Background: To analyze the effects of socioeconomic status (type of insurance and income level) and cancer stage on the survival of patients with liver cancer in Korea. Methods: A retrospective cohort study was constructed using data from the Healthcare Big Data Platform project in Korea between January 1, 2007, and December 31, 2017. A total of 143,511 patients in Korea diagnosed with liver cancer (International Classification of Diseases, 10th Revision [ICD-10] codes C22, C220, and C221) were followed for an average of 11 years. Of these, 110,443 died. The patient’s insurance type and income level were used as indicators of socioeconomic status. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards regression model to analyze the relationship between the effects of sex, age, and cancer stage at first diagnosis (Surveillance, Epidemiology, and the End Results; SEER), type of insurance, and income level on the survival of patients with liver cancer. The interactive effects of the type of insurance, income level, and cancer stage on liver cancer death were also analyzed. Results: The lowest income group (medical aid) showed a higher risk for mortality (HR (95% CI); 1.37 (1.27–1.47) for all patients, 1.44 (1.32–1.57) for men, and 1.16 (1.01–1.34) for women) compared to the highest income group (1–6) among liver cancer (ICD-10 code C22) patients. The risk of liver cancer death was also higher in the lowest income group with a distant cancer stage (SEER = 7) diagnosis than for any other group. Conclusion Liver cancer patients with lower socioeconomic status and more severe cancer stages were at greater risk of death. Reducing social inequalities is needed to improve mortality rates among patients in lower social class groups who present with advanced cancer.

Background: This study aims to elucidate clinical features, therapeutic strategies, and prognosis of pineal parenchymal tumors (PPT) by analyzing a 30-year dataset of a single institution. Methods: We reviewed data from 43 patients diagnosed with PPT at Seoul National UniversityHospital between 1990 and 2020. We performed survival analyses and assessed prognostic factors. Results: The cohort included 10 patients with pineocytoma (PC), 13 with pineal parenchymaltumor of intermediate differentiation (PPTID), and 20 with pineoblastoma (PB). Most patients presented with hydrocephalus at diagnosis. Most patients underwent an endoscopic third ventriculostomy and biopsy, with some undergoing additional resection after diagnosis confirmation. Radiotherapy was administered with a high prevalence of gamma knife radiosurgery for PC and PPTID, and craniospinal irradiation for PB. Chemotherapy was essential in the treatment of grade 3 PPTID and PB. The 5-year progression-free survival rates for PC, grade 2 PPTID, grade 3 PPTID, and PB were 100%, 83.3%, 0%, and 40%, respectively, and the 5-year overall survival rates were 100%, 100%, 40%, and 55%, respectively. High-grade tumor histology was associated with lower survival rates. Significant prognostic factors varied among tumor types, with World Health Organization (WHO) grade and leptomeningeal seeding (LMS) for PPTID, and the extent of resection and LMS for PB. Three patients experienced malignant transformations. Conclusion This study underscores the prognostic significance of WHO grades in PPT. It is nec-essary to provide specific treatment according to tumor grade. Grade 3 PPTID showed a poor prognosis. Potential LMS and malignant transformations necessitate aggressive multimodal treatment and close-interval screening.

Background: To investigate the effect of parental social class on cancer mortality in children under 5 in Korea, two birth cohorts were constructed by linking national birth data to under-5 death data from the Statistics Korea for 1995–1999 (3,323,613 births) and 2010–2014 (2,297,876 births). Methods: The Cox proportional hazards model adjusted for covariates was used in this study. Results: Social inequalities of under-5 cancer mortality risk in paternal education and paternal employment status were greater in 2010–2014 than in 1995–1999. The gap of hazard ratio (HR) of under-5 cancer mortality between lower (high school or below) and higher (university or higher) paternal education increased from 1.23 (95% confidence interval, 1.041.46) in 1995–1999 to 1.45 (1.11–1.97) in 2010–2014; the gap of HR between parents engaged in manual work and non-manual work increased from 1.32 (1.12–1.56) in 1995–1999 to 1.45 (1.12–1.89) in 2010–2014 for fathers, and from 1.18 (0.7–1.98) to 1.69 (1.03–2.79) for mothers. When the parental social class was lower, the risk of under-5 cancer mortality was higher in not only adverse but normal births. Conclusion Social inequalities must be addressed to reduce the disparity in cancer mortality of children under 5 years old.

