The alternatively spliced diacylglycerol kinase gamma-Δ exon13 transcript generated under hypoxia promotes glioblastoma progression DOI
Ming Yang, Liangzhao Chu,

Shukai Lin

et al.

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 0(0), P. 1 - 10

Published: Jan. 1, 2024

Glioblastoma (GBM) is one of the most malignant types central nervous system tumors. Oxygen deprivation in tumor microenvironment thought to be an important factor promoting GBM progression. However, mechanisms hypoxia-promoted progression remain elusive. Alternative splicing diacylglycerol kinase gamma (DGKG)-Δ exon13 was amplified and verified by PCR-Sanger sequencing. The functions DGKG DGKG-Δ were analyzed Cell counting kit-8 (CCK-8), Transwell, Matrigel-transwell experiments, vivo orthotropic animal models. Transcriptome analyses done find out regulated genes. In this study, we found that a new transcript generated under hypoxia via alternative splicing. Moreover, results CCK-8, experiments showed proliferation, migration, invasion abilities U87-MG T98G decreased after knockdown. Compared wild-type DGKG, overexpression significantly promoted cellular GBM. Furthermore, vivo, models analysis volumes much smaller knockdown group. sizes rescue groups restored, especially revealed MORC1, KLHDC7B, ATP1A2, INHBE, TMEM119, FGD3 altered when knocked down. IL-16, CCN2, EFNB3 specifically exon13. Our study hypoxia-induced promotes proliferation infiltration, which might provide potential target for clinical treatment diagnosis

Language: Английский

The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities DOI Creative Commons
Iason Psilopatis,

Kleio Vrettou,

Florian Nima Fleckenstein

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1227 - 1227

Published: April 23, 2023

Endometriosis is a chronic disorder of the female reproductive system which afflicts great number women worldwide. Histone deacetylases (HDACs) prevent relaxation chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying impact histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, literature was conducted using MEDLINE LIVIVO databases. manuscript represents most comprehensive, up-to-date focusing on particular role HDACs inhibitors context HDAC1, HDAC2, HDAC3, Sirtuin 1, 3, are five studied HDAC enzymes seem to, least partly, influence pathophysiology Both well-established novel HDACIs could possibly represent modern, efficacious anti-endometriotic drug agents. Altogether, have been proven strong

Language: Английский

Citations

12
Unraveling the Significance of EPH/Ephrin Signaling in Liver Cancer: Insights into Tumor Progression and Therapeutic Implications DOI Open Access
Stavros P. Papadakos, Ioanna Ε. Stergiou,

Nikolina Gkolemi

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(13), P. 3434 - 3434

Published: June 30, 2023

Liver cancer is a complex and challenging disease with limited treatment options dismal prognosis. Understanding the underlying molecular mechanisms driving liver progression metastasis crucial for developing effective therapeutic strategies. The EPH/ephrin system, which comprises family of cell surface receptors their corresponding ligands, has been implicated in pathogenesis HCC. This review paper aims to provide an overview current understanding role system Specifically, we discuss dysregulation signaling HCC its impact on various cellular processes, including proliferation, migration, invasion. Overall, emerges as compelling multifaceted player biology. Elucidating precise implications responses may pave way novel targeted therapies personalized approaches patients. Further research warranted unravel full potential clinical translation.

Language: Английский

Citations

10
Biological Significance of EphB4 Expression in Cancer DOI

Asmat Ullah,

Anam Razzaq,

Chuanzan Zhou

et al.

Current Protein and Peptide Science, Journal Year: 2023, Volume and Issue: 25(3), P. 244 - 255

Published: Nov. 1, 2023

Eph receptors and their receptor-interacting (ephrin) ligands comprise a vital cell communication system with several functions. In cancer cells, there was evidence of bilateral receptor signaling both tumor-suppressing tumor-promoting actions. As member the family, EphB4 has been linked to tumor angiogenesis, growth, metastasis, which makes it viable desirable target for drug development in therapeutic applications. Many investigations have conducted over last decade elucidate structure function association its ligand ephrinB2 involvement tumorigenesis. Although EphB4-targeting drugs investigated, some selective inhibitors evaluated clinical trials. This article addresses receptor, analyses possibility as an anticancer target, summarises knowledge kinase inhibitors. To summarise, is difficult but potential treatment option cancers.

