Publications by authors named "Young A Kim"

141 Publications

The generalizability of empirically derived syndromes of collateral-reported elder psychopathology across 11 societies.

Res Nurs Health 2021 Jun 14. Epub 2021 Jun 14.

Department of Psychology, Academia Pedagogiki Specjalnej, University of Warsaw, Warsaw, Poland.

The purpose of this study was to test whether a syndrome model of elder psychopathology derived from collateral ratings, such as from spouses and adult children, in the United States would be generalizable in 11 other societies. Societies represented South America, Asia, and Europe. The Older Adult Behavior Checklist (OABCL) was completed by collateral informants for 6141 60- to 102-year-olds. The tested model comprised syndromes designated as Anxious/Depressed, Worries, Somatic Complaints, Functional Impairment, Memory/Cognition Problems, Thought Problems, and Irritable/Disinhibited. The model was tested using confirmatory factor analyses in each society separately. The primary model fit index showed a good fit for all societies, while the secondary model fit indices showed acceptable to a good fit for all societies. The items loaded strongly on their respective factors, with a median item loading of 0.69 across the 11 societies. By syndrome, the overall median item loadings ranged from 0.47 for Worries to 0.77 for Functional Impairment. The OABCL syndrome structure was thus generalizable across the tested societies. The OABCL can be used for broad assessment of psychopathology for elders of diverse backgrounds in nursing services and research.
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http://dx.doi.org/10.1002/nur.22161DOI Listing
June 2021

Prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer.

Sci Rep 2021 Jun 7;11(1):11942. Epub 2021 Jun 7.

Department of Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.

We investigated the prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer patients. BCL1 and BCL2 expression statuses were assessed by immunohistochemistry using tissue microarrays from 393 breast cancer patients. The Kaplan-Meier estimator and log-rank test were used for survival analyses. The Cox proportional hazards model was used to calculate hazard ratio (HR) and the 95% confidence interval (CI) of survival analyses. BCL1 expression revealed no impact on survival. The high BCL2 group showed superior disease-free survival compared with the low BCL2 group (p = 0.002), especially regarding local recurrence-free survival (p = 0.045) and systemic recurrence-free survival (p = 0.002). BCL2 expression was a significant prognostic factor by univariable analysis (HR, 0.528; 95% CI, 0.353-0.790; p = 0.002) and by multivariable analysis (HR, 0.547; 95% CI, 0.362-0.826; p = 0.004). High BCL2 expression was associated with higher disease-free survival in the hormone receptor (HRc)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HRc(+)/HER2(-)) subtype only (p = 0.002). The high BCL2 group was associated with positive estrogen receptor (ER), positive progesterone receptor (PR), low histologic grade, and age ≤ 50 years. BCL1 expression had no prognostic impact, but BCL2 expression was a significant independent prognostic factor. High BCL2 expression was associated with higher disease-free survival, especially regarding local recurrence and systemic recurrence. The prognostic effect of BCL2 expression was effective only in the HRc(+)/HER2(-) subtype. Favorable clinicopathologic features and a strong association with the ER/PR status could partly explain the superior prognosis of the high BCL2 group. BCL2 expression could be utilized to assess the prognosis of breast cancer patients in clinical settings.
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http://dx.doi.org/10.1038/s41598-021-90506-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184896PMC
June 2021

Increased expression of thyroid hormone receptor alpha and estrogen receptor alpha in breast cancer associated with thyroid cancer.

Eur J Surg Oncol 2021 Jun 22;47(6):1316-1323. Epub 2021 Jan 22.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea. Electronic address:

Introduction: Breast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings.

Material And Methods: Tissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERβ, TRα, and TRβ expression levels were analyzed by immunohistochemistry.

Results: TRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p < 0.001).

Conclusion: Enhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.
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http://dx.doi.org/10.1016/j.ejso.2021.01.015DOI Listing
June 2021

Surveillance of COVID-19-Associated Multisystem Inflammatory Syndrome in Children, South Korea.

Emerg Infect Dis 2021 04 4;27(4):1196-1200. Epub 2021 Feb 4.

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.
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http://dx.doi.org/10.3201/eid2704.210026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007302PMC
April 2021

Comprehensive Gene Expression Analyses of Immunohistochemically Defined Subgroups of Muscle-Invasive Urinary Bladder Urothelial Carcinoma.

Int J Mol Sci 2021 Jan 10;22(2). Epub 2021 Jan 10.

Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea.

A number of urinary bladder urothelial carcinoma (UB UC) mRNA-based classification systems have been reported. It also has been observed that treatment response and prognosis are different for each molecular subtype. In this study, cytokeratin (CK)5/6 and CK20 immunohistochemistry (IHC) were performed, and IHC-based subgroup classification was applied. UB UC was classified into CK5/6 single-positive (SP), CK20 SP, double-positive (DP) and double-negative (DN) subgroups, and transcriptional analysis was performed. The results of gene ontology (GO) terms and functional analysis using differentially expressed genes indicate that, CK5/6 SP and DP subgroups were enriched in cell migration, immune activation, interleukin 6-Janus kinase-signal transducer and activator of transcription 3 (IL6-JAK-STAT3) signaling pathway and tumor necrosis factor-α signaling via the nuclear factor-κB (NF-κB) signaling pathway signature gene. In addition, compared with the other subgroups, the DN subgroup showed inhibited cell movement, cell migration, and cell activation. Furthermore, in survival analysis, the CK5/6 SP subgroup was significantly associated with poor progression-free survival ( = 0.008). The results of our study indicate that the CK5/6 positive subgroup exhibited high gene expression signature related to aggressive behavior and exhibited worse clinical outcome.
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http://dx.doi.org/10.3390/ijms22020628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828072PMC
January 2021

The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus.

Nat Commun 2021 01 11;12(1):256. Epub 2021 Jan 11.

Department of Biological Sciences, University at Buffalo, Buffalo, NY, 142604, USA.

