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1. Failed Thrombus Aspiration and Reduced Myocardial Perfusion in Patients With STEMI and Large Thrombus Burden.

Author

Jeon, Ho Sung, Kim, Young In, Lee, Jung-Hee, Park, Young Jun, Son, Jung-Woo, Lee, Jun-Won, Youn, Young Jin, Ahn, Min-Soo, Kim, Jang-Young, Yoo, Byung-Su, Ko, Sung Min, and Ahn, Sung Gyun

Abstract

Thrombus aspiration (TA) is used to decrease large thrombus burden (LTB), but it can cause distal embolization. The aim of this study was to investigate the impact of TA failure on defective myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) and LTB. In total, 812 consecutive patients with STEMI and LTB (thrombus grade ≥3) were enrolled, who underwent manual TA during the primary percutaneous coronary intervention. TA failure was defined as the absence of thrombus retrieval, presence of prestenting thrombus residue, or distal embolization. The final TIMI flow grades and other myocardial perfusion parameters of the failed TA group were matched with those of the successful TA group. The proportion of final TIMI flow grade 3 was lower (74.6% vs 82.2%; P = 0.011) in the failed TA group (n = 279 [34.4%]) than in the successful TA group (n = 533 [65.6%]). The failed TA group also had lower myocardial blush grade, lower ST-segment resolution, and a higher incidence of microvascular obstruction than the successful TA group. TA failure was independently associated with low final TIMI flow grade (risk ratio: 1.525; 95% CI: 1.048-2.218; P = 0.027). Old age, Killip class ≥III, vessel tortuosity, calcification, and a culprit vessel other than the left anterior descending coronary artery were associated with TA failure. TA failure is associated with reduced myocardial perfusion in patients with STEMI and LTB. Advanced age, hemodynamic instability, hostile coronary anatomy such as tortuosity or calcification, and non–left anterior descending coronary artery status might attenuate TA performance. (Gangwon PCI Prospective Registry [GWPCI]; NCT02038127) [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2024
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2. Dichotomous intronic polyadenylation profiles reveal multifaceted gene functions in the pan-cancer transcriptome

Author

Sun, Jiao, Kim, Jin-Young, Jun, Semo, Park, Meeyeon, de Jong, Ebbing, Chang, Jae-Woong, Cheng, Sze, Fan, Deliang, Chen, Yue, Griffin, Timothy J., Lee, Jung-Hee, You, Ho Jin, Zhang, Wei, and Yong, Jeongsik

Abstract

Alternative cleavage and polyadenylation within introns (intronic APA) generate shorter mRNA isoforms; however, their physiological significance remains elusive. In this study, we developed a comprehensive workflow to analyze intronic APA profiles using the mammalian target of rapamycin (mTOR)-regulated transcriptome as a model system. Our investigation revealed two contrasting effects within the transcriptome in response to fluctuations in cellular mTOR activity: an increase in intronic APA for a subset of genes and a decrease for another subset of genes. The application of this workflow to RNA-seq data from The Cancer Genome Atlas demonstrated that this dichotomous intronic APA pattern is a consistent feature in transcriptomes across both normal tissues and various cancer types. Notably, our analyses of protein length changes resulting from intronic APA events revealed two distinct phenomena in proteome programming: a loss of functional domains due to significant changes in protein length or minimal alterations in C-terminal protein sequences within unstructured regions. Focusing on conserved intronic APA events across 10 different cancer types highlighted the prevalence of the latter cases in cancer transcriptomes, whereas the former cases were relatively enriched in normal tissue transcriptomes. These observations suggest potential, yet distinct, roles for intronic APA events during pathogenic processes and emphasize the abundance of protein isoforms with similar lengths in the cancer proteome. Furthermore, our investigation into the isoform-specific functions of JMJD6 intronic APA events supported the hypothesis that alterations in unstructured C-terminal protein regions lead to functional differences. Collectively, our findings underscore intronic APA events as a discrete molecular signature present in both normal tissues and cancer transcriptomes, highlighting the contribution of APA to the multifaceted functionality of the cancer proteome.

Published
2024
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3. Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea

Author

Hong, Sung-Jin, Lee, Seung-Jun, Lee, Sang-Hyup, Lee, Jong-Young, Cho, Deok-Kyu, Kim, Jin Won, Kim, Sang Min, Hur, Seung-Ho, Heo, Jung Ho, Jang, Ji-Yong, Koh, Jin Sin, Won, Hoyoun, Lee, Jun-Won, Hong, Soon Jun, Kim, Dong-Kie, Choe, Jeong Cheon, Lee, Jin Bae, Kim, Soo-Joong, Yang, Tae-Hyun, Lee, Jung-Hee, Hong, Young Joon, Ahn, Jong-Hwa, Lee, Yong-Joon, Ahn, Chul-Min, Kim, Jung-Sun, Ko, Young-Guk, Choi, Donghoon, Hong, Myeong-Ki, Jang, Yangsoo, and Kim, Byeong-Keuk

Abstract

Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year.

Published
2024
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4. TFE3/PI3K/Akt/mTOR Axis in Renal Cell Carcinoma Affects Tumor Microenvironment

Author

Hwang, Chungsu, Kang, Yun Kyung, Kim, Ji Yun, Shin, So Hyun, Park, Joon Young, Song, Ji Sun, Kim, So Young, Jung, Se Jin, Lee, Jung Hee, Na, Ju-Young, Shin, Dong Hoon, Kim, Jee Yeon, Park, Sung Woo, and Lee, Hyun Jung

Abstract

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin (mTOR) and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. Data from this study indicate that TFE3 plays a role in the PI3K/Akt pathway in RCC. The results of this study suggest that PI3K/Akt inhibitors may aid in the treatment of patients with RCC by affecting the tumor microenvironment.

Published
2024
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8. Oxygen-Generating Organic/Inorganic Self-Assembled Nanocolloids for Tumor-Activated Dual-Model Imaging-Guided Photodynamic Therapy

Author

Fu, Yan, Jang, Moon-Sun, Liu, Changling, Li, Yi, Lee, Jung Hee, and Yang, Hong Yu

Abstract

Tumor phototheranostics is usually compromised by the hypoxic tumor microenvironment and poor theranostic efficiency. The interplay between organic polymers and inorganic nanoparticles in novel nanocomposites has proven to be advantageous, overcoming previous limitations and harnessing their full potential through activation via the tumor microenvironment. This study successfully fabricated hypoxia-activated nanocolloids called HOISNDs through a process of self-assembly involving superparamagnetic iron oxide nanoparticles (SPIONs) and an organic polymer ligand called tetrakis(4-carboxyphenyl) porphyrin (TCPP)-engineered organic polymer ligand [methoxy poly(ethyleneglycol)-block-poly(dopamine-ethylenediamine-conjugated-4-nitrobenzyl chloroformate)-l-glutamate, mPEG-b-P(Dopa-EDA-co-NBCF)LG-TCPP)]. The SPIONs act as an oxygen generator to overcome the challenges posed by hypoxic tumors and enable the use of hypoxic-activatable MR/fluorescence dual-modal imaging-guided photodynamic therapy (PDT). The colloid stability of these HOISNDs proved to be exceptional in diverse biomimetic environments. Furthermore, they not only augment T2-weighted contrast capability as an MRI contrast agent but also function as an oxygen-producing device to amplify the generation and release of reactive oxygen species (ROS). The HOISNDs can significantly target to tumor sites through the enhanced permeability and retention (EPR) effect with prolonged blood circulation time and subsequently are effectively endocytosed into a hypoxic intracellular environment that “turn on” the imaging function and photodynamic activity. Moreover, HOISNDs possess the ability to effectively decompose naturally occurring H2O2into oxygen (O2) within the tumor utilizing the Fenton reaction. This method can mitigate the impact of hypoxia on oxygen-dependent PDT. The outcomes of in vivodiagnostic and therapeutic evaluations indicated that HOISNDs are a highly promising tool for dual-model imaging-guided cancer theranosis by ameliorating hypoxic conditions and augmenting PDT efficiency.

Published
2023
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9. Remnant cholesterol, low-density lipoprotein cholesterol, and incident cardiovascular disease among Koreans: a national population-based study

Author

Lee, Sang Jun, Kim, Se-Eun, Go, Tae-Hwa, Kang, Dae Ryong, Jeon, Ho-Seong, Kim, Young-In, Cho, Dong-Hyuk, Park, Young Jun, Lee, Jung-Hee, Lee, Jun-Won, Youn, Young-Jin, Kim, Sang-Hyun, Kim, Jang Young, and Ahn, Sung Gyun

Abstract

Since remnant-C has recently emerged as a potential risk factor for CVD, the synergistic association of LDL-C and remnant-C with CVD has been investigated among 3 686 034 Koreans (45.6% women) without preceding CVD using nationwide population-based big data. Remnant cholesterol remained proportional to the risk of incident CVD after adjusting for multiple variables, including LDL-C levels.Low-density lipoprotein cholesterol and remnant-C synergistically contributed to incident CVD.

