1.WWP2 ubiquitin ligase promotes colorectal cancer progression by targeting p53 for degradation:an experimental study
Seung-Jun LEE ; Han-Gil KIM ; Young-Tae JU ; Young-Sool HAH ; Jeongyun HWANG ; Jihun CHOI ; Jin-Kyu CHO ; Chi-Young JEONG ; Young-Joon LEE ; Ji-Ho PARK ; Ju-Yeon KIM ; Jae-Myung KIM ; Seung-Jin KWAG
Annals of Surgical Treatment and Research 2026;110(5):331-346
Purpose:
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms.
Methods:
WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2.
Results:
WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth.
Conclusion
Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.
2.Impact of smoking and age on long-term recurrence after laparoscopic primary closure for duodenal ulcer perforation: a 5-year observational study
Tae-Han KIM ; Sang-Ho JEONG ; Young-Joon LEE ; Dong-Hwan KIM ; Han-Gil KIM ; Jae-Myung KIM ; Jin-Kyu CHO ; Seung-Jin KWAG ; Ju-Yeon KIM ; Young-Tae JU ; Chi-Young JEONG ; Ji-Ho PARK
Annals of Surgical Treatment and Research 2025;109(2):98-104
Purpose:
This study investigates risk factors for recurrence in patients who underwent laparoscopic primary closure (PC) for pyloroduodenal ulcer perforation (PUP).
Methods:
We retrospectively analyzed data from patients who underwent laparoscopic PC with or without highly selective vagotomy (HSV) for PUP at a tertiary hospital from 2010 to 2019. Demographics, surgical outcomes, proton pump inhibitor (PPI) use, Helicobacter pylori status, and endoscopic findings were reviewed. Long-term (5 years) endoscopic and clinical outcomes regarding ulcer and perforation recurrence, were collected.
Results:
A total of 139 patients were included in the analysis. Of these, 109 (78.4%) were male, and 76 (54.7%) were current smokers. Ninety-five patients (68.3%) underwent PC only, while 44 (31.7%) received PC + HSV. During the follow-up period, ulcer recurrence was observed in 19 patients (13.7%) and perforation recurrence in 9 (6.5%). In Cox proportional analysis for ulcer recurrence, smoking (hazard ratio [HR], 6.476; 95% confidence interval [CI], 1.834–22.873; P = 0.004) and older age (HR, 1.049; 95% CI, 1.012–1.088; P = 0.009) were identified as significant factors. For peptic ulcer perforation recurrence, smoking (HR, 19.129; 95% CI, 2.048–178.702; P = 0.010) and older age (HR, 1.062; 95% CI, 1.009–1.118; P = 0.021) were significant. No significant associations were found between sex, duration of PPI therapy, H. pylori eradication success, or surgery type and the risk of either ulcer or perforation recurrence.
Conclusion
Smoking and age are important factors for recurrence following laparoscopic PC for PUP. These findings emphasize the need for smoking cessation and close postoperative monitoring.
3.MicroRNA-18b regulates cell cycle progression in papillary thyroid carcinoma by targeting CDK2: an in vitro experimental study
Ju-Yeon KIM ; Jae-Myung KIM ; Eun Jung JUNG ; Youngsim SON ; Seung-Jin KWAG ; Ji-Ho PARK ; Jin-Kyu CHO ; Han-Gil KIM ; Dong-Hwan KIM ; Sang-Ho JEONG ; Chi-Young JEONG ; Young-Tae JU ; Young-Joon LEE
Annals of Surgical Treatment and Research 2025;108(6):374-389
Purpose:
Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy, and the global incidence has been steadily increasing over the years. Although PTC generally exhibits favorable prognosis, a subset of patients experiences aggressive progression and increased mortality. Current prognostic approaches, reliant on clinic-pathological factors, have limitations, underscoring the need for innovative biomarkers. MicroRNAs (miRs) have emerged as promising candidates due to their roles in cellular processes and cancer progression. Among them, the present study investigated the role of miR-18b in PTC, exploring its potential as a prognostic biomarker.
Methods:
Utilizing PTC cell lines (TPC1, K1), we examined miR-18b expression and its regulatory effects. The present study used web-based tools to predict the target of miR-18b and to investigate the prognostic impact of miR-18b on thyroid cancer.
Results:
Through a series of cell proliferation, invasion assay, gap closure, and colony formation assays, we identified that miR-18b suppresses PTC aggressiveness. Dual-luciferase assays confirmed that miR-18b directly targeted the 3’-untranslated region of CDK2 and suppressed the expression of CDK2. In addition, miR-18b significantly attenuates the interaction between cyclin A or cyclin E with cyclin-dependent kinase 2 according to co-immunoprecipitation assay.Western blotting of cell cycle proteins and flow cytometry revealed miR-18b–induced cell cycle arrest and apoptosis.
