Publications by authors named "Jong Ok Kim"

39 Publications

Deep Dichromatic Model Estimation Under AC Light Sources.

IEEE Trans Image Process 2021 10;30:7064-7073. Epub 2021 Aug 10.

The dichromatic reflection model has been popularly exploited for computer vison tasks, such as color constancy and highlight removal. However, dichromatic model estimation is an severely ill-posed problem. Thus, several assumptions have been commonly made to estimate the dichromatic model, such as white-light (highlight removal) and the existence of highlight regions (color constancy). In this paper, we propose a spatio-temporal deep network to estimate the dichromatic parameters under AC light sources. The minute illumination variations can be captured with high-speed camera. The proposed network is composed of two sub-network branches. From high-speed video frames, each branch generates chromaticity and coefficient matrices, which correspond to the dichromatic image model. These two separate branches are jointly learned by spatio-temporal regularization. As far as we know, this is the first work that aims to estimate all dichromatic parameters in computer vision. To validate the model estimation accuracy, it is applied to color constancy and highlight removal. Both experimental results show that the dichromatic model can be estimated accurately via the proposed deep network.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2021.3100550DOI Listing
August 2021

Ghost-Free Deep High-Dynamic-Range Imaging Using Focus Pixels for Complex Motion Scenes.

IEEE Trans Image Process 2021 19;30:5001-5016. Epub 2021 May 19.

Multi-exposure image fusion inevitably causes ghost artifacts owing to inaccurate image registration. In this study, we propose a deep learning technique for the seamless fusion of multi-exposed low dynamic range (LDR) images using a focus-pixel sensor. For auto-focusing in mobile cameras, a focus-pixel sensor originally provides left (L) and right (R) luminance images simultaneously with a full-resolution RGB image. These L/R images are less saturated than the RGB images because they are summed up to be a normal pixel value in the RGB image of the focus pixel sensor. These two features of the focus pixel image, namely, relatively short exposure and perfect alignment are utilized in this study to provide fusion cues for high dynamic range (HDR) imaging. To minimize fusion artifacts, luminance and chrominance fusions are performed separately in two sub-nets. In a luminance recovery network, two heterogeneous images, the focus pixel image and the corresponding overexposed LDR image, are first fused by joint learning to produce an HDR luminance image. Subsequently, a chrominance network fuses the color components of the misaligned underexposed LDR input to obtain a 3-channel HDR image. Existing deep-neural-network-based HDR fusion methods fuse misaligned multi-exposed inputs directly. They suffer from visual artifacts that are observed mostly in saturated regions because pixel values are clipped out. Meanwhile, the proposed method reconstructs missing luminance with aligned unsaturated focus pixel image first, and thus, the luma-recovered image provides the cues for accurate color fusion. The experimental results show that the proposed method not only accurately restores fine details in saturated areas, but also produce ghost-free high-quality HDR images without pre-alignment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2021.3077137DOI Listing
May 2021

Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression.

Diagnostics (Basel) 2021 Mar 1;11(3). Epub 2021 Mar 1.

Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea.

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were , , , , , , , and . TNBC had significantly lower mutation frequency in (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], = 0.009), but higher mutation frequency in (TNBC vs. HRPBC, = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC ( = 0.004) due to HRPBC ( < 0.001). TNBC with high Ki-67/unmutated /mutated appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated /mutated may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11030416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000916PMC
March 2021

Deep Dichromatic Guided Learning for Illuminant Estimation.

IEEE Trans Image Process 2021 ;30:3623-3636

A new dichromatic illuminant estimation method using a deep neural network is proposed. Previous methods based on the dichromatic reflection model commonly suffer from inaccurate separation of specularity, thus being limited in their use in a real-world. Recent deep neural network-based methods have shown a significant improvement in the estimation of the illuminant color. However, why they succeed or fail is not explainable easily, because most of them estimate the illuminant color at the network output directly. To tackle these problems, the proposed architecture is designed to learn dichromatic planes and their confidences using a deep neural network with novel losses function. The illuminant color is estimated by a weighted least mean square of these planes. The proposed dichromatic guided learning not only achieves compelling results among state-of-the-art color constancy methods in standard real-world benchmark evaluations, but also provides a map to include color and regional contributions for illuminant estimation, which allow for an in-depth analysis of success and failure cases of illuminant estimation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2021.3062729DOI Listing
January 2021

Comparison of Ki-67 Labeling Index Patterns of Diffuse Large B-Cell Lymphomas and Burkitt Lymphomas Using Image Analysis: A Multicenter Study.

Diagnostics (Basel) 2021 Feb 19;11(2). Epub 2021 Feb 19.

Department of Hospital Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul 06591, Korea.

Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma found in Korea; it manifests with a variety of cellular morphologies and a high proliferation index. It is difficult to differentiate between DLBCL and Burkitt lymphoma (BL) based on immunohistochemistry, histology, and Epstein-Barr virus infection status owing to the overlap in findings. In this study, we performed comparative morphometric analysis to understand the proportional difference in Ki-67 staining between DLBCL and BL. We analyzed Ki-67-stained slides of 103 DLBCLs and 29 BLs that were pathologically confirmed using a three-tier classification system (negative, 1+, 2+, and 3+) to compare Ki-67 expression between BL and activated B-cell and germinal center B-cell subtypes of DLBCL and DLBCL with high proliferation indices (>90% of 2+ and 3+ cells). Patients with DLBCL were older than those with BL (62.1 versus 51.0 years). The number and proportion of negative cells (passenger and true negative cells) were significantly lower in BLs than those in DLBCLs (337.4, 5.9% versus 690.3, 12.4%). The number and proportion of 3+ cells were significantly higher in BLs than those in DLBCLs (5213.6, 96.3% versus 3132.4, 62.0%). BLs and DLBCLs with a high proliferation index showed similar results as those between BLs and overall DLBCLs. We were able to differentiate BLs and DLBCLs with 98.1% sensitivity and 100.0% specificity using an optimal cut-off of 97.9% of 2+/3+ Ki-67-positive cells. Thus, the Ki-67 labeling index may be a good differential biomarker for DLBCLs and BLs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11020343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922648PMC
February 2021

Identification of Differentially Expressed Genes Associated with Extracellular Matrix Degradation and Inflammatory Regulation in Calcific Tendinopathy Using RNA Sequencing.

Calcif Tissue Int 2020 11 9;107(5):489-498. Epub 2020 Aug 9.

Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, Republic of Korea.

Calcific tendinopathy (CT), developed due to calcium hydroxyapatite deposition in the rotator cuff tendon, mostly affects women in their 40 s and 50 s and causes severe shoulder pain. However, the molecular basis of its pathogenesis and appropriate treatment methods are largely unknown. In this study, we identified 202 differentially expressed genes (DEGs) between calcific and adjacent normal tendon tissues of rotator cuff using RNA sequencing-based transcriptome analysis. The DEGs were highly enriched in extracellular matrix (ECM) degradation and inflammation-related processes. Further, matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 13 (MMP13), two of the enzymes associated with ECM degradation, were found to be highly upregulated 25.85- and 19.40-fold, respectively, in the calcific tendon tissues compared to the adjacent normal tendon tissues. Histopathological analyses indicated collagen degradation and macrophage infiltration at the sites of calcific deposit in the rotator cuff tendon. Our study acts as a foundation that may help in better understanding of the pathogenesis associated with CT, and thus in better management of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00223-020-00743-xDOI Listing
November 2020

Ambient light robust gamut mapping for optical see-through displays.

Opt Express 2020 May;28(10):15392-15406

An optical see-through (OST) display is affected more severely by ambient light than any other type of displays when placed in an outdoor environment with bright illuminance because of its transparency and thus, its inherent color distortion can worsen. It is hard to directly apply existing gamut mapping methods to an OST display because of its morphological gamut characteristic and the effect of ambient light. In this paper, we propose a new robust gamut mapping method which works against bright ambient light. The process is divided into two steps: lightness mapping (LM) and chroma reproduction. LM aligns the lightness level of sRGB gamut with OST gamut and partitions the region of OST gamut based on the relative size of the sRGB gamut and its lightness value. The second step (chroma reproduction) determines an appropriate chroma reproduction method (gamut compression or extension) and a proper direction for gamut mapping based on the characteristics of each region in order to minimize the effects of ambient light. The quality of color reproduction is qualitatively and quantitatively evaluated based on accurate measurements of the displayed colors. It has been experimentally confirmed that the proposed gamut mapping method can reduce color distortion more than the existing parametric gamut mapping algorithms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.391447DOI Listing
May 2020

Eupatilin Ameliorates Cerulein-Induced Pancreatitis Via Inhibition of the Protein Kinase D1 Signaling Pathway In Vitro.

Pancreas 2020 02;49(2):281-289

Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.

Objective: The aim of this study was to investigate the effects of eupatilin on protein kinase D1 (PKD1) and nuclear factor kappa B (NF-κB) signaling pathways in cerulein-induced in vitro pancreatitis.

Methods: We used collagenase digestion to isolate pancreatic acinar cells from male C57BL/6 mice. In vitro acute pancreatitis was induced by treatment with a supramaximal dose of cerulein. Eupatilin was pretreated before stimulation with cerulein.

Results: Eupatilin significantly reduced cerulein-induced amylase release in pancreatic acini. Eupatilin treatment downregulated cerulein-induced expression of interleukin (IL)-1β, IL-6, and CC chemokine ligands 2 and 5, but it upregulated expression of IL-4 and IL-10. We demonstrated that eupatilin pretreatment attenuated cerulein-induced necrosis in isolated pancreatic acinar cells. This effect of eupatilin was confirmed by lactic dehydrogenase assay, fluorescence-activated cell sorting analysis, and cytopathologic analysis. Eupatilin inhibited cerulein-induced activation of PKD1/NF-κB and the nuclear translocation of NF-κB.

Conclusions: Our data demonstrated that eupatilin is a potential therapeutic candidate for the treatment of pancreatitis through its ability to reduce cellular necrosis and inflammatory responses by inhibition of the PKD1/NF-κB signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001488DOI Listing
February 2020

Noise-Robust Iterative Back-Projection.