In humans, inactivating mutations in MLL4, which encodes a histone H3-lysine 4-methyltransferase, lead to Kabuki syndrome (KS). While dwarfism is a cardinal feature of KS, the underlying etiology remains unclear. Here we report that Mll4 regulates the development of growth hormone-releasing hormone (GHRH)-producing neurons in the mouse hypothalamus. Our two Mll4 mutant mouse models exhibit dwarfism phenotype and impairment of the developmental programs for GHRH-neurons. Our ChIP-seq analysis reveals that, in the developing mouse hypothalamus, Mll4 interacts with the transcription factor Nrf1 to trigger the expression of GHRH-neuronal genes. Interestingly, the deficiency of Mll4 results in a marked reduction of histone marks of active transcription, while treatment with the histone deacetylase inhibitor AR-42 rescues the histone mark signature and restores GHRH-neuronal production in Mll4 mutant mice. Our results suggest that the developmental dysregulation of Mll4-directed epigenetic control of transcription plays a role in the development of GHRH-neurons and dwarfism phenotype in mice.
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http://dx.doi.org/10.1038/s41467-020-20511-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801453PMC
January 2021

Comparative analysis of the tumor immune-microenvironment of primary and brain metastases of non-small-cell lung cancer reveals organ-specific and EGFR mutation-dependent unique immune landscape.

Cancer Immunol Immunother 2021 Jul 9;70(7):2035-2048. Epub 2021 Jan 9.

Department of Pathology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: To evaluate the characteristics of the tumor immune-microenvironment in brain metastases of non-small-cell lung cancer (NSCLC), we investigated the immunophenotype of primary NSCLC and its brain metastasis.

Methods: Expression profiling of 770 immune-related genes in 28 tissues from primary and brain metastases of NSCLC was performed using the NanoString nCounter PanCancer Immune Profiling Panel. The immune cell profiles were validated by immunohistochemistry of 42 matched samples.

Results: Based on unsupervised clustering and principal component analysis of the immune-related gene expression profile, tumors were primarily clustered according to the involved organ and further grouped according to the EGFR mutation status. Fifty-four genes were significantly differentially expressed between primary and brain metastatic tumors. Clustering using these genes showed that tumors harboring mutated EGFR tended to be grouped together in the brain. Pathway analysis revealed that various immune-related functions involving immune regulation, T cell activity, and chemokines were enriched in primary tumors compared to brain metastases. Diverse immune-related pathways were upregulated in brain metastases of EGFR-mutated compared to EGFR-wild-type adenocarcinoma, but not in primary tumors. The interferon-γ-related gene signature was significantly decreased in brain metastases. The anti-inflammatory markers TOLLIP and HLA-G were upregulated in brain metastases. The proportions of most immune cell subsets were decreased in brain metastases, but those of macrophages and CD56dim-NK-cells were increased, as was the ratios of CD163M2- to iNOSM1-macrophages and NCR1NK-cells to CD3T cells.

Conclusions: Our findings illustrate the immune landscape of brain metastases from NSCLC and reveal potential therapeutic strategies targeting cellular and non-cellular components of the tumor immune-microenvironment.
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http://dx.doi.org/10.1007/s00262-020-02840-0DOI Listing
July 2021

PD-L1 Expression in Muscle-Invasive Urinary Bladder Urothelial Carcinoma According to Basal/Squamous-Like Phenotype.

Front Oncol 2020 7;10:527385. Epub 2020 Dec 7.

Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.

Urothelial carcinoma (UC) is the most common histologic type of urinary bladder cancer, and muscle-invasive UC shows aggressive behaviors. Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockades have been approved as standard treatments for patients with advanced stage UC. A total of 166 muscle-invasive urinary bladder cancer (MIBC) patients, who underwent transurethral resection of the bladder or cystectomy from 2004 to 2010 were included. We evaluated PD-L1 expression by the SP142 and SP263 assays and classified the cases "positive" or "negative" according to the manufacturer's recommendations. We performed immunohistochemistry (IHC) for cytokeratin (CK) 5/6, CK14, GATA3, FOXA1, and CK20 and classified samples as Basal-Squamous-like (BASQ) or non-BASQ subtype. The overall concordance rate for PD-L1 expression is 91.6% (152/166) (kappa = 0.732). The SP142 assay showed 15.1% positivity; the SP263 assay showed 23.5%. The high positivity in the SP142 and SP263 assay was significantly correlated with positive CK5/6, CK14 expression, negative GATA3, FOXA1, and CK20 expression. Classification according to IHC expression resulted in 12.0% (20/166) of samples being classified as BASQ subtype and 88.0% (146/166) of samples being classified as non-BASQ subtype. High positivity in the SP142 and SP263 assay was significantly correlated with the BASQ subtype (p < 0.001, both). Our study is the first to analyze the association of immunohistochemically defined BASQ and non-BASQ subtypes with two PD-L1 assays in MIBC. In conclusion, we revealed that a high PD-L1 positive rate in all PD-L1 assays was significantly associated with the BASQ-subtype, and these results suggest that the BASQ classification may be important to apply the PD-1/PD-L1 blockades in MIBC.
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http://dx.doi.org/10.3389/fonc.2020.527385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750632PMC
December 2020

Expression of Class III Beta-Tubulin Is Associated with Invasive Potential and Poor Prognosis in Thyroid Carcinoma.

J Clin Med 2020 Nov 26;9(12). Epub 2020 Nov 26.

Department of Pathology, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Korea.