Published
2023
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10. The infusion of ex vivo, interleukin-15 and -21-activated donor NK cells after haploidentical HCT in high-risk AML and MDS patients—a randomized trial

Author

Lee, Kyoo-Hyung, Yoon, Suk Ran, Gong, Jeong-Ryeol, Choi, Eun-Ji, Kim, Hun Sik, Park, Chan-Jeoung, Yun, Sung-Cheol, Park, Soo-Yeon, Jung, Sol-Ji, Kim, Hanna, Lee, Soo Yun, Jung, Haiyoung, Byun, Jae-Eun, Kim, Mirang, Kim, Seon-Young, Kim, Jeong-Hwan, Lee, Je-Hwan, Lee, Jung-Hee, Choi, Yunsuk, Park, Han-Seung, Lee, Young-Shin, Kang, Young-Ah, Jeon, Mijin, Woo, Jimin, Kang, Hyeran, Baek, Seunghyun, Kim, Su Mi, Kim, Hoon-Min, Cho, Kwang-Hyun, and Choi, Inpyo

Abstract

Clinical effect of donor-derived natural killer cell infusion (DNKI) after HLA-haploidentical hematopoietic cell transplantation (HCT) was evaluated in high-risk myeloid malignancy in phase 2, randomized trial. Seventy-six evaluable patients (aged 21–70 years) were randomized to receive DNKI (N= 40) or not (N= 36) after haploidentical HCT. For the HCT conditioning, busulfan, fludarabine, and anti-thymocyte globulin were administered. DNKI was given twice 13 and 20 days after HCT. Four patients in the DNKI group failed to receive DNKI. In the remaining 36 patients, median DNKI doses were 1.0 × 108/kg and 1.4 × 108/kg on days 13 and 20, respectively. Intention-to-treat analysis showed a lower disease progression for the DNKI group (30-month cumulative incidence, 35% vs 61%, P= 0.040; subdistribution hazard ratio, 0.50). Furthermore, at 3 months after HCT, the DNKI patients showed a 1.8- and 2.6-fold higher median absolute blood count of NK and T cells, respectively. scRNA-sequencing analysis in seven study patients showed that there was a marked increase in memory-like NK cells in DNKI patients which, in turn, expanded the CD8+effector-memory T cells. In high-risk myeloid malignancy, DNKI after haploidentical HCT reduced disease progression. This enhanced graft-vs-leukemia effect may be related to the DNKI-induced, post-HCT expansion of NK and T cells. Clinical trial number: NCT02477787.

Published
2023
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12. SARS-CoV-2 shedding dynamics and transmission in immunosuppressed patients

Author

Lee, Jee-Soo, Yun, Ki Wook, Jeong, Hyeonju, Kim, Boram, Kim, Man Jin, Park, Jae Hyeon, Shin, Ho Seob, Oh, Hyeon Sae, Sung, Hobin, Song, Myung Gi, Cho, Sung Im, Kim, So Yeon, Kang, Chang Kyung, Choe, Pyoeng Gyun, Park, Wan Beom, Kim, Nam Joong, Oh, Myoung-Don, Choi, Eun Hwa, Park, Seungman, Kim, Taek Soo, Lee, Jung-Hee, Sung, Heungsup, Park, Sung Sup, and Seong, Moon-Woo

Abstract

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have been emerging. However, knowledge of temporal and spatial dynamics of SARS-CoV-2 is limited. This study characterized SARS-CoV-2 evolution in immunosuppressed patients with long-term SARS-CoV-2 shedding for 73–250 days, without specific treatment. We conducted whole-genome sequencing of 27 serial samples, including 26 serial samples collected from various anatomic sites of two patients and the first positive sample from patient 2‘s mother. We analysed the intrahost temporal dynamics and genomic diversity of the viral population within different sample types. Intrahost variants emerging during infection showed diversity between individual hosts. Remarkably, N501Y, P681R, and E484K, key substitutions within spike protein, emerged in vivoduring infection and became the dominant population. P681R, which had not yet been detected in the publicly available genome in Korea, appeared within patient 1 during infection. Mutually exclusive substitutions at residues R346 (R346S and R346I) and E484 (E484K and E484A) of spike protein and continuous turnover of these substitutions occurred. Unique genetic changes were observed in urine samples. A household transmission from patient 2 to his mother, at least 38 days after the diagnosis, was characterized. Viruses may differently mutate and adjust to the host selective pressure, which could enable the virus to replicate efficiently for fitness in each host. Intrahost variants could be candidate variants likely to spread to the population eventually. Our findings may provide new insights into the dynamics of SARS-CoV-2 in response to interactions between the virus and host.

Published
2022
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14. Decolorization of high refractive index glass based on SiO2-(BaO + ZrO2)-TiO2using transition metal oxides

Author

Lee, Jung Hee, Lee, Hansol, Choi, Yong Gyu, Kim, In Gun, and Chung, Woon Jin

Abstract

High refractive index glasses based on SiO2-(BaO + ZrO2)-TiO2were synthesized for road sign applications with nd> 1.9. Although the refractive index increased with the addition of TiO2, visible transmittance was deteriorated with colorization of the glasses with increasing TiO2. Visible light absorption by the multi-valenced Ti-ions within the glass matrix was responsible for the change in color and transmittance. To improve transmittance and guarantee the retro-reflectivity of the glass beads, various transition metal oxides (TMOs) CuO, NiO, MnO and CoO were introduced for color control. The transmittance change with various TMOs was monitored, and a glass with CoO showed a noticeable change in color as well as an increase in transmittance. The valence change of Ti-ions was inspected by XPS, photo-luminescence (PL) and photo-luminescence excitation (PLE) spectra of the glasses, to elucidate the color change.

Published
2022
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15. mTOR Inhibition Increases Transcription Factor E3 (TFE3) Activity and Modulates Programmed Death-Ligand 1 (PD-L1) Expression in Translocation Renal Cell Carcinoma

Author

Lee, Hyun Jung, Shin, Dong Hoon, Song, Ji Sun, Park, Joon Young, Kim, So Young, Hwang, Chung Su, Na, Ju-Young, Lee, Jung Hee, Kim, Jee Yeon, Park, Sung Woo, and Sol, Mee Young

Abstract

The efficacy of programmed death ligand (PD-L)-1/PD-1 checkpoint blockade in renal cell carcinoma (RCC) remains unknown. The effects of mTOR inhibitors are uncertain, and patients may develop resistance to them. The limited understanding of cancer cell–intrinsic mTOR-mediated pathways remains a challenge in developing effective treatments. Whether transcription factor (TF)-E3 regulates PD-L1 expression and the tumor microenvironment was investigated, and the effects of an mammalian target of rapamycin (mTOR) inhibitor on translocation RCC were explored. TFE3 was overexpressed in clear cell RCC cell lines, and PD-L1 expression was analyzed by Western blot analysis. PD-L1 activity in translocation RCC was analyzed in relation to TFE3 expression via TFE3 knockdown and treatment with an mTOR inhibitor. The results were correlated with the gene expression profile, evaluated using digital multiplex analysis. TFE3 and PD-L1 expression were positively correlated in RCC cells. TFE3 overexpression was associated with the expression of PD-L1 in RCC. Furthermore, mTOR inhibition was associated with enhanced PD-L1 expression via TFE3 activation in translocation RCC. These data support the feasibility of combination therapy based on mTOR inhibition and PD-L1 blockade as a novel strategy for the treatment of patients with translocation RCC.

Published
2021
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16. Clinical impact of blood pressure variability in patients with COVID-19 and hypertension

Author

Nam, Jong-Ho, Park, Jong Il, Kim, Byung-Jun, Kim, Hun-Tae, Lee, Jung-Hee, Lee, Chan-Hee, Son, Jang-Won, Kim, Ung, Park, Jong-Seon, Shin, Dong-Gu, Hong, Kyung Soo, Jang, Jong Geol, Ahn, June Hong, Jin, Hyun Jung, Choi, Eun Young, Shin, Kyeong-Cheol, Chung, Jin Hong, Lee, Kwan Ho, Hur, Jian, Hong, Young-Hoon, and Lee, Choong-Ki

Abstract

Supplemental Digital Content is available in the text.

Published
2021
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17. Delineation of the genetic and clinical spectrum, including candidate genes, of monogenic diabetes: a multicenter study in South Korea.

Author

Cheon, Chong Kun, Lee, Yeoun Joo, Yoo, Sukdong, Lee, Jung Hee, Lee, Jeong Eun, Kim, Hyun Ji, Choi, Im Jeong, Choi, Yeonsong, Lee, Semin, and Yoon, Ju Young

Abstract

Objectives: Monogenic diabetes includes a group of heterogeneous diabetes types. We aimed to identify the frequency, clinical and molecular features of monogenic diabetes in a Korean pediatric cohort. Methods: A retrospective cohort and multicenter study of Korean children suspected to have monogenic diabetes, managed by four pediatric endocrine centers in the southeast region of South Korea, from February 2016 to February 2020. We recruited 27 pediatric Korean patients suspected to have monogenic diabetes who had at least two of the following three criteria (age at diagnosis, family history, and clinical presentation). Targeted exome sequencing was conducted in these patients. The functional consequences of the variants were predicted by bioinformatics and protein structure analysis. Results: Molecular genetic analysis identified 16 patients (59.3%) with monogenic diabetes. We identified a total of eight unique variants, including five novel variants (HNF4A c.1088C>T, CEL c.1627C>T and c.1421C>T, PAX4 c.538+8G>C, INS c.71C>T). We also identified two potential candidate gene variants for monogenic diabetes, namely c.650T>C in the SLC2A2 gene and c.629G>A in the PTF1A gene. Other variants were identified in the WFS1and NPHP3 genes in two rare genetic disorders. Variant-positive individuals had a lower presence of autoantibody positivity at the time of diagnosis and higher glycosylated hemoglobin levels at last follow-up when compared to variant-negative patients (p<0.001 and p=0.029, respectively). Conclusions: These results further expand the spectrum of known variants as well as potential candidate gene variants associated with monogenic diabetes in Korea. [ABSTRACT FROM AUTHOR]

Published
2020
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18. CD44-Targeted and Enzyme-Responsive Photo-Cross-Linked Nanogels with Enhanced Stability for In Vivo Protein Delivery

Author

Yang, Hong Yu, Meng Du, Jia, Jang, Moon-Sun, Mo, Xin Wang, Sun, Xin Shun, Lee, Doo Sung, Lee, Jung Hee, and Fu, Yan

Abstract

One of the biggest challenges of the protein delivery system is to realize stable and high protein encapsulation efficiency in blood circulation and rapid release of protein in the targeted tumor cells. To overcome these hurdles, we fabricated enzyme-responsive photo-cross-linked nanogels (EPNGs) through UV-triggered chemical cross-linking of cinnamyloxy groups in the side chain of PEGylation hyaluronic acid (HA) for CD44-targeted transport of cytochrome c(CC). The EPNGs showed high loading efficiency and excellent stability in different biological media. Notably, CC leakage effectively suppressed under physiological conditions but accelerated release in the presence of hyaluronidase, an overexpressed enzyme in tumor cells. Moreover, thiazolylblue tetrazolium bromide (MTT) results indicated that the vacant EPNGs showed excellent nontoxicity, while CC-loaded EPNGs exhibited higher killing efficiency to CD44-positive A549 cells than to CD44-negative HepG2 cells and free CC. Confocal images confirmed that CC-loaded EPNGs could effectively be internalized by CD44-mediated endocytosis pathway and rapidly escape from the endo/lysosomal compartment. Human lung tumor-bearing mice imaging assays further revealed that CC-loaded EPNGs actively target tumor locations. Remarkably, CC-loaded EPNGs also exhibited enhanced antitumor activity with negligible systemic toxicity. These results implied that these EPNGs have appeared as stable and promising nanocarriers for tumor-targeting protein delivery.

