https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/395 Sat, 04 Apr 2026 09:39:02 GMT 2026-04-04T09:39:02Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79286 Title: Ebastine targets HER2/HER3 signaling and cancer stem cell traits to overcome trastuzumab resistance in HER2-positive breast cancer Authors: Jung, Eun Sun; Kim, Ji Young; Ko, Dongmi; Seo, Juyeon; Lee, Sang Yoon; Lee, Daeun; Kim, Subeen; Park, Minsu; Kim, Seongjae; Park, Soeun; Lee, Kyoungmin; Kang, Yong Koo; Nam, Kee Dal; Kim, Yoon-Jae; Seo, Jae Hong Abstract: Despite advances in HER2-targeted therapy for HER2-positive breast cancer, resistance to trastuzumab and tumor recurrence remain major barriers to durable outcomes. The present study evaluated the therapeutic potential of ebastine, a second-generation H1-antihistamine, as a repurposing candidate to overcome trastuzumab resistance by targeting HER2 signaling and cancer stem cell (CSC)-associated phenotypes in HER2-positive breast cancer cells. Molecular docking studies revealed that ebastine bound to the ATP-binding site of the HER2 tyrosine kinase domain, thereby suppressing the phosphorylation of HER2, p95HER2 and HER3, as assessed by immunoblotting. Immunoprecipitation assay further demonstrated that this binding disrupted HER2/HER3 and HER2/EGFR heterodimerization, leading to reduced downstream AKT activation. Ebastine significantly decreased aldehyde dehydrogenase (ALDH)1 activity, decreased the CD44high/CD24low CSC-like population, as assessed by flow cytometry, and inhibited mammosphere formation. In a trastuzumab-resistant xenograft model, ebastine markedly suppressed tumor growth, decreased the Ki-67 proliferation index and angiogenesis and induced apoptosis. These effects were accompanied by decreased expression of HER2, HER3, ALDH1, CD44, and vimentin in tumor tissues, as determined by immunohistochemistry. Furthermore, serum biochemical analyses revealed no significant hepatotoxicity or nephrotoxicity, indicating a favorable in vivo safety profile. These findings demonstrated that ebastine effectively disrupts key pathways involved in CSC-like traits and HER2 activity, even under trastuzumab-resistant conditions. Its multifaceted inhibitory effects support the repositioning of ebastine as a promising therapeutic strategy for treating refractory HER2-positive breast cancer. Wed, 01 Apr 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79286 2026-04-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79519 Title: Endoscopic resection versus surgery for T1 rectal cancer: A systematic review and meta-analysis of oncologic and safety outcomes Authors: Moon, Yeajin; Hong, Youngki; Kim, Hyun Jung; Park, Seun Ja; Ryu, Hyo Seon; Kwak, Jung Myun; Lee, Seung Hun; Kim, Jae Hyun Abstract: BackgroundSurgical resection (SR) has been recommended for T1 rectal cancer, but concerns about postoperative morbidity and impaired quality of life continue to pose a significant burden for patients. Endoscopic resection (ER) offers a minimally invasive alternative; however, its oncologic sufficiency compared to SR remains unclear. We conducted a systematic review and meta-analysis to evaluate the comparative effectiveness and safety of ER versus SR in patients with T1 rectal cancer.MethodsWe systematically searched MEDLINE, EMBASE, Cochrane Library, and KMBASE up to October 2024 for studies comparing ER and SR in patients with T1 rectal cancer. Thirty-one non-randomized observational studies involving 63,443 patients were included. Outcomes of interest were overall survival (OS), disease-free survival (DFS), recurrence, and adverse events. Risk of bias was assessed using the ROBINS-I tool, and the certainty of evidence was evaluated with the GRADE framework.ResultsCompared with SR, ER was associated with a higher risk of death and tumor recurrence, along with a non-significant trend toward higher hazards for OS and DFS. It also carried an increased risk of delayed bleeding and perforation. However, ER demonstrated significantly fewer postoperative complications, including intra-abdominal leakage, wound infection, and minor adverse events. The certainty of evidence was rated as low to very low due to confounding, selection bias, and imprecision. While many patients favored curability and recurrence prevention, others valued reduced invasiveness and faster recovery.ConclusionIn patients