Constitutive expression of c-REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome

AbstractPurposeUveal melanoma (UM) is the most common intraocular cancer with a high mortality rate that requires new research in the field of prevention and treatment. c-REL is a member of the nuclear factor κB (NF-κB) transcription factor family and an emerging regulator of tumorigenesis. Therefore, the objective of the study is to evaluate the constitutive expression of c-REL in uveal melanoma patients and its prognostic significance.MethodsDetection of c-REL expression was carried out by immunohistochemistry in all 75 patients, and qRT-PCR performed on 58 fresh cases of uveal melanoma along with IL-6 status. Immunoblot was performed to validate immunohistochemistry results. Expression of c-REL protein correlated with clinicopathological parameters and overall survival of patients.ResultsImmunohistochemistry results revealed nuclear expression of the c-REL protein (56%) in our cases. Out of 75 cases, 31 cases showed nuclear expression, and 11 cases had cytoplasmic expression. qRT-PCR showed upregulation of theREL gene in 56.89% cases at the transcriptional level. There was a statistically significant difference in the overall survival of patients with c-REL nuclear immunopositivity (p = 0.0048). On multivariate analysis, scleral invasion and c-REL nuclear expression found to be an independent prognostic factor (p 
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research

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Conclusions: Monitoring of choroidal nevi, particularly those classified as MOLES 1 or 2 (i.e., low-risk or high-risk naevi), can be accomplished safely without the need for ultrasonography. The findings of this study may remove barriers to the implementation of tele-oncology clinics for the monitoring of choroidal melanocytic tumors.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Malignant melanoma is the most deadly form of skin cancer. It originates from melanocytic cells and can also arise at other body sites. Early diagnosis and appropriate medical care offer excellent prognosis with up to 5-year survival rate in more than 95% of all patients. However, long-term survival rate for metastatic melanoma patients remains at only 5%. Indeed, malignant melanoma is known for its notorious resistance to most current therapies and is characterized by both genetic and epigenetic alterations. In cutaneous melanoma (CM), genetic alterations have been implicated in drug resistance, yet the main cause of this...
Source: Theranostics - Category: Molecular Biology Authors: Tags: Review Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. It has been demonstrated that microRNA-145 (miR-145) is correlated with the progression of various cancers by regulating the expression of multiple target genes, especially a number of genes that regulate angiogenesis and proliferation. However, the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well illustrated. Thus, we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and angiogenesis. METHODS: Totally, 24 ch...
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
In unpublished studies, we recently found that a cyclin-dependent kinase 9 (CDK9) degrader (Thal-SNS-032, TS-032) selectively inhibited BRAF/NRAS wild type melanomas. We now confirm this finding using another competitive CDK9 inhibitor, NVP-2. To further explore the context of this vulnerability, we undertook a large RNA seq analysis of 9 pigment cell lines (1 triple wild-type melanoma line, 2 uveal lines, 2 BRAF-mutated, 2 NRAS-mutated, 1 NF1-mutated, and 1 immortalized melanocyte line) in order to uncover transcriptional programs which may be preferentially extinguished or activated by TS-032 and NVP-2.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Carcinogenesis and Cancer Genetics Source Type: research
n Utikal Tumorigenesis is correlated with abnormal expression and activity of G protein-coupled receptors (GPCRs) and associated G proteins. Oncogenic mutations in both GPCRs and G proteins (GNAS, GNAQ or GNA11) encoding genes have been identified in a significant number of tumors. Interestingly, uveal melanoma driver mutations in GNAQ/GNA11 were identified for a decade, but their discovery did not lead to mutation-specific drug development, unlike it the case for BRAF mutations in cutaneous melanoma which saw enormous success. Moreover, new immunotherapies strategies such as immune checkpoint inhibitors have given und...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: REVIEW Source Type: research
Authors: Zhang Z, Ni Y, Chen G, Wei Y, Peng M, Zhang S Abstract Uveal melanoma (UM) is the most frequent primary ocular tumour among adults. Here, we aimed to establish the immune cell-based signature to predict the overall survival (OS) of UM patients. The mRNA profile and matched clinical records of 80 UM patients were downloaded from The Cancer Genome Atlas (TCGA) database. CIBERSORT was used to verify the immune cell types of individuals. The univariate analysis found the CD8+ T cell, monocyte, CD4+ memory T cell (resting) and mast cell (resting) were significantly associated with the OS of UM patients. Subsequ...
Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research
Abstract Immunotherapy has recently become a powerful weapon against cancer. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) was the first immune checkpoint used for immunotherapy. However, CTLA-4-related mechanisms in various cancers have not been comprehensively investigated. This aim of this study was an in-depth investigation of CTLA-4 in the tumor microenvironment and its relationship with other immunomodulators, immune-related pathways and survival outcomes of 33 cancer types. Overall 9,743 tumor samples and 710 normal samples of 33 cancer types from The Cancer Genome Atlas (TCGA) database were included...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
Queirolo Rosaria Gangemi Uveal melanoma (UM) is a rare tumor of the eye that leads to deadly metastases in about half of the patients. ADAM10 correlates with c-Met expression in UM and high levels of both molecules are related to the development of metastases. MiR122 and miR144 modulate ADAM10 and c-Met expression in different settings. We hypothesized a potential onco-suppressive role for miR122 and miR144 through modulation of ADAM10 and c-Met in UM. We analyzed the UM Cancer Genome Atlas data portal (TCGA) dataset, two other cohorts of primary tumors and five human UM cell lines for miR122 and miR144 expression b...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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