Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.
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ABSTRACT:
SUBMITTER: Kehrloesser S
PROVIDER: S-EPMC8096787 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe study was aimed at finding accurate and effective therapeutic targets and deepening our understanding of the mechanisms of advanced atherosclerosis (AA).MethodsWe downloaded the gene expression datasets GSE28829, GSE120521, and GSE43292 from Gene Expression Omnibus. Weighted gene coexpression network analysis (WGCNA) was performed for GSE28829, and functional enrichment analysis and protein-protein interaction network analysis were conducted on the key module. Significant genes in the key module were analyzed by molecular complex detection, and genes in the most important subnetwork were defined as hub genes. Multiple dataset analyses for hub genes were conducted. Genes that overlapped between hub genes and differentially expressed genes (DEGs) of GSE28829 and GSE120521 were defined as key genes. Further validation for key genes was performed using GSE28829 and GSE43292. Gene set enrichment analysis (GSEA) was applied to key genes.ResultsA total of 77 significant genes in the key module of GSE28829 were screened out that were mainly associated with inflammation and immunity. The subnetwork was obtained from significant genes, and 18 genes in this module were defined as hub genes, which were related to immunity and expressed in multiple diseases, particularly systemic lupus erythematosus. Some hub genes were regulated by SPI1 and associated with the blood, spleen, and lung. After overlapping with DEGs of GSE28829 and GSE120521, a total of 10 genes (HCK, ITGAM, CTSS, TYROBP, LAPTM5, FCER1G, ITGB2, NCF2, AIF1, and CD86) were identified as key genes. All key genes were validated and evaluated successfully and were related to immune response pathways.ConclusionOur study suggests that the key genes related to immune and inflammatory responses are involved in the development of AA. This may deepen our understanding of the mechanisms of and provide valuable therapeutic targets for AA.
| S-EPMC8683248 | biostudies-literature
Project description:PurposeTo identify preferred burnout interventions within a resident physician population, utilizing the Nominal Group Technique. The results will be used to design a discrete choice experiment study to inform the development of resident burnout prevention programs.MethodsThree resident focus groups met (10-14 participants/group) to prioritize a list of 23 factors for burnout prevention programs. The Nominal Group Technique consisted of three steps: an individual, confidential ranking of the 23 factors by importance from 1 to 23, a group discussion of each attribute, including a group review of the rankings, and an opportunity to alter the original ranking across participants.ResultsThe total number of residents (36) were a representative sample of specialty, year of residency, and sex. There was strong agreement about the most highly rated attributes which grouped naturally into themes of autonomy, meaning, competency and relatedness. There was also disagreement on several of the attributes that is likely due to the differences in residency specialty and subsequently rotation requirements.ConclusionThis study identified the need to address multiple organizational factors that may lead to physician burnout. There is a clear need for complex interventions that target systemic and program level factors rather than focus on individual interventions. These results may help residency program directors understand the specific attributes of a burnout prevention program valued by residents. Aligning burnout interventions with resident preferences could improve the efficacy of burnout prevention programs by improving adoption of, and satisfaction with, these programs. Physician burnout is a work-related syndrome characterized by emotional exhaustion, depersonalization, and a sense of reduced personal accomplishment [1]. Burnout is present in epidemic proportions and was estimated to occur in over 50 percent of practicing physicians and in up to 89 percent of resident physicians pre-COVID 19. The burnout epidemic is growing; a recent national survey of US physicians reported an 8.9 percent increase in burnout between 2011 and 2014 [2]. Rates of physician burnout have also increased [3] during the COVID-19 pandemic with a new classification of "pandemic burnout" experienced by over 52 percent of healthcare workers as early as June of 2020 [4]. Physician burnout can lead to depression, suicidal ideation, and relationship problems that may progress to substance abuse, increased interpersonal conflicts, broken relationships, low quality of life, major depression, and suicide [5-7]. The estimated rate of physician suicide is 300-400 annually [8-10].
| S-EPMC8932600 | biostudies-literature
Project description:This paper presents the results of a survey among key informants that was conducted between June and September 2011 in Breast Cancer Centers that were accredited according to the criteria of the German Cancer Society (DKG). The survey intended to assess the degree to which the breast cancer center concept was accepted among the key informants as well as to gain an overview over structures and processes in the centers. The Questionnaire for Breast Cancer Centres Key Informants 2011 (FRIZ 2011) was used with two reminders having been sent out. Questionnaires were sent back from 149 of the 243 initially contacted hospitals (response rate: 61.3?%). The vast majority of respondents indicated to be part of the Breast Cancer Center management. 110 of the 149 hospitals did also participate in the patient survey conducted in 2010. Among the key informants surveyed, the concept is highly accepted with regard to improvements in patient care. Overall, the concept is regarded as "good" or "very good" by almost all respondents. Both contact to resident doctors and the hospitals' reputations improved since the implementation of the concept. Quality and patient safety were more often on the agenda than financial performance in the quality circles with the main co-operation partners of the Breast Cancer Centers.