Language: Английский

Citations

10
Advances and current concepts on Eph receptors and ephrins in upper digestive tract cancers DOI Creative Commons
Luccas Lavareze, Talita de Carvalho Kimura,

João Figueira Scarini

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 7, 2025

Erythropoietin-producing hepatocellular (Eph) receptors comprise the largest group of surface and are responsible for cellular signals. Eph/ephrin signaling has been identified to play a role in key cancer development progression processes, especially upper gastrointestinal tract. The system described as tumor suppressor duodenal cancer, while esophageal, gastric, hepatic, pancreatic related progression. For their significant developing wide range malignancies, Eph ligands have proven be an important target new anticancer therapies. In this review, we present overview literature highlight evidence supporting digestive tract cancers. addition, discuss molecular findings that represent promising therapeutic targets these

Language: Английский

Citations

0
Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysis DOI Creative Commons
Xudong Zhang, Yuhao Xu, Zehan Wu

et al.

BMC Neurology, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 5, 2025

Epilepsy is a severe neurological disorder characterized by persistent seizures and, in some patients, associated neurobiological, cognitive, and psychosocial consequences. It influenced various genetic factors, including the Ephrin-B2 (EFNB2) gene. This study utilized bidirectional Mendelian randomization (MR) to explore potential causal relationship between serum levels of EFNB2 epilepsy using data from extensive genome-wide association studies (GWAS). We selected generalized traits, applying strict criteria for instrumental variables ensure validity mitigate confounding influences. The analysis included sensitivity tests like MR pleiotropy residuals outliers test, as well co-localization evaluate shared Our results indicated significant epilepsy, suggesting that could be involved pathogenesis through mechanisms may not directly linked pathways. These suggest highlighting need further clarify its role possible relevance therapeutic target.

Language: Английский

Citations

0
EPH/Ephrin Signaling in Normal Hematopoiesis and Hematologic Malignancies: Deciphering Their Intricate Role and Unraveling Possible New Therapeutic Targets DOI Open Access
Ioanna Ε. Stergiou, Stavros P. Papadakos,

Anna Karyda

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(15), P. 3963 - 3963

Published: Aug. 4, 2023

Erythropoietin-producing hepatocellular carcinoma receptors (EPHs) represent the largest family of receptor tyrosine kinases (RTKs). EPH interaction with ephrins, their membrane-bound ligands, holds a pivotal role in embryonic development, while, though less active, it is also implicated various physiological functions during adult life. In normal hematopoiesis, different patterns EPH/ephrin expression have been correlated hematopoietic stem cell (HSC) maintenance and lineage-committed progenitor (HPC) differentiation, as well functional properties mature offspring. Research field hematologic malignancies has unveiled rather complex involvement EPH/ephrinsignaling pathway pathophysiology these neoplasms. Aberrations genetic, epigenetic, protein levels identified possible players both tumor progression suppression, while correlations highlighted regarding prognosis response to treatment. Initial efforts therapeutically target axis undertaken setting neoplasia but are mainly confined preclinical level. To this end, deciphering complexity signaling malignant hematopoiesis necessary.

Language: Английский

Citations

4
Development of a novel EphA2-targeting radioligand for SPECT imaging in different tumor models DOI
Li Wang,

Hao Zhang,

Wenjing Huang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 265, P. 116105 - 116105

Published: Dec. 26, 2023

Language: Английский

Citations

2
A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence DOI Creative Commons
Claudio Festuccia, Miriam Corrado, Alessandra Rossetti

