ABSTRACT
Purpose: A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process. Methods: Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process. Results: Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes. Conclusion: We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.
Subject(s)
Macrophages , Phagocytosis , Mice , Animals , Inflammation/metabolism , Interferons/metabolism , Sequence Analysis, RNAABSTRACT
What is already known about this topic?: Coastal areas of China have a higher reported incidence of other infectious diarrheal diseases (OIDD; excluding cholera, dysentery, typhoid, and paratyphoid) than inland areas of China. What is added by this report?: The incidence of OIDD in high latitude coastal provincial-level administrative divisions (PLADs) near Bohai Sea was positively correlated with sea surface temperatures (SSTs), while in coastal PLADs near the South China Sea was negatively correlated. What are the implications for public health practice?: The marine environmental risk factors acquired by remote sensing provide a new way for diseases surveillance and early warning. SSTs can be employed as predictor of OIDD in some coastal areas in China.
ABSTRACT
Exploring spatio-temporal patterns of disease incidence can help to identify areas of significantly elevated or decreased risk, providing potential etiologic clues. The study uses the retrospective analysis of space-time scan statistic to detect the clusters of COVID-19 in mainland China with a different maximum clustering radius at the family-level based on case dates of onset. The results show that the detected clusters vary with the clustering radius. Forty-three space-time clusters were detected with a maximum clustering radius of 100 km and 88 clusters with a maximum clustering radius of 10 km from 2 December 2019 to 20 June 2020. Using a smaller clustering radius may identify finer clusters. Hubei has the most clusters regardless of scale. In addition, most of the clusters were generated in February. That indicates China's COVID-19 epidemic prevention and control strategy is effective, and they have successfully prevented the virus from spreading from Hubei to other provinces over time. Well-developed provinces or cities, which have larger populations and developed transportation networks, are more likely to generate space-time clusters. The analysis based on the data of cases from onset may detect the start times of clusters seven days earlier than similar research based on diagnosis dates. Our analysis of space-time clustering based on the data of cases on the family-level can be reproduced in other countries that are still seriously affected by the epidemic such as the USA, India, and Brazil, thus providing them with more precise signals of clustering.
Subject(s)
COVID-19 , Brazil , China/epidemiology , Cities , Cluster Analysis , Humans , India , Retrospective Studies , SARS-CoV-2 , Spatio-Temporal AnalysisABSTRACT
BACKGROUND: Although China began implementing medical reforms in 2009 aimed at fair allocation of the regional distribution of doctors, little is known of their impact. This study analyzed the geographic distribution of doctors from 2002 to 2017. METHODS: This study calculated the Gini coefficient and Theil index among doctors in the eastern, central, and western regions (Category 1) of China, and in urban and rural areas (Category 2). The statistical significance of fairness changes was analyzed using the Mann-Whitney U test. RESULTS: The annual growth rates of the number of doctors for the periods from 2002 to 2009 and 2010 to 2017 were 2.38% and 4.44%. The Gini coefficients among Category 1 were lower than those in Category 2, and statistically decreased after the medical reforms (P < 0.01) but continued to increase in Category 2 (P = 0.463). In 2017, the Theil decomposition result of Category 1 was 74.33% for the between-group, and in Category 2, it was 95.22% for the within-group. CONCLUSIONS: The fairness among the regional distribution of doctors in Category 1 is now at a high level and is better than that before the reforms. While the fairness in Category 2 is worse than that before the reforms, it causes moderate inequality and is continually decreasing. Overall unfairness was found to be derived from the between-group.
Subject(s)
Healthcare Disparities , Physicians , China , Data Analysis , Health Care Reform , Humans , Physicians/supply & distribution , Socioeconomic FactorsABSTRACT
Being a globally emerging mite-borne zoonotic disease, scrub typhus is a serious public health concern in Nepal. Mapping environmental suitability and quantifying the human population under risk of the disease is important for prevention and control efforts. In this study, we model and map the environmental suitability of scrub typhus using the ecological niche approach, machine learning modeling techniques, and report locations of scrub typhus along with several climatic, topographic, Normalized Difference Vegetation Index (NDVI), and proximity explanatory variables and estimated population under the risk of disease at a national level. Both MaxEnt and RF technique results reveal robust predictive power with test The area under curve (AUC) and true skill statistics (TSS) of above 0.8 and 0.6, respectively. Spatial prediction reveals that environmentally suitable areas of scrub typhus are widely distributed across the country particularly in the low-land Tarai and less elevated river valleys. We found that areas close to agricultural land with gentle slopes have higher suitability of scrub typhus occurrence. Despite several speculations on the association between scrub typhus and proximity to earthquake epicenters, we did not find a significant role of proximity to earthquake epicenters in the distribution of scrub typhus in Nepal. About 43% of the population living in highly suitable areas for scrub typhus are at higher risk of infection, followed by 29% living in suitable areas of moderate-risk, and about 22% living in moderately suitable areas of lower risk. These findings could be useful in selecting priority areas for surveillance and control strategies effectively.
