scholarly journals Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

2020 ◽  
Vol 3 (3) ◽  
pp. 63 ◽  
Author(s):  
Alice Bradfield ◽  
Lucy Button ◽  
Josephine Drury ◽  
Daniel C. Green ◽  
Christopher J. Hill ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
In Silico ◽  
Prognostic Markers ◽  
Treatment Strategies ◽  
Interaction Network ◽  
Telomerase Activity ◽  
Telomere Maintenance ◽  
The Cancer Genome Atlas ◽  
Future Research

Endometrial cancer (EC) is the commonest gynaecological malignancy. Current prognostic markers are inadequate to accurately predict patient survival, necessitating novel prognostic markers, to improve treatment strategies. Telomerase has a unique role within the endometrium, whilst aberrant telomerase activity is a hallmark of many cancers. The aim of the current in silico study is to investigate the role of telomere and telomerase associated genes and proteins (TTAGPs) in EC to identify potential prognostic markers and therapeutic targets. Analysis of RNA-seq data from The Cancer Genome Atlas identified differentially expressed genes (DEGs) in EC (568 TTAGPs out of 3467) and ascertained DEGs associated with histological subtypes, higher grade endometrioid tumours and late stage EC. Functional analysis demonstrated that DEGs were predominantly involved in cell cycle regulation, while the survival analysis identified 69 DEGs associated with prognosis. The protein-protein interaction network constructed facilitated the identification of hub genes, enriched transcription factor binding sites and drugs that may target the network. Thus, our in silico methods distinguished many critical genes associated with telomere maintenance that were previously unknown to contribute to EC carcinogenesis and prognosis, including NOP56, WFS1, ANAPC4 and TUBB4A. Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research.

scholarly journals Non-Coding RNAs as Prognostic Markers for Endometrial Cancer

2021 ◽  
Vol 22 (6) ◽  
pp. 3151 ◽  
Author(s):  
Roberto Piergentili ◽  
Simona Zaami ◽  
Anna Franca Cavaliere ◽  
Fabrizio Signore ◽  
Giovanni Scambia ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Markers ◽  
Classification Systems ◽  
Prognostic Role ◽  
Protein Coding ◽  
Pathological Characteristics ◽  
Epigenetic Events ◽  
Cancer Types ◽  
Non Coding Rnas

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

scholarly journals Integrative and Comprehensive Pancancer Analysis of Regulator of Chromatin Condensation 1 (RCC1)

2021 ◽  
Vol 22 (14) ◽  
pp. 7374
Author(s):  
Changwu Wu ◽  
Yingjuan Duan ◽  
Siming Gong ◽  
Sonja Kallendrusch ◽  
Nikolas Schopow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromatin Condensation ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Malignant Neoplasms ◽  
Nucleotide Exchange ◽  
Genome Database

Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors’ entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as “cell cycle” and “RNA transport” were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.

scholarly journals The Role of Alternative Lengthening of Telomeres Mechanism in Cancer: Translational and Therapeutic Implications

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 949 ◽  
Author(s):  
Marta Recagni ◽  
Joanna Bidzinska ◽  
Nadia Zaffaroni ◽  
Marco Folini
Keyword(s):  
Cancer Cells ◽  
Tumor Biology ◽  
Telomerase Activity ◽  
Telomere Maintenance ◽  
Limited Information ◽  
Adaptive Responses ◽  
Therapeutic Implications ◽  
Telomerase Inhibitors ◽  
Alternative Lengthening

Telomere maintenance mechanisms (i.e., telomerase activity (TA) and the alternative lengthening of telomere (ALT) mechanism) contribute to tumorigenesis by providing unlimited proliferative capacity to cancer cells. Although the role of either telomere maintenance mechanisms seems to be equivalent in providing a limitless proliferative ability to tumor cells, the contribution of TA and ALT to the clinical outcome of patients may differ prominently. In addition, several strategies have been developed to interfere with TA in cancer, including Imetelstat that has been the first telomerase inhibitor tested in clinical trials. Conversely, the limited information available on the molecular underpinnings of ALT has hindered thus far the development of genuine ALT-targeting agents. Moreover, whether anti-telomerase therapies may be hampered or not by possible adaptive responses is still debatable. Nonetheless, it is plausible hypothesizing that treatment with telomerase inhibitors may exert selective pressure for the emergence of cancer cells that become resistant to treatment by activating the ALT mechanism. This notion, together with the evidence that both telomere maintenance mechanisms may coexist within the same tumor and may distinctly impinge on patients’ outcomes, suggests that ALT may exert an unexpected role in tumor biology that still needs to be fully elucidated.

