach Neoplasms ,Medicine ,Humans ,Internal validation ,Aged ,Neoplasm Staging ,Retrospective Studies ,Multidisciplinary ,Receiver operating characteristic ,business.industry ,Proportional hazards model ,Stomach ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Prognosis ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Cohort ,Female ,Cancer imaging ,Radiology ,Neoplasm Recurrence, Local ,business ,Tomography, X-Ray Computed - Abstract
This study aims to evaluate the performance of a radiomic signature-based model for predicting recurrence-free survival (RFS) of locally advanced gastric cancer (LAGC) using preoperative contrast-enhanced CT. This retrospective study included a training cohort (349 patients) and an external validation cohort (61 patients) who underwent curative resection for LAGC in 2010 without neoadjuvant therapies. Available preoperative clinical factors, including conventional CT staging and endoscopic data, and 438 radiomic features from the preoperative CT were obtained. To predict RFS, a radiomic model was developed using penalized Cox regression with the least absolute shrinkage and selection operator with ten-fold cross-validation. Internal and external validations were performed using a bootstrapping method. With the final 410 patients (58.2 ± 13.0 years-old; 268 female), the radiomic model consisted of seven selected features. In both of the internal and the external validation, the integrated area under the receiver operating characteristic curve values of both the radiomic model (0.714, P P = 0.010 [external validation]) and the merged model (0.719, P P = 0.014) were significantly higher than those of the clinical model (0.616; 0.594). The radiomics-based model on preoperative CT images may improve RFS prediction and high-risk stratification in the preoperative setting of LAGC.
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- 2020
13. Predictive test for chemotherapy response in resectable gastric cancer: a multi-cohort, retrospective analysis
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Hye Seon Kim, Kyung Hee Lee, Woo Ho Kim, Myeong Cherl Kook, Hyunki Kim, Jinae Lee, Hyung Ho Kim, Ha Yan Kim, Young-Kyu Park, Young-Woo Kim, Mi Jin Gu, Jae Ho Cheong, Soon Won Hong, Eunji Jang, Woo Jin Hyung, Sung Hoon Noh, Hye Seung Lee, Yoon Young Choi, Jongwon Kim, Seung Ho Choi, Yong Min Huh, and Han-Kwang Yang
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Male ,0301 basic medicine ,Oncology ,Time Factors ,Tryptophan-tRNA Ligase ,Granzymes ,0302 clinical medicine ,Risk Factors ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Medicine ,Precision Medicine ,Prospective cohort study ,Univariate analysis ,Hazard ratio ,Treatment Outcome ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Predictive value of tests ,Cohort ,Female ,medicine.drug ,medicine.medical_specialty ,Clinical Decision-Making ,Risk Assessment ,Decision Support Techniques ,03 medical and health sciences ,Gastrectomy ,Predictive Value of Tests ,Stomach Neoplasms ,Proto-Oncogene Proteins ,Internal medicine ,Biomarkers, Tumor ,Humans ,Aged ,Neoplasm Staging ,Retrospective Studies ,Homeodomain Proteins ,business.industry ,Gene Expression Profiling ,Patient Selection ,Computational Biology ,Reproducibility of Results ,Retrospective cohort study ,Decision Support Systems, Clinical ,Oxaliplatin ,030104 developmental biology ,Transcriptome ,business - Abstract
Summary Background Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer. Methods In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival. Findings We identified four classifier genes related to relevant gastric cancer features ( GZMB, WARS, SFRP4 , and CDX1 ) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS , and SFRP4 ) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS , and CDX1 ) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% [95% CI 73·5–87·1] vs 64·5% [56·8–73·3]; univariate hazard ratio 0·47 [95% CI 0·30–0·75], p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% [66·5–79·9] in patients who received chemotherapy plus surgery vs 72·5% [65·8–79·9] in patients who only had surgery; 0·93 [0·62–1·38], p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (p interaction =0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort. Interpretation The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted. Funding Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.
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- 2018
14. Fluorescence amplified sensing platforms enabling miRNA detection by self-circulation of a molecular beacon circuit
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Hye Young Son, Taejoon Kang, Eun Kyung Lim, Juyeon Jung, Seul Gee Hwang, Yong Min Huh, Kyeonghye Guk, Jaewoo Lim, and Yuna Choi
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animal structures ,Breast Neoplasms ,Computational biology ,010402 general chemistry ,01 natural sciences ,Signal ,Catalysis ,Fluorescence ,Mice ,Molecular beacon ,Limit of Detection ,Cell Line, Tumor ,microRNA ,Materials Chemistry ,Animals ,Humans ,010405 organic chemistry ,Chemistry ,Optical Imaging ,Metals and Alloys ,Nucleic Acid Hybridization ,General Chemistry ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,MicroRNAs ,Spectrometry, Fluorescence ,Ceramics and Composites ,Female ,Signal amplification - Abstract
We have proposed a novel strategy for miRNA detection through enzyme-free signal amplification by self-circulation of the hybridization between the miRNAs and molecular beacon (MB) circuits. Unlike general MB-based miRNA detection based on the one-to-one (1 : 1) hybridization between MBs and miRNA, our system consists of four species of MBs (MBs A, B, C and D) (MB circuits) and is activated by a hybridization chain reaction. MBs stably coexist as hairpin structures that hardly show fluorescence signals in the absence of target miRNA. After miRNA detection, this MB circuit is able to generate fluorescence signals and amplify the fluorescence signal, contributing to improvement in detection sensitivity under iso-thermal conditions without an enzyme. Furthermore, in vitro and in vivo studies have proven that MB circuits can detect low levels of miRNA with high sensitivity, compared to when only one MB alone is used. Therefore, the MB circuits can provide a useful platform for target miRNA detection.
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- 2019
15. Nanovesicle-mediated systemic delivery of microRNA-34a for CD44 overexpressing gastric cancer stem cell therapy
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Eun Kyung Lim, Hwunjae Lee, Hye Young Son, Seungmin Han, Yong Min Huh, Jin Suck Suh, Eunjung Kim, Seungjoo Haam, Kwangyeol Park, Eunji Jang, and Yuna Choi
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Male ,0301 basic medicine ,Homeobox protein NANOG ,Biophysics ,Bioengineering ,Nanoconjugates ,medicine.disease_cause ,Metastasis ,Biomaterials ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Nanocapsules ,Stomach Neoplasms ,Cancer stem cell ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Mice, Inbred BALB C ,biology ,CD44 ,medicine.disease ,MicroRNAs ,Hyaluronan Receptors ,Treatment Outcome ,030104 developmental biology ,Mechanics of Materials ,MicroRNA 34a ,030220 oncology & carcinogenesis ,Cancer cell ,Immunology ,Neoplastic Stem Cells ,Ceramics and Composites ,biology.protein ,Cancer research ,Carcinogenesis - Abstract
The cancer stem cell (CSC) hypothesis postulates that cancer cells overexpressing CD44 are marked as CSCs that cause tumorigenesis and recurrence. This hypothesis suggests that CD44 is a potential therapeutic target that can interfere with CSCs qualities. MicroRNA-34a (miR-34a) is a promising candidate for CD44 repression-based cancer therapy as it has been reported to inhibit proliferation, metastasis, and survival of CD44-positive CSCs. Here, we used nanovesicles containing PLI/miR complexes (NVs/miR) to systemically deliver miR-34a and induce miR-34a-triggered CD44 suppression in orthotopically and subcutaneously implanted tumors in nude mice. Poly(l-lysine-graft-imidazole) (PLI) condenses miRs and is functionally modified to deliver miRs to the site of action by buffering effect of imidazole residues under endosomal pH. Indeed, NVs/miR consisting of PEGylated lipids enveloping PLI/miR complexes greatly reduced inevitable toxicity of polycations by compensating their surface charge and markedly improved their in vivo stability and accumulation to tumor tissue compared to PLI/miR polyplexes. Our NVs-mediated miR-34a delivery system specifically increased endogenous target miR levels, thereby attenuating proliferation and migration of gastric cancer cells by repressing the expression of CD44 with decreased levels of Bcl-2, Oct 3/4 and Nanog genes. Our strategy led to a greater therapeutic outcome than PLI-based delivery with highly selective tumor cell death and significantly delayed tumor growth in CD44-positive tumor-bearing mouse models, thus providing a fundamental therapeutic window for CSCs.