Published
2021
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20. Impact of guideline-directed medical therapy on 5-year mortality in patients with newly diagnosed peripheral artery disease.

Author

Lee, Jung-Hee, Jeon, Ho Sung, Lee, Jun-Won, Youn, Young Jin, Ahn, Sung Gyun, Kim, Hoseob, Bae, Yoonjong, Kim, Ung, Ahn, Chul-Min, and Ko, Young-Guk

Abstract

Current guidelines recommend that patients with peripheral artery disease (PAD) should be treated with antithrombotic agents, renin-angiotensin-system blockers, and statins. However, the clinical impact of guideline-directed medical therapy (GDMT) on long-term mortality in patients with newly diagnosed PAD remains unclear. We aimed to investigate the prevalence of GDMT and evaluate 5-year mortality according to GDMT after PAD diagnosis. This retrospective cohort study, using nationwide health insurance claims data in Korea, included patients newly diagnosed with PAD between 2006 and 2015. GDMT was defined as the use of all drugs, including antithrombotic agents, renin-angiotensin-system blockers, and statins, within 3 months of PAD diagnosis. The primary endpoint was all-cause mortality. We investigated 19,561 newly diagnosed patients with PAD without proven cardiovascular disease. Among the study population, 4378 patients (22.4%) were categorized in the GDMT and 15,183 (77.6%) in the non-GDMT groups. During the 5-year follow-up, GDMT showed a lower incidence of all-cause mortality than that of non-GDMT (2.8% vs 4.8%; adjusted hazard ratio, 0.329; 95% confidence interval, 0.257-0.421; P <.001). Even in the propensity-matched population, GDMT showed a lower mortality rate than non-GDMT (hazard ratio, 0.283; 95% confidence interval, 0.217-0.370; P <.001). As the number of guideline-recommended drugs increased, the mortality rate decreased proportionately. After PAD diagnosis, GDMT was associated with a lower incidence of mortality regardless of proven cardiovascular disease. This retrospective analysis showed an insufficient prevalence of GDMT among patients with PAD in real-world practice. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Design optimization of GaN diode with p-GaN multi-well structure for high-efficiency betavoltaic cell

Author

Yoon, Young Jun, Lee, Jae Sang, Kang, In Man, Lee, Jung-Hee, and Kim, Dong-Seok

Abstract

In this work, we propose and design a GaN-based diode with a p-doped GaN (p-GaN) multi-well structure for high efficiency betavoltaic (BV) cells. The short-circuit current density (JSC) and open-circuit voltage (VOC) of the devices were investigated with variations of parameters such as the doping concentration, height, width of the p-GaN well region, well-to-well gap, and number of well regions. The JSCof the device was significantly improved by a wider depletion area, which was obtained by applying the multi-well structure. The optimized device achieved a higher output power density by 8.6% than that of the conventional diode due to the enhancement of JSC. The proposed device structure showed a high potential for a high efficiency BV cell candidate.

Published
2021
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24. Increased expression of immune checkpoint programmed cell death protein‐1 (PD‐1) on T cell subsets of bone marrow aspirates in patients with B‐Lymphoblasticleukemia, especially in relapse and at diagnosis

Author

Park, Sang Hyuk, You, Eunkyoung, Park, Chan‐Jeoung, Cho, Young‐Uk, Jang, Seongsoo, Im, Ho‐Joon, Seo, Jong‐Jin, Park, Han‐Seung, and Lee, Jung‐Hee

Abstract

We analyzed expression profiles of immune checkpoint receptors on T cell subsets and ligands on leukemic blasts in patients with B‐lymphoblastic leukemia (B‐ALL). Total 149 bone marrow (BM) samples obtained from 65 B‐ALL patients with four different clinical status (41 at diagnosis, 54 in complete remission [CR], 34 in persistence, and 20 in relapse), and 32 BM control samples were prospectively enrolled. Expression of immune checkpoint receptor (programmed cell death protein‐1 [PD‐1]) on T cell subsets and ligands (PD‐L1, PD‐L2) on leukemic blasts was evaluated by flow cytometry, and was compared between patient subgroups. Relapsed patients demonstrated highest PD‐1 expression proportion and intensity on CD3+CD4+T cells with statistical significance when compared to patients in persistence/CR/BM controls (p= .027/<.001/<.001 and .012/.001/<.001, respectively). Newly diagnosed patients showed significantly lower PD‐1 expression proportion on CD3+CD4+T cells than relapsed patients (p< .001), but their intensity was not significantly different. Relapsed patients showed significantly higher PD‐1 expression proportion and intensity on CD3+CD8+T cells than patients in CR/BM controls (p= .022/.045 and .049/.005, respectively), but PD‐1 expression status on them were not significantly different between relapsed and newly diagnosed patients. PD‐L1/L2 expression on leukemic blasts was not significantly different between patient subgroups. In BM aspirates from B‐ALL patients, PD‐1 expression on T‐cell subsets is increased at diagnosis, and to a greater extent, at relapse. These data suggest the potential usefulness of PD‐1 blockade in the treatment of B‐ALL, particularly at relapse.

Published
2020
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26. Water-extracted branch of Cinnamomum cassiapromotes lung cancer cell apoptosis by inhibiting pyruvate dehydrogenase kinase activity

Author

Lee, Eun-Ji, Chung, Tae-Wook, Lee, Jung-Hee, Kim, Bo-Sung, Kim, Eun-Yeong, Lee, Syng-Ook, and Ha, Ki-Tae

Abstract

Cinnamomum cassiaBlume has been widely reported as the anti-tumor agent. However, the precise mechanism underlying its pro-apoptotic action is still not clear. Restraining aerobic glycolysis through suppression of pyruvate dehydrogenase kinase (PDHK) is a promising strategy for cancer inhibition. In this study, we performed to investigate the anti-tumor action of C. cassiais mediated by PDHK inhibition. The inhibition of water-extracted branch of C. cassia(WBCC) on the activity of PDHK using both in vitroand cell-based kinase assay were examined in several lung cancer cells. WBCC reduced viabilities of several lung cancer cells with minimal cytotoxicity on normal bronchial epithelial cells. WBCC decreased lactate production through inhibiting activity of PDHK. In consequence of PDHK inhibition, WBCC increased ROS production, which damage mitochondria membrane stability. In addition, WBCC induced ROS- and mitochondria-dependent apoptotic cell death. Among the components of WBCC, cinnamic acid was founded as a major inhibitor on PDHK activity. This is first report that WBCC induces apoptosis of lung cancer cells through inhibiting PDHK activity. Our findings suggest that WBCC and cinnamic acid can be potential candidates for developing novel anti-cancer drugs through glycolysis metabolism.

Published
2024
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29. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author

Bhatt, Deepak L, Steg, Philippe Gabriel, Mehta, Shamir R, Leiter, Lawrence A, Simon, Tabassome, Fox, Kim, Held, Claes, Andersson, Marielle, Himmelmann, Anders, Ridderstråle, Wilhelm, Chen, Jersey, Song, Yang, Diaz, Rafael, Goto, Shinya, James, Stefan K, Ray, Kausik K, Parkhomenko, Alexander N, Kosiborod, Mikhail N, McGuire, Darren K, Harrington, Robert A, Santos, Vladimir, Jain, Ashit, Lendel, Irina, Russo, Michael, Haught, W H, Bouza, Manuel, Gogia, Harinder, Banerjee, Supratim, Kichura, George, Kantaros, Louis, Padron, Francisco, Passi, Rakesh, Stone, Jay, Pursley, Michael, D'Urso, Michael, Gardner, Timothy, Bennett, James, Nour, Khaled, Saini, Satinder, Zhang, Wenwu, Kumbhani, Dharam, Thomas, Dustin, Angiolillo, Dominick, Bertolet, Barry, Roman-Miranda, Amaury, Black, Robert, Manshadi, Ramin, Vaca, Carlos, Blanco, Antonio, Napoli, Mark, Brabham, David, Akyea-Djamson, Ayim, Desai, Pratik, Prasada, Sudhir, Khaira, Ajit, Forgosh, Leslie, Lieber, Ira, Umpierrez, Guillermo, Singal, Dinesh, Londono, Juan, Fraser, Neil, Ruiz, Jose, Vega, Damaris, Rodriguez, Lilia, Brown, Christopher, Syed, Faizullah, Aggarwala, Guarav, Eaves, William, Foster, Michael, Gupta, Dinesh, Avino, David, Asfour, Wail, Tonnessen, Glen, Zhao, Xue-Qiao, Singh, Narendra, Brockmyre, Andrew, Lepor, Norman, Shammas, Nicolas, Blick, David, Hearne, Steven, Prodafikas, John, Carell, Edgar, Izzo, Mark, Karim, Amin, Zakhary, Bosh, Atieh, Mahmoud, Leichter, Steven, Meadows, Charles, Hotchkiss, David, Abu-Fadel, Mazen, Wiseman, Alan, Bander, Jeffrey, Shah, Mahesh, Banerjee, Subhash, Ganim, Ricky, Sopko, Karen, Khan, Misal, Lloret, Ramon, Weirick, Troy, Mehta, Rajendra, Thadani, Udho, Bhargava, Anuj, Kosiborod, Mikhail, Moya, Jaynier, Staniloae, Cezar, Guerra, Yamirka D, Chhabra, Anil, Kosmicki, Douglas, Shaheen, Wassim, Mohammed, Akber, Bitters, J'Cinda, Pattanayak, Jan, Javier, Julian, Srivastava, Sunny, Phillips, Roland, Al-Amin, Jessie, Lillestol, Michael, Simpson, Patrick, Hazan, Lydie, Amin, Amit, Shah, Gopi, Korpas, Denes, Platt, Bruce, Dickert, Jim, Puente, Orlando, Hiotis, Louis, Doyle, Timothy, Rajan, Raj, Meholick, Alan, Gring, Christian, Hage-Korban, Elie, Feldman, Robert, Colfer, Harry, Butman, Samuel, Foster, Malcolm, Hart, Terence, Huling, Randall, Eshaghian, Shervin, Quintana, Ofsman, Cheung, Deanna, Handel, Franklin, Rodriguez, Mara, Suh, David, Gordon, Paul, Pressman, Gregg, Bauer, Michael, French, William, Barettella, Mark, Chatrathi, Sridhar, Suresh, Damodhar, Goldberg, Ronald, Huth, Mark, Younis, Liwa, Rahman, Aref, Mascolo, Richard, Welch, Michelle, Suneja, Randeep, Smith, Stephen, Shurmur, Scott, Agaiby, John, Jingo, Ahmad, Johnston, Janice, Beth, Mary, Vlastaris, Anthony, Kemp, Susan, Taheri, Hamid, Pereira, Edward, Deyoung, Michael, Hawa, Zafir, Smith, Ray, Galski, Thomas, Garas, Samer, Reddy, M, Sharma, Susheel, Hargrove, Joeseph, Treasure, Charles, Emerson, Ronald, Haddad, Tariq, Rohr, Kathryn, Levinson, Larry, Gaona, Raul, Uretsky, Barry, Maheshwari, Hiralal, Lee, Denny, Kinnaman, Stephanie, Singal, Robert, Geohas, Jeffrey, Gigliotti, Osvaldo, Raisinghani, Ajit, Khurana, Charanjit, Hella, Brent, Kelberman, Michael, Voyce, Steven, Singh, Sanjay, Lo, Eric, Singh, Pradeep, Goodfellow, Ross, Fischer, Stuart, Lorraine, Richard, Turner, Traci, Shanes, Jeffrey, Busch, Robert, Broker, Robert, Zaniewski, Michelle, Pounds, Kevin, Debs-Perez, Giselle, Ong, Stephen, Frandsen, Brad, Fullington, Douglas, Jaffrani, Naseem, Khan, Ahtaram, Lee, Marcus, Pouzar, Joe, Revtyak, George, Gonzalez, Julian, Nakhle, Samer, Murillo, Abel, Young, Douglas, Makam, Sashi, Syed, Mushtaq, Woolf, Kevin, Grena, Paul, Alfata, Sarab, Mahal, Sharan, Hoffman, David, Kizhakekuttu, Tinoy, Deering, Joseph, Bhavsar, Janak, Mikesell, Scott, Wilson, William, Wilson, Vance, El, Salah, Spinale, Francis, Kannarkat, Vinod, Rao, Sunder, Hanson, Lenita, Bertsch, John, Gonzalez-Ortiz, Elena, Severino, Norma, Willis, John, Schock, Joel, Bakhtari, Ladan, Gazmuri, Raul, Ansari, Saadat, 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Michele, Lawson, William, Paa, Christopher, Bortnick, Anna, Krolick, Merrill, Sotolongo, Rodolfo, Cheirif, Jorge, Kumar, Priya, Nadar, Venkatesh, Jetty, Preetham, Patel, Ambar, Kruk, Mariusz, Kobielusz-Gembala, Iwona, Rewerska, Barbara, Madrzejewski, Adam, Milewski, Krzysztof, Cygler, Jerzy, Petryka-Mazurkiewicz, Joanna, Jastrzebski, Waldemar, Korecki, Janusz, Fil, Wojciech, Prokopczuk, Janusz, Bochenek, Anna, Wujkowski, Marek, Witek, Robert, Konczakowski, Piotr, Miekus, Pawel, Szczasny, Marcin, Musial, Wlodzimierz, Cymerman, Krzysztof, Lampart, Jacek, Mikosinski, Jacek, Szynal, Slawomir, Fares, Issa, Opolski, Grzegorz, Mazur, Stanislaw, Wozakowska-Kaplon, Beata, Bijata-Bronisz, Renata, Wierucki, Lukasz, Losa, Beata, Drelich, Grzegorz, Konieczny, Marek, Starczewski, Pawel, Pawlowicz, Lidia, Jesionowski, Pawel, Jurowiecki, Jaroslaw, Gniot, Jacek, Czyzycki, Mariusz, Stania, Karol, Kucharczyk-Bauman, Izabela, Busz-Papiez, Benita, Karczmarczyk, Agnieszka, Sudnik, Wanda, Koszek, Alina, Kolodziej, Piotr, Skwarna, Bartosz, Jaramillo, Nicolás, Jankowski, Maciej, Czochra, Wojciech, Kinasz, Leszek, Miklaszewicz, Beata, Stasinska, Teresa, Pluta, Wladyslaw, Basiak, Marcin, Rusicka, Teresa, Niedbal-Yahfouf, Izabela, Popenda, Grazyna, Korzeniak, Romuald, Mirek, Agnieszka, Mariankowski, Rafal, Wojnowski, Lukasz, Korol, Marek, Baszak, Jacek, Podolec, Piotr, Piesiewicz, Wojciech, Zurakowski, Aleksander, Luengas, Carlos, Skura, Marek, Pilecki, Piotr, Majchrzak, Piotr, Krzyzagórska, Ewa, Drozd, Marcin, Kaczmarek, Barbara, Sliwinska, Teresa, Zelazowska, Katarzyna, Sztembis, Rafal, Landa, Katarzyna, Matyszczak-Toniak, Lidia, Strojek, Krzysztof, Piepiorka, Marek, Malinowski, Robert, Górska, Maria, Stolarczyk-Sowa, Edyta, Romanowski, Leszek, Zinka, Elzbieta, Reszka, Zygfryd, Skierkowska, Joanna, Uzunow, Anna, Laskowska-Derlaga, Ewa, Puntus, Ekaterina, Kosmacheva, Elena D, Koziolova, Natalia, Pavlov, Prokhor, Supryadkina, Tatiana, Didenko, Yury, Kopylov, Philipp, Kazakov, Andrei, Aksentiev, Sergei, Vishneva, Elena, Repin, Alexey, Smolenskaya, Olga, Mantserova, Olga, Khrustalev, Oleg, Privalova, Elena, Konstantinov, Vladimir, Boldueva, Svetlana, Ezhov, Andrey, Chernyavsky, Alexander, Kamalov, Gadel, Galyavich, Albert, Zubeeva, Galina, Nechaeva, Galina, Shustov, Sergey, Dzhaiani, Nino, Treshkur, Tatiana, Osokina, Nataliya, Panov, Alexey, Shutemova, Elena, Makukhin, Valeriy, Kropotina, Tatiana, Tsyba, Larisa, Karpov, Yuri, Sizova, J M, Ballyuzek, Marina, Tarasov, Nikolay, Demchenko, Elena, Barbarash, Olga, Moiseev, Valentin, Markov, Valentin, Kuznetsov, Vadim, Viktorova, Inna, Sergienko, Igor, Ermoshkina, Lyudmila, Khasanov, Niyaz, Khlevchuk, Tatiana, Baglikov, Andrey, Shalaev, Sergey, Zonova, Elena, Reznik, Elena, Haisheva, Larisa, Morugova, Tatyana, Lomakin, Nikita, Vishnevsky, Alexander, Shvarts, Yuri, Magnitskaya, Olga, Mikhailusova, Marina, Pavlysh, Elena, Libov, Igor, Zateyschikova, Anna, Kostenko, Victor, Edin, Anton, Khovaeva, Yaroslava, Zakharov, Konstantin, Stryuk, Raisa, Khirmanov, Vladimir, Kanorskiy, Sergey, Yakushin, Sergey, Barabashkina, Anna, Li, Hongwei, Zhao, Qiang, Zhang, Jian, Ma, Jianhua, He, Yong, Luo, Ming, Zhang, Aidong, Zhang, Ningru, Chai, Yingru, Ma, Genshan, Wang, Hao, Liu, Zhigang, He, Lanjie, Song, Zhifang, Dong, Xiaolin, Tao, Liang, Li, Zhanquan, Su, Xi, Kong, Xiangqing, Niu, Heping, Ge, Junbo, Luo, Zhurong, Huang, Wenjun, Peng, Daoquan, Yuan, Zuyi, Milanova, Maria, Tenev, Doncho, Gogov, Antoni, Karageorgiev, Dimitar, Kolchev, Todor, Rusev, Nikolay, Georgieva, Nikolina, Kondov, Rumen, Rusinov, Veselin, Petrov, Ivo, Stanchev, Georgi, Konteva, Mariana, Dincheva, Adriana, Yaneva, Zdravka, Vatova, Ralitsa, Ilieva, Katya, Runev, Nikolai, Kolomanov, Borislav, Petrov, Ivan, Iliev, Nikolay, Tisheva, Snezhanka, Chompalova, Boryana, Tokmakova, Maria, Raev, Dimitar, Byanov, Kolyo, Markov, Dimitar, Mihov, Lenko, Mihov, Atanas, Milcheva, Nora, Minchev, Milen, Mollov, Mihail, Borisov, Borislav, Tihchev, Tihomir, Karakolev, Venelin, Dimov, Bojidar, Georgiev, Svetoslav, Smilov, Lachezar, Koo, Bon K, Ahn, Taehoon, Hong, Soon J, Yoon, Junghan, Oh, Seok K, Jeong, Myung H, Kim, Doo-Il, Chang, Kiyuk, Kim, Weon, Hahn, Joo-Yong, Cha, Kwang S, Lee, Jung-Hee, Choi, Si-Wan, Nam, Chang-Wook, Chae, In-Ho, Park, Yong H, Tahk, Seung-Jea, Shin, Won-Yong, Chae, Jei-Keon, Kim, Byung J, Bae, Jang-Whan, Park, Woo J, Rha, Seung W, Choi, Young J, Hwang, Jin-Yong, Park, Hun S, Baracioli, Luciano, Guimaraes, Fabio, Vasconcellos, Eduardo, Saraiva, José, Pereira, Adamastor, Santos, Queulla, Rossi, Paulo, Maia, Lilia, Madeira, Miguel, Pereira, Marcio, Botelho, Roberto, Reis, Gilmar, Eliaschewitz, Freddy, Borges, Joao, Nascimento, Carlos, Fortes, Jose A, de Souza, Weimar, Pimentel, Pedro, Hissa, Miguel, Franchetti, Marcos, Precoma, Dalton, Ortiz, Costantino, Hernandes, Mauro, Saporito, Wladmir, dos Santos, Fabio R, Kormann, Adrian, Neuenschwander, Fernando, Dutra, Oscar, Rassi, Nelson, Tanajura, Luiz, Souza, Juliana, Junior, Delcio S, Leaes, Paulo, Forte, Adriana, Bonansea, Teresa C, Marin, Jose, Machado, Bruno, Cerqueira, Maria J, Silva, Frederico, Michalaros, Yorghos, Manenti, Euler, Cercato, Cintia, Figueiredo, Estevao, Liu, Ming-En, Wang, Yi-Chih, Lee, Tsung-Ming, Fang, Chih, Wu, Yen-Wen, Ueng, Kwo-Chang, Sheu, Huey-Herng, Lai, Wen