Subject(s)
Environment , Forests , Geographic Mapping , Mites , Scrub Typhus/epidemiology , Animals , Humans , Models, Theoretical , Nepal/epidemiology , TemperatureABSTRACT
Wetland is one of the three major ecosystems on the earth and has fundamental ecological functions and plays an irreplaceable role in serving biological survival and human development. Considering the characteristics of five types of wetlands, this study constructed a wetland ecological health evaluation indicator system using a wide variety of data from statistical report, field sampling, remote sensing, and questionnaire survey. In this study, we have selected 13 indicators (related to water, soil, biological, landscape and social factors) for ecological health evaluation of 19 wetlands in Beijing-Tianjin-Hebei region of China which have national importance. The detailed analysis shows a comprehensive health index of 5.53. There was significant spatial heterogeneity in the health status of the 19 wetlands in this region. The evaluation results and analysis provides scientific services for developing reasonable and targeted wetland protection and utilization policies of wetlands.
Subject(s)
Conservation of Natural Resources/methods , Environmental Monitoring/methods , Remote Sensing Technology , Wetlands , BeijingABSTRACT
Dengue fever is expanding rapidly in many tropical and subtropical countries since the last few decades. However, due to limited research, little is known about the spatial patterns and associated risk factors on a local scale particularly in the newly emerged areas. In this study, we explored spatial patterns and evaluated associated potential environmental and socioeconomic risk factors in the distribution of dengue fever incidence in Jhapa district, Nepal. Global and local Moran's I were used to assess global and local clustering patterns of the disease. The ordinary least square (OLS), geographically weighted regression (GWR), and semi-parametric geographically weighted regression (s-GWR) models were compared to describe spatial relationship of potential environmental and socioeconomic risk factors with dengue incidence. Our result revealed heterogeneous and highly clustered distribution of dengue incidence in Jhapa district during the study period. The s-GWR model best explained the spatial association of potential risk factors with dengue incidence and was used to produce the predictive map. The statistical relationship between dengue incidence and proportion of urban area, proximity to road, and population density varied significantly among the wards while the associations of land surface temperature (LST) and normalized difference vegetation index (NDVI) remained constant spatially showing importance of mixed geographical modeling approach (s-GWR) in the spatial distribution of dengue fever. This finding could be used in the formulation and execution of evidence-based dengue control and management program to allocate scare resources locally.
Subject(s)
Dengue/epidemiology , Population Density , Humans , Incidence , Nepal/epidemiology , Risk Factors , Spatial Regression , Urban PopulationABSTRACT
This study describes spatiotemporal distribution and geospatial diffusion patterns of dengue outbreak of 2013 in Jhapa district, Nepal. Laboratory-confirmed dengue cases were collected from the District Public Health Office, Government of Nepal. Choropleth mapping technique, Global Moran's Index, SaTScan, and standard deviational ellipse were used to map and quantify the outbreak dynamics. The results revealed heterogeneous distribution and globally autocorrelated patterns. Local clusters were observed in 3 major urban centers. The standard deviational ellipse demonstrated the outbreak occurred from the east and diffused to the west along the east-west highway in different weeks. The results of this study could be useful to public health authorities to plan and execute dengue control strategies.
Subject(s)
Dengue/epidemiology , Disease Outbreaks , Geographic Mapping , Humans , Laboratories , Nepal/epidemiology , Public Health , Spatio-Temporal AnalysisABSTRACT
Both the number of cases of dengue fever and the areas of outbreaks within Nepal have increased significantly in recent years. Further expansion and range shift is expected in the future due to global climate change and other associated factors. However, due to limited spatially-explicit research in Nepal, there is poor understanding about the present spatial distribution patterns of dengue risk areas and the potential range shift due to future climate change. In this context, it is crucial to assess and map dengue fever risk areas in Nepal. Here, we used reported dengue cases and a set of bioclimatic variables on the MaxEnt ecological niche modeling approach to model the climatic niche and map present and future (2050s and 2070s) climatically suitable areas under different representative concentration pathways (RCP2.6, RCP6.0 and RCP8.5). Simulation-based estimates suggest that climatically suitable areas for dengue fever are presently distributed throughout the lowland Tarai from east to west and in river valleys at lower elevations. Under the different climate change scenarios, these areas will be slightly shifted towards higher elevation with varied magnitude and spatial patterns. Population exposed to climatically suitable areas of dengue fever in Nepal is anticipated to further increase in both 2050s and 2070s on all the assumed emission scenarios. These findings could be instrumental to plan and execute the strategic interventions for controlling dengue fever in Nepal.
