Abstract Objective An inflammatory-immunological marker, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), was evaluated as a predictive marker of advanced head and neck cancer patients ...receiving chemoradiotherapy. Methods This study included 104 patients with treatment-naïve head and neck cancer who underwent definitive chemoradiotherapy. An inflammatory marker was measured at baseline and after 1 month of treatment. Univariate and multivariate analyses using Cox proportional hazards model were used to identify predictors of progression-free survival (PFS) and overall survival (OS). Results A univariate analysis revealed that T,N-stage, the pre- and posttreatment NLRs were significant predictors of progression after the chemoradiotherapy. However, the posttreatment NLR remained an independent predictor of PFS in the multivariate analysis (HR = 2.23, 95% CI 1.15–2.321; P = 0.001). A high posttreatment NLR was significantly associated with an increased risk of death (HR = 1.87, 95% CI 0.89–3.31; P = 0.037). Conclusion A high posttreatment NLR is associated with poor prognostic factor. An early reduction in the NLR after treatment may indicate survival improvement in the patients.
To regenerate the bone tissue, the fabrication of scaffolds for better tissue regeneration has attracted a great deal of attention. In fact, growth factors are already used in clinical practice and ...are being investigated for enhancing the capacity for bone tissue regeneration. However, despite their strong osteoinductive activity, these growth factors have several limitations: safety issues, high treatment costs, and the potential for ectopic bone formation. The aim of this study was therefore to develop ceramic scaffolds that could promote the capacity for bone regeneration without growth factors. Three-dimensional ceramic scaffolds were successfully fabricated from hydroxyapatite (HA) and tricalcium phosphate (TCP) using projection-based microstereolithography, which is an additive manufacturing technology. The effects of calcium ions released from ceramic scaffolds on osteogenic differentiation and bone regeneration were evaluated in vitro and in vivo. The osteogenesis-related gene expression and area of new bone formation in the HA/TCP scaffolds was higher than those in the HA scaffolds. Moreover, regenerated bone tissue in HA/TCP scaffolds were more matured than that in HA scaffolds. Through this study, we were able to enhance the bone regeneration capacity of scaffolds not by growth factors but by calcium ions released from the scaffolds. Ceramic scaffolds developed in this study might be useful for enhancing the capacity for regeneration in complex bone defects.
The purpose of this study was to evaluate the efficacy and safety of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE).We performed a retrospective chart review of ...cancer patients with a pulmonary embolism, deep vein thrombosis, or both. Our analysis included all patients who received rivaroxaban from March 2013 to June 2016 at the Hemato-Oncology Division at the Pusan National University Hospital in Korea.Preliminary results identified 123 patients with a history of cancer that were treated with rivaroxaban. The average duration of rivaroxaban therapy was 95.25 days. While 35 patients had resolved VTE after the initiation of rivaroxaban, only one patient had it recur on rivaroxaban treatment. Major bleeding was observed in 6 (4.9%) patients and minor bleeding in 12 (9.8%) patients. The majority of bleeding events occurred spontaneously and most incidences of bleeding could be treated conservatively. Recurrence and major bleeding events on rivaroxaban were relatively low despite the fact that many patients had metastatic disease. Among 52 patient deaths (42.3%), none were due to VTE or bleeding complications; the cause of death in the majority of cases was cancer progression.Rivaroxaban is effective and safe for the treatment of cancer-associated VTE.
Glucose toxicity contributes to progressive β-cell failure and the development of overt diabetes. Oxidative stress is an important aspect of glucose toxicity in pancreatic β-cells. We investigated ...whether the flavonoid apigenin protects pancreatic β-cells from 2-deoxy-D-ribose (dRib)-induced oxidative cell damage. HIT-T15 pancreatic β-cells were cultured with or without apigenin in the presence of dRib. Time- and dose-dependent cell viability was monitored using a cell counting kit (CCK-8), while the induction of apoptosis was analyzed using a cell death enzyme-linked immunosorbent assay (ELISA) kit. Mitochondrial membrane potential (ΔΨm) was determined using the JC-1 kit. Intracellular oxidative stress was measured by fluorometric analysis of DCFH oxidation using 2′,7′-dichlorofluorescin diacetate (DCFH-DA) as the probe. In addition, the DNA binding activity of the oxidative stress-related transcriptional factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) were analyzed. dRib reduced cell survival and ΔΨm, while it markedly increased intracellular levels of reactive oxygen species (ROS), apoptosis, and the activity of the oxidative stress-related transcription factors NF-κB and AP-1. However, pretreatment of cells with apigenin attenuated all the dRib-induced effects. The anti-oxidants, N-acetyl-L-cysteine (NAC) and alpha lipoic acid (ALA), also prevented both dRib-induced oxidative damage and activation of NF-κB and AP-1. Taken together, these results suggest that apigenin attenuates dRib-induced cell damage in pancreatic β-cells via oxidative stress-related signaling.
