1.Quercetin-3-Methyl Ether Induces Early Apoptosis to Overcome HRV1B Immune Evasion, Suppress Viral Replication, and Mitigate Inflammatory Pathogenesis
Jae-Hyoung SONG ; Seo-Hyeon MUN ; Sunil MISHRA ; Seong-Ryeol KIM ; Heejung YANG ; Sun Shim CHOI ; Min-Jung KIM ; Dong-Yeop KIM ; Sungchan CHO ; Youngwook HAM ; Hwa-Jung CHOI ; Won-Jin BAEK ; Yong Soo KWON ; Jae-Hoon CHANG ; Hyun-Jeong KO
Biomolecules & Therapeutics 2025;33(2):388-398
Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.
2.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
3.Atypical features of hepatic veno‑occlusive disease/sinusoidal obstruction syndrome after inotuzumab ozogamicin in adult patients with acute lymphoblastic leukemia
Kyung‑Hun SUNG ; Daehun KWAG ; Gi June MIN ; Sung‑Soo PARK ; Silvia PARK ; Sung‑Eun LEE ; Byung‑Sik CHO ; Ki‑Seong EOM ; Yoo‑Jin KIM ; Hee‑Je KIM ; Chang‑Ki MIN ; Seok‑Goo CHO ; Seok LEE ; Jae‑Ho YOON
Blood Research 2025;60():28-
Purpose:
Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS.
Methods:
We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases.
Results:
Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression.
Conclusion
Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.
4.Suprasellar Ectopic Pituitary Neuroendocrine Tumor Misdiagnosed as Pineal Parenchymal Tumor: A Case Report
Seung-Bin WOO ; Chang-Young LEE ; Chang-Hyun KIM ; Min-Yong KWON ; Jae Hyun KIM ; Sang Pyo KIM ; Sae Min KWON
Brain Tumor Research and Treatment 2025;13(2):53-57
We report a rare and diagnostically challenging case of a 39-year-old male patient who presented with symptoms of dizziness and headaches, without any focal neurological symptoms. Initial imaging studies suggested a germ cell tumor, and an endoscopic biopsy led to a preliminary diagnosis of a pineal parenchymal tumor of intermediate differentiation. However, histological evaluation following surgical resection revealed the final diagnosis to be an ectopic pituitary neuroendocrine tumor (PitNET), a condition that is exceedingly rare. Ectopic PitNETs are uncommon tumors that develop outside the normal anatomical location of the pituitary gland. Their atypical presentation often leads to misdiagnosis as other intracranial neoplasms. This case highlights the diagnostic challenges posed by ectopic PitNETs and contributes to the limited literature on this rare condition. It underscores the importance of maintaining a broad differential diagnosis in patients presenting with atypical intracranial neoplasms.
5.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.
6.Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14)
Sang Min LEE ; Bum-Sup JANG ; Won PARK ; Yong Bae KIM ; Jin Ho SONG ; Jin Hee KIM ; Tae Hyun KIM ; In Ah KIM ; Jong Hoon LEE ; Sung-Ja AHN ; Kyubo KIM ; Ah Ram CHANG ; Jeanny KWON ; Hae Jin PARK ; Kyung Hwan SHIN
Cancer Research and Treatment 2025;57(1):150-158
Purpose:
This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data.
Materials and Methods:
A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed.
Results:
Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS.
Conclusion
BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.
7.Comparative analysis of postoperative outcomes of single-incision cholecystectomy: Propensity score matching of robotic surgery using the da Vinci SP system and da Vinci Xi system vs. laparoscopic surgery
Jeong-Ik PARK ; Yong-Kyu CHUNG ; Young Min LEE ; Chang Woo NAM ; Yang Won NAH
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):140-149
Background:
s/Aims: We compared the postoperative outcomes of single-incision laparoscopic cholecystectomy (SILC) with those of single-incision robotic cholecystectomy (SIRC) using the da Vinci Xi and SP systems.
Methods:
We retrospectively analyzed data from 206 patients who underwent these procedures by a single surgeon between August 2020 and April 2022. Propensity score matching was used to adjust for confounders and evaluate outcomes.
