1.A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer
Chang Min KIM ; Kyong Hwa PARK ; Yun Suk YU ; Ju Won KIM ; Jin Young PARK ; Kyunghee PARK ; Jong-Han YU ; Jeong Eon LEE ; Sung Hoon SIM ; Bo Kyoung SEO ; Jin Kyeoung KIM ; Eun Sook LEE ; Yeon Hee PARK ; Sun-Young KONG
Cancer Research and Treatment 2024;56(4):1113-1125
Purpose:
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods:
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results:
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
2.Analysis of Prognoses according to Breast MRI Results in Patients with Axillary Lymph Node Metastases from an Unknown Primary Origin
E-Ryung CHOI ; Ok Hee WOO ; Eun Young KO ; Boo-Kyung HAN ; Ji Soo CHOI ; Eun Sook KO ; Haejung KIM ; Myoung Kyoung KIM ; Jeong Eon LEE
Yonsei Medical Journal 2023;64(10):633-640
Purpose:
To compare the prognosis of patients with axillary adenocarcinoma from an unknown primary (ACUPax) origin with negative MRI results and those with MRI-detected primary breast cancers.
Materials and Methods:
The breast MRI images of 32 patients with ACUPax without signs of primary breast cancer on mammography and ultrasound (US) were analyzed. Spot compression-magnification mammography and second-look US were performed for the area of MRI abnormality in patients with positive results; any positive findings corresponding to the MRI abnormality were confirmed by biopsy. If suspicious MRI lesions could not be localized on mammography or US, MR-guided biopsy or excision biopsy after MR-guided localization was performed. We compared the prognosis of patients with negative breast MRI with that for patients with MRI-detected primary breast cancers.
Results:
Primary breast cancers were confirmed in 8 (25%) patients after breast MRI. Primary breast cancers were not detected on MRI in 24 (75%) patients, including five cases of false-positive MRI results. Twenty-three patients underwent axillary lymph node dissection (ALND) followed by whole breast radiation therapy (WBRT) and chemotherapy (n=17) or subsequent chemotherapy only (n=2). Recurrence or distant metastasis did not occur during follow up in 7/8 patients with MRI-detected primary breast cancers and 22/24 patients with negative MRI results. Regional recurrence or distant metastasis did not occur in any MR-negative patient who received adjuvant chemotherapy after ALND and WBRT.
Conclusion
The prognoses of MR-negative patients with ACUPax who received ALND and WBRT followed by chemotherapy were as good as those of patients with MRI-detected primary breast cancers.
3.Impact of Skeletal Muscle Loss and Visceral Obesity Measured Using Serial CT on the Prognosis of Operable Breast Cancers in Asian Patients
Mi-ri KWON ; Eun Sook KO ; Min Su PARK ; Woo Kyoung JEONG ; Na Young HWANG ; Jae-Hun KIM ; Jeong Eon LEE ; Seok Won KIM ; Jong Han YU ; Boo-Kyung HAN ; Eun Young KO ; Ji Soo CHOI ; Ko Woon PARK
Korean Journal of Radiology 2022;23(2):159-171
Objective:
This study aimed to investigate the impact of baseline values and temporal changes in body composition parameters, including skeletal muscle index (SMI) and visceral adipose tissue area (VAT), measured using serial computed tomography (CT) imaging on the prognosis of operable breast cancers in Asian patients.
Materials and Methods:
This study retrospectively included 627 Asian female (mean age ± standard deviation [SD], 53.6 ± 8.3 years) who underwent surgery for stage I–III breast cancer between January 2011 and September 2012. Body composition parameters, including SMI and VAT, were semi-automatically calculated on baseline abdominal CT at the time of diagnosis and follow-up CT for post-treatment surveillance. Serial changes in SMI and VAT were calculated as the delta values. Multivariable Cox regression analysis was used to evaluate the association of baseline and delta SMI and VAT values with disease-free survival.
Results:
Among 627 patients, 56 patients (9.2%) had breast cancer recurrence after a median of 40.5 months. The mean value ± SD of the baseline SMI and baseline VAT were 43.7 ± 5.8 cm2 /m2 and 72.0 ± 46.0 cm2 , respectively. The mean value of the delta SMI was -0.9 cm2 /m2 and the delta VAT was 0.5 cm2 . The baseline SMI and VAT were not significantly associated with disease-free survival (adjusted hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.937–1.031; p = 0.475 and adjusted HR, 1.001; 95% CI, 0.995–1.006; p = 0.751, respectively). The delta SMI and VAT were also not significantly associated with disease-free survival (adjusted HR, 0.894; 95% CI, 0.766–1.043; p = 0.155 and adjusted HR, 1.001; 95% CI, 0.989–1.014; p = 0.848, respectively).
