Background The purpose of this study was to compare the clinical usefulness of the seventh Union Internationale Contre le Cancer/American Joint Committee on Cancer (AJCC/UICC) staging system vs the ...sixth AJCC/UICC staging system in patients with gastric cancer. Study Design Included were 1,799 patients who underwent surgery for gastric cancer between January 2001 and June 2005 at the National Cancer Center (South Korea). For the sixth and seventh AJCC/UICC staging systems, survival outcomes stratified by stage, by T classification, and by N classification were summarized using Kaplan-Meier curves and compared statistically using a log rank test; survival differences were quantified using hazard ratios estimated from a Cox regression model. The 2 systems were compared in terms of prognostic performances using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion (AIC) in the Cox regression analysis. Results Significant survival differences between each stage were not found using the seventh staging system, especially for stages IB, IIA, and IIB (p = 0.14 and p = 0.11). The sixth staging system had higher linear trend chi-square score and likelihood ratio chi-square score, which means better discriminatory ability, monotonicity, and homogeneity, and had smaller AIC, which indicates better optimistic prognostic stratification, especially in the N classification. The modified staging system combining the T classification of the seventh AJCC/UICC system and the N classification of the sixth system showed better prognostic performance compared with each separate version (sixth or seventh) of the staging system. Conclusions The seventh AJCC/UICC staging system is not more clinically useful than the sixth system in surgically treated patients with gastric cancer because of an inappropriate N classification. A new TNM system is required with a different N classification.
Recently, the incidence of gastroesophageal junction (GEJ) cancer has been increasing in Eastern countries. Mediastinal lymph node (MLN) metastasis rates among patients with GEJ cancer are reported ...to be 5-25%. However, survival benefits associated with MLN dissection in GEJ cancer has been a controversial issue, especially in Eastern countries, due to its rarity and potential morbidity.
We retrospectively reviewed 290 patients who underwent surgery for GEJ cancer at the National Cancer Center in Korea from June 2001 to December 2015. Clinicopathologic characteristics and surgical outcomes were compared between patients without MLN dissection (Group A) and patients with MLN dissection (Group B). Prognostic factors associated with the survival rate were identified in a multivariate analysis.
Twenty-nine (10%) patients underwent MLN dissection (Group B). Three of 29 patients (10.3%) showed a metastatic MLN in Group B. For abdominal LNs, the 5-year disease-free survival rate was 79.5% in Group A and 33.9% in Group B (P < 0.001). The multivariate analysis revealed that abdominal LN dissection, pT category, and pN category were statistically significant prognostic factors. LNs were the most common site for recurrence in both groups.
Abdominal LN dissection and pathologic stage are the important prognostic factors for type II and III GEJ cancer rather than mediastinal lymph node dissection.
Humulus japonicus Siebold & Zucc. (HJ) has traditionally been administered to patients with pulmonary disease, skin disease and hypertension in Korea, and it is considered to exert anti-inflammatory, ...antioxidant, antimicrobial and antimycobacterial effects. However, its effects against Alzheimer's disease (AD) have yet to be explored. Thus, this study was carried out to investigate whether HJ has a beneficial effect on the progression of AD in an animal model. A methanolic extract of HJ (500 mg/kg/day) was intragastrically administered to 5-month-old APP/PS1 transgenic (Tg-APP/PS1) mice for 2.5 months. Novel object recognition and Y-maze alteration tests were used to assess cognitive function, and an immunohistochemical assay was performed to assess amyloid β (Aβ)deposition, tau phosphorylation and gliosis. An in vitro assay using a microglial cell line was also performed to investigate the anti-inflammatory effects of HJ. Our results revealed that HJ significantly decreased the mRNA and protein expression levels of tumor necrosis factor-α (TNF‑α), interleukin (IL)-1β, IL-6 and inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide in the microglial cell line. The administration of HJ for 2 months improved the cognitive function of Tg-APP/PS1 mice. HJ notably reduced the area occupied by Aβ and neurofibrillary tangles, and the number of activated astrocytes and microglia in the cortex of Tg-APP/PS1 mice. The findings of our study suggest that HJ has the therapeutic potential to inhibit the progression of AD and to improve cognitive deterioration in Tg-APP/PS1 mice.
Natural guanidines, molecules that contain the guanidine moiety, are structurally unique and often exhibit potent biological activities. A phytochemical investigation of the leaves of Alchornea ...rugosa (Lour.) Müll.Arg. by MS/MS-based molecular networking revealed eight undescribed guanidine-flavanol conjugates named rugonines A–H. The chemical structures of the isolated compounds were comprehensively elucidated by NMR spectroscopy, HRESIMS, and circular dichroism (CD) analysis. All isolated compounds were tested for autophagosome formation in HEK293 cells stably expressing GFP-LC3. The results revealed that compounds rugonines D–G showed potential autophagy inhibitory activity.