- Published
- 2016
16. Receptor tyrosine kinase amplified gastric cancer: Clinicopathologic characteristics and proposed screening algorithm
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Yong Min Huh, Woo Jin Hyung, Sang Kil Lee, Sung Hoon Noh, Hyunki Kim, Yong Chan Lee, Hyo Song Kim, Jae Ho Cheong, Cheol Keun Park, Sun Young Rha, and Ji Soo Park
- Subjects
Male ,Oncology ,Herpesvirus 4, Human ,Pathology ,screening algorithm ,Receptor, ErbB-2 ,Lymphovascular invasion ,medicine.medical_treatment ,amplification ,Receptor tyrosine kinase ,Targeted therapy ,0302 clinical medicine ,Molecular classification ,Early Detection of Cancer ,In Situ Hybridization ,Mismatch Repair Endonuclease PMS2 ,Tissue microarray ,biology ,Stomach ,Age Factors ,Middle Aged ,Proto-Oncogene Proteins c-met ,Prognosis ,Immunohistochemistry ,DNA-Binding Proteins ,ErbB Receptors ,MutS Homolog 2 Protein ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,RNA, Viral ,Female ,030211 gastroenterology & hepatology ,MutL Protein Homolog 1 ,Algorithms ,Research Paper ,Adult ,medicine.medical_specialty ,Mixed type ,Screening algorithm ,03 medical and health sciences ,Stomach Neoplasms ,Internal medicine ,medicine ,Humans ,Genetic Testing ,Aged ,Neoplasm Staging ,business.industry ,gastric cancer ,Gene Amplification ,Cancer ,medicine.disease ,Tissue Array Analysis ,Mutation ,receptor tyrosine kinase ,biology.protein ,Tumor Suppressor Protein p53 ,business - Abstract
// Cheol Keun Park 1 , Ji Soo Park 2 , Hyo Song Kim 2 , Sun Young Rha 2 , Woo Jin Hyung 3 , Jae-Ho Cheong 3 , Sung Hoon Noh 3 , Sang Kil Lee 4 , Yong Chan Lee 4 , Yong-min Huh 5 , Hyunki Kim 1 1 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 5 YUMS-KRIBB Medical Convergence Research Institute, Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Hyunki Kim, email: kimhyunki@yuhs.ac Keywords: gastric cancer, receptor tyrosine kinase, amplification, screening algorithm Received: June 17, 2016 Accepted: September 17, 2016 Published: September 27, 2016 ABSTRACT Although targeted therapy for receptor tyrosine kinases (RTKs) of advanced gastric cancers (AGCs) has been in the spotlight, guidelines for the identification of RTK-amplified gastric cancers (RA-GCs) have not been established. In this study, we investigate clinicopathologic characteristics of RA-GCs and propose a screening algorithm for their identification. We performed immunohistochemistry (IHC) for MLH1, MSH2, PMS2, MSH6, key RTKs (EGFR, HER2, MET), and p53, in situ hybridization for Epstein-Barr virus encoding RNA, and silver in situ hybridization (SISH) for EGFR , HER2 , and MET using tissue microarrays of 993 AGCs. On IHC, 157 (15.8%) 61, (6.15%), and 85 (8.56%) out of 993 cases scored 2+ or 3+ for EGFR, HER2, and MET, respectively. On SISH, 31.2% (49/157), 80.3% (49/61), and 30.6% (26/85) of 2+ or 3+ cases on IHC showed amplification of the corresponding genes. Of the 993 cases, 104 were classified as RA-GCs. RA-GC status correlated with older age ( P < 0.001), differentiated histology ( P = 0.001), intestinal or mixed type by Lauren classification ( P < 0.001), lymphovascular invasion ( P = 0.026), and mutant-pattern of p53 ( P < 0.001). The cases were divided into four subgroups using two classification systems, putative molecular classification and histologic-molecular classification , based on Lauren classification, IHC, and SISH results. The histologic-molecular classification showed higher sensitivity for identification of RA-GCs and predicted patient prognosis better than the putative molecular classification . In conclusion, RA-GCs show unique clinicopathologic features. The proposed algorithm based on histologic-molecular classification can be applied to select candidates for genetic examination and targeted therapy.
- Published
- 2016
17. Serially Ordered Magnetization of Nanoclusters via Control of Various Transition Metal Dopants for the Multifractionation of Cells in Microfluidic Magnetophoresis Devices
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Seungmin Han, Bongsoo Kim, Seo Ryung Bae, Moo Kwang Shin, Seungjoo Haam, Il Moon, Yong Min Huh, Bumjoon Cha, Hye Yeong Son, Eunji Jang, Unyong Jeong, Hyun Ouk Kim, and Byunghoon Kang
- Subjects
Surface Properties ,Microfluidics ,Analytical chemistry ,Cell Separation ,02 engineering and technology ,01 natural sciences ,Analytical Chemistry ,Nanoclusters ,Magnetization ,Cell Line, Tumor ,Atom ,Transition Elements ,Physics::Atomic and Molecular Clusters ,Humans ,Particle Size ,Magnetite Nanoparticles ,Dopant ,Chemistry ,Magnetic Phenomena ,010401 analytical chemistry ,Doping ,Microfluidic Analytical Techniques ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Magnetic field ,Chemical physics ,0210 nano-technology - Abstract
A novel method (i.e., continuous magnetic cell separation in a microfluidic channel) is demonstrated to be capable of inducing multifractionation of mixed cell suspensions into multiple outlet fractions. Here, multicomponent cell separation is performed with three different distinguishable magnetic nanoclusters (MnFe2O4, Fe3O4, and CoFe2O4), which are tagged on A431 cells. Because of their mass magnetizations, which can be ideally altered by doping with magnetic atom compositions (Mn, Fe, and Co), the trajectories of cells with each magnetic nanocluster in a flow are shown to be distinct when dragged under the same external magnetic field; the rest of the magnetic characteristics of the nanoclusters are identically fixed. This proof of concept study, which utilizes the magnetization-controlled nanoclusters (NCs), suggests that precise and effective multifractionation is achievable with high-throughput and systematic accuracy for dynamic cell separation.
- Published
- 2016
18. Functionalized Magnetic PLGA Nanospheres for Targeting and Bioimaging of Breast Cancer
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Jin-Chul Kim, Jong-Duk Kim, Jae Hyun Jeong, Yong Min Huh, Seung Jun Lee, Il Won Kim, and Hee-Jin Kim
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Materials science ,Biomedical Engineering ,Contrast Media ,Bioengineering ,Breast Neoplasms ,02 engineering and technology ,Conjugated system ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,Breast cancer ,Polylactic Acid-Polyglycolic Acid Copolymer ,In vivo ,Cell Line, Tumor ,medicine ,Humans ,General Materials Science ,Lactic Acid ,skin and connective tissue diseases ,Magnetite Nanoparticles ,Cancer ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Magnetic Resonance Imaging ,0104 chemical sciences ,PLGA ,chemistry ,Cell culture ,Biophysics ,Magnetic nanoparticles ,Molecular imaging ,0210 nano-technology ,Nanospheres ,Polyglycolic Acid - Abstract
Superparamagnetic iron oxide nanoparticles (SPIONs) are actively used as highly sensitive imaging probes to provide contrast in MRI. In this study, we propose the use of SPIONs encapsulated with antibody-conjugated poly(lactic-co-glycolic acid) (PLGA) as a potent theragnostic agent. The SPIONs were synthesized by a chemical co-precipitation method of ferric and ferrous ions, and subsequently encapsulated with PLGA by using an emulsification-diffusion method. Herceptin was chemically conjugated to the SPION-encapsulating PLGA nanoparticles to target the human epidermal growth factor receptor 2 (Her2/neu) overexpressing breast cancers. FACS and MR molecular imaging revealed that the Her2/neu overexpressing cell line showed a stronger contrast enhancement than the Her2/neu non-expressing cell lines, and the signal intensity of in vivo MR imaging decreased as the concentration of Herceptin increased. This strategy of encapsulating SPIONs with PLGA will be highly useful in functionalizing magnetic nanoparticles and improving the diagnostic and therapeutic efficacy of a wide array of cancer treatments.