Conclusion
Our findings underscore miR-18b’s potential as a biomarker for predicting the prognosis of PTC and suggest that it functions through direct regulation of CDK2, influencing cell cycle dynamics. This study not only enhances our understanding of miR-18b in thyroid cancer but also highlights its potential in refining prognostic evaluations and therapeutic strategies.
4.Anticancer effect of the antipsychotic agent penfluridol on epithelial ovarian cancer
Won-Ji KIM ; Ji-Yoon RYU ; Chi-Son CHANG ; Young-Jae CHO ; Jung-Joo CHOI ; Jae Ryoung HWANG ; Ju-Yeon CHOI ; Jeong-Won LEE
Journal of Gynecologic Oncology 2025;36(2):e28-
Objective:
Chemoresistant-epithelial ovarian cancer (EOC) has a poor prognosis, prompting the search for new therapeutic drugs. The diphenylbutylpiperidine (DPBP) class of antipsychotic drugs used in schizophrenia has shown anticancer effects. This study aimed to investigate the preclinical efficacy of penfluridol, fluspirilene, and pimozide (DPBP) using in vitro and in vivo models of EOC.
Methods:
Human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with penfluridol, fluspirilene, and pimozide, and cell proliferation, apoptosis, and migration were assessed. The preclinical efficacy of DPBP was also investigated using in vivo mouse models, including cell lines and patient-derived xenografts (PDX) of EOC.
Results:
DPBP drugs significantly decreased cell proliferation in chemosensitive (A2780, HeyA8, and SKOV3ip1) and chemoresistant (A2780-CP20, HeyA8-MDR, and SKOV3-TR) cell lines. Among these drugs, penfluridol exerted a relatively stronger cytotoxic effect on all cell lines. Penfluridol significantly increased apoptosis and inhibited migration of EOC cells. In the cell line xenograft mouse model with HeyA8, the penfluridol group showed significantly decreased tumor weight compared with the control group. In the paclitaxel-resistant model with HeyA8-MDR, the penfluridol group had significantly decreased tumor weight compared with the paclitaxel or control groups. Penfluridol exerted anticancer effects on the PDX model.
Conclusion
Penfluridol exerted significant anticancer effects on EOC cells and xenograft models, including PDX. Thus, penfluridol therapy, as a drug repurposing strategy, might be a potential therapeutic for EOCs.
5.Effectiveness of Buspirone in Alleviating Anxiety Symptoms in Patients with Depressive Disorder: A Multicenter Prospective Observational Study in Korea
Young Sup WOO ; Won-Seok CHOI ; Jong-Hyun JEONG ; Jonghun LEE ; Do-Hoon KIM ; Jong-Chul YANG ; Se-Hoon SHIM ; Seung-Gul KANG ; Young-Eun JUNG ; Won KIM ; Chi-Un PAE ; Won-Myong BAHK
Clinical Psychopharmacology and Neuroscience 2025;23(1):144-154
Objective:
We aimed to investigate the effectiveness of buspirone as an adjunctive therapy for alleviating anxiety symptoms in patients with depressive disorders who are already taking antidepressants.
Methods:
This was an open-label prospective multicenter non-interventional observational study conducted over 12 weeks. We enrolled 180 patients diagnosed with depressive disorders according to DSM-5 criteria and Hamilton Anxiety Rating Scale (HAMA) scores ≥ 18. Participants were already taking selective serotonin reuptake inhibitors or serotoninnorepinephrine reuptake inhibitors and were prescribed adjunctive buspirone. Efficacy was assessed using HAMA, Hamilton Depression Rating Scale (HAMD), Clinical Global Impression Scale-Improvement, Clinical Global Impression Scale-Severity, Sheehan Disability Scale (SDS), and WHO-5 Well-Being Index.
Results:
The efficacy analysis included 161 patients. HAMA scores decreased significantly from 25.2 ± 6.7 at baseline to 15.4 ± 8.6 at 12 weeks (p < 0.001), whereas HAMD scores decreased from 19.4 ± 4.6 to 12.7 ± 5.7 (p < 0.001).WHO-5 and SDS scores showed significant improvements. The HAMA response rate was 39.1% and the remission rate was 13.7% at 12 weeks. Adverse drug reactions were reported in 3.7% of participants. Subgroup analyses showed no significant differences in treatment response based on buspirone dosage, baseline anxiety/depression severity, or benzodiazepine use.