Results:
SILC exhibited shorter operation times compared to SIRC with Xi and SP (44.9 ± 14.5 min vs. 55.3 ± 12.2 min vs. 55.2 ± 16.2 min, p < 0.001). SIRC with Xi had shorter docking times (6.2 ± 2.8 min vs. 10.3 ± 2.3 min, p < 0.001), while SIRC with SP demonstrated reduced console times (11.2 ± 2.4 min vs. 18.6 ± 8.0 min, p < 0.001). Pain scores and complications did not significantly differ between the groups.
Conclusions
Both SILC and SIRC showed comparable outcomes, with the SP system providing advantages such as reduced console time and fully articulated arms, likely reducing surgeon stress.
9.Proposal of age definition for early-onset gastric cancer based on the Korean Gastric Cancer Association nationwide survey data: a retrospective observational study
Seong-A JEONG ; Ji Sung LEE ; Ba Ool SEONG ; Seul-gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; Beom Su KIM ; Moon-Won YOO ; Jeong Hwan YOOK ; In-Seob LEE ;
Annals of Surgical Treatment and Research 2025;108(4):245-255
Purpose:
This study aimed to define an optimal age cutoff for early-onset gastric cancer (EOGC) and compare its characteristics with those of late-onset gastric cancer (LOGC) using nationwide survey data.
Methods:
Using data from a nationwide survey, this comprehensive population-based study analyzed data spanning 3 years (2009, 2014, and 2019). The joinpoint analysis and interrupted time series (ITS) methodology were employed to identify age cutoffs for EOGC based on the sex ratio and tumor histology. Clinicopathologic characteristics and surgical outcomes were compared between the EOGC and LOGC groups.
Results:
The age cutoff for defining EOGC was suggested to be 50 years, supported by joinpoint and ITS analyses. Early gastric cancer was predominantly present in the EOGC and LOGC groups. Patients with EOGC comprised 20.3% of the total study cohort and demonstrated a more advanced disease stage compared to patients with LOGC. However, patients with EOGC underwent more minimally invasive surgeries, experienced shorter hospital stays, and had lower postoperative morbidity and mortality rates.
Conclusion
This study proposes an age of ≤50 years as a criterion for defining EOGC and highlights its features compared to LOGC. Further research using this criterion should guide tailored treatment strategies and improve outcomes for young patients with gastric cancer.
10.Appropriateness of multidisciplinary treatment related to the adequacy evaluation of gastric cancer from the surgeon’s point of view: a retrospective cohort study
Ba Ool SEONG ; Seul-Gi OH ; Chang Seok KO ; Sa-Hong MIN ; Chung Sik GONG ; In-Seob LEE ; Beom Su KIM ; Jeong Hwan YOOK ; Moon-Won YOO
Annals of Surgical Treatment and Research 2025;108(4):240-244
Purpose:
Multidisciplinary treatment (MDT) in gastric cancer is an effective approach for establishing treatment plans.However, the appropriateness of using “ratio of MDT” as an item for evaluating the adequacy of gastric cancer treatment in Korea has not been previously researched. The purpose of this study is to verify whether the “ratio of MDT” is appropriate as an item for gastric cancer adequacy evaluation from the surgeon’s perspective.
Methods:
This study involved 142 patients who received MDT at our hospital between December 2015 and January 2023.Patients were divided into 2 groups based on the date when gastric cancer adequacy evaluation was implemented; there were 71 patients before and after the evaluation was conducted, respectively. Based on electronic medical records, the initial plan prepared before the MDT clinic and the final plan prepared after the clinic were compared to determine whether the plan was changed.
Results:
The average age of patients who received MDT before and after the evaluation was 64.8 and 62.2 years, respectively. Overall, 50 and 21 patients were male (70.4%) and female (29.6%), respectively, in both groups. Before the evaluation, 26 patients (36.6%) who received MDT changed their treatment plans after visiting the clinic, and 15 patients (21.1%) who received MDT after the evaluation had their treatment plans modified. Groups who received MDT and changes in treatment plans were significantly correlated (P = 0.042).
Conclusion
Our findings suggest that including the “ratio of MDT” as an item of gastric cancer adequacy evaluation needs reassessment.

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