Although American Thyroid Association guidelines offer a risk stratification scheme for thyroid cancer patients, there is a continuous need for more sophisticated biomarkers that can predict disease progression. In this study, we aim to evaluate the prognostic value of class III beta-tubulin (TUBB3) and uncover the relationship between TUBB3 and invasive potential in thyroid carcinoma. Immunohistochemistry (IHC) for TUBB3 and E-cadherin was performed on a total of 254 cases of thyroid cancer specimens. Tumor budding at the invasive margin was evaluated. In vitro functional studies were also performed; the protein and mRNA levels of TUBB3 were compared among the five cell types at baseline, with transwell invasion and after blocking of TUBB3 by shRNA. IHC revealed that the levels of TUBB3 were higher in conventional papillary carcinomas (cPTCs) and anaplastic thyroid carcinomas (ATCs). In univariate analysis, high tumor budding and TUBB3 expression were associated with inferior progression-free survival in cPTC. The results of a Western blot and RT-PCR agreed with the IHC finding. The results were further validated through data from The Cancer Genome Atlas database. Our results suggest that high expression of TUBB3 in thyroid carcinoma could predict invasive potential and possibly be linked with epithelial-mesenchymal transition.
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http://dx.doi.org/10.3390/jcm9123830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760790PMC
November 2020

Wip1 controls the translocation of the chromosomal passenger complex to the central spindle for faithful mitotic exit.

Cell Mol Life Sci 2021 Mar 16;78(6):2821-2838. Epub 2020 Oct 16.

Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea.

Dramatic cellular reorganization in mitosis critically depends on the timely and temporal phosphorylation of a broad range of proteins, which is mediated by the activation of the mitotic kinases and repression of counteracting phosphatases. The mitosis-to-interphase transition, which is termed mitotic exit, involves the removal of mitotic phosphorylation by protein phosphatases. Although protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) drive this reversal in animal cells, the phosphatase network associated with ordered bulk dephosphorylation in mitotic exit is not fully understood. Here, we describe a new mitotic phosphatase relay in which Wip1/PPM1D phosphatase activity is essential for chromosomal passenger complex (CPC) translocation to the anaphase central spindle after release from the chromosome via PP1-mediated dephosphorylation of histone H3T3. Depletion of endogenous Wip1 and overexpression of the phosphatase-dead mutant disturbed CPC translocation to the central spindle, leading to failure of cytokinesis. While Wip1 was degraded in early mitosis, its levels recovered in anaphase and the protein functioned as a Cdk1-counteracting phosphatase at the anaphase central spindle and midbody. Mechanistically, Wip1 dephosphorylated Thr-59 in inner centromere protein (INCENP), which, subsequently bound to MKLP2 and recruited other components to the central spindle. Furthermore, Wip1 overexpression is associated with the overall survival rate of patients with breast cancer, suggesting that Wip1 not only functions as a weak oncogene in the DNA damage network but also as a tumor suppressor in mitotic exit. Altogether, our findings reveal that sequential dephosphorylation of mitotic phosphatases provides spatiotemporal regulation of mitotic exit to prevent tumor initiation and progression.
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http://dx.doi.org/10.1007/s00018-020-03665-xDOI Listing
March 2021

The first Korean cases of combined oxidative phosphorylation deficiency 35 with two novel TRIT1 mutations in two siblings confirmed by clinical and molecular investigation.

Brain Dev 2021 Feb 15;43(2):325-330. Epub 2020 Sep 15.

Department of Pediatrics, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University, Yangsan Hospital, Republic of Korea. Electronic address:

Background: Combined oxidative phosphorylation deficiency 35 (COXPD 35) is a very rare autosomal recessive disorder caused by homozygous or compound heterozygous mutations in the TRIT1 gene on chromosome 1p34. Only six cases of COXPD 35 and six allelic variants of TRIT1 gene mutations have been reported worldwide.

Case Description: We describe two siblings who presented with similar clinical features including severe intellectual disability and epilepsy with onset of symptom in early infancy.

Results: The whole exome sequencing results revealed a compound heterozygous novel variant, c.979G > A (p.Glu327Lys) and c.682 + 2 T > C, on TRIT1 exon 8 and intron 5, respectively, which was confirmed by Sanger sequencing. Protein structure analysis revealed that the p.Glu327Lys variant disrupts the conformation and electrostatic charge of the zinc-finger motif in the tRNA isopentenyltransferase (IPT), impairing binding of the mutant IPT to specific DNA sequences.

Conclusion: This is the first report of two Korean siblings with COXPD 35 with two novel variants in TRIT1. This study will help to understand the various phenotypic spectra in patients with COXPD 35 and to expand knowledge on the mechanisms of the disease based on genetic features.
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http://dx.doi.org/10.1016/j.braindev.2020.08.016DOI Listing
February 2021

Risk factors affecting the treatment outcome of pediatric foreign body aspiration: significance of time factors.

Pediatr Surg Int 2020 Sep 16;36(9):1061-1066. Epub 2020 Jul 16.

Department of Otolaryngology-Head and Neck Surgery, College of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.

Purpose: The aim of this study was to identify the factors affecting the prognosis of children with foreign body aspiration (FBA) after undergoing rigid bronchoscopy.

Methods: This was a case series with a chart review of 49 children under 3 years of age who underwent rigid bronchoscopy for suspected FBA at a single tertiary institution.

Results: The time from symptom onset to hospitalization positively correlated with the total hospitalization time (p < 0.001), postoperative hospitalization time (p = 0.006), and operation time (p = 0.013). The time from symptom onset to operation positively correlated with the total hospitalization time (p < 0.001) and operation time (p = 0.046). The time from hospitalization to operation and the operation time positively correlated with the total hospitalization time (p = 0.026, 0.044) and postoperative hospitalization time (p = 0.049, 0.003). The time from symptom onset to hospitalization positively correlated with the incidence of pneumonia (p = 0.028).

Conclusion: Rapid hospitalization after symptom onset, rapid surgery after symptom onset, and rapid surgery after hospitalization improve the prognosis of patients with FBA. Further, a short operation time also plays a role in improving patient prognosis.
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http://dx.doi.org/10.1007/s00383-020-04714-zDOI Listing
September 2020

Effects of B7-H3 expression on tumour-infiltrating immune cells and clinicopathological characteristics in non-small-cell lung cancer.

Eur J Cancer 2020 07 21;133:74-85. Epub 2020 May 21.

Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Purpose: B7-H3 has emerged as a promising target for cancer immunotherapy. We assessed the role of B7-H3 expression in tumour-infiltrating immune cells in non-small-cell lung cancer (NSCLC).