Conclusion
Adjunctive buspirone therapy effectively improved anxiety symptoms in depressed patients taking antidepressants, regardless of baseline symptom severity or buspirone dosage. The treatment was well-tolerated with few adverse events. Future studies using a control group are needed.
6.Comparing single-patient and multi-patient room intensive care units: a multicenter cohort study on architectural differences and clinical significance in South Korea
Daun JEONG ; Donghyoun LEE ; Kyoung Won YOON ; Hyo Jin KIM ; Sun Young CHOI ; Chi-Min PARK
Acute and Critical Care 2025;40(2):160-170
Background:
The design of intensive care units (ICUs) is increasingly acknowledged as a crucial factor affecting patient outcomes. Transitioning from multi-bed patient rooms (MPRs) to single-bed patient rooms (SPRs) aims to improve infection control, patient privacy, and quality of care. However, concerns remain regarding potential patient isolation and reduced staff situational awareness. This study aims to evaluate clinical outcomes in SPR-structured ICUs compared to mixed SPR and MPR ICUs.
Methods:
This multicenter retrospective cohort study was conducted across three university-affiliated tertiary hospitals between April 2022 and August 2023. The study population included ICU patients aged ≥18 years, excluding those admitted to cardiac and neonatal ICUs. Outcomes assessed included ICU mortality and severity scores based on Simplified Acute Physiology Score 3 and Acute Physiology and Chronic Health Evaluation II scores.
Results:
This study included 3,179 ICU patients across three sites: site A consisted exclusively of SPRs, while sites B and C had mixed SPR and MPR arrangements. ICU mortality rates were 8.3%, 15.2%, and 9.7% for sites A, B, and C, respectively (P<0.001). Propensity score matching and logistic regression analysis demonstrated that SPRs were associated with significantly reduced ICU mortality (adjusted odds ratio, 0.54; 95% CI, 0.40–0.73).
Conclusions
SPRs were associated with a protective effect, reducing ICU mortality. Clinical outcomes in ICUs appear to be influenced by structural design improvements alongside other clinical factors.
7.Prospective external validation of a deep-learning-based early-warning system for major adverse events in general wards in South Korea
Taeyong SIM ; Eun Young CHO ; Ji-hyun KIM ; Kyung Hyun LEE ; Kwang Joon KIM ; Sangchul HAHN ; Eun Yeong HA ; Eunkyeong YUN ; In-Cheol KIM ; Sun Hyo PARK ; Chi-Heum CHO ; Gyeong Im YU ; Byung Eun AHN ; Yeeun JEONG ; Joo-Yun WON ; Hochan CHO ; Ki-Byung LEE
Acute and Critical Care 2025;40(2):197-208
Background:
Acute deterioration of patients in general wards often leads to major adverse events (MAEs), including unplanned intensive care unit transfers, cardiac arrest, or death. Traditional early warning scores (EWSs) have shown limited predictive accuracy, with frequent false positives. We conducted a prospective observational external validation study of an artificial intelligence (AI)-based EWS, the VitalCare - Major Adverse Event Score (VC-MAES), at a tertiary medical center in the Republic of Korea.
Methods:
Adult patients from general wards, including internal medicine (IM) and obstetrics and gynecology (OBGYN)—the latter were rarely investigated in prior AI-based EWS studies—were included. The VC-MAES predictions were compared with National Early Warning Score (NEWS) and Modified Early Warning Score (MEWS) predictions using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and logistic regression for baseline EWS values. False-positives per true positive (FPpTP) were assessed based on the power threshold.
Results:
Of 6,039 encounters, 217 (3.6%) had MAEs (IM: 9.5%, OBGYN: 0.26%). Six hours prior to MAEs, the VC-MAES achieved an AUROC of 0.918 and an AUPRC of 0.352, including the OBGYN subgroup (AUROC, 0.964; AUPRC, 0.388), outperforming the NEWS (0.797 and 0.124) and MEWS (0.722 and 0.079). The FPpTP was reduced by up to 71%. Baseline VC-MAES was strongly associated with MAEs (P<0.001).
Conclusions
The VC-MAES significantly outperformed traditional EWSs in predicting adverse events in general ward patients. The robust performance and lower FPpTP suggest that broader adoption of the VC-MAES may improve clinical efficiency and resource allocation in general wards.