Subject(s)
Climate Change , Dengue/epidemiology , Models, Theoretical , Disease Outbreaks , Environment , Forecasting , Geography, Medical , Humans , Nepal/epidemiologyABSTRACT
BACKGROUND: Recently, the need for maintenance chemotherapy arose as a result of the significantly improved survival of patients with metastatic colorectal cancer (mCRC) without increasing adverse events. Currently used maintenance regimens are fluoropyrimidines, bevacizumab, and the combination of fluoropyrimidine with bevacizumab. A new combination with bevacizumab and erlotinib, a tyrosine kinase inhibitor of the epithelial growth factor receptor, has shown synergistic effects in preclinical tests and promising results in some clinical trials. Whether bevacizumab combined with erlotinib vs. bevacizumab alone as maintenance therapy will further improve the clinical outcomes in patients with mCRC is controversial. We conducted this meta-analysis to compare the survival benefit and safety of these two regimens in patients with mCRC. METHODS: We searched PubMed, EMBASE, and the Central Registry of Controlled Trials of the Cochrane Library up to August 2016. We also searched the Proceedings of the American Society of Clinical Oncology (1986 to August 2016). Abstracts were manually searched to identify relevant trials. A total of three randomized controlled trials with 682 patients met the inclusion criteria. RESULTS: Our results demonstrated that bevacizumab combined with erlotinib significantly improved overall survival (hazard ratio 0.78; 95 % confidence interval 0.66-0.93; p = 0.006) and progression-free survival (hazard ratio 0.79; 95 % confidence interval 0.68-0.92; p = 0.002). Significantly more grade 3 rash, diarrhea, infection total, and fatigue were observed in the bevacizumab combined with erlotinib arm, which were controllable and reversible. CONCLUSIONS: Based on current evidence, the addition of erlotinib to bevacizumab as maintenance therapy significantly increases overall survival and progression-free survival with an increased but manageable toxicity in patients with mCRC. It should be considered as a treatment option for these patients under the premise of a reasonable selection of the target population.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Angiogenesis Inhibitors , Antineoplastic Agents/administration & dosage , Bevacizumab/administration & dosage , Disease-Free Survival , Erlotinib Hydrochloride/administration & dosage , Humans , Neoplasm Metastasis , Survival AnalysisABSTRACT
Severe acute respiratory syndrome (SARS) is one of the most severe emerging infectious diseases of the 21st century so far. SARS caused a pandemic that spread throughout mainland China for 7 months, infecting 5318 persons in 194 administrative regions. Using detailed mainland China epidemiological data, we study spatiotemporal aspects of this person-to-person contagious disease and simulate its spatiotemporal transmission dynamics via the Bayesian Maximum Entropy (BME) method. The BME reveals that SARS outbreaks show autocorrelation within certain spatial and temporal distances. We use BME to fit a theoretical covariance model that has a sine hole spatial component and exponential temporal component and obtain the weights of geographical and temporal autocorrelation factors. Using the covariance model, SARS dynamics were estimated and simulated under the most probable conditions. Our study suggests that SARS transmission varies in its epidemiological characteristics and SARS outbreak distributions exhibit palpable clusters on both spatial and temporal scales. In addition, the BME modelling demonstrates that SARS transmission features are affected by spatial heterogeneity, so we analyze potential causes. This may benefit epidemiological control of pandemic infectious diseases.