Methods: Tumour-infiltrating immune cell characterisation was performed by flow cytometry in a prospective cohort, whereas the relationship between B7-H3 expression and clinicopathological features was explored in a retrospective cohort.

Results: B7-H3 expression was detected in tumour/epithelial cells and immune cells, including macrophages, monocytes, dendritic cells (DCs) and myeloid-derived suppressor cells. B7-H3 was expressed at higher levels in cells within the tumour than in cells within non-neoplastic tissues. B7-H3 expression score in tumour cells positively correlated with the amount of CD45 immune cells (rho = 0.305, P = 0.010), CD8 T-cells (rho = 0.330, P = 0.005), and the percentage of CD8/CD3 T-cells (rho = 0.403, P < 0.001). Patients with high tumoural B7-H3 expression showed increased numbers of immune cells (P = 0.002), CD8 T-cells (P = 0.011), natural killer cells (P = 0.073) and plasmacytoid DCs (P = 0.015). Tumoural B7-H3 expression was higher in males, smokers, squamous cell carcinomas, tumours with wild-type EGFR, poor differentiation, larger size and nodal metastasis (P < 0.05, all). Tumoural B7-H3 expression was associated with PD-L1 expression (P = 0.001), shorter 5-year overall survival (P = 0.012) and poor survival after anti-PD-1 blockade (P = 0.026).

Conclusions: Tumoural B7-H3 overexpression was associated with increased tumour-infiltrating cytotoxic lymphocytes and poor prognosis in NSCLC. Thus, B7-H3 is a promising prognostic biomarker and immunotherapeutic target in NSCLC.
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http://dx.doi.org/10.1016/j.ejca.2020.03.033DOI Listing
July 2020

Factors Affecting Acceptance of Cosmetic Surgery in Adults in Their 20s-30s.

Aesthetic Plast Surg 2020 10 18;44(5):1881-1888. Epub 2020 May 18.

College of Nursing, Jeju National University, 102 Jejudaehakno, Jeju-si, Jeju-do, 63243, Republic of Korea.

Background: This descriptive study investigates cosmetic surgery experience, awareness of side effects, self-esteem, and acceptance of cosmetic surgery (ACS) and aims to identify factors that affect ACS.

Methods: Data on 398 randomly selected participants from a panel of sex-stratified adults in their 20s and 30s registered online with a Korean survey company were collected in September 2019. The data were analyzed using descriptive statistics, crosstabs, Chi-square test, ANOVA, Pearson's correlation, and multiple linear regression.

Results: Among the subjects, 47.2% were male and 52.8% were female. The average age of the subjects was 29.98 years. While 91.7% of the subjects previously acquired information on side effects related to cosmetic surgery, the most frequent source was from "bus stops and subway stops," reported by 83.6% of them. Blepharoplasty was the most frequently performed procedure reported by 50 of the 89 subjects (22.4%) who underwent 1 or more cosmetic surgery procedures. Among 187 subjects (47.0%) considering cosmetic surgery in the future, "botulinum toxin" was the most frequently considered procedure. ACS of the subjects was higher with employment (β = .15, p < .001), previous experience with cosmetic surgery (β = .22, p < .001), consideration for future cosmetic surgery (β = .49, p < .001), and lower appearance satisfaction (AS) (β = -.10, p = .008), and the explanatory power of these variables was 41.7% (F = 72.08, p < .001).

Conclusions: Most of the subjects in this study were aware of the side effects of cosmetic surgery, and about half were considering cosmetic surgery in the future. Employment status, previous experience with cosmetic surgery, consideration for future cosmetic surgery, and AS were found to be factors affecting ACS. Correlations between age, BMI, ACS, AS, depression, and self-esteem were identified.

Level Of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-020-01761-8DOI Listing
October 2020

Influence of Androgen Receptor on the Prognosis of Breast Cancer.

J Clin Med 2020 Apr 10;9(4). Epub 2020 Apr 10.

Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 156-707, Korea.

We investigated the prognostic influence of androgen receptor (AR) on breast cancer. AR status was assessed using immunohistochemistry with tissue microarrays from 395 operable primary breast cancer patients who received curative surgery. The Kaplan-Meier estimator was used to analyze the survival rates and a log-rank test was used to determine the significance of the differences in survival. The Cox proportional hazards model was used to calculate the hazard ratio (HR) and the 95% confidence interval (CI) of survival. There were 203 (51.4%) subjects with a low expression of AR, and 192 patients (48.6%) with a high expression rate. The high AR expression group showed superior overall survival ( = 0.047) and disease-free survival ( = 0.004) when compared with the low AR expression group. The high AR expression group showed superior systemic recurrence-free survival when compared with the low AR expression group ( = 0.027). AR was an independent prognostic factor for both overall survival (HR, 0.586; 95% CI, 0.381-0.901; = 0.015) and disease-free survival (HR, 0.430; 95% CI, 0.274-0.674; < 0.001). A high AR expression was a significant favorable prognostic factor only in the subgroups with positive hormone receptors (HRc) and negative human epidermal growth factor receptor 2 (HER2) when considering disease-free survival ( = 0.026). The high AR expression group was significantly associated with superior overall survival and disease-free survival when compared with the low AR expression group with breast cancer patients. AR was a significant independent prognostic factor for both overall survival and disease-free survival. The prognostic impact of AR was valid in the HRc(+)/HER2(-) subtype when considering disease-free survival. These findings suggest the clinical usefulness of AR as a prognostic marker of breast cancer in clinical settings.
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http://dx.doi.org/10.3390/jcm9041083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230528PMC
April 2020

Clinicopathological features of programmed cell death-1 and programmed cell death-ligand-1 expression in the tumor cells and tumor microenvironment of angioimmunoblastic T cell lymphoma and peripheral T cell lymphoma not otherwise specified.