Conclusion
Our study revealed that baseline and early temporal changes in SMI and VAT were not independent prognostic factors regarding disease-free survival in Asian patients undergoing surgery for breast cancer.
4.Case of Polymyalgia Rheumatica Misdiagnosed as Infectious Spondylitis.
Kee Eon YOO ; Seoung Wan NAM ; Hyuk Hee KWON ; Seunghun LEE ; Jae Bum JUN ; Yoon Kyoung SUNG ; Soo Kyung CHO
Journal of Rheumatic Diseases 2018;25(2):140-143
A 60-year-old woman visited the authors' clinic with low back pain and arthralgia. Her symptoms had occurred 6 months previously, and she was treated with an epidural injection and a balloon dilatation procedure based on the assumption of spinal stenosis, but both treatments were ineffective. Her low back pain was aggravated, accompanied by fever and chills over a period of 4 months. As a result, she visited another referral hospital and was diagnosed with infective spondylitis associated with the invasive procedure. Her symptoms improved with antibiotics, but they recurred. When she visited our clinic, she still had continuous low back pain and febrile senses. Magnetic resonance imaging of her lumbar spine revealed interspinous bursitis, and 18 F-fluorodeoxyglucose positron emission tomography showed multifocal synovial inflammation. She was diagnosed with polymyalgia rheumatica and treatment was started on prednisolone and celecoxib. Her symptoms improved dramatically and the inflammatory markers normalized.
Anti-Bacterial Agents
;
Arthralgia
;
Back Pain
;
Bursitis
;
Celecoxib
;
Chills
;
Dilatation
;
Female
;
Fever
;
Humans
;
Inflammation
;
Injections, Epidural
;
Low Back Pain
;
Magnetic Resonance Imaging
;
Middle Aged
;
Polymyalgia Rheumatica*
;
Positron-Emission Tomography
;
Prednisolone
;
Referral and Consultation
;
Spinal Stenosis
;
Spine
;
Spondylitis*
5.Decision Making Regarding Key Elements of Korean Disaster Psychiatric Assistance Teams Using the Analytic Hierarchy Process.
Sun Jin JO ; Kyoung Sae NA ; Joo Eon PARK ; Myung Soo LEE
Psychiatry Investigation 2018;15(7):663-669
OBJECTIVE: The purpose of this study was to determine the key components of Korean disaster psychiatric assistant teams (K-DPATs), to set up new mental health service providing system for the disaster victims. METHODS: We conducted an analytic hierarchy process (AHP) involving disaster mental health experts, using a pairwise comparison questionnaire to compare the relative importance of the key components of the Korean disaster mental health response system. In total, 41 experts completed the first online survey; of these, 36 completed the second survey. Ten experts participated in panel meetings and discussed the results of the survey and AHP process. RESULTS: It was agreed that K-DPATs should be independent of the existing mental health system (70.1%), funding for K-DPATs should be provided by the Ministry of Public Safety, and the system should be managed by the Ministry of Health (65.8%). Experts shared the view that K-DPAT leaders would be suitable key decision makers for all types of disaster, with the exception of those involving infectious diseases. CONCLUSION: K-DPAT, a new model for disaster mental health response systems could improve the insufficiency of the current system, address problems such as fragmentation, and fulfill disaster victims’ unmet need for early professional intervention.
Communicable Diseases
;
Decision Making*
;
Disaster Victims
;
Disasters*
;
Financial Management
;
Mental Health
;
Mental Health Services
6.Therapeutic effects of orally administered CJLP55 for atopic dermatitis via the regulation of immune response.
Kyeong Eun HYUNG ; Soo Jeong KIM ; Ye Won JANG ; Da Kyoung LEE ; Kee Hyeob HYUN ; Byoung Seok MOON ; Bongjoon KIM ; Heeyoon AHN ; So Young PARK ; Uy Dong SOHN ; Eon Sub PARK ; Kwang Woo HWANG
The Korean Journal of Physiology and Pharmacology 2017;21(3):335-343
Atopic dermatitis (AD) is an inflammatory skin condition accompanied by symptoms such as edema and hemorrhage. Kimchi is a traditional fermented Korean dish consisting of various probiotics. In this study, the therapeutic effect of Lactobacillus plantarum CJLP55 isolated from Kimchi was studied in AD-induced mice. Orally administered Lactobacillus strain, CJLP55, suppressed AD symptoms and high serum IgE levels. CJLP55 administration reduced the thickness of the epidermis, infiltration of mast cells and eosinophils into the skin lesion, enlargement of axillary lymph nodes, and increase in cell population in axillary lymph nodes. CJLP55 treatment decreased the production of type 2 cytokines, such as interleukin (IL)-4, IL-5, IL-10, IL-12, interferon (IFN)-γ, and IL-6,which were stimulated by house dust mite extracts, in the axillary lymph node cells. Orally administered CJLP55 exhibited a therapeutic effect on house dust mite-induced AD in NC/Nga mice after onset of the disease by altering immune cell activation. The Lactobacillus strain, CJLP55, isolated from Kimchi, suppressed AD. Our results suggest its possible use as a potential candidate for management of AD.
