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.Endoscopic Management of Post-Sleeve Gastrectomy Leaks Using Long, Fully Covered Stents
Chan SUNWOO ; Jong Kyu PARK ; Tae Yeong LEE ; Sang Jin LEE
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2026;26(1):89-94
Gastric leaks after laparoscopic sleeve gastrectomy are serious complications with mortality rates of up to 10%. Conventional self-expanding metal stents exhibit high migration rates (up to 58%), limiting their efficacy. Large, fully covered megastents that reduce migration rates are poorly tolerated and associated with traumatic ulcers and discomfort. We present two cases of successful endoscopic management of persistent gastric leaks following laparoscopic sleeve gastrectomy using long, fully covered Gastro-Seal stents (240 mm) after failed surgical re-exploration. These patients achieved complete fistula closure without stent migration or traumatic ulceration within 26 days and 45 days, respectively. The extended length and round-ended design of the Gastro-Seal stent effectively addressed the key limitations of both conventional and mega-stents. Long, fully covered gastroseal stents may thus be an effective treatment option for managing persistent post-bariatric leaks.
3.Medical disputes involving lower gastrointestinal endoscopies: cases from the Korean Medical Dispute Mediation and Arbitration Agency
Eun Hye OH ; Jeong Eun SHIN ; Jun Yong BAE ; Yoon Suk LEE ; Yehyun PARK ; Yong Hwan KWON ; Chang Nyol PAIK ; Jun Kyu LEE ; Tae Hee LEE
The Korean Journal of Internal Medicine 2025;40(3):404-426
Background/Aims:
As the number of lower gastrointestinal endoscopies and high-risk examinees increases, the incidence of adverse events associated with these endoscopies has also increased. Medical disputes and lawsuits related to adverse events are rapidly increasing.
Methods:
Medical disputes related to lower gastrointestinal endoscopy that had been filed in Korean Medical Dispute Mediation and Arbitration Agency (K-medi) from April 2012 to August 2020 were evaluated with the corresponding medical records and written appraisal. Facilities, patients, procedures, adverse events, and outcome-related variables related to medical disputes were analyzed.
Results:
As the number of lower gastrointestinal endoscopies in Korea increases each year, the number of medical disputes related to lower gastrointestinal endoscopy appraised by K-medi has also increased yearly during the same period. Among the 121 cases analyzed, 86 (71.1%) were conciliated and 35 (28.9%) were cosigned by prosecution. Perforations accounted for the largest proportion of cases (93 cases, 76.9%). Most patients (n = 119, 98.3%) underwent non-emergent procedures, and only 10 (8.3%) underwent them for therapeutic purposes. Approximately one-fifth of the patients (n = 25, 20.7%) died.
Conclusions
The number of medical disputes related to lower gastrointestinal endoscopy are increasing. To prevent this, it is important to review the data on existing cases and establish specific response guidelines.
4.Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting
Ji-Hee KIM ; Kyu-Hee HWANG ; Jiyeon OH ; Sung-Eun KIM ; Mi-Young LEE ; Tae Sic LEE ; Seung-Kuy CHA
The Korean Journal of Physiology and Pharmacology 2025;29(1):33-43
Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.
6.Pericapsular Nerve Group Block with Periarticular Injection for Pain Management after Total Hip Arthroplasty: A Randomized Controlled Trial
Hun Sik CHO ; Bo Ra LEE ; Hyuck Min KWON ; Jun Young PARK ; Hyeong Won HAM ; Woo-Suk LEE ; Kwan Kyu PARK ; Tae Sung LEE ; Yong Seon CHOI
Yonsei Medical Journal 2025;66(4):233-239
Purpose:
The purpose of this study was to compare the effectiveness of pericapsular nerve group (PENG) block with periarticular multimodal drug injection (PMDI) on postoperative pain management and surgical outcomes in patients who underwent total hip arthroplasty (THA). We hypothesized that PENG block with PMDI would exhibit superior effects on postoperative pain control after THA compared to PMDI alone.
Materials and Methods:
From April 2022 to February 2023, 58 patients who underwent THA were randomly assigned into two groups: PENG block with PMDI group (n=29) and PMDI-only group (n=29). Primary outcomes were postoperative numeric rating scale (NRS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications (nausea and vomiting), Richards-Campbell Sleep Questionnaire (RCSQ) score, length of hospital stay, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Harris Hip Score (HHS), and total morphine usage after surgery.