| S-EPMC4168333 | biostudies-literature
Project description:BackgroundOvarian cancer is one of the most lethal malignant gynecologic tumors worldwide. We aimed to identify critical hallmarks of the surface epithelium between normal ovaries and serous ovarian carcinomas and then obtain the hub genes associated with these critical hallmarks.MethodsWe chose GSE36668, GSE54388 and GSE69428 as data sources and then determined the common gene sets through gene set enrichment analysis (GSEA) to explore essential hallmarks and hub genes driving normal ovarian cells to evolve progressively into a neoplastic state. The differentially expressed genes (DEGs) extracted separately in each gene set were analyzed again through the Metascape website. Kaplan-Meier plotter was used to obtain significant prognostic information. The hub genes were obtained through protein-protein interaction (PPI) network by Cytoscape. Hub genes were confirmed to have higher mRNA and protein expression levels in ovarian cancer tissues than in normal tissues through public databases [Gene Expression Profiling Interactive Analysis (GEPIA) and The Human Protein Atlas]. Correlation analysis of six hub genes showed a strong correlation via R.ResultsWe obtained 11 common hallmarks from GSEA of the three mentioned datasets and 22 hub genes that showed a significant association with poor survival.ConclusionsNot only the gene sets enriched by GSEA but also the hub genes extracted by the PPI network indicate that the most fundamental trait of ovarian cancer cells involves their ability to sustain chronic proliferation.
| S-EPMC8797326 | biostudies-literature
Project description:Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer-testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology.
| S-EPMC4660212 | biostudies-literature
Project description:BackgroundComprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer.Methods and resultsIn this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours.ConclusionsOverall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus.
| S-EPMC9386325 | biostudies-literature
Project description:The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited.We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression.We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement (p < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption (p < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 (p < 0.001).Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012.
| S-EPMC5555753 | biostudies-other
Project description:MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR-491 is only a passenger event or has an important role. Small-RNA sequencing of samples from GBM patients demonstrated that both mature products of MIR-491 (miR-491-5p and -3p) are downregulated in tumors compared with the normal brain. The integration of GBM data from The Cancer Genome Atlas (TCGA), miRNA target prediction and reporter assays showed that miR-491-5p directly targets EGFR, CDK6 and Bcl-xL, whereas miR-491-3p targets IGFBP2 and CDK6. Functionally, miR-491-3p inhibited glioma cell invasion; overexpression of both miR-491-5p and -3p inhibited proliferation of glioma cell lines and impaired the propagation of glioma stem cells (GSCs), thereby prolonging survival of xenograft mice. Moreover, knockdown of miR-491-5p in primary Ink4a-Arf-null mouse glial progenitor cells exacerbated cell proliferation and invasion. Therefore, MIR-491 is a tumor suppressor gene that, by utilizing both mature forms, coordinately controls the key cancer hallmarks: proliferation, invasion and stem cell propagation.
| S-EPMC4205227 | biostudies-literature
Project description:To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5-87.5% of cases); presentation to multidisciplinary tumour board (2.5-100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42-102.5 days); number of treatment interruptions ≥ 1 day (7.5-97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures.
| S-EPMC8192927 | biostudies-literature
Project description:Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12-14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and in how to improve the therapeutic approach. Here, we report miR-340 as prognostic tumor-suppressor microRNA for glioblastoma. We analyzed microRNA expression in > 500 glioblastoma patients and found that although miR-340 is strongly down-regulated in glioblastoma overall, it is up-regulated in LTS patients compared to short-term survivors (STS). Indeed, miR-340 expression predicted better prognosis in glioblastoma patients. Coherently, overexpression of miR-340 in glioblastoma cells was found to produce a tumor-suppressive activity. We identified NRAS mRNA as a critical, direct target of miR-340: in fact, miR-340 negatively influenced multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways. Thus, we demonstrate that expression of miR-340 in glioblastoma is responsible for a strong tumor-suppressive effect in LTS patients by down-regulating NRAS. miR-340 may thus represent a novel marker for glioblastoma diagnosis and prognosis, and may be developed into a tool to improve treatment of glioblastoma.
| S-EPMC4991399 | biostudies-literature