Background: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is among the most important multidrug-resistant pathogens causing bloodstream infections (BSIs).Cefotaximase (CTX-M) enzymes are the most common and highly diverse ESBL family in E.coli. CTX-M-15 in group CTX-M-1 and CTX-M-14 in group CTX-M-9 are the most extensively disseminated enzymes. Multidrug-resistant E. coli strains complicate empirical therapy and increase healthcare burden globally and in Korea. We investigated the molecular epidemiology, sequence types (STs), and ESBL genotypes of E. coli bloodstream isolates in Korea and identified clinical risk factors for cefotaxime resistance. Methods: We collected all non-duplicated isolates of E. coli and related clinical information from patients with BSIs at eight sentinel hospitals in the Korean Global Antimicrobial Resistance Surveillance System (Kor-GLASS) collection network during 2017–2021. Duplicate isolates were removed to ensure representativeness of the data. Antimicrobial susceptibility was tested using disk diffusion tests, and multilocus sequence typing and betalactamase genotyping were performed. Results: Among 9,232 E. coli blood isolates, resistance rates to cefotaxime and ceftazidime were 36.4% and 11.4%, respectively. Among the clinical factors, age > 65 yrs (adjusted odds ratio [aOR], 1.36), hospital-origin infection (aOR, 2.55), and admission type (intensive care unit [ICU] vs. general ward; aOR, 1.34) were significant cefotaxime resistance risk factors. ST131 was the most prevalent among cefotaxime-resistant E. coli (64.8%, 2,180/3,363), followed by ST1193 (5.3%, N = 177), and ST69 (5.1%, N = 170).ST131, ST648, ST405, and ST410 cefotaxime-resistant E. coli isolates frequently harbored blaCTX-M-15, whereas ST1193 and ST68 showed a high proportion of blaCTX-M-27 carriers, and most ST457 and ST5150 isolates carried blaCTX-M-55. Conclusions Continuous monitoring of ESBL-producing E. coli is required to prevent further dissemination, guide empirical therapy, inform infection control policies, and ensure early detection of multidrug-resistant clones with the potential for widespread transmission.

Purpose: Immune checkpoint inhibitor plus chemotherapy is the standard first-line treatment for advanced gastric cancer; however, predictive biomarkers for optimal patient selection remain unsatisfactory. This study was aimed at evaluating the predictive value of tumor mutational burden (TMB) and insertion/deletion (Indel) rate in patients with gastric cancer treated with nivolumab plus chemotherapy. Materials and Methods: This retrospective study included 132 patients with gastric cancer treated with first-line nivolumab plus chemotherapy and 185 patients treated with chemotherapy alone, all of whom had next-generation sequencing data available. The TMB and Indel cut-offs were set at 15.63 mutations per megabase and 18.19%, respectively, as determined based on their ability to best distinguish progression-free survival (PFS) among the patients who received nivolumab plus chemotherapy. Results: PFS was favorable for nivolumab and chemotherapy than for chemotherapy alone in both the high and low TMB groups; nevertheless, survival benefits were observed only in the high Indel group. Among the subgroups defined based on both TMB and Indel rates, the high TMB and high Indel rate subgroup showed the greatest benefit from nivolumab plus chemotherapy compared with that from chemotherapy alone. The benefit of this subgroup remained significant in patients with proficient mismatch repair (MMR) tumors, whose survival outcomes were comparable to those of patients with deficient MMR tumors.Among patients treated with nivolumab plus chemotherapy, high TMB and Indel rate were independently associated with favorable survival outcomes. Conclusions Thus, Indel rate, particularly in combination with TMB, may be a promising predictive biomarker for gastric cancer. However, further validation of their predictive value is warranted.

The gastrointestinal stromal tumor (GIST) is one of the most common mesenchymal tumors of the gastrointestinal tract. Between the 1990s and early 2000s, GIST was identified as a tumor characterized by KIT or PDGFRA mutations, resulting in imatinib being established as an effective targeted therapy. However, with advances in molecular diagnostics, approximately 10%–15% of GISTs have been reported to harbor alternative mutations, such as those in the succinate dehydrogenase subunit genes and BRAF, leading to the development of additional targeted therapies. GISTs exhibit a wide spectrum of clinical behaviors, ranging from indolent to highly aggressive, prompting the development of diverse risk classification systems. However, multiple systems remain in use, leading to inconsistent pathologic reports. Moreover, the mitotic counting method—a key factor in risk stratification—has become a major source of confusion among pathologists owing to the adoption of digital pathology and discrepancies between updated international guidelines and outdated reimbursement requirements. These inconsistencies have hindered pathologic reporting and communication between pathologists and clinicians. This review comprehensively overviews the historical background, molecular subtypes, and risk classification systems of GIST, focusing on evolving issues in mitotic rate evaluation and the application of risk classification systems in clinical practice.

