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PubMed2025

Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function.

BACKGROUND: Advanced gastric cancer (GC) exhibits a high recurrence rate and a dismal prognosis. Myocyte enhancer factor 2c (MEF2C) was found to contribute to the development of various types of cancer. Therefore, our aim is to develop a prognostic model that predicts the prognosis of GC patients and initially explore the role of MEF2C in immunotherapy for GC. METHODS: Transcriptome sequence data of GC was obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and PRJEB25780 cohort for subsequent immune infiltration analysis, immune microenvironment analysis, consensus clustering analysis and feature selection for definition and classification of gene M and N. Principal component analysis (PCA) modeling was performed based on gene M and N for the calculation of immune checkpoint inhibitor (ICI) Score. Then, a Nomogram was constructed and evaluated for predicting the prognosis of GC patients, based on univariate and multivariate Cox regression. Functional enrichment analysis was performed to initially investigate the potential biological mechanisms. Through Genomics of Drug Sensitivity in Cancer (GDSC) dataset, the estimated IC50 values of several chemotherapeutic drugs were calculated. Tumor-related transcription factors (TFs) were retrieved from the Cistrome Cancer database and utilized our model to screen these TFs, and weighted correlation network analysis (WGCNA) was performed to identify transcription factors strongly associated with immunotherapy in GC. Finally, 10 patients with advanced GC were enrolled from Sun Yat-sen University Cancer Center, including paired tumor tissues, paracancerous tissues and peritoneal metastases, for preparing sequencing library, in order to perform external validation. RESULTS: Lower ICI Score was correlated with improved prognosis in both the training and validation cohorts. First, lower mutant-allele tumor heterogeneity (MATH) was associated with lower ICI Score, and those GC patients with lower MATH and lower ICI Score had the best prognosis. Second, regardless of the T or N staging, the low ICI Score group had significantly higher overall survival (OS) compared to the high ICI Score group. For its mechanisms, consistently, for Camptothecin, Doxorubicin, Mitomycin, Docetaxel, Cisplatin, Vinblastine, Sorafenib and Paclitaxel, all of the IC50 values were significantly lower in the low ICI Score group compared to the high ICI Score group. As a result, based on univariate and multivariate Cox regression, ICI Score was considered to be an independent prognostic factor for GC. And our Nomogram showed good agreement between predicted and actual probabilities. Based on CIBERSORT deconvolution analysis, there was difference of immune cell composition found between high and low ICI Score groups, probably affecting the efficacy of immunotherapy. Then, MEF2C, a tumor-related transcription factor, was screened out by WGCNA analysis. Higher MEF2C expression is significantly correlated with a worse OS. Moreover, its higher expression is also negatively correlated with tumor mutation burden (TMB) and microsatellite instability (MSI), but positively correlated with several immunosuppressive molecules, indicating MEF2C may exert its influence on tumor development by upregulating immunosuppressive molecules. Finally, based on transcriptome sequencing data on 10 paired tumor tissues from Sun Yat-sen University Cancer Center, MEF2C expression was significantly lower in paracancerous tissues compared to tumor tissues and peritoneal metastases, and it was also lower in tumor tissues compared to peritoneal metastases, indicating a potential positive association between MEF2C expression and tumor invasiveness. CONCLUSIONS: Our prognostic model can effectively predict outcomes and facilitate stratification GC patients, offering valuable insights for clinical decision-making. The identified transcription factor MEF2C can serve as a biomarker for assessing the efficacy of immunotherapy for GC.

Humans↗
PubMed2006

Dynamic modeling of chemical fate and transport in multimedia environments at watershed scale-I: theoretical considerations and model implementation.

A geo-referenced environmental fate model was developed for analyzing unsteady-state dispersion and distribution of chemicals in multimedia environmental systems. Chemical transport processes were formulated in seven environmental compartments of air, canopy, surface soil, root-zone soil, vadose-zone soil, surface water, and sediment. The model assumed that the compartments were completely mixed and chemical equilibrium was established instantaneously between the sub-compartments within each compartment. A fugacity approach was utilized to formulate the mechanisms of diffusion, advection, physical interfacial transport, and transformation reactions. The governing equations of chemical mass balances in the environmental compartments were solved simultaneously to reflect the interactions between the compartments. A geographic information system (GIS) database and geospatial analysis were integrated into the chemical transport simulation to provide spatially explicit estimations of model parameters at watershed scale. Temporal variations of the environmental properties and source emissions were also considered in the parameter estimations. The outputs of the model included time-dependent chemical concentrations in each compartment and its sub-compartments, and inter-media mass fluxes between adjacent compartments at daily time steps.

Computer Simulation↗
PubMedDate not supplied

[Socioeconomic inequalities and mental health. II. Methodological aspects and literature review].