- Published
- 2018
19. Discrimination of single nucleotide mismatches using a scalable, flexible, and transparent three-dimensional nanostructure-based plasmonic miRNA sensor with high sensitivity
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Hee Kyung Na, Tae Geol Lee, Jung-Sub Wi, Hye Young Son, Yong Min Huh, and Jong G. Ok
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Nanostructure ,Materials science ,Base Pair Mismatch ,Biomedical Engineering ,Biophysics ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Multiplexing ,Cell Line, Tumor ,Lab-On-A-Chip Devices ,Neoplasms ,Electrochemistry ,Miniaturization ,Tumor Cells, Cultured ,Humans ,Sensitivity (control systems) ,Surface plasmon resonance ,Locked nucleic acid ,Plasmon ,General Medicine ,Equipment Design ,Surface Plasmon Resonance ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Nanostructures ,MicroRNAs ,0210 nano-technology ,Biosensor ,Biotechnology - Abstract
Localized surface plasmon resonance (LSPR) biosensors have attracted much interest due to their capacity for multiplexing, miniaturization, and high performance, which offers the potential for their integration into lab-on-a-chip platforms for point-of-care (POC) diagnostics. The need for microRNA (miRNA)-sensing platforms is particularly urgent because miRNAs are key regulators and biomarkers in numerous pathological processes and diseases. Unfortunately, however, development of such miRNA-sensing platforms has not yet been achieved. In order to realize the detection of these important biomarkers, there has been an increasing demand for POC-sensing platforms that enable label-free quantification with low sample consumption, good sensitivity, real-time responsiveness, and high throughput. Here, we developed a highly specific, sensitive LSPR miRNA-sensing platform on a flexible, scalable plasmonic nanostructure to enable single-base mismatch discrimination and attomole detection of miRNAs in clinically relevant samples. The hairpin probe contained a locked nucleic acid (LNA) that enabled the discrimination of single base mismatches based on differences in melting temperatures of perfectly matched or single base mismatched miRNAs when they formed base pairs with probes. In addition, through hybridization induced signal amplification based on precipitate formation on the gold surface through the enzyme reaction, we observed a dramatic LSPR peak shift, which enabled attomole detection. Additionally, our LSPR miRNA sensor enabled the detection of miR-200a-3p in total RNA extracts from primary cancer cell lines without purification or labeling of the miRNA. This label-free and highly specific miRNA sensing platform may have applications in POC cancer diagnostics without the need for gene amplification.
- Published
- 2018
20. 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.
- Published
- 2015
21. Nanomaterials for Theranostics: Recent Advances and Future Challenges
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Eun Kyung Lim, Soonmyung Paik, Kwangyeol Lee, Yong Min Huh, Seungjoo Haam, and Taekhoon Kim
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Diagnostic Imaging ,Drug Carriers ,Drug Delivery Systems ,Nanomedicine ,Chemistry ,Neoplasms ,Animals ,Humans ,Antineoplastic Agents ,Nanotechnology ,General Chemistry ,Nanostructures ,Nanomaterials - Published
- 2014
22. Convenient Monitoring System of Intracellular microRNA Expression during Adipogenesis via Mechanical Stimulus-Induced Exocytosis of Lipovesicular miRNA Beacon
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Seungjoo Haam, Jisun Ki, Hye Young Son, Mun Young Jeong, Eunjung Kim, Seungmin Han, Byunghoon Kang, Yong Min Huh, and Eunji Jang
- Subjects
0301 basic medicine ,Cellular differentiation ,Cell ,Biomedical Engineering ,Pharmaceutical Science ,Exocytosis ,Biomaterials ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,Humans ,Fluorescent Dyes ,Adipogenesis ,Chemistry ,Cell Differentiation ,Mesenchymal Stem Cells ,Phenotype ,Cell biology ,Molecular Imaging ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Cytoplasm ,030220 oncology & carcinogenesis ,Intracellular - Abstract
Noninvasive investigation of microRNAs (miRNAs) expression, which is deeply related to biological phenomena such as stem cell differentiation, in culture soup is particularly useful for monitoring of stem cell differentiation without phototoxicity of living cells, especially when cell morphologies remain unchanged during differentiation. However, real-time detection of miRNA in culture soup is not recommended because of insufficient miRNA amounts in culture soup. In this study, a convenient method is introduced for real-time assessing intracellular miRNA in culture soup by using lipovesicular miRNA beacon (Lipo-mB) and mechanical stimulus-mediated exocytosis. Pipetting-harvest of culture soup induces exocytosis-secretion of fluorescence signal of Lipo-mB from cytoplasm into culture soup. To demonstrate this method, Lipo-mB is applied for monitoring of adipogenesis by analyzing the expression levels of various intracellular miRNAs, which are related to adipogenesis regulators. The fluorescence intensity profile of the culture soup is correlated with the quantitative reverse-transcription-polymerase chain reaction data and absorbance of Oil Red O staining. These results demonstrate that Lipo-mB can successfully monitor stem cell differentiation by sensing changes in miRNA expression from culture soup of living cells. Lipo-mB can be further developed as an accurate sensing system for analyzing subtle differences in genotype, even when changes in phenotype cannot be observed.
- Published
- 2017
23. Instantaneous pH-Boosted Functionalization of Stellate Gold Nanoparticles for Intracellular Imaging of miRNA
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Eunji Jang, Seungmin Han, Yong Min Huh, Byunghoon Kang, Jisun Ki, Seungjoo Haam, and Moo Kwang Shin
- Subjects
animal structures ,Materials science ,Nanoparticle ,Metal Nanoparticles ,02 engineering and technology ,Hydrogen-Ion Concentration ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Molecular biology ,0104 chemical sciences ,MicroRNAs ,Cell culture ,Colloidal gold ,Molecular beacon ,microRNA ,Biophysics ,Surface modification ,Humans ,General Materials Science ,Gold ,0210 nano-technology ,Intracellular ,Gastric cancer cell - Abstract
Various types of nanoprobes have recently been utilized to monitor living organisms by detecting and imaging intracellular biomarkers, such as microRNAs (miRs). We here present a simple one-pot method to prepare stellate gold nanoparticles functionalized with miR-detecting molecular beacons (SGNP-MBs); low pH conditions permitted the rapid-high loading of MBs on the surface of SGNPs. Compared to the conventional gold nanoparticle-based MBs, SGNPs carried a 4.5-fold higher load of MBs and exhibited a 6.4-fold higher cellular uptake. We demonstrated that SGNP-MBs were successfully internalized in human gastric cancer cell lines and could be used to accurately detect and image intracellular miRs in an miR-specific manner. Furthermore, the relative levels of intracellular miRs in three different cell lines expressing miR-10b (high, moderate, and low levels) could be monitored using SGNP-MBs. Consequently, these results indicated that SGNP-MBs could have applications as highly potent, efficient nanoprobes to assess intracellular miR levels in living cells.
- Published
- 2017
24. A Multistep Photothermic-Driven Drug Release System Using Wire-Framed Au Nanobundles
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Eunkyoung Kim, Seungjoo Haam, Jihye Choi, Doyeon Bang, Taeksu Lee, Yeonji Park, and Yong Min Huh
- Subjects
Materials science ,Nanostructure ,Light ,Biomedical Engineering ,Cancer therapy ,Metal Nanoparticles ,Mice, Nude ,Pharmaceutical Science ,Nanoparticle ,Nanotechnology ,Biomaterials ,Drug Delivery Systems ,In vivo ,Cell Line, Tumor ,Animals ,Humans ,Mice, Inbred BALB C ,Spectroscopy, Near-Infrared ,Tumor region ,Temperature ,Controlled release ,Absorption, Physicochemical ,Microscopy, Fluorescence ,Drug delivery ,Drug release ,Gold ,Biomedical engineering - Abstract
Here, wire-framed Au nanobundles (WNBs), which consist of randomly oriented and mutually connected Au wires to form a bundle shape, are synthesized. In contrast to conventional nanoparticles (spheres, rods, cubes, and stars), which exhibit nanostructure only on the surface, cross-sectional view image shows that WNBs have nanostructures in a whole volume. By using this specific property of WNBs, an externally controllable multistep photothermic-driven drug release (PDR) system is demonstrated for in vivo cancer treatment. In contrast to conventional nanoparticles that encapsulate a drug on their surface, WNBs preserve the drug payload in the overall inner volume, providing a drug loading capacity sufficient for cancer therapy. An improved in vivo therapeutic efficacy of PDR therapy is also demonstrated by delivering sufficient amount of drugs to the target tumor region.
- Published
- 2014
25. Molecular recognition of proteolytic activity in metastatic cancer cells using fluorogenic gold nanoprobes
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Minhee Ku, Miran Seo, Dae Sung Yoon, Hyeon Jung Lee, Jin Suck Suh, Jong In Yook, Seungyeon Hwang, Jaemoon Yang, Dan Heo, Jihye Choi, Joseph Park, Eugene Lee, Yoochan Hong, Yong Min Huh, Eun Jig Lee, and Seungjoo Haam
- Subjects
Biomedical Engineering ,Biophysics ,Nanoprobe ,Peptide ,Biosensing Techniques ,Endocytosis ,Fluorescence ,chemistry.chemical_compound ,Cell Movement ,Cell Line, Tumor ,Neoplasms ,Matrix Metalloproteinase 14 ,Electrochemistry ,Humans ,Neoplasm Metastasis ,Fluorescein isothiocyanate ,Fluorescent Dyes ,chemistry.chemical_classification ,Optical Imaging ,General Medicine ,Ligand (biochemistry) ,Molecular biology ,In vitro ,chemistry ,Proteolysis ,Cancer cell ,MCF-7 Cells ,Nanoparticles ,HT1080 ,Gold ,Biotechnology - Abstract
We describe the development of biomarker-sensitive nanoprobes based on nanoparticle surface energy transfer (NSET) effect that enabling recognition of the expression of membrane type-1 matrix metalloproteinase (MT1-MMP) anchored on invasive cancer cells and its proteolytic activity simultaneously. First of all, we confirmed invasiveness of cancer cell lines (HT1080 and MCF7) via migration and invasion assay. We also prepared gold nanoparticle (GNP) acts as a quencher for fluorescein isothiocyanate (FITC). This FITC is conjugated in end-terminal of activatable fluorogenic peptide (ActFP). The ActFP attach to surface of GNP (GNP-ActFP) for a targeting moiety and proteolytic activity ligand toward MT1-MMP. The GNP-ActFP can generate fluorescence signal when ActFP is cleaved by proteolytic activity after targeting toward MT1-MMP. In order to study specificity for MT1-MMP, GNP-ActFP is treated to HT1080 and MCF7 cells, and then, we determine the in vitro targeting potential and fluorogenic activity of GNP-ActFP for MT1-MMP via fluorescence multi-reader. We also confirmed fluorogenic activity of GNP-ActFP via confocal microscopic imaging, and finally, endocytosis of GNP-ActFP is observed via cellular transmission electron microscopic imaging.