Virchows Arch 2020 Jul 13;477(1):131-142. Epub 2020 Mar 13.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

The expression patterns of programmed cell death-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) and their clinicopathological implications were investigated in peripheral T cell lymphoma (PTCL) including angioimmunoblastic T cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS). PTCL-NOS was further classified into nodal PTCL with follicular helper T cell (Tfh) phenotype ("PTCL-Tfh_new") and "PTCL-NOS_new". PD-1 and PD-L1 expression on tumor cells and reactive immune cells was evaluated using immunohistochemistry. PD-1 and PD-L1 expression on tumor cells (PD-1 and PD-L1, respectively) was interpreted as positive when more than 5% of tumor cells expressed PD-1 or PD-L1. For PD-1 and PD-L1 on tumor cells and/or reactive immune cells (PD-1 and PD-L1, respectively), a cutoff of 10% of cells was used. PD-1, PD-L1, and PD-L1 expressions tended to be higher in AITLs than in PTCLs-NOS. PD-1, PD-1, PD-L1, and PD-L1 expressions tended to be higher in PTCLs with Tfh phenotype including AITLs and "PTCL-Tfh_new" than in PTCLs without Tfh phenotype. The serum LDH level was significantly elevated in patients with PTCL positive for PD-L1 (P = 0.006) and PD-L1 (P < 0.001). Patients with PTCL who were positive for combined expression of PD-1/PD-L1 presented at older ages (P = 0.010), nodal diseases (P = 0.001), higher IPI (P = 0.060), and elevated LDH (P = 0.030). Combined PD-1/PD-L1 positivity was related to shorter overall survival in patients with AITL (P = 0.051). Combined PD-1/PD-L1 positivity was a significant poor prognostic factor in patients with stage IV AITL, independent of B symptoms and performance status (HR = 6.282 [CI, 1.655-23.844], P = 0.007). In summary, the PD-1/PD-L1 pathway could be a potential prognostic and therapeutic biomarker for PTCL.
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http://dx.doi.org/10.1007/s00428-020-02790-zDOI Listing
July 2020

PRMT6-mediated H3R2me2a guides Aurora B to chromosome arms for proper chromosome segregation.

Nat Commun 2020 01 30;11(1):612. Epub 2020 Jan 30.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea.

The kinase Aurora B forms the chromosomal passenger complex (CPC) together with Borealin, INCENP, and Survivin to mediate chromosome condensation, the correction of erroneous spindle-kinetochore attachments, and cytokinesis. Phosphorylation of histone H3 Thr3 by Haspin kinase and of histone H2A Thr120 by Bub1 concentrates the CPC at the centromere. However, how the CPC is recruited to chromosome arms upon mitotic entry is unknown. Here, we show that asymmetric dimethylation at Arg2 on histone H3 (H3R2me2a) by protein arginine methyltransferase 6 (PRMT6) recruits the CPC to chromosome arms and facilitates histone H3S10 phosphorylation by Aurora B for chromosome condensation. Furthermore, in vitro assays show that Aurora B preferentially binds to the H3 peptide containing H3R2me2a and phosphorylates H3S10. Our findings indicate that the long-awaited key histone mark for CPC recruitment onto mitotic chromosomes is H3R2me2a, which is indispensable for maintaining appropriate CPC levels in dynamic translocation throughout mitosis.
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http://dx.doi.org/10.1038/s41467-020-14511-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992762PMC
January 2020

A successful application of adult polymyxin B-immobilized fiber column hemoperfusion to a neonate with septic shock

Acute Crit Care 2019 11 6;34(4):284-288. Epub 2018 Nov 6.

Department of Pediatrics, Pusan National University Children's Hospital, Yangsan, Korea.

Direct hemoperfusion therapy with a polymyxin B-immobilized fiber column (PMX-HP) has been introduced as a therapeutic option for gram negative bacterial septic shock in adults. However, its use in neonates and children has not yet been established. We successfully performed hemoperfusion therapy using an adult polymyxin B-immobilized fiber column in a neonate with carbapenem resistant Acinetobacter baumannii septic shock. The application was technically feasible because the neonate was on extracorporeal membrane oxygenation (ECMO). Although it did not rescue the patient, there was significant short-lasting improvement in pulmonary oxygenation and hemodynamics, leading to wean the patient from ECMO. PMX-HP could be used as an adjunctive treatment for selected neonatal and pediatric patients with gram negative bacterial septic shock.
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http://dx.doi.org/10.4266/acc.2017.00528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895470PMC
November 2019

Programmed cell death ligand-1-mediated enhancement of hexokinase 2 expression is inversely related to T-cell effector gene expression in non-small-cell lung cancer.

J Exp Clin Cancer Res 2019 Nov 12;38(1):462. Epub 2019 Nov 12.

Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: We investigated the role of PD-L1 in the metabolic reprogramming of non-small cell lung cancer (NSCLC).

Methods: Changes in glycolysis-related molecules and glycolytic activity were evaluated in PD-L1 and PD-L1 NSCLC cells after transfection or knockdown of PD-L1, respectively. Jurkat T-cell activation was assessed after co-culture with NSCLC cells. The association between PD-L1 and immune response-related molecules or glycolysis were analyzed in patients with NSCLC and The Cancer Genome Atlas (TCGA).

Results: Transfecting PD-L1 in PD-L1 cells enhanced hexokinase-2 (HK2) expression, lactate production, and extracellular acidification rates, but minimally altered GLUT1 and PKM2 expression and oxygen consumption rates. By contrast, knocking-down PD-L1 in PD-L1 cells decreased HK2 expression and glycolysis by suppressing PI3K/Akt and Erk pathways. Interferon-γ (IFNγ) secretion and activation marker expression was decreased in stimulated Jurkat T-cells when co-cultured with HK2-overexpressing vector-transfected tumor cells rather than empty vector-transfected tumor cells. Immunohistochemistry revealed that PD-L1 expression was positively correlated with HK2 expression in NSCLC (p < 0.001). In TCGA, HK2 exhibited a positive linear association with CD274 (PD-L1) expression (p < 0.001) but an inverse correlation with the expression of CD4, CD8A, and T-cell effector function-related genes in the CD274 rather than CD274 group. Consistently, there were fewer CD8 T-cells in PD-L1/HK2 tumors compared to PD-L1/HK2 tumors in squamous cell carcinoma.