IEEE Trans Image Process 2019 Sep 16. Epub 2019 Sep 16.

Noisy image super-resolution (SR) is a significant challenging process due to the smoothness caused by denoising. Iterative back-projection (IBP) can be helpful in further enhancing the reconstructed SR image, but there is no clean reference image available. This paper proposes a novel back-projection algorithm for noisy image SR. Its main goal is to pursuit the consistency between LR and SR images. We aim to estimate the clean reconstruction error to be back-projected, using the noisy and denoised reconstruction errors. We formulate a new cost function on the principal component analysis (PCA) transform domain to estimate the clean reconstruction error. In the data term of the cost function, noisy and denoised reconstruction errors are combined in a region-adaptive manner using texture probability. In addition, the sparsity constraint is incorporated into the regularization term, based on the Laplacian characteristics of the reconstruction error. Finally, we propose an eigenvector estimation method to minimize the effect of noise. The experimental results demonstrate that the proposed method can perform back-projection in a more noise-robust manner than the conventional IBP, and harmoniously work with any other SR methods as a post-processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2019.2940414DOI Listing
September 2019

A rare collision tumor comprising intracystic papillary neoplasm associated with adenocarcinoma and angiosarcoma in the gallbladder.

Korean J Intern Med 2020 05 31;35(3):732-733. Epub 2019 Jul 31.

Department of Pathology, College of Medicine, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3904/kjim.2018.394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214352PMC
May 2020

Alternative splicing induces cytoplasmic localization of RBFOX2 protein in calcific tendinopathy.

Exp Mol Pathol 2019 08 23;109:36-41. Epub 2019 May 23.

Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, Republic of Korea. Electronic address:

Background: Calcific tendinopathy (CT) is characterized by deposits of calcium, most commonly found in the shoulder tendons. The exact cause and pathogenesis of CT are not fully understood. This study analyzed the expression pattern of RNA-binding protein fox-1 homolog 2 (RBFOX2), a crucial splicing regulator in tissue differentiation.

Methods: Normal and calcific tendons were compared for RBFOX2 mRNA level using quantitative reverse-transcription polymerase chain reaction. Intracellular localization of RBFOX2 protein was investigated using immunofluorescence microscopy. Normal and calcific tendon cDNAs were used to clone RBFOX2. Sequencing analysis identified coding sequences of the RBFOX2 isoform.

Results: The intracellular localization of RBFOX2 protein differed with disease status, with RBFOX2 localized in the cytoplasm in calcific tendons and the nucleus in normal tendons. Analysis of the RBFOX2 protein-coding sequence showed that exon 10, responsible for nuclear localization, was absent in calcific tendons. Splicing of RBFOX2 target genes CHD2 and MBNL1 was significantly affected by cytoplasmic localization of RBFOX2 in calcific tendons.

Discussion: Given the function of RBFOX2 as a splicing regulator in the nucleus, cytoplasmic localization of RBFOX2 protein in calcific tendons may have affected overall splicing events and altered gene expression. These results provide insights for comprehension of CT pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexmp.2019.104264DOI Listing
August 2019

Negative pressure is not necessary for using fine-needle aspiration biopsy to diagnose suspected thyroid nodules: a prospective randomized study.

Ann Surg Treat Res 2019 May 24;96(5):216-222. Epub 2019 Apr 24.

Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea.

Purpose: Fine-needle aspiration biopsy (FNAB) can be used to diagnose thyroid cancer and other tumors. Although FNAB without negative pressure (FNAB-P) reduces the risk of blood contamination, FNAB with negative pressure (FNAB+P) increases the sensitivity of the biopsy results. Therefore, we performed a randomized study of FNAB with or without negative pressure to identify the better diagnostic method.

Methods: Between March 2016 and February 2017, 172 consecutive patients were enrolled to investigate >0.5 cm nodules with indeterminate or suspicious malignant features. Patients were randomly assigned to the FNAB+P group (a 50 mL syringe was used to provide negative pressure) or to the FNAB-P group (passive collection of blood in the needle's hub). The 2 methods' diagnostic adequacy and quality were evaluated using an objective scoring system. The study's protocol was registered with the World Health Organization Clinical Research Information Service (http://cris.nih.go.kr/cris, KCT0001857).

Results: The patients were randomly assigned to the FNAB+P group (n = 86) or the FNAB-P group (n = 86). There were no significant intergroup differences in nodule position, size, age, consistency, calcification, mutation, or pathology. Evaluation of diagnostic adequacy parameters revealed no significant differences in background blood/clot (P = 0.728), amount of cellular material (P = 0.052), degree of cellular degeneration (P = 0.622), degree of cellular trauma (P = 0.979), or retention of appropriate architecture (P = 0.487). Furthermore, there was no significant intergroup difference in the diagnostic quality (P = 0.634).

Conclusion: This prospective randomized study failed to detect significant differences in the diagnostic adequacy and quality of FNAB with or without negative pressure. Therefore, the examiner may select whichever FNAB method they prefer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4174/astr.2019.96.5.216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483928PMC
May 2019

A rare case of multiple and huge simple bone cysts in Wilson's disease.