T, Hsieh, I-Chang, Chen, Zhih-Cherng, Lee, Mu-Jang, Chiang, Chern, Shyu, Kou-Gi, Hsia, Chien-Hsun, Mar, Guang-Yuan, Chan, Shih-Hung, Wu, Chih-Cheng, Tseng, Wei-Kung, Chang, Kuan-Cheng, Yeh, Hung-I, Wang, Ji-Hung, Hou, Charles, Sorokina, Inna, Dolzhenko, Maryna, Horoshko, Olha, Karpenko, Oleksandr, Rudenko, Leonid, Vakaliuk, Igor, Kulyk, Anna, Levchenko, Olena, Prokhorov, Oleksandr, Reshotko, Dmytro, Sorokivskyy, Mykhaylo, Velichko, Nataliia, Maslovskyi, Valentyn, Teliatnikova, Zinaida, Dotsenko, Sergiy, Krakhmalova, Olena, Kraiz, Igor, Zharinova, Viktoria, Bula, Larysa, Kaydashev, Igor, Molodtsov, Valeriy, Rasputina, Lesya, Pidlisna, Viktoriya, Lysunets, Olena, Kravchenko, Anatoliy, Glushko, Liubomyr, Khomazyuk, Tetyana, Svyshchenko, Yevgeniya, Parkhomenko, Oleksandr, Mankovsky, Boris, Abrahamovych, Orest, Yagensky, Andriy, Stanislavchuk, Mykola, Vasilyeva, Larisa, Sokolova, Liubov, Sychov, Oleg, Tseluyko, Vira, Kyrychenko, Igor, Rishko, Mykola, Furkalo, Sergiy, Gallo, Richard, Bertrand, Olivier, Mehta, Shamir, Constance, Christian, Sussex, Bruce, Zadra, Remo, Kouz, Simon, Chehayeb, Raja, Pandey, Amritanshu, Dion, Danielle, Bailey, Gordon, Hill, Laurie, Ramanathan, Krishnan, Dorsch, Micha, Nanji, Alykhan, Babapulle, Mohan, Montigny, Martine, Gosselin, Gilbert, Dehghani, Payam, Rupka, Dennis, Le May, Michel, Pichette, Francis, St-Maurice, Francois, Teefy, Patrick, Mansour, Samer, Kassam, Saleem, Cheung, Stephen, Siega, Anthony D, O'Keefe, Dennis, Sabbah, Eric, Bell, Alan, Chouinard, Guy, Wong, Brian, Miller, Mark, Gaudet, Daniel, Lachance, Pierre, Bata, Iqbal, Petrella, Robert, Gossard, Denis, Dumas, Richard, Ing, Douglas, Boyrazian, Hagop, Bessoudo, Ricardo, Huynh, Thao T, Hart, Randy, Belle-Isle, Jasmin, Shukla, Dinkar, Kelly, Allan, Mazza, Giuseppe, Cha, James, Henein, Sam, Frechette, Andre, Vizel, Saul, Liutkus, Joanne F, O'Mahony, Michael, Halperin, Frank, Kooy, Jacobus, Graham, John, Bailey, Allan, Wojcik, Ronald, Wilderman, Igor, Turi, Tibor, Motyovszki, Ákos, Merkely, Béla, Király, Csaba, Andrássy, Péter, Sárszegi, Zsolt, Fülöp, Tibor, Zilahi, Zsolt, Édes, István, Papp, Andras, Müller, Gábor, Czigány, Anna, Zólyomi, Szilárd, Korányi, László, Takács, János, Juhász, Ferenc, Benczur, Bela, Kancz, Sándor, Földi, András, Nagy, András C, Bakai, Judit, Greschik, István, Püski, László, Nagy, László, Kirschner, Róbert, Kuchar, Roman, Hajek, Petr, Busak, Ladislav, Michalik, Daniel, Matyasek, Ivo, Marusincova, Ivana, Kucera, Dusan, Jerabek, Ondrej, Honkova, Michaela, Dedek, Vratislav, Rihacek, Ivan, Kos, Pavel, Slaby, Josef, Machkova, Martina, Zidkova, Eva, Elbl, Lubomir, Grunfeldova, Hana, Carda, Jiri, Mrozek, Vladimir, Maly, Jiri, Milkovic, Richard, Malecha, Jan, Skalicka, Hana, Oral, Ivo, Krcova, Eva, Lisa, Libor, Belohlavek, Jan, Miklik, Roman, Cermak, Ondrej, Bednarova, Jana, Peroutka, Zdenek, Spinar, Jindrich, Wilke, Andreas, Appel, Karl-Friedrich, Taggeselle, Jens, Förster, Andreas, Toursarkissian, Nicole, Schmidt, Ekkehard, Bott, Jochen, Al-Zoebi, Ayham, Hennig, Dirk, Fischer, Sabine, Schön, Norbert, Sauter, Joachim, Simonis, Gregor, Nischik, Ruth, Rieker, Werner, Schenkenberger, Isabelle, Behnke, Thomas, Klausmann, Gerhard, Jeserich, Michael, Trenk, Dietmar, Weigmann, Ingo, Reuter, Hannes, Rummel, Reinhard, von Münchhausen, Candy, von Engelhardt, Charlotte, Horibe, Eishun, Shibasaki, Taro, Sato, Tomohiko, Kakuta, Tsunekazu, Michishita, Ichiro, Tan, Michinao, Ishiki, Ryoji, Aoyama, Takahiko, Higashiue, Shinichi, Niijima, Yawara, Idogaki, Akira, Hasegawa, Toru, Kiyosue, Arihiro, Tomobuchi, Yoshiaki, Kawamitsu, Katsunori, Kawasaki, Satsuki, Hata, Yoshiki, Fukui, Kazuki, Seki, Kozaburo, Takenaka, 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Adrian, van Zyl, Louis, Coetzee, Kathleen, Punt, Zelda, Bayat, Junaid, Dawood, Saleem, Mitha, Ismail, Padayachee, Trevenesan, Hoosen, Farzana, Dalby, Anthony, Prabhavathi, Gowdaiah, Prakash, Mehta, Vimal, Chag, Milan, Gadkari, Milind, Ramamurthee, Kannaiyan, Das, Asit, Sawhney, Jitendra S, Banerjee, Suvro, Sathe, Prachee, Adhyapak, Srilakshmi, Nguyen, Tuan, Pham, Vinh, Do, Huan, Nguyen, Anh, Nguyen, Hien, Truong, Binh, Jamil-Copley, Shahnaz, Lang, Chim, Pell, Alastair, Zaman, Azfar, Storey, Robert, Swanson, Neil, Smith, Simon, Sharman, David, Braganza, Denise, Hammond, Peter, Moriarty, Andrew, Bain, Stephen, Pye, Maurice, Sharp, Andrew, Blagden, Mark, Randeva, Harpal, Myhill, Timothy, Viswanathan, Girish, Keeling, Philip, Clifford, Piers, Saxena, Manish, Lyons, Kristopher, McMurray, John, Jaafar, Feeroz, Murphy, Clare, Cartwright, Simon, Abouglila, Kamal, Antalik, Lubomir, Krajci, Peter, Urban, Miroslav, Fazekas, Frantisek, Pella, Daniel, Koleny, Daniel, Vykoukalova, Tatiana, Macek, Vladimir, Vinanska, Daniela, Jamriskova, Livia, Such, Slavomir, Fulop, Peter, Farsky, Stefan, Bugan, Viliam, Strbova, Jaroslava, Micko, Karol, Palka Jr, Juraj, Sivak, Vladimir, Kristensen, Dalby, Refsgaard, Jens, Holmvang, Lene, Dixen, Ulrik, Nielsen, Henrik, Egstrup, Kenneth, Jensen, Lisette O, Sykulski, Roman, Rasmussen, Ole, Andries, Alin, Luckow, Anders, Nielsen, Gitte, Sørensen, Torben, Wongvipaporn, Chaiyasith, Chamnarnphol, Noppadol, Srimahachota, Suphot, Sansanayudh, Nakarin, Kuanprasert, Srun, Tresukosol, Damras, Sookananchai, Bancha, Kanadasi, Mehmet, Ozcan, Turkay, Kucuk, Murathan, Ongen, Zeki, Okuyan, Ertugrul, Arat, Alev, Acikel, Sadik, Yalcin, Ahmet, Guray, Umit, Ceyhan, Ceyhun, Ozer, Necla, Arslan, Sakir, Angerås, Oskar, Johnston, Nina, Weiderman, Ann-Charlotte, Bandh, Stellan, Hansen, Ole, Larnefeldt, Hans, Kusiak, Dawid, Lindholm, Carl-Johan, Hedman, Anders, Erlinge, David, Curiac, Dan, Lundman, Pia, Zucconi-Mazzini, Roberto, Aladellie, Layth, Jensen, Jens, Verwerft, Jan, Vrolix, Mathias, Faes, Dirk, Striekwold, Harry, Sinnaeve, Peter, Timmermans, Patrick, Guedes, Antoine, Delforge, Marc, Nimmegeers, Jan, Stammen, Francis, Buysschaert, Ian, Hoffer, Etienne, Hollanders, Geert, Vervoort, Geert, Coussement, Patrick, de Maeseneire, Stefan, Janssens, Luc, Gravdal, Stein A, Risberg, Knut, Gullestad, Lars, Hofseth, Ola D, Nilsen, Dennis, Lappegård, Knut T, van den Heuvel, Christian, Gibbs, Charlotte, Khusrawi, Alamdar, Arora, Satish, Tomala, Tadeusz, Kjærnli, Thorbjørn, Berg-Johansen, Jan, Hagemeier, Robert, Skjelvan, Gunnar, Colquhoun, David, Amerena, John, Morbey, Claire, Hammett, Christopher, Dart, Anthony, Lehman, Ronald, Hamilton, Andrew, Worthley, Matthew, Purnell, Peter, Whelan, Alan, MacIsaac, Richard, Arya, Ktut, Linjawi, Sultan, Proietto, Joseph, Prasad, Lakshman, Rodriguez, Aldo, Godoy, Armando, Rodriguez, Victor, Berrospi, Percy, Chavez, Carlos, Negron, Sandra, Heredia, Javier, Medina, Felix, Manrique, Helard, Cabrera, Walter, Cordova, Fernando, Quinteros, Trinidad, Haro, Jaime M, Regalado, Susana, Guitton, Javier, Arbanil, Hugo, Pansieri, Michel, Decoulx, Eric, Goube, Pascal, de Labriolle, Axel, Labeque, Jean N, Range, Gregoire, Cottin, Yves, Montalescot, Gilles, Cayla, Guillaume, Danchin, Nicolas, Angoulvant, Denis, Ferrario, Emile, Elbaz, Meyer, Dubreuil, Olivier, Steg, Philippe G, Fontaine, Caroline, Sorbets, Emmanuel, Omer, Hafiz, Al-Saif, Shukri, Al-Faleh, Hussam, Al-Shehri, Abdullah, Alshehri, Halia, Bazari, Rasha, Hei, Pak, Ying, Man, Chan, Michael, Wong, Michelle, Ma, Ronald, Siu, Shing C, Tsang, Chiu C, Ferrario, Maurizio, Assanelli, Emilio, Senni, Michele, Piatti, Piermarco, Calabrò, Paolo, Urbinati, Stefano, Michisanti, Massimo, Varbella, Ferdinando, de Cosmo, Salvatore, Trevisan, Roberto, Bellotti, Sandro, Di Pasquale, Giuseppe, Bongo, Angelo S, Uguccioni, Massimo, Mannucci, Edoardo, Mauro, Ciro, Ragonese, Mauro, Fresco, Claudio, Turturo, Maurizio, Marcucci, Rossella, Lievano Triana, Manuel J, Arana, Camilo, Accini, Jose, Botero, Rodrigo, Muzyk-Osikowicz, Marlena, Dada, Fredy T, Vallejo, Gregorio S, Manzur, Fernando, Isaza, Daniel, Molina, Dora, Mesa, Juan G, Quintero, Alvaro, Nyman, Kai, Mäkelä, Jyrki, Strand, Jorma, Nieminen, Sakari, Taurio, Jyrki, Kuusela, Matti, Valle, Timo, Pietilä, Mikko, Kekki, Sakari, Strandberg, Timo, Klutstein, Marc, Greenberg, Gabriel, Rozenman, Yoseph, Chorin, Ehud, Roguin, Ariel, Lewis, Basil, Bashkin, Amir, Tan, Edgar, Prado, Jose P, Ferrolino, Arthur, Babilonia, Noe, Barbas, Benny, Matiga, Generoso, Coching, Raul M, Drexel, Heinz, Brath, Helmut, Schnack, Christoph, Hanusch, Ursula, Fließer-Görzer, Evelyn, Paulweber, Bernhard, Ebenbichler, Christoph, Prager, Rudolf, Huber, Kurt, Wolzt, Michael, Auer, Johann, Berger, Rudolf, Schernthaner, Gerit-Holger, Stanciulescu, Gabriela, Creteanu, Mihai, Spiridon, Marilena, Dobreanu, Viorica, Vinereanu, Dragos, Iosipescu, Laura C, Istratoaie, Octavian, Coman, Ioan, Militaru, Constantin, Cinteza, Mircea, Bhatt, Deepak L, Fox, Kim, Harrington, Robert A, Leiter, Lawrence A, Mehta, Shamir R, Simon, Tabassome, Andersson, Marielle, Himmelmann, Anders, Steg, Philippe G, Diaz, Rafael, Amerena, John, Huber, Kurt, Sinnaeve, Peter R, Nicolau, José C, Kerr Saraiva, José F, Petrov, Ivo, Leiter, Lawrence A, Mehta, Shamir R, Corbalán, Ramón, Ge, Junbo, Zhao, Qiang, Botero, Rodrigo, Widimský, Petr, Kristensen, Steen D, Hartikainen, Juha, Danchin, Nicolas, Darius, Harald, Tse, Hung F, Kiss, Robert G, Pais, Prem, Lev, Eli, de Luca, Leonardo, Goto, Shinya, Ramos López, Gabriel A, Cornel, Jan H, Kontny, Frederic, Medina, Felix, Babilonia, Noe A, Opolski, Grzegorz, Vinereanu, Dragos, Zateyshchikov, Dmitry A, Ruda, Mikhail, Elamin, Omer, Kovář, František, Dalby, Anthony J, Jeong, Myung H, Bueno, Héctor, James, Stefan K, Chiang, Chern-En, Tresukosol, Damras, Ongen, Zeki, Ray, Kausik K, Parkhomenko, Alexander, McGuire, Darren K, Kosiborod, Mikhail N, Nguyen, Tuan Q, Andersson, Marielle, Chen, Jersey, Himmelmann, Anders, Leonsson-Zachrisson, Maria, and Ridderstråle, Wilhelm

