Purpose: Patient-derived cells (PDCs) and patient-derived organoids (PDOs) are complementary preclinical models widely used in translational cancer research. However, their molecular and functional differences have not been systematically characterized. This study established and analyzed paired PDC and PDO models derived from the same gastric cancer ascites to delineate platform-dependent molecular and functional profiles. Materials and Methods: Malignant ascites or pleural fluid obtained from 6 patients with advanced gastric cancer were used to establish paired PDC and PDO models. All pairs underwent comprehensive multi-omics profiling, integrating genomic, transcriptomic, and proteomic data. Phenotypic characterization included morphological, histological, proliferative, and cell cycle analyses. Drug sensitivity assays were performed using 4 chemotherapeutic agents commonly used to treat gastric cancer. Results: The 6 paired PDC and PDO models exhibited distinct morphological characteristics.Whole-genome analyses demonstrated high concordance among primary tumors, PDCs, and PDOs, confirming tumor representation across platforms. Multi-omics profiling identified platform-dependent molecular signatures; PDOs were enriched for extracellular matrix remodeling and stemness, whereas PDCs displayed proliferation- and immune-related signatures. Clinically relevant biomarkers, including HER2 and MET alterations, were concordant with primary tumors. Notably, drug responses differed between platforms and patients, indicating platform-dependent and patient-specific chemosensitivity. Conclusions Paired PDC and PDO models derived from the same patients preserved core patient-specific tumor characteristics while exhibiting distinct molecular and functional profiles. These findings underscore the culture platform as a critical determinant of experimental outcomes and therapeutic responses. Therefore, careful selection of an appropriate preclinical model is essential to accurately address biological questions and optimize precision oncology strategies.

Objective: : To investigate the clinical and radiological features of unruptured vertebral artery dissecting aneurysms (uVADAs) treated with reconstructive endovascular techniques and to evaluate the risk factors associated with unfavorable radiological outcomes while focusing on the flow diversion effect. Methods: : We retrospectively reviewed 86 patients with uVADAs treated at a single tertiary center between January 2009 and December 2022. The patients were categorized into the flow diversion group (patients with uVADAs treated with a flow diverter or multiple stents) and the non-flow diversion group (patients with one or fewer stent insertion). Unfavorable angiographic outcomes were defined as 1) recurrence after coil insertion regardless of stent deployment or 2) no regression after stent insertion without coil packing. Univariate and multivariate analyses were performed to assess the related risk factors. Results: : We observed 37 uVADAs in the flow diversion group. Recurrence or no regression occurred in two of 37 (9.1%) and 13 of 49 (27.7%) uVADAs in the flow and non-flow diversion groups, respectively. The treatment without flow diversion effect (non-flow diversion group; odds ratio [OR], 8.04; 95% confidence interval [CI], 1.23–52.57; p=0.003) and hypertension (OR, 22.09; 95% CI, 2.51–194.2; p=0.005) were significantly associated with unfavorable angiographic outcomes. Conclusion : The flow diversion effect using a flow diverter or multiple stents insertion, along with strict blood pressure control, may be an important factor in achieving favorable angiographic outcomes in uVADA treatment.

Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

Objectives: . This study aimed to elucidate the patterns of upper airway collapse in obstructive sleep apnea (OSA) patients with a low body mass index (BMI). Methods: . We designed and conducted a retrospective cohort study. Consecutive patients diagnosed with OSA who underwent drug-induced sleep endoscopy (DISE) were included. Patients were classified into four groups according to their BMI. Age, sex, and polysomnography data were investigated. The patterns of upper airway collapse were characterized by the structures involved (soft palate, tongue base, lateral pharyngeal wall, and epiglottis). We compared the patterns of upper airway collapse in the supine and lateral decubitus position among the four BMI groups using the chi-square test and multivariate binary logistic regression analysis. Results: . A total of 627 patients (male, 517; mean age, 47.6±12.8 years) were included, consisting of 45, 79, 151, and 352 patients who were underweight or lower normal-weight (defined as the low BMI group), upper normal-weight, overweight, and obese, respectively. Severity indicators of OSA, such as the overall apnea-hypopnea index and duration of SaO2 below 90%, were significantly lower in patients with a low BMI than in obese patients, while their average oxygen saturation was significantly higher. The most common obstruction site in the supine position was the tongue base in patients with a low BMI (100%), whereas this obstruction site was significantly less common in obese patients (54.8%). Tongue base obstruction was mostly relieved in the lateral position, with no discernible obstruction in 86.7% of the low BMI patients. Conclusion . Airway obstruction in OSA patients with a low BMI is mostly due to tongue base obstruction, which improves in the lateral position. These characteristics should be kept in mind when considering treatment options for this subgroup of OSA patients.

OBJECTIVETo obtain fundamental information for the standardization of herbal medicine in Korea.

METHODSWe analyzed the herbal medicine prescription data of patients at the Pusan National University Korean Medicine Hospital from March 2010 to February 2013. We used the Dongui-Bogam (Dong Yi Bao Jian) to classify prescribed herbal medicines.

RESULTSThe study revealed that the most frequently prescribed herbal medicine was 'Liuwei Dihuang Pill (LWDHP, )' which was used for invigorating 'Shen (Kidndy)-yin'. 'LWDHP' was most frequently prescribed to male patients aged 50-59, 60-69, 70-79 and 80-89 years, and 'Xionggui Tiaoxue Decoction (XGTXD, )' was most frequently prescribed to female patients aged 30-39 and 40-49 years. According to the International Classification of Diseases (ICD) codes, 'Diseases of the musculoskeletal system and connective tissue' showed the highest prevalence. 'LWDHP' and 'XGTXD' was the most frequently prescribed in categories 5 and 3, respectively. Based on the percentage of prescriptions for each sex, 'Ziyin Jianghuo Decoction ()' was prescribed to mainly male patients, and 'XGTXD' with 'Guima Geban Decoction ()' were prescribed to mainly female patients.