J Orthop Surg (Hong Kong) 2019 May-Aug;27(2):2309499019843141

3 Department of Pathology, Daejeon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Jung-gu, Daejeon, Republic of Korea.

A simple bone cyst is a tumor-like lesion that is not a true neoplasm. It usually presents as a solitary lesion within the proximal humerus and proximal femur. The etiology of simple bone cysts is still to be elucidated. We describe our experience in the successful surgical management of a rare case of two, large-sized, simple bone cysts involving the entire left humerus and right femoral head, respectively, in a 34-year-old male patient with Wilson's disease and concomitant hepatic cirrhosis. We theorized that Wilson's disease could be the cause of the delay or blockage of the natural healing process of the simple long-bone cysts, leading to their abnormal growth and development. To our knowledge, such a combined occurrence of multiple, simple long-bone cysts and Wilson's disease has not been reported in the literature to date.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2309499019843141DOI Listing
April 2020

Plasmablastic lymphoma presenting with ileocecal intussusception in an immunocompetent patient.

Korean J Intern Med 2020 07 28;35(4):1018-1019. Epub 2019 Feb 28.

Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3904/kjim.2018.405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373955PMC
July 2020

Dexamethasone Facilitates NF-κB Signal Pathway in TNF-α Stimulated Rotator Cuff Tenocytes.

J Microbiol Biotechnol 2019 Feb;29(2):297-303

Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Republic of Korea.

Corticosteroids are commonly used for pain control in rotator cuff tear. Deregulated NF-κB activation is a hallmark of chronic inflammatory diseases and has been responsible for the pathogenesis of rotator cuff tear. The Dexamethasone(DEXA) is a synthetic corticosteroid. The purpose of this study was to examine the exact effect of dexamethasone on NF-κB signaling in rotator cuff tear. We measured NF-κB expression in four groups: control, TNF-α-treated, DEXA-treated, and combined treatment with TNF-α and DEXA. Tenocytes were isolated from patients with rotator cuff tears and pre-incubated with TNF-α (10 ng/ml), DEXA (1 µM), or both of them for 10 min, 1 h, and 2 h. Expression of p65, p50, and p52 in the nuclei and cytosol was analyzed by western blotting and immunofluorescence imaging using confocal microscopy. We also evaluated nucleus/cytosol (N/C) ratios of p65, p50, and p52. In our study, the combined treatment with DEXA and TNF-α showed increased N/C ratios of p65, p50, and p52 compared with those in the TNF-α group at all time points. Additionally, in the DEXA group, N/C ratios of p65, p50, and p52 gradually increased from 10 min to 2 h. In conclusion, DEXA promoted the nuclear localization of p65, p50, and p52, but was not effective in inhibiting the inflammatory response of TNF-α-stimulated rotator cuff tear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4014/jmb.1810.10051DOI Listing
February 2019

Improving Color Constancy in an Ambient Light Environment Using the Phong Reflection Model.

IEEE Trans Image Process 2018 Apr;27(4):1862-1877

We present a physics-based illumination estimation approach explicitly designed to handle natural images under ambient light. Existing physics-based color constancy methods are theoretically perfect but do not handle real-world images well because the majority of these methods assume a single illuminant. Therefore, specular pixels selected using existing methods produce estimated dichromatic lines that are thick or curvilinear in the presence of ambient light, thus generating significant errors. Based on the Phong reflection model, we show that a group of specular pixels on a uniformly colored object, although they are subject to intensity thresholding, produce a unique dichromatic line length depending on the geometry of each image path. Assuming that the longest dichromatic line is the most desirable when estimating the chromaticity of an illuminant, ambient-robust specular pixels are also found on the same path on which the longest dichromatic line segment is generated. Therefore, we propose a method to find the optimal image path in which the specular pixels produce the longest dichromatic line. Even though the number of collected specular pixels is reduced using the proposed method, they are proven to be more accurate when determining the illuminant chromaticity even in the existing methods. Experiments with an established benchmark data set and a self-produced image set find that the proposed method is better able to locate the illuminant chromaticity compared with the state-of-the-art color constancy methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2017.2785290DOI Listing
April 2018

Autophagy-mediated upregulation of cytoplasmic claudin 1 stimulates the degradation of SQSTM1/p62 under starvation.

Biochem Biophys Res Commun 2018 01 4;496(1):159-166. Epub 2018 Jan 4.

Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, 34134, Republic of Korea. Electronic address:

Claudin 1, a major tight junction protein, is highly expressed in various types of tumors such as thyroid, breast, and colorectal cancers. Moreover, claudin 1 is frequently found in the cytoplasm in various types of tumor cells. However, the cytoplasmic function of claudin 1 in tumors still remains largely unknown. Here, we investigated the novel function of cytoplasmic claudin 1 in autophagy. The mRNA expression level of claudin 1 was higher in several types of tumors than in normal tissues. Furthermore, colon tumor tissues showed increased autophagy compared with the adjacent normal tissues. Both endogenous and exogenous claudin 1 showed a cytoplasmic punctate staining pattern and were co-stained with the lysosome-associated membrane protein 1 (LAMP1). Importantly, autophagy-induced conditions, including starvation, increased the protein stability of claudin 1. Moreover, the increased level of claudin 1 stimulated autophagy by decreasing the level of the autophagy substrate, sequestosome1/p62 (SQSTM1), under autophagy-inducing conditions; activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR). Taken together, we demonstrate that the novel function of cytoplasmic claudin 1 is related to autophagy. This study is the first to show a cytoplasmic function of claudin 1 as an autophagy regulator and provides the evidence that claudin 1-mediated autophagy regulation is an integral part of the mechanism by which claudin 1 regulates cancer progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2018.01.017DOI Listing
January 2018

Rotator cuff bridging repair using acellular dermal matrix in large to massive rotator cuff tears: histologic and clinical analysis.

J Shoulder Elbow Surg 2017 Nov 10;26(11):1897-1907. Epub 2017 Jul 10.

Department of Orthopedic Surgery, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon, Republic of Korea.

Background: This study investigated the efficacy of the bridging repair using an acellular dermal matrix (ADM) and an ADM with stem cells in rabbits. Also investigated were clinical outcomes of ADM bridging repair for large to massive rotator cuff tears.

Materials And Methods: ADM, with and without stem cells, was used to cover a 5- × 5-mm-sized cuff defect in 17 rabbits, and biomechanical, histologic, and immunohistochemical analyses were conducted. Also evaluated were 24 patients with large to massive rotator cuff tears after ADM bridging repair.

Results: In the biomechanical test, the normal rotator cuff, cuff with ADM plus stem cells, and cuff with ADM in the rabbit model showed a maximum load (N) of 287.3, 217.5, and 170.3 and ultimate tensile strength (N/mm) of 11.1, 8.0, and 5.2, respectively. Histologically, the cuff tendons with the ADM or ADM plus stem cells showed characteristically mature tendons as time passed. In the clinical study, the mean American Shoulder and Elbow Surgeons score improved from preoperative 50 to postoperative 83, the University of California Los Angeles Shoulder Rating Scale from 17 to 30, and the Simple Shoulder Test from 4 to 8, respectively. No further fatty deteriorations or muscle atrophy were observed on follow-up magnetic resonance imaging. A retear was found in 5 of 24 patients (21%).

Conclusions: Bridging repair with ADM or stem cells in the rabbit model showed cellular infiltration into the graft and some evidence of neotendon formation. Clinically, ADM repair was a safe alternative that did not show any further fatty deterioration nor muscle atrophy in large to massive rotator cuff tears.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jse.2017.04.010DOI Listing
November 2017

RBFOX3 regulates Claudin-1 expression in human lung tissue via attenuation of proteasomal degradation.

Biosci Rep 2017 02 23;37(1). Epub 2017 Feb 23.

Department of Biochemistry, Chungnam National University, Daejeon 34134, Republic of Korea

RBFOX3, a nuclear RNA-binding protein, is well known as a regulator of alternative pre-mRNA splicing during neuronal development. However, other functions of RBFOX3 are poorly understood. Here, we investigated the function of RBFOX3 in the cytoplasm with respect to regulation of Claudin-1 expression. In human lung tissue, Claudin-1 is higher in RBFOX3-positive cells than in RBFOX3-negative cells. Immunostaining and mRNA quantification revealed that protein levels, but not mRNA levels, of Claudin-1 are increased by RBFOX3. In addition, cycloheximide treatment of human lung cancer cells revealed that RBFOX3 increases the stability of Claudin-1 through attenuation of its ubiquitination. Our study provides insights into the molecular mechanisms by which RBFOX3 regulates Claudin-1 expression in human lung tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20160623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322747PMC
February 2017

Regeneration of thyroid follicles from primordial cells in a murine thyroidectomized model.

Lab Invest 2017 04 23;97(4):478-489. Epub 2017 Jan 23.

Research Center for Endocrine and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.

The functional unit of the thyroid gland, the thyroid follicle, dynamically responds to various stimuli to maintain thyroid hormone homeostasis. However, thyroid follicles in the adult human thyroid gland have a very limited regenerative capacity following partial resection of the thyroid gland. To gain insight into follicle regeneration in the adult thyroid gland, we observed the regeneration processes of murine thyroid follicles after partial resection of the lower third of the thyroid gland in 10-week-old male C57BL/6 mice. Based on sequential observation of the partially resected thyroid lobe, we found primitive follicles forming in the area corresponding to the central zone of the intact lateral thyroid lobe. The primitive thyroid follicles were multiciliated and had coarsely vacuolated cytoplasm and large vesicular nuclei. Consistently, these primitive follicular cells did not express the differentiation markers paired box gene-8 and thyroid transcription factor-1 (clone SPT24), but were positive for forkhead box protein A2 and leucine-rich repeat-containing G-protein-coupled receptor 4/GPR48. Follicles newly generated from the primitive follicles had clear or vacuolar cytoplasm with dense, darkly stained nuclei. At day 21 after partial thyroidectomy, the tall cuboidal follicular epithelial cells had clear or vacuolar cytoplasm, and the intraluminal colloid displayed pale staining. Smaller activated follicles were found in the central zone of the lateral lobe, whereas larger mature follicles were located in the peripheral zone. Based on these observations, we propose that the follicle regeneration process in the partially resected adult murine thyroid gland associated with the appearance of primitive follicular cells may be a platform for the budding of differentiated follicles in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/labinvest.2016.158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886286PMC
April 2017

Potentiation of the anticancer effects of everolimus using a dual mTORC1/2 inhibitor in hepatocellular carcinoma cells.