The formation of advanced glycation end products (AGEs) takes place during normal aging; however, their production is faster in people having diabetes. The accumulated AGEs reportedly play a role in ...the occurrence of various age-related disorders. Furthermore, the skin autofluorescence (SAF) technique can be used to detect accumulated AGEs levels. There are few reports on the association between skin accumulation of AGEs and risk of complications in type 2 diabetes mellitus.
In this study, we aimed to describe the association between the skin accumulation of AGEs and cardiovascular risk factors in Korean patients with type 2 diabetes. A total of 310 Korean patients with diabetes were enrolled, and the levels of AGEs were measured using SAP. Levels of fasting blood glucose (FBS), triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol, proteinuria, arterial pulse wave velocity (PWV), and blood vessel age were measured using an automatic waveform analyzer. General linear models were used to identify the independent effect of AGEs after adjusting for covariates (age, weight, and duration of diabetes).
The skin levels of AGEs were strongly correlated with the diabetes duration. Significant independent associations were observed for AGEs with FBS (P < 0.01), proteinuria (P < 0.001), and PWV (P < 0.001). The advanced glycated product was independently associated to the arterial pulse wave conduction velocity that is used as a representative method for measuring arteriosclerosis by analysis early cardiovascular risk factors.
Our results show that an increase in SAF levels in Korean patients with type 2 diabetes is associated with PWV and vein age, and thereby with arterial stiffness. Therefore, our results suggest that AGEs are associated with cardiovascular risk factors. The level of AGEs can thus be used as an indicator of cardiovascular diseases in the clinical diagnosis of patients with type 2 diabetes.
•Unclear association between skin accumulation of AGEs and T2DM complication risk.•Study Population: Korean patients with T2DM.•Strong correlation between skin levels of AGEs and diabetes duration.•Independent association between AGEs and arterial pulse wave conduction velocity.•Association between increased SAF levels in with PWV, vein age, arterial stiffness.
Type 2 Diabetes; Advanced glycation end products; Skin auto fluorescence.
Prediabetic subjects represent a vulnerable population, requiring special care to reduce the risk of diabetes onset. We developed and validated a diabetes risk score for prediabetic subjects using ...the Korea National Diabetes Program (KNDP) cohort. Subjects included in the multicenter and prospective cohort (n = 1162) had high diabetes risk at baseline (2005) and were followed until 2012. Survival analysis was performed to analyze the prospective cohort over time, and the bootstrap method was used to validate our model. We confirmed our findings in an external cohort. A diabetes risk score was calculated and the cut-off defined using a receiver operating characteristic curve. Age, body mass index, total cholesterol, and family history of diabetes were associated with diabetes. The model performed well after correction for optimism (C
= 0.735). A risk score was defined with a cut-off of ≥5 that maximized sensitivity (72%) and specificity (62%), with an area under the curve of 0.73. Prediabetic subjects with a family history of diabetes had a higher probability of diabetes (risk score = 5) irrespective of other variables; this result was confirmed in the external cohort. Hence, prediabetic subjects with a family history of diabetes have a higher probability of developing diabetes, regardless of other clinical factors.
Key message
This study describes a method for the regeneration of Ulleungdo hemlock through somatic embryogenesis and a protocol for the cryopreservation of embryogenic cultures.
Ulleungdo hemlock (
...Tsuga ulleungensis
) is a rare endemic forest species growing on Ulleung Island in Korea. Climate change and other factors such as insect pests and a low seed germination rate further endanger this species. Here, we established an in vitro propagation and cryopreservation system for Ulleungdo hemlock via somatic embryogenesis. Whole megagametophytes with zygotic embryos from immature Ulleungdo hemlock seeds were cultured on a modified Litvay medium supplemented with 9 µM 2,4-dichlorophenoxyacetic acid and 4.5 µM 6-benzylaminopurine. The cone collection date had a significant effect on the induction of embryogenic tissue (
P
< 0.001). Maturation medium containing Litvay salts, 50 g l
−1
polyethylene glycol 4000, 30 g l
−1
maltose, and abscisic acid (ABA) was used to test the effects of three different concentrations (30, 60, and 120 µM) of ABA on somatic embryo production. There were statistically significant effects of ABA concentration on somatic embryo production per 80 mg of embryogenic tissue (
P
< 0.001), and the most productive ABA concentration was 60 µM. We also conducted experiments to determine the effect of cryopreservation treatment on the maturation capacity of somatic embryos. Although the highest mean number of somatic embryo production per 80 mg of embryogenic tissue was obtained from a non-cryopreserved cell line (36.3 ± 3.5), no significant differences between the cryopreservation and non-cryopreservation treatment were observed (
P
= 0.093). Our results described here have great potential to contribute to the propagation and conservation of Ulleungdo hemlock in its native habitat.
