Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

<p>Abstract</p> <p>Background</p> <p>Cervical carcinoma (CC) is a leading cause of death among women worldwide. Human papilloma virus (HPV) is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways.</p> <p>Results</p> <p>We found 2,067 genes significantly up or down-modulated (at least 2-fold) in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways.</p> <p>Conclusion</p> <p>This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies.</p

Characterization of the global profile of genes expressed in cervical epithelium by Serial Analysis of Gene Expression (SAGE)

BACKGROUND: Serial Analysis of Gene Expression (SAGE) is a new technique that allows a detailed and profound quantitative and qualitative knowledge of gene expression profile, without previous knowledge of sequence of analyzed genes. We carried out a modification of SAGE methodology (microSAGE), useful for the analysis of limited quantities of tissue samples, on normal human cervical tissue obtained from a donor without histopathological lesions. Cervical epithelium is constituted mainly by cervical keratinocytes which are the targets of human papilloma virus (HPV), where persistent HPV infection of cervical epithelium is associated with an increase risk for developing cervical carcinomas (CC). RESULTS: We report here a transcriptome analysis of cervical tissue by SAGE, derived from 30,418 sequenced tags that provide a wealth of information about the gene products involved in normal cervical epithelium physiology, as well as genes not previously found in uterine cervix tissue involved in the process of epidermal differentiation. CONCLUSION: This first comprehensive and profound analysis of uterine cervix transcriptome, should be useful for the identification of genes involved in normal cervix uterine function, and candidate genes associated with cervical carcinoma

KEGG-Cellular Pathways integrating our expression data of WNT-signalling pathways

<p><b>Copyright information:</b></p><p>Taken from "Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways"</p><p>http://www.infectagentscancer.com/content/2/1/16</p><p>Infectious Agents and Cancer 2007;2():16-16.</p><p>Published online 6 Sep 2007</p><p>PMCID:PMC2034543.</p><p></p> Yellow boxes indicates a down regulation of expression in tumor cervices samples. Red boxes indicates a higher gene expression in cervical carcinoma samples. Blue boxes indicates that a member of indicated gene family is expressed in normal tissues, and other member in tumors. Green boxes indicate that the gene was not altered

KEGG-based metabolic pathways identified to be altered in cervical carcinomas

<p><b>Copyright information:</b></p><p>Taken from "Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways"</p><p>http://www.infectagentscancer.com/content/2/1/16</p><p>Infectious Agents and Cancer 2007;2():16-16.</p><p>Published online 6 Sep 2007</p><p>PMCID:PMC2034543.</p><p></p> To know cellular pathways involved and the extent of alteration in CC, we imported a list of significantly up and down-regulated genes to Pathway Express. Then the Impact Factor obtained was graphed

Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways-0

<p><b>Copyright information:</b></p><p>Taken from "Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways"</p><p>http://www.infectagentscancer.com/content/2/1/16</p><p>Infectious Agents and Cancer 2007;2():16-16.</p><p>Published online 6 Sep 2007</p><p>PMCID:PMC2034543.</p><p></p>ss. Genes with expression levels that are statistically beyond delta in either direction are plotted either above (induced, red) or below (repressed, green) the control group. Genes which expression level did not change more than the set delta in either direction were considered to be not statistically significantly different at the set false discovery rate. Cluster analysis of cDNA microarray data. Microarray data were analyzed by the Eisen Hierarchical Cluster program and visualized with TreeView. The cluster shows 2,836 genes. Each row represents a gene, whereas each column corresponds to a tissue sample, the color line below tissue samples indicates, a) green: normal samples and b) red: tumor samples. The relative abundance of each gene in the tissue correlates with color intensity (red induced; green, repressed; black, no change). On the dendogram, all eight invasive cervical cancers clustered together such as two of the tree normal samples (N and N1) cluster indicating their similarity based on expression profile