Abstract

Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor.

Published
2019
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30. The Prevalence of the Use of MIS Techniques in the Treatment of Adult Spinal Deformity (ASD) Amongst Members of the Scoliosis Research Society (SRS) in 2016

Author

Anand, Neel, Agrawal, Aniruddh, Burger, Evalina L., Ferrero, Emmanuelle, Fogelson, Jeremy L., Kaito, Takashi, LaGrone, Michael O., Le Huec, Jean-Charles, Lee, Jung-Hee, Mudiyam, Ram, Sasao, Yutaka, Sembrano, Jonathan N., Trobisch, Per D., and Yang, Shu-Hua

Abstract

Electronic survey administered to Scoliosis Research Society members.

Published
2019
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31. The Prevalence of the Use of MIS Techniques in the Treatment of Adult Spinal Deformity (ASD) Amongst Members of the Scoliosis Research Society (SRS) in 2016

Author

Anand, Neel, Agrawal, Aniruddh, Burger, Evalina L., Ferrero, Emmanuelle, Fogelson, Jeremy L., Kaito, Takashi, LaGrone, Michael O., Le Huec, Jean-Charles, Lee, Jung-Hee, Mudiyam, Ram, Sasao, Yutaka, Sembrano, Jonathan N., Trobisch, Per D., and Yang, Shu-Hua

Abstract

Study Design: Electronic survey administered to Scoliosis Research Society members. Objective: To determine the prevalence of minimally invasive surgery (MIS) techniques for the treatment of adult spinal deformity. Summary of Background Data: There is a paucity of data available on the practice pattern, prevalence of minimally invasive spine surgery, and the preferred minimally invasive techniques in the treatment of adult spine deformity. Methods: An electronic nine-question survey regarding individual usage pattern of minimally invasive spine surgery techniques was administered in 2016 to the members of the Scoliosis Research Society. Determinants included complexity in condition of patient population, prevalence of use of minimally invasive techniques in the surgeon’s practice, prevalence of use of a particular MIS technique, strategy elected during surgery, adoption of staging of procedures and timing between staging of procedures. Results: A total of 357 surgeons responded (61.3% response rate), and 154 (43.1%) of the respondents said that they use MIS as a part of their surgical treatment of adult spinal deformity. However, of these 154 respondents, 67 (43.5%) said that their MIS usage in deformity practice was between 1% and 20%. Only 11 (7.2%) said that they used MIS 81% to 100% of the time. The top MIS approaches that surgeons chose were MIS lateral lumbar interbody fusion 109 (70.59%) and MIS percutaneous screws 91 (58.8%). Conclusions: The low rate of adoption of these techniques among the SRS members may be due to the false perception that there is not enough data to support that MIS techniques are better. This and the fact that a practitioner needs to be facile at different MIS techniques may be the true impediment to the adoption of MIS techniques in the treatment of ASD. Level of Evidence: Level IV.

Published
2019
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32. Histological subtypes of hepatocellular carcinoma: Their clinical and prognostic significance.