Subject(s)
Pandemics/statistics & numerical data , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , China/epidemiology , Disease Outbreaks/statistics & numerical data , Humans , Spatio-Temporal AnalysisABSTRACT
BACKGROUND: The survival of patients with metastatic colorectal cancer (mCRC) could be improved with exposure to three active drugs, irinotecan, fluorouracil/leucovorin, and oxaliplatin, irrespective of their sequence. However, only 50%-80% of patients can be exposed to all the three drugs in a sequential strategy with two-drug combinations. We carried out this systematic assessment to compare the survival benefit and safety of FOLFOXIRI (irinotecan, fluorouracil/leucovorin, and oxaliplatin) ± bevacizumab (with or without bevacizumab) versus FOLFIRI (irinotecan and fluorouracil/leucovorin) ± bevacizumab (with or without bevacizumab) as first-line treatment for unresectable mCRC. METHODS: PubMed and EMBASE were searched for original articles written in English and published before December 2015. A total of 1,035 patients from three randomized controlled trials were included. RESULTS: Our results demonstrated that overall survival (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.73-0.97), progression-free survival (HR, 0.69; 95% CI, 0.59-0.81), and overall response rate (odds ratio, 1.96; 95% CI, 1.28-2.98) were significantly improved in the FOLFOXIRI ± bevacizumab arm compared to the FOLFIRI ± bevacizumab arm. Significantly higher incidences of neutropenia, anemia, diarrhea, stomatitis, and neuropathy were observed in the FOLFOXIRI ± bevacizumab arm. CONCLUSION: Current evidence shows that the combination of FOLFOXIRI ± bevacizumab significantly improves the overall survival, progression-free survival, and overall response rate of patients with mCRC, with an increased but manageable toxicity, compared with the combinations of FOLFIRI ± bevacizumab. The combination of FOLFOXIRI ± bevacizumab should be considered as a treatment option for these patients under the premise of reasonable selection of target population.
ABSTRACT
BACKGROUND: Due to recent emergence, dengue is becoming one of the major public health problems in Nepal. The numbers of reported dengue cases in general and the area with reported dengue cases are both continuously increasing in recent years. However, spatiotemporal patterns and clusters of dengue have not been investigated yet. This study aims to fill this gap by analyzing spatiotemporal patterns based on monthly surveillance data aggregated at district. METHODS: Dengue cases from 2010 to 2014 at district level were collected from the Nepal government's health and mapping agencies respectively. GeoDa software was used to map crude incidence, excess hazard and spatially smoothed incidence. Cluster analysis was performed in SaTScan software to explore spatiotemporal clusters of dengue during the above-mentioned time period. RESULTS: Spatiotemporal distribution of dengue fever in Nepal from 2010 to 2014 was mapped at district level in terms of crude incidence, excess risk and spatially smoothed incidence. Results show that the distribution of dengue fever was not random but clustered in space and time. Chitwan district was identified as the most likely cluster and Jhapa district was the first secondary cluster in both spatial and spatiotemporal scan. July to September of 2010 was identified as a significant temporal cluster. CONCLUSION: This study assessed and mapped for the first time the spatiotemporal pattern of dengue fever in Nepal. Two districts namely Chitwan and Jhapa were found highly affected by dengue fever. The current study also demonstrated the importance of geospatial approach in epidemiological research. The initial result on dengue patterns and risk of this study may assist institutions and policy makers to develop better preventive strategies.
Subject(s)
Dengue/epidemiology , Disease Notification/statistics & numerical data , Public Health , Cluster Analysis , Female , Humans , Incidence , Male , Nepal/epidemiology , Software , Spatio-Temporal AnalysisABSTRACT
China was attacked by a serious influenza A (H7N9) virus in 2013. The first human infection case was confirmed in Shanghai City and soon spread across most of eastern China. Using the methods of Geographic Information Systems (GIS) and ecological niche modeling (ENM), this research quantitatively analyzed the relationships between the H7N9 occurrence and the main environmental factors, including meteorological variables, human population density, bird migratory routes, wetland distribution, and live poultry farms, markets, and processing factories. Based on these relationships the probability of the presence of H7N9 was predicted. Results indicated that the distribution of live poultry processing factories, farms, and human population density were the top three most important determinants of the H7N9 human infection. The relative contributions to the model of live poultry processing factories, farms and human population density were 39.9%, 17.7% and 17.7%, respectively, while the maximum temperature of the warmest month and mean relative humidity had nearly no contribution to the model. The paper has developed an ecological niche model (ENM) that predicts the spatial distribution of H7N9 cases in China using environmental variables. The area under the curve (AUC) values of the model were greater than 0.9 (0.992 for the training samples and 0.961 for the test data). The findings indicated that most of the high risk areas were distributed in the Yangtze River Delta. These findings have important significance for the Chinese government to enhance the environmental surveillance at multiple human poultry interfaces in the high risk area.