with T1 rectal cancer, ER is associated with a lower incidence of postoperative complications compared to SR. However, current evidence does not support the superiority of ER in terms of long-term oncologic outcomes. ER may be considered a reasonable option in carefully selected patients-particularly older adults or those at high surgical risk-through shared decision-making that incorporates clinical factors and individual preferences. Sun, 01 Mar 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79519 2026-03-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78487 Title: Short-term and long-term effects of vitamin D supplementation for preterm infants: a systematic review and meta-analysis Authors: Shin, Seung Hyun; Kim, Hyun Jung; Heo, Ju Sun Abstract: Meta-analysis conducted to evaluate the effectiveness of high-dose (>= 800 IU/day) and low-dose (<800 IU/day) vitamin D supplementation on preterm infants. Study quality was evaluated using the Revised Cochrane risk-of-bias tool 2 for randomized trials. 21 studies included 1130 infants. Regarding short-term (before 40 weeks' postmenstrual age [PMA] or at discharge) outcomes, high-dose vitamin D supplementation was associated with increased serum 25-hydroxyvitamin D (25[OH]D) levels (mean difference 15.62 [13.35-17.88]) and growth velocities, as well as decreased vitamin D deficiency (VDD), skeletal hypomineralization, and mortality. In the subgroup analysis of high-dose supplementation stratified by dosage, 800 IU/day significantly increased serum 25(OH)D levels (mean difference 13.99 [9.03-18.95]) and reduced the risk of VDD (risk difference -0.21 [-0.32 to -0.10]) compared to 400 IU/day, without increasing the risk of vitamin D excess. The long-term outcomes assessed after 40 weeks' PMA or at follow-up visits showed no significant differences in vitamin D status or neurodevelopmental outcomes between the high-dose and low-dose groups. The certainty of the evidence ranges from moderate to very low. High-dose vitamin D supplementation improved short-term outcomes by increasing serum 25(OH)D levels, promoting growth, and reducing mortality. Among the high-dose regimens, 800 IU/day appeared to be the most appropriate dose. Sun, 01 Mar 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78487 2026-03-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/80180 Title: Oncogenic GPR161 Drives Melanoma Proliferation and Metabolic Activity through TXNIP Inhibition Authors: Roh, Yuna; Choi, Jinhyeon; Hwang, Jin-Seong; Lee, Yeo-Jin; Son, Taesang; Kim, Sarang; Gu, Nayeon; Ban, Hyun Seung; Jung, Eun Sun; Kim, Jang-Seong; Han, Tae-Su Abstract: Melanoma progression is driven by both oncogenic signaling and metabolic reprogramming; however, the roles of G-protein-coupled receptors (GPCRs) in these processes remain unclear. Here, we identified GPR161 as an oncogenic GPCR that is significantly upregulated in melanoma and associated with poor survival in advanced-stage melanoma. Functional studies revealed that GPR161 promotes melanoma cell proliferation and migration, whereas its suppression attenuates these malignant phenotypes. Using promoter analysis and chromatin immunoprecipitation-quantitative polymerase chain reaction, we demonstrated that signal transducer and activator of transcription 3 (STAT3) binds directly to and transcriptionally activates GPR161. Inhibition or silencing of STAT3 reduced GPR161 expression and impaired melanoma cell growth. Transcriptomic profiling further identified thioredoxin-interacting protein (TXNIP) as a key downstream target negatively regulated by GPR161. GPR161 depletion increased TXNIP expression, leading to reduced glycolytic capacity and proliferation under both physiological and high-glucose conditions. STAT3 knockdown recapitulated these effects by establishing a STAT3-GPR161-TXNIP regulatory axis. Analysis of the cancer genome atlas datasets confirmed an inverse correlation between GPR161 and TXNIP expression and showed that low TXNIP levels predicted poor overall survival. Together, our findings revealed that GPR161 promotes melanoma malignancy by linking STAT3 activation to TXNIP suppression and metabolic enhancement. This study identified GPR161 as a potential biomarker and therapeutic target in melanoma. Sun, 01 Mar 2026 00:00:00 GMT https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/80180 2026-03-01T00:00:00Z