Assessment of ferroptosis as a promising candidate for metastatic uveal melanoma treatment and prognostication DOI Creative Commons

Ellie Swords,

Breandán N. Kennedy, Valentina Tonelotto

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 1, 2024

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. Local resection, radiation therapy, and enucleation are current first-line, UM treatments. However, regardless of treatment received, around 50% patients will develop metastatic disease within five to 7 years. In largest published series unselected with (mUM), median survival time after diagnosis metastasis was 3.6 months, less than 1% surviving beyond 5 Approved drugs for mUM include systemic tebentafusp-tebn or isolated hepatic perfusion (IHP) melphalan. these only available a subset improve by few highlighting urgent need new Accurately predicting which at high risk metastases also crucial. Researchers developing gene expression signatures create reliable prognostic models aimed improving patient follow-up strategies. this review we discuss evidence supporting ferroptosis, non-apoptotic form cell death, as potential novel target prognosticator UM.

Language: Английский

1,4-dihydroxy quininib activates ferroptosis pathways in metastatic uveal melanoma and reveals a novel prognostic biomarker signature DOI Creative Commons
Valentina Tonelotto, Marcel Costa-García,

Eve O’Reilly

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 10, 2024

Uveal melanoma (UM) is an ocular cancer, with propensity for lethal liver metastases. When metastatic UM (MUM) occurs, as few 8% of patients survive beyond two years. Efficacious treatments MUM are urgently needed. 1,4-dihydroxy quininib, a cysteinyl leukotriene receptor 1 (CysLT

Language: Английский

Citations

5
In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy DOI Creative Commons
Andrea Errico, Giulia Ambrosini, Sara Vinco

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 10, 2025

Language: Английский

Citations

0
Programmed Cell Death-Related Gene Signature Associated with Prognosis and Immune Infiltration and the Roles of HMOX1 in the Proliferation and Apoptosis were Investigated in Uveal Melanoma DOI Creative Commons

Zhao Yubao,

Liang Wang, Xiaoyan Li

et al.

Genes & Genomics, Journal Year: 2024, Volume and Issue: 46(7), P. 785 - 801

Published: May 20, 2024

Abstract Background Uveal melanoma (UVM) is the most common primary ocular malignancy, with a wide range of symptoms and outcomes. The programmed cell death (PCD) plays an important role in tumor development, diagnosis, prognosis. There still no research on relationship between PCD-related genes UVM. A novel PCD-associated prognostic model urgently needed to improve treatment strategies. Objective We aim screen signature investigate its proliferation ability apoptosis UVM cells. Methods clinical information RNA-seq data patients were collected from TCGA cohort. All classified using consensus clustering by selected genes. After univariate Cox regression PPI network analysis, then submitted LASSO analysis build model. level immune infiltration 8-PCD high- low-risk was analyzed xCell. prediction chemotherapy immunotherapy response assessed GDSC TIDE algorithm. CCK-8, western blot Annexin V-FITC/PI staining used explore roles HMOX1 Results total constructed risk score PCD negatively correlated overall survival, indicating strong predictive independent value. positively CD8 Tcm, Tem Th2 Immune cells high-risk group had poorer survival. drug sensitivity demonstrated that cisplatin might impact progression better responsiveness group. Finally, Overespression (OE-HMOX1) decreased viability induced Recuse experiment results showed ferrostatin-1 (fer-1) protected MP65 necrosis caused OE-HMOX1. Conclusion may have significant microenvironment, clinicopathological characteristics, prognosis sensitivity. More importantly, depletion greatly growth inhibited fer-1 This work provides foundation for effective therapeutic strategy tumour treatment.

Language: Английский

Citations

2
A cytosolic mutp53(E285K) variant confers chemoresistance of malignant melanoma DOI Creative Commons

Luise Dunsche,

Nikita V. Ivanisenko,

Shamala Riemann

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(12)

Published: Dec. 14, 2023

Abstract Malignant melanoma (MM) is known to be intrinsically chemoresistant, even though only ~20% of MM carry mutations the tumor suppressor p53. Despite improvement systemic therapy mortality rate patients suffering from metastatic still ~70%, highlighting need for alternative treatment options or re-establishment conventional therapeutic approaches, including chemotherapy. Screening p53 mutation status in a cohort 19 patient-derived samples, we identified one rarely described missense leading E285K amino acid exchange ( mut p53(E285K)). Employing structural and computational analysis revealed major role E285 residue maintaining stable conformation wild-type wt p53). was predicted cause interruption salt-bridge network affecting C-terminal helix DNA-binding domain (DBD) thereby preventing DNA interaction. In this context, cluster frequently mutated residues cancer putatively lead similar effects as substitution (E285 cluster). Functional analysis, knockdown endogenous reconstitution with diverse mutants confirmed p53(E285K) have lost transcriptional activity, localized cytosol cells, by both means conferring chemoresistance. Re-sensitization cisplatin-induced cell death achieved using clinically approved compounds aiming restore function (PRIMA1-Met), inhibition AKT-driven MAPK survival pathways (afuresertib), cases being partially due ferroptosis induction. Consequently, active induction GPX4 inhibitor RSL3 proved superior tumorselectively fighting cells. Due high prevalence E285-cluster well variety other types, conclude serve an important development suggest new implications applications particular general.

Language: Английский

Citations

2
Spatiotemporally Controllable Covalent Bonding of RNA for Multi‐Protein Interference DOI
Hao Fang, Tingting Wang, Jun Dai

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: July 9, 2024

Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process multiple proteins show greater potential compared to single-protein in oncological diseases. However, conventional agents regulate protein still suffer from poor spatiotemporal selectivity stability. Here, a new method using dye-peptide conjugate, PRFK, for multi-protein interference reliable stability, is reported. By peptide sequence targets tumor cells, PRFK can be efficiently taken up, followed by specific binding KDELR (KDEL receptor) located endoplasmic reticulum (ER). The dye generates

Language: Английский

Citations

0
Assessment of ferroptosis as a promising candidate for metastatic uveal melanoma treatment and prognostication DOI Creative Commons

Ellie Swords,

Breandán N. Kennedy, Valentina Tonelotto

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 1, 2024

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. Local resection, radiation therapy, and enucleation are current first-line, UM treatments. However, regardless of treatment received, around 50% patients will develop metastatic disease within five to 7 years. In largest published series unselected with (mUM), median survival time after diagnosis metastasis was 3.6 months, less than 1% surviving beyond 5 Approved drugs for mUM include systemic tebentafusp-tebn or isolated hepatic perfusion (IHP) melphalan. these only available a subset improve by few highlighting urgent need new Accurately predicting which at high risk metastases also crucial. Researchers developing gene expression signatures create reliable prognostic models aimed improving patient follow-up strategies. this review we discuss evidence supporting ferroptosis, non-apoptotic form cell death, as potential novel target prognosticator UM.

Language: Английский

Citations

0