Conclusions: PD-L1 enhances glycolysis in NSCLC by upregulating HK2, which might dampen anti-tumor immunity. PD-L1 may contribute to NSCLC oncogenesis by inducing metabolic reprogramming and immune checkpoint.
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http://dx.doi.org/10.1186/s13046-019-1407-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852926PMC
November 2019

Cosmetic Surgery and Self-esteem in South Korea: A Systematic Review and Meta-analysis.

Aesthetic Plast Surg 2020 02 21;44(1):229-238. Epub 2019 Oct 21.

College of Nursing, Jeju National University, 102 Jejudaehakno, Jeju-si, Jeju-do, 63243, Republic of Korea.

Purpose: Advances in medical technology coupled with rapid growth of web-based mass media and social networking services have considerably increased public access to cosmetic surgery. In South Korea, in particular, the number of people undergoing cosmetic surgery has been rapidly increasing, and studies related to cosmetic surgery have markedly increased. We report an integrative review of studies examining the relationship between cosmetic surgery and self-esteem in Korea. We aimed to identify relevant variables and determine their overall effect sizes.

Methods: This study was designed based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Two researchers separately performed the literature search, selected 16 papers based on the inclusion and exclusion criteria, and analyzed them.

Results: Of the 16 papers on cosmetic surgery and self-esteem, 5 (33.3%) involved both men and women, and the remaining 11 (66.7%) involved only women. The respondents included teenagers and adults. The total number of respondents was 6296, with an average of 393.5 per paper. Most studies (n = 13, 81.3%) used the Rosenberg Self-Esteem Scale. Self-esteem was correlated with variables grouped into the following six categories: appearance management intention, cosmetic surgery intention, sociocultural attitude, body satisfaction, BMI, and stress. The effect sizes from the meta-analysis with correlation coefficients were 0.157, - 0.118, 0.023, 0.175, - 0.045, and - 0.085.

Conclusions: Among the relevant variables categorized in this study, sociocultural attitude, BMI, and stress showed weak effect sizes, and the appearance management intention, cosmetic surgery intention, and body satisfaction categories showed intermediate effect sizes. The results of this study are expected to serve as a concrete basis for the development of strategies to minimize the adverse effects of the ever-growing cosmetic surgery industry. This information can help elucidate the psychologic characteristics of individuals seeking cosmetic surgery and contribute to optimal medical outcomes.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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http://dx.doi.org/10.1007/s00266-019-01515-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957555PMC
February 2020

CXCL16 positively correlated with M2-macrophage infiltration, enhanced angiogenesis, and poor prognosis in thyroid cancer.

Sci Rep 2019 09 16;9(1):13288. Epub 2019 Sep 16.

Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Although various chemokines have pro-tumorigenic actions in cancers, the effects of CXCL16 remain controversial. The aim of this study was to investigate the molecular characteristics of CXCL16-expressing papillary thyroid cancers (PTCs). CXCL16 expressions were significantly higher in PTCs than benign or normal thyroid tissues. In the TCGA dataset for PTCs, a higher CXCL16 expression was associated with M2 macrophage- and angiogenesis-related genes and poor prognostic factors including a higher TNM staging and the BRAF mutation. PTCs with a higher expression of 3-gene panel including CXCL16, AHNAK2, and THBS2 showed poor recurrence-free survivals than that of the lower expression group. Next, shCXCL16 was introduced into BHP10-3SCp cells to deplete the endogenous CXCL16, and then, the cells were subcutaneously injected to athymic mice. Tumors from the BHP10-3SCp exhibited a delayed tumor growth with decreased numbers of ERG endothelial cells and F4/80 macrophages than those from the BHP10-3SCp. CXCL16-related genes including AHNAK2 and THBS2 were downregulated in the tumors from the BHP10-3SCp compared with that from the BHP10-3SCp. In conclusion, a higher CXCL16 expression was associated with macrophage- and angiogenesis-related genes and aggressive phenotypes in PTC. Targeting CXCL16 may be a good therapeutic strategy for advanced thyroid cancer.
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http://dx.doi.org/10.1038/s41598-019-49613-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746802PMC
September 2019

MET Receptor Tyrosine Kinase Regulates the Expression of Co-Stimulatory and Co-Inhibitory Molecules in Tumor Cells and Contributes to PD-L1-Mediated Suppression of Immune Cell Function.

Int J Mol Sci 2019 Sep 1;20(17). Epub 2019 Sep 1.

Cancer Research Institute, Seoul National University, Seoul 03080, Korea.

The MET tyrosine receptor kinase is essential for embryonic development and tissue regeneration by promoting cell survival, proliferation, migration, and angiogenesis. It also contributes to tumor development and progression through diverse mechanisms. Using human cancer cell lines, including Hs746T (-mutated/amplified), H596 (-mutated), and H1993 (-amplified) cells, as well as BEAS-2B bronchial epithelial cells, we investigated whether MET is involved in the regulation of immune checkpoint pathways. In a microarray analysis, MET suppression using a MET inhibitor or siRNAs up-regulated co-stimulatory molecules, including 4-1BBL, OX40L, and CD70, and down-regulated co-inhibitory molecules, especially PD-L1, as validated by measuring total/surface protein levels in Hs746T and H1993 cells. MET activation by HGF consistently increased PD-L1 expression in H596 and BEAS-2B cells. Co-culture of human peripheral blood mononuclear cells with Hs746T cells suppressed interferon-γ production by the immune cells, which was restored by MET inhibition or PD-L1 blockade. A significant positive correlation between MET and PD-L1 expression in lung cancer was determined in an analysis based on The Cancer Genome Atlas (TCGA) and in an immunohistochemistry study. The former also showed an association of MET overexpression in a PD-L1 tumor with the decreased expressions of T-cell effector molecules. In summary, our results point to a role for MET overexpression/activation in the immune escape of tumors by PD-L1 up-regulation. MET-targeted-therapy combined with immunotherapy may therefore be an effective treatment strategy in patients with MET-dependent cancer.
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http://dx.doi.org/10.3390/ijms20174287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747314PMC
September 2019

High tumoral PD-L1 expression and low PD-1 or CD8 tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system.