Animals
;
Cytokines
;
Dermatitis
;
Dermatitis, Atopic*
;
Dermatophagoides farinae
;
Dust
;
Edema
;
Eosinophils
;
Epidermis
;
Hemorrhage
;
Immunoglobulin E
;
Interferons
;
Interleukin-10
;
Interleukin-12
;
Interleukin-5
;
Interleukins
;
Lactobacillus
;
Lactobacillus plantarum
;
Lymph Nodes
;
Mast Cells
;
Mice
;
Probiotics
;
Pyroglyphidae
;
Skin
;
Th2 Cells
;
Therapeutic Uses*
7.Anticancer effect of silibinin on the xenograft model using MDA-MB-468 breast cancer cells.
Won Ho KIL ; Sang Min KIM ; Jeong Eon LEE ; Kyoung Sik PARK ; Seok Jin NAM
Annals of Surgical Treatment and Research 2014;87(4):167-173
PURPOSE: The aim of this study is to know whether silibinin has an anticancer effect on triple negative breast cancer xenograft model using MDA-MB-468 cells. METHODS: To establish the xenograft model, we injected the MDA-MB-468 cells into female Balb/c-nude mice. After establishing a xenograft model, oral silibinin was administered to the tested mice in the way of 200 mg/kg for 45 days. The difference of mean tumor volume between silibinin fed mice and control mice was analyzed. The epidermal growth factor receptor (EGFR) phosphorylation in MDA-MB-468 cells was analyzed by Western blotting. The expression of VEGF, COX-2, and MMP-9 genes in tumor tissue was analyzed by real-time polymerase chain reaction (PCR). RESULTS: In the xenograft model using MDA-MB-468 cells, we found that oral administration of silibinin significantly suppressed the tumor volume (silibinin treated mice vs. control mice; 230.3 +/- 61.6 mm3 vs. 435.7 +/- 93.5 mm3, P < 0.001). The phosphorylation of EGFR in MDA-MB-468 cells was inhibited by treatment with 50 microg/mL of silibinin. In real time-PCR analysis of tumor tissue obtained from sacrificed mice, the gene expression of MMP-9, VEGF, and COX-2 was 51.8%-80% smaller in silibinin group than that of control group and we can also verify the similar result using Western blotting analysis. CONCLUSION: We verified that silibinin had anticancer effect on xenograft model of MDA-MB-468 cells in the way of preventing the phosphorylation of EGFR and eventually suppressed the production of COX-2, VEGF, and MMP-9 expression. Finally, the tumor volume of xenograft models was decreased after administration of Silibinin.
Administration, Oral
;
Animals
;
Blotting, Western
;
Breast Neoplasms*
;
Female
;
Gene Expression
;
Heterografts*
;
Humans
;
Mice
;
Phosphorylation
;
Real-Time Polymerase Chain Reaction
;
Receptor, Epidermal Growth Factor
;
Triple Negative Breast Neoplasms
;
Tumor Burden
;
Vascular Endothelial Growth Factor A
8.Development of Loop-Mediated Isothermal Amplification Targeting 18S Ribosomal DNA for Rapid Detection of Azumiobodo hoyamushi (Kinetoplastea).
Su Min SONG ; Dinzouna Boutamba SYLVATRIE-DANNE ; So Young JOO ; Yun Kyung SHIN ; Hak Sun YU ; Yong Seok LEE ; Ji Eon JUNG ; Noboru INOUE ; Won Kee LEE ; Youn Kyoung GOO ; Dong Il CHUNG ; Yeonchul HONG
The Korean Journal of Parasitology 2014;52(3):305-310
Ascidian soft tunic syndrome (AsSTS) caused by Azumiobodo hoyamushi (A. hoyamushi) is a serious aquaculture problem that results in mass mortality of ascidians. Accordingly, the early and accurate detection of A. hoyamushi would contribute substantially to disease management and prevention of transmission. Recently, the loop-mediated isothermal amplification (LAMP) method was adopted for clinical diagnosis of a range of infectious diseases. Here, the authors describe a rapid and efficient LAMP-based method targeting the 18S rDNA gene for detection of A. hoyamushi using ascidian DNA for the diagnosis of AsSTS. A. hoyamushi LAMP assay amplified the DNA of 0.01 parasites per reaction and detected A. hoyamushi in 10 ng of ascidian DNA. To validate A. hoyamushi 18S rDNA LAMP assays, AsSTS-suspected and non-diseased ascidians were examined by microscopy, PCR, and by using the LAMP assay. When PCR was used as a gold standard, the LAMP assay showed good agreement in terms of sensitivity, positive predictive value (PPV), and negative predictive value (NPV). In the present study, a LAMP assay based on directly heat-treated samples was found to be as efficient as DNA extraction using a commercial kit for detecting A. hoyamushi. Taken together, this study shows the devised A. hoyamushi LAMP assay could be used to diagnose AsSTS in a straightforward, sensitive, and specific manner, that it could be used for forecasting, surveillance, and quarantine of AsSTS.
