Abstract
In breast cancer, cancer associated fibroblasts (CAF) express podoplanin but little is known about its mechanism of expression and modulation. This might be crucial for cancer cell movements ...and for the ability to escape from the tumor site. Podoplanin showed anti-adhesive activity towards tumor and immune cells. A key control of tumor microenvironment is exerted by microRNAs on gene expression. Therefore miRNAs profiling was performed with 3D-Gene microarray technology on a breast CAF model, on cell lysates and on secreted exosomes, in hypoxia versus normoxia culture conditions.
Systems biology enrichment analyses were carried out through bioinformatics using mathematical models that simulate in silico the behaviour of human physiology. Targets linked to the set of differential miRNAs, both up-regulated and down-regulated, have been analyzed with various methods including a hypergeometric distribution method. Processes linked to hypoxia, glycosylation, angiogenesis, extracellular matrix and pathways associated with PI3K-AKT, mTOR, P53 and chemokines signaling were studied.
We showed that podoplanin expression strongly affected miRNAs involved in these processes. Hypoxia increased expression of miR-210, miR-21 and miR-29b in cells over-expressing podoplanin. miR-21 is an oncogenic regulator in most cancer cells through its downstream target proteins among which stands the tumor suppressor PTEN, a candidate to alleviate hypoxia in tumors, regulating tumor angiogenesis and modulating tumor hypoxia. miR-29b is a tumor suppressor, it also correlates with PTEN repression.
We highlighted miRNA regulation of podoplanin expression through downregulation of upstream genes for tumor suppressor PTEN. The combination of miRNome analysis and systems biology bioinformatics uncovered potential miRNAs involved in the regulation of podoplanin activity in CAF. Such data analysis may be applied to protein and mRNA biomarkers and extended to other pathology pathways.
Citation Format: Anna Tejchman, Eric Mennesson, Isabelle Fixe, Alexandra Foucher, Simon Perera, Laura Artigas, Jose Manuel Mas, Catherine Grillon, Maciej Ugorski, Nadia Normand, Claudine Kieda. miRNome analyses reveal that activity of CAF expressed podoplanin in tumor microenvironment is modulated by exosome miRNAs involved in the PTEN-PI3K-AKT-mTOR signaling abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1460. doi:10.1158/1538-7445.AM2017-1460
There are different biological and clinical patterns of lung cancer between genders indicating intrinsic differences leading to increased sensitivity to cigarette smoke-induced DNA damage, mutational ...patterns of KRAS and better clinical outcomes in women while differences between genders at gene-expression levels was not previously reported. Here we show an enrichment of immune genes in NSCLC in women compared to men. We found in a GSEA analysis (by biological processes annotated from Gene Ontology) of six public datasets a repeated observation of immune gene sets enrichment in women. "Immune system process", "immune response", "defense response", "cellular defense response" and "regulation of immune system process" were the gene sets most over-represented while APOBEC3G, APOBEC3F, LAT, CD1D and CCL5 represented the top-five core genes. Characterization of immune cell composition with the platform CIBERSORT showed no differences between genders; however, there were differences when tumor tissues were compared to normal tissues. Our results suggest different immune responses in NSCLC between genders that could be related with the different clinical outcome.
Introduction: Heart failure (HF) is a frequent cause of readmissions. Despite caring for underresourced patients and dependence on government funding, safety net hospitals frequently incur penalties ...for failing to meet pay-for-performance readmission metrics. Limited research exists on the causes of HF readmissions in safety net hospitals. Therefore, we sought to investigate predictors of 30-day all-cause readmission in HF patients in the safety net setting. Methods: We performed a retrospective chart review of patients admitted for HF from October 2018 to April 2019. We extracted data on demographics and medical comorbidities and performed patient-specific review of social determinants and mental health in 4 domains: race/ethnicity, housing status, substance use, and mental illness. Multivariable Poisson regression modeling was employed to evaluate associations with 30-day all-cause readmission. Results: The study population included 290 patients, among whom the mean age was 59 years and 71% (n = 207) were male; 42% (120) were Black/African American (AA), 22% (64) were Hispanic/Latino, and 96% (278) had public insurance; 28% (79) were not housed, 19% (56) had a diagnosis of mental illness, and active substance use was common. The 30-day readmission rate was 25.5% (n = 88). Factors that were associated with increased risk of readmission included self-identifying as Black/AA (relative risk 2.28, 95% confidence interval 1.00-5.20) or Hispanic/Latino (2.53, 1.07-6.00), experiencing homelessness (2.07, 1.21-3.56), living in a shelter (3.20, 1.27-8.02), or intravenous drug use (IVDU) (2.00, 1.08-3.70). Conclusion: Race/ethnicity, housing status, and substance use were associated with increased risk of 30-day all-cause readmission in HF patients in a safety net hospital. In contrast to prior studies, medical comorbidities were not associated with increased risk of readmission.
Abstract
The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a ...3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (
p
= 0.030). Shorter telomere length was associated with cognitive performance (working memory,
r
= 0.31
p
= 0.015; verbal fluency,
r
= 0.28
p
= 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages.
Patients with end-stage heart failure are at high risk for sudden cardiac death. However, implantable cardioverter-defibrillator (ICD) is not routinely implanted given the high competing risk of pump ...failure. A unique population worth separate consideration are patients with end-stage heart failure awaiting heart transplantation, as prolonged survival improves the chances of receiving transplant.
To compare clinical outcomes of heart failure patients with and without an ICD awaiting heart transplant.