Eight undescribed natural guanidines and one known compound were isolated from the leaves of Alchornea rugosa. Rugonines D-G showed strong autophagy inhibitory activity in HEK293 cells stably expressing GFP-LC3. Display omitted
•Unique guanidine-conjugated catechins were isolated from Alchornea rugosa.•HRESI-MS/MS-based molecular networking was applied for isolation of natural guanidines.•Rugonines D-G showed potential autophagy inhibitory activity on HEK293 cells stably expressing GFP-LC3.
Limacia scandens is traditionally used to treat depression and affective disorders in Malaysia. The chemical compositions have been reported to include bisbenzylisoquinoline and aporphine-type ...alkaloids in the genus Limacia Lour., but studies on the components of L. scandens have rarely been reported. Therefore, this study was conducted to determine new benzylisoquinoline alkaloid derivatives with autophagy regulation activity from this plant. Bioactivity-guided isolation was applied to various column chromatography methods using RP-18, Sephadex LH-20 open column chromatography, and preparative HPLC. The chemical structures of the isolated compounds were elucidated through spectroscopic data analysis, including NMR, HR-ESI-MS, and ECD data. In addition, isolated compounds were tested for autophagy-regulating activity in HEK293 cells expressing GFP-L3. Three new dimeric benzylisoquinoline alkaloids (1−3), one new 4-hydroxybenzoic acid-conjugated benzylisoquinoline alkaloid (4), and six known compounds (5−10) were isolated from the stems of L. scandens. All compounds (1–10) were screened for autophagy regulation in HEK293 cells stably expressing the GFP-LC3 plasmid. Among the isolated compounds, 1, 2, and 4 showed autophagic regulation activity that blocked the process of combining autophagosomes and lysosomes. They also inhibit the protein degradation process from the autolysosome as inhibitors of autophagy. Novel benzylisoquinoline alkaloids from L. scandens showed potent potency for the inhibition of autophagic flux. This study provides potential candidates for developing natural autophagy inhibitors for disease prevention and treatment.
Chemical investigation of the plant Gymnema latifolium led to the isolation of seven undescribed 23-glycosyl oleanane triterpenoids, gymlatinosides GLF1-GLF7, and two known compounds, gymnemosides D ...and E. The structures of the isolated compounds were elucidated using diverse spectroscopic methods. The extract of G. latifolium and all isolated compounds significantly enhanced 2-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino-2-deoxyglucose (2-NBDG) uptake into 3T3-L1 adipocytes at 20 μM. Among them, gymlatinosides GLF2 and gymlatinosides GLF4 showed particularly potent stimulatory effects on glucose uptake in a dose-dependent manner. Further investigation revealed that gymlatinosides GLF2 at 20 μM upregulated the expression of phosphorylated AMPK (p-AMPK). The results suggested that gymlatinosides GLF2 may enhance glucose uptake via regulating the AMPK signaling pathway.
Seven undescribed 23-glycosyl oleanane triterpenoids were isolated from Gymnema latifolium. All isolated compounds significantly enhanced 2-NBDG uptake into 3T3-L1 adipocytes. Compound 2 strongly upregulated the expression of phosphorylated AMPK (p-AMPK). Display omitted
•Seven undescribed 23-glycosyl oleanane glycosides (1–7) were isolated from Gymnema latifolium.•All isolated compounds were evaluated for glucose uptake activity by using 2-NBDG in 3T3-L1 adipocytes.•Compounds 2 and 4 may enhance glucose uptake by controlling the AMPK pathway.
Treatment strategy for early gastric cancer depends on the probability of lymph node metastasis. The aim of this study is to develop a nomogram predicting lymph node metastasis in early gastric ...cancer using clinicopathological factors and biomarkers.
A literature review was performed to identify biomarkers related to lymph node metastasis in gastric cancer. Seven markers were selected and immunohistochemistry was performed in 336 early gastric cancer tissues. Based on the multivariable analysis, a prediction model including clinicopatholgical factors and biomarkers was developed, and benefit of adding biomarkers was evaluated using the area under the receiver operating curve and net reclassification improvement. Functional study in gastric cancer cell line was performed to evaluate mechanism of biomarker.
Of the seven biomarkers studied, α1 catenin and CD44v6 were significantly associated with lymph node metastasis. A conventional prediction model, including tumor size, histological type, lymphatic blood vessel invasion, and depth of invasion, was developed. Then, a new prediction model including both clinicopathological factors and CD44v6 was developed. Net reclassification improvement analysis revealed a significant improvement of predictive performance by the addition of CD44v6, and a similar result was shown in the internal validation using bootstrapping. Prediction nomograms were then constructed based on these models. In the functional study, CD44v6 was revealed to affect cell proliferation, migration and invasion.