- Published
- 2014
26. Gadolinium-Enriched Polyaniline Particles (GPAPs) for Simultaneous Diagnostic Imaging and Localized Photothermal Therapy of Epithelial Cancer
- Author
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Yong Min Huh, Eunkyoung Kim, Donghun Kim, Sun Hee Kim, Yeonji Park, Doyeon Bang, Taeksu Lee, Jin Suck Suh, Seungjoo Haam, Jihye Choi, and Joseph Park
- Subjects
Diagnostic Imaging ,Materials science ,Gadolinium ,Biomedical Engineering ,Contrast Media ,Pharmaceutical Science ,chemistry.chemical_element ,Epithelial cancer ,Cell Line ,Biomaterials ,Mice ,chemistry.chemical_compound ,Nuclear magnetic resonance ,Polyaniline ,Medical imaging ,Animals ,Humans ,Neoplasms, Glandular and Epithelial ,Aniline Compounds ,Hyperthermia, Induced ,Photothermal therapy ,Magnetic Resonance Imaging ,Xenograft Model Antitumor Assays ,chemistry ,Biomedical engineering - Abstract
By loading Gd(III) inside NIR-absorbing polyaniline nanostructures, a novel diagnostic and photothermal agent with enhanced MR sensitivity, targeting ability, and photothermal ability to treat epithelial cancer is developed.
- Published
- 2014
27. Single Patient Classifier Assay, Microsatellite Instability, and Epstein-Barr Virus Status Predict Clinical Outcomes in Stage II/III Gastric Cancer: Results from CLASSIC Trial
- Author
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Woo Jin Hyung, Hye Seon Kim, Yoon Young Choi, Jae Ho Cheong, Yong Min Huh, Seohee Choi, Chul Kyu Roh, Won Jun Seo, Minah Cho, Eunji Jang, Sung Hoon Noh, Taeil Son, and Hyoung Il Kim
- Subjects
Male ,Oncology ,Herpesvirus 4, Human ,medicine.medical_treatment ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,medicine.disease_cause ,law.invention ,Cohort Studies ,0302 clinical medicine ,Randomized controlled trial ,law ,Hazard ratio ,General Medicine ,Middle Aged ,Prognosis ,Treatment Outcome ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Original Article ,Female ,Microsatellite Instability ,medicine.drug ,medicine.medical_specialty ,animal structures ,single patient classifier ,Disease-Free Survival ,Capecitabine ,03 medical and health sciences ,EBV ,Stomach Neoplasms ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Neoplasm Staging ,Proportional Hazards Models ,Chemotherapy ,business.industry ,fungi ,Microsatellite instability ,medicine.disease ,Epstein–Barr virus ,digestive system diseases ,Confidence interval ,Oxaliplatin ,Multivariate Analysis ,Gastric cancer ,business - Abstract
Purpose Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. Materials and Methods Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. Results There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. Conclusion SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.
- Published
- 2019
28. Isolation of mesenchymal stem-like cells in meningioma specimens
- Author
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Jong Hee Chang, Bo Kyung Kim, Kyung-Min Kim, Yong Min Huh, Seok Gu Kang, Hyo Yeol Lim, Se Hoon Kim, Su Jae Lee, Jin Kyoung Shim, Sun Ho Kim, Yong Kil Hong, Kyu Won Shim, Eui Hyun Kim, Eun Kyung Park, Dong Seok Kim, and Ji Hyun Lee
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Bone Marrow Cells ,Receptors, Cell Surface ,Cell Separation ,Biology ,Flow cytometry ,Meningioma ,Mice ,Antigen ,Antigens, CD ,Osteogenesis ,Glioma ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,neoplasms ,Cells, Cultured ,Adipogenesis ,medicine.diagnostic_test ,Mesenchymal stem cell ,Endoglin ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell sorting ,Flow Cytometry ,medicine.disease ,nervous system diseases ,Oncology ,Immunohistochemistry ,Chondrogenesis - Abstract
Cells resembling bone marrow mesenchymal stem cells (BM-MSCs) have been isolated from glioma specimens; however, little is known about the existence of mesenchymal stem-like cells (MSLCs) in meningioma. Here, we hypothesized that cells similar to BM-MSCs exist in meningioma specimens and sought to investigate whether these putative meningioma stroma MSLCs (MS-MSLCs) could be isolated. To this end, we cultured fresh meningioma specimens using the same protocols as used previously to isolate BM-MSC. Cultured cells were analyzed for surface markers associated with BM-MSCs by fluorescence-activated cell sorting (FACS) and candidate cells were exposed to mesenchymal differentiation conditions. Possible locations of MS-MSLCs were determined by immunohistochemical analysis of sections of meningioma specimens. Spindle-shaped and, adherent cells similar to BM-MSCs were isolated in 2 of 20 meningioma specimens. FACS analysis showed that the surface markers of MS-MSLCs were similar to those of BM-MSCs and the chosen cells demonstrated an ability to differentiate into osteogenic, adipogenic and chondrogenic cells. The tumorigenicity of MS-MSLCs was tested by injection of these cells into the brain of athymic nude mice; no tumors were subsequently discovered. Immunohistochemical analyses indicated that CD105+ cells were closely associated with endothelial cells and pericytes in meningioma specimens. Our results established for the first time that cells similar to BM-MSCs exist in meningioma specimens. These cells, termed MS-MSLCs, could be one component of the meningioma cellular microenvironment.
- Published
- 2013
29. Isolation of tumor spheres and mesenchymal stem-like cells from a single primitive neuroectodermal tumor specimen
- Author
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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
- Subjects
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.
- Published
- 2013
30. Inhibition of glioblastoma tumorspheres by combined treatment with 2-deoxyglucose and metformin
- Author
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Mijin Yun, Junjeong Choi, Eui Hyun Kim, Yoonjee Oh, Jin Kyoung Shim, Jong Hee Chang, Yong Min Huh, Kyung-Sup Kim, Jae Ho Cheong, Pilnam Kim, Ilkyoo Koh, Junseong Park, Sun Ho Kim, Jeong Yong Jeon, Seok Gu Kang, and Ji Hyun Lee
- Subjects
0301 basic medicine ,Cancer Research ,Bioenergetics ,Antimetabolites ,Mice, Nude ,Apoptosis ,Pharmacology ,Biology ,Deoxyglucose ,Oxidative Phosphorylation ,Transcriptome ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Hypoglycemic Agents ,Glycolysis ,Cell Proliferation ,Brain Neoplasms ,Mesenchymal stem cell ,Drug Synergism ,Xenograft Model Antitumor Assays ,Metformin ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Basic and Translational Investigations ,Drug Therapy, Combination ,Neurology (clinical) ,Energy Metabolism ,Glioblastoma ,medicine.drug - Abstract
Background Deprivation of tumor bioenergetics by inhibition of multiple energy pathways has been suggested as an effective therapeutic approach for various human tumors. However, this idea has not been evaluated in glioblastoma (GBM). We hypothesized that dual inhibition of glycolysis and oxidative phosphorylation could effectively suppress GBM tumorspheres (TS). Methods Effects of 2-deoxyglucose (2DG) and metformin, alone and in combination, on GBM-TS were evaluated. Viability, cellular energy metabolism status, stemness, invasive properties, and GBM-TS transcriptomes were examined. In vivo efficacy was tested in a mouse orthotopic xenograft model. Results GBM-TS viability was decreased by the combination of 2DG and metformin. ATP assay and PET showed that cellular energy metabolism was also decreased by this combination. Sphere formation, expression of stemness-related proteins, and invasive capacity of GBM-TS were also significantly suppressed by combined treatment with 2DG and metformin. A transcriptome analysis showed that the expression levels of stemness- and epithelial mesenchymal transition-related genes were also significantly downregulated by combination of 2DG and metformin. Combination treatment also prolonged survival of tumor-bearing mice and decreased invasiveness of GBM-TS. Conclusion The combination of 2DG and metformin effectively decreased the stemness and invasive properties of GBM-TS and showed a potential survival benefit in a mouse orthotopic xenograft model. Our findings suggest that targeting TS-forming cells by this dual inhibition of cellular bioenergetics warrants expedited clinical evaluation for the treatment of GBM.