Objective: This study aimed to evaluate the feasibility, safety, and oncologic outcomes of irreversible electroporation (IRE) using a clustered electrode in patients with locally advanced pancreatic cancer (LAPC). Materials and Methods: In this single-center prospective cohort study, 13 patients with LAPC (median age, 60 years; range, 48–78 years) underwent clustered electrode IRE between September 2022 and September 2024. Patient characteristics, procedural details, and clinical outcomes were recorded. Endpoints included technical success, procedure-related complications, overall survival (OS), and progression-free survival (PFS). Results: Tumors were located in the pancreatic head in four patients (30.8%) and in the body/tail in nine (69.2%). The median tumor size was 2.4 cm (1.5–4.0 cm), and vascular invasion was present in all patients. Technical success was achieved in all patients. Intraoperative IRE was performed in 11 (84.6%) patients, and 2 (15.4%) patients underwent percutaneous IRE. Gastrointestinal bleeding events as major complications occurred in two patients (15.4%) and, both were successfully controlled by embolization. No 60-day mortality was observed. At a median follow-up of 24.5 months (range, 9.9–33.4 months) after IRE, median OS and PFS from IRE were 20.1 and 14.5 months, respectively. Conclusion IRE using clustered electrodes for LAPC appears to be a feasible therapeutic approach, offering reliable technical success and acceptable safety. Survival outcomes are encouraging; however, larger, controlled studies are required.

Purpose: Due to its rarity, treatment guidelines for appendiceal cancer have traditionally followed those established for colorectal cancer, despite showing distinct histologic and clinical features. This study aimed to compare the clinicopathologic characteristics and long-term oncologic outcomes of appendiceal cancer with those of right-sided colon cancers. Methods: We retrospectively reviewed the records of patients with stage I–III appendiceal, cecal, or ascending colon cancer who underwent curative resection between 2010 and 2020 at our center. A 1:3:3 exact matching for age, sex, TNM stage, and adjuvant chemotherapy was performed. Survival outcomes were analyzed using the Kaplan-Meier and Cox regression methods. Results: Overall, 245 patients with appendiceal cancer (n = 35), ascending colon cancer (n = 105), and cecal cancer (n = 105) were analyzed. Appendiceal cancer exhibited a higher proportion of T4 tumors and fewer harvested lymph nodes compared with ascending or cecal cancers. The mean follow-up duration was 9.5 years. The 5- and 10-year overall survival rates were lower in appendiceal cancer (66.2% and 52.9%) than in ascending (91.2% and 78.4%) or cecal cancer (88.5% and 78.3%). Similarly, the 10-year disease-free survival rate was lower in appendiceal cancer (59.2%) compared with ascending (83.1%) and cecal cancers (78.4%). Cox regression analysis identified age (≥65 years), perforation, nodal metastasis, and lymphovascular invasion as independent predictors of poor prognosis. Conclusion Appendiceal cancer exhibited significantly worse long-term survival compared to cecal or ascending colon cancer. Tumor perforation, nodal metastasis, and lymphovascular invasion were adverse prognostic factors for overall and disease-free survival.

Conventional aryl hydrocarbon receptor (AhR) antagonists, which play a critical role in modulating tumor immune evasion, have shown limited clinical translation due to poor solubility, restricted systemic exposure, and dose-limiting toxicities. To overcome these limitations, we developed SB5794, a phosphate prodrug of the potent AhR antagonist SB2617, designed to improve aqueous solubility and pharmacokinetic properties. SB5794 exhibited markedly enhanced solubility and achieved more than six-fold higher systemic exposure in mice compared with SB2617, while fully retaining its in vitro AhR antagonistic activity. In syngeneic tumor models, SB5794 significantly inhibited tumor growth, and its combination with anti–PD-1 therapy further enhanced antitumor efficacy. However, repeated-dose studies revealed dose-dependent histopathological changes in the gastrointestinal tract, liver, and immune organs. Collectively, these findings demonstrate that SB5794 possesses improved drug-like properties and strong immunomodulatory activity, supporting its potential as a next-generation AhR-targeted immunotherapeutic candidate.

This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Purpose: This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Materials and Methods: During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation. Results: CRFs were collected from 64 investigators at 64 sites for 1,079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 treatment-emergent adverse events (TEAEs) were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9-11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months. Conclusion This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.