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(10), P. 1452 - 1452

Published: Oct. 13, 2023

The Eph kinases are the largest receptor tyrosine (RTKs) family in humans. PC3 human prostate adenocarcinoma cells a well-established model for studying Eph-ephrin pharmacology as they naturally express high level of EphA2, promising target new cancer therapies. A pharmacological approach with agonists did not show significant efficacy on tumor growth orthotopic murine models, but reduced distal metastasis formation. In order to improve comprehension targeting receptors cancer, present work, we investigated antagonism both vitro and vivo, using UniPR1331, small orally bioavailable interaction inhibitor. UniPR1331 was able inhibit cells' dose-dependent manner, affecting cell cycle inducing apoptosis. Moreover, promoted epithelial phenotype, downregulating mesenchymal transition (EMT) markers. As consequence, migration, invasion, vasculomimicry capabilities. antitumor activity confirmed vivo when administered alone or combination cytotoxic drugs PC3-xenograft mice. Our results demonstrated that is strategy inhibiting growth, especially drugs.

Language: Английский

Citations

1
Over-Expression of EFNA2 in Lung Adenocarcinoma: EFNA2 Gene Expression Correlates with Shortened Survival DOI Open Access
Chunmei Liu,

Yanjiao Wu,

Huandi Zhou

et al.

Journal of Pharmaceutical Research International, Journal Year: 2024, Volume and Issue: 36(3), P. 10 - 23

Published: March 18, 2024

Background: The incidence of lung adenocarcinoma (LUAD) is increasing worldwide with different prognosis. Ephrin-A2（EFNA2), a member the Eph/ephrin family, associated tumor progression. However, correlations EFNA2 prognosis in LUAD remain unclear. purpose this article to analyze impact on patients through TCGA, Oncomine, and GEPIA databases, explore its possible mechanisms. Methods: This found significant correlation between shortened survival database analysis. Therefore, we further invested relationship expression prognostic value gene patients. Sequential data filtering (survival analysis, independent clinicalcorrelation analysis) was performed. analyzed by Oncomine Tumor Immune Estimation Resource (TIMER). We evaluated influence clinical using Kaplan-Meier plotter, PrognoScan Gene Expression Profiling Interactive Analysis (GEPIA). cancer immune infiltrates investigated TIMER. In addition, marker sets were TIMER GEPIA. enrichment analysis performed Metascape. Finally, co-expression database. Results: A cohort showed that high poorer overall (OS), disease-free (DFS) significantly stage LUAD. positively correlated infiltrating levels B cells CD8+ T cells. Moreover, differential higher compared normal controls. Specifically, ADAMTSL5, REEP6, PCSK4, C19orf25, ANAPC2. Conclusions: Our indicate potential diagnostic biomarker promising molecular therapeutic target attenuate

Language: Английский

Citations

0
Didang decoction attenuates cancer‐associated thrombosis by inhibiting PAD4‐dependent NET formation in lung cancer DOI Creative Commons

Xiaoyan Zeng,

Jiuxi Li,

Liyuan Pei

et al.

Pulmonary Circulation, Journal Year: 2024, Volume and Issue: 14(4)

Published: Oct. 1, 2024

Abstract This research aims to investigate the impact of Didang decoction (DD) on formation neutrophil extracellular traps (NETs) and cancer‐associated thrombosis in lung cancer. BALB/c nude mice were used establish xenograft models for inducing deep vein thrombosis. Tumor growth thrombus length assessed. The DD NET generation was analyzed using enzyme‐linked immunosorbent assay, immunofluorescence staining, quantitative real‐time PCR, western blot analysis, both vivo vitro. CI‐amidine, a PAD4 inhibitor, employed evaluate role NETs. In studies demonstrated that treatment with reduced tumor growth, inhibited formation, decreased levels markers serum, tissues, neutrophils, tissues mice. Additional data indicated could suppress counts, release tissue factor (TF), activation thrombin‐activated platelets, all which contributed increased NETs mouse models. vitro, following incubation conditioned medium (CM) derived from Lewis carcinoma cells, expression neutrophils significantly elevated, an fibrous network structure observed. Nevertheless, these NET‐associated changes partially counteracted by DD. Additionally, CI‐amidine CM‐treated consistent effects Collectively, inhibits cancer decreasing PAD4‐dependent through regulation TF‐mediated thrombin‐platelet activation. presents promising therapeutic strategy preventing treating venous thromboembolism

Language: Английский

Citations

0