Results:
There was no significant difference in postoperative pain for either resting NRS or active NRS. Postoperative nausea and vomiting, RCSQ score, length of hospital stay, WOMAC index, HHS, and total morphine usage exhibited no significant differences between the two groups.
Conclusion
Both groups showed no significant differences in postoperative pain and clinical outcomes, indicating that the addition of PENG block to PMDI does not improve pain management after applying the posterolateral approach of THA. PMDI alone during THA would be an efficient, fast, and safe method for managing postoperative pain. This article was registered with ClinicalTrials.gov (Gov ID: NCT05320913).
7.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.
8.Association of Age, Sex and Education With Access to the Intravenous Thrombolysis for Acute Ischemic Stroke
Yoona KO ; Beom Joon KIM ; Youngran KIM ; Jong-Moo PARK ; Kyusik KANG ; Jae Guk KIM ; Jae-Kwan CHA ; Tai Hwan PARK ; Kyungbok LEE ; Jun LEE ; Keun-Sik HONG ; Byung-Chul LEE ; Kyung-Ho YU ; Dong-Eog KIM ; Joon-Tae KIM ; Jay Chol CHOI ; Jee Hyun KWON ; Wook-Joo KIM ; Kyu Sun YUM ; Sung-Il SOHN ; Hyungjong PARK ; Sang-Hwa LEE ; Kwang-Yeol PARK ; Chi Kyung KIM ; Sung Hyuk HEO ; Moon-Ku HAN ; Anjail Z. SHARRIEF ; Sunil A. SHETH ; Hee-Joon BAE ;
Journal of Korean Medical Science 2025;40(13):e49-
Background:
Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients.
Methods:
We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates.
Results:
Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively).
Conclusion
Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.
9.Importance of Preoperative Pupillary Reflex in Traumatic Optic Neuropathy
Journal of Korean Neurosurgical Society 2025;68(1):19-24
Objective:
: Traumatic optic neuropathy (TON) refers to a pathological condition caused by direct or indirect injury to the optic nerves. In the case of patients with traumatic brain injury, adequate vision evaluation is difficult in many cases due to altered mentality. In order to address this problem, we investigated preoperative pupillary light reflex in TON patients as a predictive factor of surgical outcomes after optic nerve decompression.
Methods:
: From April 2020 to September 2022, we enrolled patients who were diagnosed with TON and underwent endoscopic optic nerve decompression at our institution. Vision and pupil reflex tests were performed by an ophthalmologist before and after surgery.
Results:
: Seven patients were enrolled. Their ages ranged from 9 to 78 years and all were male. Among the seven patients, the patient whose pupillary light reflex was sluggish with 6 mm-sized pupil and absent with 7 mm-sized pupil before surgery showed no improvement in vision. Patients with some response to direct reflex or contralateral indirect reflex testing preoperative showed vision improvement after operation.
Conclusion
: Direct and indirect pupillary reflexes can be important factors determining treatment outcome for TON. In unconscious patients with a fracture involving the optic canal, timely surgical intervention based on pupillary reflex can prevent permanent loss of vision.
10.Early Administration of Nelonemdaz May Improve the Stroke Outcomes in Patients With Acute Stroke
Jin Soo LEE ; Ji Sung LEE ; Seong Hwan AHN ; Hyun Goo KANG ; Tae-Jin SONG ; Dong-Ick SHIN ; Hee-Joon BAE ; Chang Hun KIM ; Sung Hyuk HEO ; Jae-Kwan CHA ; Yeong Bae LEE ; Eung Gyu KIM ; Man Seok PARK ; Hee-Kwon PARK ; Jinkwon KIM ; Sungwook YU ; Heejung MO ; Sung Il SOHN ; Jee Hyun KWON ; Jae Guk KIM ; Young Seo KIM ; Jay Chol CHOI ; Yang-Ha HWANG ; Keun Hwa JUNG ; Soo-Kyoung KIM ; Woo Keun SEO ; Jung Hwa SEO ; Joonsang YOO ; Jun Young CHANG ; Mooseok PARK ; Kyu Sun YUM ; Chun San AN ; Byoung Joo GWAG ; Dennis W. CHOI ; Ji Man HONG ; Sun U. KWON ;
Journal of Stroke 2025;27(2):279-283

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