BACKGROUND: Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives. METHODS: This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses. RESULTS: The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group.Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity. CONCLUSION These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.

We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-Pgp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206).However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations.Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

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.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Background/Aims: The study investigated the incidence, risk factors, and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with ulcerative colitis (UC). Methods: This single-center retrospective study included patients with UC who underwent total proctocolectomy with ileal pouch-anal anastomosis at the Asan Medical Center in Korea between January 1987 and December 2022. The primary outcomes were endoscopic remission and pouch failure. The Cox’s proportional hazard model was used to identify the risk factors for CARP. Results: The clinical data of 232 patients were analyzed. The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). Among 74 patients (31.9%) with chronic pouchitis (CP), 31 (13.4%) had CARP, and 43 (18.5%) had chronic antibiotic-dependent pouchitis (CADP). The most frequent endoscopic phenotype was focal inflammation of the pouch (CP, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to use concomitant probiotics than patients with CADP (29.0% vs 72.1%, p<0.01). The endoscopic remission rate of CP, CARP, and CADP was 14.9%, 9.7%, and 18.6%, respectively.The pouch failure rate associated with CP, CARP, and CADP was 13.5%, 16.1%, and 11.6%, respectively. Current smoking status (adjusted hazard ratio [aHR], 2.96; 95% confidence interval [CI], 1.27 to 6.90; p=0.01) and previous use of biologics/small molecules (aHR, 2.40; 95% CI, 1.05 to 5.53; p=0.04) were significantly associated with CARP development. Conclusions UC patients who were current smokers and previously used biologics/small molecules had a higher risk of developing CARP. Concomitant use of probiotics was less likely to be associated with CARP development.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Objective: Acute coronary syndrome often requires urgent intervention. The 2023 European Society of Cardiology guidelines recommend invasive procedures within 24 hours for high-risk cases. Nevertheless, there have been limited studies on non-ST-segment elevation myocardial infarction (NSTEMI) in South Korea. This study compared the risk of complications based on the timing of intervention. Methods: A retrospective observational study was conducted on patients with chest pain and elevated high-sensitivity troponin T from January to December 2021 in the emergency department. Patients were categorized into early (≤24 hr) and late (>24 hr) intervention groups. Primary outcomes (death, restenosis, or stroke) at 12 months were compared. Survival and subgroup analyses were performed to examine the factors affecting the outcomes in the two groups. Results: Three hundred seventy six patients were enrolled in the study, and 115 patients were excluded. Among 261 patients, 106 and 155 patients were in the early intervention group (≤24 hr), and late intervention group (>24 hr), respectively. The primary outcome (death or restenosis) showed no significant difference (hazard ratio [HR] in the early intervention group at 12 mo; 1.03; 95% confidence interval [CI], 0.63-1.70; P=0.905). However, risk of stroke was lower in the early intervention group (HR in the early, 0.08; 95% CI, 0.00-0.66; P=0.013). Subgroup analysis showed no significant advantage for early intervention. Conclusion In NSTEMI patients, early intervention does not reduce death or restenosis but lowers stroke incidence. No specific risk factors favored early intervention.

Anticancer treatment for acute lymphocytic leukemia is based on drugs such as methotrexate, 6-mercaptopurine, vincristine, and asparaginase. Asparaginase-related pancreatitis is known to have an incidence of up to 18%, and is a major cause of discontinuation of anticancer treatment for leukemia due to acute onset and chronic complications. There were various cases of treatment of peripancreatic fluid retention caused by anticancer drugs in leukemia patients. Use of lumen-apposing metal stents (LAMS) for walled-off necrosis (WON) drainage has recently increased. The electrocautery-enhanced delivery system allowed simpler and faster stent placement, streamlining the overall procedure and potentially reducing procedure time. Therefore, favorable outcomes have been reported with the use of LAMS for endoscopic drainage of various conditions. In this paper, we discuss a case in which hot-system LAMS was performed to treat L-asparaginase-induced acute pancreatitis and pancreatic pseudocyst in an adult patient with acute lymphoblastic leukemia.