Overexpression of CD44v6 was a significant predictor of lymph node metastasis in early gastric cancer. The prediction nomograms incorporating CD44v6 can be useful to determine treatment plans in patients with early gastric cancer.
Countries differ in their treatment expertise and research results regarding gastric cancer; hence, treatment guidelines are diverse based on evidence and medical situations. A comprehensive and ...comparative review of each country's guidelines is imperative to understand the similarities and differences among countries. We reviewed and compared five gastric cancer treatment guidelines in terms of endoscopic, surgical, perioperative, and palliative systemic treatment based on evidence levels and recommendation grades, as well as the postoperative follow-up strategies for each guideline. The Korean, Chinese, and European guidelines provided evidence and grading of the recommendations. The United States guidelines suggested categories for evidence and consensus. The Japanese guidelines suggested evidence and recommendations only for systemic treatment. The Korean and Japanese guidelines described endoscopic treatment, surgery, and lymphadenectomy in detail. The Chinese, United States, and European guidelines more intensively considered perioperative chemotherapy. In particular, the indications for chemotherapy and the regimens recommended by each guideline differed slightly. Considering their medical situations, each guideline had some diversity in terms of adopting evidence, which resulted in heterogeneous recommendations. This review will help medical personnel to comprehensively understand the diversity in gastric cancer treatment guidelines for each country in terms of evidence and recommendations.
LiMn2O4, Li1.05Mn1.95O4, and Li1.05Mn1.95O3.95Cl0.05 are prepared by a solution-based process to investigate the influences of codoping of Li and Cl on the electrochemical performance and structural ...stability of Li1+x Mn2‑x O4‑y Cl y (x, y = 0, 0.05). Li1.05Mn1.95O3.95Cl0.05 features an improved cycling performance and rate capability compared with LiMn2O4 and Li1.05Mn1.95O4, which originate from the improved structural stability and the reduction in Mn dissolution into electrolyte by the codoping of Li and Cl. The improvement in the cycling performance of Li1.05Mn1.95O3.95Cl0.05 is more appreciable at a higher temperature. Further, the electrode resistance of Li1.05Mn1.95O3.95Cl0.05 is much lower than that of LiMn2O4 over the first charge, suggesting that LiMn2O4 with high electrode resistance is structurally unstable during cycling. Both the suppressed Mn dissolution and the reduced electrode resistance of Li1.05Mn1.95O3.95Cl0.05 are attributed to the reinforcement of MnO6 octahedral in Li1.05Mn1.95O3.95Cl0.05 framework by the strong ionic Mn–Cl bonds formed by the codoping of Li and Cl.
Background
The effects of obesity on prognosis in gastric cancer are controversial.
Aims
To evaluate the association between body mass index (BMI) and mortality in patients with gastric cancer.
...Methods
A single-institution cohort of 7765 patients with gastric cancer undergoing curative gastrectomy between October 2000 and June 2016 was categorized into six groups based on BMI: underweight (< 18.5 kg/m
2
), normal (18.5 to < 23 kg/m
2
), overweight (23 to < 25 kg/m
2
), mildly obese (25 to < 28 kg/m
2
), moderately obese (28 to < 30 kg/m
2
), and severely obese (≥ 30 kg/m
2
). Hazard ratios (HRs) for overall survival (OS) and disease-specific survival (DSS) were calculated using Cox proportional hazard models.
Results
We identified 1279 (16.5%) all-cause and 763 (9.8%) disease-specific deaths among 7765 patients over 83.05 months (range 1.02–186.97) median follow-up. In multivariable analyses adjusted for statistically significant clinicopathological characteristics, preoperative BMI was associated with OS in a non-linear pattern. Compared with normal-weight patients, underweight patients had worse OS HR 1.42; 95% confidence interval (CI) 1.15–1.77, whereas overweight (HR 0.84; 95% CI 0.73–0.97), mildly obese (HR 0.77; 95% CI 0.66–0.90), and moderately obese (HR 0.77; 95% CI 0.59–1.01) patients had better OS. DSS exhibited a similar pattern, with lowest mortality in moderately obese patients (HR 0.58; 95% CI 0.39–0.85). Spline analysis showed the lowest all-cause mortality risk at a BMI of 26.67 kg/m
2
.
Conclusion
In patients undergoing curative gastric cancer surgery, those who were overweight or mildly-to-moderately obese (BMI 23 to < 30 kg/m
2
) preoperatively had better OS and DSS than normal-weight patients.
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