Exploring VEGF-Linked Pathways: Investigating Multiple miRNAs for Their Therapeutic Potential in Angiogenesis Targets and as Biomarkers in Recurrent Glioblastoma Multiforme. DOI
Morteza Hadizadeh, Ramin Soltani, Taimour Langaee

et al.

PubMed, Journal Year: 2022, Volume and Issue: 11(4), P. 306 - 319

Published: Jan. 1, 2022

Alternative pathways frequently operate as the origins of resistance to drugs that block vascular endothelial growth factor (VEGF) pathway. To find possible therapeutic targets and indicators, this study explored VEGF pathway how miRNAs control it in recurrent glioblastoma multiforme (rGBM). Differentially expressed (DEmiRNAs) were identified by using GBM GSE profiles (GSE32466). containing DEmiRNAs, genes, their related DIANA-miRPath v3.0 ToppGene database utilized. linked signaling interactional DEmiRNAs discovered extracting common pathways. The ability these distinguish rGBM patients from those with primary was assessed ROC analysis. revealed rGBM, 30 significantly up-regulated 49 considerably down-regulated. Among them, connected 22 29 down-regulated miRNAs. MAPK shared most genes pathway, accounting for 1,014 interacting which have interactions genes. Furthermore, 14 having a great deal potential molecular biomarkers rGBM. results indicate is regulated number interrelated hold promise targets, offering possibilities novel therapy strategies aiding diagnosis prognosis.

Language: Английский

Unveiling Gene Interactions in Alzheimer’s Disease by Integrating Genetic and Epigenetic Data with a Network-Based Approach DOI Creative Commons
Keith L. Sanders, Astrid M. Manuel, Andi Liu

et al.

Epigenomes, Journal Year: 2024, Volume and Issue: 8(2), P. 14 - 14

Published: April 1, 2024

Alzheimer’s Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects AD’s pathogenesis that may contribute drug repurposing efforts by integrating DNA methylation genetic data. Implementing network-based tool, dense module search genome-wide association studies (dmGWAS), we integrated large-scale GWAS dataset with data identify gene network modules associated AD. Our analysis yielded 286 significant modules. Notably, foremost included BIN1 gene, showing largest signal, GNAS most significantly hypermethylated. conducted Web-based Cell-type-Specific Enrichment Analysis (WebCSEA) on genes within top 10% dmGWAS modules, highlighting monocyte as cell type (p < 5 × 10−12). Functional enrichment revealed Gene Ontology Biological Process terms relevant AD pathology (adjusted p 0.05). Additionally, target identified five FDA-approved targets (p-value = 0.03) for further research. In summary, integration epigenetic signals unveiled new interactions related AD, offering promising avenues future studies.

Language: Английский

Citations

0
Computational modeling and synthesis of Pyridine variants of Benzoyl-Phenoxy-Acetamide with high glioblastoma cytotoxicity and brain tumor penetration DOI Creative Commons

Charles H. Ingraham,

Joanna Stalińska,

Sean C. Carson

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: April 20, 2023

Abstract Glioblastomas are highly aggressive brain tumors for which therapeutic options very limited. In a quest new anti-glioblastoma drugs, we focused on specific structural modifications of benzoyl-phenoxy-acetamide (BPA) present in common lipid-lowering drug, fenofibrate, and our first prototype glioblastoma PP1. Here, propose extensive computational analyses to improve selection the most effective drug candidates. Initially over 100 BPA variations were analyzed their physicochemical properties such as water solubility (-logS), calculated partition coefficient (ClogP), probability BBB crossing (BBB_SCORE), CNS penetration (CNS-MPO) cardiotoxicity (hERG), evaluated. This integrated approach allowed us select pyridine variants that show improved penetration, solubility, low cardiotoxicity. Herein top 24 compounds synthesized cell culture. Six them demonstrated toxicity with IC50 ranging from 0.59 3.24mM. Importantly, one compounds, HR68, accumulated tumor tissue at 3.7+/-0.5mM, exceeds its (1.17mM) by 3-fold.

Language: Английский

Citations

0
Advancements in stem cell-based therapeutics in phospholipase A2-dependent colorectal cancer DOI

Diptimayee Das,

C. Cynthia,

Surajit Pathak

et al.