OBJECTIVE: This study provides a framework for mental health inequalities beginners. It describes the methods used to measure socio economic inequalities and the inter-relations with different aspects of mental health: residence, mental health services organisation and main diagnostic categories. METHOD: Literature electronic-search on Medline, Psyclit, Econlit, Social Science Index and SocioSearch using and relating the key-words inequalities, deprivation, poverty, socio-economic status, social class, occupational class, mental health for the period 1965-2002 (June). The articles selected were integrated with manual search (publications of the same authors, cross-references, working documents and reports of international and regional organisations). RESULTS: Inequality is not an absolute concept and, mainly, it has been changing during the last years. For example, the integration and re-definition of variables that capture, in simple indices, a complex reality; the accent on social more than on economic aspects; the geo-validity and time-reference of the inequality's indices. Moreover, the inequalities could be the result of individual preferences, in this case, the social selection and social causation issues will raise the suitability for a public intervention. CONCLUSIONS: Up to now, research has been mainly concentrated in describing and measuring health inequalities. For designing effective interventions, policy makers need to ground decisions on health-socioeconomic inequalities explanatory models.

Databases as Topic↗
PubMed2003

Systematic prediction of new ferroelectrics in space groups P3(1) and P3(2).

Release 2002/2 of the Inorganic Crystal Structure Database (FIZ Karlsruhe, Germany, and Institute Laue-Langevin, Grenoble, France) contains 62 entries in space group P3(1) and ten entries in space group P3(2) for 49 different materials including eight families with two or more isostructural members. The structural criteria for ferroelectricity are satisfied for 16 new structure types at a confidence level that depends on the reliability of each determination. LaBGeO(5), a mineral with stillwellite structure, was previously reported as ferroelectric and forms an additional family with seven other members or related structures that satisfy the criteria. Ten structures reported in space group P3(1) or P3(2) are dubious or incorrect, with atomic coordinates that satisfy supergroup symmetry. One material is probably pyroelectric but is unlikely to become ferroelectric, and three others are either incompletely solved or incompletely refined. Among the predicted new ferroelectrics are Cu(2)BaGeS(4,) Fe(3)(Fe,Si)O(4)(OH)(5), Se(4)S(5), K(2)HCr(2)AsO(10), IV-RbNO(3), Rb(2)Sc(NO(3))(5), Na(3)ReO(5), Nd(14)(GeO(4))(2)(BO(3))(6)O(8), CsHgCl(3,) Ba(2)Cu(2)AlF(11), KYF(4), SrS(2)O(6).4H(2)O, Cu(3)PbTeO(6)(OH)(2), ReH(CO)(4), Ni(2)(NH(3))(9)Mo(CN)(8).2H(2)O and the 6T polytype of Ca(1.89)Ta(1.80)Sm(0.16)Ti(0.10)O(7), in addition to beta-LaBSiO(5), PbBAsO(5) and BaBAsO(5) in the stillwellite family.

Journal Article↗
PubMed2005

Where not to live: a geo-demographic classification of mortality for England and Wales, 1981-2000.

The aim of this paper is to pilot a method for geo-demographic classification for mortality patterns in Britain. Age and sex directly standardised mortality ratios (DSMRs) for 100 grouped International Classification of Disease series 9 causes of death (ICD-9) were calculated. The 84 European Parliamentary (EP) constituencies as defined in 1999 were used as the spatial basis of this study to allow regional comparisons to be made while comparing units of similar population sizes. Scotland was excluded from the final analysis, leaving 76 regions. This paper is a preliminary investigation of the patterns of the causes of death over time and space in England and Wales using cluster analysis to summarise some of the structure in the data. Seven major and three minor cluster profiles were developed.

Cause of Death↗
PubMed2002

Porcine gene discovery by normalized cDNA-library sequencing and EST cluster assembly.

Genetic and environmental factors affect the efficiency of pork production by influencing gene expression during porcine reproduction, tissue development, and growth. The identification and functional analysis of gene products important to these processes would be greatly enhanced by the development of a database of expressed porcine gene sequence. Two normalized porcine cDNA libraries (MARC 1PIG and MARC 2PIG), derived respectively from embryonic and reproductive tissues, were constructed, sequenced, and analyzed. A total of 66,245 clones from these two libraries were 5?-end sequenced and deposited in GenBank. Cluster analysis revealed that within-library redundancy is low, and comparison of all porcine ESTs with the human database suggests that the sequences from these two libraries represent portions of a significant number of independent pig genes. A Porcine Gene Index (PGI), comprising 15,616 tentative consensus sequences and 31,466 singletons, includes all sequences in public repositories and has been developed to facilitate further comparative map development and characterization of porcine genes (http://www.tigr.org/tdb/ssgi/). The clones and sequences from these libraries provide a catalog of expressed porcine genes and a resource for development of high-density hybridization arrays for transcriptional profiling of porcine tissues. In addition, comparison of porcine ESTs with sequences from other species serves as a valuable resource for comparative map development. Both arrayed cDNA libraries are available for unrestricted public use.

