Unveiling ferroptosis: a new frontier in skin disease research DOI Creative Commons
Ke Wang,

Yumeng Lin,

Dan Zhou

et al.

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

Published: Oct. 4, 2024

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation lipid peroxidation, ferroptosis has been implicated the progression various conditions, including psoriasis, photosensitive dermatitis, melanoma. This review provides an in-depth analysis molecular mechanisms underlying compares cellular effects with other forms context health disease. We systematically examine five specific diseases, ichthyosis, polymorphous light eruption (PMLE), vitiligo, melanoma, detailing influence on pathogenesis progression. Moreover, we explore current clinical landscape ferroptosis-targeted therapies, discussing their potential managing treating diseases. Our aim to shed therapeutic modulating research practice.

Language: Английский

The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway DOI Creative Commons
Md Ashiq Mahmud, Abu Bakar Siddique, Afsana Tajmim

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(1), P. 139 - 139

Published: Jan. 1, 2025

Melanoma is among the most abundant malignancies in US and worldwide. Ligstroside aglycone (LA) a rare extra-virgin olive oil-derived monophenolic secoiridoid with diverse bioactivities. LA dose–response screening at NCI 60 cancer cells panel identified high sensitivity of Malme-3M cell line, which harbors BRAF V600E mutation. Daily oral 10 mg/kg exhibited potent vivo antitumor effects against xenograft nude mouse model by targeting signaling pathway. A human Clariom S microarray analysis collected Malme- 3M tumors 571 dysregulated genes, downregulation pathways critical for melanoma growth survival. Western blot animal further validated mutated BRAF–MAPK axis, as well GPD1 ELOVL6 expression levels. histopathological tumor sections showed extensive focal necrosis treated mice. An immunofluorescence study notable reductions proliferation marker ki67 vasculogenesis CD31 tumors. These findings promote potential nutraceutical lead control mutant melanoma.

Language: Английский

Citations

0
BRAF Targeting Across Solid Tumors: Molecular Aspects and Clinical Applications DOI Open Access
Hiba Mechahougui,

James Gutmans,

Roumaïssa Gouasmi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3757 - 3757

Published: April 16, 2025

BRAF mutations are critical drivers in cancers such as melanoma, colorectal cancer, and non-small-cell lung cancer. The most common mutation, V600E, is a key therapeutic target. Targeted treatments with MEK inhibitors have significantly improved progression-free overall survival melanoma patients. However, like metastatic associated poor outcomes due to aggressive disease behavior resistance conventional chemotherapy. Despite progress, BRAF/MEK remains major challenge, often driven by secondary the mitogen-activated protein kinase (MAPK) pathway, activation of alternative pathways phosphoinositide 3-kinases (PI3Ks)/protein B (AKT), or changes tumor microenvironment. These challenges motivated ongoing research into combining immunotherapies enhance prolong treatment effectiveness. Future must also account for role cancer’s tissue origin, biological context influences response targeted therapies, highlighting need deeper understanding biology, micro-environment, genetics.

Language: Английский

Citations

0
The evolution of BRAF-targeted therapies in melanoma: overcoming hurdles and unleashing novel strategies DOI Creative Commons
Saber İmani, Ghazaal Roozitalab, Mahdieh Emadi

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Nov. 8, 2024

Melanoma, a highly aggressive form of skin cancer, poses significant global health burden, with 331,647 new cases and 58,645 deaths reported in 2022. The development melanoma is influenced by various factors, including sunlight exposure BRAF

Language: Английский

Citations

2
Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue DOI Creative Commons
Błażej Ochman, Piotr Limanówka, Sylwia Mielcarska

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(9), P. 10218 - 10248

Published: Sept. 15, 2024

Semaphorins (SEMAs), ADAM, and ADAMTS family members are implicated in various cancer progression events within the tumor microenvironment across different cancers. In this study, we aimed to evaluate expression of SEMA7A, SEMA4D, ADAM8, ADAMTS10 colorectal (CRC) relation mutational landscape KRAS, NRAS, BRAF, PIK3CA, AKT genes, microsatellite instability (MSI) status, clinicopathological features. We also examined associations between these proteins selected cytokines, chemokines, growth factors, assessed using a multiplex assay. Protein concentrations were quantified ELISA CRC tumors tumor-free surgical margin tissue homogenates. Gene mutations evaluated via RT-PCR, MSI status was determined immunohistochemistry (IHC). GSEA statistical analyses performed R Studio. observed significantly elevated SEMA7A BRAF-mutant an overexpression ADAM8 KRAS 12/13-mutant tumors. The decreased PIK3CA-mutant No significant differences based on status. SEMA4D expressions correlated with numerous cytokines associated immune processes. potential immunomodulatory functions molecules their suitability as therapeutic targets require further investigation.

Language: Английский

Citations

1
Green One-Pot Synthesis of Thiazole Scaffolds Catalyzed by Reusable NiFe2O4 Nanoparticles: In Silico Binding Affinity and In Vitro Anticancer Activity Studies DOI Creative Commons

Satish Gudala,

Archi Sharma,

Aruna Lankada

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(36), P. 38262 - 38271

Published: Aug. 29, 2024

A facile, green, one-pot multicomponent synthesis strategy was employed to fabricate novel thiazole scaffolds incorporating phthalazine, pyridazine, and pyrido-pyridazine derivatives (4a–4o). This synthetic route entailed the reaction of an α-halo carbonyl compound (1) with thiosemicarbazide (2) various anhydrides (3a–3o), utilizing NiFe2O4 nanoparticles as a reusable catalyst in ethanol:water (1:1) solvent system. The cytotoxicity synthesized compounds meticulously assessed against three cancer cell lines, A375, HeLa, MCF-7, employing IC50 values (μM) benchmark, compared reference drug erlotinib. Compound 4n displayed remarkable efficacy A375 (0.87 ± 0.31 μM), HeLa (1.38 1.24 MCF-7 (1.13 0.96 μM) significantly surpassing erlotinib's values. Additionally, 4k, 4l, 4m, 4o demonstrated notable across all tested indicating their potential effective anticancer agents. In silico docking studies Hsp82 Hsp90 proteins indicated that ligands 4c, 4j, 4o, 4l had superior binding affinities ADME analysis showed 4n, favorable pharmacokinetic profiles, including nontoxicity, high human intestinal absorption, low CYP inhibitory promiscuity. Structure–activity relationship revealed cyano benzylidene substitutions enhanced activity. Overall, compounds, particularly efficacy, interactions, promising making them strong candidates for further development

Language: Английский

Citations

0
Unveiling ferroptosis: a new frontier in skin disease research DOI Creative Commons
Ke Wang,

Yumeng Lin,

Dan Zhou

et al.

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

Published: Oct. 4, 2024

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation lipid peroxidation, ferroptosis has been implicated the progression various conditions, including psoriasis, photosensitive dermatitis, melanoma. This review provides an in-depth analysis molecular mechanisms underlying compares cellular effects with other forms context health disease. We systematically examine five specific diseases, ichthyosis, polymorphous light eruption (PMLE), vitiligo, melanoma, detailing influence on pathogenesis progression. Moreover, we explore current clinical landscape ferroptosis-targeted therapies, discussing their potential managing treating diseases. Our aim to shed therapeutic modulating research practice.

Language: Английский

Citations

0