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1.
Int J Mol Sci ; 21(24)2020 Dec 17.
Article in English | MEDLINE | ID: mdl-33348918

ABSTRACT

Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR. ddPCR was employed to assess UM-specific GNA11, GNAQ, PLCß4, and CYSLTR2 mutations in plasma DNA. Moreover, microarray analysis was performed on total RNA isolated from tumor tissues to estimate the prognostic value of EMT-associated gene expression. In total, 42 primary UM and 11 metastatic patients were enrolled. All CD45-depleted samples were negative for CTC when compared to the peripheral blood fraction of 60 healthy controls. Tumor-specific mutations were detected in the plasma of 21.4% patients, merely, in 9.4% of primary UM, while 54.5% in metastatic patients. Unsupervised hierarchical clustering of differentially expressed EMT genes showed significant differences between monosomy 3 and disomy 3 tumors. Newly identified genes can serve as non-invasive prognostic biomarkers that can support therapeutic decisions.


Subject(s)
Biomarkers, Tumor/genetics , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Melanoma/genetics , Neoplastic Cells, Circulating/pathology , Uveal Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Chromosome Deletion , Chromosomes, Human, Pair 3/genetics , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , Female , Follow-Up Studies , Humans , Liquid Biopsy , Male , Melanoma/secondary , Melanoma/therapy , Middle Aged , Neoplastic Cells, Circulating/metabolism , Prognosis , Uveal Neoplasms/secondary , Uveal Neoplasms/therapy
2.
Int J Mol Sci ; 21(15)2020 Jul 27.
Article in English | MEDLINE | ID: mdl-32726977

ABSTRACT

Uveal melanoma (UM), the most common intraocular malignancy in adults, is a rare subset of melanoma. Despite effective primary therapy, around 50% of patients will develop the metastatic disease. Several clinical trials have been evaluated for patients with advanced UM, though outcomes remain dismal due to the lack of efficient therapies. Epigenetic dysregulation consisting of aberrant DNA methylation, histone modifications, and small non-coding RNA expression, silencing tumor suppressor genes, or activating oncogenes, have been shown to play a significant role in UM initiation and progression. Given that there is no evidence any approach improves results so far, adopting combination therapies, incorporating a new generation of epigenetic drugs targeting these alterations, may pave the way for novel promising therapeutic options. Furthermore, the fusion of effector enzymes with nuclease-deficient Cas9 (dCas9) in clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) system equips a potent tool for locus-specific erasure or establishment of DNA methylation as well as histone modifications and, therefore, transcriptional regulation of specific genes. Both, CRISPR-dCas9 potential for driver epigenetic alterations discovery, and possibilities for their targeting in UM are highlighted in this review.


Subject(s)
DNA Methylation , DNA, Neoplasm , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Genetic Therapy , Melanoma , Uveal Neoplasms , CRISPR-Cas Systems , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Histones/genetics , Histones/metabolism , Humans , Melanoma/genetics , Melanoma/metabolism , Melanoma/therapy , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Protein Processing, Post-Translational , Uveal Neoplasms/genetics , Uveal Neoplasms/metabolism , Uveal Neoplasms/therapy
3.
J Cell Physiol ; 234(9): 16290-16294, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30756376

ABSTRACT

INTRODUCTION: Toll-like receptors (TLRs) are innate immunity receptors, which have an important role in modulating inflammation in disease. Cerebrolysin is a biotechnologically prepared peptide that stimulates neurotrophic regulation in the central nervous system. The aim of the present study was to investigate the effect of experimenting cerebrolysin on TLR2 and TLR4 in alcoholic liver disease (ALD). MATERIALS AND METHODS: TLR2 and TLR4 expressions were determined using real-time polymerase chain reaction in rats, which have used alcohol and they were separated into five groups. RESULTS: The results of the present study showed that in mild dose of cerebrolysin, the expression of TLR2 and TLR4 was decreased significantly than other groups. Also, the results of the western blot analysis proved the same. CONCLUSION: The present study demonstrated that the anti-inflammatory effect of cerebrolysin can decrease the TLR2 and TLR4 expressions through downregulating nuclear factor-κB pathway in the ALD disease.

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