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- 2016
31. Terahertz reflectometry imaging for low and high grade gliomas
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Seungri Song, Seok Gu Kang, Jung Heo, Seung Jae Oh, Seungjoo Haam, Se Hoon Kim, Young Bin Ji, Jin Suck Suh, Chulmin Joo, Yuna Choi, Jong Hee Chang, Ji Hyun Lee, Hye Young Son, Sang-Hoon Kim, and Yong Min Huh
- Subjects
Male ,medicine.medical_specialty ,H&E stain ,Mice, Nude ,01 natural sciences ,World health ,Article ,010309 optics ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Terahertz Imaging ,Glioma ,0103 physical sciences ,medicine ,Animals ,Humans ,Survival rate ,Low grade tumor ,Mice, Inbred BALB C ,Multidisciplinary ,business.industry ,Neoplasms, Experimental ,Who grade ,medicine.disease ,Gross Total Resection ,Highly sensitive ,Radiology ,business ,030217 neurology & neurosurgery - Abstract
Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.
- Published
- 2016
32. Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)
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Ilkyoo Koh, Eui Hyun Kim, Junseong Park, Michael Pollak, Ji Hyun Lee, Jeong Yong Jeon, Mijin Yun, Junjeong Choi, Jin Kyoung Shim, Se Hoon Kim, Pilnam Kim, Seok Gu Kang, Su Jae Lee, Jong Hee Chang, Yong Min Huh, Sun Ho Kim, Jong In Yook, and Jae Ho Cheong
- Subjects
0301 basic medicine ,Oncology ,Male ,Pyrrolidines ,HL156A ,Apoptosis ,biguanide ,Guanidines ,Mice ,0302 clinical medicine ,Tumor Cells, Cultured ,tumorsphere ,Mice, Inbred ICR ,Biguanide ,Brain Neoplasms ,invasion ,Dacarbazine ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Drug Therapy, Combination ,Medical science ,medicine.drug ,Research Paper ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,medicine.drug_class ,Line of therapy ,Mice, Nude ,03 medical and health sciences ,Combined treatment ,Internal medicine ,medicine ,Temozolomide ,Animals ,Humans ,Neoplasm Invasiveness ,Inhibitory effect ,Antineoplastic Agents, Alkylating ,Cell Proliferation ,business.industry ,glioblastoma ,medicine.disease ,Xenograft Model Antitumor Assays ,Regimen ,030104 developmental biology ,business ,Glioblastoma - Abstract
// Junjeong Choi 1, 2, * , Ji-Hyun Lee 3, * , Ilkyoo Koh 4, * , Jin-Kyoung Shim 3 , Junseong Park 3 , Jeong Yong Jeon 5 , Mijin Yun 5 , Se Hoon Kim 6 , Jong In Yook 7 , Eui Hyun Kim 3 , Jong Hee Chang 3 , Sun Ho Kim 3 , Yong Min Huh 8 , Su Jae Lee 9 , Michael Pollak 10 , Pilnam Kim 4 , Seok-Gu Kang 3 , Jae-Ho Cheong 11 1 Department of Pharmacy, College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea 2 Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea 3 Departments of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea 5 Departments of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 6 Departments of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 7 Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Republic of Korea 8 Departments of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 9 Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea 10 Department of Oncology and Medicine, McGill University, Gerald Bronfman Centre, Montreal, Quebec, Canada 11 Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea * These authors have contributed equally to this work Correspondence to: Pilnam Kim, email: pkim@kaist.ac.kr Seok-Gu Kang, email: seokgu9@gmail.com Keywords: biguanide, glioblastoma, HL156A, invasion, tumorsphere Received: January 26, 2016 Accepted: August 13, 2016 Published: August 25, 2016 ABSTRACT Studies have investigated biguanide-derived agents for the treatment of cancers and have reported their effects against tumorspheres (TSs). The purpose of this study was determining the effects of HL156A, a newly designed biguanide with improved pharmacokinetics, on glioblastoma TSs (GMB TSs) and assess the feasibility of this drug as a new line of therapy against glioblastoma, alone or combined with a conventional therapeutic agent, temozolomide(TMZ). The effects of HL156A, alone and combined with TMZ, on the stemness and invasive properties of GBM TSs and survival of orthotopic xenograft animals were assessed. HL156A, combined with TMZ, inhibited the stemness of GBM TSs, proven by neurosphere formation assay and marker expression. Three-dimensional collagen matrix invasion assays provided evidence that combined treatment inhibited invasive properties, compared with control and TMZ-alone treatment groups. TMZ alone and combined treatment repressed the expression of epithelial-mesenchymal transition-related genes. A gene ontology comparison of TMZ and combination-treatment groups revealed altered expression of genes encoding proteins involved in cellular adhesion and migration. Combined treatment with HL156A and TMZ showed survival benefits in an orthotopic xenograft mouse model. The inhibitory effect of combination treatment on the stemness and invasive properties of GBM TSs suggest the potential usage of this regimen as a novel strategy for the treatment of GBM.
- Published
- 2016
33. Consecutive Targetable Smart Nanoprobe for Molecular Recognition of Cytoplasmic microRNA in Metastatic Breast Cancer
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Seungjoo Haam, Nam Hee Kim, Jaemoon Yang, Jong In Yook, Jin Suck Suh, Soonhag Kim, Yong Min Huh, Eunjung Kim, and Joseph Park
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Endocytic cycle ,General Physics and Astronomy ,Nanoprobe ,Breast Neoplasms ,Biology ,Endocytosis ,Mice ,Nanocapsules ,Molecular beacon ,Cell Line, Tumor ,medicine ,Animals ,Humans ,General Materials Science ,CD44 ,General Engineering ,Cancer ,medicine.disease ,Molecular biology ,Metastatic breast cancer ,Molecular Imaging ,MicroRNAs ,Microscopy, Fluorescence ,biology.protein ,Cancer research ,Molecular imaging - Abstract
We report smart nanoprobe, hyaluronic acid (HA)-based nanocontainers containing miR-34a beacons (bHNCs), for the intracellular recognition of miR-34a levels in metastatic breast cancer cells, which is distinct from the imaging of biomarkers such of cell membrane receptors such as HER2. In this study, we demonstrate that a nanoscale vesicle that couples a targeting endocytic route, CD44, and a molecular imaging probe enables the efficient detection of specific miRNAs. Furthermore, bHNCs showed no cytotoxicity and high stability due to the anchored HA molecules on the surface of nanocontainers, and enables the targeted delivery of beacons via CD44 receptor-mediated endocytosis. In vitro and in vivo optical imaging using bHNCs also allow the measurement of miR-34a expression levels due to the selective recognition of the beacons released from the internalized bHNCs. We believe that the technique described herein can be further developed as a cancer diagnostic as well as a miRNA-based therapy of metastatic cancer.
- Published
- 2012
34. Real-Time Quantitative Monitoring of Specific Peptide Cleavage by a Proteinase for Cancer Diagnosis
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Sang Woo Lee, Joo Kyung Ryu, Kilho Eom, Jaemoon Yang, Nam Hee Kim, Taeyun Kwon, Dae Sung Yoon, Seungjoo Haam, Gyudo Lee, Jong In Yook, Joseph Park, and Yong Min Huh
- Subjects
chemistry.chemical_classification ,Cantilever ,medicine.diagnostic_test ,Chemistry ,Atomic force microscopy ,Proteolysis ,Peptide ,Biosensing Techniques ,General Chemistry ,General Medicine ,Matrix metalloproteinase ,Microscopy, Atomic Force ,Molecular biology ,Catalysis ,HEK293 Cells ,Neoplasms diagnosis ,Cell Line, Tumor ,Neoplasms ,Matrix Metalloproteinase 14 ,medicine ,Humans ,Peptide cleavage ,Peptides ,Biosensor - Abstract
…(MMPs;greenmissilesinthepicture)expressedonacancercellsurfacecanbesensedby a resonant cantilever device (satellite arm in the picture), as J. Yang, D. S. Yoon, T.Kwon et al. report in their Communication on page 5837 ff. Active MMPs attack thepeptide sequence that is immobilized on the cantilever surface. The peptide cleavageleads to an increase in the resonant frequency of the cantilever, owing to a decrease inthe mass of immobilized peptide.