8.A practical guide for enteral nutrition from the Korean Society for Parenteral and Enteral Nutrition: Part I. prescribing enteral nutrition orders
Ye Rim CHANG ; Bo-Eun KIM ; In Seok LEE ; Youn Soo CHO ; Sung-Sik HAN ; Eunjung KIM ; Hyunjung KIM ; Jae Hak KIM ; Jeong Wook KIM ; Sung Shin KIM ; Eunhee KONG ; Ja Kyung MIN ; Chi-Min PARK ; Jeongyun PARK ; Seungwan RYU ; Kyung Won SEO ; Jung Mi SONG ; Minji SEOK ; Eun-Mi SEOL ; Jinhee YOON ; Jeong Meen SEO ;
Annals of Clinical Nutrition and Metabolism 2025;17(1):3-8
Purpose:
This study aimed to develop a comprehensive practical guide for enteral nutrition (EN) designed to enhance patient safety and reduce complications in Korea. Under the leadership of the Korean Society for Parenteral and Enteral Nutrition (KSPEN), the initiative sought to standardize EN procedures, improve decision-making, and promote effective multidisciplinary communication.
Methods:
The KSPEN EN committee identified key questions related to EN practices and organized them into seven sections such as prescribing, delivery route selection, formula preparation, administration, and quality management. Twenty-one experts, selected based on their expertise, conducted a thorough literature review to formulate evidence-based recommendations. Drafts underwent peer review both within and across disciplines, with final revisions completed by the KSPEN Guideline Committee. The guide, which will be published in three installments, addresses critical elements of EN therapy and safety protocols.
Results:
The practical guide recommends that EN orders include detailed elements and advocates the use of electronic medical records for communication. Standardized prescription forms and supplementary safety measures are outlined. Review frequency is adjusted according to patient condition—daily for critically ill or unstable patients and as dictated by institutional protocols for stable patients. Evidence indicates that adherence to these protocols reduces mortality, complications, and prescription errors.
Conclusion
The KSPEN practical guide offers a robust framework for the safe delivery of EN tailored to Korea’s healthcare context. It emphasizes standardized protocols and interdisciplinary collaboration to improve nutritional outcomes, patient safety, and operational efficiency. Rigorous implementation and monitoring of adherence are critical for its success.
9.A practical guide for enteral nutrition from the Korean Society for Parenteral and Enteral Nutrition: Part I. prescribing enteral nutrition orders
Ye Rim CHANG ; Bo-Eun KIM ; In Seok LEE ; Youn Soo CHO ; Sung-Sik HAN ; Eunjung KIM ; Hyunjung KIM ; Jae Hak KIM ; Jeong Wook KIM ; Sung Shin KIM ; Eunhee KONG ; Ja Kyung MIN ; Chi-Min PARK ; Jeongyun PARK ; Seungwan RYU ; Kyung Won SEO ; Jung Mi SONG ; Minji SEOK ; Eun-Mi SEOL ; Jinhee YOON ; Jeong Meen SEO ;
Annals of Clinical Nutrition and Metabolism 2025;17(1):3-8
Purpose:
This study aimed to develop a comprehensive practical guide for enteral nutrition (EN) designed to enhance patient safety and reduce complications in Korea. Under the leadership of the Korean Society for Parenteral and Enteral Nutrition (KSPEN), the initiative sought to standardize EN procedures, improve decision-making, and promote effective multidisciplinary communication.
Methods:
The KSPEN EN committee identified key questions related to EN practices and organized them into seven sections such as prescribing, delivery route selection, formula preparation, administration, and quality management. Twenty-one experts, selected based on their expertise, conducted a thorough literature review to formulate evidence-based recommendations. Drafts underwent peer review both within and across disciplines, with final revisions completed by the KSPEN Guideline Committee. The guide, which will be published in three installments, addresses critical elements of EN therapy and safety protocols.
Results:
The practical guide recommends that EN orders include detailed elements and advocates the use of electronic medical records for communication. Standardized prescription forms and supplementary safety measures are outlined. Review frequency is adjusted according to patient condition—daily for critically ill or unstable patients and as dictated by institutional protocols for stable patients. Evidence indicates that adherence to these protocols reduces mortality, complications, and prescription errors.
Conclusion
The KSPEN practical guide offers a robust framework for the safe delivery of EN tailored to Korea’s healthcare context. It emphasizes standardized protocols and interdisciplinary collaboration to improve nutritional outcomes, patient safety, and operational efficiency. Rigorous implementation and monitoring of adherence are critical for its success.
10.Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data
Kyu Yean KIM ; Ho Cheol KIM ; Tae Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang Gun SUH ; Chang Hoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jae Hyun JEON ; Chi Young JUNG ; Jeong Su CHO ; Yoo Duk CHOI ; Seung Sik HWANG ; Chang Min CHOI ; Seung Hun JANG ; Jeong Uk LIM ;
Cancer Research and Treatment 2025;57(1):83-94
Purpose:
Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.
Materials and Methods:
Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.
Results:
A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.
Conclusion
Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

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