We performed an extensive literature search and systematic review of studies that compared end-stage heart failure patients with and without an ICD awaiting heart transplantation. We separately assessed the rates of total mortality, sudden cardiac death, nonsudden cardiac death, and heart transplantation. Risk ratio (RR) and 95% confidence intervals were measured using the Mantel-Haenszel method. The random effects model was used owing to heterogeneity across study cohorts.
Ten studies with a total of 36,112 patients were included. A total of 62.5% of patients had an ICD implanted. Patients with an ICD had decreased total mortality (RR 0.60, 95% CI 0.51–0.71, P < .00001) and sudden cardiac death (RR 0.27, 95% CI 0.11–0.66, P = .004) and increased rates of heart transplantation (RR 1.09, 95% CI 1.05–1.14, P < .0001). There was no difference in prevalence of nonsudden cardiac death (RR 0.68, 95% CI 0.44–1.04, P = .07).
ICD implantation is associated with improved outcomes in patients awaiting heart transplant, characterized by decreased total mortality and sudden cardiac death as well as higher rates of heart transplantation.
Abstract
INTRODUCTION:
There is different susceptibility to DNA damage induced by tobacco smoking between women and men. In despite of the great advances in the knowledge of the genomic landscape of ...lung cancer, is not explored the molecular differences between man and women. Our aim was to evaluate differentially enriched gene sets between the two genders.
METHODS:
We evaluated 03 public databases containing gene expression values from lung adenocarcinoma patients: GSE50081 (HG-U133_Plus_2; n = 181 samples), GSE47115 (Illumina HumanHT-12 WG-DASL V4.0 R2; n = 46 samples), GSE10072 (HG-U133A; n = 107 samples). We perform the Gene Set Enrichment Analysis (GSEA) to find differences between the genders. Each dataset was analyzed individually and was divided in cohorts of smokers and non-smokers (and healthy tissues by smoking status when it was included in the dataset). Cases with unknown smoking status and former smokers were excluded from the analysis. We use the Gene Ontology biological process terms to find similar enriched pathways between cohorts. We consider enriched process with statistical differences (p<0.05) or trends (P<0.08) in at least a cohort.
RESULTS:
The analysis did show immune genes enrichment in women such as cytokine production, defense response to bacteria and response to other organisms. In another hand, regulation of JNK and MAPKKK cascades was enriched in tumors and healthy tissues from non-smokers women. In men, the oxidoreductase activity acting on sulfur group of donors was enriched in smoking men.
CONCLUSION:
There are differences between tumors from women and men that should be deeply explored.
Citation Format: Joseph A. Pinto, Jhajaira M. Araujo, Alexandra Prado, Claudio Flores, Nadezhda K. Cardenas, Mayer Zaharia, Gustavo Sarria, Alfredo Aguilar, Silvia Neciosup, Henry Gomez, Luis Mas. Different gene expression between men and women patients with lung adenoarcinoma reveals enrichment of immune gene sets. abstract. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2188. doi:10.1158/1538-7445.AM2015-2188
The widely recognized burden of liver diseases makes training in pediatric hepatology (PH) imperative. The aim of this survey, which was part of a global survey on training in pediatric ...gastroenterology, hepatology and nutrition (PGHN) across Europe, was to assess the PH and liver transplantation (LT) infrastructure, staff and training programs in PGHN training centers.
Standardized questionnaires were collected from training centers via the presidents/representatives of the National Societies Network of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) from June 2016 to December 2019.
A total of 100 PGHN training centers participated in the survey (14/100 were national referral centers in PH and/or LT). Dedicated PH clinics were available in 75%, but LT clinics in only 11%. Dedicated beds for PGHN inpatients were available in 47/95 (49%) centers. Full-time or part-time specialists for PH care were available in 31/45 (69%) and 11/36 (31%) centers, respectively. Liver biopsies (LB) were performed in 93% of centers by: a PGHN specialist (35%); an interventional radiologist (26%); a pediatric surgeon (4%); or a combination of them (35%). Dividing the annual number of LBs in the centers performing LBs by the number of trainees gave a median (range) of 10 (1-125) per trainee. Transient elastography was available in 60/92 (65%) of centers.
The survey highlighted the differences and shortcomings in PH training across Europe. ESPGHAN should take initiatives together with National Societies to ensure the acquisition of PH knowledge and skills according to the ESPGHAN curriculum.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic-Hepatology-training-paper.pdf.
This survey evaluated the effects of the recognition of pediatric gastroenterology, hepatology and nutrition (PGHN) on European PGHN training centers.
Standardized questionnaires were collected from ...training centers via the presidents/representatives of the National Societies Network of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, from June 2016 to December 2019.
A total of 100 training centers from 19 countries participated in the survey: 55 from 12 countries where PGHN is formally recognized (Group 1) and 45 from 7 countries where it is not (Group 2). Training centers in Group 2 were less likely to have an integrated endoscopy suite, a written training curriculum and a training lead (P=0.059, P<0.001 and P=0.012, respectively). Trainees in Group 2 were less likely to be exposed to an adequate number of diagnostic endoscopies, while no differences were found in relation to liver biopsies. Half of the training centers in both Groups do not have dedicated beds for PGHN patients, while in 64% and 58%, respectively, trainees do not participate in on-call programs for PGHN emergencies. Research training is mandatory in 26% of the centers. The duration of training, as well as the assessment and accreditation policies, vary between countries.
This study has revealed significant discrepancies and gaps in infrastructure and training programs, training leadership, and assessment of training and certification across European training centers in PGHN. Strategies to support the recognition of PGHN and to standardize and improve training conditions should be developed and implemented.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic_AG-6496.pdf.
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