Purpose: This study aims to explore income-based disparities in breast cancer (BC) incidence and stage at presentation in a national population in South Korea, where a National Cancer Screening Program (NCSP) has been implemented. Methods: In 2007, new patients with BC were identified using the Korea Central Cancer Registry database. We calculated adjusted odds ratios (aORs) to evaluate the association between individual income level and the risk of distant stage BC at presentation, adjusting for women’s age, body mass index, disability registration, employment, region of residence, and year of diagnosis. Results: The cumulative age-standardized incidence of BC in the 11 years was highest among women in the richest quintile (2,040 per 100,000 women for 11 years), whereas the proportion of distant stage at presentation was the highest (10.2%) among the medical aid beneficiaries. The aOR of distant stage diagnosis at presentation was higher for lowerincome quintiles, and the risk was the highest in the medical aid beneficiaries (aOR, 2.25;95% confidence interval, 1.97–2.58) than in the richest quintile. The income-based gradient in aORs for distant stage did not differ between younger (< 40 years) and older patients. Conclusion A higher risk of distant stage BC at presentation among the lower-income and medical aid groups in the context of a NCSP was observed. A more focused approach toward women in lower-income groups is necessary to alleviate the disparity in the risk of advanced BC.

Objective: To investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN). Methods: We reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke– Fahn–Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRSD scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6–12, 24–36, and 60–72 months postoperatively. Results: Five classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6–12, 24–36, and 60–72 months, respectively. In four patients with full regular evaluations until 60–72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24–36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities. Conclusion The benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients’ subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN.

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

The safety and efficacy of fimasartan have been evaluated through post-marketing surveillance in real world clinical practice. The multi-center, prospective, open-label and non-interventional study. A total of 3,945 patients (3,729 patients for safety assessment and 3,473 patients for efficacy assessment) were screened in patients with essential hypertension in 89 study centers from 9 September 2010 through 8 September 2016. Among the total patients, 2,893 patients (77.6%) were administered fimasartan for 24 weeks or longer and were classified as ‘patients with long-term follow-up’, and the additional safety and efficacy analysis were performed. The improvement was defined as systolic blood pressure (SBP) controlled to ≤ 140 mmHg or decreased SBP differences ≥ 20 mmHg after treatment or diastolic blood pressure (DBP) controlled to ≤ 90 mmHg or decreased DBP differences ≥ 10 mmHg after treatment. Adverse drug reactions (ADRs) were reported in 3.8% patients; dizziness, and hypotension were the most frequently reported ADRs in total patients. The results of patients with long-term follow-up were comparable with total patients. The overall improvement rate in all efficacy assessment at the last visit was 87.1% (3,025/3,473 patients). The overall improvement rate of the patients with long-term follow-up was 88.9%. Fimasartan was well tolerated, with no new safety concerns identified and an effective treatment in the real world clinical practice for Korean patients with hypertension.
Blood Pressure ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Follow-Up Studies ; Humans ; Hypertension ; Hypotension ; Korea ; Marketing ; Prospective Studies

Various functional activities have been reported for the fermented soybean products doenjang (DJ) and cheonggukjang (CGJ), although no systemic investigations of their immune functions have been conducted to date. We examined the effects of an experimental diet of DJ, CGJ, or a mixture of unfermented raw material for 4 weeks on overall immunity and immune safety in mice. No significant alterations were observed in peripheral or splenic immune cells among groups. Enhanced splenic natural killer cell activity was observed in the DJ and CGJ groups compared with the plain diet group. T helper type-1 (Th1)-mediated immune responses were enhanced in the DJ and CGJ groups with an upregulated production ratio of IFN-γ vs. IL-4 and IgG2a vs. IgG1 in stimulated splenic T and B cells, respectively. Resistance to Listeria monocytogenes infection was observed in the DJ and CGJ groups. Overall, the results of this study suggest that DJ and CGJ intake consolidates humoral and cellular immunity to Th1 responses.
Animals ; B-Lymphocytes ; Diet ; Immunity, Cellular ; Immunoglobulin G ; Interleukin-4 ; Killer Cells, Natural ; Listeria monocytogenes ; Mice* ; Soybeans*

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.
Anoxia ; Brain Neoplasms ; Cell Death* ; Cell Line ; Dichloroacetic Acid ; Glioblastoma* ; Glucose ; Glycolysis ; Metabolism ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphotransferases ; Pyruvic Acid