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.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Bon Seok KOO ; Hyungju KWON ; Keunyoung KIM ; Mijin KIM ; Bo Hyun KIM ; Won Gu KIM ; Won Bae KIM ; Won Woong KIM ; Jung-Han KIM ; Hee Kyung KIM ; Hee Young NA ; Shin Je MOON ; Jung-Eun MOON ; Sohyun PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Dong Yeob SHIN ; Su-Jin SHIN ; Hwa Young AHN ; So Won OH ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Jee Hee YOON ; Ka Hee YI ; Min Kyoung LEE ; Sang-Woo LEE ; Seung Eun LEE ; Sihoon LEE ; Young Ah LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Kyung JEON ; Kyong Yeun JUNG ; Ari CHONG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Chae Moon HONG ; Ho-Cheol KANG ; Sun Wook KIM ; Woong Youn CHUNG ; Do Joon PARK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):1-20
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
3.The Association between Social Support, Metabolic Syndrome, and Incidence of Cardio-Cerebrovascular Diseases in Older Adults: The ARIRANG Study
Hae-Kweun NAM ; Sei-Jin CHANG ; Chun-Bae KIM ; Kyoung Sook JEONG ; Sung-Kyung KIM ; Dae Ryong KANG ; Yong Whi JEONG ; Hocheol LEE ; Bo ZHAO ; Sang-Baek KOH
Yonsei Medical Journal 2024;65(6):363-370
Purpose:
We investigated the association between social support, metabolic syndrome, and incident cardio-cerebrovascular disease (CCVD) in rural Koreans aged ≥50 years.
Materials and Methods:
We conducted a prospective study using the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) dataset. From the baseline of 5169 adults, 1682 participants were finally included according to the exclusion criteria. For outcomes, myocardial infarction, angina, and stroke were included. For independent variables, the social support score and metabolic syndrome were used. Descriptive statistics and multivariate logistic regression were performed to investigate the association among the variables. Paired t-test was conducted to analyze the longitudinal variation of social support scores.
Results:
During the 6.37 years of median follow-up, 137 participants developed CCVD. The adjusted odds ratio (aOR) of metabolic syndrome with persistently high social support was 2.175 [95% confidence interval (CI): 1.479–3.119]. The aOR of metabolic syndrome with persistently low social support was 2.494 (95%CI: 1.141–5.452). The longitudinal variation of the social support score of persistently high social support group was increased significantly by 4.26±26.32. The score of the persistently low social support group was decreased by 1.34±16.87 with no statistical significance.
Conclusion
The presence of metabolic syndrome increases the likelihood of developing onset CCVD. Within the metabolic syndrome positive group, when social support was persistently low, the cohort developed more cardio-cerebrovascular disease compared to the persistently higher social support group. The social support score of the persistently low social support group could be improved through proper intervention. To prevent CCVD, metabolic syndrome components and low social support should be improved in the study participants.
4.Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis
Soo-Kyung CHO ; Hyoungyoung KIM ; Yeo-Jin SONG ; Hye Won KIM ; Eunwoo NAM ; Shin-Seok LEE ; Hye-Soon LEE ; Sung-Hoon PARK ; Yeon-Ah LEE ; Min-Chan PARK ; Sung Hae CHANG ; Hyoun-Ah KIM ; Seung-Ki KWOK ; Hae-Rim KIM ; Hyun-Sook KIM ; Bo Young YOON ; Wan-Sik UHM ; Yong-Gil KIM ; Jae Hoon KIM ; Jisoo LEE ; Jeongim CHOI ; Yoon-Kyoung SUNG
The Korean Journal of Internal Medicine 2023;38(4):546-556
Background/Aims:
We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs.
Methods:
A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs).
Results:
Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups.
Conclusions
Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.
5.Clinical Practice Guidelines for Oropharyngeal Dysphagia
Seoyon YANG ; Jin-Woo PARK ; Kyunghoon MIN ; Yoon Se LEE ; Young-Jin SONG ; Seong Hee CHOI ; Doo Young KIM ; Seung Hak LEE ; Hee Seung YANG ; Wonjae CHA ; Ji Won KIM ; Byung-Mo OH ; Han Gil SEO ; Min-Wook KIM ; Hee-Soon WOO ; Sung-Jong PARK ; Sungju JEE ; Ju Sun OH ; Ki Deok PARK ; Young Ju JIN ; Sungjun HAN ; DooHan YOO ; Bo Hae KIM ; Hyun Haeng LEE ; Yeo Hyung KIM ; Min-Gu KANG ; Eun-Jae CHUNG ; Bo Ryun KIM ; Tae-Woo KIM ; Eun Jae KO ; Young Min PARK ; Hanaro PARK ; Min-Su KIM ; Jungirl SEOK ; Sun IM ; Sung-Hwa KO ; Seong Hoon LIM ; Kee Wook JUNG ; Tae Hee LEE ; Bo Young HONG ; Woojeong KIM ; Weon-Sun SHIN ; Young Chan LEE ; Sung Joon PARK ; Jeonghyun LIM ; Youngkook KIM ; Jung Hwan LEE ; Kang-Min AHN ; Jun-Young PAENG ; JeongYun PARK ; Young Ae SONG ; Kyung Cheon SEO ; Chang Hwan RYU ; Jae-Keun CHO ; Jee-Ho LEE ; Kyoung Hyo CHOI
Journal of the Korean Dysphagia Society 2023;13(2):77-106
Objective:
Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia.