Animals
;
Euglenozoa Infections/diagnosis/veterinary
;
Kinetoplastida/*classification/genetics/*isolation & purification
;
Nucleic Acid Amplification Techniques/*methods
;
Predictive Value of Tests
;
RNA, Ribosomal, 18S/*genetics
;
Sensitivity and Specificity
;
Urochordata
9.Anti-Allodynic Effects of Levodopa in Neuropathic Rats.
Hue Jung PARK ; Hwan Seok JOO ; Young Hoon KIM ; Ou Kyoung KWON ; Jaemin LEE ; Eun Sung KIM ; Dong Eon MOON
Yonsei Medical Journal 2013;54(2):330-335
PURPOSE: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats. MATERIALS AND METHODS: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not. RESULTS: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p<0.01). In addition, levodopa induced biphasic analgesia. Different dosage of levodopa did not impact on the rotarod time (p>0.05). CONCLUSION: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.
Animals
;
Carbidopa/administration & dosage/adverse effects/therapeutic use
;
Dopamine Agents/administration & dosage/adverse effects/*therapeutic use
;
Hyperalgesia/*drug therapy
;
Levodopa/administration & dosage/adverse effects/*therapeutic use
;
Male
;
Neuralgia/*drug therapy
;
Rats
;
Rats, Sprague-Dawley
;
Rotarod Performance Test
10.Invasive Pleomorphic Lobular Carcinoma of the Breast: Clinicopathologic Characteristics and Prognosis Compared with Invasive Ductal Carcinoma.
Seung Pil JUNG ; Se Kyoung LEE ; Sangmin KIM ; Min Young CHOI ; Soo Youn BAE ; Jiyoung KIM ; Minkuk KIM ; Won Ho KIL ; Eun Yoon CHO ; Jun Ho CHOE ; Jung Han KIM ; Jee Soo KIM ; Seok Jin NAM ; Jeong Eon LEE
Journal of Breast Cancer 2012;15(3):313-319
PURPOSE: Invasive pleomorphic lobular carcinoma (IPLC) is a very rare and distinct morphological variant of invasive lobular carcinoma (ILC), characterized by nuclear atypia and pleomorphism contrasted with the cytologic uniformity of ILC. This study evaluated clinicopathologic characteristics and prognosis of IPLC compared with invasive ductal carcinoma (IDC). METHODS: We retrospectively reviewed the medical records of 35 patients with IPLC and 6,184 patients with IDC, not otherwise specified. We compared the clinicopathologic characteristics, relapse-free survival (RFS) and disease specific survival (DSS) of patients who were surgically treated between January 1997 and December 2010. RESULTS: Patients with IPLC presented at an older age with larger tumor size, worse histologic grade, higher rates of N3 stage, more multifocal/multicentric tumors, and more nipple-areolar complex involvement than those of patients with IDC. During the follow-up period, the IPLC group experienced five cases (14.3%) of disease recurrence and three cases (8.6%) of disease specific mortality compared with 637 cases (10.4%) of recurrence and 333 cases (5.4%) of disease specific mortality in the IDC group. Univariate analysis using the Kaplan-Meier method revealed that the IPLC group showed a significantly poorer prognosis than that of the IDC group (RFS, p=0.008; DSS, p<0.001). However, after adjusting for clinicopathologic factors, a multivariate analysis showed no statistical differences in RFS (p=0.396) and DSS (p=0.168) between the IPLC and the IDC groups. CONCLUSION: Our data suggest that patients with IPLC present with poor prognostic factors such as large tumor size, poor histologic grade and advanced stage at diagnosis. These aggressive clinicopathologic characteristics may result in poor clinical outcomes. Although our study could not link IPLC histology to poor prognosis, considering the aggressive characteristics of IPLC, early detection and considerate treatment, including proper surgical and adjuvant intervention, could be helpful for disease progression and survival.
Aluminum Hydroxide
;
Breast
;
Carbonates
;
Carcinoma, Ductal
;
Carcinoma, Lobular
;
Disease Progression
;
Follow-Up Studies
;
Humans
;
Medical Records
;
Multivariate Analysis
;
Prognosis
;
Recurrence
;
Retrospective Studies

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