Subject(s)
Influenza A Virus, H7N9 Subtype , Influenza, Human/epidemiology , Models, Theoretical , Agriculture , Animals , China/epidemiology , Environmental Monitoring , Humans , Population Density , Poultry , Risk FactorsABSTRACT
Hepatocellular carcinoma (HCC) is a lethal liver malignancy worldwide. In this study, we reported that protein phosphatase magnesium-dependent 1δ (PPM1D) was highly expressed in the majority of HCC cases (approximately 59%) and significantly associated with high serum α-fetoprotein (AFP) level (P = 0.044). Kaplan- Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor of HCCspecific overall survival (HR, 2.799; 95% CI, 1.346-5.818, P = 0.006). Overexpressing PPM1D promoted cell viability and invasion, whereas RNA interference-mediated knockdown of PPM1D inhibited proliferation, invasion, and migration of cultured HCC cells. In addition, PPM1D suppression by small interfering RNA decreased the tumorigenicity of HCC cells in vivo. Overall, results suggest that PPM1D is a potential prognostic marker and therapeutic target for HCC.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Protein Phosphatase 2C/blood , Animals , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnosis , Cell Line, Tumor , Female , Gene Knockdown Techniques , Humans , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Male , Mice, Inbred BALB C , Middle Aged , Neoplasm Invasiveness , Neoplasm Transplantation , Prognosis , RNA, Small Interfering , Survival Analysis , alpha-Fetoproteins/analysisABSTRACT
OBJECTIVE: Gemcitabine-based chemotherapy is widely used for unresectable advanced pancreatic cancer which contains locally advanced and metastatic pancreatic cancer. We performed meta-analysis to examine whether gemcitabine plus S-1 could improve treatment efficacy as first-line chemotherapy for those patients when compared with gemcitabine alone. METHODS: STATA was used to estimate the summary hazard ratios or odds ratios and their 95% confidence intervals. Heterogeneity among trials was examined by Cochran's χ(2) test. Publication bias was evaluated by Begg's and Egger's tests. Subgroup analysis based on the extent of disease was performed. RESULTS: Four randomized controlled trials including 878 Asian patients were analyzed. In total meta-analysis, gemcitabine plus S-1 significantly improved overall survival (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96; P = 0.015), progression-free survival (hazard ratio, 0.64; 95% confidence interval, 0.55-0.74; P < 0.001), overall response rate (odds ratio, 3.00; 95% confidence interval, 2.04-4.41; P < 0.001) and disease control rate (odds ratio, 1.78; 95% confidence interval, 1.32 to 2.39; P < 0.001), and was associated with more but manageable hematologic (leukocytopenia, neutropenia, thrombocytopenia) and non-hematologic (diarrhea, stomatitis, nausea, rash) adverse events. In subgroup analysis, gemcitabine plus S-1, comparing with gemcitabine, significantly improved overall survival in locally advanced patients (hazard ratio, 0.69; 95% confidence interval, 0.48 to 0.99; P = 0.022) but not in metastatic patients (hazard ratio, 0.75; 95% confidence interval, 0.46-1.23; P = 0.256). CONCLUSION: This meta-analysis confirmed the survival benefits of gemcitabine plus S-1 as first-line treatment for unresectable advanced pancreatic cancer at least in Asia, while good Eastern Cooperative Oncology group performance status was warranted. Importantly, we highlighted the significant overall survival benefit of gemcitabine plus S-1 in locally advanced patients but not in metastatic patients.
Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asian People , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Adult , Aged , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Drug Administration Schedule , Drug Combinations , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Odds Ratio , Oxonic Acid/administration & dosage , Oxonic Acid/adverse effects , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Randomized Controlled Trials as Topic , Research Report/standards , Tegafur/administration & dosage , Tegafur/adverse effects , Treatment Outcome , GemcitabineABSTRACT
The orphan nuclear receptor (NR5A2), which belongs to the NR5A subfamily of nuclear receptors, is expressed in developing and adult tissues of endodermal origin, and can contribute to the development of several cancers through regulating cell proliferation. NR5A2 (rs3790843 and rs3790844) single nucleotide polymorphisms (SNPs) genotyping were examined in DNA samples, extracted from paraffin-embedded cancer tissue. Clinicopathologic and follow-up data were collected from 944 patients with gastric cancer (GC). Associations of the 2 SNPs with the progression and prognosis in gastric cancer patients were analyzed using the SPSS version 18.0. We found that NR5A2 rs3790843 polymorphism was significantly associated with the risk of GC which had regional lymph node metastasis (p = 0.044) or distant metastasis (p = 0.020). Our results also indicated that rs3790844 polymorphism was associated with the increased overall survival (OS) of GC patients in the dominant model (GG vs. GA/AA, HR (hazard ratio) = 0.823, 95% CI (confidence interval) = 0.679-0.997), suggesting a potential protective role of the variant A allele. Additionally, in the stratified analysis, both NR5A2 rs3790843 and rs3790844 polymorphism were associated with significantly lower risk of death in the groups of female, tumor size >5 cm in a dominant model. Our results represent the first demonstration that the NR5A2 rs3790844 polymorphism is associated with increased OS of GC patients in the dominant model, and similar results were found among the female group and tumor size >5 cm group for NR5A2 rs3790843 polymorphism. Further validation in other larger studies with different ethnic populations and functional evaluations are needed.