CONCLUSIONThis study analysis successfully determined the frequency of a variety of herbal medicines, and many restorative herbal medicines were identified and frequently administered.

Adult ; Aged ; Cross-Sectional Studies ; Drug Prescriptions ; Electronic Health Records ; Female ; Herbal Medicine ; Hospitals ; Humans ; Male ; Medicine, Korean Traditional ; Middle Aged ; Phytotherapy ; Republic of Korea

Drug-induced liver injury (DILI) is an increasingly common cause of acute hepatitis. We examined clinical features and types of liver injury of 65 affected patients who underwent liver biopsy according DILI etiology. The major causes of DILI were the use of herbal medications (43.2%), prescribed medications (21.6%), and traditional therapeutic preparations and dietary supplements (35%). DILI from herbal medications, traditional therapeutic preparations, and dietary supplements was associated with higher elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than was DILI from prescription medications. The types of liver injury based on the R ratio were hepatocellular (67.7%), mixed (10.8%), and cholestatic (21.5%). Herbal medications and traditional therapeutic preparations were more commonly associated with hepatocellular liver injury than were prescription medications (P = 0.002). Herbal medications and traditional therapeutic preparations induce more hepatocellular DILI and increased elevations in AST and ALT than prescribed medications.
Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Dietary Supplements/adverse effects ; Drug-Induced Liver Injury/enzymology/*etiology/pathology ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy/adverse effects ; Plant Preparations/adverse effects ; Prescription Drugs/adverse effects ; Republic of Korea ; Retrospective Studies

BACKGROUND/AIMS: To evaluate the diagnostic value of contrast (SonoVue(R)) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses. METHODS: CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass characterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI. RESULTS: The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with kappa values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a kappa value of 0.765. CONCLUSIONS: If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses.
Adult ; Aged ; Contrast Media/diagnostic use ; Female ; Humans ; Liver Diseases/pathology/radiography/*ultrasonography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Sensitivity and Specificity ; Tomography, X-Ray Computed

BACKGROUND: Gabapentin is a safe and well-tolerated anticonvulsant with a wide therapeutic index, and it is used for neuropathic pain. The aim of this study was to compare previous dosing methods with the administration of four different doses of gabapentin while maintaining the same maximum daily dose for the safe administration of high doses of the medication. METHODS: The subjects were outpatients with various neuropathic pain syndromes, with at least two of the following symptoms: allodynia, burning pain, shooting pain, or hyperalgesia. The TID group received equal doses of gabapentin 3 times per day, while the QID group received 4 different doses of gabapentin per day. The pain score, frequency of breakthrough pain (BTP), severity and the duration of pain, sleep disturbance due to nocturnal pain, and adverse effects were recorded each day. RESULTS: The average daily pain score and sleep disturbance were significantly reduced in the QID group between days 3 and 10 of the experiment. The adverse effects of the medication were also reduced in the QID group. However, the frequency of BTP and severity and duration of pain were not significantly different between two groups. CONCLUSIONS: Administration of 4 different doses of gabapentin during the initial titration in outpatients with neuropathic pain resulted in a significant reduction in awakening from breakthrough pain and a reduction in the adverse effects of the medication.
Ambulatory Care ; Amines ; Breakthrough Pain ; Burns ; Cyclohexanecarboxylic Acids ; Drug Administration Schedule ; gamma-Aminobutyric Acid ; Humans ; Hyperalgesia ; Neuralgia ; Outpatients

PURPOSE: Macrophage migration inhibitory factor (MIF) may serve as a general marker for systemic inflammation in septic and nonseptic acute critical illness. Additionally, our previous experiment has demonstrated that immunosuppressant Prostaglandin E2 (PGE2) lowered MIF levels and inhibited T-cells proliferation when compared to control levels. The addition of hypertonic saline (HTS) increased MIF production as compared with PGE2-stimulated T-cells in concordance with restore PGE2-suppressed T-cells proliferation. Generally, HTS has been well known for its anti-inflammatory effect so far. Therefore, the experiments were conducted to evaluate MIF after stimulating lipopolysaccharide (LPS) either in the presence or absence of HTS in monocyte, in response to early phase injury. METHODS: Human acute monocytic leukemic cell line (THP-1) cells were cultured in RPMI media, to a final concentration of 1 x 10(6) cells/mL. The effect of HTS on LPS-induced MIF was evaluated in monocyte with 1 microg/mL LPS. HTS at 10, 20 or 40 mmol/L above isotonicity was added. MIF concentrations of the supernatant were determined by enzyme-linked immunosorbent assay, and cell lysates were used for Western blots analysis to determine the MIF expression. RESULTS: MIF concentrations in the cell supernatant increased in LPS-induced cells compared to control cells. Also, levels of MIF protein expression were higher in LPS stimulating cells. However, the addition of HTS to LPS stimulated cell restored MIF concentrations and MIF expression. CONCLUSION: The role of HTS in maintaining physiological balance in human beings, at least in part, should be mediated through the MIF pathway.
Anti-Inflammatory Agents ; Blotting, Western ; Cell Line ; Critical Illness ; Dinoprostone ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunosuppression ; Inflammation ; Lipopolysaccharides ; Macrophage Migration-Inhibitory Factors ; Macrophages ; Monocytes ; Saline Solution, Hypertonic ; T-Lymphocytes