TNFα signalling predicts poor prognosis of patients with endometrial cancer

2020 ◽  
Vol 41 (8) ◽  
pp. 1065-1073
Author(s):  
Verena Wieser ◽  
Samira Abdel Azim ◽  
Susanne Sprung ◽  
Katharina Knoll ◽  
Johanna Kögl ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Clinical Outcome ◽  
The Cancer Genome Atlas ◽  
Western World ◽  
Low Grade ◽  
Necrosis Factor Alpha ◽  
Cancer Genome Atlas ◽  
Factor Alpha ◽  
The Impact

Abstract Endometrial cancer (EC) is the most common gynaecologic tumour in the Western world. Previous studies have implicated an imbalance of oestrogens and progestogens in the development of most ECs, while the role of low-grade tissue inflammation remains largely unexplored. We investigated the impact of tumour necrosis factor alpha (TNFα), a central mediator of inflammation and spermatogenesis-associated protein 2 (SPATA2), a regulator of TNF receptor signalling, on clinical outcomes in EC. We evaluated TNFA and SPATA2 transcript levels in 239 EC patients and 25 non-malignant control tissues. Findings were validated in a cohort of 332 EC patients from The Cancer Genome Atlas (TCGA). Expression of TNFA and SPATA2 was increased in EC when compared with control tissues (P < 0.001). TNFA expression correlated with SPATA2 expression in non-malignant (P = 0.003, rS = 0.568) and EC tissue (P = 0.005, rS = 0.179). High TNFA and SPATA2 expression were associated with poor recurrence-free survival (RFS; P = 0.049 and P = 0.018) and disease-specific (P = 0.034 and P = 0.002) survival. Increased SPATA2 expression was also associated with decreased overall survival (OS; P = 0.013). In multivariate analysis, both TNFA and SPATA2 were predictors of clinical outcome. The impact of SPATA2 on RFS and OS could be validated in the TCGA cohort. Our study demonstrates that ECs exhibit a TNF signature which predicts clinical outcome. These findings indicate that TNF signalling modulates the course of EC, which could be therapeutically utilized in the future.

scholarly journals In Silico Discovery of Candidate Drugs against Covid-19

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 404 ◽  
Author(s):  
Claudia Cava ◽  
Gloria Bertoli ◽  
Isabella Castiglioni
Keyword(s):  
Gene Expression ◽  
In Silico ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Basic Mechanism ◽  
Cell Receptor ◽  
The Cancer Genome Atlas ◽  
Pathway Enrichment Analysis

Previous studies reported that Angiotensin converting enzyme 2 (ACE2) is the main cell receptor of SARS-CoV and SARS-CoV-2. It plays a key role in the access of the virus into the cell to produce the final infection. In the present study we investigated in silico the basic mechanism of ACE2 in the lung and provided evidences for new potentially effective drugs for Covid-19. Specifically, we used the gene expression profiles from public datasets including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, Gene Ontology and pathway enrichment analysis to investigate the main functions of ACE2-correlated genes. We constructed a protein-protein interaction network containing the genes co-expressed with ACE2. Finally, we focused on the genes in the network that are already associated with known drugs and evaluated their role for a potential treatment of Covid-19. Our results demonstrate that the genes correlated with ACE2 are mainly enriched in the sterol biosynthetic process, Aryldialkylphosphatase activity, adenosylhomocysteinase activity, trialkylsulfonium hydrolase activity, acetate-CoA and CoA ligase activity. We identified a network of 193 genes, 222 interactions and 36 potential drugs that could have a crucial role. Among possible interesting drugs for Covid-19 treatment, we found Nimesulide, Fluticasone Propionate, Thiabendazole, Photofrin, Didanosine and Flutamide.