Animals↗
PubMed2004

Environmental concentrations of boron, LAS, EDTA, NTA and Triclosan simulated with GREAT-ER in the river Itter.

A computer simulation of the environmental concentrations of some typical consumer-product ingredients was performed using the geo-referenced exposure model GREAT-ER (Geo-referenced Regional Environmental Assessment Tool for European Rivers) in the river Itter. Boron and LAS were chosen as typical detergent ingredients along with EDTA, NTA and Triclosan as examples of household and cosmetic product ingredients. The simulations were based on consumption figures of the respective chemical in consumer products in the year 2000. For EDTA, the consumption figure used for the calculation had to be extended to commercial products since the EDTA-use in domestic products could not account for the measured concentrations alone. The resulting PEC (Predicted Environmental Concentration) for all investigated compounds showed very good accordance to the measured concentrations in the Itter which were monitored in the same year. The concentrations did not deviate more than by a factor of 3. GREAT-ER's calculated 90th-percentile was never exceeded by the monitoring result thus reflecting a reasonable accuracy.

Arylsulfonates↗
PubMedDate not supplied

Comparison of drug transporter levels in normal colon, colon cancer, and Caco-2 cells: impact on drug disposition and discovery.

A critical step in early phase drug development is the determination of oral bioavailability. In part, the ability to predict whether a drug will be effectively transported across the gastrointestinal mucosa can be estimated from the physicochemical properties of the compound. Although advancements through rational drug design have more correctly predicted bioavailability, considerable variability remains to be explained. Transporter expression throughout the gastrointestinal tract may explain much of this variation. ATP-binding cassette (ABC) transporters were the first family of transporters identified to modify bioavailability. More recently, the solute carrier family has also been shown to alter the pharmacokinetic profile of drugs. Currently, the Caco-2 human colon carcinoma cell line is often used by the pharmaceutical industry to evaluate intestinal absorption of drugs; however, in vivo/in vitro permeabilities with carrier mediated drugs do not correlate well, suggesting that Caco-2 transporter expression varies from that of the small intestine. With this is mind, we integrated U133A GeneChip expression data from the NCBIs Gene Expression Omnibus (GEO) collection and then compared the expression pattern of Caco-2 cells to normal colon to determine if the Caco-2 cell line is a reliable model for colonic delivery. Furthermore, transporter expression of Caco-2 cells was compared to that of human colon tumors to assess whether this cell line could be useful to predict drug absorption for colon cancer. Our analysis shows that the expression pattern for Caco-2 cells closely resembles the gene expression profile of transporters within the normal colon, suggesting that this cell line may serve as an in vitro model of colonic drug adsorption. However, the molecular "fingerprint" of Caco-2 was distinctly different from tumor samples, indicating that the Caco-2 model would unlikely predict accurate drug absorption for colon cancer sites.

ATP-Binding Cassette Transporters↗
PubMed2006

Linking childhood cancer with potential environmental exposure determinants.

Childhood chronic diseases, especially cancer, are of growing concern. Research has focused on 2 developmental periods, prenatal and postnatal. While it is hypothesized that chemical contaminants in the physical environment may play a role in the development and exacerbation of many chronic diseases, the role of environmental exposures in the etiology of these conditions remains uncertain. This can be somewhat attributed to the fact that it is very difficult to efficiently link chronic health effects with environmental exposures that are likely to have occurred temporally and spatially distant from diagnosis. This study explored the utility of linking childhood cancer cases with their birth certificate data as a method for increasing the number of geo-referenced data points available for linking health effect data with environmental monitoring data. This would begin to quantify the transiency of 1 subset of the population, and provide a basis for characterizing and estimating potentials for exposure to numerous environmental contaminants during prenatal and postnatal periods. A total of 441 unduplicated cancer diagnosis records of children who were both born and diagnosed with cancer in Wisconsin between 1995 and 2002 were linked with birth records to explore the variability between address at birth and diagnosis. The majority of records were matched to a birth record file (81.0%). Of these matched records, 86% moved <1 mile from birth to time of diagnosis. The results suggest that administrative and public health surveillance data can be used to quantify transiency. Data from the sample tested indicate that during the given time period children do not move far from their birth homes, suggesting minimal changes in exposure potential related to residence location from birth to diagnosis. This background is useful for future epidemiological investigations linking environmental factors with chronic health effects.

Child↗