This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Purpose: To determine the prevalence of tamoxifen retinopathy and assess the utility of a screening protocol using non-mydriatic fundus photography and optical coherence tomography (OCT). Methods: Between May and October 2024, patients on tamoxifen therapy at a breast surgery clinic were offered screening including non-mydriatic fundus photography and OCT. Among those who consented, 290 patients (580 eyes) were included after excluding other retinal diseases. We investigated tamoxifen duration, cumulative dose, central retinal thickness, BMI, underlying diseases, menopausal status, and history of chemotherapy, hormone therapy, or oral contraceptives. Results: All patients were taking 20 mg of tamoxifen daily. The mean treatment duration was 55.7 ± 29.5 months for those treated longer than two years (n = 193), with a mean BMI of 22.1 ± 3.0 kg/m2. Systemic comorbidities included dyslipidemia (n = 27, 14.0%), hypertension (n = 19, 9.8%), diabetes mellitus (n = 13, 6.7%), and cardiovascular disease (n = 4, 2.1%). Additionally, patient histories included chemotherapy (n = 84, 43.7%), postmenopausal status (n = 56, 29.1%), hormone therapy (n = 52, 27.0%), and oral contraceptive use (n = 14, 7.2%). Tamoxifen retinopathy was not observed in any of the patients. Conclusions In this cross-sectional study, the prevalence of tamoxifen retinopathy, as assessed by non-mydriatic fundus photography and OCT in this study, was 0%, which is lower than previously reported rates (0.9%–12%). Although specialized examination by an ophthalmologist, including a dilated fundus examination and OCT remains the diagnostic gold standard, practical constraints can limit its routine clinical use. Our study evaluated a screening protocol performed without ophthalmologist intervention. However, we found that limitations in image quality compromised the detection of subtle lesions, such as crystalline deposits. Consequently, this approach may be insufficient to serve as a primary screening strategy.

Background: Epidermal growth factor (EGF) is widely applied in dermatology for its regenerative effects; however, its clinical utility is limited by low stability and high production costs.To overcome these limitations, we developed a novel probiotic-derived epidermal growth factor (pEGF) by engineering Pediococcus pentosaceus CBT SL4 to express and secrete EGF. Objective: To investigate the anti-photoaging effects of topical pEGF in a ultraviolet B (UVB)-irradiated mice by assessing histological and molecular changes related to collagen synthesis, extracellular matrix (ECM) remodeling, oxidative stress, and inflammation. Methods: SKH1 hairless mice were exposed to UVB for twelve weeks to induce photoaging and treated with topical 10% pEGF cream from week 9 to 12. Skin samples were analyzed using dermoscopy, histology, immunohistochemistry, quantitative real-time polymerase chain reaction, western blotting, and proteomics to evaluate morphological and molecular alterations in ECM components and inflammatory markers. Results: Topical pEGF treatment improved skin texture and reduced wrinkles. Histological evaluation revealed that EGF significantly attenuated UVB-induced epidermal thickening and restored collagen density, with the strongest effects observed in the pEGF group. Molecular analysis showed downregulation of matrix metalloproteinases (MMPs; MMP-1, MMP-3), upregulation of collagen (type I collagen, type III collagen) and tissue inhibitors of metalloproteinases (TIMPs; TIMP-1, TIMP-2). Additionally, pEGF reduced pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β) and oxidative stress markers. Conclusion pEGF demonstrated potent anti-photoaging effects through ECM restoration, inflammation modulation, and barrier reinforcement. These findings support the therapeutic potential of pEGF as a stable, cost-effective alternative to conventional EGF in dermatological applications.

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.

Over the past two decades, experimental and clinical evidence has established the interleukin-23 (IL-23)/interleukin-17 (IL-17) axis as a key mediator of psoriatic inflammation. IL-23, primarily derived from activated dendritic cells, supports the survival and pathogenic function of type 17 immune cells, which subsequently release IL-17A, IL-17F, and IL-22 to promote keratinocyte activation and recruit inflammatory leukocytes. These mechanistic insights have directly translated into the development of highly effective biologic therapies targeting IL-17 or IL-23, substantially improving the management of psoriasis. Beyond injectable biologics, growing efforts to overcome limitations related to long-term adherence, cost, and accessibility have accelerated the development of non-injectable therapeutic approaches. Oral and topical small-molecule agents, including selective tyrosine kinase 2 (TYK2) inhibitors and IL-23 receptor antagonists, are now broadening the therapeutic options. At the same time, progress in molecular engineering, artificial intelligence–guided protein design, and spatial multi-omic technologies are refining therapeutic discovery and enabling more precise targeting of pathogenic immune circuits. In this review, we outline the current understanding of the IL-23/IL-17 pathway in psoriasis pathogenesis and provide a critical overview of approved and emerging therapies directed at this pathway. We also address key biological and translational challenges, including tissue-specific cytokine functions, interspecies differences, and long-term safety considerations, and discuss how these factors may inform future strategies for precision immunotherapy in psoriasis.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Purpose: Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs. Materials and Methods: This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor. Results: Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively. Conclusion Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