Oncotarget 2017 Jan;8(2):2936-2948

Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

There is lots of evidence to support the critical involvement of mTOR signaling in the carcinogenesis of hepatocellular carcinoma (HCC). However, it has not been determined how the roles of individual mTORC1 and mTORC2 inhibitors played in the HCC therapeutics. We thus compared the effects of everolimus, Ku0063794, and a combination of the two therapies on HCC cells, using various in vitro studies (HepG2, Hep3B, and Huh7 cells), ex vivo culturing of HCC tissues obtained from patients, and the in vivo mouse xenograft model of HCC cells. Our in vitro, ex vivo, and in vivo experiments consistently demonstrated that everolimus and Ku0063794 combination therapy was superior to individual monotherapies, as manifested by higher reduction of proliferation, migration, and invasion of HCC cells, and the higher inhibition of EMT process as well. Although individual monotherapies could not inhibit SIRT1 (positive regulator of EMT) expression, the combination therapy significantly inhibited SIRT1 expression. However, overexpression of SIRT1 mitigated the EMT-inhibiting effect of the combination therapy, suggesting that the combination therapy inhibits the EMT by way of suppressing SIRT1 expression. Therefore, when considering everolimus as an anti-HCC agent, the improved anticancer effects provided by combining it with an inhibitor of both mTORC1 and mTORC2 should be recognized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356853PMC
January 2017

Defective ciliogenesis in thyroid hürthle cell tumors is associated with increased autophagy.

Oncotarget 2016 Nov;7(48):79117-79130

Research Center for Endocrine and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine, Jung-gu, Daejeon 35015, Republic of Korea.

Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hürthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland. However, most Hürthle cells found in benign and malignant thyroid diseases were devoid of primary cilia. Conventional variant of papillary carcinoma (PTC) displayed longer primary cilia than those of healthy tissue, whereas both the frequency and length of primary cilia were decreased in oncocytic variant of PTC. In addition, ciliogenesis was markedly defective in primary Hürthle cell tumors, including Hürthle cell adenomas and carcinomas, which showed higher level of autophagosome biogenesis. Remarkably, inhibition of autophagosome formation by Atg5 silencing or treatment with pharmacological inhibitors of autophagosome formation restored ciliogenesis in the Hürthle cell carcinoma cell line XTC.UC1 which exhibits a high basal autophagic flux. Moreover, the inhibition of autophagy promoted the accumulation of two factors critical for ciliogenesis, IFT88 and ARL13B. These results suggest that abnormal ciliogenesis, a common feature of Hürthle cells in diseased thyroid glands, is associated with increased basal autophagy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.12997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346702PMC
November 2016

Transforming Growth Factor-β-Induced RBFOX3 Inhibition Promotes Epithelial-Mesenchymal Transition of Lung Cancer Cells.

Mol Cells 2016 Aug 19;39(8):625-30. Epub 2016 Jul 19.

Department of Biochemistry, Chungnam National University, Daejeon 34134, Korea.

The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-β (TGF-β) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-β1 treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as E-cadherin and Claudin-1, during TGF-β1-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-β-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14348/molcells.2016.0150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990755PMC
August 2016

Secretome from human adipose-derived stem cells protects mouse liver from hepatic ischemia-reperfusion injury.

Surgery 2015 May 20;157(5):934-43. Epub 2015 Feb 20.

Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea. Electronic address:

Background: Despite widespread interest in stem cells, their clinical application is largely limited owing to safety and cost concerns. We intended to overcome these limitations by evaluating whether the secretome of human adipose tissue-derived stem cells (ASCs) could be used to reverse ischemia/reperfusion (IR) injury in mice.

Methods: After establishment of hepatic IR injury in BALB/c mice, the mice were infused with saline solution (saline group), 1.0 × 10⁶ human ASCs (ASC group), 25-fold-concentrated ASC-conditioned medium (ASC-secretome group), which was the same volume as used for the ASC infusion, or concentrated control medium (medium-only group). After reperfusion, we obtained serum and liver specimens and compared parameters reflecting the degree of injury and mechanisms between the groups.

Results: At 6 hours after reperfusion, serum interleukin (IL)-6 levels were decreased in both ASC and ASC-secretome groups (P < .05). At 12 and 24 hours after reperfusion, both ASC and ASC-secretome groups also demonstrated lesser histologic scores than did their controls (P < .05). In addition, the decreases in the expression of the cell adhesion markers intercellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1 and in neutrophil infiltration into the liver were noted in the ASC-secretome group as well as in the ASC group.