Author

Shin, So Hyun, Park, Joon Young, Hwang, Chungsu, Lee, Hyun Jung, Shin, Dong Hoon, Kim, Jee Yeon, Ryu, Je Ho, Yang, Kwang Ho, Lee, Tae Beom, and Lee, Jung Hee

Abstract

Assigning a hepatocellular carcinoma (HCC) to an appropriate subtype is important because this guarantees the diagnosis and treatment and allows decisions regarding the prognosis of the patient. HCC subtyping is usually based on the World Health Organization (WHO) classification and the 2019 fifth edition is the latest version. However, the WHO classification system is still in evolution and has limited clinical relevance. We aimed to evaluate the clinical relevance of HCC subtyping and to reappraise some of the major subtypes of HCC. Our archived cases (n = 589) were reclassified according to the 2019 WHO system. The percentage of each subtype was mostly similar to that in the WHO classification. However, on the contrary to the 2019 WHO system, clear cell type HCC was associated with more frequent recurrence or metastasis. Meanwhile, macrotrabecular massive HCC was related to poor prognosis as demonstrated in the 2019 WHO system and should be described in the pathology report. For steatohepatitic HCC, there is a debate on whether it is a true subtype because the steatohepatitis morphology may or may not be present in the background liver. In our study, 44 % of steatohepatitic HCCs (n = 19/43) presented underlying steatohepatitis. Additionally, the background cirrhosis did not influence survival in the HCC patients, although the 2019 WHO system indicates the presence of cirrhosis as a poor prognostic factor. In conclusion, although it is not perfect yet, HCC subtyping based on the 2019 WHO system provides valuable information to manage patients with HCC. • Clinical relevance of HCC subtyping was clarified with the 2019 WHO classification. • Clear cell type HCC was associated with more frequent recurrence or metastasis than the NOS type. • Macrotrabecular massive HCC was related to poor prognosis and should be described in the pathology report. [ABSTRACT FROM AUTHOR]

Published
2023
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33. The Optimal Busulfan Dose of Conditioning Regimens for Allogeneic Hematopoietic Cell Transplantation in Younger Patients with Acute Myeloid Leukemia

Author

Choi, Yunsuk, Choi, Eun-Ji, Park, Han-Seung, Lee, Jung-Hee, Lee, Kyoo-Hyung, Lee, Young-Shin, Kang, Young-A, Jeon, Mijin, Woo, Ji Min, Kang, Hyeran, and Lee, Je-Hwan

Abstract

Background:In allogeneic hematopoietic cell transplantation (HCT) for younger patients with acute myeloid leukemia (AML), myeloablative conditioning (MAC) regimens have been considered as standard conditioning. MAC can reduce the risk of relapse, but increase non-relapse mortality, including organ toxicity and severe graft versus host disease. Therefore, the optimal busulfan dose in conditioning regimens has not been established in younger patients with AML. Thus, we aimed to investigate post-HCT outcomes according to the busulfan dose of conditioning regimens in younger patients with AML.

Published
2023
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35. A randomized clinical trial comparing long-term clopidogrel vs aspirin monotherapy beyond dual antiplatelet therapy after drug-eluting coronary stent implantation: Design and rationale of the Harmonizing Optimal Strategy for Treatment of coronary...

Author

Lee, Heesun, Koo, Bon-Kwon, Park, Kyung Woo, Shin, Eun-Seok, Lim, Sang Wook, Rha, Seung-Woon, Bae, Jang-Whan, Jeon, Dong Woon, Oh, Seok-Kyu, Hur, Seung-Ho, Kim, Bum-Su, Lee, Jung-Hee, Park, Tae-Ho, Lee, Nam Ho, Kim, Hyo-Soo, and HOST-EXAM investigators

Abstract

Percutaneous coronary intervention (PCI) has been developed by drug-eluting stent (DES), but stent implantation has brought the issue of stent thrombosis and optimal antiplatelet therapy. Guidelines recommend at least 6- to 12 months of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor such as clopidogrel. Beyond DAPT after PCI with DES, however, there has been still a debate for antiplatelet regimen. Therefore, we report on the upcoming HOST-EXAM trial (NCT02044250), which will evaluate the efficacy and safety of aspirin and clopidogrel monotherapies beyond DAPT after DES implantation.Trial Design: The HOST-EXAM is a prospective, randomized, open-label, multicenter, comparative effectiveness trial, to compare between clopidogrel (75 mg once daily) and aspirin (100 mg once daily) as long-term antiplatelet agents. A total of 5,530 patients with no clinical events during combined antiplatelet therapy for 12±6 months after index PCI will be screened, enrolled, and randomized to either group (1:1 ratio) receiving antiplatelet monotherapy for 2 years. The primary endpoint will be the rate of clinical events defined as a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, or major bleeding at 24 months after randomization.Conclusions: The HOST-EXAM will be the first large-scale randomized controlled study to directly compare the efficacy and safety of long-term antiplatelet monotherapy beyond DAPT after DES implantation. This study will provide clinical evidence to establish optimal regimen for long-term antiplatelet therapy after DES implantation. [ABSTRACT FROM AUTHOR]

Published
2017
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37. Thermotherapy for Na+/I− symporter-expressing cancer using anti-Na+/I− symporter antibody-conjugated magnetite nanoparticles.

Author

Jee, Hyeon-Gun, Ban, Hyun Seung, Lee, Jung Hee, Lee, Sang Hun, Kwon, Oh Seok, and Choe, Jun Ho

Subjects
THERMOTHERAPY, MAGNETITE, NANOPARTICLES, CARCINOMA, SODIUM
Abstract

Surgery, followed by remnant ablation with radioactive iodine (I-131), is used for treating differentiated thyroid carcinoma (DTC) as the sodium–iodine (Na-I) symporter (NIS) is highly expressed in the thyroid and DTC cells. Our aim was to investigate the feasibility of using anti-NIS antibody-conjugated magnetite nanoparticles (NIS-MNPs) as a diagnostic and therapeutic agent for DTC by studying NIS-MNP in an NIS over-expressing HeLa (HeLa-NIS) cell line and a subcutaneous HeLa-NIS tumor-bearing mouse model. Immunofluorescence was used to determine if NIS-MNP could bind to HeLa-NIS, and its therapeutic effect was investigated using HeLa-NIS cells after alternating magnetic field (AMF) irradiation. Magnetic resonance imaging (MRI) was performed to visualize the normal thyroid gland of nude mice after intravenous injection of NIS-MNP. NIS-MNPs were injected into the cancer nodules of the mouse model, which were irradiated under AMF for 1 h twice at 24-h intervals. Accumulation of NIS-MNP was examined using MRI and tumor volume was measured over seven days. Results showed that NIS-MNP bound effectively to the surface of HeLa-NIS cells, and AMF inhibited growth of NIS-MNP-treated HeLa-NIS cells. Normal thyroid glands of mice were enhanced by NIS-MNP treatment in T2-weighted MRI. Inhibition of tumor growth was observed after AMF irradiation in the NIS-MNP group. In conclusion, NIS-MNP is a feasible diagnostic and therapeutic tool for localizing and treating NIS-expressing tumors such as DTC when coupled with AMF irradiation. [ABSTRACT FROM AUTHOR]

Published
2018
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38. Increased circulating plasma cells detected by flow cytometry predicts poor prognosis in patients with plasma cell myeloma

Author

Bae, Mi Hyun, Park, Chan‐Jeoung, Kim, Bo Hyun, Cho, Young‐Uk, Jang, Seongsoo, Lee, Dong‐Hyun, Seo, Eul‐Ju, Yoon, Dok Hyun, Lee, Jung‐Hee, and Suh, Cheolwon

Abstract

Flow cytometry (FC) is a reliable tool for diagnosing and monitoring of plasma cell myeloma (PCM). Recent studies used FC for quantifying plasma cells (PCs) in peripheral blood (PB) using various panels, and an adverse prognostic effect of circulating PCs (cPCs) has been reported. We investigated the prognostic implication of cPCs quantified using a simple panel in patients with PCM. Bone marrow (BM) and PB of 85 patients with PCM were analyzed by five‐color FC at time of diagnosis. A serial gating strategy for quantification used CD38/CD138 to gate PCs in 100,000–200,000 acquired events, with subsequent gating for CD19, CD56, and CD45, to identify aberrant immunophenotypes. cPCs were observed in 74.1% patients (63/85, median 0.067% leukocytes). Patients were grouped based on a cPC cut‐off level of 0.02% derived using the receiver operating characteristic curves. Compared with patients with cPCs < 0.02% (n= 28), those with cPCs ≥ 0.02% (n= 57) showed lower hemoglobin (P= 0.003) and platelets (P= 0.014), but higher calcium, M‐protein and BM PCs (P= 0.013, 0.029, and P< 0.001, respectively). Survival analysis of 74 patients showed that cPCs ≥ 0.02% predicted shorter progression‐free and overall survival (P= 0.001 and 0.013, respectively), and this negative prognostic impact was retained in multivariate analysis (P= 0.023). Flow cytometric quantification of cPCs using five surface antigens (CD138, CD38, CD56, CD19, and CD45) is a sensitive and simple method that can be used for assessing PCM prognosis; it would allow clinical laboratories to readily adopt a risk stratification strategy based on cPC levels in PCM patients. © 2017 International Clinical Cytometry Society

Published
2018
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39. Prognostic Impact of Lymphocyte Subpopulations in Peripheral Blood after Hematopoietic Stem Cell Transplantation for Hematologic Malignancies

Author

Park, Sang Hyuk, Park, Chan-Jeoung, Park, Borae G., Bae, Mi-Hyun, Kim, Bo-Hyun, Cho, Young-Uk, Jang, Seongsoo, Park, Ae-Ja, Kim, Dae-Young, Lee, Jung-Hee, Lee, Je-Hwan, and Lee, Kyoo-Hyung

Abstract

We prospectively evaluated prognostic value of lymphocyte subpopulations in peripheral blood of allogeneic hematopoietic stem cell transplant (HSCT) recipients. 113 allogeneic HSCT (47 sibling matched, 37 unrelated matched, 29 haploidentical)-performed patients diagnosed as AML (n= 66), ALL (n= 28), and MDS (n= 19) were prospectively enrolled. 14 lymphocyte subpopulations were quantified by flow cytometry of PB at specific time-points after HSCT, and their prognostic impacts were analyzed. At 1, 2, and 3 months post-HSCT, significant adverse impact on overall survival (OS) and/or event free survival (EFS) was exhibited by low levels of natural killer (NK) cells (=32 and =90/µL at 1 and 2 months on OS and EFS); regulatory T cells (=1/µL) on EFS at 2 months; and B cells (=19 and =92/µL for OS and EFS at 3 months). At 12 months, low levels of T cells (=1180/µL), helper/inducer (H/I) T cells (=250/µL), cytotoxic/suppressor (C/S) T cells (=541/µL), and NK cells (=138/µL) were associated with significantly higher risk of relapse. Low levels of T cells (=879/µL) and C/S T cells (=541/µL), and high level of naïve thymic T cells (>115/µL) showed a significant association with poor OS; low levels of C/S T cells (=541/µL) and NK cells (=138/µL) showed a significant adverse impact on EFS. Low levels of NK cells, regulatory T cells, and B cells at early stage post-HSCT are adverse prognostic indicators. At late stage, low levels of T cells and their subpopulations, NK cells, and high level of naïve thymic T cells are adverse prognostic indicators. © 2017 International Clinical Cytometry Society

Published
2018
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42. Attainment of low-density lipoprotein cholesterol goal after endovascular treatment is associated with reduced cardiovascular events in patients with peripheral arterial disease.