- Published
- 2012
35. Targetable Gold Nanorods for Epithelial Cancer Therapy Guided by Near-IR Absorption Imaging
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Jihye Choi, Jaemoon Yang, Jin Suck Suh, Doyeon Bang, Yong Min Huh, Joseph Park, and Seungjoo Haam
- Subjects
Materials science ,Biocompatibility ,Infrared Rays ,Cetuximab ,Metal Nanoparticles ,Mice, Nude ,Nanotechnology ,Polyethylene glycol ,Antibodies, Monoclonal, Humanized ,Absorption ,Polyethylene Glycols ,Biomaterials ,Mice ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,PEG ratio ,Animals ,Humans ,General Materials Science ,Carbodiimide ,Mice, Inbred BALB C ,Nanotubes ,Antibodies, Monoclonal ,Hyperthermia, Induced ,General Chemistry ,Phototherapy ,Photothermal therapy ,Microscopy, Fluorescence ,chemistry ,Cancer cell ,Nanorod ,Gold ,Biotechnology - Abstract
Well-designed nanoparticle-mediated, image-guided cancer therapy has attracted interest for increasing the efficacy of cancer treatment. A new class of smart theragnostic nanoprobes employing cetuximab (CET)-conjugated polyethylene glycol (PEG)ylated gold nanorods (CET-PGNRs) is presented; these nanoprobes target epithelial cancer cells using near-infrared light. The cetyltrimethylammonium bromide bilayer on GNRs is replaced with heterobifunctional PEG (COOH-PEG-SH) to serve as a biocompatible stabilizer and to increase specificity. The carboxylated GNRs are further functionalized with CET using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC-NHS) chemistry. To assess the potential of such GNRs, their optical properties, biocompatibility, colloidal stability, in vitro/in vivo binding affinities for cancer cells, absorption imaging, and photothermal therapy effects are investigated. CET-PGNRs exhibit excellent tumor targeting ability and strong potential for simultaneous absorption imaging and photothermal ablation of epithelial cancer cells.
- Published
- 2012
36. Anchored Proteinase-Targetable Optomagnetic Nanoprobes for Molecular Imaging of Invasive Cancer Cells
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Joo Kyung Ryu, Nam Hee Kim, Jaemoon Yang, Jihye Choi, Joseph Park, Jong In Yook, Jin Suck Suh, Eun Kyung Lim, Eunjung Kim, Yong Min Huh, and Seungjoo Haam
- Subjects
Contrast Media ,Nanotechnology ,Catalysis ,Mice ,stomatognathic system ,Cell Line, Tumor ,Neoplasms ,Matrix Metalloproteinase 14 ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Magnetite Nanoparticles ,Fluorescent Dyes ,Invasive carcinoma ,Chemistry ,Cancer ,General Medicine ,General Chemistry ,medicine.disease ,Magnetic Resonance Imaging ,Biomarker (cell) ,Disease Models, Animal ,Cancer research ,Molecular imaging ,Peptides - Abstract
Herein, we describe the development of a bimodalimaging probe enabling precise recognition of the expressionof MT1-MMP anchored on invasive cancer cells and itsprotease activity simultaneously. MT1-MMP may be atargetable biomarker for a specific delivery and possessesproteolytic activity for certain substrates.
- Published
- 2011
37. Gold Nanostructures as Photothermal Therapy Agent for Cancer
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Eunji Jang, Jaemoon Yang, Kwangyeol Lee, Seungjoo Haam, Jin Suck Suh, Jihye Choi, and Yong Min Huh
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Pharmacology ,Cancer Research ,Materials science ,Nanostructure ,Nanoparticle ,Cancer ,Nanotechnology ,Hyperthermia, Induced ,Photothermal therapy ,medicine.disease ,Nanoshell ,Nanostructures ,Nanocages ,Neoplasms ,medicine ,Animals ,Humans ,Molecular Medicine ,Photothermal ablation ,Nanorod ,Gold - Abstract
Well-designed photothermal nanostructures have attracted many scientists pursuing a better means to accurately diagnose cancer and assess the efficacy of treatment. Recently, gold-based nanostructures (nanoshells, nanorods and nanocages) have enabled photothermal ablation of cancer cells with near-infrared (NIR) light without damaging normal human tissues and in particular, animal studies and early clinical testing showed the great promise for these materials. In this review article, we first discuss the mechanism of the cellular death signaling by thermal stress and introduce the intrinsic properties of gold nanostructures as photothermal agent for cancer treatment. Then the overview follows for evolving researches for the synthesis of various types of gold nanostructures and for their biomedical applications. Finally we introduce the optimized therapeutic strategies involving nanoparticle surface modification and laser operation method for an enhanced accumulation of gold nanostructures to the target cancer as well as for an effective cancer cell ablation.
- Published
- 2011
38. Hyaluronan-modified magnetic nanoclusters for detection of CD44-overexpressing breast cancer by MR imaging
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Seungjoo Haam, Eunji Jang, Joseph Park, Hyun Ouk Kim, Jin Suck Suh, Yong Min Huh, Kwangyeol Lee, and Eun Kyung Lim
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Magnetic Resonance Spectroscopy ,Materials science ,Biocompatibility ,Cell Survival ,Angiogenesis ,Static Electricity ,Biophysics ,Mice, Nude ,Breast Neoplasms ,Bioengineering ,Metastasis ,Nanoclusters ,Biomaterials ,Mice ,Nuclear magnetic resonance ,Cell Line, Tumor ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Humans ,Tissue Distribution ,Hyaluronic Acid ,Particle Size ,Micelles ,biology ,medicine.diagnostic_test ,Magnetic Phenomena ,Photoelectron Spectroscopy ,CD44 ,Temperature ,Cancer ,Magnetic resonance imaging ,equipment and supplies ,medicine.disease ,Magnetic Resonance Imaging ,Hyaluronan Receptors ,Mechanics of Materials ,Magnets ,Ceramics and Composites ,biology.protein ,Nanoparticles ,Female ,Molecular imaging ,human activities - Abstract
We fabricated hyaluronan-modified magnetic nanoclusters (HA-MNCs) for detection of CD44-overexpressing breast cancer using magnetic resonance (MR) imaging. CD44 is closely associated with cancer growth, including proliferation, metastasis, invasion, and angiogenesis. Hence, pyrenyl hyaluronan (Py-HA) conjugates were synthesized as CD44-targetable surfactants with hyaluronan (HA) and 1-pyrenylbutyric acid (Py) to modify hyaluronan on hydrophobic magnetic nanocrystals. Subsequently, HA-MNCs were fabricated using the nano-emulsion method; magnetic nanocrystals were simultaneously self-assembled with Py-HA conjugates, and their physical and magnetic properties depended on the degree of substitution (DS) of Py in Py-HA conjugates. HA-MNCs exhibited superior targeting efficiency with MR sensitivity as well as excellent biocompatibility through in vitro/in vivo studies. This suggests that HA-MNCs can be a potent cancer specific molecular imaging agent via targeted detection of CD44 with MR imaging.
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- 2011
39. Ambidextrous magnetic nanovectors for synchronous gene transfection and labeling of human MSCs
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Eun Kyung Lim, Seung Hyun Kim, Yong Min Huh, Jaemoon Yang, Seong-Ho Koh, Arum Yoo, Min Young Noh, Kwangyeol Lee, Eun Sook Lee, Seungjoo Haam, and Jin Suck Suh
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Genetic Vectors ,Cell ,Biophysics ,Bioengineering ,Biology ,Gene delivery ,Transfection ,Biomaterials ,Magnetics ,In vivo ,Spectroscopy, Fourier Transform Infrared ,Gene expression ,medicine ,Animals ,Humans ,Cells, Cultured ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Immunohistochemistry ,Molecular biology ,Rats ,Cell biology ,Transplantation ,medicine.anatomical_structure ,Mechanics of Materials ,Ceramics and Composites ,Nanoparticles ,Stem cell - Abstract
The synchronization of gene expression and cell trafficking in transfected stem cells is crucial for augmentation of stem cell functions (differentiation and neurotropic factor secretion) and real time in vivo monitoring. We report a magnetic nanoparticle-based gene delivery system that can ensure simultaneous gene delivery and in vivo cell trafficking by high resolution MR imaging. The polar aprotic solvent soluble MnFe₂O₄ nanoparticles were enveloped using cationic polymers (branched polyethyleneimine, PEI) by the solvent shifting method for a gene loading. Using our magnetic nanovector system (PEI-coated MnFe₂O₄ nanoparticles), thus, we synchronized stem cell migration and its gene expression in a rat stroke model.
- Published
- 2011
40. 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.