Obesity is commonly associated with a high risk of metabolic disorders, and obesity-related metabolic abnormalities are affected by some specific obesity phenotypes, regional fat distribution, and ...body mass index. However, few studies have investigated the relationship between obesity phenotypes and regional fat distribution in Korean subjects. This study aimed to assess regional fat distribution by gender using magnetic resonance imaging (MRI), and to identify a link between fat distribution and metabolic disorders in Korean subjects.
This study included 35 Korean subjects (20 women, 15 men) who were classified into two groups by gender, and further divided into two groups based on their obesity phenotype: a metabolically abnormal obesity (MAO) and metabolically healthy obesity (MHO) group. Fat distribution was measured using MRI. The blood parameters were measured using a commercially available kit.
Women in the MAO group had more risk factors for metabolic abnormalities than those in the MHO group. Serum glucose, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels were also significantly higher in women with MAO than in those with MHO. The intermuscular adipose tissue (IMAT) of women with MAO was significantly higher than that of women with MHO. Serum HDL-C level was negatively correlated with IMAT, whereas leptin showed a positive correlation with IMAT in all subjects.
Metabolic abnormalities according to obesity phenotype posed a higher risk in women than that in men. These findings suggest that an understanding of gender differences in relation to the association between obesity and metabolic risk would be helpful to reduce the prevalence of obesity.
Purpose The incidence of maxillary sinus cancer (MSC) is extremely rare, representing less than 1% of all cancers. Because of its rarity, the management of locally advanced MSC is a challenging ...issue. The objective of the present study was to retrospectively compare the efficacy of 2 traditional treatment strategies, concurrent chemoradiotherapy (CCRT) versus combination of surgery and radiotherapy and/or chemotherapy (SRCT) in MSC. Patients and Methods From 1989 to 2010, 65 patients with histologically confirmed stage III or IVA/IVB were retrospectively analyzed. Results The median age of our subjects was 60 years (range 36 to 81). The present study involved 18 women (27.7%) and 47 men (72.3%). Of the 65 patients, 52 (80.0%) had squamous cell carcinoma. The TNM stage was stage III, as determined by the American Joint Committee on Cancer, 6th edition, in 27 patients (41.5%). Stage IVA or IVB was observed in 38 patients (58.5%). Of the 65 patients, 41 underwent treatment. Of these 41 patients, 26 and 15 patients underwent SRCT and CCRT, respectively. During the 75.6 months (range 6.4 to 249.4) of median follow-up, the median progression-free survival duration was 45.1 months (95% confidence interval 0.0 to 142.7). The 5-year overall survival rate was 64.8%. However, the patients who had undergone surgery had better progression-free survival (hazard ratio 2.363, 95% confidence interval 1.098 to 5.085, P = .028) and overall survival (hazard ratio 4.989, 95% confidence interval 1.646 to 15.118, P = .004). The SRCT group had a better progression-free survival ( P = .043) and overall survival ( P = .029) duration than did the CCRT group. Conclusion SRCT might be superior to CCRT for locally advanced MSC. Additional studies comparing the treatment outcomes of CCRT with SRCT are warranted.
Background
Previously, we identified eight novel minisatellites in the
MUC2
, of which allelic variants in
MUC2
-MS6 were examined to influence susceptibility to gastric cancer. However, studies on ...the susceptibility to gastrointestinal cancer of other minisatellites in the
MUC2
region still remain unprogressive.
Objective
In this study, we investigated whether polymorphic variations in the
MUC2
-MS8 region are related to susceptibility to gastrointestinal cancer.
Methods
We assessed the association between
MUC2
-MS8 and gastrointestinal cancers by a case–control study with 1229 controls, 486 gastric cancer cases, 220 colon cancer cases and 278 rectal cancer cases. To investigate whether intronic minisatellites affect gene expression, various minisatellites were inserted into the luciferase-reporter vector and their expression levels were examined. We also examined the length of
MUC2
-MS8 alleles in blood and cancer tissue matching samples of 107 gastric cancer patients, 125 colon cancer patients, and 85 rectal cancer patients, and investigated whether the repeat sequence affects genome instability.
Results
A statistically significant association was identified between rare
MUC2
-MS8 alleles and the occurrence of rectal cancer: odds ratio (OR), 6.66; 95% confidence interval (CI), 1.11–39.96; and
P
= 0.0165. In the younger group (age, < 55), rare alleles were significant associated with an increased risk of rectal cancer (odds ratio, 24.93 and
P
= 0.0001). Suppression of expression was found in the reporter vector inserted with minisatellites, and loss of heterozygosity (LOH) of the
MUC2
-MS8 region was confirmed in cancer tissues of gastrointestinal cancer patients (0.8–5.9%).
Conclusion
Our results suggest that the rare alleles of
MUC2
-MS8 could be used to identify the risk of rectal cancer and that this repeat region is related to genomic instability.
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