Oncoimmunology 2019;8(9):e1626653. Epub 2019 Jun 10.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

We investigated the clinicopathological role of the PD-1/PD-L1 pathway in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) arising in the immune-privileged site. PD-L1 immunostaining of ≥30% of tumor cells was defined as tPD-L1+, and PD-L1 immunostaining of ≥30% of total cellularity, including tumor and non-tumoral cells, as tmPD-L1+ . PD-1 and CD8 tumor-infiltrating lymphocytes (TILs) were enumerated. Thirty-five cases (35.7%) were tPD-L1+ and 47 cases (48%) were tmPD-L1+ . The number of TILs was greater in tmPD-L1+ cases than in tmPD-L1- cases (CD8, = .050; PD-1, = .019). tPD-L1+ and tmPD-L1+ cases tended to have a poor performance status. In contrast, the numbers of CD8 and PD-1 TILs tended to be higher in patients with a good performance status and MYC/BCL2 negativity. Patients with tPD-L1+ had a worse overall survival (= .026), and those with increased CD8 or PD-1 TILs tended to have a better overall survival (= .081 and 0.044, respectively). Tumoral PD-L1 expression and the number of PD-1 TILs were independent prognostic factors. tPD-L1+ patients with a small number of CD8 or PD-1 TILs had the worst prognosis, and tPD-L1- patients with a large number of CD8 or PD-1 TILs had the best prognosis. In validation group, increased CD8 or PD-1 TILs were significantly associated with a prolonged survival, but PD-L1 had no prognostic significance. In conclusion, PD-L1 is frequently expressed in tumor cells and the immune microenvironment of PCNS-DLBCL and is correlated with increased TILs. PD-L1 and CD8 and PD-1 TILs have potential as prognostic biomarkers and therapeutic targets in PCNS-DLBCL.
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http://dx.doi.org/10.1080/2162402X.2019.1626653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685509PMC
February 2021

Intraocular medulloepithelioma in children: clinicopathologic features itself hardly differentiate it from retinoblastoma.

Int J Ophthalmol 2019 18;12(7):1227-1230. Epub 2019 Jul 18.

Department of Ophthalmology, Seoul National University College of Medicine, Seoul 03080, Korea.

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http://dx.doi.org/10.18240/ijo.2019.07.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629819PMC
July 2019

Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer.

Nat Commun 2019 06 24;10(1):2764. Epub 2019 Jun 24.

Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea.

Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAF and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.
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http://dx.doi.org/10.1038/s41467-019-10680-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591357PMC
June 2019

Clinical Outcomes of Isolated Regional Lymph Node Recurrence in Patients With Malignant Cutaneous Melanoma.

Anticancer Res 2019 Jun;39(6):3147-3157

Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background/aim: Regional lymph node recurrence (RLNR) is the most common pattern of recurrence within 2 years from the diagnosis of patients with non-metastatic malignant cutaneous melanoma. However, isolated RLNR without distant metastasis has been rarely studied.

Patients And Methods: Forty patients with isolated RLNR as a first recurrence were analyzed retrospectively. The clinical outcomes and prognostic impact of clinicopathologic parameters were analyzed. Immunostaining for FOXP3, VEGF, pAKT, and pS6 was also performed.

Results: The median disease-free interval from first diagnosis to isolated RLNR and post-recurrence recurrence-free survival (pRFS) were 12 months and 7.2 months, respectively. Distant failure was the most common pattern of failure after isolated RLNR (67.5%). The number of initially harvested lymph nodes (LN) >7 and LN ratio >22.2% at the time of recurrence were prognosticators for pRFS in multivariate analysis. None of the tested biomarkers were significantly related to prognosis. The 5-year post-recurrence overall survival rate was 84.9%.

Conclusion: Most patients with isolated RLNR will experience a second failure within months, especially distantly. The number of initially harvested LNs and LN ratio at the time of recurrence could predict pRFS.
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http://dx.doi.org/10.21873/anticanres.13452DOI Listing
June 2019

A Novel Orally Active Inverse Agonist of Estrogen-related Receptor Gamma (ERRγ), DN200434, A Booster of NIS in Anaplastic Thyroid Cancer.

Clin Cancer Res 2019 08 22;25(16):5069-5081. Epub 2019 Apr 22.

Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea.

Purpose: New strategies to restore sodium iodide symporter (NIS) expression and function in radioiodine therapy-refractive anaplastic thyroid cancers (ATCs) are urgently required. Recently, we reported the regulatory role of estrogen-related receptor gamma (ERRγ) in ATC cell NIS function. Herein, we identified DN200434 as a highly potent (functional IC = 0.006 μmol/L), selective, and orally available ERRγ inverse agonist for NIS enhancement in ATC.

Experimental Design: We sought to identify better ERRγ-targeting ligands and explored the crystal structure of ERRγ in complex with DN200434. After treating ATC cells with DN200434, the change in iodide-handling gene expression, as well as radioiodine avidity was examined. ATC tumor-bearing mice were orally administered with DN200434, followed by I-positron emission tomography/CT (PET/CT). For radioiodine therapy, ATC tumor-bearing mice treated with DN200434 were administered I (beta ray-emitting therapeutic radioiodine) and then bioluminescent imaging was performed to monitor the therapeutic effects. Histologic analysis was performed to evaluate ERRγ expression status in normal tissue and ATC tissue, respectively.

Results: DN200434-ERRγ complex crystallographic studies revealed that DN200434 binds to key ERRγ binding pocket residues through four-way interactions. DN200434 effectively upregulated iodide-handling genes and restored radioiodine avidity in ATC tumor lesions, as confirmed by I-PET/CT. DN200434 enhanced ATC tumor radioiodine therapy susceptibility, markedly inhibiting tumor growth. Histologic findings of patients with ATC showed higher ERRγ expression in tumors than in normal tissue, supporting ERRγ as a therapeutic target for ATC.