scholarly journals CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Di Yang ◽  
Jian Ma ◽  
Xiao-Xin Ma
Keyword(s):  
Endometrial Cancer ◽  
Immune Cell ◽  
Quantitative Polymerase Chain Reaction ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Immune Infiltration ◽  
Lncrna Expression ◽  
Ec Cells

The prognosis of patients with endometrial cancer (EC) is closely associated with immune cell infiltration. Although abnormal long non-coding RNA (lncRNA) expression is also linked to poor prognosis in patients with EC, the function and action mechanism of immune infiltration-related lncRNAs underlying the occurrence and development of EC remains unclear. In this study, we analyzed lncRNA expression using The Cancer Genome Atlas and clinical data and identified six lncRNAs as prognostic markers for EC, all of which are associated with the infiltration of immune cell subtypes, as illustrated by ImmLnc database and ssGSEA analysis. Real-time quantitative polymerase chain reaction showed that CDKN2B-AS1 was significantly overexpressed in EC, whereas its knockdown inhibited the proliferation and invasion of EC cells and the in vivo growth of transplanted tumors in nude mice. Finally, we constructed a competing endogenous RNA regulatory network and conducted Gene Ontology enrichment analysis to elucidate the potential molecular mechanism underlying CDKN2B-AS1 function. Overall, we identified molecular targets associated with immune infiltration and prognosis and provide new insights into the development of molecular therapies and treatment strategies against EC.

scholarly journals A radiogenomics application for prognostic profiling of endometrial cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Erling A. Hoivik ◽  
Erlend Hodneland ◽  
Julie A. Dybvik ◽  
Kari S. Wagner-Larsen ◽  
Kristine E. Fasmer ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Treatment Strategies ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Tumor Segmentation ◽  
Poor Survival ◽  
Cancer Genome Atlas ◽  
Automated Machine Learning ◽  
Magnetic Resonance Imaging Mri

AbstractPrognostication is critical for accurate diagnosis and tailored treatment in endometrial cancer (EC). We employed radiogenomics to integrate preoperative magnetic resonance imaging (MRI, n = 487 patients) with histologic-, transcriptomic- and molecular biomarkers (n = 550 patients) aiming to identify aggressive tumor features in a study including 866 EC patients. Whole-volume tumor radiomic profiling from manually (radiologists) segmented tumors (n = 138 patients) yielded clusters identifying patients with high-risk histological features and poor survival. Radiomic profiling by a fully automated machine learning (ML)-based tumor segmentation algorithm (n = 336 patients) reproduced the same radiomic prognostic groups. From these radiomic risk-groups, an 11-gene high-risk signature was defined, and its prognostic role was reproduced in orthologous validation cohorts (n = 554 patients) and aligned with The Cancer Genome Atlas (TCGA) molecular class with poor survival (copy-number-high/p53-altered). We conclude that MRI-based integrated radiogenomics profiling provides refined tumor characterization that may aid in prognostication and guide future treatment strategies in EC.

STEM-24. INTERFERON SIGNALING REGULATES THE PROLIFERATION AND MESENCHYMAL PHENOTYPE OF GLIOBLASTOMA STEM CELLS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi26-vi26
Author(s):  
Sabbir Khan ◽  
Rajasekaran Mahalingam ◽  
Shayak Sen ◽  
Kaitlin Gandy ◽  
Kristin Alfaro-Munoz ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Single Cell ◽  
In Silico ◽  
The Cancer Genome Atlas ◽  
Cytokine Signaling ◽  
Rna Seq ◽  
Mesenchymal Phenotype ◽  
Cancer Genome Atlas ◽  
Stat1 Signaling