Conclusion: ASC and ASC-secretome infusions both alleviated liver damage and improved the liver microenvironment after hepatic IR injury. Our results indicate that the therapeutic potential of ASCs may result from a paracrine effect mediated by the ASC secretome; our work suggests a novel secretome-based therapeutic strategy to treat hepatic IR injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2014.12.016DOI Listing
May 2015

A case of rapidly progressing leiomyosarcoma combined with squamous cell carcinoma in the esophagus.

World J Gastroenterol 2013 Aug;19(32):5385-8

Division of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary's Hospital, Catholic University of Korea, Daejeon 301-723, South Korea.

Esophageal leiomyosarcoma is a rare tumor that accounts for less than 1% of all malignant esophageal tumors. Esophageal leiomyosarcoma combined with squamous cell carcinoma is even rarer than solitary leiomyosarcoma. We experienced a case of leiomyosarcoma combined with squamous cell carcinoma that progressed very rapidly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v19.i32.5385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752576PMC
August 2013

A rare case of primary malignant small cell carcinoma combined with urothelial cell carcinoma in the ureter.

World J Surg Oncol 2013 Aug 8;11(1):181. Epub 2013 Aug 8.

Department of Urology, The Catholic University of Korea Daejeon St, Mary's Hospital, Daeheung-dong, Jung-gu, Daejeon, 301-723, Korea.

Background: Extrapulmonary small cell carcinomas have been reported in a variety of organs, and their incidence in the genitourinary tract is second only to that in the gastrointestinal tract. To date, however, only a few cases of small cell carcinoma of the ureter have been reported. Because the extreme rarity of this type of carcinoma, its clinical behaviour, diagnostic methods, and effective treatment modalities have not yet been determined.

Case Presentation: A 59-year-old man presented with a 1-month history of painless gross haematuria. Urine cytopathology revealed a urothelial carcinoma and computed tomography revealed left hydronephroureterosis with a distal ureteral stone and a mildly enhanced fungating mass just below the stone-impacted site. The preoperative TNM stage was T2N0M0. The patient underwent simultaneous diagnostic ureterorenoscopy and left laparoscopic nephroureterectomy with bladder cuff resection. Gross examination showed a 3.5 × 3.0 × 0.8 cm white, partly yellow mass in the left distal ureter. Light microscopy showed a small cell carcinoma, overlaid on a urothelial carcinoma in situ, invading the ureter and external lateral resection margins. The small cell carcinoma was diffusely positive for neuron-specific enolase, and exhibited focal positivity for CD 56, synaptophysin, chromogranin and cytokeratin 20. The patient was treated with adjuvant chemotherapy, consisting of cisplatin and etoposide, and radiation therapy, and has been well, without evidence of tumour recurrence or metastasis in the 10 months after surgery.

Conclusion: Small cell carcinoma of the ureter is rare. Although its clinical behaviour and diagnostic modalities have not been determined and it has yet to be diagnosed immunohistopathologically, multimodality treatment including surgery, chemotherapy and radiotherapy may improve patient survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1477-7819-11-181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751368PMC
August 2013

Factors influencing the detection of the BRAF T1799A mutation in papillary thyroid carcinoma.

Oncol Rep 2011 Jun 22;25(6):1639-44. Epub 2011 Mar 22.

Department of Internal Medicine, Daejeon St Mary's Hospital, College of Medicine, The Catholic University of Korea, 520-2 Daeheung-dong, Jung-gu, Daejeon 301-723, Republic of Korea.

The BRAF T1799A mutation is a heterozygous point mutation and its reported prevalence in papillary thyroid carcinoma (PTC) has varied from 29 to 83%, with an overall mean of 44%. In Korea, the reported mutation rate reached 83% in PTC and 52% in micropapillary carcinoma. We hypothesized that the differences in prevalence may be influenced by the methods of mutation analysis, the sizes of tumor and ethnic differences. Three types of DNA samples from the same PTC mass (0.4-1.6 cm, mean 0.83 cm sized) per each patient (n=17) were isolated. The first type was obtained from frozen PTC tissues using laser-captured microdissection (Frozen-laser, n=17), the second was obtained from frozen tissue by manual tumor margin dissection using a blade (Frozen-blade, n=17) and the third was obtained from formalin-fixed, paraffin-embedded tissue by manual margin dissection (Paraffin-blade, n=15, 2 failed). The mutation rates of the three-matched DNA samples were compared by the SNP mode and AQ mode of pyrosequencing, and direct DNA sequencing. Both the AQ mode of pyrosequencing and the direct DNA sequencing detected the BRAF T1799A mutation in 100% of the 'Frozen-laser' samples, but the mutation was omitted in 1/17 of the 'Frozen-blade' samples and in 5/15 of the 'Paraffin-blade' samples, while the former was more rapid and objective than the latter. The SNP mode of pyrosequencing variably detected the mutation from 40 to 100%, and it showed the lowest sensitivity. Our results indicate that the reported prevalence of the BRAF T1799A mutation in PTC can be underestimated due the mutation analysis methods, and especially in small PTCs. The BRAF T1799A mutation may be an early and essential carcinogenic event in nearly all Korean PTCs, and even in micro-PTCs. For the accurate detection of the BRAF T1799A mutation from small PTCs, fresh or frozen tissues and more cautious microdissection are required, and the AQ mode of pyrosequencing assay is preferred.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2011.1225DOI Listing
June 2011

A rare calcified thrombosis of the dilated epidural venous plexus presenting with lumbar radiculopathy: a case report.