- Published
- 2011
41. Convertible Organic Nanoparticles for Near-Infrared Photothermal Ablation of Cancer Cells
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Kyung Hwa Yoo, Kwangyeol Lee, Yong Min Huh, Jaemoon Yang, Eunjung Kim, Doyeon Bang, Eun Kyung Kim, Eun Kyung Lim, Jihye Choi, Huiyul Park, Seungjoo Haam, and Jin Suck Suh
- Subjects
Aniline Compounds ,Spectroscopy, Near-Infrared ,Materials science ,Near infrared light ,Infrared Rays ,Temperature ,Mice, Nude ,Nanoparticle ,Neoplasms therapy ,Nanotechnology ,General Medicine ,General Chemistry ,Hydrogen-Ion Concentration ,Photothermal therapy ,Catalysis ,Mice ,Cell Line, Tumor ,Neoplasms ,Cancer cell ,Animals ,Humans ,Nanoparticles ,Photothermal ablation - Abstract
Well-designed photothermal nanomaterials have attractedthe interest of many scientists pursuing a better means toaccurately diagnose cancer and assess the efficacy of treat-ment, because these materials enable therapies in which thetumor region is pin-pointed with a laser-guided light sourcewithout surgical intervention.
- Published
- 2010
42. Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex
- Author
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Yong Min Huh, Hyangtae Choi, Seungjoo Haam, Jaemoon Yang, Eunjung Kim, Kunhong Kim, Jin Suck Suh, and Yu-Kyung Jung
- Subjects
Male ,Materials science ,Cell ,bcl-X Protein ,Biophysics ,Bioengineering ,macromolecular substances ,urologic and male genital diseases ,Polyethylene Glycols ,Biomaterials ,Small hairpin RNA ,Cell Line, Tumor ,Combination cancer therapy ,Materials Testing ,LNCaP ,medicine ,Humans ,Polyethyleneimine ,Doxorubicin ,Viability assay ,RNA, Small Interfering ,Drug Carriers ,Antibiotics, Antineoplastic ,Cell Death ,technology, industry, and agriculture ,Prostatic Neoplasms ,Aptamers, Nucleotide ,Molecular biology ,medicine.anatomical_structure ,Mechanics of Materials ,Lipofectamine ,Cancer cell ,Ceramics and Composites ,medicine.drug - Abstract
We investigated the synergism between shRNAs against Bcl-xL and doxorubicin (DOX) using aptamer-conjugated polyplexes (APs) in combination cancer therapy. Synergistic and selective cancer cell death was achieved by AP-mediated co-delivery of very small amounts of DOX and Bcl-xL-specific shRNA, which simultaneously activated an intrinsic apoptotic pathway. A branched polyethyleneimine (PEI) was grafted to polyethylene glycol (PEI-PEG) to serve as a vehicle for shRNA delivery, and its surface was further conjugated with an anti-PSMA aptamer (APT) for the selective delivery of APs to prostate cancer cells that express prostate-specific membrane antigens (PSMA) on their cell surface. The APs were finally obtained after intercalation of DOX to form shRNA/PEI-PEG-APT/DOX conjugates. Cell viability assays and FACS analysis of GFP expression against PC3 (PSMA deficient) and LNCaP (PSMA overexpressed) cells demonstrated that the synthesized APs inhibited the growth of PSMA-abundant prostate cancer cells with strong cell selectivity. Consequently, IC(50) values of APs loaded with both DOX and shRNA were approximately 17-fold less than those for the simple mixture of shRNA plus drug (shRNA/Lipofectamine + DOX). These results suggest that AP-mediated co-delivery of an anti-cancer drug and shRNA against Bcl-xL may widen the therapeutic window and allow for the selective destruction of cancer cells.
- Published
- 2010
43. In Situ Detection of Live Cancer Cells by Using Bioprobes Based on Au Nanoparticles
- Author
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Seungjoo Haam, Kilho Eom, Sungsoo Na, Yong Min Huh, Jaemoon Yang, Dae Sung Yoon, Jinsung Park, Yoonah Kang, Eui Kwan Koh, Jin Suck Suh, Eun Kyung Lim, and Taeyun Kwon
- Subjects
Metal Nanoparticles ,Nanoparticle ,Nanotechnology ,Microscopy, Atomic Force ,Microscopy, Electron, Transmission ,Cell Line, Tumor ,Neoplasms ,Electrochemistry ,medicine ,Humans ,General Materials Science ,Epidermal growth factor receptor ,Spectroscopy ,chemistry.chemical_classification ,Cetuximab ,biology ,Biomolecule ,Substrate (chemistry) ,Surfaces and Interfaces ,Condensed Matter Physics ,Nanolithography ,Microscopy, Fluorescence ,chemistry ,Molecular Probes ,Cancer cell ,biology.protein ,Spectrophotometry, Ultraviolet ,Gold ,A431 cells ,medicine.drug - Abstract
We fabricate the high-performance probes based on Au nanoparticles (AuNP) for detection of live cancer cell. AuNP were synthesized with narrow sized distribution (ca. 10 nm) by Au salt reduction method and deposited onto the aminated substrate as a cross-linker and hot spot. Herein, AuNP has enabled the easy and efficient immobilization of the antibody (Cetuximab), which can selectively interact with epidermal growth factor receptor (EGFR) on the surface of epidermal cancer, as detecting moiety onto the AuNP-deposited substrate without nanolithography process. After conjugation of Cetuximab with AuNP-deposited substrate, Cetuximab-conjugated probe as a live cancer cell detector (LCCD) could detect EGFR-highexpressed A431 cells related to epithelial cancer with 54-times larger specificity and sensitivity in comparison with EGFR-deficient MCF7 cells. This implies that AuNP-based probes demonstrate abundant potentials for detection and separation of small biomolecules, cells and other chemicals.
- Published
- 2008
44. Fluorescent magnetic nanohybrids as multimodal imaging agents for human epithelial cancer detection
- Author
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Ho-Geun Yoon, Kwangyeol Lee, Sang Cheon Lee, Hong Jae Lee, Yong Min Huh, Jaemoon Yang, Jin Suck Suh, Joseph Park, Seungjoo Haam, and Eun Kyung Lim
- Subjects
Materials science ,Biocompatibility ,Polyesters ,Biophysics ,Cetuximab ,Bioengineering ,Nanotechnology ,Epithelial cancer ,Conjugated system ,Antibodies, Monoclonal, Humanized ,Biomaterials ,Optical imaging ,Polymethacrylic Acids ,Cell Line, Tumor ,medicine ,Humans ,Fluorescent Dyes ,Multimodal imaging ,Pyrenes ,medicine.diagnostic_test ,Antibodies, Monoclonal ,Epithelial Cells ,Magnetic resonance imaging ,Flow Cytometry ,equipment and supplies ,Magnetic Resonance Imaging ,Fluorescence ,ErbB Receptors ,Microscopy, Fluorescence ,Mechanics of Materials ,Ceramics and Composites ,Nanoparticles ,Cancer cell lines ,human activities - Abstract
Cetuximab conjugated fluorescent magnetic nanohybrids (CET-FMNHs) were synthesized for detection of human epithelial cancer via magnetic resonance (MR) and optical imaging. Spherical FMNHs consist of MnFe 2 O 4 magnetic nanocrystals encapsulated in pyrene-labeled PCL- b -PMAA as a surfactant prepared by a nano-emulsion method. FMNHs demonstrated excellent colloidal stability and biocompatibility for biomedical application. Antibody conjugated fluorescent magnetic nanohybrids (CET-FMNHs) served as effective agents for both magnetic resonance (MR) and fluorescence optical imaging of cancer cell lines.
- Published
- 2008
45. Synthesis of water soluble PEGylated magnetic complexes using mPEG-fatty acid for biomedical applications
- Author
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Joseph Park, Seungjoo Haam, Jaemoon Yang, Ho-Geun Yoon, Mee ye Park, Jin Suck Suh, Yong Min Huh, and Eun Kyung Lim
- Subjects
Polymers ,Tetrazolium Salts ,Biocompatible Materials ,Tissue Adhesions ,Polyethylene glycol ,Ferric Compounds ,Polyethylene Glycols ,Magnetics ,chemistry.chemical_compound ,Colloid ,Colloid and Surface Chemistry ,Amphiphile ,Copolymer ,Humans ,Organic chemistry ,Physical and Theoretical Chemistry ,Solubility ,chemistry.chemical_classification ,Drug Carriers ,Fatty Acids ,Aqueous two-phase system ,Water ,Fatty acid ,Surfaces and Interfaces ,General Medicine ,equipment and supplies ,Combinatorial chemistry ,Thiazoles ,Manganese Compounds ,chemistry ,Drug delivery ,Nanoparticles ,human activities ,HeLa Cells ,Biotechnology - Abstract
We report the successful fabrication of the various types of water soluble PEGylated magnetic complexes (PMCs) for magnetism-related biomedical applications. Various types of PMCs were synthesized and tested to accomplish phase transfer from organic to aqueous phase using monomethoxy polyethylene glycol (mPEG)-fatty acid amphiphilic block copolymers (PFs) through conjugation of the hydroxyl group of mPEG with the carboxyl group of fatty acids. We also carefully investigate their colloidal stabilities in aqueous phase according to the ratio of hydrophilic and hydrophobic lengths relying on different types of fatty acids. Synthesized PMCs clearly demonstrated high magnetic sensitivity under magnetic field as magnetic resonance (MR) contrast agents. Furthermore, PMCs exhibited sufficient cell viabilities and excellent cell affinities in an in vitro model. Our results demonstrated that our PMCs possessed the potential for highly efficient magnetism-related biomedical applications such as MR image agents, drug delivery and tracking of cells.