Subject(s)
Genetic Association Studies , Polymorphism, Genetic , Receptors, Cytoplasmic and Nuclear/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Alleles , Female , Follow-Up Studies , Genotype , Haplotypes , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Patient Outcome Assessment , Prognosis , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Tumor BurdenABSTRACT
Whether S-1 could replace 5-Fluorouracil (5-Fu) or not in the treatment of advanced gastrointestinal (GI) cancer (including advanced gastric cancer [AGS] and metastatic colorectal cancer [mCRC]) in Asian patients has been controversial. This meta-analysis was performed to compare the activity, efficacy and toxicity of S-1-based versus 5-Fu-based chemotherapy in those Asian patients. Randomized controlled trials (RCTs) were identified by electronic search of Pubmed. Relevant abstracts were manually searched to identify relevant trials. A total of 2182 patients from eight RCTs were included, and our results demonstrated that S-1-based chemotherapy significantly improved overall survival (OS) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-1.00) and overall response rate (ORR) (odds ratio [OR], 1.72; 95% CI, 1.09-2.70), but no significant progression-free survival (PFS) benefit was found between arms (HR, 0.87; 95% CI, 0.72-1.06). Subgroup analyses revealed that S-1-based chemotherapy significantly improved OS and ORR in subgroups of patients with non-platinum containing regimens (P = 0.041; P = 0.034) and patients with no prior chemotherapy history (P = 0.025; P = 0.016). Statistically significant improvements of PFS and ORR in the S-1-based chemotherapy were observed in the subgroup of patients with AGC (P < 0.001; P = 0.005). S-1-based chemotherapy was characterized by significantly higher incidences of diarrhea, fatigue and thrombocytopenia, and a lower incidence of nausea. This analysis provided strong evidence for survival benefits of S-1, and S-1-based chemotherapy could be considered to replace 5-Fu-based therapy for the treatment of advanced GI cancer in Asian patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Fluorouracil/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Oxonic Acid/therapeutic use , Tegafur/therapeutic use , Asian People , Drug Combinations , Gastrointestinal Neoplasms/mortality , Humans , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
PURPOSE: Oral fluoropyrimidine (S-1, capecitabine) has been considered as an important part of various regimens. We aimed to evaluate the efficacy and safety of S-1-based therapy versus capecitabine -based therapy in gastrointestinal cancers. METHODS: Eligible studies were identified from Pubmed, EMBASE. Additionally, abstracts presented at American Society of Clinical Oncology (ASCO) conferences held between 2000 and 2013 were searched to identify relevant clinical trials. The outcome included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and advent events. RESULTS: A total of 6 studies (4 RCTs and 2 retrospective analysis studies) containing 790 participants were included in this meta-analysis, including 401 patients in the S-1-based group and 389 patients in the capecitabine-based group. Results of our meta-analysis indicated that S-1-based and capecitabine-based regimens showed very similar efficacy in terms of PFS (HR 0.92, 95% CI 0.78-1.09, Pâ=â0.360), OS (HR 1.01, 95% CI 0.84-1.21, Pâ=â0.949), ORR (HR 1.04, 95% CI 0.87-1.25, Pâ=â0.683) and DCR (HR 1.02, 95% CI 0.94-1.10, Pâ=â0.639). There was also no significant difference in toxicity between regimens other than mild more hand-foot syndrome in capecitabine-based regimens. CONCLUSION: Both the S-1-based and capecitabine-based regimens are equally active and well tolerated, and have the potential of backbone chemotherapy regimen in further studies of gastrointestinal cancers.