Conclusions: DN200434 shows potential clinical applicability for diagnosis and treatment of ATC or other poorly differentiated thyroid cancers.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3007DOI Listing
August 2019

Metabolomic study of polyamines in rat urine following intraperitoneal injection of γ-hydroxybutyric acid.

Metabolomics 2019 04 2;15(4):58. Epub 2019 Apr 2.

College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon, 540-950, Republic of Korea.

Introduction: Recently, illegal abuse of γ-hydroxybutyric acid (GHB) has increased in drug-facilitated crimes, but the determination of GHB exposure and intoxication is difficult due to rapid metabolism of GHB. Its biochemical mechanism has not been completely investigated. And a metabolomic study by polyamine profile and pattern analyses was not performed in rat urine following intraperitoneal injection with GHB.

Objectives: Urinary polyamine (PA) profiling by gas chromatography-tandem mass spectrometry was performed to monitor an altered PA according to GHB administration.

Methods: Polyamine profiling analysis by gas chromatography-mass spectrometry combined with star pattern recognition analysis was performed in this study. The multivariate statistical analysis was used to evaluate discrimination among control and GHB administration groups.

Results: Six polyamines were determined in control, single and multiple GHB administration groups. Star pattern showed distorted hexagonal shapes with characteristic and readily distinguishable patterns for each group. N-Acetylspermine (p < 0.001), putrescine (p < 0.006), N-acetylspermidine (p < 0.009), and spermine (p < 0.027) were significantly increased in single administration group but were significantly lower in the multiple administration group than in the control group. N-Acetylspermine was the main polyamine for discrimination among control, single and multiple administration groups. Spermine showed similar levels in single and multiple administration groups.

Conclusions: The polyamine metabolic pattern was monitored in GHB administration groups. N-Acetylspermine and spermine were evaluated as potential biomarkers of GHB exposure and addiction.
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http://dx.doi.org/10.1007/s11306-019-1517-2DOI Listing
April 2019

Subglottic stenosis in children: Our experience at a pediatric tertiary center for 8 years in South Korea.

Int J Pediatr Otorhinolaryngol 2019 Jun 27;121:64-67. Epub 2019 Feb 27.

Department of Otolaryngology - Head and Neck Surgery, College of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea. Electronic address:

Objective: The incidence of SGS has been reported to be less than 8% after endotracheal intubation. Therefore there is an increasing trend in the number of patients with acute acquired SGS due to mechanical ventilation in the intensive care unit. However, there have been no reports describing the treatment of SGS in children in South Korea. The objective of this study was to evaluate the management and outcomes of children with SGS at a pediatric tertiary center in South Korea over an 8-year period.

Methods: All patients underwent microlaryngobronchoscopy (MLB) with bougination, incision using cold knife or laser and balloon dilatation. Data on age, sex, grade of SGS, number of management interventions, tracheostomy, comorbidities, mean follow-up period, complications, and outcome were reviewed from patient medical charts.

Results: Twenty patients (13 [65%] males, 7 [35%] females; mean [±SD] age at the diagnostic procedure 15.26 ± 22.54 months) underwent MLB between March 2009 and December 2017. According to the Myer-Cotton scale, twelve of the 20 (60%) patients had grade III SGS, 7 (35%) had grade II and 1 (5%) had grade 1; there were no patients with grade IV SGS. Nine (45%) patients were diagnosed with acute SGS, and 11 (55%) with chronic SGS. Patients with SGS underwent MLB with interventions (mean 2.41 ± 2.23 per patient). Tracheostomy was performed in 13 of 20 (65%) patients, 2 of 9 (22.2%) with acute SGS, and 11 of 11 (100%) with chronic SGS. Two of 13 (15.3%) patients underwent successful decannulation. One of 2 (50%) patients with acute SGS underwent successful decannulation. Seven of 9 (77.7%) patients with acute SGS underwent MLB only without tracheostomy.

Conclusions: In patients with acute acquired SGS, the outcome was good due to the lower rate of tracheostomy and higher decannulation rate. Therefore, it is recommended that MLB with balloon laryngoplasty be performed at the earliest in patients with acute acquired SGS.
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http://dx.doi.org/10.1016/j.ijporl.2019.02.044DOI Listing
June 2019

Longitudinal change of cardiac electrical and autonomic function and potential risk factors in children with dravet syndrome.

Epilepsy Res 2019 05 28;152:11-17. Epub 2019 Feb 28.

Department of Pediatrics, Kosin University Gospel Hospital, Kosin University, Busan, Republic of Korea.

Purpose: This study aimed to investigate cardiac electrical and autonomic function, the longitudinal changes, and the associated risk factors in children with Dravet syndrome (DS).

Methods: Twenty-four children with DS (11 boys, 13 girls; mean age, 7.2 ± 2.9 years) and 21 control subjects (9 boys, 12 girls; mean age, 8.2 ± 3.0 years) were enrolled in this study. P dispersion, QTc and QTc dispersion, and heart rate variability (HRV) were evaluated using standard electrocardiography and 24-hr Holter monitoring at the initial and follow-up study of the 6-12 months intervals.

Results: The DS group had significantly higher P dispersion (p = 0.017), QT and QTc dispersion values (p <  0.001 for two parameters) than the control group. Most HRV parameters, such as SDNN (p <  0.001), SDANN5 (p <  0.001), SDANN-index (p = 0.001), and RMSSD (p = 0.006) were all significantly lower in the DS group than in the control group. The mean values of initial QTc, QTc dispersion, and HRV parameters showed significantly increase (QTc and QTc dispersion) and decrease (HRV) in the follow-up study (mean duration: 1.2 ± 0.5 years) in 13 DS children. ± On multivariate regression analysis, epilepsy duration had an independently significant effect for the longitudinal change of QTc, QTc dispersion, and HRV.

Conclusions: DS children had significant different values of cardiac electrical and autonomic function compared with control group. Particularly, longer duration of epilepsy was significantly negative effect on the longitudinal change of cardiac autonomic function.
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http://dx.doi.org/10.1016/j.eplepsyres.2019.02.018DOI Listing
May 2019