Abstract Interferon (IFN) signaling contributes to stemness, cell proliferation, cell death, and cytokine signaling in cancer and immune cells; however, the role of IFN signaling in glioblastoma (GBM) and GBM stem-like cells (GSCs) is unclear. This study aimed to investigate the cancer cell-intrinsic IFN signaling in tumorigenesis and malignant phenotype of GBM. We characterized cell-intrinsic IFN signaling in The Cancer Genome Atlas, patient-derived cohorts of GSCs, and published single-cell RNA sequencing datasets by in-silico analyses. The in-silico findings were further validated by evaluating the cytokine secretion and using pharmacological activators and blockers of IFN/transducer and activator of transcription 1 (STAT1) signaling. We found that GSCs and GBM tumors exhibited differential cell-intrinsic IFN signaling, and high IFN/STAT1 signaling is associated with mesenchymal phenotype and poor survival outcomes. Ruxolitinib, a pharmacological inhibitor of IFN/STAT1, abolished the IFN/STAT1 signaling in GSCs with intrinsically high IFN signaling. IFN-γ treatment for 1 week promotes the mesenchymal phenotype in GSCs with low IFN signature. In addition, chronic inhibition of IFN/STAT1 signaling with ruxolitinib decreased cell proliferation and mesenchymal signatures (CD44, YKL40, and TIMP1) in GSCs with intrinsically active IFN/STAT1 signaling. Publicly available human glioma single-cell RNA-seq (scRNA-seq) datasets analyses showed that both tumor and nontumor cells expressed IFN signaling genes, and the mesenchymal signature was highly expressed in the same cluster where IFN signaling genes were upregulated. We demonstrated that cell-intrinsic IFN signaling in GSCs and GBM tumors is associated with mesenchymal signatures and cell proliferation. Our study provides evidence for the possibility of targeting IFN signaling in a specific group of GBM patients.

scholarly journals The Role of Ghrelin in Anorexia Nervosa

2018 ◽  
Vol 19 (7) ◽  
pp. 2117 ◽  
Author(s):  
Martha Schalla ◽  
Andreas Stengel
Keyword(s):  
Body Weight ◽  
Anorexia Nervosa ◽  
Endocrine Cells ◽  
Body Weight Gain ◽  
Treatment Strategies ◽  
Peptide Hormone ◽  
Future Research ◽  
Amino Acid Peptide ◽  
Pronounced Reduction

Ghrelin, a 28-amino acid peptide hormone expressed in X/A-like endocrine cells of the stomach, is the only known peripherally produced and centrally acting peptide that stimulates food intake and therefore attracted a lot of attention with one major focus on the treatment of conditions where an increased energy intake or body weight gain is desired. Anorexia nervosa is an eating disorder characterized by a pronounced reduction of body weight, a disturbed body image and hormonal alterations. Ghrelin signaling has been thoroughly investigated under conditions of anorexia nervosa. The present review will highlight these alterations of ghrelin in anorexia and discuss possible treatment strategies targeting ghrelin signaling. Lastly, gaps in knowledge will be mentioned to foster future research.

Psychosocial Approaches to the Treatment and Prevention of Bipolar Disorder

2016 ◽  
pp. 489-498
Author(s):  
Noreen A. Reilly-Harrington
Keyword(s):  
Bipolar Disorder ◽  
Behavioral Therapy ◽  
Treatment Strategies ◽  
Psychosocial Treatment ◽  
Future Research ◽  
Pediatric Bipolar Disorder ◽  
Treatment And Prevention ◽  
Social Rhythm ◽  
Psychosocial Approaches

Over the past two decades, adjunctive psychosocial treatments for bipolar disorder have been shown to hasten recovery, reduce relapse, and improve patients’ medication adherence, functioning, and quality of life. This chapter reviews four of the most widely studied psychosocial approaches for bipolar disorder: psychoeducation, cognitive-behavioral therapy (CBT), family-focused treatment (FFT), and interpersonal and social rhythm therapy (IPSRT). Core treatment strategies for each modality are presented, and key outcome studies are reviewed. The role of psychosocial treatment in pediatric bipolar disorder and in the prevention of bipolar disorder in youth at high risk for bipolar disorder is also presented. Suggestions for future research and the critical need for dissemination are also briefly discussed.

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