Spine J 2011 Feb;11(2):e28-31

Department of Radiology, Daejeon St. Mary's Hospital, The Catholic University of Korea, 520-2 Deaheung-dong, Jung-gu, Daejeon 301-723, Republic of Korea.

Background Context: Lumbar radiculopathies may occur in the course of many diseases but are rarely caused by abnormalities or pathologic changes in the epidural venous plexus. We describe a patient with lumbar radiculopathy attributable to a thrombolith of the epidural venous plexus, as diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI), and who was treated by hemilaminectomy and removal of the thrombolith.

Purpose: To document the first report of thrombolith in the dilated vertebral epidural venous plexus presenting as a lumbar radiculopathy.

Study Design/setting: A case report and literature review.

Methods: A 72-year-old woman presented with a 2-year history of back pain radiating to the left buttock without a history of any trauma. Lumbar spinal CT and MRI showed a calcified lesion in the left epidural space at the L1 level.

Results: The patient was treated by hemilaminectomy at the T12-L1 level and left epidural mass excision. Histopathology confirmed a thrombolith in the left epidural malformed venous plexus.

Conclusions: A thrombolith causing a lumbar radiculopathy in the dilated epidural venous plexus is a rare condition. If CT or MRI shows a vertebral epidural calcified lesion, an epidural venous thrombolith may be included in the differential diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.spinee.2010.12.016DOI Listing
February 2011

Epidural block-induced ligamentum flavum hematoma mimicking epidural hematoma in the lumbar spine: a case report.

Spine J 2011 Feb;11(2):e23-7

Department of Radiology, Daejeon St. Mary's Hospital, The Catholic University of Korea, 520-2 Daeheung-dong, Jung-gu, Daejeon 301-723, Republic of Korea.

Background Context: The ligamentum flavum may undergo various pathologic changes, including hypertrophy, calcification, ossification, and cyst formation. Ligamentum flavum hematoma (LFH) is a rare cause of spinal nerve root or cord compression and usually occurs in the lumbar spine. We report a 66-year-old woman with LFH occurring after an epidural block, mimicking epidural hematoma on lumbar spine magnetic resonance imaging (MRI).

Purpose: To document MRI findings of epidural block-induced LFH mimicking epidural hematoma.

Study Design/setting: A case report.

Methods: A 66-year-old woman presented with a 6-month history of pain in the left buttock and suffered abrupt weakness and numbness in her left leg after an epidural block procedure without any other trauma history. Lumbar spine MRI with enhancement showed a hematoma-like mass in the posterior epidural space at L3-L4 level.

Results: The patient underwent a left hemilaminectomy at the L3 level, and a surgeon found a small hematoma between inner and outer walls of ligamentum flavum instead of an epidural hematoma and performed the removal of the hypertrophied ligamentum flavum including the intraligamentary lesion. Histopathologic examination confirmed the lesion as hematoma in the left ligamentum flavum. After surgery, the patient recovered without significant neurologic deficit.

Conclusions: Epidural block-induced LFH can mimic posterior epidural hematoma on MRI. Careful evaluation of hematoma, location, and imaging findings is required for accurate diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.spinee.2010.12.014DOI Listing
February 2011

Serial MR imaging of intramuscular hematoma: experimental study in a rat model with the pathologic correlation.

Korean J Radiol 2011 Jan-Feb;12(1):66-77. Epub 2011 Jan 3.

Department of Radiology, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon 301-723, Korea.

Objective: We wanted to demonstrate the temporal changes of the magnetic resonance imaging (MRI) findings in experimentally-induced intramuscular hematomas in rats and to correlate these data with the concurrent pathologic observations.

Materials And Methods: Intramuscular hematoma was induced in 30 rats. The MR images were obtained at 1, 4, 7 and 10 days and at 2, 3, 4, 6 and 8 weeks after muscle injury. The characteristic serial MRI findings were evaluated and the relative signal intensities were calculated. Pathologic specimens were obtained at each time point.

Results: On the T1-weighted imaging (T1WI), the intramuscular hematomas exhibited isointensity compared to that of muscle or the development of a high signal intensity (SI) rim on day one after injury. The high SI persisted until eight weeks after injury. On the T2-weighted imaging (T2WI), the hematomas showed high SI or centrally low SI on day one after injury, and mainly high SI after four days. A dark signal rim was apparent after seven days, which was indicative of hemosiderin on the pathology. The gradient echo (GRE) imaging yielded dark signal intensities at all stages.

Conclusion: Unlike brain hematomas, experimentally-induced intramuscular hematomas show increased SI on both the T1WI and T2WI from the acute stage onward, and this is pathologically correlated with a rich blood supply and rapid healing response to injury in the muscle. On the T2WI and GRE imaging, high SI with a peripheral dark signal rim is apparent from seven days to the chronic stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2011.12.1.66DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017886PMC
April 2011
-->