Subglottic stenosis (SGS) and tracheal stenosis (TS) are rare conditions that can cause significant breathing difficulties and, if not properly managed, may lead to life-threatening complications. Despite their clinical importance, debate continues regarding the optimal management of adult SGS and TS, and no comprehensive guidelines have been established to date. The Korean Bronchoesophagological Society appointed a task force to develop clinical practice guidelines with the goal of providing evidence-based recommendations for managing SGS and TS in adults. The task force conducted a systematic review of the relevant literature by searching PubMed, Embase, and the Cochrane Library using predefined search terms aligned with key clinical questions. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, which also informed the formulation and reporting of the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for eligible patients. After drafting the guidelines, feedback was obtained through Delphi questionnaires completed by members of the Korean Bronchoesophagological Society. Ultimately, the committee developed 17 evidence-based recommendations across four categories: initial evaluation, medical management, surgical treatment, and postoperative management and rehabilitation. These guidelines aim to support clinicians in delivering optimal care to adult patients with SGS and TS.

Background: Vascular smooth muscle cells (VSMCs) play a crucial role in the development of occlusive vascular diseases through abnormal proliferation and migration. This pathological behavior is closely associated with mitochondrial reactive oxygen species (ROS)-mediated mitochondrial DNA (mtDNA) damage. The mitochondrial carrier protein solute carrier family 25 member 33 (SLC25A33), essential for nucleoside transport, is integral to mtDNA production. This study aimed to investigate the effects of SLC25A33 inhibition on the proliferation and migration of VSMCs, as well as its impact on neointima formation. Methods: VSMCs were isolated from the thoracic aorta of 4-week-old Sprague-Dawley rats. The effects of small interfering RNAinduced silencing of SLC25A33 mRNA on platelet-derived growth factor (PDGF)-induced proliferation and migration of VSMCs were analyzed. The in vivo effects of targeting the SLC25A33 gene on neointima formation were evaluated using a murine carotid artery ligation model by perivascularly applying Lenti-shSLC25A33 with Pluronic F-127 gel. Results: First, we observed an upregulation of the SLC25A33 protein in the carotid artery ligation-induced neointima in mice. Silencing of SLC25A33 suppressed the PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Knockdown of SLC25A33 inhibited PDGF-induced production of mtDNA and ROS, consequently inactivating the cyclic GMP-AMP synthesis (cGAS)-stimulator of interferon genes (STING)-TANK-binding kinase 1 (TBK1)-nuclear factor kappa B (NF-κB) pathway. Furthermore, the downregulation of SLC25A33 reduced carotid artery ligation-induced neointima in mice. Conclusion This study suggests that targeting SLC25A33 in VSMCs could be a novel therapeutic strategy to prevent occlusive vascular diseases.

Background: Chromosomal alterations serve as diagnostic and prognostic markers in acute leukemia. Given the evolving landscape of chromosomal abnormalities in acute leukemia, we previously studied these over two periods. In this study, we investigated the frequency of these abnormalities and clinical trends in acute leukemia in Korea across three time periods. Methods: We retrospectively analyzed data from 1,787 patients with acute leukemia (319 children and 1,468 adults) diagnosed between 2006 and 2020. Conventional cytogenetics, FISH, and multiplex quantitative PCR were used for analysis. The patient groups were divided according to the following three study periods: 2006–2009 (I), 2010–2015 (II), and 2016–2020 (III). Results: Chromosomal aberrations were detected in 92% of patients. The PML::RARA translocation was the most frequent. Over the 15-yr period, chromosomal aberrations showed minimal changes, with specific fusion transcripts being common among patients.ALL was more prevalent in children than in adults and correlated significantly with the ETV6::RUNX1 and RUNX1::RUNX1T1 aberrations. The incidence of ALL increased during the three periods, with PML::RARA remaining common. Conclusions The frequency of chromosomal abnormalities in acute leukemia has changed subtly over time. Notably, the age of onset of adult AML has continuously increased. Our results may help in establishing diagnoses and clinical treatment strategies and developing various molecular diagnostic platforms.