Cancers, Vol. 11, Pages 1202: Soluble HLA in the Aqueous Humour of Uveal Melanoma Is Associated with Unfavourable Tumour Characteristics

Cancers, Vol. 11, Pages 1202: Soluble HLA in the Aqueous Humour of Uveal Melanoma Is Associated with Unfavourable Tumour Characteristics Cancers doi: 10.3390/cancers11081202 Authors: Annemijn P. A. Wierenga Gülçin Gezgin Els van Beelen Michael Eikmans Marijke Spruyt-Gerritse Niels J. Brouwer Mieke Versluis Robert M. Verdijk Sjoerd G. van Duinen Marina Marinkovic Gregorius P. M. Luyten Martine J. Jager A high HLA expression in uveal melanoma (UM) is part of the prognostically unfavorable inflammatory phenotype. We wondered whether the presence of soluble HLA (sHLA) in the aqueous humour is associated with clinical, histopathological or genetic tumour characteristics, and represents tumour HLA expression and intratumoural inflammation. Aqueous humour from 108 UM patients was analysed for the presence of sHLA, using a Luminex assay specific for HLA Class I. Clinical and genetic parameters were compared between sHLA-positive and negative eyes. A qPCR analysis was performed on tumour tissue using a Fluidigm assay. In 19/108 UM-containing eyes, the sHLA level in the aqueous was above the detection limit. Tumours in sHLA-positive eyes were significantly larger, more frequently involved the ciliary body, and more often showed monosomy 3, gain of chromosome 8q and loss of BAP1 staining. Melanoma-related survival was worse in patients with sHLA-positive aqueous humour. sHLA in the aqueous did not represent the tumour’s HLA expression ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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We present a 48-year-old woman affected by metastatic uveal melanoma treated with nivolumab (3 mg/kg every 2 weeks). The patient had no previous history of autoimmune disease or dermatologic conditions. At the fourth month of treatment, on cutaneous examination, she presented multiple whitish vitiligo-like patches on the trunk, axillae, hands and face. Diagnosis of melanoma-associated leukoderma vitiliginous reaction was made. Over the following months, the melanoma-associated leukoderma lesions slowly progressed with cigarette paper-like appearance and indurated texture. A skin biopsy leaded the diagnosis of extragenital ...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Case Reports Source Type: research
Heinzelmann Uveal melanoma (UM) is the most common primary intraocular tumor that arises from neoplastic melanocytes in the choroid, iris, and ciliary body. Electrochemotherapy (ECT) has been successfully established for the treatment of skin and soft tissue metastatic lesions, deep-seated tumors of the liver, bone metastases, and unresectable pancreas lesions. The aim of this study was to evaluate the effect of ECT in vitro in 3D spheroid culture systems in primary and metastatic UM cell lines. We also investigated the chick embryo chorioallantoic membrane (CAM) as an in vivo model system for the growth and treatment ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Uveal melanoma (UM) has a high mortality rate due to liver metastasis. The insulin-like growth factor-1 receptor (IGF-1R) is highly expressed in UM and has been shown to be associated with hepatic metastases. Targeting IGF signalling may be considered as a promising approach to inhibit the process of metastatic UM cells. Pristimerin (PRI) has been demonstrated to inhibit the growth of several cancer cells, but its role and underlying mechanisms in the IGF-1-induced UM cell proliferation are largely unknown. The present study examined the anti-proliferative effect of PRI on UM cells and its possible role i...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Authors: Gencia I, Baderca F, Avram S, Gogulescu A, Marcu A, Seclaman E, Marian C, Solovan C Abstract MicroRNAs (miRNAs) have been proven to regulate the development and progression of cancer through various mechanisms. The aim of the present study was to compare miRNA expression between primary melanomas from different sites. We analyzed the expression of 84 miRNAs in 27 primary melanoma and 5 nevus formalin-fixed paraffin-embedded (FFPE) samples using the Human Cancer PathwayFinder miScript miRNA PCR Array. The FFPE samples were obtained from the archives of the Municipal Clinical Emergency Hospital of Timisoara ...
Source: Bosnian Journal of Basic Medical Sciences - Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research
eraro Mor Presta Fibroblast growth factors (FGFs) play non-redundant autocrine/paracrine functions in various human cancers. The Cancer Genome Atlas (TCGA) data mining indicates that high levels of FGF and/or FGF receptor (FGFR) expression are associated with reduced overall survival, chromosome 3 monosomy and BAP1 mutation in human uveal melanoma (UM), pointing to the FGF/FGFR system as a target for UM treatment. Here, we investigated the impact of different FGF trapping approaches on the tumorigenic and liver metastatic activity of liver metastasis-derived murine melanoma B16-LS9 cells that, similar to human UM...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Germline mutations of BRCA1 and BRCA2 predispose individuals to a high risk of breast and ovarian cancer, and elevated risk of other cancers, including those of the pancreas and prostate. BRCA2 mutation carriers may have increased risk of uveal melanoma (UM) and cutaneous melanoma (CM), but associations with these cancers in BRCA1 mutation carriers have been mixed. Here, we further assessed whether UM and CM are associated with BRCA1 or BRCA2 by assessing the presence, segregation and reported/predicted pathogenicity of rare germline mutations (variant allele frequency
Source: Melanoma Research - Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
In conclusion, 5-HTR1B, 5-HTR2B, DRD1, and DRD2 show mRNA overexpression in a broad spectrum of common and rare cancers. 5-HTR2B protein is frequently highly expressed in human cancers, especially on endothelial cells. These findings support further investigation of especially 5HTR2B as a potential treatment target. PMID: 31478179 [PubMed - as supplied by publisher]
Source: Pathology Oncology Research - Category: Pathology Authors: Tags: Pathol Oncol Res Source Type: research
This study has shown that sister chromatid exchange (SCE) is low in UM which is likely due to a reduced expression of FANCD2. As FANCD2 can function to suppress non-homologous end joining (NHEJ), this study therefore investigated NHEJ in UM. The activation of the catalytic subunit of the NHEJ pathway protein DNA-dependent protein kinase (DNA-PK) was measured by analysing the foci formation and the ligation efficiency by NHEJ determined using a plasmid-based end-joining assay. Using small-interfering RNA (siRNA) knock-down, and chemical inhibitors of DNA-PK, the survival of primary UM cultures and two cell lines were determ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, which has a high rate of metastases and can induce vision loss and even death to the patients. To identify suitable prognostic markers of UM for the early detection or prognosis prediction would be an essential step toward successful management of the disease. Herein, we extracted the mRNA expression data along with the clinical information from The Cancer Genome Atlas (TCGA) database. A total of eight co-expression modules were constructed by 5,000 genes based on the weighted gene co-expression network analysis (WGCNA)....
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
Conclusions: Whereas in myelodysplastic syndrome predominantly missense SRSF2 mutations are described, the observed SRSF2 mutations in UM are all in-frame deletions of 8–9 amino acids. This suggests that the R625 missense SF3B1 mutations and SRSF2 mutations in UM are different compared to the spliceosome gene mutations in hematological cancers, and probably target a different, as yet unknown, set of genes involved in uveal melanoma etiology.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Communication Source Type: research
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