Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

International Journal of Ophthalmology, Journal Year: 2024, Volume and Issue: 17(6), P. 1018 - 1027

Published: May 24, 2024

AIM: To explore the effect of epidermal growth factor receptor (EGFR) inhibition by erlotinib and EGFR siRNA on (EGF)-induced activation retinal pigment epithelium (RPE) cells. METHODS: Human RPE cell line (ARPE-19 cells) was activated 100 ng/mL EGF. Erlotinib were used to intervene EGF treatment. Cellular viability, proliferation, migration detected methyl thiazolyl tetrazolium (MTT) assay, bromodeoxyuridine (BrdU) staining assay wound healing respectively. EGFR/protein kinase B (AKT) pathway proteins N-cadherin, α-smooth muscle actin (α-SMA), vimentin tested Western blot assay. also determined immunofluorescence staining. RESULTS: treatment for 24h induced a significant increase ARPE-19 cells’ proliferation migration, phosphorylation EGFR/AKT proteins, decreased total expression. suppressed through down regulating AKT protein expressions. inhibited EGF-induced an proliferative migrative ability in cells clearly expression α-SMA, proteins. Similarly, significantly affected up-regulation CONCLUSION: EGFR-knockdown suppress via may be possible therapeutic approach vitreoretinopathy (PVR).

Language: Английский

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Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15110 - 15110

Published: Oct. 12, 2023

Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, new treatment options are needed. Recent studies have indicated alterations cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate frequency mTOR ERK pathway upregulation a retrospective series 139 ITAC test efficacy mechanism action candidate targeted inhibitors cell line ITAC-3. An immunohistochemical analysis on p-AKT, p-mTOR, p-S6, p-4E-BP1, p-ERK indicated, respectively, 68% 57% activation. In vitro using low doses inhibitor everolimus selumetinib showed significant growth inhibition monotherapy especially combined therapy. This effect accompanied by downregulation protein expression. data open promising possibility personalized patients.

Language: Английский

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Protein phosphatase 6 regulates trametinib sensitivity, a mitogen-activated protein kinase kinase (MEK) inhibitor, by regulating MEK1/2-ERK1/2 signaling in canine melanoma cells

Journal of Veterinary Medical Science, Journal Year: 2023, Volume and Issue: 85(9), P. 977 - 984

Published: Jan. 1, 2023

Melanoma is a highly aggressive and metastatic cancer occurring in both humans dogs. Canine melanoma accounts for significant proportion of neoplastic diseases dogs, despite standard treatments, overall survival rates remain low. Protein phosphatase 6 (PP6), an evolutionarily conserved serine/threonine protein phosphatase, regulates various biological processes. Additionally, the loss PP6 function reportedly leads to development humans. However, there are no reports regarding role canine cells. We, therefore, conducted study investigating by using four cell lines: CMec1, CMM, KMeC LMeC. knockdown increased phosphorylation levels mitogen-activated kinase 1/2 (MEK1/2) extracellular signal-regulated (ERK1/2) but not Akt. Furthermore, decreased sensitivity trametinib, MEK inhibitor, did alter Akt inhibitor. These findings suggest that may as tumor suppressor modulate response trametinib treatment. Understanding could lead more effective treatment strategies this disease.

Language: Английский

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Transcriptomic Analysis of Metastatic Uveal Melanoma and Differences in Male and Female Patients

Cancer Genomics & Proteomics, Journal Year: 2024, Volume and Issue: 21(4), P. 350 - 360

Published: June 29, 2024

Background/Aim: Uveal melanoma is an ocular malignancy whose prognosis severely worsens following metastasis. In order to improve the understanding of molecular physiology metastatic uveal melanoma, we identified genes and pathways implicated in vs non-metastatic melanoma. Patients methods: A previously published dataset from Gene Expression Omnibus (GEO) was used identify differentially expressed between samples as well conduct pathway perturbagen analyses using Set Enrichment Analysis (GSEA), EnrichR, iLINCS. Results: male samples, gene LOC401052 significantly down-regulated FHDC1 up-regulated compared samples. female no significant differently were found. Additionally, many immune response including "T cell activation response". contrast, top involve iron metabolism, "heme biosynthetic process". iLINCS analysis that both have similar discordant activity with growth factor receptors, but only progesterone receptor agonists. Conclusion: Our results analyzing genes, pathways, perturbagens demonstrate differences processes sexes.

Language: Английский

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Novel Uveal Melanoma Patient-Derived Organoid Models Recapitulate Human Disease to Support Translational Research

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(13), P. 60 - 60

Published: Nov. 27, 2024

Purpose: A lack of representative human disease models has limited the translation new and more effective treatments in uveal melanoma (UM), most common primary adult intraocular malignancy. To fill this critical need, we developed characterized a multicenter biobank UM patient-derived organoids (PDOs). Methods: patients requiring enucleation from 2019 to 2024 donated tumor tissue for PDO generation. PDOs were cultured Cultrex compared donor using exome sequencing, RNA immunohistochemistry. The ability maintain transformed phenotype was evaluated an orthotopic xenograft model monitored with fundus imaging. ATAC sequencing drug response assays done subset explore feasibility their use mechanistic translational studies. Results: successfully established 40 44 cases (91%), retained clinically relevant mutations molecular markers tumor, displayed similar gene expression profiles well-validated clinical prognostic disease. tumorigenic capacity vivo resembling progression. Finally, demonstrated that feasible platform identify evaluate novel therapeutic targets investigate differential, personalized response. Conclusions: offer improved representation aid research dismal condition.

Language: Английский

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A New Human Uveal Melanoma Cell Line: Melanin Production and Molecular Markers for Targeted Therapy

Biochemistry (Moscow) Supplement Series B Biomedical Chemistry, Journal Year: 2023, Volume and Issue: 17(4), P. 165 - 171

Published: Dec. 1, 2023

Language: Английский

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