Author

Lee, Jung-Hee, Ko, Young-Guk, Shin, Dong-Ho, Kim, Jung-Sun, Kim, Byeong-Keuk, Choi, Donghoon, Hong, Myeong-Ki, and Jang, Yangsoo

Abstract

Objective The relationship between attainment of low-density lipoprotein cholesterol (LDL-C) levels and clinical outcomes in patients with peripheral arterial disease (PAD) has received little attention. We sought to investigate clinical outcomes in relation to attainment of LDL-C goals in patients with PAD after endovascular treatment. Methods We reviewed 342 PAD patients treated with endovascular therapy from 2010 through 2012. We categorized patients into two groups based on the attained LDL-C levels at short-term follow-up (mean, 4.8 ± 2.8 months): group A (n = 160), with LDL-C <70 mg/dL; and group B (n = 182), with LDL-C ≥70 mg/dL. The primary end point was major adverse cardiovascular events (MACEs), a composite of all-cause death, nonfatal myocardial infarction, and stroke. Results Baseline characteristics were similar between group A and group B except for obstructive pulmonary disease (0% vs 7%; P = .001). More patients in group A received statin therapy than those in group B (93% vs 76%; P < .001). MACEs (4% vs 10%; P = .002) and all-cause mortality (2% vs 7%; P = .007) occurred less frequently in group A than in group B at 2 years. A Cox proportional hazards multivariate regression model identified attainment of LDL-C goal <70 mg/dL at short-term follow-up as an independent predictor of reduced MACEs (hazard ratio, 0.25; 95% confidence interval, 0.09-0.67; P = .006) along with age as a predictor of increased MACEs (hazard ratio, 1.04; 95% confidence interval, 1.00-1.08; P = .031). Conclusions Attainment of LDL-C goal <70 mg/dL at short-term follow-up is an independent predictor of reduced mortality and cardiovascular events after endovascular therapy in patients with PAD. [ABSTRACT FROM AUTHOR]

Published
2016
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43. Multifunctional and Redox-Responsive Self-Assembled Magnetic Nanovectors for Protein Delivery and Dual-Modal Imaging

Author

Yang, Hong Yu, Jang, Moon-Sun, Li, Yi, Lee, Jung Hee, and Lee, Doo Sung

Abstract

Nanoparticle (NP) based model carriers present an emerging strategy for protein delivery. However, constructing a multifunctional nanocarrier with high loading capacity, diagnostic imaging capacity, and controlled release capability is a tremendous challenge for protein delivery systems. Thus, we herein report on the fabrication of redox-responsive magnetic nanovectors (termed RMNs) through self- assembly of Fe3O4NPs and redox-responsive polymer ligands, which could effectively transport protein and trigger intracellular protein release. These RMNs also exhibited low toxicity, high stability, biocompatibility, and T2-weighted contrast-enhancement properties. In addition, they presented a quantized positively charged surface that had the capacity to load cyanine 5.5 (Cy5.5) labeled human serum albumin (HSA) with high loading efficiency (∼84%) via electrostatic interactions and which favored cellular uptake. Notably, studies of the in vitro protein release showed that HSA-Cy5.5-loaded RMNs (RMNs-HSA-Cy5.5) presented minimal cumulative release behavior under physiological conditions but release was rapidly enhanced under high glutathione concentration conditions. Confocal microscopy further revealed that protein was delivered and localized at the perinuclear region of tumor cells. Moreover, the in vivo imaging results confirmed that RMNs-HSA-Cy5.5 could serve as a dual-modal probe for simultaneous near-infrared fluorescence (NIRF) imaging and magnetic resonance (MR) imaging, which can be used for breast cancer diagnosis, and verified higher tumor accumulation of transported protein in a living body. Overall, we believe that these multifunctional RMNs exhibit great promise for protein delivery, cancer diagnosis and therapy, and multimodal imaging, as well as clinical applications.

Published
2017
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45. Multifunctional Polymer Ligand Interface CdZnSeS/ZnS Quantum Dot/Cy3-Labeled Protein Pairs as Sensitive FRET Sensors

Author

Yang, Hong Yu, Fu, Yan, Jang, Moon-Sun, Li, Yi, Lee, Jung Hee, Chae, Heeyeop, and Lee, Doo Sung

Abstract

High-quality CdZnSeS/ZnS alloyed core/thick-shell quantum dots (QDs) as energy donors were first exploited in Förster resonance energy transfer (FRET) applications. A highly efficient ligand-exchange method was used to prepare low toxicity, high quantum yield, stabile, and biocompatible CdZnSeS/ZnS QDs densely capped with multifunctional polymer ligands containing dihydrolipoic acid (DHLA). The resulting QDs can be applied to construct QDs-based Förster resonance energy transfer (FRET) systems by their high affinity interaction with dye cyanine 3 (Cy3)-labeled human serum albumin (HSA). This QD-based FRET protein complex can serve as a sensitive sensor for probing the interaction of clofazimine with proteins using fluorescence spectroscopic techniques. The ability of FRET imaging both in vitro and in vivo not only reveals that the current FRET system can remain intact for 2 h but also confirms the potential of the FRET system to act as a nanocarrier for intracellular protein delivery or to serve as an imaging probe for cancer diagnosis.

Published
2016
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49. Long-Term Outcomes of Neointimal Hyperplasia Without Neoatherosclerosis After Drug-Eluting Stent Implantation.

Author

Kim, Jung-Sun, Lee, Jung-Hee, Shin, Dong-Ho, Kim, Byeong-Keuk, Ko, Young-Guk, Choi, Donghoon, Jang, Yangsoo, and Hong, Myeong-Ki

Abstract

Objectives The aim of this study was to investigate the correlation between in-stent neointimal tissue without features of neoatherosclerosis and long-term clinical outcomes. Background Recent studies have reported differential morphological characteristics of in-stent neointimal tissue assessed by optical coherence tomography (OCT). Methods The study population consisted of 336 patients with 368 drug-eluting stent-treated lesions. Patients received a follow-up OCT examination without any intervention. OCT-based neointima was categorized as homogeneous (n = 227 lesions in 208 patients), heterogeneous (n = 79 lesions in 73 patients), or layered (n = 62 lesions in 55 patients). Major adverse cardiac events (MACE) (a composite of cardiac death, nonfatal myocardial infarction, or target lesion revascularization) were assessed according to neointimal patterns during long-term clinical follow-up after OCT examination. Results The time interval between stent implantation and OCT examination was similar among the 3 groups (p = 0.64). On multivariate logistic regression analysis, the significant determinant for the heterogeneous neointima was age (odds ratio [OR]: 1.037, 95% confidence interval [CI]: 1.007 to 1.068, p = 0.015) and an initial clinical presentation of acute coronary syndrome (OR: 1.967, 95% CI: 1.159 to 3.339, p = 0.012). The overall median follow-up duration for all patients after follow-up OCT examination was 31.0 months, and this was statistically different among the heterogeneous group (22.0 months), the homogeneous group (34.0 months), and the layered group (28.0 months, overall p = 0.002). MACE occurred more frequently in patients with heterogeneous neointima over a median 31-month follow-up period after OCT examination (13.7% vs. 2.9% in homogeneous vs. 7.3% in layered, p = 0.001). A propensity score–adjusted Cox regression analysis showed that independent risk factors for MACE were inclusion in the heterogeneous neointima (hazard ratio: 3.925, 95% CI: 1.445 to 10.662, p = 0.007) and minimal lumen cross-sectional area (hazard ratio: 0.368, 95% CI: 0.242 to 0.560, p < 0.001). Conclusions Determination of neointimal characteristics is helpful in predicting long-term clinical outcomes. Our data suggest that heterogeneous lesions are linked to poor long-term clinical prognoses. [ABSTRACT FROM AUTHOR]

Published
2014
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50. Abolished ischemic tricuspid regurgitation by revascularization of left anterior descending artery: The role of collateral circulation.

Author

Cho, Sungsoo, Lee, Jung-Hee, Shim, Chi Young, Chang, Hyuck-Jae, Hong, Geu-Ru, Ha, Jong-Won, Hong, Myeong-Ki, Chung, Namsik, and Cho, Seung-Yun

Abstract

A 74-year-old man presented with recent inferior wall myocardial infarction. The right ventricle (RV) was strikingly dilated and akinetic along the free wall compatible with right ventricular infarction. Accordingly, severe functional tricuspid regurgitation (TR) was detected. Coronary angiogram revealed total occlusion on the proximal right coronary artery (RCA). There was collateral blood flow from the left anterior descending (LAD) artery to the right ventricular ischemic region. The LAD artery also had a significant stenosis which might limit the required amount of blood supply to collateral blood vessels. Because of the technical difficulty in the intervention of RCA, the patient underwent percutaneous intervention on the LAD artery. After the revascularization of LAD artery, severe TR was abolished accompanied by the right ventricular functional recovery. < Learning objective: Isolated ischemic tricuspid regurgitation was rarely manifested because the right ventricle has a more favorable oxygen supply–demand ratio than the left ventricle and receives extensive collateral flow from the left-to-right collateral system. In our case, the right ventricle was receiving blood flow through collateral circulation from septal branches of the left anterior descending coronary artery due to the total occlusion of proximal right coronary artery. This case displays the remarkable role of collateral circulation in restoring right ventricular function and in treating ischemic tricuspid regurgitation.> [ABSTRACT FROM AUTHOR]

Published
2014
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