Elsevier eBooks, Journal Year: 2023, Volume and Issue: unknown, P. 63 - 85

Published: Jan. 1, 2023

Language: Английский

Citations

0
Modulation von Stammzellcharakteristika in Gliom-initiierenden Zellen durch GANT61 oder Arsentrioxid und (-)-Gossypol DOI Creative Commons
Andrej Wehle

Published: Jan. 1, 2023

Das Glioblastom ist eine tödliche maligne Erkrankung des zentralen Nervensystems. Etablierte Therapiekonzepte resultieren in einer Fünfjahresüberlebensrate von fünf Prozent. Die derart infauste Prognose wird unter anderem bedingt durch die Heterogenität Tumors. Insbesondere Population stammzellartiger Zellen Verantwortung für Resistenz und Rekurrenz Glioblastoms zugesprochen. genuine Plastizität mit entsprechender Fähigkeit zur Änderungen tumorweiter Expressionsprofile Ausbildung einzigartiger funktioneller Fähigkeiten kann ohne gezielte Beeinträchtigung stammzellartigen womöglich nicht ausreichend überwunden werden. Als Urheber kritischer Eigenschaften erscheint erfolgreiche Elimination dieser innerhalb notwendig um nachhaltige Therapieerfolge zu erzielen. Mögliche Strategien der setzen an Differenzierung Ausbeutung stammzelltypischer Signalwege Modulation an. Hierdurch sollen zentrale Zellen, wie Selbsterneuerung, gegenüber Strahlen- Chemotherapie erneute Formation heterogener Tumore, Zentrale zelluläre Prozesse, welche zum Erhalt Zustandes beitragen, sind Hedgehog- Notch-Signalweg. Einer wohnt effektiven zentraler inne. Neben diesen Signalwegen gibt es Reihe weiterer welchen Urheberschaft zugesprochen wird. Hierzu zählt beispielweise Prozess Autophagie. Autophagie ein hochkonservierter zellulärer Mechanismus Selbsterneuerung Selbstdegradation fehlerhafter Komponenten. Gleichzeitig Überaktivität einem spezifischen, autophagischen Zelltod beitragen. dieses Dualismus Vielzahl Tumoren, so auch im Glioblastom, das Schicksal tumorfördernden antitumorale ändern. Im Rahmen Arbeit wurde erstmalig Beeinflussung ihrer zellulären Prozesse mittels kombinierter Therapie Arsentrioxid oder GANT (-)-Gossypol gezeigt. wirkt unspezifisch als Inhibitor Notch- Hedgehog-Signalweg. Diese Inhibition den untersuchten nachgewiesen führte Reduktion stammzelltypischen Markerproteinen Tumorgenese -vitro ex -vivo, sowie Sensitivierung strahleninduzierten Schäden. Gegenüber spezifischen Hedgehog-Inhibition GANT-vermittelte Bindung Gli-Transkriptionsfaktoren zeigten sich deutliche Vorteile dualen hinsichtlich genannten Eigenschaften. Kombination Substanzen dem pan-Bcl-Inhibitor synergistischen Steigerung antitumoralen Effekte. Gliomzellen insbesondere Maschinerie Auslösung eines Zelltodes Verbindung gebracht. Ergebnisse weisen parallele Signalweginteraktionen effektiver DNA-Damage-Response-Systems Proteins CHEK kausalen Synergismus aus. beobachteten typischen implizieren lohnende Folgeuntersuchungen weiteren Evaluation Effekte zukünftig translationale Ableitungen erlauben. seine lassen erfolgreich multiple Eingriffe unterschiedliche hierunter Hedgehog-Signaling, modulieren. könnten eventuell effektiv verändert

Citations

0
Exploring VEGF-Linked Pathways: Investigating Multiple miRNAs for Their Therapeutic Potential in Angiogenesis Targets and as Biomarkers in Recurrent Glioblastoma Multiforme. DOI
Morteza Hadizadeh, Ramin Soltani, Taimour Langaee

et al.

PubMed, Journal Year: 2022, Volume and Issue: 11(4), P. 306 - 319

Published: Jan. 1, 2022

Alternative pathways frequently operate as the origins of resistance to drugs that block vascular endothelial growth factor (VEGF) pathway. To find possible therapeutic targets and indicators, this study explored VEGF pathway how miRNAs control it in recurrent glioblastoma multiforme (rGBM). Differentially expressed (DEmiRNAs) were identified by using GBM GSE profiles (GSE32466). containing DEmiRNAs, genes, their related DIANA-miRPath v3.0 ToppGene database utilized. linked signaling interactional DEmiRNAs discovered extracting common pathways. The ability these distinguish rGBM patients from those with primary was assessed ROC analysis. revealed rGBM, 30 significantly up-regulated 49 considerably down-regulated. Among them, connected 22 29 down-regulated miRNAs. MAPK shared most genes pathway, accounting for 1,014 interacting which have interactions genes. Furthermore, 14 having a great deal potential molecular biomarkers rGBM. results indicate is regulated number interrelated hold promise targets, offering possibilities novel therapy strategies aiding diagnosis prognosis.

Language: Английский

Citations

0