- Published
- 2008
46. Multifunctional Magneto-Polymeric Nanohybrids for Targeted Detection and Synergistic Therapeutic Effects on Breast Cancer
- Author
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Yong Min Huh, Jaemoon Yang, Seungjoo Haam, Choong Hwan Lee, Jin Suck Suh, Hyun Ko, Ho-Geun Yoon, and Kwangyeol Lee
- Subjects
Materials science ,Polymers ,Antineoplastic Agents ,Breast Neoplasms ,Nanotechnology ,Catalysis ,Magnetics ,Mice ,Drug Delivery Systems ,Breast cancer ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Targeted detection ,Magneto ,medicine.diagnostic_test ,Magnetic resonance imaging ,General Medicine ,Neoplasms, Experimental ,General Chemistry ,medicine.disease ,Magnetic Resonance Imaging ,Nanomedicine ,Drug delivery ,Nanoparticles ,Female - Published
- 2007
47. Overcoming Artifacts from Metallic Orthopedic Implants at High-Field-Strength MR Imaging and Multi-detector CT
- Author
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Yong Min Huh, Sung-Ah Lee, Sungjun Kim, Daehong Kim, Seung Hwan Han, Mi Jung Lee, Jin Suck Suh, and Ho Taek Song
- Subjects
medicine.diagnostic_test ,Orientation (computer vision) ,business.industry ,Magnetic resonance imaging ,Field of view ,Reconstruction algorithm ,Pulse sequence ,Prostheses and Implants ,Image Enhancement ,Magnetic Resonance Imaging ,Mr imaging ,Collimated light ,Multi detector ct ,Nuclear magnetic resonance ,Metals ,Image Interpretation, Computer-Assisted ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Artifacts ,Tomography, X-Ray Computed ,business ,Biomedical engineering - Abstract
At magnetic resonance (MR) imaging and multidetector computed tomography (CT), artifacts arising from metallic orthopedic hardware are an obstacle to obtaining optimal images. Although various techniques for reducing such artifacts have been developed and corroborated by previous researchers, a new era of more powerful MR imaging and multidetector CT modalities has renewed the importance of a systematic consideration of methods for artifact reduction. Knowledge of the factors that contribute to artifacts, of related theories, and of artifact reduction techniques has become mandatory for radiologists. Factors that affect artifacts on MR images include the composition of the metallic hardware, the orientation of the hardware in relation to the direction of the main magnetic field, the strength of the magnetic field, the pulse sequence type, and other MR imaging parameters (mainly voxel size, which is determined by the field of view, image matrix, section thickness, and echo train length). At multidetector CT, the factors that affect artifacts include the composition of the hardware, orientation of the hardware, acquisition parameters (peak voltage, tube charge, collimation, and acquired section thickness), and reconstruction parameters (reconstructed section thickness, reconstruction algorithm used, and whether an extended CT scale was used). A comparison of images obtained with different hardware and different acquisition and reconstruction parameters facilitates an understanding of methods for reducing or overcoming artifacts related to metallic implants.
- Published
- 2007
48. Chronic Tibiofibular Syndesmosis Injury of Ankle: Evaluation with Contrast-enhanced Fat-suppressed 3D Fast Spoiled Gradient-recalled Acquisition in the Steady State MR Imaging
- Author
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Jin Woo Lee, Sung Ah Lee, Yong Min Huh, Sungjun Kim, Jin Suck Suh, In Hyuk Chung, Jong Eun Lee, and Ho Taek Song
- Subjects
Adult ,Male ,medicine.medical_specialty ,Steady state (electronics) ,Adolescent ,media_common.quotation_subject ,Contrast Media ,Gadolinium ,Sensitivity and Specificity ,Arthroscopy ,Imaging, Three-Dimensional ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Contrast (vision) ,Radiology, Nuclear Medicine and imaging ,Ankle Injuries ,media_common ,medicine.diagnostic_test ,business.industry ,Reproducibility of Results ,Magnetic resonance imaging ,Middle Aged ,Image Enhancement ,Magnetic Resonance Imaging ,Mr imaging ,Endoscopy ,medicine.anatomical_structure ,Adipose Tissue ,Coronal plane ,Chronic Disease ,Sprains and Strains ,Female ,Radiology ,Ankle ,Lateral Ligament, Ankle ,business ,Nuclear medicine ,Algorithms - Abstract
To retrospectively determine the accuracy of coronal contrast material-enhanced fat-suppressed three-dimensional (3D) fast spoiled gradient-recalled acquisition in the steady state (SPGR) magnetic resonance (MR) imaging, as compared with that of routine transverse MR imaging, in the assessment of distal tibiofibular syndesmosis injury, with arthroscopy as the reference standard.The review board of the College of Medicine in Yonsei University approved this study; informed consent was waived. The study group comprised 45 patients (26 men, 19 women; mean age, 32.1 years; range, 18-58 years) with a chronic ankle injury who had undergone MR imaging and arthroscopic surgery. Three independent readers retrospectively reviewed the two sets of MR images (one set of gadolinium-enhanced 3D fast SPGR images and one set of routine T1-, T2-, and intermediate-weighted images). Scores from 1 to 5 in increasing order of the probability of injury were assigned to both sets. Arthroscopy was the reference standard. Syndesmotic recess height was measured on contrast-enhanced images. The two sets of images were compared for diagnostic performance with receiver operating characteristic (ROC) analysis. Dissection and histologic examination of six cadaveric ankles was performed to assess the syndesmotic area and ascertain the enhancing structure at MR imaging.At arthroscopy, syndesmotic injury was found in 24 ankles but not in 21 ankles. Areas under the ROC curve were significantly higher for the contrast-enhanced images (P.05). The contrast-enhanced set showed higher accuracy, sensitivity, and specificity compared with the routine set for the assessment of syndesmosis injury. Mean syndesmotic recess height was significantly greater (P.05) in patients with syndesmotic injury. Dissection and histologic examination revealed a highly vascular synovial fold in the syndesmotic area that is expected to enhance at MR imaging.In the assessment of chronic syndesmosis injury, coronal gadolinium-enhanced fat-suppressed 3D fast SPGR MR images were more sensitive, specific, and accurate than routine MR images.
- Published
- 2007
49. Co-delivery of paclitaxel and gemcitabine via CD44-targeting nanocarriers as a prodrug with synergistic antitumor activity against human biliary cancer
- Author
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Hyun Ouk Kim, Seungjoo Haam, Jihye Choi, Ilkoo Noh, Dong Ki Lee, Yong Min Huh, and Yuna Choi
- Subjects
Paclitaxel ,Biophysics ,Bioengineering ,Pharmacology ,Deoxycytidine ,Biomaterials ,chemistry.chemical_compound ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Viability assay ,Drug Carriers ,biology ,Chemistry ,CD44 ,Cancer ,Prodrug ,medicine.disease ,Gemcitabine ,Biliary Tract Neoplasms ,Hyaluronan Receptors ,Mechanics of Materials ,Cancer cell ,Ceramics and Composites ,biology.protein ,Nanoparticles ,Nanocarriers ,medicine.drug - Abstract
Multi-drug delivery focuses on different signaling pathways in cancer cells that have synergistic anti-proliferative effects. In this study, we developed multi-prodrug nanocarriers (MPDNCs) consisting of poly ( l -lysine)–carboxylate PTX (PLL-PTX) and hyaluronic acid-conjugated GEM (HA-GEM) for CD44-targeted synergistic biliary cancer therapy. An in vitro study of cell viability and mRNA expression levels and an in vivo study showed that MPDNCs more effectively inhibit proliferation in CD44-overexpressing cancer cells (HuCCT1) than in cells with lower CD44 expression (SCK) by synergistically inducing apoptosis. Consequently, these results demonstrate that MPDNCs are prodrugs with synergistic cancer therapeutic efficacy and effective cellular uptake at target cells compared to free drugs, indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.
- Published
- 2015
50. Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging
- Author
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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
- Subjects
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.
- Published
- 2006
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