Methods:
Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology.
Results:
Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended.
Conclusion
This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.
6.Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery
Jun-Ook PARK ; Joo Hyun KIM ; Young Hoon JOO ; Sang-Yeon KIM ; Geun-Jeon KIM ; Hyun Bum KIM ; Dong-Hyun LEE ; Hyun Jun HONG ; Young Min PARK ; Eun-Jae CHUNG ; Yong Bae JI ; Kyoung Ho OH ; Hyoung Shin LEE ; Dong Kun LEE ; Ki Nam PARK ; Myung Jin BAN ; Bo Hae KIM ; Do Hun KIM ; Jae-Keun CHO ; Dong Bin AHN ; Min-Su KIM ; Jun Girl SEOK ; Jeon Yeob JANG ; Hyo Geun CHOI ; Hee Jin KIM ; Sung Joon PARK ; Eun Kyung JUNG ; Yeon Soo KIM ; Yong Tae HONG ; Young Chan LEE ; Ho-Ryun WON ; Sung-Chan SHIN ; Seung-Kuk BAEK ; Soon Young KWON
Clinical and Experimental Otorhinolaryngology 2023;16(1):1-19
The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.
7.Growth inhibition by fusidic acid in cervical, thyroid, and breast carcinoma cell lines
Jin Young KIM ; Bo Seul JEGAL ; A Ra KOH ; Kyoung Sik PARK ; Jong Bin KIM ; Jaeman BAE
Obstetrics & Gynecology Science 2023;66(2):100-106
Objective:
We investigated the effects of fusidic acid (FA) on human cervical, thyroid, and breast carcinoma cell lines to determine the potential usefulness of FA in cancer treatment.
Methods:
Six cancer cell lines (cervical cancer: Caski, HeLa; thyroid cancer: 8505C, TPC1; and breast cancer: MCF-7, MDA-MB-231) were treated with FA. Furthermore the changes in cell growth, cell cycle duration, and extent of apoptosis were analyzed.
Results:
After FA treatment, the cancer cells showed a decrease in growth rate. In the cell death assay, the cell populations were similar in each cell type after treatment with FA, indicating that growth inhibition by FA was not related to the induction of apoptosis. FA induced cell cycle arrest at a dose that inhibited growth rate, which varied in different cell types. G0/G1 phase arrest occurs in breast cancer, S phase arrest in 8505C thyroid cancer, and G2/M phase arrest in cervical cancer. These results indicate that FA reduces growth rates by inducing cell cycle arrest.
Conclusion
FA treatment can interfere with cell proliferation by inducing cell cycle arrest in human cervical, thyroid, and breast carcinoma cell lines. Thus, FA can be useful in treating human cervical, thyroid, and breast carcinomas.
8.High Levels of Hyaluronic Acid Synthase-2 Mediate NRF2-Driven Chemoresistance in Breast Cancer Cells
Bo-Hyun CHOI ; Ingeun RYOO ; Kyeong Hwa SIM ; Hyeon-jin AHN ; Youn Ju LEE ; Mi-Kyoung KWAK
Biomolecules & Therapeutics 2022;30(4):368-379
Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/ NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.
9.The Impact of Auricular Acupressure on Depression among Nurses
Eun Kyeoung KIM ; Ja Kyoung YOU ; Su Ja JI ; Sung Hee CHOI ; Bo Mi JIN ; Cheong Ah LEE ; Eun Jin LEE
Journal of Korean Academy of Psychiatric and Mental Health Nursing 2022;31(3):365-372
Purpose:
This study evaluated the impact of auricular acupressure on depression among nurses.
Methods:
This study used a randomized control group pretest-posttest design. Shift-work nurses with the Patient Health Questionnaire-9 (PHQ-9) score over 5 points were randomized to the experimental group(n=20) or the control group(n=20). For the experimental group, auricular acupressure was conducted at the corresponding points of depression (TGI, AH1) weekly for seven days as well as for two weeks. The PHQ-9 was completed before intervention, as well as two weeks after intervention.
Results:
The mean difference in the PHQ-9 score before and after auricular acupressure in the experimental group (-4.11±2.27), was more significant than in the control group (-1.72±3.82) (t=2.28, p=.03).
Conclusion
Result showed that nurses who received auricular acupressure had a decrease in depression, compared to those who did not receive auricular acupressure. Further research is required, to apply the other auricular acupressure points, to evaluate the impact on depressive symptoms.
10.Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group
Kyung Mi PARK ; Keon Hee YOO ; Seong Koo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Hee Young JU ; Hong Hoe KOO ; Chuhl Joo LYU ; Seung Min HAN ; Jung Woo HAN ; Jung Yoon CHOI ; Kyung Taek HONG ; Hyoung Jin KANG ; Hee Young SHIN ; Ho Joon IM ; Kyung-Nam KOH ; Hyery KIM ; Hoon KOOK ; Hee Jo BAEK ; Bo Ram KIM ; Eu Jeen YANG ; Jae Young LIM ; Eun Sil PARK ; Eun Jin CHOI ; Sang Kyu PARK ; Jae Min LEE ; Ye Jee SHIM ; Ji Yoon KIM ; Ji Kyoung PARK ; Seom Gim KONG ; Young Bae CHOI ; Bin CHO ; Young Tak LIM
Cancer Research and Treatment 2022;54(1):269-276
Purpose:
Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.
Materials and Methods:
Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.
Results:
Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).
Conclusion
This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

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