Data from: Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients

Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis. Chromatin immunoprecipitation (ChIP) assays derived from non-small cell lung carcinomas (NSCLC) hybridized on gene promoter tiling arrays and bioinformatics analyses were performed, and quantitative, functional and clinical validation were also carried out. We statistically identified a common profile consisting of 78 gene promoter targets, including Hedgehog-GLI1 gene promoter sequences (FDR≤0.1 and FDR≤0.2). The GLI-1 gene promoter region from -2,192 to -109 was occupied by MEOX2, accompanied by transcriptionally active RNA Pol II and was epigenetically linked to the active histones H3K27Ac and H3K4me3; these associations were quantitatively validated. Moreover, siRNA genetic silencing assays identified a MEOX2-GLI1 axis involved in cellular cytotoxic resistance to cisplatinum in a dose-dependent manner, as well as cellular migration and proliferation. Finally, Kaplan-Maier survival analyses identified significant MEOX2-dependent GLI-1 protein expression associated with clinical progression and poorer overall survival using an independent cohort of NSCLC patients undergoing platinum-based oncological therapy with both epidermal growth factor receptor (EGFR)-non-mutated and EGFR-mutated status. In conclusion, this is the first study to investigate epigenome-wide MEOX2-transcription factor occupation identifying a novel overexpressed MEOX2-GLI1 axis and its clinical association with platinum-based cancer drug resistance and EGFR-tyrosine kinase inhibitor (TKI)-based therapy responses in NSCLC patients

Lung Cancer Epigenomics Data_MEOX2/RNA Pol II_ratio_peaks

Identification of Fluorescence peaks derived from the MEOX2 and RNA POL II Immuno-precipitation assays, derived from lung carcinoma patients, using gene promoter tiling microarrays (NIMBLEGEN Platform, 3X720K format). Shown peak ID, chromosome, start and end of peaks, score and FDR, and Access number

Identification of Radiomic Signatures in Brain MRI Sequences T1 and T2 That Differentiate Tumor Regions of Midline Gliomas with H3.3K27M Mutation

Background: Radiomics refers to the acquisition of traces of quantitative features that are usually non-perceptible to human vision and are obtained from different imaging techniques and subsequently transformed into high-dimensional data. Diffuse midline gliomas (DMG) represent approximately 20% of pediatric CNS tumors, with a median survival of less than one year after diagnosis. We aimed to identify which radiomics can discriminate DMG tumor regions (viable tumor and peritumoral edema) from equivalent midline normal tissue (EMNT) in patients with the positive H3.F3K27M mutation, which is associated with a worse prognosis. Patients and methods: This was a retrospective study. From a database of 126 DMG patients (children, adolescents, and young adults), only 12 had H3.3K27M mutation and available brain magnetic resonance DICOM file. The MRI T1 post-gadolinium and T2 sequences were uploaded to LIFEx software to post-process and extract radiomic features. Statistical analysis included normal distribution tests and the Mann–Whitney U test performed using IBM SPSS® (Version 27.0.0.1, International Business Machines Corp., Armonk, NY, USA), considering a significant statistical p-value ≤ 0.05. Results: EMNT vs. Tumor: From the T1 sequence 10 radiomics were identified, and 14 radiomics from the T2 sequence, but only one radiomic identified viable tumors in both sequences (p p < 0.05) (CONVENTIONAL_Kurtosis, CONVENTIONAL_ExcessKurtosis, DISCRETIZED_Kurtosis, and DISCRETIZED_ExcessKurtosis). There were no radiomics useful for distinguishing tumor tissue from peritumoral edema in both sequences. Conclusions: Less than 5% of the radiomic characteristics identified tumor regions of medical–clinical interest in T1 and T2 sequences of conventional magnetic resonance imaging. The first-order and second-order radiomic features suggest support to investigators and clinicians for careful evaluation for diagnosis, patient classification, and multimodality cancer treatment planning

Memoria del tercer simposium sobre Historia, sociedad y cultura de México y América Latina

Esta Memoria del Tercer Simposium sobre Historia, Sociedad y Cultura de México y América Latina no sólo reúne 38 trabajos presentados durante el evento celebrado del 9 al 11 de octubre de 2007, sino que es constancia del interés de los investigadores y de las instituciones participantes por abordar temas que preocupan a la sociedad latinoamericana actual.El objetivo principal de este trabajo es doble. En el primer apartado, “Democracia y autoritarismo”, se establecen y comentan sendas definiciones de democracia y autoritarismo que, en principio, se podrían aplicar a cualquier sistema político de la historia de la humanidad. En el segundo apartado, “Aspectos por considerar en estudios de caso sobre cualquier tipo de democracia”, se mencionan algunos tópicos concretos involucrados en la concepción de democracia expuesta en el apartado anterior, con la finalidad de proporcionar elementos de análisis a quienes deseen aplicarlos a estudios de caso

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p&lt;0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology